WorldWideScience

Sample records for e2br clinical safety

  1. Understanding Clinical Alarm Safety.

    Science.gov (United States)

    Lukasewicz, Carol L; Mattox, Elizabeth Andersson

    2015-08-01

    Patient safety organizations and health care accreditation agencies recognize the significance of clinical alarm hazards. The Association for the Advancement of Medical Instrumentation, a nonprofit organization focused on development and use of safe and effective medical equipment, identifies alarm management as a major issue for health care organizations. ECRI Institute, a nonprofit organization that researches approaches for improving patient safety and quality of care, identifies alarm hazards as the most significant of the "Top Ten Health Technology Hazards" for 2014. A new Joint Commission National Patient Safety Goal focusing on clinical alarm safety contains new requirements for accredited hospitals to be fully implemented by 2016. Through a fictional unfolding case study, this article reviews selected contributing factors to clinical alarm hazards present in inpatient, high-acuity settings. Understanding these factors improves contributions by nurses to clinical alarm safety practice.

  2. Patient safety trilogy: perspectives from clinical engineering.

    Science.gov (United States)

    Gieras, Izabella; Sherman, Paul; Minsent, Dennis

    2013-01-01

    This article examines the role a clinical engineering or healthcare technology management (HTM) department can play in promoting patient safety from three different perspectives: a community hospital, a national government health system, and an academic medical center. After a general overview, Izabella Gieras from Huntington Hospital in Pasadena, CA, leads off by examining the growing role of human factors in healthcare technology, and describing how her facility uses clinical simulations in medical equipment evaluations. A section by Paul Sherman follows, examining patient safety initiatives from the perspective of the Veterans Health Administration with a focus on hazard alerts and recalls. Dennis Minsent from Oregon Health & Science University writes about patient safety from an academic healthcare perspective, and details how clinical engineers can engage in multidisciplinary safety opportunities.

  3. GOLIMUMAB SAFETY ACCORDING TO CLINICAL FINDINGS

    Directory of Open Access Journals (Sweden)

    G. V. Lukina

    2015-01-01

    Full Text Available                                                      The review analyzes trials dealing with the safety of golimumab (GLM  used in rheumatology.  This drug was the latest Contact: Galina Lukina;gvl3@yandex.ru Поступила 12.05.14tumor necrosis factor α (TNF-α inhibitor introduced  into clinical practice and therefore the estimation of its tolerability is particularly relevant. The data obtained in large-scale clinical trials suggest that GLM has a good safety profile. The most common  adverse events (AE were infections, more often mild. The rate of infections was higher with the use of GLM 100 mg than with that of 50 mg. The overall cancer rate did not increase during a follow-up of less than 160 weeks. However, the rate of lymphomas in patients receiving GLM 100 mg proved to be higher than in those taking GLM 50 mg, in the general population, and in the placebo group in particular. AE were evenly distributed among patients with rheumatoid  arthritis, psoriatic arthritis, or ankylosing spondylitis. Overall, the findings are in agreement with the data on the safety of previously used TNF-α inhibitors. No fundamentally new AE have been encountered. It is necessary to accumulate  data on the use of GLM in real clinical practice, which will be able to more objectively define its place in the current therapy of rheumatic diseases.

  4. A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety ...

    African Journals Online (AJOL)

    A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety and Cost Effectiveness of ... Log in or Register to get access to full text downloads. ... Pharmacological control of pain is the mainstay of management of osteoarthritis.

  5. Safety of amisulpride (Solian): a review of 11 clinical studies.

    Science.gov (United States)

    Coulouvrat, C; Dondey-Nouvel, L

    1999-07-01

    We assessed the overall safety profile of amisulpride based on the results from 11 clinical studies performed in patients suffering from schizophrenia with predominance of positive or negative symptoms. A total of 1933 patients were randomly assigned to treatment with amisulpride (n = 1247) or haloperidol (n = 309), risperidone (n = 113), flupentixol (n = 62) and placebo (n = 202). Safety data collection was performed using open reporting, UKU scales or specific extrapyramidal side-effect scales; electrocardiogram recording and vital signs examination; laboratory data collection. Amisulpride demonstrated a satisfactory global safety profile in the range of doses usually prescribed. The number of patients having at least one extrapyramidal side-effect was higher in haloperidol patients compared with both amisulpride and risperidone patients (50% versus 30% in the two latter groups). For endocrine events, a similar rate was observed between amisulpride and risperidone groups (4% versus 6%, respectively) versus 1% in the haloperidol group. Electrocardiogram results were satisfactory, confirmed by the absence of cardiovascular events. The overall laboratory safety profile of amisulpride did not show clinically relevant abnormalities in liver function tests nor haematological abnormalities. Our extensive clinical data confirm the satisfactory safety profile of amisulpride which is superior to standard reference compounds.

  6. Enhancing Patient Safety Using Clinical Nursing Data: A Pilot Study.

    Science.gov (United States)

    Choi, Jeeyae; Choi, Jeungok E

    2016-01-01

    To enhance patient safety from falls, many hospital information systems have been implemented to collect clinical data from the bedside and have used the information to improve fall prevention care. However, most of them use administrative data not clinical nursing data. This necessitated the development of a web-based Nursing Practice and Research Information Management System (NPRIMS) that processes clinical nursing data to measure nurses' delivery of fall prevention care and its impact on patient outcomes. This pilot study developed computer algorithms based on a falls prevention protocol and programmed the prototype NPRIMS. It successfully measured the performance of nursing care delivered and its impact on patient outcomes using clinical nursing data from the study site. Results of the study revealed that NPRIMS has the potential to pinpoint components of nursing processes that are in need of improvement for preventing patient from falls.

  7. MR arthrography: pharmacology, efficacy and safety in clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Schulte-Altedorneburg, G.; Gebhard, M.; Wohlgemuth, W.A.; Fischer, W.; Zentner, J.; Bohndorf, K. [Department of Radiology, Klinikum Augsburg, Stenglinstrasse 2, 86156 Augsburg (Germany); Wegener, R.; Balzer, T. [Clinical Development Diagnostics and Radiopharmaceuticals II, Schering AG, Berlin (Germany)

    2003-01-01

    A meta-analysis was carried out of clinical trials published between 1987 and 2001 in respect of the clinical pharmacology and safety as well as the diagnostic efficacy of gadolinium-DTPA (Gd-DTPA) for direct intra-articular injection before MRI examination.Design. Scientific papers (clinical, postmortem and experimental studies) and information from the manufacturer regarding intra-articular injection of Gd-DTPA that addressed questions of mode of action, optimal concentration and dose, elimination and safety were reviewed. Clinical studies were classified according to their study design. The sensitivity, specificity and accuracy of MR arthrography (MRA) were compared with a ''gold standard'' (arthroscopy, arthrotomy) and other radiological evidence for different joints.Results. Fifty-two clinical studies of the overall 112 studies addressed aspects of diagnostic efficacy of MRA in patients or in healthy volunteers. The shoulder was the most assessed joint (29 of 52 studies). Good (>80%) or even excellent (90-100%) sensitivity, specificity and accuracy were found for MRA in most indications, especially for the shoulder and knee joints and induced extension of rotator cuff lesions, labrum abnormalities and postoperative meniscal tears. Two millimoles per liter has proven to be the best concentration for intra-articular administration of Gd-DTPA. After passive complete diffusion from the joint within 6-24 h, complete and rapid renal elimination takes place after intra-articular injection. Local safety proved to be excellent after intra-articular administration of Gd-DTPA. Regarding systemic tolerance almost no side effects have been reported, but the same safety considerations apply for intra-articular administration of Gd-DTPA as for intravenous injection.Conclusions. The diagnostic efficacy of intra-articular MRA in most clinical conditions affecting major joints is greater than that of plain MRI. In some diagnostic problems MRA achieves almost

  8. Clinical safety and professional liability claims in Ophthalmology.

    Science.gov (United States)

    Dolz-Güerri, F; Gómez-Durán, E L; Martínez-Palmer, A; Castilla Céspedes, M; Arimany-Manso, J

    2017-06-29

    Patient safety is an international public health priority. Ophthalmology scientific societies and organisations have intensified their efforts in this field. As a tool to learn from errors, these efforts have been linked to the management of medical professional liability insurance through the analysis of claims. A review is performed on the improvements in patient safety, as well as professional liability issues in Ophthalmology. There is a high frequency of claims and risk of economic reparation of damage in the event of a claim in Ophthalmology. Special complaints, such as wrong surgery or lack of information, have a high risk of financial compensation and need strong efforts to prevent these potentially avoidable events. Studies focused on pathologies or specific procedures provide information of special interest to sub-specialists. The specialist in Ophthalmology, like any other doctor, is subject to the current legal provisions and appropriate mandatory training in the medical-legal aspects of health care is essential. Professionals must be aware of the fundamental aspects of medical professional liability, as well as specific aspects, such as defensive medicine and clinical safety. The understanding of these medical-legal aspects in the routine clinical practice can help to pave the way towards a satisfactory and safe professional career, and help in increasing patient safety. The aim of this review is to contribute to this training, for the benefit of professionals and patients. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Bayesian hierarchical modeling for detecting safety signals in clinical trials.

    Science.gov (United States)

    Xia, H Amy; Ma, Haijun; Carlin, Bradley P

    2011-09-01

    Detection of safety signals from clinical trial adverse event data is critical in drug development, but carries a challenging statistical multiplicity problem. Bayesian hierarchical mixture modeling is appealing for its ability to borrow strength across subgroups in the data, as well as moderate extreme findings most likely due merely to chance. We implement such a model for subject incidence (Berry and Berry, 2004 ) using a binomial likelihood, and extend it to subject-year adjusted incidence rate estimation under a Poisson likelihood. We use simulation to choose a signal detection threshold, and illustrate some effective graphics for displaying the flagged signals.

  10. Do clinical safety charts improve paramedic key performance indicator results? (A clinical improvement programme evaluation).

    Science.gov (United States)

    Ebbs, Phillip; Middleton, Paul M; Bonner, Ann; Loudfoot, Allan; Elliott, Peter

    2012-07-01

    Is the Clinical Safety Chart clinical improvement programme (CIP) effective at improving paramedic key performance indicator (KPI) results within the Ambulance Service of New South Wales? The CIP intervention area was compared with the non-intervention area in order to determine whether there was a statistically significant improvement in KPI results. The CIP was associated with a statistically significant improvement in paramedic KPI results within the intervention area. The strategies used within this CIP are recommended for further consideration.

  11. MRI with cardiac pacing devices – Safety in clinical practice

    Energy Technology Data Exchange (ETDEWEB)

    Kaasalainen, Touko, E-mail: touko.kaasalainen@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Department of Physics, University of Helsinki (Finland); Pakarinen, Sami, E-mail: sami.pakarinen@hus.fi [HUS Department of Cardiology, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Kivistö, Sari, E-mail: sari.kivisto@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Holmström, Miia, E-mail: miia.holmstrom@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Hänninen, Helena, E-mail: helena.hanninen@hus.fi [HUS Department of Cardiology, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Peltonen, Juha, E-mail: juha.peltonen@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Department of Biomedical Engineering and Computational Science, School of Science, Aalto University, Helsinki (Finland); Lauerma, Kirsi, E-mail: kirsi.lauerma@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland); Sipilä, Outi, E-mail: outi.sipila@hus.fi [HUS Medical Imaging Center, Helsinki University Central Hospital, POB 340 (Haartmaninkatu 4), 00290 Helsinki (Finland)

    2014-08-15

    Objectives: The aim of this study was to introduce a single centre “real life” experience of performing MRI examinations in clinical practice on patients with cardiac pacemaker systems. Additionally, we aimed to evaluate the safety of using a dedicated safety protocol for these patients. Materials and methods: We used a 1.5 T MRI scanner to conduct 68 MRI scans of different body regions in patients with pacing systems. Of the cardiac devices, 32% were MR-conditional, whereas the remaining 68% were MR-unsafe. We recorded the functional parameters of the devices prior, immediately after, and approximately one month after the MRI scanning, and compared the device parameters to the baseline values. Results: All MRI examinations were completed safely, and each device could be interrogated normally following the MRI. We observed no changes in the programmed parameters of the devices. For most of the participants, the distributions of the immediate and one-month changes in the device parameters were within 20% of the baseline values, although some changes approached clinically important thresholds. Furthermore, we observed no differences in the variable changes between MR-conditional and MR-unsafe pacing systems, or between scans of the thorax area and other scanned areas. Conclusion: MRI in patients with MR-conditional pacing systems and selected MR-unsafe systems could be performed safely under strict conditions in this study.

  12. [Research on establishment of clinical safety intensive hospital monitoring net of traditional Chinese medicine injection].

    Science.gov (United States)

    Wang, Lian-Xin; Xie, Yan-Ming; Wang, Zhi-Fei

    2012-09-01

    The establishment of clinical safety monitoring net of traditional Chinese medicine (TCM) injection is the one of the key issues of the monitoring work. The monitoring net is including varieties of types of net, such as clinical monitoring net, multimedia network platform, the net of experts or talents. The paper will introduce the establishing method of clinical safety monitoring net, the establishing of clinical safety monitoring net, and the establishing of network based on the internet, the knowledge network construction of experts, the net construction of talents are all included, to assure the development for clinical safety monitoring work.

  13. Non-clinical safety evaluation of intranasal iota-carrageenan.

    Directory of Open Access Journals (Sweden)

    Alexandra Hebar

    Full Text Available Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

  14. Ethics of safety reporting of a clinical trial

    Directory of Open Access Journals (Sweden)

    Amrita Sil

    2017-01-01

    Full Text Available Clinical trial related injury and serious adverse events (SAE are a major area of concern. In all such scenarios the investigator is responsible for medical care of the trial participant and also ethically bound to report the event to all the stakeholders of the clinical trial. The trial sponsor is responsible for ongoing safety evaluation of the investigational product, reporting and compensating the participant in case of any SAE. The Ethics Committee and regulatory body of the country are to uphold the ethical principles of beneficence, justice, non-maleficence in such cases. Any unwanted and noxious effect of a drug when used in recommended doses is an adverse drug reaction (ADR whereas if causal association is not yet established it is termed adverse event (AE. An AE or ADR that is associated with death, in-patient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, a congenital anomaly, or is otherwise life threatening is termed as an SAE. The principal investigator reports the event to the licensing authority (DCGI, sponsor and Chairperson of the Ethics Committee (EC within 24 hours of occurrence of the SAE. This report is furthered by a detailed report by both the investigator and the EC and given to the DCGI who then gives a final decision on the amount of compensation to be given by the sponsor or the sponsor's representative to the grieving party.

  15. [Innovation in healthcare processes and patient safety using clinical simulation].

    Science.gov (United States)

    Rojo, E; Maestre, J M; Díaz-Mendi, A R; Ansorena, L; Del Moral, I

    2016-01-01

    Many excellent ideas are never implemented or generalised by healthcare organisations. There are two related paradigms: thinking that individuals primarily change through accumulating knowledge, and believing that the dissemination of that knowledge within the organisation is the key element to facilitate change. As an alternative, a description and evaluation of a simulation-based inter-professional team training program conducted in a Regional Health Service to promote and facilitate change is presented. The Department of Continuing Education completed the needs assessment using the proposals presented by clinical units and management. Skills and behaviors that could be learned using simulation were selected, and all personnel from the units participating were included. Experiential learning principles based on clinical simulation and debriefing, were used for the instructional design. The Kirkpatrick model was used to evaluate the program. Objectives included: a) decision-making and teamwork skills training in high prevalence diseases with a high rate of preventable complications; b) care processes reorganisation to improve efficiency, while maintaining patient safety; and, c) implementation of new complex techniques with a long learning curve, and high preventable complications rate. Thirty clinical units organised 39 training programs in the 3 public hospitals, and primary care of the Regional Health Service during 2013-2014. Over 1,559 healthcare professionals participated, including nursing assistants, nurses and physicians. Simulation in healthcare to train inter-professional teams can promote and facilitate change in patient care, and organisational re-engineering. Copyright © 2016 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Patients' perceptions of safety and quality of maternity clinical handover

    Directory of Open Access Journals (Sweden)

    Chin Georgiana SM

    2011-08-01

    Full Text Available Abstract Background Maternity clinical handover serves to address the gaps in knowledge existing when transitions between individuals or groups of clinicians occur throughout the antenatal, intra-partum and postnatal period. There are limited published studies on maternity handover and a paucity of information about patients' perceptions of the same. This paper reports postnatal patients' perceptions of how maternity handover contributes to the quality and safety of maternity care. Methods This paper reports on a mixed-methods study consisting of qualitative interviews and quantitative medical record analysis. Thirty English-speaking postnatal patients who gave birth at an Australian tertiary maternity hospital participated in a semi-structured interview prior to discharge from hospital. Interview data were coded thematically using the constant comparative method and managed via NVivo software; this data set was supplemented by medical record data analysed using STATA. Results Almost half of the women were aware of a handover process. Clinician awareness of patient information was seen as evidence that handover had taken place and was seen as representing positive aspects of teamwork, care and communication by participants, all important factors in the perception of quality health care. Collaborative cross-checking, including the use of cognitive artefacts such as hand held antenatal records and patient-authored birth plans, and the involvement of patients and their support people in handover were behaviours described by participants to be protective mechanisms that enhanced quality and safety of care. These human factors also facilitated team situational awareness (TSA, shared decision making and patient motivation in labour. Conclusions This study illustrates that many patients are aware of handover processes. For some patients, evidence of handover, through clinician awareness of information, represented positive aspects of teamwork, care and

  17. [Clinical safety audits for primary care centers. A pilot study].

    Science.gov (United States)

    Ruiz Sánchez, Míriam; Borrell-Carrió, Francisco; Ortodó Parra, Cristina; Fernàndez I Danés, Neus; Fité Gallego, Anna

    2013-01-01

    To identify organizational processes, violations of rules, or professional performances that pose clinical levels of insecurity. Descriptive cross-sectional survey with customized externally-behavioral verification and comparison of sources, conducted from June 2008 to February 2010. Thirteen of the 53 primary care teams (PCT) of the Catalonian Health Institute (ICS Costa de Ponent, Barcelona). Employees of 13 PCT classified into: director, nurse director, customer care administrators, and general practitioners. Non-random selection, teaching (TC)/non-teaching, urban (UC)/rural and small/large (LC) health care centers (HCC). A total of 33 indicators were evaluated; 15 of procedures, 9 of attitude, 3 of training, and 6 of communication. Level of uncertainty: <50% positive answers for each indicator. no collaboration. A total of 55 professionals participated (84.6% UC, 46.2% LC and 76.9% TC). Rank distribution: 13 customer care administrators, 13 nurse directors, 13 HCC directors, and 16 general practitioners. Levels of insecurity emerged from the following areas: reception of new medical professionals, injections administration, nursing weekend home calls, urgent consultations to specialists, aggressive patients, critical incidents over the agenda of the doctors, communication barriers with patients about treatment plans, and with immigrants. Clinical safety is on the agenda of the health centers. Identified areas of uncertainty are easily approachable, and are considered in the future system of accreditation of the Catalonian Government. General practitioners are more critical than directors, and teaching health care centers, rural and small HCC had a better sense of security. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  18. Deriving meaningful insights from clinical trial and postmarketing safety data: Perspectives from India

    Directory of Open Access Journals (Sweden)

    Anand Harugeri

    2017-01-01

    Full Text Available Today, drug safety data collection in India is both manual and electronic with reporting of potential overlapping and duplicate data, which is likely incomplete for further review and analysis. Furthermore, standardized data collection and timelines are not aligned with international standards. Complete coverage of safety data from all sources throughout the life of the drug cannot be ensured. There is no requirement to submit periodic safety data in clinical trials to regulatory authority. There is clearly a lack of emphasis on deriving meaningful safety data insights for ensuring patient safety. Efforts toward the early detection of drug safety issues are minimal. There is no mandate to publicly disclose drug safety findings. Benefit-risk evaluation of investigational and marketed products cannot be assured merely through annual status reports and periodic safety update reports, respectively. Focused initiatives involving stakeholders from regulatory, health-care, and pharmaceutical industries are required to change the current situation and enable derivation of meaningful insights from safety data. Equal emphasis on assessing real-time safety of the drugs and protection of patients' rights, safety, and well-being is required. Periodic safety data reporting in clinical trials, proactive safety data collection related to potential safety concerns, electronic medical records, electronic expedited reporting, collection of targeted data from stakeholders, and standardized and harmonized data collection aligned to the International Council for Harmonization guidelines are required. The Central Drugs Standard Control Organization should implement requirements to submit Development Safety Update Reports, Periodic Benefit-Risk Evaluation Reports, and Risk Management Plans. Access to clinical trials and postmarketing safety data through central repository would enable researchers to explore the data for application in clinical practice.

  19. Deriving meaningful insights from clinical trial and postmarketing safety data: Perspectives from India

    Science.gov (United States)

    Harugeri, Anand; Shastri, Vineet; Patel, Chanakya

    2017-01-01

    Today, drug safety data collection in India is both manual and electronic with reporting of potential overlapping and duplicate data, which is likely incomplete for further review and analysis. Furthermore, standardized data collection and timelines are not aligned with international standards. Complete coverage of safety data from all sources throughout the life of the drug cannot be ensured. There is no requirement to submit periodic safety data in clinical trials to regulatory authority. There is clearly a lack of emphasis on deriving meaningful safety data insights for ensuring patient safety. Efforts toward the early detection of drug safety issues are minimal. There is no mandate to publicly disclose drug safety findings. Benefit-risk evaluation of investigational and marketed products cannot be assured merely through annual status reports and periodic safety update reports, respectively. Focused initiatives involving stakeholders from regulatory, health-care, and pharmaceutical industries are required to change the current situation and enable derivation of meaningful insights from safety data. Equal emphasis on assessing real-time safety of the drugs and protection of patients' rights, safety, and well-being is required. Periodic safety data reporting in clinical trials, proactive safety data collection related to potential safety concerns, electronic medical records, electronic expedited reporting, collection of targeted data from stakeholders, and standardized and harmonized data collection aligned to the International Council for Harmonization guidelines are required. The Central Drugs Standard Control Organization should implement requirements to submit Development Safety Update Reports, Periodic Benefit-Risk Evaluation Reports, and Risk Management Plans. Access to clinical trials and postmarketing safety data through central repository would enable researchers to explore the data for application in clinical practice. PMID:28447016

  20. Fesoterodine in randomised clinical trials: an updated systematic clinical review of efficacy and safety.

    Science.gov (United States)

    Dell'Utri, Chiara; Digesu, G Alessandro; Bhide, Alka; Khullar, Vik

    2012-10-01

    This is a systematic review of clinical data assessing the safety, efficacy and tolerability of fesoterodine in randomised control trials (RCTs) in the treatment of overactive bladder (OAB). We performed a MEDLINE literature search of articles published between 2005 and 2010 regarding the efficacy and safety of fesoterodine. The US Food and Drug Administration Web site was also searched for RCTs. Two studies demonstrated significant improvement of OAB symptoms with fesoterodine compared with placebo. Two phase III studies showed both doses of fesoterodine to be more effective than placebo for most symptoms. Another phase III trial confirmed the superiority of 8 mg fesoterodine compared with tolterodine ER 4 mg. Dry mouth was the commonest side effect. Fesoterodine is effective for treating OAB symptoms. Its once-daily dosing regime and the flexibility to increase the dose are appealing factors.

  1. Measuring patient safety in a UK dental hospital: development of a dental clinical effectiveness dashboard.

    Science.gov (United States)

    Pemberton, M N; Ashley, M P; Shaw, A; Dickson, S; Saksena, A

    2014-10-01

    Patient safety is an important marker of quality for any healthcare organisation. In 2008, the British Government white paper entitled High quality care for all, resulting from a review led by Lord Darzi, identified patient safety as a key component of quality and discussed how it might be measured, analysed and acted upon. National and local clinically curated metrics were suggested, which could be displayed via a 'clinical dashboard'. This paper explains the development of a clinical effectiveness dashboard focused on patient safety in an English dental hospital and how it has helped us identify relevant patient safety issues in secondary dental care.

  2. Safety of telemental healthcare delivered to clinically unsupervised settings: a systematic review.

    Science.gov (United States)

    Luxton, David D; Sirotin, Anton P; Mishkind, Matthew C

    2010-01-01

    The safety of telemental healthcare delivered to clinically unsupervised settings, such as a personal residence, must be established to inform policy and further the dissemination of telemental health programs. The aim of this article is to provide an overview of safety issues associated with telemental healthcare and, through a systematic literature review, evaluate the safety of telemental healthcare delivered to unsupervised settings. The review resulted in a total of nine studies that specifically evaluated the delivery of telemental healthcare to unsupervised settings. Six of the nine studies reviewed explicitly described safety plans or specific precautions that could be used if necessary. Two of the nine studies reported events that required the researchers to use safety procedures to effectively respond to concerns they had regarding participant safety. In both of these studies, the issues were resolved with prescribed safety procedures. Recommendations and future directions for the development and evaluation of safety protocols are discussed.

  3. Safety of Mesenchymal Stem Cells for Clinical Application

    Directory of Open Access Journals (Sweden)

    Youwei Wang

    2012-01-01

    Full Text Available Mesenchymal stem cells (MSCs hold great promise as therapeutic agents in regenerative medicine and autoimmune diseases, based on their differentiation abilities and immunosuppressive properties. However, the therapeutic applications raise a series of questions about the safety of culture-expanded MSCs for human use. This paper summarized recent findings about safety issues of MSCs, in particular their genetic stability in long-term in vitro expansion, their cryopreservation, banking, and the role of serum in the preparation of MSCs.

  4. Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

    Science.gov (United States)

    Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

    2016-12-15

    Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

  5. [Strategies for patient participation in continuing improvement of clinical safety].

    Science.gov (United States)

    Saturno, Pedro J

    2009-06-01

    Strategies for patient participation in quality improvement, as an active part of processes or providing relevant information when asked, have progressed to a great extent for the last few years, influenced by the emphasis on patient-focused care as a key dimension for quality and, lately, by the emphasis on patient safety -a dimension for which the patient contribution can not be ignored. However, these strategies have not been fully implemented and used in most quality management systems. This article aims to make it easier to select the appropriate strategies for a given context, by describing them, grouped in three main themes (mobilising patients for patient safety; promoting active participation of patients in the prevention of safety incidents; requesting and using the relevant information for quality improvement that patients can provide), illustrating them with examples, and pointing out some of the obstacles for implementing them.

  6. Efficacy and Safety of Rituximab in Children with Refractory Nephrotic Syndrome; A Multicenter Clinical Trial

    Directory of Open Access Journals (Sweden)

    Yo Han Ahn

    2014-06-01

    Conclusions: In this interim analysis of clinical trial to evaluate the efficacy and safety of RTX in children with refractory NS, RTX treatment for refractory NS was safe and effective, especially in patients with DNS.

  7. Analysis of Safety from a Human Clinical Trial with Pterostilbene

    Directory of Open Access Journals (Sweden)

    Daniel M. Riche

    2013-01-01

    Full Text Available Objectives. The purpose of this trial was to evaluate the safety of long-term pterostilbene administration in humans. Methodology. The trial was a prospective, randomized, double-blind placebo-controlled intervention trial enrolling patients with hypercholesterolemia (defined as a baseline total cholesterol ≥200 mg/dL and/or baseline low-density lipoprotein cholesterol ≥100 mg/dL. Eighty subjects were divided equally into one of four groups: (1 pterostilbene 125 mg twice daily, (2 pterostilbene 50 mg twice daily, (3 pterostilbene 50 mg + grape extract (GE 100 mg twice daily, and (4 matching placebo twice daily for 6–8 weeks. Safety markers included biochemical and subjective measures. Linear mixed models were used to estimate primary safety measure treatment effects. Results. The majority of patients completed the trial (91.3%. The average age was 54 years. The majority of patients were females (71% and Caucasians (70%. There were no adverse drug reactions (ADRs on hepatic, renal, or glucose markers based on biochemical analysis. There were no statistically significant self-reported or major ADRs. Conclusion. Pterostilbene is generally safe for use in humans up to 250 mg/day.

  8. Analysis of safety from a human clinical trial with pterostilbene.

    Science.gov (United States)

    Riche, Daniel M; McEwen, Corey L; Riche, Krista D; Sherman, Justin J; Wofford, Marion R; Deschamp, David; Griswold, Michael

    2013-01-01

    Objectives. The purpose of this trial was to evaluate the safety of long-term pterostilbene administration in humans. Methodology. The trial was a prospective, randomized, double-blind placebo-controlled intervention trial enrolling patients with hypercholesterolemia (defined as a baseline total cholesterol ≥200 mg/dL and/or baseline low-density lipoprotein cholesterol ≥100 mg/dL). Eighty subjects were divided equally into one of four groups: (1) pterostilbene 125 mg twice daily, (2) pterostilbene 50 mg twice daily, (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily, and (4) matching placebo twice daily for 6-8 weeks. Safety markers included biochemical and subjective measures. Linear mixed models were used to estimate primary safety measure treatment effects. Results. The majority of patients completed the trial (91.3%). The average age was 54 years. The majority of patients were females (71%) and Caucasians (70%). There were no adverse drug reactions (ADRs) on hepatic, renal, or glucose markers based on biochemical analysis. There were no statistically significant self-reported or major ADRs. Conclusion. Pterostilbene is generally safe for use in humans up to 250 mg/day.

  9. SAFETY

    CERN Document Server

    Niels Dupont

    2013-01-01

    CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

  10. Safety profile of Cerebrolysin: clinical experience from dementia and stroke trials.

    Science.gov (United States)

    Thome, J; Doppler, E

    2012-04-01

    The safety of Cerebrolysin has been shown through many years of clinical use, observations from postmarketing surveillance studies, and safety data from randomized, controlled clinical trials. The reported events showed that adverse reactions to Cerebrolysin were generally mild and transient. Most common adverse events included vertigo, agitation and feeling hot. In the controlled clinical trials analyzed for this report, the incidence of adverse events was similar in Cerebrolysin- and placebo-treated groups. Cerebrolysin seems to be safe when used in combination with recombinant tissue-type plasminogen activator or cholinesterase inhibitors such as donepezil or rivastigmine. To our knowledge, Cerebrolysin was not associated with major changes in vital signs or laboratory parameters.

  11. Safety

    CERN Multimedia

    2003-01-01

    Please note that the safety codes A9, A10 AND A11 (ex annexes of SAPOCO/42) entitled respectively "Safety responsibilities in the divisions" "The safety policy committee (SAPOCO) and safety officers' committees" and "Administrative procedure following a serious accident or incident" are available on the web at the following URLs: Code A9: http://edms.cern.ch/document/337016/LAST_RELEASED Code A10: http://edms.cern.ch/document/337019/LAST_RELEASED Code A11: http://edms.cern.ch/document/337026/LAST_RELEASED Paper copies can also be obtained from the TIS divisional secretariat, e-mail: tis.secretariat@cern.ch. TIS Secretariat

  12. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

    Directory of Open Access Journals (Sweden)

    W. B. Mattes

    2013-01-01

    Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

  13. Effectiveness and safety of natalizumab in real-world clinical practice: Review of observational studies.

    Science.gov (United States)

    van Pesch, Vincent; Sindic, Christian J; Fernández, Oscar

    2016-10-01

    Clinical trials have shown that natalizumab is highly effective for treating relapsing forms of multiple sclerosis (MS). The purpose of this analysis was to conduct a targeted review of data from country-specific observational studies and registries of natalizumab-treated patients with relapsing MS in order to more fully investigate the longer-term effectiveness and safety of this disease-modifying therapy in real-world clinical practice settings. A PubMed search was conducted on March 13, 2014, using the terms (natalizumab AND multiple sclerosis) AND (observational OR registry OR post-marketing OR clinical practice). Only English-language papers that reported effectiveness (in terms of effects on relapses, disability progression, and magnetic resonance imaging findings) and/or safety results from studies were included. Data from 22 studies/registries were included. Annualized relapse rates decreased by 73%-94% from baseline across the studies, with improvement maintained for up to 5 years during natalizumab treatment. Natalizumab effectiveness was also demonstrated via assessment of disability progression (Expanded Disability Status Scale), radiological measures, and no-evidence-of-disease-activity measures (clinical, radiological, and overall). Results were similar among patient groups stratified by level of disease activity. Safety outcomes were consistent with natalizumab's known safety profile. Data from country-specific observational studies and registries varying in size and scope support the effectiveness and safety of natalizumab in a broad range of patients in clinical practice.

  14. Preclinical and clinical safety studies on DNA vaccines.

    NARCIS (Netherlands)

    Schalk, Johanna A C; Mooi, Frits R; Berbers, Guy A M; Aerts, Leon A G J M van; Ovelgönne, Hans; Kimman, Tjeerd G

    2007-01-01

    DNA vaccines are based on the transfer of genetic material, encoding an antigen, to the cells of the vaccine recipient. Despite high expectations of DNA vaccines as a result of promising preclinical data their clinical utility remains unproven. However, much data is gathered in preclinical and

  15. Preclinical and clinical safety studies on DNA vaccines.

    NARCIS (Netherlands)

    Schalk, Johanna A C; Mooi, Frits R; Berbers, Guy A M; Aerts, Leon A G J M van; Ovelgönne, Hans; Kimman, Tjeerd G

    2007-01-01

    DNA vaccines are based on the transfer of genetic material, encoding an antigen, to the cells of the vaccine recipient. Despite high expectations of DNA vaccines as a result of promising preclinical data their clinical utility remains unproven. However, much data is gathered in preclinical and clini

  16. Joint modeling of clinical efficacy and safety with an application to diabetes studies.

    Science.gov (United States)

    Zhao, Yang; Shen, Wei; Fu, Haoda

    2013-01-01

    The purpose of drug development is to evaluate a drug's efficacy and safety profile. For a personalized medicine, it is important for patients and health care providers to understand the efficacy and safety trade-off when selecting a dose for a patient. In this article, we propose three different methods for jointly modeling the clinical safety and efficacy endpoints. These three methods model the correlation relationship in three different ways: modeling the joint distribution by a copula method, modeling conditional distributions, and modeling their correlations through individual means by a hierarchical model. We compare these three methods through simulations and apply these methods to a data set from a diabetes study.

  17. Prediction of Driving Safety in Individuals with Homonymous Hemianopia and Quadrantanopia from Clinical Neuroimaging

    Directory of Open Access Journals (Sweden)

    Michael S. Vaphiades

    2014-01-01

    Full Text Available Background. This study aimed to determine whether it is possible to predict driving safety of individuals with homonymous hemianopia or quadrantanopia based upon a clinical review of neuroimages that are routinely available in clinical practice. Methods. Two experienced neuroophthalmologists viewed a summary report of the CT/MRI scans of 16 participants with homonymous hemianopic or quadrantanopic field defects which indicated the site and extent of the lesion and they made predictions regarding whether participants would be safe/unsafe to drive. Driving safety was independently defined at the time of the study using state-recorded motor vehicle crashes (all crashes and at-fault for the previous 5 years and ratings of driving safety determined through a standardized on-road driving assessment by a certified driving rehabilitation specialist. Results. The ability to predict driving safety was highly variable regardless of the driving safety measure, ranging from 31% to 63% (kappa levels ranged from −0.29 to 0.04. The level of agreement between the neuroophthalmologists was only fair (kappa = 0.28. Conclusions. Clinical evaluation of summary reports of currently available neuroimages by neuroophthalmologists is not predictive of driving safety. Future research should be directed at identifying and/or developing alternative tests or strategies to better enable clinicians to make these predictions.

  18. [Clinical analysis of safety and effectiveness of electroconvulsive therapy].

    Science.gov (United States)

    Dabrowski, Marek; Parnowski, Tadeusz

    2012-01-01

    The aim of the study was to assess efficacy and safety of electroconvulsive therapy. 43 patients included into the study were hospitalised in The Institute of Psychiatry and Neurology and received all together over 400 bilateral electroconvulsive procedures. Most of the patients (N = 25) were qualified for electroconvulsive therapy due to treatment resistant depression (58.1%). Six patients: 2 with catatonia and 4 with depression had life saving indications for electroconvulsive therapy. Three patients (7%) were excluded from electroconvulsive therapy, following 1 or 2 electroconvulsive procedures. Forty patients continued electroconvulsive therapy. There were no complications and serious adverse events in patients who continued electroconvulsive therapy. Generally, electroconvulsive therapy was well tolerated and treatment had been cut down in only one case due to adverse events and high risk related to the procedure. Transient cardiac arrhythmias (10% of patients) were the most often occurring adverse events and patients (35%) mostly reported headaches. We observed remission in 22 patients (58%) and improvement in 14 patients (35%) following electroconvulsive treatment. Only 4 patients (10%) had no benefit after a series of electroconvulsive procedures. Electroconvulsive treatment was most effective in patients with catatonia (80% patients had full recovery) and in depressive patients with bipolar disorder (73% patients had full recovery). Electroconvulsive procedures were safe and effective. Electroconvulsive treatment was most effective in catatonic patients with schizophrenia and in depressive patients with bipolar disorder.

  19. Efficacy and Safety of Saffron Supplementation: Current Clinical Findings.

    Science.gov (United States)

    Broadhead, G K; Chang, A; Grigg, J; McCluskey, P

    2016-12-09

    Saffron (Crocus savitus) is a Middle-Eastern herb with strong antioxidant properties. Its major constituents, safranal, crocin, and crocetin, are also antioxidants and bear structural similarities to other well-known natural antixodant substances, such as zeaxanthin. Given the role of oxidative stress in many diseases, considerable interest has been shown into the potential role of saffron supplementation as a treatment for a range of diseases. In vitro and animal studies have provided evidence that saffron and its constituents may be potent therapies for a range of pathologies, including Alzheimer's disease, age-related macular degeneration (AMD) and cardiac ischemia. Whether these findings translate into clinical efficacy, however, has as of yet been incompletely assessed. This makes assessing the role of saffron supplementation in these diseases difficult. Here, we review the current human clinical evidence supporting saffron supplementation as a treatment for a range of pathologies and the underlying science supporting its use.

  20. Clinical Office Safety: Strategies to Enhance the Safety of Staff and Clients

    Science.gov (United States)

    Wilson, Richard M.

    2012-01-01

    Mental health practitioners' exposure to threats and acts of nonfatal violence are among the highest of all professions. Implementing a comprehensive workplace violence prevention program specific to the clinical setting is paramount to decreasing these risks. However, generic security recommendations at times come in conflict with the…

  1. Clinical Outcome and Safety of Multilevel Vertebroplasty: Clinical Experience and Results

    Energy Technology Data Exchange (ETDEWEB)

    Mailli, Leto, E-mail: lmailli@hotmail.com; Filippiadis, Dimitrios K.; Brountzos, Elias N.; Alexopoulou, Efthymia; Kelekis, Nikolaos; Kelekis, Alexios [Attikon University Hospital, Second Department of Radiology, Athens University School of Medicine (Greece)

    2013-02-15

    To compare safety and efficacy of percutaneous vertebroplasty (PVP) when treating up to three vertebrae or more than three vertebrae per session. We prospectively compared two groups of patients with symptomatic vertebral fractures who had no significant response to conservative therapy. Pathologic substrate included osteoporosis (n = 77), metastasis (n = 24), multiple myeloma (n = 13), hemangioma (n = 15), and lymphoma (n = 1). Group A patients (n = 94) underwent PVP of up to three treated vertebrae (n = 188). Group B patients (n = 36) underwent PVP with more than three treated vertebrae per session (n = 220). Decreased pain and improved mobility were recorded the day after surgery and at 12 and 24 months after surgery per clinical evaluation and the use of numeric visual scales (NVS): the Greek Brief Pain Inventory, a linear analogue self-assessment questionnaire, and a World Health Organization questionnaire. Group A presented with a mean pain score of 7.9 {+-} 1.1 NVS units before PVP, which decreased to 2.1 {+-} 1.6, 2.0 {+-} 1.5 and 2.0 {+-} 1.5 NVS units the day after surgery and at 12 and 24 months after surgery, respectively. Group B presented with a mean pain score of 8.1 {+-} 1.3 NVS units before PVP, which decreased to 2.2 {+-} 1.3, 2.0 {+-} 1.5, and 2.1 {+-} 1.6 NVS units the day after surgery and at 12 and 24 months after surgery, respectively. Overall pain decrease and mobility improvement throughout the follow-up period presented no statistical significance neither between the two groups nor between different underlying aetiology. Reported cement leakages presented no statistical significance between the two groups (p = 0.365). PVP is an efficient and safe technique for symptomatic vertebral fractures independently of the vertebrae number treated per session.

  2. Patient safety and quality of care: How may clinical simulation contribute?

    Directory of Open Access Journals (Sweden)

    Sanne Jensen

    2015-09-01

    Full Text Available The usability of health information technology (IT is increasingly recognized as critically important to the development of systems that ensure patient safety and quality of care. The substantial complexity of organizations, work practice and physical environments within the healthcare sector influences the development and application of health IT. When health IT is introduced in local clinical work practices, potential patient safety hazards and insufficient support of work practices need to be examined. Qualitative methods, such as clinical simulation, may be used to evaluate new technology in correlation with the clinical context and to study the interaction between users, technology and work practice. Compared with the “classic” methods, such as heuristic inspection and usability testing, clinical simulation takes the clinical context into account. Clinical simulation can be useful in many processes in the human-centred design cycle. In the requirement specification, clinical simulation can be useful to analyze user requirements and work practice as well to evaluate requirements. In the design of health IT, clinical simulation can be used to evaluate clinical information systems and serve as common ground to help to achieve a shared understanding between various communities of practice. In a public procurement process, a clinical simulation-based assessment can help give insight into different solutions and how they support work practice. Before organizational implementation, clinical simulation is a very suitable means, by which to assess an application in connection with work practice.

  3. Safety and tolerability of rufinamide in children with epilepsy: a pooled analysis of 7 clinical studies.

    Science.gov (United States)

    Wheless, James W; Conry, Joan; Krauss, Gregory; Mann, Allison; LoPresti, Antonia; Narurkar, Milind

    2009-12-01

    Rufinamide is a novel antiepileptic agent recently approved in the United States for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome. To help inform clinical decision making, the authors analyzed safety and tolerability data from the entire pediatric population in the rufinamide epilepsy clinical development program. The analysis population comprised 212 rufinamide-treated (age range 3-16 years) and 197 placebo patients (age range 4-17 years) in the double-blind studies, and 391 patients receiving rufinamide in the double-blind and/or open-label extensions. The most common adverse effects observed in rufinamide-treated patients in the double-blind studies were somnolence, vomiting, and headache. Changes in laboratory values, vital signs, and weight were generally clinically insignificant. This pooled analysis of data from pediatric patients in clinical studies of rufinamide for the treatment of seizures, mainly as adjunctive therapy, suggests a favorable safety and tolerability profile in this patient population.

  4. Factors shaping effective utilization of health information technology in urban safety-net clinics.

    Science.gov (United States)

    George, Sheba; Garth, Belinda; Fish, Allison; Baker, Richard

    2013-09-01

    Urban safety-net clinics are considered prime targets for the adoption of health information technology innovations; however, little is known about their utilization in such safety-net settings. Current scholarship provides limited guidance on the implementation of health information technology into safety-net settings as it typically assumes that adopting institutions have sufficient basic resources. This study addresses this gap by exploring the unique challenges urban resource-poor safety-net clinics must consider when adopting and utilizing health information technology. In-depth interviews (N = 15) were used with key stakeholders (clinic chief executive officers, medical directors, nursing directors, chief financial officers, and information technology directors) from staff at four clinics to explore (a) nonhealth information technology-related clinic needs, (b) how health information technology may provide solutions, and (c) perceptions of and experiences with health information technology. Participants identified several challenges, some of which appear amenable to health information technology solutions. Also identified were requirements for effective utilization of health information technology including physical infrastructural improvements, funding for equipment/training, creation of user groups to share health information technology knowledge/experiences, and specially tailored electronic billing guidelines. We found that despite the potential benefit that can be derived from health information technologies, the unplanned and uninformed introduction of these tools into these settings might actually create more problems than are solved. From these data, we were able to identify a set of factors that should be considered when integrating health information technology into the existing workflows of low-resourced urban safety-net clinics in order to maximize their utilization and enhance the quality of health care in such settings.

  5. Safety reporting in developing country vaccine clinical trials-a systematic review.

    Science.gov (United States)

    Muehlhans, Susann; Richard, Georgina; Ali, Mohammad; Codarini, Gabriela; Elemuwa, Chris; Khamesipour, Ali; Maurer, Wolfgang; Mworozi, Edison; Kochhar, Sonali; Rundblad, Gabriella; Vuitton, Dominique; Rath, Barbara

    2012-05-09

    With more vaccines becoming available worldwide, vaccine research is on the rise in developing countries. To gain a better understanding of safety reporting from vaccine clinical research in developing countries, we conducted a systematic review in Medline and Embase (1989-2011) of published randomized clinical trials (RCTs) reporting safety outcomes with ≥50% developing country participation (PROSPERO systematic review registration number: CRD42012002025). Developing country vaccine RCTs were analyzed with respect to the number of participants, age groups studied, inclusion of safety information, number of reported adverse events following immunization (AEFI), type and duration of safety follow-up, use of standardized AEFI case definitions, grading of AEFI severity, and the reporting of levels of diagnostic certainty for AEFI. The systematic search yielded a total number of 50 randomized vaccine clinical trials investigating 12 different vaccines, most commonly rotavirus and malaria vaccines. In these trials, 94,459 AEFI were reported from 446,908 participants receiving 735,920 vaccine doses. All 50 RCTs mentioned safety outcomes with 70% using definitions for at least one AEFI. The most commonly defined AEFI was fever (27), followed by local (16) and systemic reactions (14). Logistic regression analysis revealed a positive correlation between the implementation of a fever case definition and the reporting rate for fever as an AEFI (p=0.027). Overall, 16 different definitions for fever and 7 different definitions for erythema were applied. Predefined AEFI case definitions by the Brighton Collaboration were used in only two out of 50 RCTs. The search was limited to RCTs published in English or German and may be missing studies published locally. The reported systematic review suggests room for improvement with respect to the harmonization of safety reporting from developing country vaccine clinical trials and the implementation of standardized case definitions.

  6. Integrating quality and safety education into clinical nursing education through a dedicated education unit.

    Science.gov (United States)

    Masters, Kelli

    2016-03-01

    The Institute of Medicine and American Association of Colleges of Nursing are calling for curriculum redesign that prepares nursing students with the requisite knowledge and skills to provide safe, high quality care. The purpose of this project was to improve nursing students' knowledge of quality and safety by integrating Quality and Safety Education for Nurses into clinical nursing education through development of a dedicated education unit. This model, which pairs nursing students with front-line nursing staff for clinical experiences, was implemented on a medical floor in an acute care hospital. Prior to implementation, nurses and students were educated about the dedicated education unit and quality and safety competencies. During each clinical rotation, students collaborated with their nurses on projects related to these competencies. Students' knowledge was assessed using questions related to quality and safety. Students who participated in the dedicated education unit had higher scores than those with traditional clinical rotations. Focus groups were held mid-semester to assess nurses' perceptions of the experience. Five themes emerged from the qualitative data including thirsting for knowledge, building teamwork and collaboration, establishing trust and decreasing anxiety, mirroring organization and time management skills, and evolving confidence in the nursing role. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Medication Safety in Clinical Trials: Role of the Pharmacist in Optimizing Practice, Collaboration, and Education to Reduce Errors.

    Science.gov (United States)

    Brown, Jamie N; Britnell, Sara R; Stivers, Andrew P; Cruz, Jennifer L

    2017-03-01

    Standardized safety practices for investigational drugs in clinical research protocols are limited and the vast majority of research pharmacists have concerns regarding its safety. Identified areas for medication safety risks include protocol complexity, medication ordering, and the processes for packaging, storage, and dispensing investigational medications. Inclusion of a pharmacist creates multiple mechanisms to promote safety and improve the quality of clinical research. This is accomplished through collaborating in the development of a research protocol, reviewing as a member of an advisory committee, developing mechanisms that contribute to safety, and assuring compliance with local and national regulations and standards. Ultimately, the profession of pharmacy has foundational responsibility for assuring the safe and effective use of medications, including investigational drugs in clinical research. It is through multidisciplinary collaboration that a research study will attain the highest standards for safety and maximize the quality and effectiveness of the data obtained in the clinical trial.

  8. Medication Safety in Clinical Trials: Role of the Pharmacist in Optimizing Practice, Collaboration, and Education to Reduce Errors

    Science.gov (United States)

    Brown, Jamie N.; Britnell, Sara R.; Stivers, Andrew P.; Cruz, Jennifer L.

    2017-01-01

    Standardized safety practices for investigational drugs in clinical research protocols are limited and the vast majority of research pharmacists have concerns regarding its safety. Identified areas for medication safety risks include protocol complexity, medication ordering, and the processes for packaging, storage, and dispensing investigational medications. Inclusion of a pharmacist creates multiple mechanisms to promote safety and improve the quality of clinical research. This is accomplished through collaborating in the development of a research protocol, reviewing as a member of an advisory committee, developing mechanisms that contribute to safety, and assuring compliance with local and national regulations and standards. Ultimately, the profession of pharmacy has foundational responsibility for assuring the safe and effective use of medications, including investigational drugs in clinical research. It is through multidisciplinary collaboration that a research study will attain the highest standards for safety and maximize the quality and effectiveness of the data obtained in the clinical trial. PMID:28356900

  9. Patient-centered medical home intervention at an internal medicine resident safety-net clinic.

    Science.gov (United States)

    Hochman, Michael E; Asch, Steven; Jibilian, Arek; Chaudry, Bharat; Ben-Ari, Ron; Hsieh, Eric; Berumen, Margaret; Mokhtari, Shahrod; Raad, Mohamad; Hicks, Elisabeth; Sanford, Crystal; Aguirre, Norma; Tseng, Chi-hong; Vangala, Sitaram; Mangione, Carol M; Goldstein, David A

    2013-10-14

    The patient-centered medical home (PCMH) model holds promise for improving primary care delivery, but it has not been adequately tested in teaching settings. We implemented an intervention guided by PCMH principles at a safety-net teaching clinic with resident physician providers. Two similar clinics served as controls. Using a cross-sectional design, we measured the effect on patient and resident satisfaction using the Consumer Assessment of Healthcare Providers and Systems survey and a validated teaching clinic survey, respectively. Both surveys were conducted at baseline and 1 year after the intervention. We also measured the effect on emergency department and hospital utilization. Following implementation of our intervention, the clinic’s score on the National Committee for Quality Assurance’s PCMH certification tool improved from 35 to 53 of 100 possible points, although our clinic did not achieve all must-pass elements to qualify as a PCMH. During the 1-year study period, 4676 patients were exposed to the intervention; 39.9% of these used at least 1 program component. Compared with baseline, patient-reported access and overall satisfaction improved to a greater extent in the intervention clinic, and the composite satisfaction rating increased from 48% to 65% in the intervention clinic vs from 50% to 59% in the control sites (P = .04). The improvements were particularly notable for questions relating to access. For example, satisfaction with urgent appointment scheduling increased from 12% to 53% in the intervention clinic vs from 14% to 18% in the control clinics (P < .001). Resident satisfaction also improved in the intervention clinic: the composite satisfaction score increased from 39% to 51% in the intervention clinic vs a decrease from 46% to 42% in the control clinics (P = .01). Emergency department utilization did not differ significantly between the intervention and control clinics, and hospitalizations increased from 26 to 27 visits

  10. Increasing Research Capacity in a Safety Net Setting Through an Academic Clinical Partnership.

    Science.gov (United States)

    Brooks Carthon, J Margo; Holland, Sara; Gamble, Kerry; Rothwell, Helyn; Pancir, Darcy; Ballinghoff, Jim; Aiken, Linda

    2017-06-01

    Safety net settings care for a disproportionate share of low-resource patients often have fewer resources to invest in nursing research. To address this dilemma, an academic-clinical partnership was formed in an effort to increase nursing research capacity at a safety net setting. Penn Presbyterian Medical Center and the Center for Health Outcomes and Policy Research located at the University of Pennsylvania partnered researchers and baccalaureate-prepared nurses in an 18-month research skill development program. This article describes the programmatic design, conceptual framework, resource requirements, and effect on the institutional partners and participants.

  11. Clinically relevant safety issues associated with St. John's wort product labels

    Directory of Open Access Journals (Sweden)

    Rutledge Jennifer C

    2008-07-01

    Full Text Available Abstract Background St. John's wort (SJW, used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA. Methods Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin, contraindications (bipolar disorder, therapeutic duplication (antidepressants, and general considerations (phototoxicity and advice to consult a healthcare professional (HCP. A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings. Results Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1% provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%, SJW-immunosupressants (5.4%, SJW-OCPs (8.1%, SJW-warfarin (5.4%, bipolar (1.4%, antidepressants (23.0%, phototoxicity (51.4%, and consult HCP (87.8%. Other safety-related information on labels included warnings about pregnancy (74.3%, lactation (64.9%, discontinue if adverse reaction (23.0%, and not for use in patients under 18 years old (13.5%. The average number of a priori safety issues included on a product label was 1.91 (range 0–8 for 23.9% completeness. Conclusion The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety

  12. Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

    Directory of Open Access Journals (Sweden)

    Mpimbaza Arthur

    2008-06-01

    Full Text Available Abstract Background New antimalarial regimens, including artemisinin-based combination therapies (ACTs, have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. Case description Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. Discussion and evaluation Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. Conclusion Although the World Health Organization has supported the development of

  13. Clinical Trial of a Home Safety Toolkit for Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Kathy J. Horvath

    2013-01-01

    Full Text Available This randomized clinical trial tested a new self-directed educational intervention to improve caregiver competence to create a safer home environment for persons with dementia living in the community. The sample included 108 patient/caregiver dyads: the intervention group (n=60 received the Home Safety Toolkit (HST, including a new booklet based on health literacy principles, and sample safety items to enhance self-efficacy to make home safety modifications. The control group (n=48 received customary care. Participants completed measures at baseline and at twelve-week follow-up. Multivariate Analysis of Covariance (MANCOVA was used to test for significant group differences. All caregiver outcome variables improved in the intervention group more than in the control. Home safety was significant at P≤0.001, caregiver strain at P≤0.001, and caregiver self-efficacy at P=0.002. Similarly, the care receiver outcome of risky behaviors and accidents was lower in the intervention group (P≤0.001. The self-directed use of this Home Safety Toolkit activated the primary family caregiver to make the home safer for the person with dementia of Alzheimer's type (DAT or related disorder. Improving the competence of informal caregivers is especially important for patients with DAT in light of all stakeholders reliance on their unpaid care.

  14. SAFETY

    CERN Multimedia

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

    Fire Safety – Essential for a particle detector The CMS detector is a marvel of high technology, one of the most precise particle measurement devices we have built until now. Of course it has to be protected from external and internal incidents like the ones that can occur from fires. Due to the fire load, the permanent availability of oxygen and the presence of various ignition sources mostly based on electricity this has to be addressed. Starting from the beam pipe towards the magnet coil, the detector is protected by flooding it with pure gaseous nitrogen during operation. The outer shell of CMS, namely the yoke and the muon chambers are then covered by an emergency inertion system also based on nitrogen. To ensure maximum fire safety, all materials used comply with the CERN regulations IS 23 and IS 41 with only a few exceptions. Every piece of the 30-tonne polyethylene shielding is high-density material, borated, boxed within steel and coated with intumescent (a paint that creates a thick co...

  15. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

      “Safety is the highest priority”: this statement from CERN is endorsed by the CMS management. An interpretation of this statement may bring you to the conclusion that you should stop working in order to avoid risks. If the safety is the priority, work is not! This would be a misunderstanding and misinterpretation. One should understand that “working safely” or “operating safely” is the priority at CERN. CERN personnel are exposed to different hazards on many levels on a daily basis. However, risk analyses and assessments are done in order to limit the number and the gravity of accidents. For example, this process takes place each time you cross the road. The hazard is the moving vehicle, the stake is you and the risk might be the risk of collision between both. The same principle has to be applied during our daily work. In particular, keeping in mind the general principles of prevention defined in the late 1980s. These principles wer...

  16. International Conference on Harmonisation; guidance on Addendum to E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs; availability. Notice.

    Science.gov (United States)

    2004-02-05

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Addendum to E2C Clinical Safety Data Management: Periodic Safety Update Reports for Marketed Drugs" (the ICH E2C guidance). The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). In the Federal Register of May 19, 1997 (62 FR 27470), FDA published the ICH E2C guidance, which recommends a unified standard for the format, content, and reporting frequency for postmarketing periodic safety update reports (PSURs) for drug and biological products. This guidance, an addendum to the ICH E2C guidance, provides additional information on the content and format of PSURs, including clarification of the objectives, general principles, and model for PSURs. This guidance is intended to help harmonize collection and submission of postmarketing clinical safety data.

  17. Postmarketing Safety Surveillance and Reevaluation of Danhong Injection: Clinical Study of 30888 Cases

    Directory of Open Access Journals (Sweden)

    Xue-Lin Li

    2015-01-01

    Full Text Available Traditional Chinese medicine injections (TCMIs have played an irreplaceable role for treating some clinical emergency, severe illness, and infectious diseases in China. In recent years, the incidence rates of adverse drug reactions (ADRs of TCMIs have increased year by year. Danhong injection (DHI is one representative TCMI comprised of Danshen and Honghua for treating cardiovascular and cerebrovascular diseases in clinic. In present study, the postmarketing safety surveillance and reevaluation of DHI were reported. Total 30888 patients in 37 hospitals from 6 provinces participated in the study. The results showed that the ADR incidence rate of DHI was 3.50‰. Seventeen kinds of new adverse reactions of DHI were found. The main type of ADRs of DHI was type A (including sweating, dizziness, headache, flushing, vasodilation, eye hemorrhage, faintness, chest pain, palpitations, breathlessness, anxious, nausea, flatulence, vomiting, hypotension, hypertension, local numbness, dyspnea, joint disease, and tinnitus accounting for 57.75%. The severities of most ADRs of DHI were mild and moderate reactions accounting for 25.93% and 66.67%, respectively. The main disposition of ADRs of DHI was drug withdrawal and without any treatments. The results can provide basis for amendment and improvement of the instructions of DHI, as well as demonstration and reference for the postmarketing safety surveillance and reevaluation of other TCMIs. And the rationality, scientificity, and safety of clinical applications of TCMIs could be improved.

  18. Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials.

    Science.gov (United States)

    Alberts, David S; Muggia, Franco M; Carmichael, James; Winer, Eric P; Jahanzeb, Mohammad; Venook, Alan P; Skubitz, Keith M; Rivera, Edgardo; Sparano, Joseph A; DiBella, Nicholas J; Stewart, Simon J; Kavanagh, John J; Gabizon, Alberto A

    2004-12-01

    Preclinical studies have established the pharmacologic advantages of liposomal anthracyclines, including pharmacokinetic profiles after bolus dosing that resemble continuous infusion of conventional anthracyclines, increased drug concentrations in tumor cells compared with the surrounding tissues, and reduced toxicity relative to conventional anthracycline treatment. Based on these studies, many phase I and phase II clinical trials were conducted to assess the safety and potential activity of liposomal anthracyclines in the management of both solid and hematologic tumors. These studies provided valuable insight into the safety of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), nonpegylated liposomal doxorubicin (Myocet [NPLD]), and liposomal daunorubicin (DaunoXome [DNX]) over a range of doses, either as single-agent therapy or in combination with other cytotoxic agents. Other liposomal anthracyclines in development may be well tolerated but their activity remains to be elucidated by clinical trials. The available data also suggest that liposomal anthracyclines have activity not only against tumor types with known sensitivity to conventional anthracyclines, but also potentially for tumors that are typically anthracycline-resistant. Despite the availability of clinical data from a wide variety of tumor types and patient populations, further studies of liposomal anthracycline therapy are needed to fully establish their safety, efficacy, and dosing in the treatment of these patients.

  19. Postmarketing Safety Surveillance and Reevaluation of Danhong Injection: Clinical Study of 30888 Cases.

    Science.gov (United States)

    Li, Xue-Lin; Tang, Jin-Fa; Li, Wei-Xia; Li, Chun-Xiao; Zhao, Tao; Zhao, Bu-Chang; Wang, Yong; Zhang, Hui; Chen, Xiao-Fei; Xu, Tao; Zhu, Ming-Jun

    2015-01-01

    Traditional Chinese medicine injections (TCMIs) have played an irreplaceable role for treating some clinical emergency, severe illness, and infectious diseases in China. In recent years, the incidence rates of adverse drug reactions (ADRs) of TCMIs have increased year by year. Danhong injection (DHI) is one representative TCMI comprised of Danshen and Honghua for treating cardiovascular and cerebrovascular diseases in clinic. In present study, the postmarketing safety surveillance and reevaluation of DHI were reported. Total 30888 patients in 37 hospitals from 6 provinces participated in the study. The results showed that the ADR incidence rate of DHI was 3.50‰. Seventeen kinds of new adverse reactions of DHI were found. The main type of ADRs of DHI was type A (including sweating, dizziness, headache, flushing, vasodilation, eye hemorrhage, faintness, chest pain, palpitations, breathlessness, anxious, nausea, flatulence, vomiting, hypotension, hypertension, local numbness, dyspnea, joint disease, and tinnitus) accounting for 57.75%. The severities of most ADRs of DHI were mild and moderate reactions accounting for 25.93% and 66.67%, respectively. The main disposition of ADRs of DHI was drug withdrawal and without any treatments. The results can provide basis for amendment and improvement of the instructions of DHI, as well as demonstration and reference for the postmarketing safety surveillance and reevaluation of other TCMIs. And the rationality, scientificity, and safety of clinical applications of TCMIs could be improved.

  20. Review on the efficacy, safety and clinical applications of polihexanide, a modern wound antiseptic.

    Science.gov (United States)

    Hübner, N-O; Kramer, A

    2010-01-01

    Infected wounds are still one of the great challenges in medicine. In the last decade, it has become increasingly clear that antimicrobial chemotherapy is limited by the spread of antimicrobial resistance. Fortunately, new, highly effective antiseptic substances with a broad antimicrobial spectrum are available, so local treatment is expected to get increasingly more important in wound therapy. This paper reviews the antiseptic agent polihexanide (polyhexamethylene biguanide, PHMB), one of the most promising substances available today, from a clinical point of view, focusing on efficacy, safety and clinical applications.

  1. Meta-Analysis of the Clinical Effectiveness and Safety of Ligustrazine in Cerebral Infarction

    Directory of Open Access Journals (Sweden)

    Tian Yu

    2016-01-01

    Full Text Available Objectives. To evaluate the efficacy and safety of ligustrazine in the treatment of cerebral infarction. Methods. A systematic literature search was conducted in 6 databases until 30 June 2016 to identify randomized controlled trials (RCTs of ligustrazine in the treatment of cerebral infarction. The quality of all the included studies was evaluated. All data were analyzed by Review Manager 5.1 Software. Results. 19 RCTs totally involving 1969 patients were included. The primary outcome measures were Neurological Deficit Score (NDS and clinical effective rate. The secondary outcome measure was adverse events. Meta-analysis showed that ligustrazine could improve clinical efficacy and NDS of cerebral infarction with [OR = 3.60, 95% CI (2.72, 4.78, P<0.00001] and [WMD = −3.87, 95% CI (−4.78, −2.95, P<0.00001]. Moreover, ligustrazine in treatment group exerted better clinical effects in improving the Blood Rheology Index (BRI in patients compared with control group. Ten trials contained safety assessments and stated that no obvious side effects were found. Conclusions. Ligustrazine demonstrated definite clinical efficacy for cerebral infarction, and it can also improve NDS in patients without obvious adverse events. However, due to the existing low-quality research, more large-scale and multicentric RCTs are required to provide clear evidence for its clinical efficacy in the near future.

  2. Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

    Science.gov (United States)

    Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

    2016-11-23

    Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Ten years of clinical experience with biosimilar human growth hormone: a review of safety data.

    Science.gov (United States)

    Borrás Pérez, Maria Victoria; Kriström, Berit; Romer, Tomasz; Walczak, Mieczyslaw; Höbel, Nadja; Zabransky, Markus

    2017-01-01

    Safety concerns for recombinant human growth hormone (rhGH) treatments include impact on cancer risk, impact on glucose homeostasis, and the formation of antibodies to endogenous/exogenous GH. Omnitrope(®) (biosimilar rhGH) was approved by the European Medicines Agency in 2006, with approval granted on the basis of comparable quality, safety, and efficacy to the reference medicine (Genotropin(®)). Additional concerns that may exist in relation to biosimilar rhGH include safety in indications granted on the basis of extrapolation and the impact of changing to biosimilar rhGH from other rhGH treatments. A substantial data set is available to fully understand the safety profile of biosimilar rhGH, which includes data from its clinical development studies and 10 years of post-approval experience. As of June 2016, 106,941,419 patient days (292,790 patient-years) experience has been gathered for biosimilar rhGH. Based on the available data, there have been no unexpected or unique adverse events related to biosimilar rhGH treatment. There is no increased risk of cancer, adverse glucose homeostasis, or immunogenic response with biosimilar rhGH compared with the reference medicine and other rhGH products. The immunogenicity of biosimilar rhGH is also similar to that of the reference and other rhGH products. Physicians should be reassured that rhGH products have a good safety record when used for approved indications and at recommended doses, and that the safety profile of biosimilar rhGH is in keeping with that of other rhGH products.

  4. Rivaroxaban real-world evidence: Validating safety and effectiveness in clinical practice.

    Science.gov (United States)

    Beyer-Westendorf, Jan; Camm, A John; Coleman, Craig I; Tamayo, Sally

    2016-09-28

    Randomised controlled trials (RCTs) are considered the gold standard of clinical research as they use rigorous methodologies, detailed protocols, pre-specified statistical analyses and well-defined patient cohorts. However, RCTs do not take into account the complexity of real-world clinical decision-making. To tackle this, real-world data are being increasingly used to evaluate the long-term safety and effectiveness of a given therapy in routine clinical practice and in patients who may not be represented in RCTs, addressing key clinical questions that may remain. Real-world evidence plays a substantial role in supporting the use of non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) in clinical practice. By providing data on patient profiles and the use of anticoagulation therapies in routine clinical practice, real-world evidence expands the current awareness of NOACs, helping to ensure that clinicians are well-informed on their use to implement patient-tailored clinical decisions. There are various issues with current anticoagulation strategies, including under- or overtreatment and frequent monitoring with VKAs. Real-world studies have demonstrated that NOAC use is increasing (Dresden NOAC registry and Global Anticoagulant Registry in the FIELD-AF [GARFIELD-AF]), as well as reaffirming the safety and effectiveness of rivaroxaban previously observed in RCTs (XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation [XANTUS] and IMS Disease Analyzer). This article will describe the latest updates in real-world evidence across a variety of methodologies, such as non-interventional studies (NIS), registries and database analyses studies. It is anticipated that these studies will provide valuable clinical insights into the management of thromboembolism, and enhance the current knowledge on anticoagulant use and outcomes for patients.

  5. Biased safety reporting in blinded randomized clinical trials: meta-analysis of angiotensin receptor blocker trials.

    Directory of Open Access Journals (Sweden)

    Nobuyoshi Takabayashi

    Full Text Available BACKGROUND: Cough is listed as an adverse drug reaction (ADR on the labels of angiotensin receptor blockers (ARB. However, a causal association with cough has also been reported for angiotensin converting enzyme inhibitors (ACEI, which have frequently been used as comparator drugs in the registration clinical trials of ARBs. This prompted us to examine the possible influence of using comparator drugs with well-known ADRs on the safety reporting of investigational drugs in blinded randomized clinical trials. METHODS AND FINDINGS: The double-blinded, randomized clinical trials with comparator drugs were identified in the Japanese dossiers for the new drug applications of ARBs. The risk ratios (RR of reporting cough and headache in ARB arms were calculated for each ARB by comparing trials using ACEIs and trials using non-ACEIs, were then combined with a meta-analysis. 23 trials with a total of 6643 patients were identified, consisting 6 trials using an ACEI comparator including 819 ARB patients and 17 trials using a non-ACEI comparator including 5824 ARB patients. The combined RR of cough reporting was significantly elevated (20.77; 95% confidence interval [CI], 7.47 to 57.76, indicating more frequent reporting of cough in clinical trials using an ACEI comparator. In contrast, the combined RR of headache, a negative control, was insignificant (1.45; 95% CI, 0.34 to 6.22. CONCLUSION: The use of comparators with well-known ADRs in blinded randomized trials produces potential bias in the reporting frequency of ADRs for investigational drugs. The selection of appropriate comparator drugs should be critical in unbiased safety assessment in double-blinded, randomized clinical trials and thus have relevance in reviewing the safety results from a regulatory point of view.

  6. Meta-Analysis of the Clinical Effectiveness and Safety of Ligustrazine in Cerebral Infarction.

    Science.gov (United States)

    Yu, Tian; Guo, Xiaoheng; Zhang, Zhen; Liu, Rong; Zou, Liang; Fu, Jia; Shi, Zheng

    2016-01-01

    Objectives. To evaluate the efficacy and safety of ligustrazine in the treatment of cerebral infarction. Methods. A systematic literature search was conducted in 6 databases until 30 June 2016 to identify randomized controlled trials (RCTs) of ligustrazine in the treatment of cerebral infarction. The quality of all the included studies was evaluated. All data were analyzed by Review Manager 5.1 Software. Results. 19 RCTs totally involving 1969 patients were included. The primary outcome measures were Neurological Deficit Score (NDS) and clinical effective rate. The secondary outcome measure was adverse events. Meta-analysis showed that ligustrazine could improve clinical efficacy and NDS of cerebral infarction with [OR = 3.60, 95% CI (2.72, 4.78), P effects in improving the Blood Rheology Index (BRI) in patients compared with control group. Ten trials contained safety assessments and stated that no obvious side effects were found. Conclusions. Ligustrazine demonstrated definite clinical efficacy for cerebral infarction, and it can also improve NDS in patients without obvious adverse events. However, due to the existing low-quality research, more large-scale and multicentric RCTs are required to provide clear evidence for its clinical efficacy in the near future.

  7. Intravenous bisphosphonates for postmenopausal osteoporosis: safety profiles of zoledronic acid and ibandronate in clinical practice.

    Science.gov (United States)

    Sieber, Patricia; Lardelli, Patrizia; Kraenzlin, Claude A; Kraenzlin, Marius E; Meier, Christian

    2013-02-01

    Intravenous bisphosphonates are widely used for treatment of postmenopausal osteoporosis. They are associated with transient influenza-like symptoms, predominantly after the first zoledronic acid (up to 32 %) or ibandronate (up to 5 %) administration. The experience in clinical practice suggests that the incidence of post-dose symptoms is higher than has been reported in clinical trials. We assessed the safety of annual infusions of zoledronic acid and 3-monthly injections of ibandronate in women with postmenopausal osteoporosis. In this retrospective study we analysed safety data from 272 postmenopausal women treated with zoledronic acid (n = 127; mean age 68.6 ± 9.4 years) or intravenous (IV) ibandronate (n = 145; mean age 69.1 ± 9.0 years). Safety data (including occurrence of acute-phase reactions and osteonecrosis of the jaw) were gathered in phone call interviews by using a standardized questionnaire. The number of patients with adverse events was significantly higher in zoledronic acid as compared to ibandronate-treated patients, primarily because of a larger number of post-dose symptoms after bisphosphonate administrations (54.3 % vs. 33.1 %, p 3 days in approximately 50 % of patients. The incidence of symptoms decreased after subsequent infusions. The rate of influenza-like symptoms was more frequent after zoledronic acid than after IV ibandronate in bisphosphonate-naïve patients but comparable in patients pretreated with oral bisphosphonates. There were no spontaneous reports of osteonecrosis of the jaw, arrhythmia or delayed fracture healing. Although IV bisphosphonates are generally safe, the occurrence of transient influenza-like symptoms after IV bisphosphonates seems to be more frequent in clinical practice than has been reported in clinical trials.

  8. Clinical Pharmacist Patient-Safety Initiative to Reduce Against-Label Prescribing of Statins With Cyclosporine.

    Science.gov (United States)

    Lamprecht, Donald G; Todd, Brittany A; Denham, Anne M; Ruppe, Leslie K; Stadler, Sheila L

    2017-02-01

    Against-label prescribing of statins with interacting drugs, such as cyclosporine, represents an important patient safety concern. To implement and evaluate the effectiveness of a clinical pharmacist patient-safety initiative to minimize against-label prescribing of statins with cyclosporine. Kaiser Permanente Colorado clinical pharmacists identified patients receiving both cyclosporine and against-label statin through prescription claims data. Academic detailing on this interaction was provided to health care providers. Clinical pharmacists collaborated with physicians to facilitate conversion to on-label statin. Conversion rates along with changes in low-density lipoprotein cholesterol (LDL-C) were assessed. Of the 157 patients identified as taking cyclosporine, 48 were receiving concurrent statin therapy. Of these 48 patients, 33 (69%) were on an against-label statin regimen; 25 (76%) of these patients were converted to on-label statin. Overall, patients converted to on-label statin had a mean LDL-C prior to conversion of 82.9 (±26.4) mg/dL and mean LDL-C after conversion of 90.7 (±31.2) mg/dL ( P = 0.21). In all, 17 patients (68%) were switched to pravastatin 20 mg daily and 8 patients (32%) to rosuvastatin 5 mg daily. In patients converted to pravastatin 20 mg daily, the mean LDL-C was 13.5 mg/dL higher than prior to conversion ( P = 0.066). In patients converted to rosuvastatin 5 mg daily, the mean LDL-C was 3.8 mg/dL lower than prior to conversion ( P = 0.73). Utilizing a patient-safety-centered approach, clinical pharmacists were able to reduce the number of patients on against-label statin with cyclosporine while maintaining a comparable level of LDL-C control.

  9. Safety and regulatory issues regarding stem cell therapies: one clinic's perspective.

    Science.gov (United States)

    Centeno, Christopher J; Bashir, Jamil

    2015-04-01

    Stem cells therapies have been in preclinical development for the past 2 decades. A rapidly evolving regulatory landscape has restrained many of these technologies from advancing from the bench to the bedside. Although the large-scale clinical safety of stem cell therapies remains to be fully tested, the total number of patients who have safely received these therapies is large and growing. Prima facie evidence would dictate that certain types of cell therapy are likely safer than others. Understanding the current regulation regarding stem cells involves a discussion of their safety profile, as the 2 issues are closely intertwined. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  10. Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program

    Directory of Open Access Journals (Sweden)

    Strowitzki T

    2015-04-01

    Full Text Available Thomas Strowitzki,1 Thomas Faustmann,2 Christoph Gerlinger,3,4 Ulrike Schumacher,5,6 Christiane Ahlers,7 Christian Seitz8 1Department of Gynecological Endocrinology and Reproductive Medicine, University of Heidelberg, Heidelberg, Germany; 2Bayer Pharma AG, Global Medical Affairs Women’s Healthcare, Berlin, Germany; 3Bayer Pharma AG, Global Research and Development Statistics, Berlin, Germany; 4Department of Gynecology, Obstetrics, and Reproductive Medicine, University Medical School of Saarland, Homburg/Saar, Germany; 5Jenapharm GmbH & Co KG, Medical Affairs Support, Jena, Germany; 6Center for Clinical Studies, Universitätsklinikum Jena, Jena, Germany; 7Bayer Pharma AG, Global Integrated Analysis and Lifecycle Management Statistics, Wuppertal, Germany; 8Bayer Pharma AG, Global Clinical Development Therapeutic Area Primary Care and Women’s Healthcare, Berlin, Germany Background: In four randomized, controlled, European trials, dienogest 2 mg once daily demonstrated significant efficacy for lesion reduction and reduction in pain intensity in endometriosis. We describe a pooled analysis of the safety and tolerability data from these trials to confirm and further characterize the safety profile of dienogest in the treatment of endometriosis.Methods: All 332 women treated with dienogest 2 mg who participated in the four clinical trials were included in the pooled analyses for safety assessments, including adverse events, laboratory tests, vital signs, body weight, and bleeding patterns. Safety variables were analyzed using descriptive statistics.Results: Pooled analyses of this large patient population confirmed that dienogest 2 mg is well tolerated, with a favorable safety profile extending over a period up to 65 weeks in women with endometriosis. The most common adverse drug reactions were headache, breast discomfort, depressed mood, and acne, each occurring in <10% of women. All these adverse events were generally of mild

  11. Safety Analysis of Panax Ginseng in Randomized Clinical Trials: A Systematic Review

    Science.gov (United States)

    Kim, Young-Sook; Woo, Jung-Yoon; Han, Chang-Kyun; Chang, Il-Moo

    2015-01-01

    Background: Panax ginseng C.A. Meyer is one of the most frequently used herbs in the world. The roots of Panax ginseng have been used as a traditional tonic and medicine for thousands of years in Korea and China. Today, ginseng root is used as a dietary supplement and complementary medicine and for adjuvant therapeutics worldwide. The efficacy of ginseng has been studied in a wide range of basic research and clinical studies. However, it has been reported that the results from clinical studies are conflicting, and they depend on the parameters of the protocol design including the conditions of the participants and the types of ginseng used such as red ginseng, white ginseng, fermented ginseng and cultured ginseng. Meanwhile, in addition to clinical efficacy, the safety of ginseng is a highly important matter for customers. With globally increasing demand for Panax ginseng as a dietary supplement or complementary medicine, it is necessary to provide information on its safe use to customers to improve their health conditions. Although the safety of Panax ginseng in pre-clinical studies is well known, the evaluation of safety in clinical studies has so far been insufficient. This systematic review was conducted to assess the safety of ginseng in randomized controlled clinical trials (RCT) over the last 10 years. We chose the last 10 years because many clinical trials have been conducted in the past 10 years, and it will help to understand the recent trends in RCTs of ginseng. Methods: Articles on ginseng studies were searched with keywords in MEDLINE and four other Korean online database sites. Studies with ginseng as a monopreparation were selected while studies with single administration, preparations combined with other herbs or drug combinations were excluded from the selected studies. Data from the selected studies meeting the criteria were extracted and reviewed in terms of study design, condition and number of participants, type of ginseng, dosage, duration

  12. Bioactive properties and clinical safety of a novel milk protein peptide

    Directory of Open Access Journals (Sweden)

    Chen Helen

    2011-09-01

    Full Text Available Abstract Background Milk protein fractions and peptides have been shown to have bioactive properties. This preliminary study examined the potential mechanisms of action and clinical safety of novel milk protein peptide (MP. Findings A novel MP mixture inhibits the tyrosine kinase activity of epidermal growth factor receptor (EGFR, vascular endothelial growth factor receptor 2 (VEGFR2, and insulin receptor (IR with IC50 of 9.85 μM, 7.7 μM, and 6.18 μM respectively. In vitro, this multi-kinase inhibitor causes apoptosis in HT-29 colon cancer cells, and in a C. elegans worm study, showed a weak but significant increase in lifespan. A six week double-blind, placebo-controlled study involving 73 healthy volunteers demonstrated that the MP mixture is safe to consume orally. All clinical blood markers remained within normal levels and no clinically significant side effects were reported. There was some evidence of improved insulin sensitivity, neutrophil-to-lymphocyte ratio (NLR, and quality of life assessment of role of physical function. Conclusions These data in combination with the observed in vitro anti-cancer properties warrant further clinical studies to investigate this MP mixture as a potential clinical nutrition intervention for improving the quality of life and clinical outcomes in cancer patients. Trial Registration NCT01412658

  13. [Effectiveness and safety of probiotics in children on the basis of clinical trials].

    Science.gov (United States)

    Kamińska, Ewa

    2012-01-01

    Probiotics may be helpful if they are used according to current medical knowledge based on the results of properly designed and well-conducted clinical trials. Their effects depend on the specific strain and defined dose of the probiotic microorganism, and should not be extrapolated on other, even closely related strains. Meta-analyses of randomized clinical trials performed in children showed the greatest probiotic efficacy of Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii strains in the treatment of acute viral infectious diarrhea and in prevention of non-difficile antibiotic associated-diarrhea (AAD). The clinical efficacy of probiotics in other indications in children has not been substantiated until now, however the results of some clinical trials (e.g. in necrotizing enterocolitis (NEC) or atopic dermatitis) are promising. When using probiotics, it is necessary to rely on the results of well-designed clinical trials, not on commercials. This paper provides information based on recent knowledge concerning the efficacy and safety of probiotics according to the results of clinical trials performed in children.

  14. [Analysis of patient complaints in Primary Care: An opportunity to improve clinical safety].

    Science.gov (United States)

    Añel-Rodríguez, R M; Cambero-Serrano, M I; Irurzun-Zuazabal, E

    2015-01-01

    To determine the prevalence and type of the clinical safety problems contained in the complaints made by patients and users in Primary Care. An observational, descriptive, cross-sectional study was conducted by analysing both the complaint forms and the responses given to them in the period of one year. At least 4.6% of all claims analysed in this study contained clinical safety problems. The family physician is the professional who received the majority of the complaints (53.6%), and the main reason was the problems related to diagnosis (43%), mainly the delay in diagnosis. Other variables analysed were the severity of adverse events experienced by patients (in 68% of cases the patient suffered some harm), the subsequent impact on patient care, which was affected in 39% of cases (7% of cases even requiring hospital admission), and the level of preventability of adverse events (96% avoidable) described in the claims. Finally the type of response issued to each complaint was analysed, being purely bureaucratic in 64% of all cases. Complaints are a valuable source of information about the deficiencies identified by patients and healthcare users. There is considerable scope for improvement in the analysis and management of claims in general, and those containing clinical safety issues in particular. To date, in our area, there is a lack of appropriate procedures for processing these claims. Likewise, we believe that other pathways or channels should be opened to enable communication by patients and healthcare users. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  15. Assessing the Safety of Human Pluripotent Stem Cells and Their Derivatives for Clinical Applications

    Directory of Open Access Journals (Sweden)

    Peter W. Andrews

    2017-07-01

    Full Text Available Pluripotent stem cells may acquire genetic and epigenetic variants during culture following their derivation. At a conference organized by the International Stem Cell Initiative, and held at The Jackson Laboratory, Bar Harbor, Maine, October 2016, participants discussed how the appearance of such variants can be monitored and minimized and, crucially, how their significance for the safety of therapeutic applications of these cells can be assessed. A strong recommendation from the meeting was that an international advisory group should be set up to review the genetic and epigenetic changes observed in human pluripotent stem cell lines and establish a framework for evaluating the risks that they may pose for clinical use.

  16. Safety and clinical efficacy of golimumab in the treatment of arthritides

    Directory of Open Access Journals (Sweden)

    Ismail Simsek

    2010-09-01

    Full Text Available Ismail Simsek, Yusuf YaziciNew York University School of Medicine, NYU Hospital for Joint Diseases, New York, USAAbstract: Golimumab is a human anti-tumor necrosis factor (TNF-alpha monoclonal antibody that was recently approved for the treatment of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. This review covers the published clinical trial data on the use of golimumab for the approved indications mentioned above with respect to efficacy and safety. The various ongoing trials for golimumab have yielded promising results in terms of efficacy and safety in methotrexate-naive and -resistant patients with rheumatoid arthritis, as well as in patients who were previously treated with other anti-TNF agents. In addition, the efficacy of golimumab in psoriatic arthritis and ankylosing spondylitis has also been demonstrated. The real safety information will be available only once the drug has been used in many more patients, who frequently have comorbid conditions.Keywords: arthritis, rheumatoid, psoriatic arthritis, ankylosing spondylitis

  17. [Clinical safety and professional liability claims in Orthopaedic Surgery and Traumatology].

    Science.gov (United States)

    Bori, G; Gómez-Durán, E L; Combalia, A; Trilla, A; Prat, A; Bruguera, M; Arimany-Manso, J

    2016-01-01

    The specialist in orthopaedic and traumatological surgery, like any other doctor, is subject to the current legal provisions while exercising their profession. Mandatory training in the medical-legal aspects of health care is essential. Claims against doctors are a reality, and orthopaedic and traumatological surgery holds first place in terms of frequency of claims according to the data from the General Council of Official Colleges of Doctors of Catalonia. Professionals must be aware of the fundamental aspects of medical professional liability, as well as specific aspects, such as defensive medicine and clinical safety. The understanding of these medical-legal aspects in the routine clinical practice can help to pave the way towards a satisfactory and safe professional career. The aim of this review is to contribute to this training, for the benefit of professionals and patients. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

  18. Echinacea purpurea L. in children: safety, tolerability, compliance, and clinical effectiveness in upper respiratory tract infections.

    Science.gov (United States)

    Saunders, Paul Richard; Smith, Fraser; Schusky, Read Weaver

    2007-11-01

    Echinacea purpurea (L.) Moench was mistakenly taken from North America to Germany in 1939 where it was cultivated and various extractions were prepared and subsequently used to treat upper respiratory tract infections. Parents often administer Echinacea to their children, but safety data on the use of Echinacea in Canadian children is lacking. A screening history, physical examination, and daily record of symptoms from an initial visit through to a the follow-up visit 13 days later were used to increase patient safety. Each subject was administered an aerial part Echinacea extract. The dose was based on age (2.5 mL three times per day for children aged 2-5 years, and 5 mL two times per day for children aged 6-12 years) and administered for 10 days in an open-label trial. A rating scale was used to measure tolerance to the treatment. We assessed the safety and compliance of use of the Echinacea extract by measuring the amount of extract returned at the end of the study, having the parents complete and return a daily symptom diary, and recording the subjects' use of other natural health products or medications during the trial. Clinical effectiveness of the Echinacea extract could not be accurately assessed because of the small trial size and because the extract had been administered when some of the subjects had an upper respiratory tract infection that had begun 1 or more days prior to the study; however, each subject's symptoms improved. No allergic or adverse reaction occurred and no safety issues arose.

  19. Practice-based evidence: profiling the safety of cilostazol by text-mining of clinical notes.

    Science.gov (United States)

    Leeper, Nicholas J; Bauer-Mehren, Anna; Iyer, Srinivasan V; Lependu, Paea; Olson, Cliff; Shah, Nigam H

    2013-01-01

    Peripheral arterial disease (PAD) is a growing problem with few available therapies. Cilostazol is the only FDA-approved medication with a class I indication for intermittent claudication, but carries a black box warning due to concerns for increased cardiovascular mortality. To assess the validity of this black box warning, we employed a novel text-analytics pipeline to quantify the adverse events associated with Cilostazol use in a clinical setting, including patients with congestive heart failure (CHF). We analyzed the electronic medical records of 1.8 million subjects from the Stanford clinical data warehouse spanning 18 years using a novel text-mining/statistical analytics pipeline. We identified 232 PAD patients taking Cilostazol and created a control group of 1,160 PAD patients not taking this drug using 1:5 propensity-score matching. Over a mean follow up of 4.2 years, we observed no association between Cilostazol use and any major adverse cardiovascular event including stroke (OR = 1.13, CI [0.82, 1.55]), myocardial infarction (OR = 1.00, CI [0.71, 1.39]), or death (OR = 0.86, CI [0.63, 1.18]). Cilostazol was not associated with an increase in any arrhythmic complication. We also identified a subset of CHF patients who were prescribed Cilostazol despite its black box warning, and found that it did not increase mortality in this high-risk group of patients. This proof of principle study shows the potential of text-analytics to mine clinical data warehouses to uncover 'natural experiments' such as the use of Cilostazol in CHF patients. We envision this method will have broad applications for examining difficult to test clinical hypotheses and to aid in post-marketing drug safety surveillance. Moreover, our observations argue for a prospective study to examine the validity of a drug safety warning that may be unnecessarily limiting the use of an efficacious therapy.

  20. The role of the Data and Safety Monitoring Board in a clinical trial: The CRISIS Study

    Science.gov (United States)

    Holubkov, Richard; Casper, T. Charles; Dean, J. Michael; Anand, K. J. S.; Zimmerman, Jerry; Meert, Kathleen L.; Newth, Christopher J. L.; Berger, John; Harrison, Rick; Willson, Douglas F.; Nicholson, Carol

    2012-01-01

    Objective Randomized clinical trials are commonly overseen by a data and safety monitoring board (DSMB) comprised of experts in medicine, ethics, and biostatistics. DSMB responsibilities include protocol approval, interim review of study enrollment, protocol compliance, safety, and efficacy data. DSMB decisions can affect study design and conduct, as well as reported findings. Researchers must incorporate DSMB oversight into the design, monitoring, and reporting of randomized trials. Design Case study, narrative review. Methods The DSMB’s role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial is described. Findings The NIH-appointed CRISIS DSMB was charged with monitoring sample size adequacy and feasibility, safety with respect to adverse events and 28-day mortality, and efficacy with respect to the primary nosocomial infection/sepsis outcome. The Federal Drug Administration also requested DSMB interim review before opening CRISIS to children below one year of age. The first interim analysis found higher 28-day mortality in one treatment arm. The DSMB maintained trial closure to younger children, and requested a second interim data review six months later. At this second meeting, mortality was no longer of concern, while a weak efficacy trend of lower infection/sepsis rates in one study arm emerged. As over 40% of total patients had been enrolled, the DSMB elected to examine conditional power, and unmask treatment arm identities. Upon finding somewhat greater efficacy in the placebo arm, the DSMB recommended stopping CRISIS due to futility. Conclusions The design and operating procedures of a multicenter randomized trial must consider a pivotal DSMB role. Maximum study design flexibility must be allowed, and investigators must be prepared for protocol modifications due to interim findings. The DSMB must have sufficient clinical and statistical expertise to assess potential importance of interim

  1. Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial.

    Science.gov (United States)

    da Cruz, Lyndon; Dorn, Jessy D; Humayun, Mark S; Dagnelie, Gislin; Handa, James; Barale, Pierre-Olivier; Sahel, José-Alain; Stanga, Paulo E; Hafezi, Farhad; Safran, Avinoam B; Salzmann, Joel; Santos, Arturo; Birch, David; Spencer, Rand; Cideciyan, Artur V; de Juan, Eugene; Duncan, Jacque L; Eliott, Dean; Fawzi, Amani; Olmos de Koo, Lisa C; Ho, Allen C; Brown, Gary; Haller, Julia; Regillo, Carl; Del Priore, Lucian V; Arditi, Aries; Greenberg, Robert J

    2016-10-01

    The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients' native residual vision compared with their vision with the Argus II. Thirty participants in 10 centers in the United States and Europe. The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  2. [Clinical efficacy and safety of mifepristone in the treatment of abortive remnants of induced abortion].

    Science.gov (United States)

    Zhuge, Ting; Li, Bin; Huang, Zi-rong

    2012-01-03

    To evaluate the efficacy and safety of treating abortive remnants of induced abortion with different doses of mifepristone. A total of 101 women undergoing post-abortion treatment at our family planning clinic from October 2009 to February 2011 were recruited and divided randomly into 4 groups. They were diagnosed as abortive remnants by ultrasound and blood level of β-HCG (human chorionic gonadotrophin). Three test groups received different doses of mifepristone and one group as control. The efficacy and safety of four groups were evaluated by clinical observations, ultrasonic examinations and blood level of β-HCG. The effective rates of mifepristone test and control groups were 61.60% and 21.40% respectively. And there were statistical significances between two groups (P ultrasound were better than those of the control group. And there were significant statistical differences (P 0.05). There was statistical significance in pairwise comparison on reduction of residual size tested by ultrasound among test groups (P 0.05). Mifepristone is effective in the treatment of induced incomplete abortion. And a short-term large dose offers a better efficacy.

  3. Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Gajofatto A

    2015-12-01

    Full Text Available Alberto Gajofatto,1,2 Marco Turatti,2 Salvatore Monaco,1,2 Maria Donata Benedetti2 1Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy; 2Division of Neurology B, Verona University Hospital, Verona, Italy Abstract: Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS, a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management. Keywords: multiple sclerosis, fingolimod, safety, tolerability, efficacy

  4. Clinic-based screening for domestic violence: use of a child safety questionnaire

    Directory of Open Access Journals (Sweden)

    Sisk Doris J

    2004-06-01

    Full Text Available Abstract Background Domestic violence affects many women during their lifetime. Children living in homes where they are or have been exposed to violence are at increased risk for adverse outcomes. The American Academy of Pediatrics, the American Academy of Family Practice, and the American College of Obstetrics/Gynecology have recently joined in recommending routine screening of all families for the presence of domestic violence. We present our experience with an office-based domestic violence screening questionnaire. Methods A series of four child safety questionnaires (designed for parents of infant, preschool-age, school-age, and adolescent patients, which included specific questions about domestic violence, was given to all mothers presenting to a university out-patient general pediatric clinic. The questionnaires, offered in both English and Spanish, were reviewed for the presence of domestic violence exposure, usually at the time of the clinic visit. The number of women who reported either current or past exposure to domestic violence as disclosed by this active screening process was compared to the number discovered prior to the use of these questionnaires. Results Prior to the use of active screening with a child safety questionnaire, five cases of domestic violence were identified in our clinic population of approximately 5000 children over a 3 month period. Active screening of this population with a parent questionnaire resulted in the identification of 69 cases of current domestic violence exposure (2% of those screened during each of 2 years of screening. Use of the child safety questionnaire was associated with a significantly increased odds of detecting current domestic violence (OR = 3.6, 95% CI [1.4, 9.1], P = 0.007, with 72% [26–84%] of the cases identified being attributable to the use of the questionnaire. Of children screened, 2% were currently exposed to domestic violence, and 13% had been exposed to past domestic violence

  5. Using quality and safety education for nurses to guide clinical teaching on a new dedicated education unit.

    Science.gov (United States)

    McKown, Terri; McKeon, Leslie; McKown, Leslie; Webb, Sherry

    2011-12-01

    Gaps exist in health professional education versus the demands of current practice. Leveraging front-line nurses to teach students exemplary practice in a Dedicated Education Unit (DEU) may narrow this gap. The DEU is an innovative model for experiential learning, capitalizing on the expertise of staff nurses as clinical teachers. This study evaluated the effectiveness of a new academic-practice DEU in facilitating quality and safety competency achievement among students. Six clinical teachers received education in clinical teaching and use of Quality and Safety Education for Nurses (QSEN) competencies to guide acquisition of essential knowledge, skills, and attitudes for continuous health care improvement. Twelve students assigned to the six teachers completed daily logs for the 10-week practicum. Findings suggest that DEU students achieved QSEN competencies through clinical teacher mentoring in interdisciplinary collaboration, using electronic information for best practice and patient teaching, patient/family decision making, quality improvement, and resolution of safety issues.

  6. Clinical efficacy and safety of parenteral nutrition in adolescent girls with anorexia nervosa.

    Science.gov (United States)

    Diamanti, A; Basso, M S; Castro, M; Bianco, G; Ciacco, E; Calce, A; Caramadre, A M; Noto, C; Gambarara, M

    2008-02-01

    Anorexia nervosa (AN) is a common chronic disorder characterized by severe malnutrition and psychological disturbances. Parenteral nutrition (PN) is not usually used in nutritional rehabilitation of AN. The aim of our study was to retrospectively evaluate the indications, clinical efficacy, and safety of PN as assessed by short- and long-term outcomes in AN inpatient girls. During the last 10 years a total of 198 inpatients were included in our study: 104 (53%) received oral and parenteral refeeding (group A) and 94 (47%) oral refeeding alone (group B). For each nutritional treatment, clinical efficacy was evaluated by short- and long-term outcomes, and safety was assessed by complication rate. Short-term outcome assessment indicated weekly weight gain and maximum caloric intake to be higher in PN-treated patients. Long-term outcome evaluation showed rehospitalization and recovery rate to be similar in the two groups, but failure of first nutritional rehabilitation requiring PN significantly greater in group B (17.5%) than in group A (3%) (p = .01). The number of complications was significantly higher in group A than in group B (p = .004), although all complications resolved. Among all nutritional rehabilitation strategies, PN offers an alternative and safe way to successfully treat AN patients. Presence of clinical complications and reduced compliance with individual, group, and family therapy seem to be the main indications for PN, as it promptly improves nutritional status. At pediatric and adolescent ages, psychological disturbances can also contraindicate the use of enteral nutrition, and therefore represent an additional indication for PN.

  7. Safety of bevacizumab in clinical practice for recurrent ovarian cancer: A retrospective cohort study

    Science.gov (United States)

    SELLE, FRÉDÉRIC; EMILE, GEORGE; PAUTIER, PATRICIA; ASMANE, IRÈNE; SOARES, DANIELE G.; KHALIL, AHMED; ALEXANDRE, JEROME; LHOMMÉ, CATHERINE; RAY-COQUARD, ISABELLE; LOTZ, JEAN-PIERRE; GOLDWASSER, FRANÇOIS; TAZI, YOUSSEF; HEUDEL, PIERRE; PUJADE-LAURAINE, ERIC; GOUY, SÉBASTIEN; TREDAN, OLIVIER; BARBAZA, MARIE O.; ADY-VAGO, NORA; DUBOT, CORALINE

    2016-01-01

    The poor outcome of patients with recurrent ovarian cancer constitutes a continuous challenge for decision-making in clinical practice. In this setting, molecular targets have recently been identified, and novel compounds are now available. Bevacizumab has been introduced for the treatment of patients with ovarian cancer and is, to date, the most extensively investigated targeted therapy in this setting. However, potential toxicities are associated with the use of this monoclonal antibody. These toxicities have been reported in clinical trials, and can also be observed outside of trials. As limited data is currently available regarding the safety of bevacizumab treatment in daily clinical practice, the current retrospective study was designed to evaluate this. Data from 156 patients with recurrent ovarian cancer who had received bevacizumab treatment between January 2006 and June 2009 were retrospectively identified from the institutional records of five French centers. In contrast to clinical trials, the patients in the present study were not selected and had a heterogeneous profile according to their prior medical history, lines of treatment prior to bevacizumab introduction and number of relapses. The results first confirm the effect of heavy pretreatment on the occurrence of serious and fatal adverse events in clinical practice, as previously reported for clinical trials and for other retrospective cohort studies. Importantly, the data also demonstrates, for the first time, that medical history of hypertension is an independent predictive risk factor for the development of high-grade hypertension during bevacizumab treatment. These results thus suggest that treating physicians must consider all risk factors for managing bevacizumab toxicity prior to its introduction. Such risk factors include the time of bevacizumab introduction, a patient's history of hypertension and a low incidence of pre-existing obstructive disease. PMID:26998090

  8. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

    Science.gov (United States)

    Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

    2016-12-12

    The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

  9. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies

    Directory of Open Access Journals (Sweden)

    E.L. Andrade

    Full Text Available The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics, absorption, distribution, metabolism and elimination (ADME and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

  10. Using clinical supervision to improve the quality and safety of patient care: a response to Berwick and Francis.

    Science.gov (United States)

    Tomlinson, Jonathon

    2015-06-11

    After widely publicised investigations into excess patient deaths at Mid Staffordshire hospital the UK government commissioned reports from Robert Francis QC and Professor Don Berwick. Among their recommendations to improve the quality and safety of patient care were lifelong learning, professional support and 'just culture'. Clinical supervision is in an excellent position to support these activities but opportunities are in danger of being squeezed out by regulatory and managerial demands. Doctors who have completed their training are responsible for complex professional judgements for which narrative supervision is particularly helpful. With reference to the literature and my own practice I propose that all practicing clinicians should have regular clinical supervision. Clinical supervision has patient-safety and the quality of patient care as its primary purposes. After training is completed, doctors may practice for the rest of their career without any clinical supervision, the implication being that the difficulties dealt with in clinical supervision are no longer difficulties, or are better dealt with some other way. Clinical supervision is sufficiently flexible to be adapted to the needs of experienced clinicians as its forms can be varied, though its functions remain focused on patient safety, good quality clinical care and professional wellbeing. The evidence linking clinical supervision to the quality and safety of patient care reveals that supervision is most effective when its educational and supportive functions are separated from its managerial and evaluative functions. Among supervision's different forms, narrative-based-supervision is particularly useful as it has been developed for clinicians who have completed their training. It provides ways to explore the complexity of clinical judgements and encourages doctors to question one another's authority in a supportive culture. To be successful, supervision should also be professionally led and

  11. [Good Practice of Clinical Physiology Examination for Patient Safety with a Team-Based Approach: Quality Practice in Ultrasonographic Examination].

    Science.gov (United States)

    Asai, Satomi; Miyachi, Hayato

    2015-07-01

    For the safety of patient care, a team-based approach has been advocated as an effective measure. In clinical physiology examination, we have been making efforts to promote good practice for patient safety based on such an approach in Tokai University Hospital, as represented by quality practice in ultrasonographic examination. The entire process of ultrasonographic examination can be divided into three parts: pre-examination, examination, and post-examination processes. In each process of the examination, specific quality issues must be considered, eventually ensuring the quality and safety of patient care. A laboratory physician is responsible for not only quality assurance of examination, diagnosis, and reporting, but also patient safety. A laboratory physician can play a key role in all aspects of patient safety related to each process of the examination by taking a leadership role in the team-based approach.

  12. Describing clinical faculty experiences with patient safety and quality care in acute care settings: A mixed methods study.

    Science.gov (United States)

    Roney, Linda; Sumpio, Catherine; Beauvais, Audrey M; O'Shea, Eileen R

    2017-02-01

    A major safety initiative in acute care settings across the United States has been to transform hospitals into High Reliability Organizations. The initiative requires developing cognitive awareness, best practices, and infrastructure so that all healthcare providers including clinical faculty are accountable to deliver quality and safe care. To describe the experience of baccalaureate clinical nursing faculty concerning safety and near miss events, in acute care hospital settings. A mixed method approach was used to conduct the pilot study. Nurse faculty (n=18) completed study surveys from the Agency for Healthcare Research and Quality (AHRQ) to track patient safety concerns: Incidents; Near misses; or Unsafe conditions, during one academic semester, within 9 different acute care hospitals. Additionally, seven nurse faculty participated in end of the semester focus groups to discuss the semester long experience. Clinical faculty identified a total of 24 patient occurrences: 15 Incidents, 1 Near miss event, and 8 Unsafe conditions. Focus group participants (n=7) described benefits and challenges experienced by nursing clinical faculty and students in relation to the culture of safety in acute care hospital settings. Six themes resulted from the content analysis. Utilizing nursing clinical faculty and students may add significant value to promoting patient safety and the delivery of quality care, within acute care hospital settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Safety and efficacy assessment of two new leprosy skin test antigens: randomized double blind clinical study.

    Directory of Open Access Journals (Sweden)

    Becky L Rivoire

    Full Text Available New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials.A Phase I safety trial was first conducted in a non-endemic region for leprosy (U.S.A.. Healthy non-exposed subjects (n = 10 received three titrated doses (2.5 µg, 1.0 µg and 0.1 µg of MLSA-LAM (n = 5 or MLCwA (n = 5 and control antigens [Rees MLSA (1.0 µg and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal, but involved only the 1.0 µg (high dose and 0.1 µg (low dose of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose, each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT leprosy patients, 20 household contacts of leprosy patients (HC, and 20 tuberculosis (TB patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration.In the small Phase I safety trial, reactions were primarily against the 2.5 µg dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50 showed induration against the high dose of each antigen, and 4% (2 of 50 reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens showed lower specificity (70% and 60

  14. Safety and Efficacy Assessment of Two New Leprosy Skin Test Antigens: Randomized Double Blind Clinical Study

    Science.gov (United States)

    Rivoire, Becky L.; Groathouse, Nathan A.; TerLouw, Stephen; Neupane, Kapil Dev; Ranjit, Chaman; Sapkota, Bishwa Raj; Khadge, Saraswoti; Kunwar, Chatra B.; Macdonald, Murdo; Hawksworth, Rachel; Thapa, Min B.; Hagge, Deanna A.; Tibbals, Melinda; Smith, Carol; Dube, Tina; She, Dewei; Wolff, Mark; Zhou, Eric; Makhene, Mamodikoe; Mason, Robin; Sizemore, Christine; Brennan, Patrick J.

    2014-01-01

    Background New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials. Methods A Phase I safety trial was first conducted in a non-endemic region for leprosy (U.S.A.). Healthy non-exposed subjects (n = 10) received three titrated doses (2.5 µg, 1.0 µg and 0.1 µg) of MLSA-LAM (n = 5) or MLCwA (n = 5) and control antigens [Rees MLSA (1.0 µg) and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal), but involved only the 1.0 µg (high dose) and 0.1 µg (low dose) of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose), each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration. Findings In the small Phase I safety trial, reactions were primarily against the 2.5 µg dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50) showed induration against the high dose of each antigen, and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens

  15. Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia

    Science.gov (United States)

    Bhusal, Santosh; Diomampo, Sherilyn; Magrey, Marina N

    2016-01-01

    Fibromyalgia is a chronic debilitating medical syndrome with limited therapeutic options. Pregabalin, an anticonvulsant and α-2-Δ subunit receptor ligand, is one of the anchor drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. The drug has shown clinically meaningful benefits across multiple symptom domains of fibromyalgia. Efficacy of pregabalin in fibromyalgia pain has been evaluated in at least five high-quality randomized trials, two long-term extension studies, a meta-analysis, a Cochrane database systematic review, and several post hoc analyses. These studies also hint towards a meaningful benefit on sleep, functioning, quality of life, and work productivity. Side effects of pregabalin, although common, are mild to moderate in intensity. They are noted early during therapy, improve or disappear with dose reduction, and are not usually life- or organ threatening. In most patients, tolerance develops to the most common side effects, dizziness, and somnolence, with time. With close clinical monitoring at initiation or dose titration, pregabalin can be effectively used in primary care setting. Pregabalin is cost saving with long-term use and its cost-effectiveness profile is comparable, if not better, to that of other drugs used in fibromyalgia. In the present era of limited therapeutic options, pregabalin undoubtedly retains its role as one of cardinal drugs used in the treatment of fibromyalgia. This review intends to discuss the clinical utility of pregabalin in the management of fibromyalgia with a focus on efficacy, safety, and cost-effectiveness. PMID:26937205

  16. Safety and efficacy of roxatidine acetate. Evidence from pharmacodynamic and clinical trials.

    Science.gov (United States)

    Merki, H S; Bender, W; Labs, R

    1989-01-01

    The effects of a new H2-receptor antagonist, roxatidine acetate, have been investigated in both clinical and pharmacodynamic trials in Europe and the United States. A series of four double-blind randomized studies are reviewed, reporting the effects of different dose regimens of roxatidine acetate compared with ranitidine and placebo in healthy volunteers using continuous intragastric pH monitoring. These pharmacodynamic studies clearly demonstrate that roxatidine acetate is an effective gastric antisecretory agent, which is up to twice as potent as ranitidine. The results of several clinical studies of roxatidine acetate in patients with gastric as well as duodenal ulcer conducted in Europe, Japan, and the United States are also reviewed. These studies show that roxatidine acetate is comparable to other potent H2-receptor antagonists in terms of cumulative healing rates, pain relief, and safety. Overall, the pharmacodynamic and clinical data indicate that the efficacy of roxatidine acetate 75 mg twice-daily (b.i.d.) does not differ significantly from ranitidine 150 mg b.i.d. Roxatidine acetate is equally effective in the treatment of peptic disease including gastric ulcer, duodenal ulcer, and reflux esophagitis.

  17. Improving health IT through understanding the cultural production of safety in clinical settings.

    Science.gov (United States)

    Novak, Laurie Lovett

    2010-01-01

    Health IT is said to have the potential to improve the safety and effectiveness of care. However, it is known that the implementation of health IT can introduce new risks into the environment of care as a result of design failures, implementation failures, and unintended consequences. The design and implementation of health IT systems reflect explicit or implicit assumptions about what constitutes safe practice. These assumptions may clash with those held by patients and clinicians who are the intended users and subjects of the technology. Current perspectives on risk are discussed and an anthropological approach to understanding the construction of safe practices in the clinical setting is explored using research in barcode medication administration.

  18. Efficacy and safety of midazolam for sedation in pediatric dentistry: a controlled clinical trial.

    Science.gov (United States)

    Azevedo, Isabelita Duarte; Ferreira, Maria Angela Fernandes; da Costa, Anna Paula Serejo; Bosco, Vera Lúcia; Moritz, Rachel Duarte

    2013-01-01

    Pharmacological management of uncooperative children is becoming increasingly common in the dental setting. The purpose of this study was to determine the efficacy and safety of 3 different doses of midazolam for sedation in 2- to 4- year-old children with multiple dental needs and negative behavior. Ten children participated in this crossover, controlled, double-blinded clinical trial, which evaluated their behavior, appointment length and patient response after administration of 3 different doses of midazolam or placebo. Oxygen saturation, heart rate, respiratory rate, and blood pressure were monitored in all sessions. Sedated children exhibited a more positive behavior compared to the placebo group, both at the beginning of the appointment (sitting in the chair) and during administration of local anesthesia (P=.008 and Ppediatric sedation in the dosages studied.

  19. Internet access and online cancer information seeking among Latino immigrants from safety net clinics.

    Science.gov (United States)

    Selsky, Claire; Luta, George; Noone, Anne-Michelle; Huerta, Elmer E; Mandelblatt, Jeanne S

    2013-01-01

    Internet use is widespread, but little is known about Internet use for cancer information among Latinos, especially those who rely on safety net clinics. The authors investigated access to and intended use of the Internet for cancer information among low income, immigrant Latinos predominately from Central and South America. A cross-sectional study of 1,273 Latinos 21 years and older attending safety net clinics or health fairs was conducted from June 2007 to November 2008. The authors used logistic regression models to evaluate associations of age, acculturation, psychosocial factors and other covariates with Internet access and intended use of the Internet for cancer information among those with access. Of the sample, 44% reported Internet access. Higher information self-efficacy and greater trust in the Internet were independently associated with Internet access (p = .05 and p cancer help online if they needed information. Those with younger age and higher acculturation, education and self-efficacy had higher odds of intended Internet use for cancer information, considering covariates. In addition, those with high (vs. low) perceived risk of cancer (OR = 1.76; 95% CI [1.14, 2.73]; p = .01) and higher levels of trust in online health information (OR = 1.47 per one-point increase; 95% [CI 1.19, 1.82]; p = .0004) were more likely to intend to seek cancer information online. These findings that Internet access is fairly high in the immigrant Latino population and that the Internet is a trusted source of cancer information suggest that the Internet may be a channel for cancer control interventions.

  20. Clinical utility, safety and tolerability of capsule endoscopy in urban Southeast Asian population

    Institute of Scientific and Technical Information of China (English)

    Tiing-Leong Ang; Kwong-Ming Fock; Tay-Meng Ng; Eng-Kiong Teo; Yi-Lyn Tan

    2003-01-01

    AIM:Capsule endoscopy has demonstrated its clinical utility in the evaluation of small bowel pathology in several Western studies. In this prospective study, we aimed to determine the clinical utility, safety and tolerability of capsule endoscopy in the evaluation of suspected small bowel disease in an urban Southeast Asian population.METHODS: We used the given (M2A) capsule endoscopy system in 16 consecutive patients with suspected small bowel pathology. In 9 patients the indication was obscure gastrointestinal bleeding, while in 6 patients it was to determine the extent of small bowel involvement in Crohn's disease. One patient underwent capsule endoscopy for evaluation of chronic abdominal pain. Patient's tolerability to the procedure was evaluated by standardized questionnaires and all patients were reviewed at one week to ensure that the capsule had been excreted without any adverse events.RESULTS: Abnormal findings were present in 8 patients (50%). The cause of obscure gastrointestinal bleeding was determined in 5 out of 9 patients. Findings included 2 cases of angiodysplasia, 2 cases of jejunal ulcers and 1 case of both angiodysplasia and jejunal ulcer. One patient had small bowel erosions and foci of erythema of doubtful significance.Ileal lesions were diagnosed in 2 out of 6 patients with Crohn's disease. Capsule endoscopy was well tolerated by all patients. One patient with Crohn's disease had a complication of capsule retention due to terminal ileum stricture. The capsule eventually passed out spontaneously after 1 month.CONCLUSION: Our study, which represented the first Asian series, further confirms the diagnostic utility, safety and tolerability of wireless capsule endoscopy.

  1. Practice-based evidence: profiling the safety of cilostazol by text-mining of clinical notes.

    Directory of Open Access Journals (Sweden)

    Nicholas J Leeper

    Full Text Available BACKGROUND: Peripheral arterial disease (PAD is a growing problem with few available therapies. Cilostazol is the only FDA-approved medication with a class I indication for intermittent claudication, but carries a black box warning due to concerns for increased cardiovascular mortality. To assess the validity of this black box warning, we employed a novel text-analytics pipeline to quantify the adverse events associated with Cilostazol use in a clinical setting, including patients with congestive heart failure (CHF. METHODS AND RESULTS: We analyzed the electronic medical records of 1.8 million subjects from the Stanford clinical data warehouse spanning 18 years using a novel text-mining/statistical analytics pipeline. We identified 232 PAD patients taking Cilostazol and created a control group of 1,160 PAD patients not taking this drug using 1:5 propensity-score matching. Over a mean follow up of 4.2 years, we observed no association between Cilostazol use and any major adverse cardiovascular event including stroke (OR = 1.13, CI [0.82, 1.55], myocardial infarction (OR = 1.00, CI [0.71, 1.39], or death (OR = 0.86, CI [0.63, 1.18]. Cilostazol was not associated with an increase in any arrhythmic complication. We also identified a subset of CHF patients who were prescribed Cilostazol despite its black box warning, and found that it did not increase mortality in this high-risk group of patients. CONCLUSIONS: This proof of principle study shows the potential of text-analytics to mine clinical data warehouses to uncover 'natural experiments' such as the use of Cilostazol in CHF patients. We envision this method will have broad applications for examining difficult to test clinical hypotheses and to aid in post-marketing drug safety surveillance. Moreover, our observations argue for a prospective study to examine the validity of a drug safety warning that may be unnecessarily limiting the use of an efficacious therapy.

  2. Percutaneous left atrial appendage closure devices: safety, efficacy, and clinical utility

    Directory of Open Access Journals (Sweden)

    Swaans MJ

    2016-09-01

    Full Text Available Martin J Swaans, Lisette IS Wintgens, Arash Alipour,  Benno JWM Rensing, Lucas VA Boersma Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands Abstract: Atrial fibrillation (AF is the most common arrhythmia treated in the clinical practice. One of the major complications of AF is a thromboembolic cerebral ischemic event. Up to 20% of all strokes are caused by AF. Thromboembolic cerebral ischemic event in patients with AF occurs due to atrial thrombi, mainly from the left atrial appendage (LAA. Prevention of clot formation with antiplatelet agents and especially oral anticoagulants (­vitamin K antagonists or newer oral anticoagulants has been shown to be effective in reducing the stroke risk in patients with AF but has several drawbacks with (major bleedings as the most important disadvantage. Therefore, physical elimination of the LAA, which excludes the site of clot formation by surgical or percutaneous techniques, might be a good alternative. In this review, we discuss the safety, efficacy, and clinical utility of the Watchman™ LAA closure device. Keywords: stroke, left atrial appendage, prevention, atrial fibrillation

  3. Reducing medication errors and increasing patient safety: case studies in clinical pharmacology.

    Science.gov (United States)

    Benjamin, David M

    2003-07-01

    Today, reducing medication errors and improving patient safety have become common topics of discussion for the president of the United States, federal and state legislators, the insurance industry, pharmaceutical companies, health care professionals, and patients. But this is not news to clinical pharmacologists. Improving the judicious use of medications and minimizing adverse drug reactions have always been key areas of research and study for those working in clinical pharmacology. However, added to the older terms of adverse drug reactions and rational therapeutics, the now politically correct expression of medication error has emerged. Focusing on the word error has drawn attention to "prevention" and what can be done to minimize mistakes and improve patient safety. Webster's New Collegiate Dictionary has several definitions of error, but the one that seems to be most appropriate in the context of medication errors is "an act that through ingnorance, deficiency, or accident departs from or fails to achieve what should be done." What should be done is generally known as "the five rights": the right drug, right dose, right route, right time, and right patient. One can make an error of omission (failure to act correctly) or an error of commission (acted incorrectly). This article now summarizes what is currently known about medication errors and translates the information into case studies illustrating common scenarios leading to medication errors. Each case is analyzed to provide insight into how the medication error could have been prevented. "System errors" are described, and the application of failure mode effect analysis (FMEA) is presented to determine the part of the "safety net" that failed. Examples of reengineering the system to make it more "error proof" are presented. An error can be prevented. However, the practice of medicine, pharmacy, and nursing in the hospital setting is very complicated, and so many steps occur from "pen to patient" that there

  4. Pre-Clinical Study of a Novel Recombinant Botulinum Neurotoxin Derivative Engineered for Improved Safety.

    Science.gov (United States)

    Vazquez-Cintron, Edwin; Tenezaca, Luis; Angeles, Christopher; Syngkon, Aurelia; Liublinska, Victoria; Ichtchenko, Konstantin; Band, Philip

    2016-01-01

    Cyto-012 is a recombinant derivative of Botulinum neurotoxin Type A (BoNT/A). It primarily differs from wild type (wt) BoNT/A1 in that it incorporates two amino acid substitutions in the catalytic domain of the light chain (LC) metalloprotease (E224 > A and Y366 > A), designed to provide a safer clinical profile. Cyto-012 is specifically internalized into rat cortical and hippocampal neurons, and cleaves Synaptosomal-Associated Protein 25 (SNAP-25), the substrate of wt BoNT/A, but exhibits slower cleavage kinetics and therefore requires a higher absolute dose to exhibit pharmacologic activity. The pharmacodynamics of Cyto-012 and wt BoNT/A have similar onset and duration of action using the Digital Abduction Assay (DAS). Intramuscular LD50 values for Cyto-012 and wt BoNT/A respectively, were 0.63 ug (95% CI = 0.61, 0.66) and 6.22 pg (95% CI = 5.42, 7.02). ED50 values for Cyto-012 and wt BoNT/A were respectively, 0.030 ug (95% CI = 0.026, 0.034) and 0.592 pg (95% CI = 0.488, 0.696). The safety margin (intramuscular LD50/ED50 ratio) for Cyto-012 was found to be improved 2-fold relative to wt BoNT/A (p < 0.001). The DAS response to Cyto-012 was diminished when a second injection was administered 32 days after the first. These data suggest that the safety margin of BoNT/A can be improved by modulating their activity towards SNAP-25.

  5. Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia

    Directory of Open Access Journals (Sweden)

    Bhusal S

    2016-02-01

    Full Text Available Santosh Bhusal,1 Sherilyn Diomampo,1 Marina N Magrey2 1Division of Rheumatology, Metrohealth Medical Center, 2Case Western Reserve University School of Medicine at Metrohealth Medical Center, Cleveland OH, USA Abstract: Fibromyalgia is a chronic debilitating medical syndrome with limited therapeutic options. Pregabalin, an anticonvulsant and α-2-Δ subunit receptor ligand, is one of the anchor drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. The drug has shown clinically meaningful benefits across multiple symptom domains of fibromyalgia. Efficacy of pregabalin in fibromyalgia pain has been evaluated in at least five high-quality randomized trials, two long-term extension studies, a meta-analysis, a Cochrane database systematic review, and several post hoc analyses. These studies also hint towards a meaningful benefit on sleep, functioning, quality of life, and work productivity. Side effects of pregabalin, although common, are mild to moderate in intensity. They are noted early during therapy, improve or disappear with dose reduction, and are not usually life- or organ threatening. In most patients, tolerance develops to the most common side effects, dizziness, and somnolence, with time. With close clinical monitoring at initiation or dose titration, pregabalin can be effectively used in primary care setting. Pregabalin is cost saving with long-term use and its cost-effectiveness profile is comparable, if not better, to that of other drugs used in fibromyalgia. In the present era of limited therapeutic options, pregabalin undoubtedly retains its role as one of cardinal drugs used in the treatment of fibromyalgia. This review intends to discuss the clinical utility of pregabalin in the management of fibromyalgia with a focus on efficacy, safety, and cost-effectiveness. Keywords: fibrositis, myofascial pain, diffuse pain syndrome, lyrica

  6. Building clinical and organizational resilience to reconcile safety threats, tensions and trade-offs: insights from theory and evidence.

    Science.gov (United States)

    Jeffs, Lianne; Tregunno, Deborah; MacMillan, Kathleen; Espin, Sherry

    2009-01-01

    Healthcare delivery settings are complex adaptive and tightly coupled, interrelated systems. Within the larger healthcare system, a key subsystem is the "clinical microsystem" level. It is at this level that clinicians are faced with high levels of uncertainty in their daily work - uncertainty that impacts the quality and safety of care that patients receive. The first aim of this paper is to enhance healthcare leaders' understanding of what is currently known about safety threats and strategies to manage the inherent tensions and trade-offs that occur in everyday practice. The second aim is to inform strategies that build clinical and organizational resilience through a multi-level framework derived from the collective theoretical and empirical work. Together, this information can strengthen safety practices throughout healthcare organizations.

  7. Clinical effectiveness and safety of gemifloxacin versus cefpodoxime in acute exacerbation of chronic bronchitis: A randomized, controlled trial

    Directory of Open Access Journals (Sweden)

    S Chatterjee

    2011-01-01

    Conclusion : The results of this randomized, single-blind trial demonstrated that a 7-day course of gemifloxacin is therapeutically comparable to cefpodoxime in terms of both clinical effectiveness and safety for the treatment of type II Anthonisen category AECB patients.

  8. Safety and immunogenicity of recombinant human thrombin: a pooled analysis of results from 10 clinical trials.

    Science.gov (United States)

    Singla, Neil K; Foster, Kevin N; Alexander, W Allan; Pribble, John P

    2012-11-01

    To evaluate the safety and immunogenicity of recombinant human thrombin (rThrombin), an active topical stand-alone hemostatic agent. Analysis of pooled data from 10 rThrombin clinical trials. A total of 644 adult and pediatric patients treated with rThrombin; 609 patients were included in the immunogenicity analysis. In all studies, rThrombin was applied during a single surgical procedure (day 1); the procedures consisted of spinal procedures, major hepatic resection, peripheral arterial bypass, arteriovenous graft formation for hemodialysis access, and synchronous burn wound excision and skin grafting. A dosage of 1000 IU/ml of rThrombin was administered for more than 99% of patients. Adverse events and clinical laboratory values were monitored through day 29. Blood samples were obtained for immunogenicity analyses before the procedure and on day 29. Adverse events were mild or moderate in severity for the majority of patients; no patients discontinued from an rThrombin study due to adverse events. The most commonly reported adverse events in the 644 patients were incision site pain (305 patients [47.4%]), procedural pain (215 patients [33.4%]), and nausea (170 patients [26.4%]). Five patients (0.8%) died during the studies; all deaths were considered unrelated to rThrombin treatment. Antibodies to the rThrombin product developed in 5 (0.8%, 95% confidence interval 0.4-2.8%) of 609 patients by day 29, approximately 1 month after treatment; these antibodies did not neutralize the activity of native human thrombin. The development of antibodies did not appear to differ substantively by type of surgical procedure, amount of rThrombin administered, or patient age. Recombinant human thrombin was well tolerated, and adverse events were consistent with those reported in the postoperative setting in the surgical populations studied. Approximately 1 month after treatment, less than 1% of the patients had developed antibodies to the rThrombin product, and these

  9. Safety and efficacy of a raltegravir-based dual antiretroviral therapy in clinical practice

    Directory of Open Access Journals (Sweden)

    G Cenderello

    2012-11-01

    Full Text Available Background: HAART has revolutionized HIV disease management and increased life expectancy for most HIV-infected individuals on treatment. A nucleoside/tide reverse transcriptase (NRTI inhibitor backbone is a recommended component of standard first-line HAART. Nevertheless, NRTI-sparing alternatives are warranted in order to reduce long-term toxicities in many patients (pts. Aim of the study was to evaluate safety of raltegravir-based dual antiretroviral therapy (DUAL in a clinical practice setting. Methods: All pts on DUAL regimen followed at our outpatient HIV service on May 31st 2012 were recruited. Their clinical files were retrospectively studied. Collected data included: demographics, CDC staging, reason to DUAL switching, cholesterol (total and HDL, creatinine, CK, CD4+ count and HIV RNA were recorded at switch and every six months after for the first year. Change in CD4 count after the switch was evaluated by Student t-test. Results: The cohort included 55 pts (27 M; mean age was 54 years (38–72. HIV infection was acquired through: injective drug abuse (25, unprotected homosexual (24 and heterosexual (16 intercourse. CDC staging was: A=16, B=26, C=13. Mean previous treatment regimens were 4. At time of study pts had been on DUAL regimen for 23 months. They had been switched to DUAL therapy for: drug resistance (14; 25.5% (DRR or drug toxicity (41; 74.5%. The most frequently associated drug was darunavir/rtv (19; 34.5%, followed by atazanavir (13; 23.6%; 5 were unboosted; lopinavir/rtv (12; 21.8%, and NVP (11; 20%. DRR pts presented at baseline a mean viral load of 40,153 copies of HIV-RNA/ml; after at 12 months all but 3 showed undetectable (<40 copies viral load and a mean CD4 gain of 142 cells/ml. Pts switched to DUAL for toxicity presented persistent undetectable viral load and a mean CD4+gain of 94 cells/ml. The observed CD4+ increase in both groups (DRR and toxicity presented a statistical significance (p<0.01. Total and HDL

  10. Safety and Effects of the Vector for the Leber Hereditary Optic Neuropathy Gene Therapy Clinical Trial

    Science.gov (United States)

    Koilkonda, Rajeshwari D.; Yu, Hong; Chou, Tsung-Han; Feuer, William J.; Ruggeri, Marco; Porciatti, Vittorio; Tse, David; Hauswirth, William W.; Chiodo, Vince; Boye, Sanford L.; Lewin, Alfred S.; Neuringer, Martha; Renner, Lauren; Guy, John

    2014-01-01

    IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON. EXPOSURE Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3

  11. Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial.

    Science.gov (United States)

    Koilkonda, Rajeshwari D; Yu, Hong; Chou, Tsung-Han; Feuer, William J; Ruggeri, Marco; Porciatti, Vittorio; Tse, David; Hauswirth, William W; Chiodo, Vince; Boye, Sanford L; Lewin, Alfred S; Neuringer, Martha; Renner, Lauren; Guy, John

    2014-04-01

    IMPORTANCE We developed a novel strategy for treatment of Leber hereditary optic neuropathy (LHON) caused by a mutation in the nicotinamide adenine dinucleotide dehydrogenase subunit IV (ND4) mitochondrial gene. OBJECTIVE To demonstrate the safety and effects of the gene therapy vector to be used in a proposed gene therapy clinical trial. DESIGN AND SETTING In a series of laboratory experiments, we modified the mitochondrial ND4 subunit of complex I in the nuclear genetic code for import into mitochondria. The protein was targeted into the organelle by agency of a targeting sequence (allotopic expression). The gene was packaged into adeno-associated viral vectors and then vitreally injected into rodent, nonhuman primate, and ex vivo human eyes that underwent testing for expression and integration by immunohistochemical analysis and blue native polyacrylamide gel electrophoresis. During serial follow-up, the animal eyes underwent fundus photography, optical coherence tomography, and multifocal or pattern electroretinography. We tested for rescue of visual loss in rodent eyes also injected with a mutant G11778A ND4 homologue responsible for most cases of LHON. EXPOSURE Ocular infection with recombinant adeno-associated viral vectors containing a wild-type allotopic human ND4 gene. MAIN OUTCOMES AND MEASURES Expression of human ND4 and rescue of optic neuropathy induced by mutant human ND4. RESULTS We found human ND4 expressed in almost all mouse retinal ganglion cells by 1 week after injection and ND4 integrated into the mouse complex I. In rodent eyes also injected with a mutant allotopic ND4, wild-type allotopic ND4 prevented defective adenosine triphosphate synthesis, suppressed visual loss, reduced apoptosis of retinal ganglion cells, and prevented demise of axons in the optic nerve. Injection of ND4 in the ex vivo human eye resulted in expression in most retinal ganglion cells. Primates undergoing vitreal injection with the ND4 test article and followed up for 3

  12. Preclinical and phase 1 clinical safety of Setarud (IMOD™, a novel immunomodulator

    Directory of Open Access Journals (Sweden)

    P Khairandish

    2009-10-01

    Full Text Available "n "n  Background: A new herbal drug, Setarud (IMODTM that has been shown to have beneficial immune effects was tested to determine its acute and chronic toxicity in animals and to establish its intravenous form maximum tolerated dose (MTD in an open-labeled phase I clinical trial. Methods: BALB/c and C57BL/6 mice and Wistar rats were monitored for general state and biochemical markers for chronic test. At the end of chronic test, animals examined macroscopically and histologically. HIV-infected asymptomatic male patients with CD4 counts more than 200, were enrolled in the trial. Baseline dose was calculated from the 10% lethal dose (LD10 established in laboratory animal studies. Dose escalation was performed in four cohorts of 3 patients receiving IMODTM intravenously at a cohort-specific dose of 2, 4, 6.7, and 10 ml daily for 4 weeks. Patients were clinically examined at days of 1, 2, 3 and then weekly; and the safety was assessed on the basis of reports of adverse events, laboratory-test data and toxicity signs. Results: LD50 values in acute toxicity test were 42-66 and 50-56 ml/kg in i.m. and i.p. injections, respectively. Total scores of embryotoxicity during pregnancy were significantly lower in the Setarud group (p < 0.05. Pre-implantational deaths in the Setarud group were significantly higher, but post-implantational deaths level was lower than those in the control group. Inhibition of ossification in the skeletons of the fetuses and incidence of still birth were significantly higher while body weight of new-born rats of treatment group in the first month of their lifes were lower than those of the control group.In all four cohorts, there were no major side effects or dose-limiting toxicity, except for a mild sweating and weight loss in two patients from the first group that was reversed without discontinuation of the treatment. No clinically relevant trends in laboratory test results or ECG changes were noted. No adverse effect due to

  13. Translating Clinical Findings into Knowledge in Drug Safety Evaluation - Drug Induced Liver Injury Prediction System (DILIps)

    Science.gov (United States)

    Liu, Zhichao; Shi, Qiang; Ding, Don; Kelly, Reagan; Fang, Hong; Tong, Weida

    2011-01-01

    Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60–70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the “Rule of Three” was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity. PMID:22194678

  14. Clinical efficacy and safety in relapsed/refractory mantle cell lymphoma: a systematic literature review.

    Science.gov (United States)

    Njue, Annete; Colosia, Ann; Trask, Peter C; Olivares, Robert; Khan, Shahnaz; Abbe, Adeline; Police, Rachel; Wang, Jianmin; Ruiz-Soto, Rodrigo; Kaye, James A; Awan, Farrukh

    2015-01-01

    A systematic literature review was performed to collect and review information on the clinical efficacy and safety of treatments for relapsed/refractory (R/R) mantle cell lymphoma (MCL), with a meta-analysis, if possible. PubMed, Embase, and the Cochrane Library were searched for studies published in English from January 1, 1997, to August 2, 2012. Conference proceedings, bibliographic reference lists of included articles, recent reviews, and ClinicalTrials.gov were searched for phase II to IV studies displaying results. Studies were included if they reported on patients with R/R MCL who were ineligible to receive high-dose chemotherapy with stem cell transplant. Studies of patients with several non-Hodgkin lymphoma subtypes were only included if they reported MCL outcomes separately. We identified 59 studies in R/R MCL. Forty distinct treatment regimens were evaluated. Thirty studies included more than 15 patients with R/R MCL. Six studies were comparative (including 5 randomized controlled trials [RCTs]); 53 were single-arm. There were no common treatments among the RCTs; therefore, a meta-analysis was not feasible. Thirty-one of 59 studies reported baseline data for patients with R/R MCL. Of the 30 studies with > 15 patients with R/R MCL, 30 reported overall response rate data, 14 reported progression-free survival (PFS), and 12 reported overall survival (OS). The small number of RCTs in R/R MCL precludes identifying an optimal treatment. Small sample sizes, infrequent reporting of OS and PFS, and limited information on patient characteristics made a comparison of results difficult. High-quality comparative studies of novel therapies that have the potential to demonstrate OS advantages in R/R MCL are needed.

  15. Clinical efficacy and safety of topical versus oral ivermectin in treatment of uncomplicated scabies.

    Science.gov (United States)

    Ahmad, Hesham M; Abdel-Azim, Eman S; Abdel-Aziz, Rasha T

    2016-01-01

    Many medications are available for scabies treatment including oral and topical ivermectin. However, studies comparing these two forms as a scabies treatment are few. This study compares efficacy and safety of topical versus oral ivermectin as scabies treatment. The study included 62 confirmed uncomplicated scabies patients, divided into: Group I (32 patients, received topical ivermectin) and Group II (30 patients, received oral ivermectin). Patients were assessed, clinically and by KOH smear at 1, 2 and 4 weeks. Treatment was repeated after one week in patients with persistent infection. Adverse events were recorded. Most patients (87.5% and 73.5% in group I and group II respectively) were symptom free after a single treatment. A second treatment was required in 4 patients of group I and 8 patients of group II. However, 2 weeks after treatment symptoms and signs completely resolved in all cases with no recurrence at 4 weeks. This study suggests that both topical and oral ivermectin are safe and equally effective in treatment of uncomplicated scabies. Single treatment, whether topical or oral, is associated with high cure rate in a week post treatment. However, repeating treatment after one week may be required to achieve 100% cure.

  16. Scleral fixation of intraocular lenses using Gore-Tex suture: clinical outcomes and safety profile.

    Science.gov (United States)

    Khan, M Ali; Gupta, Omesh P; Smith, Ryan G; Ayres, Brandon D; Raber, Irving M; Bailey, Robert S; Hsu, Jason; Spirn, Marc J

    2016-05-01

    To report the short-term safety profile and clinical outcomes of scleral fixation of intraocular lenses (IOLs) using Gore-Tex suture. Retrospective, interventional case series. 85 eyes of 84 patients undergoing ab externo scleral fixation of a Bausch and Lomb Akreos AO60 or Alcon CZ70BD IOL using Gore-Tex suture. Primary outcome measures were change in visual acuity and occurrence of intraoperative and postoperative complications with minimum follow-up of 90 days. 85 eyes of 84 patients were identified. Mean logarithm of the minimum angle of resolution visual acuity improved from 1.43±0.72 (20/538 Snellen equivalent) preoperatively to 0.64±0.61 (20/87 Snellen equivalent) postoperatively (pGore-Tex suture was well tolerated in all cases. No suture-related complications were encountered. This procedure led to improvement in visual acuity and was not associated with significant intraoperative or postoperative complications. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Continuous infusion of porcine factor VIII: stability, microbiological safety and clinical experience.

    Science.gov (United States)

    DiMichele, D M; Gorman, P O; Kasper, C K; Mannucci, P M; Santagostino, E; Hay, C R M

    2002-01-01

    Porcine factor VIII (pFVIII) is an effective haemostatic treatment for bleeding in selected patients with FVIII inhibitors. Its use is sometimes associated with a transient fall in platelet count and transfusion reactions, the risk of which may be related to the rate of administration. Theoretical considerations suggest that the administration of pFVIII by continuous infusion should be effective, and could have pharmacokinetic advantages that lead to an improvement in the side-effect profile. The results of a retrospective survey of continuous infusion of pFVIII with respect to clinical safety and efficacy are reported. Porcine FVIII stability and microbiological studies are included. It is concluded that pFVIII given by continuous infusion is safe and effective. The risk of transfusion reactions and fall in platelet count appears to be reduced, compared with bolus administration. Stability studies showed that pFVIII activity declined at room temperature, most rapidly in the dilute solution (5-10 U mL(-1)). More concentrated mixtures showed acceptable stability for up to 24 h using a variety of infusion devices. Various concentrations of pFVIII did not support the growth of Escherichia coli or Staphylococcus aureus. These observations suggest that the porcine factor is suitable for continuous infusion (CI).

  18. A real-time safety and quality reporting system: assessment of clinical data and staff participation.

    Science.gov (United States)

    Rahn, Douglas A; Kim, Gwe-Ya; Mundt, Arno J; Pawlicki, Todd

    2014-12-01

    To report on the use of an incident learning system in a radiation oncology clinic, along with a review of staff participation. On September 24, 2010, our department initiated an online real-time voluntary reporting system for safety issues, called the Radiation Oncology Quality Reporting System (ROQRS). We reviewed these reports from the program's inception through January 18, 2013 (2 years, 3 months, 25 days) to assess error reports (defined as both near-misses and incidents of inaccurate treatment). During the study interval, there were 60,168 fractions of external beam radiation therapy and 955 brachytherapy procedures. There were 298 entries in the ROQRS system, among which 108 errors were reported. There were 31 patients with near-misses reported and 27 patients with incidents of inaccurate treatment reported. These incidents of inaccurate treatment occurred in 68 total treatment fractions (0.11% of treatments delivered during the study interval). None of these incidents of inaccurate treatment resulted in deviation from the prescription by 5% or more. A solution to the errors was documented in ROQRS in 65% of the cases. Errors occurred as repeated errors in 22% of the cases. A disproportionate number of the incidents of inaccurate treatment were due to improper patient setup at the linear accelerator (Psafety and quality in patient care. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Promoting Safety in Hypnosis: A Clinical Instrument for the Assessment of Alertness.

    Science.gov (United States)

    Howard, Hedy A

    2017-04-01

    Hypnosis has long demonstrated its power to facilitate various approaches to psychotherapy. Like other potent modalities, hypnosis may produce unwanted effects. Although its negative sequelae are usually mild and transient, more serious complications may occur. Recently, attention has been drawn to the powerful role of failures of dehypnosis or alerting/realerting in producing unwanted effects. Traditionally, alerting has been viewed as a relatively uncomplicated process that requires little more than the simple suggestion that the subject will return or awaken from trance, and exiting from trance has generally been considered the cessation of the phenomena suggested during induction and thereafter. Newer findings challenge these assumptions and suggest that restoring the subject to a prehypnotic baseline level of alertness is of equal or greater importance. Here, I describe the Howard Alertness Scale (HAS), with which subjects can be made aware of their baseline levels of alertness to help them understand the unique ways that their trance states differ from their normal alert states, and assess and measure their subjective perception of alertness before and after hypnosis. Furthermore, regular use of the HAS holds potential to enhance both the therapeutic alliance and the patient's sense of safety and mastery. The development and use of the HAS is discussed along with three vignettes illustrating its clinical application.

  20. Efficacy and safety of far infrared radiation in lymphedema treatment: clinical evaluation and laboratory analysis.

    Science.gov (United States)

    Li, Ke; Zhang, Zheng; Liu, Ning Fei; Feng, Shao Qing; Tong, Yun; Zhang, Ju Fang; Constantinides, Joannis; Lazzeri, Davide; Grassetti, Luca; Nicoli, Fabio; Zhang, Yi Xin

    2017-01-26

    Swelling is the most common symptom of extremities lymphedema. Clinical evaluation and laboratory analysis were conducted after far infrared radiation (FIR) treatment on the main four components of lymphedema: fluid, fat, protein, and hyaluronan. Far infrared radiation is a kind of hyperthermia therapy with several and additional benefits as well as promoting microcirculation flow and improving collateral lymph circumfluence. Although FIR therapy has been applied for several years on thousands of lymphedema patients, there are still few studies that have reported the biological effects of FIR on lymphatic tissue. In this research, we investigate the effects of far infrared rays on the major components of lymphatic tissue. Then, we explore the effectiveness and safety of FIR as a promising treatment modality of lymphedema. A total of 32 patients affected by lymphedema in stage II and III were treated between January 2015 and January 2016 at our department. After therapy, a significant decrease of limb circumference measurements was noted and improving of quality of life was registered. Laboratory examination showed the treatment can also decrease the deposition of fluid, fat, hyaluronan, and protein, improving the swelling condition. We believe FIR treatment could be considered as both an alternative monotherapy and a useful adjunctive to the conservative or surgical lymphedema procedures. Furthermore, the real and significant biological effects of FIR represent possible future applications in wide range of the medical field.

  1. Clinical efficacy and safety of HX575, a biosimilar recombinant human erythropoietin, in the management of anemia

    Directory of Open Access Journals (Sweden)

    Abraham I

    2012-09-01

    Full Text Available Ivo Abraham,1,2,3 Karen MacDonald21Department of Pharmacy Practice and Science, and Center for Health Outcomes and PharmoEconomic Research, University of Arizona, Tucson, Arizona; 2Department of Family and Community Medicine, University of Arizona, Tucson, Arizona; 3Matrix45, Tucson, Arizona, USAAbstract: Since the expiration of the patent for epoetin alfa in Europe in 2004, the European Medicines Agency has approved three biosimilar erythropoietins. Using the European Medicines Agency’s European Public Assessment Reports and scientific publications, we review the evidence regarding the clinical efficacy and safety of HX575 (Sandoz/Novartis relative to the originator product Eprex/Erypo (Johnson & Johnson. Clinical efficacy is assessed as a function of therapeutic equivalence of a biosimilar and originator product, while safety is evaluated in terms of immunogenicity, venous thromboembolism, and mortality. Five studies that examined chronic renal failure and oncology populations are reviewed. In the renal setting, these studies include a randomized controlled trial on Hb maintenance in patients receiving long-term hemodialysis, a randomized safety trial in patients with chronic kidney disease not yet requiring renal replacement therapy, and a post-approval saftey commitment study. Studies in the cancer setting include a clinical validation study in patients with solid tumors receiving antineoplastic chemotherapy and a retrospective clinical audit of Binocrit in routine clinical practice. Based on available therapeutic equivalence and safety data, the clinical and safety outcomes of treatment with HX575 are likely to be similar to those of the originator product Eprex/Erypo. Both products can be considered interchangeable in the management of anemia in the approved indications, and patients transferred from the reference product to the biosimilar product are expected to show the same efficacy and safety outcomes. There is no evidence of the

  2. Clinical efficacy and safety of Tevagrastim® (XM02, a biosimilar recombinant human granulocyte colony-stimulating factor

    Directory of Open Access Journals (Sweden)

    Bagalagel A

    2013-08-01

    Full Text Available Alaa Bagalagel,1,2 Abdulaziz Mohammed,1,2 Karen MacDonald,3 Ivo Abraham1,3–5 1Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, Tucson, AZ, USA; 2College of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 3Matrix45, Tucson, AZ, USA; 4Department of Pharmacy Practice and Science, University of Arizona, Tucson, AZ, USA; 5Department of Family and Community Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA Abstract: Since the expiration of the patent for filgrastim in Europe in 2006, the European Medicines Agency has approved three biosimilar granulocyte colony-stimulating factors, while the US Food and Drug Administration has approved one of these agents. Using the European Medicines Agency’s and the Food and Drug Administration’s regulatory reports and scientific publications, we review the evidence about the clinical efficacy and safety of XM02 (Tevagrastim® relative to the originator product filgrastim (Neupogen®. Clinical efficacy is assessed in terms of equivalence of XM02 and Neupogen®, while safety is evaluated in terms of immunogenicity, bone pain, splenomegaly, allergic reactions, acute respiratory distress syndrome, and mortality. Three Phase III studies in breast cancer patients treated with docetaxel/doxorubicin chemotherapy, lung cancer patients receiving platinum-based chemotherapy, and non-Hodgkin’s lymphoma receiving chemotherapy are reviewed. Also included is a postapproval, single-center experience study on peripheral blood stem mobilization. Based on the available therapeutic equivalence and safety data, the clinical and safety outcomes of XM02 are likely to be similar to those of Neupogen®. XM02 and Neupogen® can be considered interchangeable in the approved indications. Patients previously on Neupogen® and converted to XM02 can be expected to show similar efficacy and safety outcomes. Keywords: biosimilars, biosimilar pharmaceuticals, efficacy, safety

  3. Antibiotic resistance and molecular characterization of probiotic and clinical Lactobacillus strains in relation to safety aspects of probiotics.

    Science.gov (United States)

    Klein, Günter

    2011-02-01

    The evaluation of the safety of probiotic strains includes the exclusion of antibiotic resistance of clinical importance. Ninety-two strains from the genus Lactobacillus isolated from probiotics, food, and clinical sources were included in the investigation. Species tested were the L. acidophilus group, L. casei group, L. reuteri/fermentum group, and L. sakei/curvatus group. Cell and colony morphology, fermentation patterns, and growth characteristics as well as soluble whole cell proteins were analyzed. Antibiotic resistance against clinically important agents was determined by broth dilution tests. The vanA and tet genes were confirmed. Resistances occurred mainly against gentamicin, ciprofloxacin, clindamycin, sulfonamides, and, in some cases, glycopeptides. The natural glycopeptide resistance within the L. casei group and L. reuteri appears to be not of clinical relevance, as there was no vanA gene present. Therefore, the transfer of this resistance is very unlikely. Tet-(A), -(B), -(C), -(M), or -(O) gene could not be detected. The protein fingerprinting within the L. casei group proved that L. rhamnosus strains of clinical origin clustered together with probiotic strains. For safety evaluations resistance patterns of a broad range of strains are a useful criterion together with the exclusion of known resistance genes (like the vanA gene) and can be used for decision making on the safety of probiotics, both by authorization bodies and manufacturers.

  4. Frontline experiences of a practice redesign to improve self-management of obesity in safety net clinics.

    Science.gov (United States)

    AuYoung, Mona; Duru, O Kenrik; Ponce, Ninez A; Mangione, Carol M; Rodriguez, Hector P

    2015-01-01

    Teamlets of physicians and medical assistants may help improve obesity management in primary care settings. We aimed to understand the barriers and facilitators of implementing a teamlet approach to managing obesity in 3 safety net clinics. Key stakeholder interviews (n = 21) were conducted both during early implementation of practice change and 6 months later. Patient surveys (n = 393) examined obese patient activation and health status. Insufficient program resources and limited patient engagement due to external factors were implementation barriers despite fairly high patient activation. Staff members need time and resources to execute new responsibilities to support obesity management in safety net settings. Because of high turnover, multiple supporters may improve sustainability.

  5. Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the Göttingen minipig

    DEFF Research Database (Denmark)

    Bjarkam, Carsten R; GLUD, AN; Margolin, Lee

    2010-01-01

    Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the Göttingen minipig......Safety and function of a new clinical intracerebral microinjection instrument for stem cells and therapeutics examined in the Göttingen minipig...

  6. Role of Large Clinical Datasets From Physiologic Monitors in Improving the Safety of Clinical Alarm Systems and Methodological Considerations: A Case From Philips Monitors.

    Science.gov (United States)

    Sowan, Azizeh Khaled; Reed, Charles Calhoun; Staggers, Nancy

    2016-09-30

    Large datasets of the audit log of modern physiologic monitoring devices have rarely been used for predictive modeling, capturing unsafe practices, or guiding initiatives on alarm systems safety. This paper (1) describes a large clinical dataset using the audit log of the physiologic monitors, (2) discusses benefits and challenges of using the audit log in identifying the most important alarm signals and improving the safety of clinical alarm systems, and (3) provides suggestions for presenting alarm data and improving the audit log of the physiologic monitors. At a 20-bed transplant cardiac intensive care unit, alarm data recorded via the audit log of bedside monitors were retrieved from the server of the central station monitor. Benefits of the audit log are many. They include easily retrievable data at no cost, complete alarm records, easy capture of inconsistent and unsafe practices, and easy identification of bedside monitors missed from a unit change of alarm settings adjustments. Challenges in analyzing the audit log are related to the time-consuming processes of data cleaning and analysis, and limited storage and retrieval capabilities of the monitors. The audit log is a function of current capabilities of the physiologic monitoring systems, monitor's configuration, and alarm management practices by clinicians. Despite current challenges in data retrieval and analysis, large digitalized clinical datasets hold great promise in performance, safety, and quality improvement. Vendors, clinicians, researchers, and professional organizations should work closely to identify the most useful format and type of clinical data to expand medical devices' log capacity.

  7. Cardiovascular Safety of One-Year Escitalopram Therapy in Clinically Nondepressed Patients With Acute Coronary Syndrome

    DEFF Research Database (Denmark)

    Hanash, Jamal A; Hansen, Baiba H; Hansen, Jørgen F

    2012-01-01

    : Selective serotonin reuptake inhibitors are commonly used for treatment of depression in patients with cardiac diseases. However, evidence of cardiovascular (CV) safety from randomized trials is based on studies of no longer than 6-month duration. We examined the CV safety of 1-year treatment w...... with Selective serotonin reuptake inhibitor escitalopram compared with placebo in patients with recent acute coronary syndrome (ACS)....

  8. Impact of Safety-Related Regulatory Action on Clinical Practice A Systematic Review

    NARCIS (Netherlands)

    Piening, Sigrid; Haaijer-Ruskamp, Flora M.; de Vries, Jonie T. N.; van der Elst, Menno E.; de Graeff, Pieter A.; Straus, Sabine M. J. M.; Mol, Peter G. M.

    2012-01-01

    Background: After market approval, new serious safety issues are regularly identified for drugs that lead to regulatory action to inform healthcare professionals. However, the effectiveness of these safety-related regulatory actions is under question. We currently lack a comprehensive overview of th

  9. Safety pharmacology: an essential interface of pharmacology and toxicology in the non-clinical assessment of new pharmaceuticals.

    Science.gov (United States)

    Claude, Jean-Roger; Claude, Nancy

    2004-06-15

    Safety pharmacology studies are defined as the studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure. In consequence, these studies are an integral part of the non-clinical safety assessment of new pharmaceuticals, in association with toxicological studies. A retrospective shows the evolution of the discipline in these last years. Safety pharmacology studies are of special interest, and some drawbacks and pitfalls must be considered (i.e. invasive methods, difficulties related to GLP (good laboratory practices) requirements, choice of a strategy). In the future, some priority should be given to education, promotion of scientific activities, reinforcement of the links between pharmacologists and toxicologists and implementation of relevant guidelines.

  10. Clinical safety and tolerability issues in use of triazole derivatives in management of fungal infections

    Directory of Open Access Journals (Sweden)

    Dionissios Neofytos

    2010-04-01

    Full Text Available Dionissios Neofytos1, Edina Avdic2, Anna-Pelagia Magiorakos31Transplant and Oncology Infectious Disease Program, The Johns Hopkins University School of Medicine, Division of Infectious Diseases, 2Department of Pharmacy, The Johns Hopkins Hospital, Baltimore, USA; 3Scientific Advice Unit, European Centre for Disease Prevention and Control, Stockholm, SwedenAbstract: There has been an increase in the number of patients susceptible to invasive fungal infections (IFIs leading to a greater need for effective, well tolerated, and easily administered antifungal agents. The advent of triazoles has revolutionized the care of patients requiring treatment or prophylaxis for IFIs. However, triazoles have been associated with a number of adverse events and significant drug–drug interactions. While commonly used, physicians and patients should be aware of the distinct properties of these agents in order to ensure that patients are optimally treated with the least amount of toxicity possible. Clinicians should have a full understanding of the basic pharmacokinetics, absorption, and bioavailability of triazoles. Moreover, knowledge of the drug–drug interactions and potential toxicities of each agent is critical prior to administering a triazole. Careful history taking, thorough review of the patient’s medication list, and detailed discussion with the patients and their families about the efficacy, safety, and tolerability of these agents should be performed. Clinicians treating patients with triazoles should closely follow them, monitor pertinent laboratory tests, and consider measuring drug levels as needed. This article will review the basic pharmacokinetic properties and most frequently encountered adverse events and pitfalls associated with triazoles in clinical practice. Keywords: triazoles, fluconazole, voriconazole, posaconazole, itraconazole, review, invasive fungal infections, adverse events, drug–drug interactions

  11. The Safety of Multiple Flexible Sigmoidoscopies with Mucosal Biopsies in Healthy Clinical Trial Participants.

    Science.gov (United States)

    Chiu, Wai Kan; Brand, Rhonda M; Camp, Danielle; Edick, Stacey; Mitchell, Carol; Karas, Sherri; Zehmisch, Amanda; Ho, Ken; Brand, Randall E; Harrison, Janet; Abo, Steven; Cranston, Ross D; McGowan, Ian

    2017-08-01

    During Phase 1 pharmacokinetic/pharmacodynamics studies, participants may undergo multiple sigmoidoscopies, with a collection of 10-20 biopsies during each procedure. This article characterizes the safety of flexible sigmoidoscopies in clinical trial participants. We determined the number of flexible sigmoidoscopies and rectal biopsies that participants underwent and analyzed the frequency, duration, and severity of flexible sigmoidoscopy-related adverse events (AEs). During the study period, 278 participants underwent 1,004 flexible sigmoidoscopies with the collection of 15,930 rectal biopsies. The average number of procedures per participant was 3.6 (median 3; range 1-25), with an average time interval between procedures of 61.8 days (median 28 days; range 1-1,159). There were no serious AEs. Sixteen AEs were related to flexible sigmoidoscopy and occurred in 16 participants, leading to an overall 1.6% (16/1,004) AE rate per procedure and 0.1% (16/15,930) AE rate per biopsy. Of the 16 AEs, 8 (50%) involved abdominal pain, diarrhea, bleeding, flatulence, and bloating, with an average duration of 4.7 days (median 1 day; range 1-28). Most (14/16) AEs were categorized as Grade 1 (mild), whereas two of the AEs were Grade 2 (moderate). No participant withdrew due to procedure-related AEs. Overall, the number of AEs caused by flexible sigmoidoscopy with multiple biopsies was low and the severity was mild, suggesting that this procedure can be safely integrated into protocols requiring repeated intestinal mucosal sampling.

  12. A phase II clinical trial to assess the safety of clonidine in acute organophosphorus pesticide poisoning

    Directory of Open Access Journals (Sweden)

    Karunatilake Harindra

    2009-08-01

    Full Text Available Abstract Background An estimated 2–3 million people are acutely poisoned by organophosphorus pesticides each year, mostly in the developing world. There is a pressing need for new affordable antidotes and clonidine has been shown to be effective in animal studies. Our aim was to determine the safety of clonidine given as an antidote in adult patients presenting with signs or symptoms of acute organophosphate ingestion. Methods This study was a dose finding, open-label, multicentre, phase II trial. Forty eight patients with acute organophosphate poisoning were randomized to receive either clonidine or placebo: Four to receive placebo and twelve to receive clonidine at each dose level. The first dose level was an initial loading dose of 0.15 mg followed by an infusion of 0.5 mg of clonidine over 24 hours. The initial loading dose was increased to 0.3 mg, 0.45 and 0.6 mg. at all dosing levels however the subsequent infusion remained at 0.5 mg of clonidine over 24 hours. Results The baseline characteristics of both groups were similar. The trial was stopped after completion of the 3rd dosing level. At the 1st and 2nd dosing level there were no reported adverse drug reactions. At the 3rd dosing level 5 patients (42% developed significant hypotension during clonidine treatment that responded to intravenous fluids. There were no statistical differences in ventilation rate, pre and post GCS, and mortality rates over all levels. Conclusion Our findings suggest use of moderate doses of clonidine in acute organophosphate poisoning can be used without causing frequent clinical problems but that higher doses are associated with a high incidence of hypotension requiring intervention. Further studies are needed to study the efficacy of clonidine as an antidote in organophosphate poisoning. Trial registration Current Controlled Trial ISRCTN89917816.

  13. Safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis therapy for ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Takayuki Yamamoto; Satoru Umegae; Koichi Matsumoto

    2006-01-01

    Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions.Typical adverse reactions were dizziness, nausea,headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC.GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However,most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, doubleblind, sham-controlled trials are necessary. A seriousproblem with GMCAP is cost; a single session costs (¥)145 000 ($1 300

  14. Safety of efalizumab in patients with moderate to severe chronic plaque psoriasis: review of clinical data. part II.

    Science.gov (United States)

    Papp, Kim A; Camisa, Charles; Stone, Stephen P; Caro, Ivor; Wang, Xiaolin; Compton, Peter; Walicke, Patricia A; Gottlieb, Alice B

    2005-12-01

    The efficacy and safety of efalizumab have been evaluated in multiple clinical trials. The purpose of this review is to provide an overview of the safety profile of efalizumab during the clinical trials. Twelve-week data from four placebo-controlled trials were pooled and analyzed. Data from patients receiving 13-60 weeks of efalizumab therapy were pooled to evaluate longer-term safety. The most common adverse events were mild to moderate, self-limiting, flu-like symptoms that were most frequent following the first two efalizumab doses; by the third dose the incidence was comparable to placebo. Serious adverse events were observed in 2.2% and 1.7% of efalizumab- and placebo-treated patients, respectively. Nonserious adverse events leading to withdrawal were infrequent and similar to placebo (2.8% vs 1.8%). There does not appear to be increased risk of end-organ toxicity, infection, or malignancy in efalizumab-treated patients. Efalizumab was well tolerated, with a favorable safety profile.

  15. Undergraduate baccalaureate nursing students' self-reported confidence in learning about patient safety in the classroom and clinical settings: an annual cross-sectional study (2010-2013).

    Science.gov (United States)

    Lukewich, Julia; Edge, Dana S; Tranmer, Joan; Raymond, June; Miron, Jennifer; Ginsburg, Liane; VanDenKerkhof, Elizabeth

    2015-05-01

    Given the increasing incidence of adverse events and medication errors in healthcare settings, a greater emphasis is being placed on the integration of patient safety competencies into health professional education. Nurses play an important role in preventing and minimizing harm in the healthcare setting. Although patient safety concepts are generally incorporated within many undergraduate nursing programs, the level of students' confidence in learning about patient safety remains unclear. Self-reported patient safety competence has been operationalized as confidence in learning about various dimensions of patient safety. The present study explores nursing students' self-reported confidence in learning about patient safety during their undergraduate baccalaureate nursing program. Cross-sectional study with a nested cohort component conducted annually from 2010 to 2013. Participants were recruited from one Canadian university with a four-year baccalaureate of nursing science program. All students enrolled in the program were eligible to participate. The Health Professional Education in Patient Safety Survey was administered annually. The Health Professional Education in Patient Safety Survey captures how the six dimensions of the Canadian Patient Safety Institute Safety Competencies Framework and broader patient safety issues are addressed in health professional education, as well as respondents' self-reported comfort in speaking up about patient safety issues. In general, nursing students were relatively confident in what they were learning about the clinical dimensions of patient safety, but they were less confident about the sociocultural aspects of patient safety. Confidence in what they were learning in the clinical setting about working in teams, managing adverse events and responding to adverse events declined in upper years. The majority of students did not feel comfortable speaking up about patient safety issues. The nested cohort analysis confirmed these

  16. Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

    Science.gov (United States)

    Avigan, Mark I; Bjornsson, Einar S; Pasanen, Markku; Cooper, Charles; Andrade, Raul J; Watkins, Paul B; Lewis, James H; Merz, Michael

    2014-11-01

    A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration.

  17. Clinical efficacy and safety of SB309, a biosimilar recombinant human erythropoietin, in the management of anemia

    Directory of Open Access Journals (Sweden)

    Bagalagel A

    2013-08-01

    Full Text Available Alaa Bagalagel,1,2 Abdulaziz Mohammed,1,2 Karen MacDonald,3 Ivo Abraham1,3–5 1Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, Tucson, AZ, USA; 2College of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 3Matrix45, Tucson, AZ, USA; 4Department of Pharmacy Practice and Science, College of Pharmacy, 5Department of Family and Community Medicine, College of Medicine, University of Arizona, Tucson, AZ, USA Abstract: In this second part of a series of three reviews of approved biosimilar erythropoietins, we review the evidence pertaining to the clinical efficacy and safety of SB309 relative to the originator product Eprex®/Erypo®. As in the first review, clinical efficacy is assessed with respect to the therapeutic equivalence of the biosimilar and originator product, while safety is evaluated in terms of immunogenicity, venous thromboembolism, and mortality. Seven studies in chronic renal failure and oncology populations are reviewed. In the renal setting, these include two randomized controlled trials on hemoglobin correction and maintenance in patients receiving long-term hemodialysis; open extension safety studies from both trials analyzed as a pooled database; a post hoc analysis on biosimilar and originator switching; a therapeutic equivalence study of subcutaneously administered SB309 and Eprex/Erypo; and a single-center experience study. In the cancer setting, one open-label non-controlled study is reported. Based on the available therapeutic equivalence and safety data, the clinical and safety outcomes of treatment with SB309 are likely to be similar to those of the originator product Eprex/Erypo. Both products can be considered interchangeable in the management of anemia for the approved indications. Patients transferred from reference product to biosimilar can be expected to show the same efficacy and safety outcomes. There is no evidence of the interchangeability of SB309 with other biosimilar

  18. The role of clinical pharmacology and pharmacogenetics in electroconvulsive therapy : from safety to efficacy

    NARCIS (Netherlands)

    Mirzakhani, Hooman

    2016-01-01

    Electroconvulsive therapy (ECT) is the transcutaneous application of small electrical stimuli to the brain to produce generalized seizure for the treatment of selected psychiatric disorders, mostly treatment resistant depression, acute mania, and schizophrenic syndromes. Safety of ECT increases the

  19. Pre-clinical safety assessment of Ad[I/PPT-E1A], a novel oncolytic adenovirus for prostate cancer.

    Science.gov (United States)

    Schenk, Ellen; Essand, Magnus; Kraaij, Robert; Adamson, Rachel; Maitland, Norman; Bangma, Chris H

    2014-02-18

    Prostate cancer is the most common malignancy in the Western world. Patients can only be cured when the tumour has not metastasised outside the prostate. However, treatment with curative intent fails in a significant number of men, often resulting in untreatable progressive disease with a fatal outcome. Oncolytic adenovirus therapy may be a promising adjuvant treatment to reduce local failure or the outgrowth of micrometastatic disease. Within the European gene therapy consortium GIANT, we have developed a novel prostate-specific oncolytic adenovirus: Ad[I/PPT-E1A] that specifically kills prostate cells via prostate-specific replication. This paper describes the clinical development of Ad[I/PPT-E1A] with particular reference to the pre-clinical safety assessment of this novel virus. The pre-clinical safety assessment involved an efficacy study in a human orthotopic xenograft mouse model, a specificity study in human primary cells and a toxicity study in normal mice. These studies confirmed that Ad[I/PPT-E1A] efficiently kills prostate tumour cells in vivo, is not harmful to other organs and is well-tolerated in mice after systemic delivery. The safety, as well as the immunological effects of Ad[I/PPT-E1A] as a local adjuvant therapy will now be studied in a phase I dose-escalating trial in patients with localised prostate cancer who are scheduled for curative radical prostatectomy and can be used as an updated paradigm for similar therapeutic viruses.

  20. Clinical efficacy and safety of Zarzio® (EP2006, a biosimilar recombinant human granulocyte colony-stimulating factor

    Directory of Open Access Journals (Sweden)

    Tharmarajah S

    2014-03-01

    Full Text Available Soba Tharmarajah,1,2 Abdulaziz Mohammed,3,4 Alaa Bagalagel,3,4 Karen MacDonald,2 Ivo Abraham2,3,5 1College of Pharmacy, University of Arizona, Tucson, AZ, USA; 2Matrix45, Tucson, AZ, USA; 3Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, University of Arizona, Tucson, AZ, USA; 4College of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ, USA Abstract: This second review of biosimilar granulocyte colony-stimulating factors approved by the European Medicines Agency evaluates the evidence on the clinical efficacy and safety of prophylaxis of (febrile neutropenia with Zarzio® in chemotherapy-treated cancer patients relative to the originator product filgrastim (Neupogen®. Source documents include: publicly available documents of the European Medicines Agency; a published article reviewing the (preapproval clinical development of EP2006 (Zarzio®; and published (postapproval single-center experience reports on prophylaxis with Zarzio®, including two reports in the cancer setting and one in the setting of autologous peripheral blood stem cell mobilization. Also included is: a pooled analysis of these and other postapproval studies in the cancer setting that includes (interim data from the two single cancer center reports; one additional single-center experience study; one completed study; and one ongoing multicenter postapproval study. Based on the available therapeutic equivalence and safety data, the clinical and safety outcomes of Zarzio® are likely to be similar to those of Neupogen®. Thus, Zarzio® and Neupogen® may be assumed interchangeable. Keywords: biosimilars, biosimilar pharmaceuticals, efficacy, safety, granulocyte colony stimulating factor, recombinant proteins

  1. Safety and tolerability of duloxetine in the treatment of patients with fibromyalgia: pooled analysis of data from five clinical trials.

    Science.gov (United States)

    Choy, Ernest H S; Mease, Philip J; Kajdasz, Daniel K; Wohlreich, Madelaine M; Crits-Christoph, Paul; Walker, Daniel J; Chappell, Amy S

    2009-09-01

    The purpose of this report is to describe the overall safety profile of both short- and longer-term duloxetine treatment of fibromyalgia. Data from four double-blind, randomized, placebo-controlled studies (two with 6-month open-label extension phases) and a 1-year, open-label safety study were included. Safety measures included treatment-emergent adverse events (TEAEs), adverse events leading to discontinuation, serious adverse events (SAEs), clinical laboratory tests, vital signs, and electrocardiograms. The most common TEAEs for short-term treatment with duloxetine were nausea (29.3%), headache (20.0%), dry mouth (18.2%), insomnia (14.5%), fatigue (13.5%), constipation (14.5%), diarrhea (11.6%), and dizziness (11.0%; all p treatment studies, with no new adverse events emerging at a notable rate. About 20% of patients discontinued due to adverse events in the short-term treatment studies and in the 1-year study. SAEs were uncommon, and none occurred at a significantly higher frequency for duloxetine compared with placebo. Mean changes in vital signs and weight were small. Rates of treatment-emergent potentially clinically significant (PCS) vital sign, laboratory, and electrocardiogram measures were low, with only PCS rates of alanine aminotransferase being significantly higher for duloxetine compared with placebo in the placebo-controlled treatment studies. In the 1-year study, four patients (1.1%) had suicide-related behavior. The data provided here summarize short- and long-term safety from five clinical studies in patients treated with duloxetine for fibromyalgia. In addition, postmarketing surveillance continues for adverse events reported with duloxetine in fibromyalgia, as in other indications.

  2. Advances in stent technologies and their effect on clinical efficacy and safety

    Directory of Open Access Journals (Sweden)

    Nikam N

    2014-06-01

    Full Text Available Navin Nikam, Toby B Steinberg, Daniel H SteinbergDivision of Cardiology, Medical University of South Carolina, Charleston, SC, USAAbstract: The introduction of intracoronary stents represented a major advance in interventional cardiology. While bare metal stents set the benchmark for improved safety over angioplasty, intimal hyperplasia and subsequent restenosis were important limitations. First-generation drug-eluting stents demonstrated significant improvements in efficacy, but not necessarily safety, and further technologic developments have focused on optimizing both. Current advances and understanding in stent design continue to improve on these concepts. This review summarizes past and present technology with particular emphasis on the principles underlying the efficacy and safety of drug-eluting stents, and offers a glimpse into the next generations of stents aimed at treating symptomatic coronary artery disease.Keywords: drug-eluting stents percutaneous coronary intervention, coronary artery disease, bioabsorbable polymers, bioabsorbable struts, polymer free

  3. Role of Large Clinical Datasets From Physiologic Monitors in Improving the Safety of Clinical Alarm Systems and Methodological Considerations: A Case From Philips Monitors

    Science.gov (United States)

    Reed, Charles Calhoun; Staggers, Nancy

    2016-01-01

    Background Large datasets of the audit log of modern physiologic monitoring devices have rarely been used for predictive modeling, capturing unsafe practices, or guiding initiatives on alarm systems safety. Objective This paper (1) describes a large clinical dataset using the audit log of the physiologic monitors, (2) discusses benefits and challenges of using the audit log in identifying the most important alarm signals and improving the safety of clinical alarm systems, and (3) provides suggestions for presenting alarm data and improving the audit log of the physiologic monitors. Methods At a 20-bed transplant cardiac intensive care unit, alarm data recorded via the audit log of bedside monitors were retrieved from the server of the central station monitor. Results Benefits of the audit log are many. They include easily retrievable data at no cost, complete alarm records, easy capture of inconsistent and unsafe practices, and easy identification of bedside monitors missed from a unit change of alarm settings adjustments. Challenges in analyzing the audit log are related to the time-consuming processes of data cleaning and analysis, and limited storage and retrieval capabilities of the monitors. Conclusions The audit log is a function of current capabilities of the physiologic monitoring systems, monitor’s configuration, and alarm management practices by clinicians. Despite current challenges in data retrieval and analysis, large digitalized clinical datasets hold great promise in performance, safety, and quality improvement. Vendors, clinicians, researchers, and professional organizations should work closely to identify the most useful format and type of clinical data to expand medical devices’ log capacity. PMID:27694097

  4. Efficacy and Safety of Cariprazine in Acute Exacerbation of Schizophrenia: Results From an International, Phase III Clinical Trial.

    Science.gov (United States)

    Kane, John M; Zukin, Stephen; Wang, Yao; Lu, Kaifeng; Ruth, Adam; Nagy, Krisztián; Laszlovszky, István; Durgam, Suresh

    2015-08-01

    This phase III study evaluated the efficacy and safety of cariprazine, a dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, in patients with acute exacerbation of schizophrenia. Patients were randomized to 6-week double-blind treatment with placebo, cariprazine 3 to 6 mg/d, or cariprazine 6 to 9 mg/d. Primary and secondary efficacy: change from baseline to week 6 in Positive and Negative Syndrome Scale total and Clinical Global Impressions-Severity scores, respectively, analyzed using a mixed-effects model for repeated measures adjusting for multiple comparisons. Safety included treatment-emergent adverse events, clinical laboratory values, vital signs, electrocardiograms, ophthalmologic examination, Columbia-Suicide Severity Rating Scale, and extrapyramidal symptom scales. In the Safety Population (placebo, n = 147; cariprazine 3-6 mg/d, n = 151; cariprazine 6-9 mg/d, n = 148), 60.5% of patients completed the study. At week 6, statistically significant least squares mean differences in favor of cariprazine versus placebo were observed for Positive and Negative Syndrome Scale total score (3-6 mg/d: -6.8, P = 0.003; 6-9 mg/d: -9.9, P Global Impressions-Severity (3-6 mg/d: -0.3, P = 0.012; 6-9 mg/d: -0.5, P effective treatment for schizophrenia.

  5. Translating self-persuasion into an adolescent HPV vaccine promotion intervention for parents attending safety-net clinics.

    Science.gov (United States)

    Baldwin, Austin S; Denman, Deanna C; Sala, Margarita; Marks, Emily G; Shay, L Aubree; Fuller, Sobha; Persaud, Donna; Lee, Simon Craddock; Skinner, Celette Sugg; Wiebe, Deborah J; Tiro, Jasmin A

    2017-04-01

    Self-persuasion is an effective behavior change strategy, but has not been translated for low-income, less educated, uninsured populations attending safety-net clinics or to promote human papillomavirus (HPV) vaccination. We developed a tablet-based application (in English and Spanish) to elicit parental self-persuasion for adolescent HPV vaccination and evaluated its feasibility in a safety-net population. Parents (N=45) of age-eligible adolescents used the self-persuasion application. Then, during cognitive interviews, staff gathered quantitative and qualitative feedback on the self-persuasion tasks including parental decision stage. The self-persuasion tasks were rated as easy to complete and helpful. We identified six question prompts rated as uniformly helpful, not difficult to answer, and generated non-redundant responses from participants. Among the 33 parents with unvaccinated adolescents, 27 (81.8%) reported deciding to get their adolescent vaccinated after completing the self-persuasion tasks. The self-persuasion application was feasible and resulted in a change in parents' decision stage. Future studies can now test the efficacy of the tablet-based application on HPV vaccination. The self-persuasion application facilitates verbalization of reasons for HPV vaccination in low literacy, safety-net settings. This self-administered application has the potential to be more easily incorporated into clinical practice than other patient education approaches. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Mobile health and patient engagement in the safety net: a survey of community health centers and clinics.

    Science.gov (United States)

    Broderick, Andrew; Haque, Farshid

    2015-05-01

    Patient-centered technologies have emerged as a way to actively engage patients in care. The reach and potential of cell phones to engage diverse patient populations is great. Evidence of their effectiveness in improving health-related outcomes is limited. Researchers conducted an online survey of community health centers and clinics to assess if and how health care providers in the safety net use cell phones to support patient engagement. The findings indicate that the use of cell phones in patient care is at an early stage of deployment across the safety net. Organizations identify chronic disease management as an area where cell phones offer considerable potential to effectively engage patients. To promote widespread adoption and use, technical assistance to support the implementation and management of interventions, evidence-based or best practice models that highlight successful implementation strategies in care delivery, and the introduction of new payment or reimbursement policies will be essential.

  7. Patient safety and quality of care: how may clinical simulation contribute?

    DEFF Research Database (Denmark)

    Jensen, Sanne

    2015-01-01

    The usability of health information technology (IT) is increasingly recognized as critically important to the development of systems that ensure patient safety and quality of care. The substantial complexity of organizations, work practice and physical environments within the healthcare sector in...

  8. Glucagon-Like Peptide-1 Receptor Agonists for Type 2 Diabetes:A Clinical Update of Safety and Efficacy

    Science.gov (United States)

    Drab, Scott R.

    2016-01-01

    Abstract: Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly being used for the treatment of type 2 diabetes mellitus, but consideration of benefits and potential adverse events is required. This review examines the state of glycemic control, weight loss, blood pressure, and tolerability, as well as the current debate about the safety of GLP-1 RAs, including risk of pancreatitis, pancreatic cancer, and thyroid cancer. Methods A MEDLINE search (2010-2015) identified publications that discussed longer-acting GLP-1 RAs. Search terms included GLP-1 receptor agonists, liraglutide, exenatide, lixisenatide, semaglutide, dulaglutide, albiglutide, efficacy, safety, pancreatitis, pancreatic cancer, and thyroid cancer. Abstracts from the American Diabetes Association, European Association for the Study of Diabetes, and American Association of Clinical Endocrinologists from 2010 to 2015 were also searched. Efficacy and safety studies, pooled analyses, and meta-analyses were prioritized. Results Research has confirmed that GLP-1 RAs provide robust glycemic control, weight loss, and blood pressure re-duction. Current studies do not prove increased risk of pancreatitis, pancreatic cancer, or thyroid cancer but more trials are needed since publications that indicate safety or suggest increased risk have methodological flaws that prevent firm conclusions to be drawn about these rare, long-term events. Conclusion GLP-1 RA therapy in the context of individualized, patient-centered care continues to be supported by current literature. GLP-1 RA therapy provides robust glycemic control, blood pressure reduction, and weight loss, but studies are still needed to address concerns about tolerability and safety, including pancreatitis and cancer. PMID:26694823

  9. Curbing the urge to care : A Bourdieusian analysis of the effect of the caring disposition on nurse middle managers’ clinical leadership in patient safety practices

    NARCIS (Netherlands)

    Lalleman, P. C B; Smid, G. A C; Lagerwey, M. D.; Shortridge-Baggett, L. M.; Schuurmans, M. J.

    2016-01-01

    Background Nurse managers play an important role in implementing patient safety practices in hospitals. However, the influence of their professional background on their clinical leadership behaviour remains unclear. Research has demonstrated that concepts of Bourdieu (dispositions of habitus,

  10. Safety and efficacy of gadoteric acid in pediatric magnetic resonance imaging: overview of clinical trials and post-marketing studies.

    Science.gov (United States)

    Balassy, Csilla; Roberts, Donna; Miller, Stephen F

    2015-11-01

    Gadoteric acid is a paramagnetic gadolinium macrocyclic contrast agent approved for use in MRI of cerebral and spinal lesions and for body imaging. To investigate the safety and efficacy of gadoteric acid in children by extensively reviewing clinical and post-marketing observational studies. Data were collected from 3,810 children (ages 3 days to 17 years) investigated in seven clinical trials of central nervous system (CNS) imaging (n = 141) and six post-marketing observational studies of CNS, musculoskeletal and whole-body MR imaging (n = 3,669). Of these, 3,569 children were 2-17 years of age and 241 were younger than 2 years. Gadoteric acid was generally administered at a dose of 0.1 mmol/kg. We evaluated image quality, lesion detection and border delineation, and the safety of gadoteric acid. We also reviewed post-marketing pharmacovigilance experience. Consistent with findings in adults, gadoteric acid was effective in children for improving image quality compared with T1-W unenhanced sequences, providing diagnostic improvement, and often influencing the therapeutic approach, resulting in treatment modifications. In studies assessing neurological tumors, gadoteric acid improved border delineation, internal morphology and contrast enhancement compared to unenhanced MR imaging. Gadoteric acid has a well-established safety profile. Among all studies, a total of 10 children experienced 20 adverse events, 7 of which were thought to be related to gadoteric acid. No serious adverse events were reported in any study. Post-marketing pharmacovigilance experience did not find any specific safety concern. Gadoteric acid was associated with improved lesion detection and delineation and is an effective and well-tolerated contrast agent for use in children.

  11. Safety and efficacy of gadoteric acid in pediatric magnetic resonance imaging: overview of clinical trials and post-marketing studies

    Energy Technology Data Exchange (ETDEWEB)

    Balassy, Csilla [Medical University of Vienna, Vienna General Hospital, Department of Radiology, Division of General and Pediatric Radiology, Vienna (Austria); Roberts, Donna [Medical University of South Carolina, Department of Radiology, Charleston, SC (United States); Miller, Stephen F. [LeBonheur Children' s Hospital, Department of Radiology, Memphis, TN (United States)

    2015-11-15

    Gadoteric acid is a paramagnetic gadolinium macrocyclic contrast agent approved for use in MRI of cerebral and spinal lesions and for body imaging. To investigate the safety and efficacy of gadoteric acid in children by extensively reviewing clinical and post-marketing observational studies. Data were collected from 3,810 children (ages 3 days to 17 years) investigated in seven clinical trials of central nervous system (CNS) imaging (n = 141) and six post-marketing observational studies of CNS, musculoskeletal and whole-body MR imaging (n = 3,669). Of these, 3,569 children were 2-17 years of age and 241 were younger than 2 years. Gadoteric acid was generally administered at a dose of 0.1 mmol/kg. We evaluated image quality, lesion detection and border delineation, and the safety of gadoteric acid. We also reviewed post-marketing pharmacovigilance experience. Consistent with findings in adults, gadoteric acid was effective in children for improving image quality compared with T1-W unenhanced sequences, providing diagnostic improvement, and often influencing the therapeutic approach, resulting in treatment modifications. In studies assessing neurological tumors, gadoteric acid improved border delineation, internal morphology and contrast enhancement compared to unenhanced MR imaging. Gadoteric acid has a well-established safety profile. Among all studies, a total of 10 children experienced 20 adverse events, 7 of which were thought to be related to gadoteric acid. No serious adverse events were reported in any study. Post-marketing pharmacovigilance experience did not find any specific safety concern. Gadoteric acid was associated with improved lesion detection and delineation and is an effective and well-tolerated contrast agent for use in children. (orig.)

  12. Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Sophia Gailhardou

    2016-07-01

    Full Text Available A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2-60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged ≥9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target

  13. Non-clinical and Pre-clinical Testing to Demonstrate Safety of the Barostim Neo Electrode for Activation of Carotid Baroreceptors in Chronic Human Implants

    Directory of Open Access Journals (Sweden)

    Seth J. Wilks

    2017-08-01

    Full Text Available The Barostim neo™ electrode was developed by CVRx, Inc.to deliver baroreflex activation therapy (BAT™ to treat hypertension and heart failure. The neo electrode concept was designed to deliver electrical stimulation to the baroreceptors within the carotid sinus bulb, while minimizing invasiveness of the implant procedure. This device is currently CE marked in Europe, and in a Pivotal (akin to Phase III Trial in the United States. Here we present the in vitro and in vivo safety testing that was completed in order to obtain necessary regulatory approval prior to conducting human studies in Europe, as well as an FDA Investigational Device Exemption (IDE to conduct a Pivotal Trial in the United States. Stimulated electrodes (10 mA, 500 μs, 100 Hz were compared to unstimulated electrodes using optical microscopy and several electrochemical techniques over the course of 27 weeks. Electrode dissolution was evaluated by analyzing trace metal content of solutions in which electrodes were stimulated. Lastly, safety testing under Good Laboratory Practice guidelines was conducted in an ovine animal model over a 12 and 24 week time period, with results processed and evaluated by an independent histopathologist. Long-term stimulation testing indicated that the neo electrode with a sputtered iridium oxide coating can be stimulated at maximal levels for the lifetime of the implant without clinically significant dissolution of platinum or iridium, and without increasing the potential at the electrode interface to cause hydrolysis or significant tissue damage. Histological examination of tissue that was adjacent to the neo electrodes indicated no clinically significant signs of increased inflammation and no arterial stenosis as a result of 6 months of continuous stimulation. The work presented here involved rigorous characterization and evaluation testing of the neo electrode, which was used to support its safety for chronic implantation. The testing

  14. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies.

    Science.gov (United States)

    Iffland, Kerstin; Grotenhermen, Franjo

    2017-01-01

    Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs. Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients' compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam's side effects. Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.

  15. CLINICAL EVALUATION OF EFFICACY AND SAFETY OF DEXMEDETOMEDINE AS AN ADJUNCT TO CAUDAL ROPIVACAINE IN PEDIATRIC INFRAUMBILICAL SURGERIES

    Directory of Open Access Journals (Sweden)

    Urmila

    2014-05-01

    Full Text Available BACKGROUND: Caudal epidural is one of the most popular reliable & safe technique mainly used for intra and post-op analgesia in pediatric patients undergoing infra umbilical surgeries. To prolong the duration of analgesia various adjuvants like epinephrine, opioids, ketamine, midazolam, tramadol, clonidine, were added to local anesthetic. The aim of this study was to evaluate the clinical efficacy and safety of CAUDAL administration of plain Ropivacaine 0.2% (1miligram/kilogram body weight with and without dexmedetomedine (2 microgram/kilogram body weight in children undergoing infraumbilical surgeries; in terms of quality of surgical anesthesia and the duration of post-operative analgesia.

  16. Clinical safety and wear resistance of the phospholipid polymer-grafted highly cross-linked polyethylene liner.

    Science.gov (United States)

    Moro, Toru; Takatori, Yoshio; Tanaka, Sakae; Ishihara, Kazuhiko; Oda, Hiromi; Kim, Yoon Taek; Umeyama, Takashige; Fukatani, Eisei; Ito, Hideya; Kyomoto, Masayuki; Oshima, Hirofumi; Tanaka, Takeyuki; Kawaguchi, Hiroshi; Nakamura, Kozo

    2016-11-03

    To reduce the production of wear particles and subsequent aseptic loosening, we created a human articular cartilage-mimicked surface for a highly cross-linked polyethylene liner, whose surface grafted layer consisted of a biocompatible phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine). Although our previous in vitro findings showed that poly(2-methacryloyloxyethyl phosphorylcholine)-grafted particles were biologically inert and caused no subsequent bone resorptive responses, and poly(2-methacryloyloxyethyl phosphorylcholine) grafting markedly decreased wear in hip joint simulator tests, the clinical safety, and in vivo wear resistance of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners remained open to question. Therefore, in the present study, we evaluated clinical and radiographic outcomes of poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners 5 years subsequent to total hip replacement in 68 consecutive patients. No reoperation was required for any reason, and no adverse events were associated with the implanted liners. The average Harris Hip Score increased from 38.6 preoperatively to 96.5 5 years postoperatively, and health-related quality of life, as indicated by the Short Form 36 Health Survey, improved. Radiographic analyses showed no periprosthetic osteolysis or implant migration. Between 1 and 5 years postoperatively, the mean steady-state wear rate was 0.002 mm/year, which represented a marked reduction relative to other highly cross-linked polyethylene liners, and appeared to be unaffected by patient-related or surgical factors. Although longer follow up is required, poly(2-methacryloyloxyethyl phosphorylcholine)-grafted highly cross-linked polyethylene liners improved mid-term clinical outcomes. The clinical safety and wear-resistance results are encouraging with respect to the improvement of long-term clinical outcomes with poly(2

  17. The clinical efficiency and safety of bisorpolol hydrochlorothiazide in patients with mild to moderate essential hypertension

    Institute of Scientific and Technical Information of China (English)

    姜红

    2006-01-01

    Objective To investigate the efficacy and safety of bisorpolol/hydroehlorothiazide (Lodoz) in patients with mild and moderate essential hypertension. Methods After 2 weeks of placebo run-in period, 90 hypertensive patients with sitting diastolic blood pressure (DBP) between 95 and 109 mm Hg(1 mm Hg =0. 133 kPa) and systolic blood pressure (SBP) below 180 mm Hg were treated by Lodoz(2. 5 mg/6. 25 mg/day) for 4 weeks.

  18. The Clinical Study of the Safety Time Limitation with One-lung Ventilation

    Institute of Scientific and Technical Information of China (English)

    QIN Haiqing; ZHAO Ruming; ZOU Xuechao; LIU Ji

    2002-01-01

    Objective To explore an extension of the safety time limitation during adult lung operations with one - lung ventilation(OLV). Methods Sixteen adult patients, all were introduced double lumen endobronchial tubes. Its demands were that counterpoints must be well. A compound solution of Procaine was dripped in vein to maintain anesthesia. Using anesthesia machine controlled ventilation: VT10ml/kg, RR 12b/min, FiO2 > 0.95, I:E = 1:2. Regularly sampling arterial blood made gases analysis from preanesthesia to the end of operations. Results PaO2 was the lowest at 30 minute after OLV in these patients. But it was still in the safety limitation. At 45 minute, it started to rise again and kept it at the high level to the end. Its length may attain four hours and a half. Meanwhile the circulation was stable. There were no postoperative anesthetic complication with hypoxemia during operations. Conclusion So long as the counterpoint of endobronchial tubes is accurate, ventilation properly managed, selectin from anesthetic suitable, circulatory function normal, the safety time limitation might last more than three hours and a half during adult lung operations with OLV.

  19. Clinical efficacy and safety of biosimilar epoetin: focus on epoetin zeta

    Directory of Open Access Journals (Sweden)

    Mikhail A

    2015-09-01

    Full Text Available Ashraf Mikhail , Christopher BrownRenal Unit, Morriston Hospital, Wales, UK Abstract: Biosimilars have been developed for several biologic therapeutic agents, including erythropoiesis-stimulating agents. Biosimilars cannot be assumed to be completely identical to the reference product. Several regulatory bodies have issued stringent guidelines to regulate the licensing of biosimilars. These guidelines, although share a unified aim of ensuring the safety and efficacy of biosimilars, show several differences. Such differences may reflect the difficulties facing regulatory bodies in defining a biosimilar, identifying sensitive means to assess equivalence in efficacy, and designing robust methodologies to monitor long-term safety. This review will discuss some of the aspects of differences in licensing requirements for biosimilars, comparing the European Medicines Agency guidelines and the American Food and Drug Administration guidelines. The pathway adopted by the manufacturer of a biosimilar (epoetin zeta to gain licensing within the European market will be assessed, analyzing its compliance with the European Medicines Agency guidelines for the approval process. Since many patients are likely to be switched from original drugs to biosimilars in future, there is a need to establish strict guidelines on interchangeability and substitution of biosimilars and original products and to make it an integral part of the pre-registration assessment of any biosimilar in future. Eventually, long-term, observational post-marketing data will provide further reassurance on safety and tolerability of biosimilars. Keywords: biosimilars, erythropoiesis-stimulating agents, epoetin zeta, biologic therapeutic agents

  20. 5% Lidocaine Medicated Plaster for the Treatment of Postherpetic Neuralgia: A Review of the Clinical Safety and Tolerability.

    Science.gov (United States)

    Navez, Marie Louise; Monella, Christopher; Bösl, Irmgard; Sommer, Daniela; Delorme, Claire

    2015-06-01

    Postherpetic neuralgia (PHN) is a common, very painful, and often long-lasting complication of herpes zoster which is frequently underdiagnosed and undertreated. It mainly affects the elderly, many of whom are already treated for comorbidities with a variety of systemic medications and are thus at high risk of drug-drug interactions. An efficacious and safe treatment with a low interaction potential is therefore of high importance. This review focuses on the safety and tolerability of the 5% lidocaine medicated plaster, a topical analgesic indicated for the treatment of PHN. The available literature (up to June 2014) was searched for publications containing safety data regarding the use of the 5% lidocaine medicated plaster in PHN treatment; unpublished clinical safety data were also included in this review. The 5% lidocaine medicated plaster demonstrated good short- and long-term tolerability with low systemic uptake (3 ± 2%) and minimal risk for systemic adverse drug reactions (ADRs). ADRs related to topical lidocaine treatment were mainly application site reactions of mild to moderate intensity. The treatment discontinuation rate was generally below 5% of patients. In one trial, the 5% lidocaine medicated plaster was better tolerated than systemic treatment with pregabalin. The 5% lidocaine medicated plaster provides a safe alternative to systemic medications for PHN treatment, including long-term pain treatment.

  1. Clinical safety and efficacy of implantation of octacalcium phosphate collagen composites in tooth extraction sockets and cyst holes

    Directory of Open Access Journals (Sweden)

    Tadashi Kawai

    2016-09-01

    Full Text Available It was demonstrated that octacalcium phosphate collagen composite achieved notable bone regeneration in bone defects in preclinical studies. On the basis of the research results, an investigator-initiated exploratory clinical trial was conducted after approval from a local Institutional Review Board. This clinical study was performed as a single-arm non-randomized intervention study. Octacalcium phosphate collagen composite was implanted into a total of 10 cases of alveolar bone defects after tooth extractions and cystectomy. Safety assessment was performed in terms of the clinical course and several consecutive laboratory examinations, and sequential radiographs were used for efficacy assessment. All participants uneventfully completed the clinical trial without major problems in their general condition. Postoperative wound swelling was observed, as also commonly seen in tooth extraction or cystectomy. Although no serious liver dysfunction, renal dysfunction, electrolyte imbalance, or abnormal urinalysis results were recognized, the number of white blood cells and C-reactive protein level temporarily increased after the operation. An increase in radiopacity in the octacalcium phosphate collagen composite–implanted site was observed in all cases. Finally, the border between the original bone and the octacalcium phosphate collagen composite–implanted site became indistinguishable. These results suggest that octacalcium phosphate collagen composite could be utilized safely in clinical situations in the future.

  2. Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

    Science.gov (United States)

    Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

    2014-09-15

    A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173.

  3. Safety and Efficacy of 5-Aminolevulinic Acid for High Grade Glioma in Usual Clinical Practice: A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Pilar Teixidor

    Full Text Available During the last decade, the use of 5-aminolevulinic acid (5-ALA has been steadily increasing in neurosurgery. The study's main objectives were to prospectively evaluate the effectiveness and safety of 5-ALA when used in clinical practice setting on high-grade gliomas' patients.National, multicenter and prospective observational study.authorized conditions of use of 5-ALA.contraindication to 5-ALA, inoperable or partial resected tumors, pregnancy and children. Epidemiological, clinical, laboratory, radiological, and safety data were collected. Effectiveness was assessed using complete resection of the tumor, and progression-free and overall survival probabilities.Between May 2010 and September 2014, 85 patients treated with 5-ALA were included, and 77 were suitable for the effectiveness analysis. Complete resection was achieved in 41 patients (54%. Surgeons considered suboptimal the fluorescence of 5-ALA in 40% of the patients assessed. The median duration of follow-up was 12.3 months. The progression-free survival probability at 6 months was 58%. The median duration overall survival was 14.2 months. Progression tumor risk factors were grade of glioma, age and resection degree; and death risk factors were grade of glioma and gender. No severe adverse effects were reported. At one month after surgery, new or increased neurological morbidity was 6.5%. Hepatic enzymes were frequently increased within the first month after surgery; however, they subsequently normalized, and this was found to have no clinical significance.In clinical practice, the 5-ALA showed a good safety profile, but the benefits related to 5-ALA have not been yet clearly shown. The improved differentiation expected by fluorescence between normal and tumor cerebral tissue was suboptimal in a relevant number of patients; in addition, the expected higher degree of resection was lower than in clinical trials as well as incomplete resection was not identified as a prognostic factor

  4. Fesoterodine clinical efficacy and safety for the treatment of overactive bladder in relation to patient profiles: a systematic review.

    Science.gov (United States)

    Chapple, Christopher; Oelke, Matthias; Kaplan, Steven A; Scholfield, David; Arumi, Daniel; Wagg, Adrian S

    2015-06-01

    To summarize published evidence on the pharmacology, efficacy, and safety of fesoterodine for the treatment of overactive bladder (OAB) symptoms in relation to patient clinical and demographic profiles. A systematic review of published articles on fesoterodine was conducted via a PubMed search. Articles were identified using the search term fesoterodine, with limits of human species and abstract available. Review and meta-analysis articles, validation studies, articles focused on treatment compliance/adherence, meeting abstracts, and articles not focused on oral fesoterodine administration in human subjects were excluded. Data from retained articles were summarized descriptively. Of 137 articles identified, 61 (15 articles on the pharmacology and 46 articles on the efficacy and/or safety of fesoterodine) met inclusion criteria. Superiority trials demonstrated the additional efficacy of fesoterodine 8 mg versus fesoterodine 4 mg and tolterodine extended release 4 mg in treating OAB. Prospective trials in specific patient populations indicated beneficial effects of fesoterodine in elderly patients, vulnerable elderly patients, patients dissatisfied with or with a suboptimal response to previous antimuscarinic therapy, patients with urge urinary incontinence (UUI) or nocturnal urgency, and men with persistent LUTS during alpha-blocker treatment. With two effective doses, the fesoterodine dose can be adjusted to achieve optimal efficacy and tolerability in individual patients. The most common adverse events during fesoterodine treatment are dry mouth and constipation. Extensive evidence demonstrates the efficacy and safety of fesoterodine in relieving OAB symptoms, including urgency, urinary frequency, UUI, and nocturnal urgency, in patients with various clinical and demographic profiles. Trial results provide valuable information on fesoterodine treatment in specific patient populations, including both elderly and vulnerable elderly patients. Potential

  5. ASSESSMENT OF RELATED ANAMNESTIC AND CLINICAL FACTORS ON EFFICACY AND SAFETY OF ANTI-HELICOBACTER PYLORI THERAPY

    Directory of Open Access Journals (Sweden)

    D. N. Andreev

    2016-01-01

    Full Text Available The article presents the results of a prospective clinical study in which 100 patients with H. pylori-associated peptic ulcer disease of stomach/duodenum were examined. The aim of the study was to assess the effect of concomitant anamnestic and clinical factors on the efficacy and safety of eradication therapy (ET. Type 2 diabetes mellitus is a factor that significantly reduces the efficiency of ET with OR 0.21 (95% CI 0,06-0,69, p = 0,0102. Using a macrolide antibiotics prior to ET during the previous 12 months is associated with a reduction in the effectiveness of H. pylori eradication with OR 0.27 (95% CI 0,08-0,90, p = 0,0342. Despite the lack of statistical significance observed negative effect on the efficiency of ET factors such as smoking and increased BMI. Smoking, female gender, age over 50 years and the presence of type 2 diabetes mellitus had no significant impact on the safety profile of ET. 

  6. Carbon-11 labeled diacylglycerol for signal transduction imaging by positron CT. Evaluation of the quality and safety for clinical use

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Ryou [Nishijin Hospital, Kyoto (Japan); Imahori, Yoshio; Ido, Tatsuo [and others

    1995-02-01

    To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-{sup 11}C]butyryl-2-palmitoyl-rac-glycerol: {sup 11}C-DAG) using positron emission computed tomography (PET), we evaluated the quality and the safety of {sup 11}C-DAG as the solution for injection. As a result, {sup 11}C-DAG was synthesized within 50 minutes, including the preparation step for injection. The half life time and energy spectrum of {sup 11}C-DAG were the same as the physical character of carbon-11, and other radioisotopes were not detected. In the quality control, {sup 11}C-DAG solution was negative in the examination of bacterial contamination and the pyrogen test in three successive synthesis procedures. In the acute toxicity test by administration of {sup 11}C-DAG and 100 {mu}mol/kg of non-radioactive DAG to the rat intravenously, the systemic condition of the rat was not changed and no abnormalities were found in any organ 24 hours after administration. These findings indicated the safety of {sup 11}C-DAG solution. Clinical application of {sup 11}C-DAG using positron emission tomography may be useful to elucidate the dysfunction of intracellular signaling in disorders of higher cortical function such as Alzheimer disease. (author).

  7. An update on the safety and tolerability of pimecrolimus cream 1%: evidence from clinical trials and post-marketing surveillance.

    Science.gov (United States)

    Langley, Richard G B; Luger, Thomas A; Cork, Michael J; Schneider, Dirk; Paul, Carle

    2007-01-01

    In this report, we review the data on the safety and tolerability of pimecrolimus cream 1% (Elidel) from clinical trials and post-marketing surveillance in patients with atopic dermatitis. These data demonstrate that topically applied pimecrolimus is minimally absorbed through the skin and has a favourable safety margin. The most common treatment-related adverse events are transient local reactions, particularly skin burning (16.1 and 12.9 events per 1,000 patient-months of follow-up in adults and children, respectively). When compared to the vehicle, the use of pimecrolimus cream 1% is associated with an increased incidence of herpes simplex virus infections in children (relative risk: 2.5; 95% confidence interval: 1.2-5.8; p = 0.017). However, pimecrolimus cream 1% does not increase the incidence of any skin infection in comparison with moderately potent topical corticosteroids and lacks other corticosteroid-related side effects such as skin atrophy. While cases of malignancy have been reported in patients who have used pimecrolimus cream 1%, there is no clinical evidence to establish that treatment with pimecrolimus cream 1% increases the risk of malignancy.

  8. Medication safety.

    Science.gov (United States)

    Keohane, Carol A; Bates, David W

    2008-03-01

    Patient safety is a state of mind, not a technology. The technologies used in the medical setting represent tools that must be properly designed, used well, and assessed on an on-going basis. Moreover, in all settings, building a culture of safety is pivotal for improving safety, and many nontechnologic approaches, such as medication reconciliation and teaching patients about their medications, are also essential. This article addresses the topic of medication safety and examines specific strategies being used to decrease the incidence of medication errors across various clinical settings.

  9. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

    Directory of Open Access Journals (Sweden)

    Solmi M

    2017-06-01

    -generation antipsychotics (SGAs ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis. Keywords: antipsychotics, side effects, tolerability, safety, psychosis, psychiatry

  10. Cross matching observations on toxicological and clinical data for the assessment of tolerability and safety of Ginkgo biloba leaf extract.

    Science.gov (United States)

    Heinonen, Tuula; Gaus, Wilhelm

    2015-01-02

    Ginkgo biloba is one of the most widely used herbal remedies in Europe and the US. It may be purchased in different types of formulations, but most of the clinical studies have been performed with the controlled G. biloba extract EGb761(®). Indications include Alzheimers disease, cardiovascular disease, dementia, memory loss, and cerebral ischemia. The pharmacological modes of action cover antioxidant effects, radical scavenging, inhibition of platelet activating factor, alterations in membrane fluidity (signal transduction), and inhibition of glucocorticoid synthesis. Due to the widespread and long-term use of G. biloba - about a million doses of EGb761(®) are sold per day - tolerability and safety are a crucial issue. Based on broad and long-term clinical use of G. biloba extracts, it is regarded as well tolerated in man. Cross matching, a tool we introduced, combines different fields of knowledge and types of data to a consolidated result. In this article, we combine toxicological and clinical data and utilize other sources of information to assess tolerability and safety of G. biloba. It is well known that because of biological differences between animals and man or even between animal species, animal experiments do not necessarily mimic the effects in humans. Therefore, for adequate risk assessment, the relevance of non-clinical toxicological findings should be correlated with human data. The cross matching of toxicological data and results from clinical studies is possible because many toxicological and clinical studies are available on G. biloba. We give an in depth analysis of the modes of action in animals and describe toxicological studies with regard to metabolism, pharmacokinetics, genotoxicity, as well as carcinogenicity (e.g., the Technical Report TR 578 of the US National Toxicology Program). In addition, 75 clinical trials with high methodological quality are summarized. They included a total of 7115 patients treated with G. biloba. Based on this

  11. Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder.

    Science.gov (United States)

    Chapple, Christopher; Van Kerrebroeck, Philip; Tubaro, Andrea; Haag-Molkenteller, Cornelia; Forst, Hans-Theo; Massow, Ute; Wang, Joseph; Brodsky, Marina

    2007-10-01

    To determine the efficacy, tolerability, and safety of fesoterodine in subjects with overactive bladder (OAB). This was a multicentre, randomised, double-blind, placebo- and active-controlled trial with tolterodine extended release (ER) to assess the efficacy and safety of fesoterodine. Eligible subjects (> or =18 yr) with increased micturition frequency and urgency and/or urgency urinary incontinence (UUI) were randomised to placebo, fesoterodine 4 mg, fesoterodine 8 mg, or tolterodine ER 4 mg for 12 wk. The primary efficacy variable was a change from baseline to week 12 in micturitions per 24 h. Co-primary end points included change from baseline to week 12 in UUI episodes per 24 h and Treatment Response ("yes" or "no," based on four-point treatment benefit scale). Secondary efficacy variables included mean volume voided per micturition, continent days per week, and number of urgency episodes. At the end of treatment, subjects taking fesoterodine 4 and 8 mg had significant (pfesoterodine 8 mg at most end points. Both doses of fesoterodine were significantly better than placebo in improving the symptoms of OAB and produced a significantly greater Treatment Response versus placebo. Efficacy was more pronounced with fesoterodine 8 mg compared with the other treatments. Active treatments were well tolerated.

  12. In the Ethos of the Safety Net: An Expanded Role for Clinical Ethics Mediation.

    Science.gov (United States)

    McGreevy, Jolion

    2015-01-01

    Clinical ethics mediation is invaluable for resolving intractable disputes in the hospital. But it is also a critical day-to-day skill for clinicians, especially those who serve a disproportionate number of vulnerable patients. While mediation is typically reserved for intractable cases, there are two important opportunities to expand its use. First is preventative mediation, in which clinicians incorporate clinical ethics mediation into their daily routine in order to address value-laden conflicts before they reach the point at which outside consultation becomes necessary. Second is guided mediation, in which clinical teams resolve conflicts with patients or surrogates with guidance from an ethics consultant, who operates at some distance from the conflict and, rather than recommending a single action, counsels clinicians on the process they can use to resolve the conflict on their own. These approaches build the capacity of all clinicians to use clinical ethics mediation to improve the care of vulnerable patients.

  13. Clinical efficacy and safety of catheter ablation for atrial fibrillation in elderly patients

    Institute of Scientific and Technical Information of China (English)

    董静

    2013-01-01

    Objective To evaluate the clinical efficacy and safty of catheter ablation for atrial fibrillation in elderly patients.Methods From September 2008 to October 2011,a total of 420 consecutive patients undergoing cathete rablation

  14. Clinical efficacy and safety of Chinese herbal medicine for Wilson's disease: a systematic review of 9 randomized controlled trials.

    Science.gov (United States)

    Wang, Yan; Xie, Cheng-long; Fu, Deng-lei; Lu, Lin; Lin, Yan; Dong, Qi-qian; Wang, Xiao-tong; Zheng, Guo-qing

    2012-06-01

    Wilson's disease is an autosomal recessive disorder of copper metabolism. Despite being treatable, there is no universally accepted treatment regimen. Currently, various Chinese herbal medicines (CHMs) are widely used in the treatment of Wilson's disease in China, but there is a lack of reliable scientific evidence for the effectiveness of such therapies. The objective of this systematic review is to assess the clinical efficacy and safety of CHM as an alternative or/and adjuvant therapy for Wilson's disease. A systematic literature search in different medical databases was performed to identify randomized controlled trials comparing CHM as monotherapy or CHM as adjuvant therapy with western conventional medical therapy in the treatment of Wilson's disease. A total of 687 participants were included in nine eligible studies. The main findings are that CHM as monotherapy or adjuvant therapy for Wilson's disease may be able to improve the clinical symptoms, to promote the urinary copper excretion, to ameliorate liver function and/or liver cirrhosis, and has fewer adverse effects in comparison with western conventional medication. Furthermore, CHM generally appeared to be safe and well tolerated in patients with Wilson's disease. However, the evidence presented in this review are insufficient to warrant a clinical recommendation due to the generally low methodological quality of the included studies. In conclusion, CHM seems to be beneficial and safe for Wilson's disease, but high-quality evidences are still needed to further evaluate this therapy. Therefore, additional well-designed, randomized, placebo-controlled clinical trials are needed.

  15. Analysis of the safety evaluation for premarketing clinical trials of hemodialyzer and of postmarketing safety reports of hemodialyzer in Japan and the US: insights into the construction of a sophisticated premarketing evaluation.

    Science.gov (United States)

    Saito, Masami; Iwasaki, Kiyotaka

    2017-03-01

    Our aim was to conduct a scoping review of the regulations for hemodialyzers in the safety evaluation in Japan and the United States, and to evaluate the criteria for premarketing clinical trials and postmarketing safety reports to inform the development of a sophisticated premarketing evaluation in Japan. Regulations for approval of hemodialyzers were identified from the databases of the Ministry of Health, Labor and Welfare in Japan and the Federal Drug Agency (FDA) in the United States (US). The criteria for premarket clinical trials and postmarketing safety reports were evaluated for both countries. Standards in Japan required evaluation of blood compatibility and reporting of acute adverse effects by a premarketing clinical trial in 6 of 86 applications with semipermeable membrane materials deemed to be different to those of previously approved devices from 1983 to 31 August 2015. By comparison, the clinical trial was required in one of 545 approvals in the US from 1976 to 29 January 2016, but blood compatibility was not the point. All postmarketing adverse effects identified in Japan were included in the set of 'warnings'. The more stringent requirements for evaluation of blood compatibility and acute adverse effects in Japan seemed to be related to differences in the history of quality management systems for medical devices between the two countries. This study revealed that there were differences between Japan and the US in requiring the premarketing clinical trials for the hemodialyzers. Our findings could be useful for constructing sophisticated premarketing safety evaluation.

  16. Intervertebral disc repair with activated nucleus pulposus cell transplantation: a three-year, prospective clinical study of its safety

    Directory of Open Access Journals (Sweden)

    J Mochida

    2015-03-01

    Full Text Available Degeneration of the lumbar intervertebral discs is irreversible, with no treatment currently available. Building upon experimental studies that demonstrated the importance of the nucleus pulposus (NP in preserving disc structure, we demonstrated that reinsertion of NP cells slowed further disc degeneration and that direct cell-to-cell contact co-culture with mesenchymal stromal cells (MSCs significantly upregulated the viability of NP cells in basic and pre-clinical studies in vitro and in vivo using animal models and human cells. Here, we report a 3-year result of a prospective clinical study, aimed to assess the safety and efficacy of activated NP cell transplantation in the degenerate lumbar intervertebral disc. Candidates were 9 patients aged 20-29 years who had Pfirrmann’s grade III disc degeneration at the level adjacent to the level scheduled for posterior lumbar intervertebral fusion. Viable NP cells from the fused disc were co-cultured in direct contact with autologous bone marrow-derived MSCs. One million activated NP cells were transplanted into the degenerated disc adjacent to the fused level at 7 d after the first fusion surgery. No adverse effects were observed during the 3-year follow-up period. Magnetic resonance imaging did not show any detrimental effects to the transplanted discs and revealed a mild improvement in 1 case. No cases reported any low back pain. Our clinical study confirmed the safety of activated NP cell transplantation, and the findings suggest the minimal efficacy of this treatment to slow the further degeneration of human intervertebral discs.

  17. A cross-sectional study of barriers to personal health record use among patients attending a safety-net clinic.

    Directory of Open Access Journals (Sweden)

    Joan F Hilton

    Full Text Available BACKGROUND: Personal health records (PHR may improve patients' health by providing access to and context for health information. Among patients receiving care at a safety-net HIV/AIDS clinic, we examined the hypothesis that a mental health (MH or substance use (SU condition represents a barrier to engagement with web-based health information, as measured by consent to participate in a trial that provided access to personal (PHR or general (non-PHR health information portals and by completion of baseline study surveys posted there. METHODS: Participants were individually trained to access and navigate individualized online accounts and to complete study surveys. In response to need, during accrual months 4 to 12 we enhanced participant training to encourage survey completion with the help of staff. Using logistic regression models, we estimated odds ratios for study participation and for survey completion by combined MH/SU status, adjusted for levels of computer competency, on-study training, and demographics. RESULTS: Among 2,871 clinic patients, 70% had MH/SU conditions, with depression (38% and methamphetamine use (17% most commonly documented. Middle-aged patients and those with a MH/SU condition were over-represented among study participants (N = 338. Survey completion was statistically independent of MH/SU status (OR, 1.85 [95% CI, 0.93-3.66] but tended to be higher among those with MH/SU conditions. Completion rates were low among beginner computer users, regardless of training level (70%. CONCLUSIONS: Among patients attending a safety-net clinic, MH/SU conditions were not barriers to engagement with web-based health information. Instead, level of computer competency was useful for identifying individuals requiring substantial computer training in order to fully participate in the study. Intensive on-study training was insufficient to enable beginner computer users to complete study surveys.

  18. Clinical Alarms in intensive care: implications of alarm fatigue for the safety of patients.

    Science.gov (United States)

    Bridi, Adriana Carla; Louro, Thiago Quinellato; da Silva, Roberto Carlos Lyra

    2014-01-01

    to identify the number of electro-medical pieces of equipment in a coronary care unit, characterize their types, and analyze implications for the safety of patients from the perspective of alarm fatigue. this quantitative, observational, descriptive, non-participatory study was conducted in a coronary care unit of a cardiology hospital with 170 beds. a total of 426 alarms were recorded in 40 hours of observation: 227 were triggered by multi-parametric monitors and 199 were triggered by other equipment (infusion pumps, dialysis pumps, mechanical ventilators, and intra-aortic balloons); that is an average of 10.6 alarms per hour. the results reinforce the importance of properly configuring physiological variables, the volume and parameters of alarms of multi-parametric monitors within the routine of intensive care units. The alarms of equipment intended to protect patients have increased noise within the unit, the level of distraction and interruptions in the workflow, leading to a false sense of security.

  19. Nebulized formoterol: a review of clinical efficacy and safety in COPD

    Directory of Open Access Journals (Sweden)

    Nicholas J Gross

    2010-06-01

    Full Text Available Nicholas J Gross1, James F Donohue21Hines VA Hospital, Stritch Loyola School of Medicine, Hines, IL, USA; 2University of North Carolina School of Medicine, Chapel Hill, NC, USAAbstract: A nebulized formulation of formoterol, Perforomist®, 20 μg/2 ml, has been available since 2007 for the maintenance treatment of chronic obstructive pulmonary disease (COPD. We review the safety and efficacy data obtained during its development. In a dose-finding study, formoterol inhalation solution (FFIS was similar to the formoterol originator, Foradil® 12 μg DPI (FA in patients with COPD. In a 12-week efficacy study, FFIS manifested a rapid onset of action and FEV1 peak, AUC0–12, and trough levels similar to FA. No loss of efficacy, tachyphylaxis, was observed over 12 weeks of regular administration. In placebo-controlled studies in COPD patients receiving maintenance tiotropium, the addition of FFIS significantly augmented bronchodilation over the 6-week treatment duration, signifying that nebulized formoterol can further improve lung function in patients who are receiving tiotropium without an observed increase in adverse reactions. The safety profile of FFIS during 12-week and 1-year studies revealed adverse events that were similar to those of placebo and FA. Cardiac rhythm studies, including frequent ECGs and Holter monitoring, did not indicate any increase in rate or rhythm disturbances greater than placebo or FA. We conclude that maintenance use of Perforomist® is appropriate for patients with COPD who require or prefer a nebulizer for management of their disease.Keywords: long-acting bronchodilator, β-agonist, chronic bronchitis, pulmonary emphysema, Perforomist®, chronic obstructive pulmonary disease

  20. Efficacy and safety of parecoxib in the treatment of acute renal colic: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Sidney Glina

    2011-12-01

    Full Text Available PURPOSE: Although nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs and opioids are effective treatments for acute renal colic, they are associated with adverse events (AEs. As cyclooxygenase-2 selective NSAIDs may provide a safer alternative, we compared the efficacy and safety of parecoxib versus an nsNSAID in subjects with acute renal colic. MATERIALS AND METHODS: Phase IV., multicenter, double-blind, noninferiority, active-controlled study: 338 subjects with acute renal colic were randomized to parecoxib 40 mg i.v. plus placebo (n = 174 or ketoprofen 100 mg IV plus placebo (n = 164. 338 subjects with acute renal colic were randomized to parecoxib 40 mg IV (n = 174 or ketoprofen 100 mg IV(n = 164 plus placebo. Subjects were evaluated 15, 30, 45, 60, 90 and 120 minutes after treatment start and 24 hours after discharge. Primary endpoint was the mean pain intensity difference (PID at 30 minutes by visual analog scale (VAS (per-protocol population. An ANCOVA model was used with treatment group, country, and baseline score as covariates. Non-inferiority of parecoxib to ketoprofen was declared if the lower bound of the 95% confidence interval (CI for the difference between the two groups excluded the pre-established margin of 10 mm for the primary endpoint. RESULTS: Baseline demographics were similar. The mean (SD mPID30 min was 33.84 (24.61 and 35.16 (26.01 for parecoxib and ketoprofen, respectively. For treatment difference (parecoxib-ketoprofen the lower bound of the 95% CI was 6.53. The mean change from baseline in VAS 30 minutes after study medication was ~43 mm; AEs were comparable between treatments. CONCLUSIONS: Parecoxib is as effective as ketoprofen in the treatment of pain due to acute renal colic, is well tolerated, and has a comparable safety profile.

  1. National Use of Safety-Net Clinics for Primary Care among Adults with Non-Medicaid Insurance in the United States.

    Directory of Open Access Journals (Sweden)

    Oanh Kieu Nguyen

    Full Text Available To describe the prevalence, characteristics, and predictors of safety-net use for primary care among non-Medicaid insured adults (i.e., those with private insurance or Medicare.Cross-sectional analysis using the 2006-2010 National Ambulatory Medical Care Surveys, annual probability samples of outpatient visits in the U.S. We estimated national prevalence of safety-net visits using weighted percentages to account for the complex survey design. We conducted bivariate and multivariate logistic regression analyses to examine characteristics associated with safety-net clinic use.More than one-third (35.0% of all primary care safety-net clinic visits were among adults with non-Medicaid primary insurance, representing 6,642,000 annual visits nationally. The strongest predictors of safety-net use among non-Medicaid insured adults were: being from a high-poverty neighborhood (AOR 9.53, 95% CI 4.65-19.53, being dually eligible for Medicare and Medicaid (AOR 2.13, 95% CI 1.38-3.30, and being black (AOR 1.97, 95% CI 1.06-3.66 or Hispanic (AOR 2.28, 95% CI 1.32-3.93. Compared to non-safety-net users, non-Medicaid insured adults who used safety-net clinics had a higher prevalence of diabetes (23.5% vs. 15.0%, p<0.001, hypertension (49.4% vs. 36.0%, p<0.001, multimorbidity (≥2 chronic conditions; 53.5% vs. 40.9%, p<0.001 and polypharmacy (≥4 medications; 48.8% vs. 34.0%, p<0.001. Nearly one-third (28.9% of Medicare beneficiaries in the safety-net were dual eligibles, compared to only 6.8% of Medicare beneficiaries in non-safety-net clinics (p<0.001.Safety net clinics are important primary care delivery sites for non-Medicaid insured minority and low-income populations with a high burden of chronic illness. The critical role of safety-net clinics in care delivery is likely to persist despite expanded insurance coverage under the Affordable Care Act.

  2. Clinical effectiveness and safety of montelukast in asthma. What are the conclusions from clinical trials and meta-analyses?

    Directory of Open Access Journals (Sweden)

    Hon KLE

    2014-06-01

    Full Text Available Kam Lun Ellis Hon,1 Ting Fan Leung,1 Alexander KC Leung21Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong; 2Department of Pediatrics, The University of Calgary, Calgary, AB, CanadaAbstract: Asthma is a common childhood atopic disease associated with chronicity and impaired quality of life. As there is no cure for this disease, treatment relies on avoidance of triggers such as food and aeroallergens, the use of inhaled bronchodilators/corticosteroids and antiallergic or immunomodulating therapies. Inhaled corticosteroids (ICSs and bronchodilators have been the mainstay. However, in Asia, myths and fallacies regarding Western medicine and corticosteroids are prevalent and lead to nonadherence to treatment. Also, use of traditional and proprietary herbal medicines is popular. In the past decades, a novel class of nonsteroidal immunomodulating montelukasts has become available. This article reviews the evidence for the effectiveness and clinical efficacy of these medications. A number of randomized and controlled trials have been performed over the years. The majority of studies confirm the usefulness of montelukast as monotherapy and add-on therapy to ICS in mild to moderate childhood asthma across all age groups. ICSs are generally superior to montelukasts for asthma management. However, montelukast has a place in the treatment of young children with viral-triggered wheezing diseases, exercise-induced asthma, and in children whose parents are steroid-phobic and find ICS unacceptable.Keywords: cysteinyl leukotriene receptor antagonist, inhaled corticosteroid, randomized control trial, meta analysis

  3. Depression Care for Low-Income, Minority, Safety Net Clinic Populations with Comorbid Illness

    Science.gov (United States)

    Ell, Kathleen; Lee, Pey-Jiuan; Xie, Bin

    2010-01-01

    Objective: Increasingly, mental health care is provided within the general health care sector. Accompanying this significant change is the demand for evidence-based as well as cost-effective or cost-neutral care models. Method: The authors present a pooled analysis of three large randomized clinical trials in which social workers provide…

  4. CLINICAL SAFETY OF LONG-TERM ADMINISTRATION OF GOSSYPOL-A 32 CASE STUDY

    Institute of Scientific and Technical Information of China (English)

    XUDuo; CAIWen-Juan; ZHUBao-Han; DONGCai-Jin; ZHENGJi-Cheng; GAOZheng-Quan

    1989-01-01

    Clinical trials of gossypol have been carried out in 1, 300 male volunteers in our Province since 1974. The treatment was discontinued within a period of 2 years in most of the purtieipants, while there were 81 volunteers who had received gossypol for more than 6 years.

  5. Clinical Models to Compare the Safety and Efficacy of Inhaled Corticosteroids in Patients with Asthma

    Directory of Open Access Journals (Sweden)

    Krishnan Parameswaran

    2003-01-01

    Full Text Available There is no consensus on the methods to compare the clinical efficacy of different inhaled corticosteroids. A comparison needs to be made in terms of relative potency, and studies should include two-, or preferably, three-dose comparisons. A number of clinical models and outcomes are available; they have their relative advantages and disadvantages. While measurements of symptoms and spirometry are easy and readily available, they show a flat dose-response relationship. Measurements of bronchial hyper-responsiveness to exercise and adenosine monophosphate, allergen-induced airway responses, and measurements of inflammation in sputum and exhaled air show steep dose-response relationships, particularly to low doses of inhaled steroids. An uncontrolled asthma model followed by stabilization with a short course of additional steroid, with measurements of airway responsiveness and airway inflammation, in a crossover study seems more promising than the other models. Drug deposition studies and mathematical modelling of drug pharmacokinetics in the airway may provide complementary information to clinical drug relative potency studies. Fine particle dose and emitted doses, rather than the nominal dose, should be considered in the estimation of clinical and systemic effects, respectively. When a second entry (generic drug is being evaluated in comparison with the innovator drug (same compound and same device, it may be appropriate to consider accepting a generic as bioequivalent if it satisfies pharmaceutical equivalence.

  6. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

    Science.gov (United States)

    Westhovens, R; Robles, M; Ximenes, A C; Nayiager, S; Wollenhaupt, J; Durez, P; Gomez-Reino, J; Grassi, W; Haraoui, B; Shergy, W; Park, S-H; Genant, H; Peterfy, C; Becker, J-C; Covucci, A; Helfrick, R; Bathon, J

    2009-01-01

    Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile. PMID:19124524

  7. Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial.

    Science.gov (United States)

    ElSherif, May S; Brown, Catherine; MacKinnon-Cameron, Donna; Li, Li; Racine, Trina; Alimonti, Judie; Rudge, Thomas L; Sabourin, Carol; Silvera, Peter; Hooper, Jay W; Kwilas, Steven A; Kilgore, Nicole; Badorrek, Christopher; Ramsey, W Jay; Heppner, D Gray; Kemp, Tracy; Monath, Thomas P; Nowak, Teresa; McNeil, Shelly A; Langley, Joanne M; Halperin, Scott A

    2017-06-19

    The 2013-2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing Zaire Ebolavirus glycoprotein (rVSVΔG-ZEBOV-GP) was evaluated in humans. In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18-65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo. Follow-up visits spanned 180 days postvaccination for safety monitoring, immunogenicity testing and any rVSV virus shedding. Forty participants were injected with rVSVΔG-ZEBOV-GP vaccine (n = 30) or saline placebo (n = 10). No serious adverse events related to the vaccine or participant withdrawals were reported. Solicited adverse events during the 14-day follow-up period were mild to moderate and self-limited, with the exception of injection-site pain and headache. Viremia following vaccination was transient and no longer detectable after study day 3, with no virus shedding in saliva or urine. All vaccinated participants developed serum immunoglobulin G (IgG), as measured by Ebola virus envelope glycoprotein-based enzyme-linked immunosorbent assay (ELISA). Immunogenicity was comparable across all dose groups, and sustained IgG titers were detectable through to the last visit, at study day 180. In this phase 1 study, there were no safety concerns after a single dose of rVSVΔG-ZEBOV-GP vaccine. IgG ELISA showed persistent high titers at 180 days postimmunization. There was a period of reactogenicity, but in general, the vaccine was well tolerated. This study provides evidence of the safety and immunogenicity of rVSVΔG-ZEBOV-GP vaccine and importance of its further investigation. Trial registration: Clinical-Trials.gov no., NCT02374385. © 2017 Canadian Medical Association or its licensors.

  8. Paediatric pharmacovigilance: use of pharmacovigilance data mining algorithms for signal detection in a safety dataset of a paediatric clinical study conducted in seven African countries

    OpenAIRE

    Kajungu, Dan K.; Annette Erhart; Ambrose Otau Talisuna; Quique Bassat; Corine Karema; Carolyn Nabasumba; Michael Nambozi; Halidou Tinto; Peter Kremsner; Martin Meremikwu; Umberto D'Alessandro; Niko Speybroeck

    2014-01-01

    BACKGROUND: Pharmacovigilance programmes monitor and help ensuring the safe use of medicines which is critical to the success of public health programmes. The commonest method used for discovering previously unknown safety risks is spontaneous notifications. In this study we examine the use of data mining algorithms to identify signals from adverse events reported in a phase IIIb/IV clinical trial evaluating the efficacy and safety of several Artemisinin-based combination therapies (ACTs) for...

  9. An Integrated Intervention for Increasing Clinical Nurses' Knowledge of HIV/AIDS-Related Occupational Safety.

    Science.gov (United States)

    He, Liping; Lu, Zhiyan; Huang, Jing; Zhou, Yiping; Huang, Jian; Bi, Yongyi; Li, Jun

    2016-11-07

    Background: Approximately 35 new HIV (Human Immunodeficiency Virus, HIV) cases and at least 1000 serious infections are transmitted annually to health care workers. In China, HIV prevalence is increasing and nursing personnel are encountering these individuals more than in the past. Contaminated needle-stick injuries represent a significant occupational burden for nurses. Evidence suggests that nurses in China may not fully understand HIV/AIDS (Acquired immunodeficiency syndrome, AIDS) and HIV-related occupational safety. At this time, universal protection precautions are not strictly implemented in Chinese hospitals. Lack of training may place nurses at risk for occupational exposure to blood-borne pathogens. Objectives: To assess the effectiveness of integrated interventions on nurses' knowledge improvement about reducing the risk of occupationally acquired HIV infection. Methods: We audited integrated interventions using 300 questionnaires collected from nurses at the Affiliated Hospital of Xiangnan University, a public polyclinic in Hunan Province. The intervention studied was multifaceted and included appropriate and targeted training content for hospital, department and individual levels. After three months of occupational safety integrated interventions, 234 participants who completed the program were assessed. Results: Of the subjects studied, 94.3% (283/300) were injured one or more times by medical sharp instruments or splashed by body fluids in the last year and 95.3% considered their risk of occupational exposure high or very high. After the intervention, awareness of HIV/AIDS-related knowledge improved significantly (χ² = 86.34, p = 0.00), and correct answers increased from 67.9% to 82.34%. Correct answers regarding risk perception were significantly different between pre-test (54.4%) and post-test (66.6%) (χ² = 73.2, p = 0.00). When coming into contact with patient body fluids and blood only 24.0% of subjects used gloves regularly. The pre

  10. Metabolites in safety testing assessment in early clinical development: a case study with a glucokinase activator.

    Science.gov (United States)

    Sharma, Raman; Litchfield, John; Atkinson, Karen; Eng, Heather; Amin, Neeta B; Denney, William S; Pettersen, John C; Goosen, Theunis C; Di, Li; Lee, Esther; Pfefferkorn, Jeffrey A; Dalvie, Deepak K; Kalgutkar, Amit S

    2014-11-01

    The present article summarizes Metabolites in Safety Testing (MIST) studies on a glucokinase activator, N,N-dimethyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide (PF-04937319), which is under development for the treatment of type 2 diametes mellitus. Metabolic profiling in rat, dog, and human hepatocytes revealed that PF-04937319 is metabolized via oxidative (major) and hydrolytic pathways (minor). N-Demethylation to metabolite M1 [N-methyl-5-((2-methyl-6-((5-methylpyrazin-2-yl)carbamoyl)benzofuran-4-yl)oxy)pyrimidine-2-carboxamide] was the major metabolic fate of PF-04937319 in human (but not rat or dog) hepatocytes, and was catalyzed by CYP3A and CYP2C isoforms. Qualitative examination of circulating metabolites in humans at the 100- and 300-mg doses from a 14-day multiple dose study revealed unchanged parent drug and M1 as principal components. Because M1 accounted for 65% of the drug-related material at steady state, an authentic standard was synthesized and used for comparison of steady-state exposures in humans and the 3-month safety studies in rats and dogs at the no-observed-adverse-effect level. Although circulating levels of M1 were very low in beagle dogs and female rats, adequate coverage was obtained in terms of total maximal plasma concentration (∼7.7× and 1.8×) and area under the plasma concentration-time curve (AUC; 3.6× and 0.8× AUC) relative to the 100- and 300-mg doses, respectively, in male rats. Examination of primary pharmacology revealed M1 was less potent as a glucokinase activator than the parent drug (compound PF-04937319: EC50 = 0.17 μM; M1: EC50 = 4.69 μM). Furthermore, M1 did not inhibit major human P450 enzymes (IC50 > 30 μM), and was negative in the Salmonella Ames assay, with minimal off-target pharmacology, based on CEREP broad ligand profiling. Insights gained from this analysis should lead to a more efficient and focused development plan for fulfilling MIST requirements with

  11. Endoscopic thyroidectomy: an evidence-based research on feasibility, safety and clinical effectiveness

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-dong; PENG Bing; GONG Ri-xiang; WANG Li; LIAO Bo; LI Chun-lin

    2008-01-01

    Background The feasibility and safety of endoscopic thyroidectomy were evaluated by an approach of systematic review of published studies in the past decade.Methods A database searching was performed on MEDLINE, Cochrane Database of Systematic Reviews, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials. Both comparative and non-comparative studies about endoscopic thyroidectomy were selected and analyzed. For the comparative studies, RevMan 4.2 was used for statistical analysis; and for the non-comparative studies, data analysis was performed by SPSS 13.0.Results Seven comparative studies involving 367 patients (video-assisted thyroidectomy (VAT), 174 patients; conventional thyroidectomy (CT), 193 patients) were included in VAT-CT group. Age, gender, operative types, and pathological diagnosis were similar. Compared with CT, the mean operative time for VAT was significantly longer (VAT, 80.0 minutes; CT, 61.9 minutes, P <0.01), but the postoperative hospital stay was shorter (VAT, 1.7 days; CT, 2.5 days, P <0.01). The complication rate for VAT was 6.9%, while that for CT was 9.3% (P=0.35). Three studies analyzed the postoperative pain and cosmetic evaluation, and indicated that the VAT group was superior to the CT group, but there was no significant difference after a meta-analysis. Three comparative studies involving 273 patients (totally endoscopic thyroidectomy (TET), 145 patients; CT, 128 patients) were included in TET-CT group and the results generally resembled that of VAT-CT group. There were 18 and 14 non-comparative studies reporting the results of VAT and TET, respectively. The mean operative time for VAT was 76.8 minutes compared with 135.8 minutes for TET. The postoperative hospital stay was 1.8 and 3.8 days for VAT and TET respectively. The rates of conversion to open surgery for VAT and TET were similar (VAT, 2.8%; TET, 3.9%, P=0.105). The complication rate for VAT

  12. [A prospective multicenter randomized controlled clinical study on the efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution].

    Science.gov (United States)

    Lu, Quan

    2010-03-01

    To evaluate efficacy and safety of Guaifenesin compound pseudoephedrine hydrochloride oral solution for the treatment of cough, expectoration, nasal congestion and runny nose in children. This was a prospective multicenter randomized single-blind, parallel-controlled clinical study. A total of 10 centers participated in this study, the actual number of cases in line with the program was 412, of whom 205 cases in trial group were treated with Guaifenesin compound pseudoephedrine hydrochloride oral solution, and 207 cases in control group with ambroxol hydrochloride oral solution, treatment of both groups persisted for 7 days. The improvement rate of each single symptom and the combined symptoms and the overall effective rate were compared between the two groups. The adverse drug reactions and compliance were assessed as well. The treatment of both groups showed efficacy. Except sputum stickiness, the improvement of all symptoms in trial group was superior to that in the control group on the 3rd day after treatment (P Guaifenesin compound pseudoephedrine hydrochloride oral solution was 82.9% and the overall efficacy rate was 89.3%. Guaifenesin compound Pseudoephedrine hydrochloride oral solution had higher compliance and its adverse event rate was merely 0.92%. Guaifenesin compound pseudoephedrine hydrochloride oral solution showed significant efficacy and safety in children for treatment of cough, expectoration, nasal congestion and runny nose caused by common cold or acute tracheobronchitis.

  13. [Skin test: guide of post-marketed re-evaluation of clinical safety in traditional Chinese medicine injection].

    Science.gov (United States)

    Wei, Xu; Xie, Yanming; Wang, Yongyan

    2011-10-01

    Anaphylaxis is the most common adverse reaction caused by traditional Chinese medicine (TCM) injection, the most serious of which is type I, so post-marketed safety re-evaluation is necessary. Skin test can be used to screen type I allergy reaction, which is of great significance for TCM injection safe use. Skin test is not only able to find the population sensitization situation of TCM injection, but also is a way of understanding the mechanism of allergy reaction. TCM injection varieties that often occur type I anaphylaxis are applicable to skin test, and study population include healthy volunteers and patients whose disease is listed in the drug specification, intracutaneous test and prick test are the alternative method. The concentration of skin-test solution may influence the positive rate of skin test, penicillin skin-test solution preparation method can be used as the reference in TCM injection. Different doses of TCM injection skin-test solution,glucose injection and normal saline, histamine hydrochloride are comprised in comparison. Given the characteristics of type I allergy reaction,we should be pay close attention to skin test reaction in half an hour, and observation index need be designed based on post-marketed re-evaluation of clinical safety.

  14. Anticalculus efficacy and safety of a novel whitening dentifrice containing sodium hexametaphosphate: a controlled six-month clinical trial.

    Science.gov (United States)

    Liu, Henry; Segreto, Vincent A; Baker, Robert A; Vastola, Kathleen A; Ramsey, Lorie L; Gerlach, Robert W

    2002-01-01

    This study was undertaken to establish the tartar control efficacy and long-term safety of a new dentifrice containing sodium hexametaphosphate. In a randomized, examiner blind, parallel group clinical trial, the experimental dentifrice with 7% sodium hexametaphosphate (5% hexametaphosphate anion), a non-abrasive cleaning agent that provides whitening and tartar control benefits, was compared to two currently marketed controls, a regular sodium fluoride dentifrice and a triclosan/copolymer dentifrice. The 8-month trial model included a 2-month pretest period to establish calculus formation after prophylaxis, and a 6-month test period to evaluate anti-calculus efficacy and safety. Following the pretest period, 551 subjects were allocated to one of the three treatment groups and then monitored for calculus accumulation and soft tissue tolerance. After 6 months, the sodium hexametaphosphate group exhibited superior calculus inhibition compared to the regular sodium fluoride dentifrice and triclosan/copolymer dentifrice (p < 0.01). Over the 6-month observation period, the sodium hexametaphosphate and the marketed control dentifrices were comparable in terms of adverse event type and severity, and no subject discontinued treatment due to an oral soft tissue adverse event.

  15. Clinical safety of cardiac magnetic resonance imaging at 3 T early after stent placement for acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Jehl, Jerome; Comte, Alexandre; Aubry, Sebastien; Kastler, Bruno [Hopital Jean Minjoz, Service de Radiologie A and C, Centre Hospitalier Universitaire de Besancon, Besancon (France); Meneveau, Nicolas; Schiele, Francois [Hopital Jean Minjoz, Service de Cardiologie, Centre Hospitalier Universitaire de Besancon, Besancon (France)

    2009-12-15

    The purpose of this study was to prospectively evaluate the safety of cardiac magnetic resonance (CMR) imaging at 3 T performed early (less than 14 days) after bare metal or drug-eluting coronary stent implantation in patients with acute myocardial infarction (AMI). Seventy-two consecutive patients with AMI treated by percutaneous revascularisation with a stent underwent CMR examination with a median delay of 6 days. Patients were followed-up for major adverse cardiac events, during hospitalisation and at 6 months. After CMR imaging, no acute stent thrombosis, death or repeated AMI were recorded at 6-month follow-up. Two symptomatic in-stent restenoses and two silent in-stent restenoses were recorded, at a mean delay of 106 days. In our population, we found a target revascularisation rate of 5.6%. This is consistent with the 6-month event rates after coronary artery stent (CAS) placement for AMI, evaluated by several studies. This preliminary clinical study supports the safety of 3-T CMR imaging performed early after coronary stent placement. (orig.)

  16. Biospecimen Sharing Among Hispanic Women in a Safety-Net Clinic: Implications for the Precision Medicine Initiative

    Science.gov (United States)

    Nodora, Jesse N.; Komenaka, Ian K.; Bouton, Marcia E.; Ohno-Machado, Lucila; Schwab, Richard; Kim, Hyeon-eui; Farcas, Claudiu; Perez, Giovanna

    2017-01-01

    Biospecimen donation is key to the Precision Medicine Initiative, which pioneers a model for accelerating biomedical research through individualized care. Personalized medicine should be made available to medically underserved populations, including the large and growing US Hispanic population. We present results of a study of 140 Hispanic women who underwent a breast biopsy at a safety-net hospital and were randomly assigned to receive information and request for consent for biospecimen and data sharing by the patient’s physician or a research assistant. Consent rates were high (97.1% and 92.9% in the physician and research assistant arms, respectively) and not different between groups (relative risk [RR] = 1.05, 95% confidence interval [CI] = 0.96 to 1.10). Consistent with a small but growing literature, we show that perceptions of Hispanics’ unwillingness to participate in biospecimen sharing for research are not supported by data. Safety-net clinics and hospitals offer untapped possibilities for enhancing participation of underserved populations in the exciting Precision Medicine Initiative. PMID:27688295

  17. Clinical efficacy and safety of fluoxetine in generalized anxiety disorder in Chinese patients

    Directory of Open Access Journals (Sweden)

    Zou C

    2013-11-01

    Full Text Available Chuan Zou,1 Xiang Ding,1 Joseph H Flaherty,2 Birong Dong1 1The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, People's Republic of China; 2St Louis University, St Louis, MO, USA Background: Generalized anxiety disorder (GAD is a prevalent, disabling disease and is highly comorbid with other psychiatric disorders both in Western countries and the People's Republic of China. Fluoxetine, a selective inhibitor of serotonin reuptake (SSRI, is widely utilized in the management of GAD in clinical practice despite the lack of strong evidence. This article reviews fluoxetine trials to investigate fluoxetine's efficacy and tolerability in Chinese patients with GAD. Methods: A literature review was conducted using the following databases up to and including April 2013: Chinese BioMedical Literature, China National Knowledge Infrastructure, EMBASE, MEDLINE, and PsycINFO. We selected clinical studies that utilized fluoxetine for GAD in which all participants were Chinese. Results: Fifteen open-label, non-placebo trials were identified and analyzed; eleven anxiolytics were compared with fluoxetine separately. Short-term efficacy of fluoxetine had been established in these open-label, head-to-head controlled trials. Fluoxetine had rapid onset of action (approximately 1–2 weeks and seemed to be effective in maintenance treatment. Fluoxetine was generally well-tolerated with the most common side effect of dry month and nausea. Compared to other anxiolytic agents, fluoxetine was equivalent with all of the comparative anxiolytics in terms of efficacy except mirtazapine which showed conflicting results with fluoxetine in two studies. In terms of side effects, fluoxetine was better tolerated than diazepam, doxepine, and amitriptyline, less tolerated than escitalopram, and had similar tolerability with duloxetine as well as alprazolam. Conclusion: Given the high risk of bias of the included studies, the overall small sample

  18. Clinical Pharmacist Team-Based Care in a Safety Net Medical Home: Facilitators and Barriers to Chronic Care Management.

    Science.gov (United States)

    Price-Haywood, Eboni G; Amering, Sarah; Luo, Qingyang; Lefante, John J

    2017-04-01

    Collaborative care models incorporating pharmacists have been shown to improve quality of care for patients with hypertension and/or diabetes. Little is known about how to integrate such services outside of clinical trials. The authors implemented a 22-month observational study to evaluate pharmacy collaborative care for hypertension and diabetes in a safety net medical home that incorporated population risk stratification, clinical decision support, and medication dose adjustment protocols. Patients in the pharmacy group saw their primary care provider (PCP) more often and had higher baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) and A1c levels compared to patients who only received care from their PCPs. There were no significant differences in the proportion of patients achieving treatment goals (SBP patients who underwent collaborative care versus those who did not. Age, race, and number of PCP encounters were associated with BP and A1c trends. The median time to achieve disease control was longer in the pharmacy group. Although 70% of all patients with poorly controlled hypertension achieved treatment goals within 7 months, less than 50% of patients with poorly controlled diabetes achieved A1c culture, health information technology and related workflows, and pharmacy caseload optimization. Future studies should further examine implementation strategies that work best in specific settings to optimize the benefits of team-based care with clinical pharmacists.

  19. Identifying Subgroups of Adult Superutilizers in an Urban Safety-Net System Using Latent Class Analysis: Implications for Clinical Practice.

    Science.gov (United States)

    Rinehart, Deborah J; Oronce, Carlos; Durfee, Michael J; Ranby, Krista W; Batal, Holly A; Hanratty, Rebecca; Vogel, Jody; Johnson, Tracy L

    2016-09-14

    Patients with repeated hospitalizations represent a group with potentially avoidable utilization. Recent publications have begun to highlight the heterogeneity of this group. Latent class analysis provides a novel methodological approach to utilizing administrative data to identify clinically meaningful subgroups of patients to inform tailored intervention efforts. The objective of the study was to identify clinically distinct subgroups of adult superutilizers. Retrospective cohort analysis. Adult patients who had an admission at an urban safety-net hospital in 2014 and 2 or more admissions within the preceding 12 months. Patient-level medical, mental health (MH) and substance use diagnoses, social characteristics, demographics, utilization and charges were obtained from administrative data. Latent class analyses were used to determine the number and characteristics of latent subgroups that best represented these data. In this cohort (N=1515), a 5-class model was preferred based on model fit indices, clinical interpretability and class size: class 1 (16%) characterized by alcohol use disorder and homelessness; class 2 (14%) characterized by medical conditions, MH/substance use disorders and homelessness; class 3 (25%) characterized primarily by medical conditions; class 4 (13%) characterized by more serious MH disorders, drug use disorder and homelessness; and class 5 (32%) characterized by medical conditions with some MH and substance use. Patient demographics, utilization, charges and mortality also varied by class. The overall cohort had high rates of multiple chronic medical conditions, MH, substance use disorders, and homelessness. However, the patterns of these conditions were different between subgroups, providing important information for tailoring interventions.

  20. Systematic Review of Randomized Clinical Trials on Safety and Efficacy of Pharmacological and Nonpharmacological Treatments for Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Marta Sacchetti

    2015-01-01

    Full Text Available Aims. Several treatments have been proposed to slow down progression of Retinitis pigmentosa (RP, a hereditary retinal degenerative condition leading to severe visual impairment. The aim of this study is to systematically review data from randomized clinical trials (RCTs evaluating safety and efficacy of medical interventions for the treatment of RP. Methods. Randomized clinical trials on medical treatments for syndromic and nonsyndromic RP published up to December 2014 were included in the review. Visual acuity, visual field, electroretinogram, and adverse events were used as outcome measures. Results. The 19 RCTs included in this systematic review included trials on hyperbaric oxygen delivery, topical brimonidine tartrate, vitamins, docosahexaenoic acid, gangliosides, lutein, oral nilvadipine, ciliary neurotrophic factor, and valproic acid. All treatments proved safe but did not show significant benefit on visual function. Long term supplementation with vitamin A showed a significantly slower decline rate in electroretinogram amplitude. Conclusions. Although all medical treatments for RP appear safe, evidence emerging from RCTs is limited since they do not present comparable results suitable for quantitative statistical analysis. The limited number of RCTs, the poor clinical results, and the heterogeneity among studies negatively influence the strength of recommendations for the long term management of RP patients.

  1. Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine, and hydrochlorothiazide in clinical practice.

    Science.gov (United States)

    Bramlage, Peter; Fronk, Eva-Maria; Wolf, Wolf-Peter; Smolnik, Rüdiger; Sutton, Gemma; Schmieder, Roland E

    2015-01-01

    Clinical trials indicate that the use of fixed-dose combinations (FDCs) is associated with a higher level of treatment adherence and prolonged blood pressure (BP) control. The aim of this study was to document the safety and effectiveness of the FDC olmesartan/amlodipine/hydrochlorothiazide in patients with essential hypertension in clinical practice. This multicenter, prospective, 24-week, noninterventional study enrolled 5,831 patients from primary care offices in Germany and Austria. Inclusion criteria were a diagnosis of essential hypertension and newly initiated treatment with the FDC. The mean age of patients was 63.5 years, almost 50% of patients had a time since diagnosis of essential hypertension of over 5 years, and approximately 70% of patients had at least one cardiovascular risk factor, including 29.4% of patients with diabetes mellitus. Following approximately 24 weeks of treatment, the mean reduction in systolic/diastolic BP was 29.0/14.0 mmHg, a BP response was observed by 94.2% of patients, and a target BP of risk (low/high), and concomitant medication (no/yes). This study demonstrates that in clinical practice, treatment with the three-drug combination as an FDC tablet resulted in a very high proportion of patients with a BP response and control, accompanied by a very low rate of ADRs.

  2. Clinical Alarms in intensive care: implications of alarm fatigue for the safety of patients1

    Science.gov (United States)

    Bridi, Adriana Carla; Louro, Thiago Quinellato; da Silva, Roberto Carlos Lyra

    2014-01-01

    OBJECTIVES: to identify the number of electro-medical pieces of equipment in a coronary care unit, characterize their types, and analyze implications for the safety of patients from the perspective of alarm fatigue. METHOD: this quantitative, observational, descriptive, non-participatory study was conducted in a coronary care unit of a cardiology hospital with 170 beds. RESULTS: a total of 426 alarms were recorded in 40 hours of observation: 227 were triggered by multi-parametric monitors and 199 were triggered by other equipment (infusion pumps, dialysis pumps, mechanical ventilators, and intra-aortic balloons); that is an average of 10.6 alarms per hour. CONCLUSION: the results reinforce the importance of properly configuring physiological variables, the volume and parameters of alarms of multi-parametric monitors within the routine of intensive care units. The alarms of equipment intended to protect patients have increased noise within the unit, the level of distraction and interruptions in the workflow, leading to a false sense of security. PMID:25591100

  3. Clinical Alarms in intensive care: implications of alarm fatigue for the safety of patients

    Directory of Open Access Journals (Sweden)

    Adriana Carla Bridi

    2014-12-01

    Full Text Available OBJECTIVES: to identify the number of electro-medical pieces of equipment in a coronary care unit, characterize their types, and analyze implications for the safety of patients from the perspective of alarm fatigue.METHOD: this quantitative, observational, descriptive, non-participatory study was conducted in a coronary care unit of a cardiology hospital with 170 beds.RESULTS: a total of 426 alarms were recorded in 40 hours of observation: 227 were triggered by multi-parametric monitors and 199 were triggered by other equipment (infusion pumps, dialysis pumps, mechanical ventilators, and intra-aortic balloons; that is an average of 10.6 alarms per hour.CONCLUSION: the results reinforce the importance of properly configuring physiological variables, the volume and parameters of alarms of multi-parametric monitors within the routine of intensive care units. The alarms of equipment intended to protect patients have increased noise within the unit, the level of distraction and interruptions in the workflow, leading to a false sense of security.

  4. The potential carcinogenic risk of tanning beds: clinical guidelines and patient safety advice

    Directory of Open Access Journals (Sweden)

    Mette Mogensen

    2010-10-01

    Full Text Available Mette Mogensen1, Gregor BE Jemec21Department of Dermatology, Gentofte Hospital, Hellerup, Denmark; 2Department of Dermatology, Roskilde Hospital, Health Sciences Faculty, University of Copenhagen, Roskilde, DenmarkIntroduction: In 2009, the WHO listed ultraviolet (UV radiation as a group 1 carcinogen. In spite of this, each year, millions of people tan indoor in Western countries. The aim of this review is to summarize evidence of tanning bed carcinogenesis and to present guidelines for use of tanning beds and patient safety advice.Methods: A narrative review of the literature was conducted based on both PubMed and Medline searches and on literature review of the retrieved papers.Results: Use of indoor tanning beds represents a significant and avoidable risk factor for the development of both melanoma and nonmelanoma skin cancers. Frequent tanners are more often adolescent females. Tanning beds have additional potential adverse effects such as burns, solar skin damage, infection, and possibly also addictive behavior.Discussion: The effort in preventing UV light-induced carcinogenesis should currently be aimed at developing new strategies for public health information. Tanning beds are one preventable source of UV radiation. In the majority of people solar UV radiation continues to be the major factor and therefore anti-tanning campaigns must always include sunbathers.Keywords: tanning beds, skin cancers, melanoma, nonmelanoma

  5. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction.

    Science.gov (United States)

    Henry, Courtney A; Lyon, Ronald A; Ling, Hua

    2016-01-01

    Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost-benefit ratio.

  6. Factors associated with health information exchange system usage in a safety-net ambulatory care clinic setting.

    Science.gov (United States)

    Vest, Joshua R; Gamm, Larry D; Ohsfeldt, Robert L; Zhao, Hongwei; Jasperson, 'Jon Sean

    2012-08-01

    The Meaningful Use criteria promises to make health information exchange (HIE) much more widespread. However, the usage of the information systems made available by existing HIE efforts tends to be very low. This study sought to examine the factors associated with usage of an operational HIE system during ambulatory care visits to safety-net clinics. Overall the HIE system was accessed for 21% of encounters. However, system access took on two distinct forms. In general, usage was more likely for patients with recent emergency department visits and chronic conditions. This study indicates the organizational commitment to engage in HIE does not necessarily mean that the information systems will be always used. In addition, system usage will take on various forms for different reasons. These results reveal considerations for the development, operation and evaluation of HIE efforts.

  7. Isavuconazole for the treatment of invasive aspergillosis and mucormycosis: current evidence, safety, efficacy, and clinical recommendations

    Science.gov (United States)

    Natesan, Suganthini Krishnan; Chandrasekar, Pranatharthi H

    2016-01-01

    The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA) and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both Aspergillus sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles. Polyenes including lipid formulations pose a problem with infusion-related side effects, electrolyte imbalance, and nephrotoxicity. Echinocandins are ineffective against mucorales and are approved as salvage therapy for refractory IA. Given that all available antifungal agents have limitations, there has been an unmet need for a broad-spectrum anti-mold agent with a favorable profile. Following phase III clinical trials that started in 2006, isavuconazole (ISZ) seems to fit this profile. It is the first novel triazole agent recently approved by the United States Food and Drug Administration (FDA) for the treatment of both IA and mucormycosis. This review provides a brief overview of the salient features of ISZ, its favorable profile with regard to spectrum of antifungal activity, pharmacokinetic and pharmacodynamic parameters, drug interactions and tolerability, clinical efficacy, and side effects. PMID:27994475

  8. Analysis of effectiveness, safety and optimization of tocilizumab in a cohort of patients with rheumatoid arthritis in clinical practice.

    Science.gov (United States)

    Mena-Vázquez, Natalia; Manrique-Arija, Sara; Rojas-Giménez, Marta; Ureña-Garnica, Inmaculada; Jiménez-Núñez, Francisco G; Fernández-Nebro, Antonio

    2017-07-01

    To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimized regimen and switching from intravenous (IV) to subcutaneous (SC) therapy. Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan-Meier. The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6-86.7]). Twenty-one of 53 patients (39.6%) optimized the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. Tocilizumab appears to be effective and safe in RA in clinical practice. The optimized regimen appears to be effective in most patients in remission, even when they change from IV to SC. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  9. The changing nature of clinical decision support systems: a focus on consumers, genomics, public health and decision safety.

    Science.gov (United States)

    Coiera, E; Lau, A Y S; Tsafnat, G; Sintchenko, V; Magrabi, F

    2009-01-01

    To review the recent research literature in clinical decision support systems (CDSS). A review of recent literature was undertaken, focussing on CDSS evaluation, consumers and public health, the impact of translational bioinformatics on CDSS design, and CDSS safety. In recent years, researchers have concentrated much less on the development of decision technologies, and have focussed more on the impact of CDSS in the clinical world. Recent work highlights that traditional process measures of CDSS effectiveness, such as document relevance are poor proxy measures for decision outcomes. Measuring the dynamics of decision making, for example via decision velocity, may produce a more accurate picture of effectiveness. Another trend is the broadening of user base for CDSS beyond front line clinicians. Consumers are now a major focus for biomedical informatics, as are public health officials, tasked with detecting and managing disease outbreaks at a health system, rather than individual patient level. Bioinformatics is also changing the nature of CDSS. Apart from personalisation of therapy recommendations, translational bioinformatics is creating new challenges in the interpretation of the meaning of genetic data. Finally, there is much recent interest in the safety and effectiveness of computerised physician order entry (CPOE) systems, given that prescribing and administration errors are a significant cause of morbidity and mortality. Of note, there is still much controversy surrounding the contention that poorly designed, implemented or used CDSS may actually lead to harm. CDSS research remains an active and evolving area of research, as CDSS penetrate more widely beyond their traditional domain into consumer decision support, and as decisions become more complex, for example by involving sequence level genetic data.

  10. Systematic review: treatment pattern and clinical effectiveness and safety of pharmaceutical therapies for Crohn’s disease in Europe

    Directory of Open Access Journals (Sweden)

    Lelli F

    2016-10-01

    Full Text Available Filippo Lelli,1 Solomon Nuhoho,2 Xin Ying Lee,3 Weiwei Xu4 1EMEA Hemar, Janssen, Milan, Italy; 2Health Economics, Market Access and Reimbursement, Johnson & Johnson Middle East FZ LLC, Dubai, United Arab Emirates; 3EMEA Hemar, Janssen, Birkerød, Denmark; 4Pharmerit International, Rotterdam, the Netherlands Background: Although many clinical trials have been conducted in treatments of Crohn’s ­disease (CD, whether the trial results were representative of daily practice needs to be supported by studies conducted in real-world settings. Aim: This study aims to identify how CD is treated and what are the clinical effectiveness and safety of the pharmaceutical therapies of CD in real-world settings. Methods: A systematic literature review was conducted based on Medline®, Embase®, and Cochrane. All publications were assessed for title/abstract and full-text according to a predefined study protocol. Data were extracted and reported.Results: A total of 1,998 publications were identified. Fifty studies including six publications reporting treatment pattern and 44 studies reporting clinical effectiveness and safety of pharmaceutical therapies in CD management in Europe were included. 5-Aminosalicylic acid and corticosteroids were reported to be used among 14%–74% of CD patients. Immunomodulators were used by 14%–25% and 29%–31% of CD patients as an initial and follow-up treatment, respectively. Biological therapies were used by 25%–33% of CD patients. A trend toward an increasing use of immunomodulators and biological therapies in Europe has been reported in recent years. Approximately 50% of patients achieved remission on immunomodulator or biologic treatment, although a relapse rate of up to 23% has been reported.Conclusion: There is a trend of treatment shift to immunomodulators and biologics in CD management. Clinical effectiveness of immunomodulators and biologics has been demonstrated, though with a lack of sustainability of the

  11. Clinical efficacy and safety of lamotrigine monotherapy in newly diagnosed pediatric patients with epilepsy

    Directory of Open Access Journals (Sweden)

    Ji Hye Han

    2010-04-01

    Full Text Available Purpose : To verify the efficacy and safety of lamotrigine (LTG monotherapy in newly diagnosed children with epilepsy. Methods : We prospectively enrolled 148 children who had undergone LTG monotherapy at our institution between September 2002 and June 2009. Twenty-nine patients were excluded: 19 due to incomplete data and 10 were lost to follow up. The data of the remaining 119 patients was analyzed. Results : We enrolled 119 pediatric epilepsy patients (aged 2.8-19.3 years; 66 males and 53 females in this study. Out of 119 patients, 29 (25.2% had generalized epilepsy and 90 (74.8% had partial epilepsy. The responses of seizure reduction were as follows: Seizure freedom (no seizure attack for at least 6 months in 87/111 (78.4%, n=111 patients; partial response (reduced seizure frequency compared to baseline in 13 (11.7% patients; and persistent seizure in 11 (9.9% patients. The seizure freedom rate was in 81.6% in patients with partial seizure (75.9% for complex partial seizure and 90.9% for benign rolandic epilepsy and 44.8% in patients with generalized epilepsy (30.0% for absence seizure, 35.7% for juvenile myoclonic epilepsy patients, and 100.0% for idiopathic generalized epilepsy patients. Adverse reactions were reported in 17 (14.3% patients, and 8 patients (6.7% discontinued LTG because of rash and tic. No patient experienced severe adverse reaction such as Stevens-Johnson syndrome. Conclusion : LTG showed excellent therapeutic response and had few significant adverse effects. Our findings report may contribute in promoting the use of LTG monotherapy in epileptic children.

  12. Safety, clinical and immunologic efficacy of a Chinese herbal medicine (FAHF-2) for food allergy

    Science.gov (United States)

    Wang, Julie; Jones, Stacie M.; Pongracic, Jacqueline A.; Song, Ying; Yang, Nan; Sicherer, Scott H.; Makhija, Melanie M.; Robison, Rachel G.; Moshier, Erin; Godbold, James; Sampson, Hugh A.; Li, Xiu-Min

    2015-01-01

    Background FAHF-2 is a 9-herb formula based on Traditional Chinese Medicine that blocks peanut anaphylaxis in a murine model. In Phase I studies, FAHF-2 was found to be safe, and well tolerated. Objective To evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy. Methods In this double-blind, randomized, placebo-controlled study, 68 subjects, 12-45 years of age, with allergies to peanut, tree nut, sesame, fish, and/or shellfish, confirmed by baseline double-blind, placebo controlled food challenge (DBPCFC), received FAHF-2 (n=46) or placebo (n=22). After 6 months of therapy, subjects underwent DBPCFC. For those who demonstrated increases in eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy. Results Treatment was well-tolerated with no serious adverse events. By intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose (p=0.05) at the end of treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions (p=0.55). There were no significant differences in allergen-specific IgE and IgG4, cytokine production by PBMCs or basophil activation between active and placebo groups. In vitro immunological studies performed on subject baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 and increased numbers of Tregs than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one-third of the study period. Conclusion FAHF-2 is a safe herbal medication for food allergic individuals and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used. PMID:26044855

  13. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction

    Directory of Open Access Journals (Sweden)

    Henry CA

    2016-04-01

    Full Text Available Courtney A Henry, Ronald A Lyon, Hua Ling Department of Pharmacy Practice, School of Pharmacy, Hampton University, Hampton, VA, USA Abstract: Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9 was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2 directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost–benefit ratio. Keywords: PCSK9, hyperlipidemia, evolocumab, LDL-C, familial hypercholesterolemia

  14. Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Cuffari C

    2016-02-01

    Full Text Available Carmen Cuffari,1 David Pierce,2 Bartosz Korczowski,3 Krzysztof Fyderek,4 Heather Van Heusen,5 Stuart Hossack,6 Hong Wan,5 Alena YZ Edwards,7 Patrick Martin5 1Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Shire, Basingstoke, UK; 3Medical College, University of Rzeszów, Rzeszów, Poland; 4University Children’s Hospital of Cracow, Cracow, Poland; 5Shire, Wayne, PA, USA; 6Covance Clinical Research Unit Limited, Leeds, UK; 7ICON Early Phase Services, Marlow, Buckinghamshire, UK Background: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA use in pediatric ulcerative colitis (UC.Aim: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC.Methods: Participants (5–17 years of age; 18–82 kg, stratified by weight with UC received multimatrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model.Results: Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg] were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%–45%, respectively were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were

  15. Isavuconazole for the treatment of invasive aspergillosis and mucormycosis: current evidence, safety, efficacy, and clinical recommendations

    Directory of Open Access Journals (Sweden)

    Natesan SK

    2016-12-01

    Full Text Available Suganthini Krishnan Natesan,1,2 Pranatharthi H Chandrasekar1 1Division of Infectious Diseases, Department of Internal Medicine, Wayne State University, 2John D Dingell VA Medical Center, Detroit, MI, USA Abstract: The majority of invasive mold infections diagnosed in immunocompromised cancer patients include invasive aspergillosis (IA and mucormycosis. Despite timely and effective therapy, mortality remains considerable. Antifungal agents currently available for the management of these serious infections include triazoles, polyenes, and echinocandins. Until recently, posaconazole has been the only triazole with a broad spectrum of anti-mold activity against both Aspergillus sp. and mucorales. Other clinically available triazoles voriconazole and itraconazole, with poor activity against mucorales, have significant drug interactions in addition to a side effect profile inherent for all triazoles. Polyenes including lipid formulations pose a problem with infusion-related side effects, electrolyte imbalance, and nephrotoxicity. Echinocandins are ineffective against mucorales and are approved as salvage therapy for refractory IA. Given that all available antifungal agents have limitations, there has been an unmet need for a broad-spectrum anti-mold agent with a favorable profile. Following phase III clinical trials that started in 2006, isavuconazole (ISZ seems to fit this profile. It is the first novel triazole agent recently approved by the United States Food and Drug Administration (FDA for the treatment of both IA and mucormycosis. This review provides a brief overview of the salient features of ISZ, its favorable profile with regard to spectrum of antifungal activity, pharmacokinetic and pharmacodynamic parameters, drug interactions and tolerability, clinical efficacy, and side effects. Keywords: isavuconazole, aspergillosis, mucormycosis, efficacy, antifungal therapy, novel azole, tolerability, drug interactions

  16. Efficacy and safety of telavancin in clinical trials: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Konstantinos A Polyzos

    Full Text Available INTRODUCTION: The epidemiology and antibiotic resistance of Staphylococcus aureus have evolved, underscoring the need for novel antibiotics, particularly against methicillin-resistant S. aureus (MRSA. Telavancin is a bactericidal lipoglycopeptide with potent activity against Gram-positive pathogens. OBJECTIVE: To systematically review and synthesize the available evidence from randomized controlled trials (RCTs evaluating telavancin in the treatment of patients with infections due to Gram-positive organisms with the methodology of meta-analysis. RESULTS: Six RCTs comparing telavancin with vancomycin were included; 4 (2229 patients referred to complicated skin and soft tissue infections (cSSTIs and 2 (1503 patients to hospital-acquired pneumonia (HAP. Regarding cSSTIs, telavancin and vancomycin showed comparable efficacy in clinically evaluable patients (odds ratio [OR] =1.10 [95% confidence intervals: 0.82-1.48]. Among patients with MRSA infection, telavancin showed higher eradication rates (OR=1.71 [1.08-2.70] and a trend towards better clinical response (OR=1.55 [0.93-2.58]. Regarding HAP, telavancin was non-inferior to vancomycin in terms of clinical response in two Phase III RCTs; mortality rates for the pooled trials were comparable with telavancin (20% and vancomycin (18.6%. Pooled data from cSSTIs and HAP studies on telavancin 10 mg/kg indicated higher rates of serum creatinine increases (OR=2.22 [1.38-3.57], serious adverse events (OR=1.53 [1.05-2.24], and adverse event-related withdrawals (OR=1.49 [1.14-1.95] among telavancin recipients. CONCLUSION: Telavancin might be an alternative to vancomycin in cases of difficult-to-treat MRSA infections. The potent antistaphylococcal activity of telavancin should be weighted against the potential for nephrotoxicity.

  17. Patient safety and the integration of graduate nurses into effective organizational clinical risk management systems and processes: an Australian study.

    Science.gov (United States)

    Johnstone, Megan-Jane; Kanitsaki, Olga

    2008-01-01

    This article explores and describes key processes facilitating the integration of neophyte graduate nurses into safe and effective organizational systems and processes as part of a hospital's overall local clinical governance and clinical risk management (CRM) program. This study was undertaken using an exploratory descriptive case study method. Four sample units of analysis were used, notably, 2 cohorts of graduate nurses (n = 11) undertaking a 12-month graduate nurse transition program; key stakeholders (n = 34), that is, nurse unit managers, clinical teachers, preceptors, a quality manager, a librarian, and senior nurse administrators employed by the participating health service; and pertinent literature sources. Data revealed that the cohort of graduate nurses under study became substantively integrated into the hospital's organizational and patient safety system processes within the first 3 to 4 months of their employment. Processes most contributing to this integration included the graduates receiving pertinent information about CRM at the very beginning of their employment (at induction) and thereafter throughout their graduate nurse year. In addition, the graduates needed focused support to assist their efforts to integrate the CRM systems and processes of their employer organization into their "normal working practices." In order for new graduate nurses to become integrated into safe and effective organizational systems and processes as part of a hospital's overall local clinical governance and CRM program, they needed pertinent information on CRM at the beginning of their employment and thereafter be supported throughout their graduate nurse year to develop and translate that information into their "routine" (everyday) practice. Further comparative research involving larger cohorts of graduate nurses is required.

  18. Clinical efficacy and safety of olmesartan/hydrochlorothiazide combination therapy in patients with essential hypertension

    Directory of Open Access Journals (Sweden)

    Luis M Ruilope

    2008-12-01

    Full Text Available Luis M RuilopeUnidad de Hipertensión, Hospital 12 de Octubre, Madrid, SpainAbstract: Hypertension is a major risk factor for cardiovascular disease that contributes to the premature death of millions of people each year, and identification and treatment of hypertension continues to be a challenge. Guidelines recommend that many patients will require two or more antihypertensive agents from different classes. Combining an angiotensin II receptor blocker (ARB with hydrochlorothiazide (HCTZ has been shown in clinical studies to increase the antihypertensive efficacy of both agents compared with either agent alone. This review covers several clinical trials and aims to examine several aspects of the efficacy of the combination of olmesartan and HCTZ, including dose-responsiveness, long-term efficacy, goal rate achievement, and efficacy in patients with moderate to severe hypertension. The results presented here demonstrate that olmesartan is effective when added to HCTZ monotherapy or when HCTZ is added to olmesartan monotherapy, both over the short and long term. Moderate to severe hypertension responds well to olmesartan/HCTZ combination therapy, and the great majority of patients are able to achieve recommended blood pressure targets. Thus olmesartan/HCTZ is a well-tolerated option for patients who fail to respond to monotherapy and as initial therapy in those who require large reductions in diastolic blood pressure or systolic blood pressure to achieve goal blood pressure.Keywords: hypertension, olmesartan medoxomil; hydrochlorothiazide, angiotensin II receptor blocker, thiazide diuretic

  19. Clinical efficacy and safety of olmesartan/hydrochlorothiazide combination therapy in patients with essential hypertension

    Science.gov (United States)

    Ruilope, Luis M

    2008-01-01

    Hypertension is a major risk factor for cardiovascular disease that contributes to the premature death of millions of people each year, and identification and treatment of hypertension continues to be a challenge. Guidelines recommend that many patients will require two or more antihypertensive agents from different classes. Combining an angiotensin II receptor blocker (ARB) with hydrochlorothiazide (HCTZ) has been shown in clinical studies to increase the antihypertensive efficacy of both agents compared with either agent alone. This review covers several clinical trials and aims to examine several aspects of the efficacy of the combination of olmesartan and HCTZ, including dose-responsiveness, long-term efficacy, goal rate achievement, and efficacy in patients with moderate to severe hypertension. The results presented here demonstrate that olmesartan is effective when added to HCTZ monotherapy or when HCTZ is added to olmesartan monotherapy, both over the short and long term. Moderate to severe hypertension responds well to olmesartan/HCTZ combination therapy, and the great majority of patients are able to achieve recommended blood pressure targets. Thus olmesartan/HCTZ is a well-tolerated option for patients who fail to respond to monotherapy and as initial therapy in those who require large reductions in diastolic blood pressure or systolic blood pressure to achieve goal blood pressure. PMID:19337537

  20. American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards.

    Science.gov (United States)

    Jacobson, Joseph O; Polovich, Martha; McNiff, Kristen K; LeFebvre, Kristine B; Cummings, Charmaine; Galioto, Michele; Bonelli, Katherine R; McCorkle, Michele R

    2009-11-01

    Standardization of care can reduce the risk of errors, increase efficiency, and provide a framework for best practice. In 2008, the American Society of Clinical Oncology (ASCO) and the Oncology Nursing Society (ONS) invited a broad range of stakeholders to create a set of standards for the administration of chemotherapy to adult patients in the outpatient setting. At the close of a full-day structured workshop, 64 draft standards were proposed. After a formal process of electronic voting and conference calls, 29 draft standards were eliminated, resulting in a final list of 35 draft measures. The proposed set of standards was posted for 6 weeks of open public comment. Three hundred twenty-two comments were reviewed by the Steering Group and used as the basis for final editing to a final set of standards. The final list includes 31 standards encompassing seven domains, which include the following: review of clinical information and selection of a treatment regimen; treatment planning and informed consent; ordering of treatment; drug preparation; assessment of treatment compliance; administration and monitoring; assessment of response and toxicity monitoring. Adherence to ASCO and ONS standards for safe chemotherapy administration should be a goal of all providers of adult cancer care.

  1. Clinical trial of the efficacy and safety of ticarcillin and clavulanic acid.

    Science.gov (United States)

    Roselle, G A; Bode, R; Hamilton, B; Bibler, M; Sullivan, R; Douce, R; Staneck, J L; Bullock, W E

    1985-01-01

    Forty-three hospitalized patients were treated with a new antibiotic combination containing ticarcillin plus the beta-lactamase inhibitor, clavulanic acid, in a fixed combination for intravenous use. A variety of infections were treated, including pneumonia, bacteremia, urinary tract infection, and osteomyelitis. Of 50 episodes of infection in 43 patients, 44 clinical cures were obtained, with 5 patients improving and 1 patient failing to respond to treatment. In vitro susceptibility testing of 101 clinical isolates was notable for the rarity of resistance to the combination antibiotic. Of specific interest, all 14 isolates of Staphylococcus aureus were susceptible to ticarcillin plus clavulanic acid, whereas only 2 of the 14 isolates were susceptible to ticarcillin alone. Adverse reactions to the study drug were minimal; eosinophilia, unaccompanied by other allergic phenomena, and oral candidiasis were most frequent. Overall, the combination of ticarcillin with the beta-lactamase inhibitor, clavulanic acid, appears to be a safe and effective drug for the treatment of infections caused by susceptible organisms. PMID:3888101

  2. Trends in Qualifying Biomarkers in Drug Safety. Consensus of the 2011 Meeting of the Spanish Society of Clinical Pharmacology

    Science.gov (United States)

    Agúndez, José A. G.; del Barrio, Jaime; Padró, Teresa; Stephens, Camilla; Farré, Magí; Andrade, Raúl J.; Badimon, Lina; García-Martín, Elena; Vilahur, Gemma; Lucena, M. Isabel

    2012-01-01

    In this paper we discuss the consensus view on the use of qualifying biomarkers in drug safety, raised within the frame of the XXIV meeting of the Spanish Society of Clinical Pharmacology held in Málaga (Spain) in October, 2011. The widespread use of biomarkers as surrogate endpoints is a goal that scientists have long been pursuing. Thirty years ago, when molecular pharmacogenomics evolved, we anticipated that these genetic biomarkers would soon obviate the routine use of drug therapies in a way that patients should adapt to the therapy rather than the opposite. This expected revolution in routine clinical practice never took place as quickly nor with the intensity as initially expected. The concerted action of operating multicenter networks holds great promise for future studies to identify biomarkers related to drug toxicity and to provide better insight into the underlying pathogenesis. Today some pharmacogenomic advances are already widely accepted, but pharmacogenomics still needs further development to elaborate more precise algorithms and many barriers to implementing individualized medicine exist. We briefly discuss our view about these barriers and we provide suggestions and areas of focus to advance in the field. PMID:22294980

  3. Nonsurgical Facial Rejuvenation: Outcomes and Safety of Neuromodulator and Soft-Tissue Filler Procedures Performed in a Resident Cosmetic Clinic.

    Science.gov (United States)

    Qureshi, Ali A; Parikh, Rajiv P; Sharma, Ketan; Myckatyn, Terence M; Tenenbaum, Marissa M

    2017-05-25

    The ability to perform nonsurgical facial rejuvenation procedures is a core competency requirement for plastic surgery residents. However, limited data exist on training models to achieve competency in nonsurgical facial rejuvenation and on outcomes of these procedures performed by residents. The purpose here is to evaluate patient-reported outcomes and safety of nonsurgical facial rejuvenation procedures performed by plastic surgery residents. We prospectively enrolled 50 patients undergoing neuromodulator and/or soft-tissue filler injections in a resident cosmetic clinic between April and August 2016. Patients completed FACE-Q modules pre-procedure, and at 1 week and 1 month post-procedure. Paired t-tests were used to calculate statistical significance of changes between pre- and post-procedure scores. Effect sizes were calculated to assess clinical improvement from pre- to post-procedure. The magnitude of change was interpreted using Cohen's arbitrary criteria (small 0.20, moderate 0.50, large 0.80). Forty-five patients completed the study. Patients experienced significant improvements (p Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

  4. Safety and quality of nurse independent prescribing: a national study of experiences of education, continuing professional development clinical governance.

    Science.gov (United States)

    Smith, Alesha; Latter, Sue; Blenkinsopp, Alison

    2014-11-01

    To determine the adequacy of initial nurse independent prescribing education and identify continuing professional development and clinical governance strategies in place for non-medical prescribing. In 2006, new legislation in England enabled nurses with an independent prescribing qualification to prescribe, within their competence. In 2006, non-medical prescribing policies released by the Department of Health outlined the recommendations for education, continuing professional development and governance of non-medical prescribing; however, there was no evidence on a national scale about the extent of implementation and effectiveness of these strategies. National surveys of: (i) nurse independent prescribers; and (ii) non-medical prescribing leaders in England. Questionnaire surveys (August 2008-February 2009) covering educational preparation, prescribing practice (nurse independent prescribers) and structures/processes for support and governance (non-medical prescribing leaders). Response rates were 65% (976 prescribers) and 52% (87 leaders). Most nurses felt their prescribing course met their learning needs and stated course outcomes and that they had adequate development and support for prescribing to maintain patient safety. Some types of community nurse prescribers had less access to support and development. The prescribing leaders reported lacking systems to ensure continuity of non-medical prescribing and monitoring patient experience. Educational programmes of preparation for nurse prescribing were reported to be operating satisfactorily and providing fit-for-purpose preparation for the expansion to the scope of nurse independent prescribing. Most clinical governance and risk management strategies for prescribing were in place in primary and secondary care. © 2014 John Wiley & Sons Ltd.

  5. Clinical feasibility and safety of a novel miniature mobile cardiac catheterization laboratory in diagnosis and treatment for coronary heart disease

    Institute of Scientific and Technical Information of China (English)

    Liang Ming; Han Yaling; Wang Geng; Yao Tianming; Sun Jingyang; Li Fei; Xu Kai

    2014-01-01

    Background The lack of medical facilities causes delayed diagnosis and treatment of coronary heart disease in remote mountainous area and/or at disaster site.The miniature mobile cardiac catheterization laboratory was developed to be an intervention platform for coronary heart disease diagnosis and treatment by our team.Pre-clinical research indicated that the miniature mobile cardiac catheterization laboratory performed well in the rescue of critical cardiovascular diseases,even ST-segment elevation myocardial infarction.The present study aimed to evaluate the clinical safety and timeliness of the miniature mobile cardiac catheterization laboratory for emergent coronary interventional diagnosis and treatment.Methods X-ray radiation safety and disinfection efficacy in the miniature mobile cardiac catheterization laboratory were tested during working status.Coronary angiography and/or percutaneous coronary intervention were performed in remote mountainous areas on patients who were first diagnosed as having coronary heart disease by senior interventional cardiologists.The percutaneous coronary intervention procedures and results from patients in the miniature mobile cardiac catheterization laboratory were compared with patients who were treated in the hospital catheter lab.Results The X-ray radiation dosages in the miniature mobile cardiac catheterization laboratory were 39.55 μGy/s,247.4 μGy/h,90.3 μGy/h and 39.4 μGy/h which were corresponded to 0 m,1 m,2 m and 3 m away from the tube central of the medium C-arm.And the radiation dosages used in the miniature mobile cardiac catheterization laboratory were less than the corresponding positions in the hospital catheter lab.The numbers of bacteria colonies in the miniature mobile cardiac catheterization laboratory in different environments range from (60±8) cfu/m3 to (120±10) cfu/m3 and met the demands of percutaneous coronary intervention.A total of 17 patients who received angiography in the miniature mobile

  6. Clinical safety of magnetic resonance imaging in patients with implanted SynchroMed EL infusion pumps

    Energy Technology Data Exchange (ETDEWEB)

    Diehn, Felix E.; Wood, Christopher P.; Watson, Robert E.; Hunt, Christopher H. [Mayo Clinic, Department of Radiology, Rochester, MN (United States); Mauck, William D. [Mayo Clinic, Department of Anesthesiology, Rochester, MN (United States); Burke, Michelle M. [Mayo Clinic, Department of Psychiatry and Psychology, Rochester, MN (United States)

    2011-02-15

    Patients with implanted SynchroMed spinal infusion pumps (Medtronic, Inc., Minneapolis, MN) routinely undergo magnetic resonance imaging at our institution. In August 2008, Medtronic issued an urgent medical device correction report regarding several pumps. Because of the rare potential ''for a delay in the return of proper drug infusion'' and ''for a delay in the logging of motor stall events,'' ''a patient's pump must be interrogated after MRI exposure in order to confirm proper pump functionality.'' This is particularly important in patients receiving intrathecal baclofen, for whom a delay in return of proper pump infusion could lead to life-threatening baclofen withdrawal syndrome. The objective of this report is to present our experience and protocol of performing magnetic resonance imaging in patients with implanted SynchroMed EL pumps. We retrospectively reviewed records of 86 patients with implanted SynchroMed EL spinal infusion pumps who underwent 112 examinations on 1.5-T magnetic resonance imaging scanners from September 1, 1998 to July 7, 2004. No SynchroMed EL pumps were damaged by magnetic resonance imaging, and the programmable settings remained unchanged in all patients. Our data suggest that SynchroMed EL pump malfunction is indeed rare after routine clinical 1.5-T magnetic resonance imaging examinations. However, based on the Medtronic correction report, we perform pump interrogation before and after imaging. (orig.)

  7. Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Yushmanova Irina

    2011-03-01

    Full Text Available Abstract It is important for patients that treatments for diabetes not increase cardiovascular (CV risk. The objective of this analysis was to examine retrospectively the CV safety of exenatide BID, a GLP-1 receptor agonist approved for treating hyperglycemia in patients with type 2 diabetes not adequately controlled with diet and exercise. Individual participant data was pooled to assess the relative risk (RR of CV events with exenatide BID versus a pooled comparator (PC group treated with either placebo or insulin from 12 controlled, randomized, clinical trials ranging from 12-52 weeks. Mean baseline values for HbA1c (8.33-8.38%, BMI (31.3-31.5 kg/m2, and duration of diabetes (8 y were similar between groups. Trials included patients with histories of microvascular and/or macrovascular disease. Customized primary major adverse CV events (MACE included stroke, myocardial infarction, cardiac mortality, acute coronary syndrome, and revascularization procedures. The Primary MACE RR (0.7; 95% CI 0.38, 1.31, calculated by the Mantel-Haenszel method (stratified by study, suggested that exenatide use (vs. PC did not increase CV risk; this result was consistent across multiple analytic methods. Because the trials were not designed to assess CV outcomes, events were identified retrospectively from a list of preferred terms by physicians blinded to treatment. Other limitations included the low number of CV events, the short duration of trials (≤1 y, and a single active comparator (insulin. The results of these analyses are consistent with those of a recent retrospective analysis of a large insurance database that found that patients treated with exenatide twice daily were less likely to have a CV event than were patients treated with other glucose-lowering therapies. Keywords: GLP-1 receptor agonist, diabetes, cardiovascular safety

  8. Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial.

    Science.gov (United States)

    Charytan, C; Levin, N; Al-Saloum, M; Hafeez, T; Gagnon, S; Van Wyck, D B

    2001-02-01

    Iron sucrose has been used to provide intravenous (IV) iron therapy to patients outside the United States for more than 50 years. In a multicenter North American clinical trial, we determined the efficacy and safety of iron sucrose therapy in patients with dialysis-associated anemia, evidence of iron deficiency, and below-target hemoglobin (Hgb) levels despite epoetin therapy. Evidence of iron deficiency included a transferrin saturation (Tsat) less than 20% and ferritin level less than 300 ng/mL, and below-target Hgb levels included values less than 11.0 g/dL. We administered iron sucrose in 10 doses, each administered undiluted as 100 mg IV push over 5 minutes, without a prior test dose. We assessed efficacy by determining the subsequent change in Hgb, Tsat, and ferritin values. We assessed safety by recording blood pressure and adverse events after iron sucrose injection and comparing results with those for the same patients during an observation control period. Results showed a significant increase in Hgb level that was first evident after three doses of iron sucrose and persisted at least 5 weeks after the 10th dose. Tsat and ferritin levels also increased significantly and remained elevated. In 77 enrolled patients, including those with previous iron dextran sensitivity, other drug allergies, or concurrent angiotensin-converting enzyme inhibitor use, we saw no serious adverse drug reactions and no change in intradialytic blood pressure associated with iron sucrose administration. We conclude that iron sucrose injection administered as 1,000 mg in 10 divided doses by IV push without a prior test dose is safe and effective for the treatment of iron deficiency in patients with dialysis-associated anemia.

  9. [Evaluation of the Effectiveness and Safety in a Multi-center Clinical Trial of VIBRANT SOUNDBRIDGE in Japan].

    Science.gov (United States)

    Doi, Katsumi; Kanzaki, Sho; Kumakawa, Kozo; Usami, Shin-ichi; Iwasaki, Satoshi; Yamanaka, Noboru; Naito, Yasushi; Gyo, Kiyofumi; Tono, Tetsuya; Takahashi, Haruo; Kanda, Yukihiko

    2015-12-01

    Middle ear implants (MEIs) such as the Vibrant Soundbridge (VSB) are attractive and alternative treatments for patients with conductive, sensorineural, and mixed hearing loss who do not benefit from, or who choose not to wear, conventional hearing aids (HAs). Recent studies suggest that MEIs can provide better improvements in functional gain, speech perception, and quality of life than HAs, although there are certain risks associated with the surgery which should be taken into consideration, including facial nerve or chorda tympanic nerve damage, dysfunctions of the middle and inner ears, and future device failure/explantation. In Japan, a multi-center clinical trial of VSB was conducted between 2011-2014. A round window vibroplasty via the transmastoid approach was adopted in the protocol. The bony lip overhanging the round window membrane (RWM) was extensively but very carefully drilled to introduce the Floating Mass Transducer (FMT). Perichondrium sheets were used to stabilize the FMT onto the RWM. According to the audiological criteria, the upper limit of bone conduction should be 45 dB, 50 dB, and 65 dB from 500 Hz to 4, 000 Hz. Twenty-five patients underwent the surgery so far at 13 different medical centers. The age at the surgery was between 26-79 years old, and there were 15 males and 10 females. The cause of conductive or mixed hearing loss was middle ear diseases in 23 cases and congenital aural atresia in two cases. The data concerning on the effectiveness and safety of VSB was collected before the surgery and 20 weeks after the surgery. Significant improvements of free-field Pure Tone Audiogram (PTA) from 250 Hz to 8, 000 Hz were confirmed (p VSB. However, the long-term efficacy and safety of these devices should be established.

  10. The Vena Tech LP Permanent Caval Filter: Effectiveness and Safety in the Clinical Setting in Three Chinese Medical Centers.

    Science.gov (United States)

    Zhang, Fuxian; Li, Dajun; Liu, Jianlong; Zhang, Huan

    2015-07-01

    The effectiveness, safety, and patient outcomes after Vena Tech LP caval filter placement were evaluated retrospectively in China. From January 2002 to January 2013, 1,200 patients received Tech LP caval filters to prevent PE at three Beijing University medical centers. The patients' general condition, reasons for DVT formation, filter placement method, indication for filter placement, complications, safety of the filter, treatment post-filter, and follow-up were recorded. The patients' mean age was 65 (range, 19-87) years, and 840 were males. Before filter placement, all had ultrasonic-diagnosed DVT, 84% (1008/1200) were assessed for PE, and 73% (736/1008) had PE. Filters were placed via the femoral or jugular vein, with 62 placements at the SVC and 1,138 at the IVC. Filter placement via various venous access routes was 100% successful. Anticoagulation therapy was continued in 88% patients (n=1056) for ≥6 months after filter placement. Follow-up was accomplished in 80% (n=960) of patients for an average of 6 years (range, 3 months to 10 years). The patency rate of the vena cava was 90% at 5 years. The morbidity was 2% and the mortality was 0.5% during 30 days post-filter placement. After 30 days, the mortality rate was 2.4%, no PE reoccurred, and there were no other clinical adverse events. Vena Tech LP caval filter placement was effective and safe, with demonstrated stability and a good long-term patency rate at the IVC and SVC in China. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Clinical efficacy and safety in relapsed/refractory diffuse large B-cell lymphoma: a systematic literature review.

    Science.gov (United States)

    Colosia, Ann; Njue, Annete; Trask, Peter C; Olivares, Robert; Khan, Shahnaz; Abbe, Adeline; Police, Rachel; Wang, Jianmin; Ruiz-Soto, Rodrigo; Kaye, James A; Awan, Farrukh

    2014-10-01

    This systematic literature review was designed to assess information on the clinical efficacy and safety of interventions used in the treatment of refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL) and to perform a meta-analysis if possible. We searched databases (PubMed, EMBASE, and Cochrane Library for articles from 1997 to August 2, 2012 reported in English), conference abstracts, bibliographic reference lists, and the ClinicalTrials.gov database for phase II to IV studies with results. Studies had to report on patients with R/R DLBCL who were not eligible to receive high-dose therapy (HDT) with stem cell transplantation (SCT) (autologous or allogeneic). Mixed-type non-Hodgkin lymphoma (NHL) studies were required to report R/R DLBCL outcomes separately. We identified 55 studies that presented outcomes data separately for patients with R/R DLBCL. Of 7 comparative studies, only 4 were randomized controlled trials (RCTs). In the 2 RCTs with a common regimen, the patient populations differed too greatly to perform a valid meta-analysis. The 48 single-arm studies identified were typically small (n < 50 in most), with 31% reporting median progression-free survival (PFS) or overall survival (OS) specifically for the R/R DLBCL population. In these studies, median OS ranged from 4 to 13 months. The small number of RCTs in R/R DLBCL precludes identifying optimal treatments. Small sample size, infrequent reporting of OS and PFS separated by histologic type, and limited information on patient characteristics also hinder comparison of results. Randomized studies are needed to demonstrate which current therapies have advantages for improving survival and other important clinical outcomes in patients with R/R DLBCL.

  12. Antiretroviral simplification with darunavir/ritonavir monotherapy in routine clinical practice: safety, effectiveness, and impact on lipid profile.

    Directory of Open Access Journals (Sweden)

    José R Santos

    Full Text Available BACKGROUND: Simplification of antiretroviral treatment (ART with darunavir/ritonavir (DRV/r monotherapy has achieved sustained suppression of plasma viral load (pVL in clinical trials; however, its effectiveness and safety profile has not been evaluated in routine clinical practice. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective cohort analysis of HIV-1-infected patients who initiated DRV/r monotherapy once daily with a pVL 50 copies/mL at week 48, and time to VF. Other causes of treatment discontinuation and changes in lipid profile were evaluated up to week 48. Ninety-two patients were followed for a median (IQR of 73 (57-92 weeks. The median baseline and nadir CD4+ T-cell counts were 604 (433-837 and 238 (150-376 cells/mm3, respectively. Patients had previously received a median of 5 (3-9 ART lines and maintained a pVL<50 copies/mL for a median of 76 (32-176 weeks before initiating DRV/r monotherapy. Nine (9.8% patients developed VF at week 48; time to VF was 47.1 (IQR: 36.1-47.8 weeks among patients with VF. Other reasons for changing ART were gastrointestinal disturbances (n = 3, rash (n = 1, and impaired CD4 recovery (n = 2. Median low-density lipoprotein cholesterol levels increased from 116.1 mg/dL at baseline to 137.3 mg/dL at 48 weeks (p = 0.001. CONCLUSIONS/SIGNIFICANCE: Treatment simplification with DRV/r monotherapy seems safe and effective in routine clinical practice. Further research is needed to elucidate the effect of DRV/r monotherapy on cholesterol levels.

  13. Safety of methotrexate in rheumatoid arthritis: a retrospective cohort study in clinical practice

    Directory of Open Access Journals (Sweden)

    G. Mennillo

    2011-09-01

    Full Text Available Objective. To evaluate the treatment duration with MTX monotherapy or in association with DMARDs or anti TNFa inhibitors and the incidence and typology of adverse events (AE occurred in rheumatoid arthritis (RA patients. Methods. A retrospective large cohort study of RA outpatients, consecutively seen from January 2000 to June 2005 was performed. Study group were RA patients classified according to the 1984 ACR criteria for the classification of rheumatoid arthritis. The patients were divided in 3 groups according to the treatment regimen: MTX monotherapy, MTX in combination with DMARD or with anti TNFa agents. We analyzed 348 therapeutic cycles, 177 of whom using MTX monotherapy. Results. The 224 RA patients accumulated 800 person-years of follow up. Follow up for each of the groups was: MTX monotherapy 479.4 person-years, MTX in combination with DMARDs 244.5, or with anti TNFa inhibitors, 75.7 person- years. From the Kaplan-Meier analysis, the probability of patients remaining on treatment 5 years was 58.5 after starting MTX. The incidence of any AE was 8.87 per 100 person-years. From all, 69 (97.2% AE were no severe. Among those, more frequently were observed at gastrointestinal tract (31%, liver (19.7%, skin (15.5%. Incidence of severe AE (lung adenocarcinoma, 1 case; pancreatitis, 1 case was 0.25 per 100 person-years, occurring in patients taking MTX monotherapy or MTX in combination with DMARDs, respectively. Conclusions. These data confirm that methotrexate is well tolerated in clinical practice in the medium-long term. Nevertheless, the occurrence of severe AE require an accurate vigilance for methotrexate toxicity.

  14. Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial.

    Science.gov (United States)

    Van Wyck, D B; Cavallo, G; Spinowitz, B S; Adhikarla, R; Gagnon, S; Charytan, C; Levin, N

    2000-07-01

    Sensitivity to iron dextran is a potent obstacle to maintaining optimum iron status in patients with dialysis-associated anemia. As part of the North American clinical trials for iron sucrose injection, we examined the effect of intravenous (IV) iron sucrose in 23 hemodialysis patients with documented sensitivity to iron dextran, ongoing epoetin alfa therapy, and below-target-range hemoglobin (Hgb) levels (iron dextran were judged to be mild (n = 16; group A) or severe (n = 7; group B). We prospectively examined adverse events and vital signs after administering 100 mg of IV iron sucrose in each of 10 consecutive dialysis treatment sessions and compared results with those recorded in each of three consecutive dialysis sessions without iron treatment. We administered iron sucrose by IV push over 5 minutes to group A patients and by IV push over 5 minutes or IV infusion over 15 to 30 minutes to group B patients. We did not administer a test dose. Results showed no serious adverse drug reactions after a total of 223 doses of iron sucrose (184 doses by IV push, 39 doses by IV infusion). Intradialytic blood pressure changes after IV iron sucrose injection did not differ from those recorded during dialysis sessions without treatment. An increase in values for Hgb, hematocrit, transferrin saturation, and ferritin, coupled with no significant change in epoetin dose and a decrease in total iron-binding capacity, confirmed the efficacy of iron sucrose injection in managing anemia. We conclude that iron sucrose injection is safe and effective in the management of anemia in patients sensitive to iron dextran and can be administered without a test dose by IV push or infusion.

  15. Acceptability, efficacy and safety of two treatment protocols for dental fluorosis: a randomized clinical trial.

    Science.gov (United States)

    Castro, Kaline Silva; Ferreira, Ana Cláudia de Araújo; Duarte, Rosângela Marques; Sampaio, Fábio Correia; Meireles, Sônia Saeger

    2014-08-01

    This parallel randomized clinical trial evaluated the efficacy of two treatments for removing fluorosis stains. Seventy individuals living in an area endemic for fluorosis, with at least four maxillary anterior teeth presenting fluorosis with a Thylstrup and Fejerskov index from 1 to 7, were randomized into two treatment groups (n=35): GI - enamel microabrasion or GII - microabrasion associated with at-home bleaching. Microabrasion was performed using 37% phosphoric acid and pumice and, at-home tooth bleaching was performed with 10% carbamide peroxide. Areas of enamel opacities were recorded by digital camera at baseline and 1-month (1M) after treatment. Two blinded examiners evaluated the reduction in the area (mm(2)) of opacity using software. Two visual analogue scales were used: one for recording tooth sensitivity and/or gingival irritation ranging from 1 (none) to 5 (severe) and the other to evaluate participant satisfaction with the treatment used ranging from 1 (no improvement) to 7 (exceptional improvement). 1M after treatment, both groups showed a significant reduction in the area of enamel opacity (p=0.0001) and there was no difference between groups (p=0.1). Most of the participants from both treatment groups reported no or mild tooth sensitivity and gingival irritation (p>0.05). Participants reported that they were happy with the improvement in dental appearance, however, individuals from GII reported that they were happier than those from GI (p=0.004). Both treatment protocols were effective in reducing fluoride stains, however, when home bleaching was associated to enamel microabrasion, patients reported a major satisfaction with dental appearance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Non-clinical safety and pharmacokinetic evaluations of propylene glycol aerosol in Sprague-Dawley rats and Beagle dogs.

    Science.gov (United States)

    Werley, Michael S; McDonald, Paddy; Lilly, Patrick; Kirkpatrick, Daniel; Wallery, Jeffrey; Byron, Peter; Venitz, Jürgen

    2011-09-05

    Aerosolized propylene glycol (PG) was generated as log-normally distributed particulate clouds in different concentrations using a novel capillary aerosol generator (CAG) and evaluated in a battery of non-clinical studies intended to assess its potential inhalation and systemic toxicity in 2 species before ICH-compliant "first-time-in-man" studies. Exposures were nose-only in rats, and via face mask with oropharyngeal tube in dogs. The CAG-generated PG aerosol had a mass median aerodynamic diameter (MMAD) of 2.29μm, with a 1.56 geometric standard deviation (GSD) in the rat studies, and a MMAD of 1.34μm (1.45 GSD) in the dog studies, consistent with expected particle size exposures in man. International Congress on Harmonization (ICH) Guidelines were followed, which recommend preliminary non-clinical safety studies using the vehicle and device (CAG-PG) prior to the first human exposure including safety pharmacology, pharmacokinetic (PK) studies, single dose toxicity studies, and repeated dose toxicity studies in two species. In the rat, the only biologically relevant findings included clinical signs of ocular and nasal irritation indicated by minor bleeding around the eyes and nose, and minimal laryngeal squamous metaplasia. This finding is commonly observed in inhalation studies in the rat, and likely related to the unique sensitivity of the tissue, as well as the circuitous airflow pathway through the larynx which increases particle deposition. In the female Beagle dog, treatment-related decreases in hemoglobin, red blood cells and hematocrit were observed in the two highest exposure groups, equivalent to approximately 18 and 60mg/kg/day. In male dogs from the high dose group, similar small decreases, albeit, non-statistically significant decreases were observed in these hematological markers as well. PK studies in rats and dogs showed that the absorption of PG following pulmonary inhalation exposure occurs rapidly, and equilibrium between lung tissue and plasma

  17. Clinical Trial Using Sodium Pertechnetate 99mTc Produced with Medium-Energy Cyclotron: Biodistribution and Safety Assessment in Patients with Abnormal Thyroid Function.

    Science.gov (United States)

    Selivanova, Svetlana; Lavallée, Éric; Senta, Helena; Caouette, Lyne; McEwan, Alexander Jb; Guérin, Brigitte; Lecomte, Roger; Turcotte, Eric

    2016-10-13

    A single-site prospective open-label clinical study with cyclotron-produced sodium pertechnetate (99m)Tc ([(99m)Tc]NaTcO4, (99m)Tc-pertechnetate) was performed in patients with indication for a thyroid scan to demonstrate the clinical safety and diagnostic efficacy of the drug and confirm its equivalence with conventional sodium pertechnetate (99m)Tc eluted from a generator.

  18. Clinical potential, safety, and tolerability of arbaclofen in the treatment of autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Frye RE

    2014-05-01

    the treatment of gastroesophageal reflux suggest that arbaclofen is safe and well-tolerated. Clearly, further clinical studies are needed in order to refine the symptoms and characteristics of children with ASD that are best treated with arbaclofen.Keywords: autism spectrum disorder, Fragile X, gamma-aminobutyric acid, arbaclofen, R-baclofen, STX209

  19. A new method for the assessment of patient safety competencies during a medical school clerkship using an objective structured clinical examination

    Directory of Open Access Journals (Sweden)

    Renata Mahfuz Daud-Gallotti

    2011-01-01

    Full Text Available INTRODUCTION: Patient safety is seldom assessed using objective evaluations during undergraduate medical education. OBJECTIVE: To evaluate the performance of fifth-year medical students using an objective structured clinical examination focused on patient safety after implementation of an interactive program based on adverse events recognition and disclosure. METHODS: In 2007, a patient safety program was implemented in the internal medicine clerkship of our hospital. The program focused on human error theory, epidemiology of incidents, adverse events, and disclosure. Upon completion of the program, students completed an objective structured clinical examination with five stations and standardized patients. One station focused on patient safety issues, including medical error recognition/disclosure, the patient-physician relationship and humanism issues. A standardized checklist was completed by each standardized patient to assess the performance of each student. The student's global performance at each station and performance in the domains of medical error, the patient-physician relationship and humanism were determined. The correlations between the student performances in these three domains were calculated. RESULTS: A total of 95 students participated in the objective structured clinical examination. The mean global score at the patient safety station was 87.59 ± 1.24 points. Students' performance in the medical error domain was significantly lower than their performance on patient-physician relationship and humanistic issues. Less than 60% of students (n = 54 offered the simulated patient an apology after a medical error occurred. A significant correlation was found between scores obtained in the medical error domains and scores related to both the patient-physician relationship and humanistic domains. CONCLUSIONS: An objective structured clinical examination is a useful tool to evaluate patient safety competencies during the medical

  20. A pilot study to evaluate the safety and clinical performance of Leucopatch, an autologous, additive-free, platelet-rich fibrin for the treatment of recalcitrant chronic wounds

    DEFF Research Database (Denmark)

    Jørgensen, Bo; Karlsmark, Tonny; Vogensen, Hanne;

    2011-01-01

    This prospective, uncontrolled pilot study evaluated the safety and clinical performance of Leucopatch an additive-free, autologous platelet-rich fibrin in the treatment of recalcitrant chronic wounds. Fifteen patients, with 16 lower extremity chronic wounds of varying etiologies were treated...

  1. Good Laboratory Practice (GLP) status of Asian countries and its implementation in non-clinical safety studies in pharmaceutical drug development.

    Science.gov (United States)

    Sasaki, Madoka; Hinotsu, Shiro; Kawakami, Koji

    2009-10-01

    Non-clinical animal studies to assess the safety of compounds under development have to comply with Good Laboratory Practice (GLP). The Organization for Economic Co-operation and Development (OECD) has established the Mutual Acceptance of Data (MAD) system in OECD member countries for the mutual acceptance of non-clinical safety study data. Since 1997 non-OECD-member countries have also been able to participate in the MAD system, if the country meets the level of standardized compliance with OECD GLP. Thus, several Asian non-OECD countries are trying to develop their GLP standards in order to become official members of the MAD system. Pharmaceutical companies face significant expense in the drug-development process, including the cost of non-clinical safety studies; in response, companies in Asian countries are seeking to establish GLP facilities to provide cost-effective services for drug development. To assess the quality and cost of GLP performance in Asian countries, in this study we approached GLP facilities in a number of Asian countries to obtain price and quality information on a 'virtual compound' to be assessed in non-clinical safety studies. Also, the development status of GLP in Asian countries in terms of policy and infrastructure was analyzed. We found that, among Asian countries, India and Singapore may be candidates for participation in te MAD system in terms of their compliance with GLP, language, and costs. These findings will be beneficial to pharmaceutical companies planning GLP studies in Asian countries.

  2. Examining variations in prescribing safety in UK general practice: cross sectional study using the Clinical Practice Research Datalink

    Science.gov (United States)

    Kontopantelis, Evangelos; Akbarov, Artur; Rodgers, Sarah; Avery, Anthony J; Ashcroft, Darren M

    2015-01-01

    Study question What is the prevalence of different types of potentially hazardous prescribing in general practice in the United Kingdom, and what is the variation between practices? Methods A cross sectional study included all adult patients potentially at risk of a prescribing or monitoring error defined by a combination of diagnoses and prescriptions in 526 general practices contributing to the Clinical Practice Research Datalink (CPRD) up to 1 April 2013. Primary outcomes were the prevalence of potentially hazardous prescriptions of anticoagulants, anti-platelets, NSAIDs, β blockers, glitazones, metformin, digoxin, antipsychotics, combined hormonal contraceptives, and oestrogens and monitoring by blood test less frequently than recommended for patients with repeated prescriptions of angiotensin converting enzyme inhibitors and loop diuretics, amiodarone, methotrexate, lithium, or warfarin. Study answer and limitations 49 927 of 949 552 patients at risk triggered at least one prescribing indicator (5.26%, 95% confidence interval 5.21% to 5.30%) and 21 501 of 182 721 (11.8%, 11.6% to 11.9%) triggered at least one monitoring indicator. The prevalence of different types of potentially hazardous prescribing ranged from almost zero to 10.2%, and for inadequate monitoring ranged from 10.4% to 41.9%. Older patients and those prescribed multiple repeat medications had significantly higher risks of triggering a prescribing indicator whereas younger patients with fewer repeat prescriptions had significantly higher risk of triggering a monitoring indicator. There was high variation between practices for some indicators. Though prescribing safety indicators describe prescribing patterns that can increase the risk of harm to the patient and should generally be avoided, there will always be exceptions where the indicator is clinically justified. Furthermore there is the possibility that some information is not captured by CPRD for some practices—for example, INR results in

  3. Curbing the urge to care: A Bourdieusian analysis of the effect of the caring disposition on nurse middle managers' clinical leadership in patient safety practices.

    Science.gov (United States)

    Lalleman, P C B; Smid, G A C; Lagerwey, M D; Shortridge-Baggett, L M; Schuurmans, M J

    2016-11-01

    Nurse managers play an important role in implementing patient safety practices in hospitals. However, the influence of their professional background on their clinical leadership behaviour remains unclear. Research has demonstrated that concepts of Bourdieu (dispositions of habitus, capital and field) help to describe this influence. It revealed various configurations of dispositions of the habitus in which a caring disposition plays a crucial role. We explore how the caring disposition of nurse middle managers' habitus influences their clinical leadership behaviour in patient safety practices. Our paper reports the findings of a Bourdieusian, multi-site, ethnographic case study. Two Dutch and two American acute care, mid-sized, non-profit hospitals. A total of 16 nurse middle managers of adult care units. Observations were made over 560h of shadowing nurse middle managers, semi-structured interviews and member check meetings with the participants. We observed three distinct configurations of dispositions of the habitus which influenced the clinical leadership of nurse middle managers in patient safety practices; they all include a caring disposition: (1) a configuration with a dominant caring disposition that was helpful (via solving urgent matters) and hindering (via ad hoc and reactive actions, leading to quick fixes and 'compensatory modes'); (2) a configuration with an interaction of caring and collegial dispositions that led to an absence of clinical involvement and discouraged patient safety practices; and (3) a configuration with a dominant scientific disposition showing an investigative, non-judging, analytic stance, a focus on evidence-based practice that curbs the ad hoc repertoire of the caring disposition. The dispositions of the nurse middle managers' habitus influenced their clinical leadership in patient safety practices. A dominance of the caring disposition, which meant 'always' answering calls for help and reactive and ad hoc reactions, did not

  4. Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine, and hydrochlorothiazide in clinical practice

    Directory of Open Access Journals (Sweden)

    Bramlage P

    2014-12-01

    Full Text Available Peter Bramlage,1 Eva-Maria Fronk,2 Wolf-Peter Wolf,3 Rüdiger Smolnik,3 Gemma Sutton,1 Roland E Schmieder4 1Institut für Pharmakologie und präventive Medizin, Mahlow, Germany; 2Daiichi Sankyo Europe GmbH, Munich, Germany; 3Daiichi Sankyo Deutschland GmbH, Munich, Germany; 4Abteilung für Nephrologie und Hypertensiologie, Universitätsklinikum Erlangen, Erlangen, Germany Background: Clinical trials indicate that the use of fixed-dose combinations (FDCs is associated with a higher level of treatment adherence and prolonged blood pressure (BP control. The aim of this study was to document the safety and effectiveness of the FDC olmesartan/amlodipine/hydrochlorothiazide in patients with essential hypertension in clinical practice. Methods: This multicenter, prospective, 24-week, noninterventional study enrolled 5,831 patients from primary care offices in Germany and Austria. Inclusion criteria were a diagnosis of essential hypertension and newly initiated treatment with the FDC. Results: The mean age of patients was 63.5 years, almost 50% of patients had a time since diagnosis of essential hypertension of over 5 years, and approximately 70% of patients had at least one cardiovascular risk factor, including 29.4% of patients with diabetes mellitus. Following approximately 24 weeks of treatment, the mean reduction in systolic/diastolic BP was 29.0/14.0 mmHg, a BP response was observed by 94.2% of patients, and a target BP of <140/90 mmHg was attained in 67.5% of patients. At least one adverse drug reaction (ADR was experienced by 1.2% of patients, with the most common being peripheral edema. Subanalyses demonstrated that the following factors did not have a significant influence on the ADR rate: age (<65 years versus ≥65 years, diabetes mellitus (no/yes, cardiovascular risk (low/high, and concomitant medication (no/yes. Conclusion: This study demonstrates that in clinical practice, treatment with the three-drug combination as an FDC tablet

  5. Clinical Safety and Parameters of Maximum Oxygen Uptake (VO₂Max) Testing in Pakistani Patients With Heart Failure.

    Science.gov (United States)

    Hussain, Sajjad; Kayani, Azhar Mahmood; Munir, Rubab

    2015-09-01

    To determine the parameters of maximum oxygen uptake (VO2max) in a Pakistani systolic heart failure cohort and its safety in a clinical setting. Descriptive study. Armed Forces Institute of Cardiology, National Institute of Heart Diseases, Rawalpindi, from June 2011 to January 2013. Maximum oxygen uptake test was performed in patients with severe heart failure, who could perform the VO2max treadmill test. Age, Body Mass Index (BMI) ejection fraction, VO2max and respiratory exchange ratios and their correlations were determined. Out of 135 patients, 77% (n=104) were males, with a mean age of 45.9 ±15.7 years. Weight of patients ranged from 30 kg to 107 kg (mean 63.29 ±13.6 kg); mean BMI was 23.16 ±4.56 kg/m2. All patients presented with either NYHA class of III (50.3%; n=68) or IV (49.7%; n=67); mean ejection fraction was 22.54 ±5.7% (10 - 35%, IQ:20 - 25). The VO2 max of the patients ranged from 3 to 32 ml/kg/minute (mean 12.85 ±4.49 ml/kg/minute). Respiratory exchange ratio was over 1 for all patients (1.12 - 1.96, mean = 1.36 ±0.187). There was a negative correlation with age (r = -0.204; p = 0.028) whereas a positive correlation was found with exercise time (r = 0.684; p = 0.000), hemoglobin (r = 0.190; p = 0.047) and ejection fraction (r = 0.187 ; p = 0.044). Cardiopulmonary exercise testing in a high-risk heart failure cohort is safe and provides information beyond the routine clinical evaluation of heart failure patients.

  6. Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).

    Science.gov (United States)

    Liu, Zhichao; Shi, Qiang; Ding, Don; Kelly, Reagan; Fang, Hong; Tong, Weida

    2011-12-01

    Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60-70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the "Rule of Three" was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity.

  7. Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps.

    Directory of Open Access Journals (Sweden)

    Zhichao Liu

    2011-12-01

    Full Text Available Drug-induced liver injury (DILI is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps. The DILIps yielded 60-70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the "Rule of Three" was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91% when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity.

  8. DRUG SAFETY MONITORING IN PATIENTS ATTENDING EPILEPSY CLINIC IN A TERTIARY CARE TEACHING HOSPITAL IN RURAL BENGAL

    Directory of Open Access Journals (Sweden)

    Sourav

    2016-02-01

    Full Text Available BACKGROUND Epilepsy is the second most common neurological disorder affecting fifty million people globally. Antiepileptic Drugs (AEDs are the mainstay of management in epilepsy. Use of AEDs over prolonged duration makes occurrence of multiple Adverse Drug Reactions (ADRs frequently, especially with polytherapy. OBJECTIVES To estimate the incidence of all the ADRs among patients taking AEDs and to assess their causalities and to quantify their severity. MATERIAL AND METHODS This prospective, observational study was carried out at an Outpatient Referral Epilepsy Clinic at Neurology Department at Bankura Sammilani Medical College, West Bengal, between 1st June and 30th September 2015. The demographic data, diagnosis, drugs prescribed and ADRs experienced by the patients were recorded. Causality and severity assessment was done using Naranjo’s Scale and Hartwig’s Severity Assessment Scale respectively. RESULTS Incidence of ADRs among the patients who attended the clinic was 3.3% (105 patients among 3146 experienced at least one ADR. Total 161 ADRs were detected, among which 55.3% were CNS adverse events followed by 15.5% gastrointestinal, 14.3% endocrine, 10.6% psychiatric abnormalities and 4.3% related to dermatological and allergic manifestations. Nearly one-third of the ADRs (32.3% were found to be possible and 109 (67.7% are of probable category, whereas none were deemed to be doubtful or definite. The most commonly implicated suspect drug was valproate (51.5% followed by Phenytoin (22.9%. Most of the ADRs were mild (93.2%, 5.6% were moderate and only 1.2% were deemed severe. CONCLUSION Incidence of ADRs is found to be common in patients on AEDs. Though rare, but they can be life-threatening. Routine safety assessments and pharmacovigilance is necessary in this set up to reduce the incidence and also improve pharmacotherapy and patient compliance

  9. Comparison of clinical efficacy and safety between indacaterol and tiotropium in COPD: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Kim, Jung Soo; Park, Jinkyeong; Lim, Seong Yong; Oh, Yeon-Mok; Yoo, Kwang Ha; Park, Yong Bum; Sheen, Seung Soo; Kim, Min-Ji; Carriere, K C; Jung, Ji Ye; Park, Hye Yun

    2015-01-01

    Two once-daily inhaled bronchodilators, indacaterol and tiotropium, are widely used as first-line therapy in stable COPD patients. This study was performed to compare the clinical efficacy and safety between indacaterol and tiotropium in patients with moderate-to-severe COPD. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched to identify all published randomized controlled trials (RCTs). The primary outcome was trough forced expiratory volume in 1 second (FEV1) at week 12. Four RCTs were eligible for inclusion (three RCTs with moderate-to-severe COPD patients and one RCT with only severe COPD patients). Trough FEV₁ at weeks 12 and 26 were not significantly different between indacaterol and tiotropium by the standardized mean difference with 0.014 (95% CI, -0.036, 0.063, I²= 23.5%) and with 0.037 (95% CI, -0.059 to 0.133, I²= 0%) along with differences in means of 0.003L and 0.014L, respectively. Indacaterol and tiotropium also showed similar St. George's Respiratory Questionnaire (SGRQ) total scores and percentages of patients with SGRQ improvement (≥ 4 units) at week 26. The incidences of nasopharyngitis, serious cardiovascular events, and serious adverse events were not different between indacaterol and tiotropium, while those of cough (OR = 1.68, P indacaterol than tiotropium. However, when one study with only severe COPD patients was removed from the meta-analysis, the difference in the incidence of COPD worsening between indacaterol and tiotropium became non-significant (OR = 1.13, P = 0.204, and RR = 1.09). The clinical efficacy and serious adverse events between indacaterol and tiotropium were equivocal in patients with moderate-to-severe COPD. Cough is a common complaint associated with indacaterol, and COPD worsening needs to be carefully monitored in severe COPD patients when treated with indacaterol.

  10. Knowledge and willingness to provide research biospecimens among foreign-born Latinos using safety-net clinics.

    Science.gov (United States)

    Loffredo, Christopher A; Luta, Gheorghe; Wallington, Sherrie; Makgoeng, Solomon B; Selsky, Claire; Mandelblatt, Jeanne S; Adams-Campbell, Lucile L

    2013-08-01

    Latinos tend to be under-represented in cancer research and in bio-repositories. We conducted a Spanish-language, interviewer-administered cross-sectional survey of 331 foreign-born Latinos from Central and South America attending safety-net clinics in order to describe factors associated with knowledge about and intention to provide bio-specimens for research purposes. We used logistic regression and multiple imputation methods to evaluate associations between socio-cultural measures, medical trust, demographics, as well as knowledge about and intentions to provide bio-specimens. Almost half (47 %) of respondents knew what bio-specimens were, and 67 % said that they would provide a specimen after being given information about what this involved; this increased to 72 % among those with prior knowledge. Controlling for covariates, Latinos with a high school education and above were more likely to know what a bio-specimen was and to say they would provide bio-specimens than were those with lower levels of education [adjusted OR (aOR) 2.85, 95 % CI 1.37-5.96; and 3.49, 95 % CI 1.41-8.63, p ≤ 0.01, respectively]. Those with greater social integration were more likely to know about bio-specimens than those with less integration (aOR 2.54, 95 % CI 1.45-4.46, p = 0.001). Higher endorsement of family values was independently associated with intent to give bio-specimens (aOR 1.11, 95 % CI 1.02-1.20, p = 0.017 per five-point increase in "familism" score). Medical mistrust was not related to intentions to provide specimens. Our results suggest that interventions to increase willingness to provide bio-specimens could leverage trusted clinics or social networks and should consider individuals' education and socio-cultural perspectives.

  11. Safety and Efficacy of MLC601 in Iranian Patients after Stroke: A Double-Blind, Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    A. A. Harandi

    2011-01-01

    Full Text Available Objective. To investigate the safety and efficacy of MLC601 (NeuroAid as a traditional Chinese medicine on motor recovery after ischemic stroke. Methods. This study was a double-blind, placebo-controlled clinical trial on 150 patients with a recent (less than 1 month ischemic stroke. All patients were given either MLC601 (100 patients or placebo (50 patients, 4 capsules 3 times a day, as an add-on to standard stroke treatment for 3 months. Results. Sex, age, elapsed time from stroke onset, and risk factors in the treatment group were not significantly different from placebo group at baseline (P>.05. Repeated measures analysis showed that Fugl-Meyer assessment was significantly higher in the treatment group during 12 weeks after stroke (P<.001. Good tolerability to treatment was shown, and adverse events were mild and transient. Conclusion. MLC601 showed better motor recovery than placebo and was safe on top of standard ischemic stroke medications especially in the severe and moderate cases.

  12. Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma

    Directory of Open Access Journals (Sweden)

    Daniel Tusé

    2015-01-01

    Full Text Available We report the first evaluation of plant-made conjugate vaccines for targeted treatment of B-cell follicular lymphoma (FL in a Phase I safety and immunogenicity clinical study. Each recombinant personalized immunogen consisted of a tumor-derived, plant-produced idiotypic antibody (Ab hybrid comprising the hypervariable regions of the tumor-associated light and heavy Ab chains, genetically grafted onto a common human IgG1 scaffold. Each immunogen was produced in Nicotiana benthamiana plants using twin magnICON vectors expressing the light and heavy chains of the idiotypic Ab. Each purified Ab was chemically linked to the carrier protein keyhole limpet hemocyanin (KLH to form a conjugate vaccine. The vaccines were administered to FL patients over a series of ≥6 subcutaneous injections in conjunction with the adjuvant Leukine (GM-CSF. The 27 patients enrolled in the study had previously received non-anti-CD20 cytoreductive therapy followed by ≥4 months of immune recovery prior to first vaccination. Of 11 patients who became evaluable at study conclusion, 82% (9/11 displayed a vaccine-induced, idiotype-specific cellular and/or humoral immune response. No patients showed serious adverse events (SAE related to vaccination. The fully scalable plant-based manufacturing process yields safe and immunogenic personalized FL vaccines that can be produced within weeks of obtaining patient biopsies.

  13. Comparing the Efficacy and Safety of Ultrasonic Versus Pneumatic Lithotripsy in Percutaneous Nephrolithotomy: A Randomized Clinical Trial.

    Science.gov (United States)

    Radfar, Mohammad Hadi; Basiri, Abbas; Nouralizadeh, Akbar; Shemshaki, Hamidreza; Sarhangnejad, Reza; Kashi, Amir Hossein; Narouie, Behzad; Soltani, Amir Mohammad; Nasiri, Mahmoudreza; Sotoudeh, Mehdi

    2017-02-01

    Percutaneous nephrolitotomy (PCNL) is the preferred treatment for large renal stones. There is a need for more comparative data for different lithotripters used in PCNL. To evaluate the comparative safety and efficacy of ultrasonic and pneumatic lithotripsy in patients undergoing PCNL. This randomized clinical trial was conducted at Labbafinejad University Hospital, Tehran, Iran. A total of 180 patients were selected and divided randomly into two groups: 88 patients to pneumatic and 92 to ultrasonic lithotripsy. Standard fluoroscopy-guided PCNL was performed using pneumatic or ultrasonic lithotripsy. The primary outcome was the procedure success rate. We also evaluated other outcome measures including operation time, stone fragmentation and removal time (SFRT), length of hospital stay, and postoperative complications. We used SPSS software version 18.0 for data analysis. The two groups were similar in baseline characteristics. There were no significant differences between the groups in stone fragmentation and removal time (p=0.63), stone free rate (p=0.44), and hospital stay (p=0.66). SFRT for hard stones was shorter using pneumatic lithotripsy (ppneumatic and ultrasonic lithotripsy. SFRT was significantly shorter using pneumatic lithotripsy for hard stones, and ultrasonic lithotripsy for soft stones. We found no significant differences in the success rate and complications of percutaneous nephrolitotomy using pneumatic and ultrasonic lithotripsy. Ultrasonic and pneumatic lithotripsy differed in the time for stone fragmentation and removal for hard and soft stones. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  14. Is the large simple trial design used for comparative, post-approval safety research? A review of a clinical trials registry and the published literature.

    Science.gov (United States)

    Reynolds, Robert F; Lem, Joanna A; Gatto, Nicolle M; Eng, Sybil M

    2011-10-01

    Post-approval, observational drug safety studies face well known difficulties in controlling for confounding, particularly confounding by indication for drug use. A study design that addresses confounding by indication is the large simple trial (LST). LSTs are characterized by large sample sizes, often in the thousands; broad entry criteria consistent with the approved medication label; randomization based on equipoise, i.e. neither physician nor patient believes that one treatment option is superior; minimal, streamlined data collection requirements; objectively-measured endpoints (e.g. death, hospitalization); and follow-up that minimizes interventions or interference with normal clinical practice. In theory then, the LST is a preferred study design for drug and vaccine safety research because it controls for biases inherent to observational research while still providing results that are generalizable to 'real-world' use. To evaluate whether LSTs are used for comparative safety evaluation and if the design is, in fact, advantageous compared with other designs, we conducted a review of the published literature (1949 through 31 December 2010) and the ClinicalTrials.gov registry (2000 through 31 December 2010). Thirteen ongoing or completed safety LSTs were identified. The design has rarely been used in comparative drug safety research, which is due to the operational, financial and scientific hurdles of implementing the design. The studies that have been completed addressed important clinical questions and, in some cases, led to re-evaluation of medical practice. We conclude the design has demonstrated utility for comparative safety research of medicines and vaccines if the necessary scientific and operational conditions for its use are met.

  15. IRQN award paper: Operational rounds: a practical administrative process to improve safety and clinical services in radiology.

    Science.gov (United States)

    Donnelly, Lane F; Dickerson, Julie M; Lehkamp, Todd W; Gessner, Kevin E; Moskovitz, Jay; Hutchinson, Sally

    2008-11-01

    As part of a patient safety program in the authors' department of radiology, operational rounds have been instituted. This process consists of radiology leaders' visiting imaging divisions at the site of imaging and discussing frontline employees' concerns about patient safety, the quality of care, and patient and family satisfaction. Operational rounds are executed at a time to optimize the number of attendees. Minutes that describe the issues identified, persons responsible for improvement, and updated improvement plan status are available to employees online. Via this process, multiple patient safety and other issues have been identified and remedied. The authors believe that the process has improved patient safety, the quality of care, and the efficiency of operations. Since the inception of the safety program, the mean number of days between serious safety events involving radiology has doubled. The authors review the background around such walk rounds, describe their particular program, and give multiple illustrative examples of issues identified and improvement plans put in place.

  16. A pilot study to evaluate the safety and clinical performance of Leucopatch, an autologous, additive-free, platelet-rich fibrin for the treatment of recalcitrant chronic wounds

    DEFF Research Database (Denmark)

    Jørgensen, Bo; Karlsmark, Tonny; Vogensen, Hanne;

    2011-01-01

    This prospective, uncontrolled pilot study evaluated the safety and clinical performance of Leucopatch an additive-free, autologous platelet-rich fibrin in the treatment of recalcitrant chronic wounds. Fifteen patients, with 16 lower extremity chronic wounds of varying etiologies were treated...... events. Two adverse events, one of noncompliance and one infection, were observed; neither was considered to be related to treatment. The results indicate that Leucopatch is easy to prepare and apply in the clinic, is safe, and may be a clinically effective treatment of recalcitrant chronic wounds....

  17. 临床用药护理安全管理的做法与效果%practice and effects of drug safety management in clinical nursing

    Institute of Scientific and Technical Information of China (English)

    雷泽秋; 何方; 周宁

    2012-01-01

    Objective To discuss the practice and effects of drug safety management in clinical nursing. Methods The management measures included setting up a drug safety management group,finding out clinical drug safety problems,designing and making drug administration cards,standardizing the use of various types of drug labels,perfecting the nursing work system and establishing continuous training system of clinical safe nursing medication. Results Hie incidence of medication errors and defects declined, and the incidence of drug overtime declined, the differences were statistically significant (P < 0.01 or P <0.05 ). Conclusion The implementation of drug safety management can ensure the safety of drugs for clinical nursing.%目的 探讨临床用药护理安全管理的做法与效果.方法 成立临床用药护理安全管理小组;查找临床护理用药安全隐患;设计并制作专门的药品管理卡;规范各类药品标识的使用;完善护理工作制度;建立临床用药护理安全持续培训制度.结果 用药差错及缺陷发生率、药物过期发生率均下降,差异具有统计学意义(P<0.01或P<0.05).结论 实施临床用药护理安全管理可以使临床用药护理安全得到有效保障.

  18. Long-term safety of icatibant treatment of patients with angioedema in real-world clinical practice

    DEFF Research Database (Denmark)

    Zanichelli, A; Maurer, M; Aberer, W

    2017-01-01

    The Icatibant Outcome Survey (IOS) is an observational study monitoring safety and effectiveness of icatibant in the real-world setting. We analyzed safety data from 3025 icatibant-treated attacks in 557 patients (enrolled between July 2009 and February 2015). Icatibant was generally well tolerat...

  19. The safety and clinical outcomes of chemoembolization in child-pugh class C patients with hepatocellular carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Tae Won; Kim, Hyo Cheol; Lee, Jeong Hoon; Yu, Su Jong; Kang, Beom Sik; Hur, Sae Beom; Lee, Myung Su; Jae, Hwan Jun; Chung, Jin Wook [Seoul National University College of Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-12-15

    To evaluate the safety and clinical outcomes of chemoembolization in Child-Pugh class C patients with hepatocellular carcinomas (HCC). The study comprised 55 patients with HCC who were classified as Child-Pugh class C and who underwent initial chemoembolization between January 2003 and December 2012. Selective chemoembolization was performed in all technically feasible cases to minimize procedure-related complications. All adverse events within 30 days were recorded using the Common Terminology Criteria for Adverse Events (CTCAE). The tumor response to chemoembolization was evaluated using the modified Response Evaluation Criteria In Solid Tumors. Thirty (54.5%) patients were within the Milan criteria, and 25 (45.5%) were beyond. The mortality of study subjects at 30 days was 5.5%. Major complications were observed in five (9.1%) patients who were all beyond the Milan criteria: two hepatic failures, one hepatic encephalopathy, and two CTCAE grade 3 increases in aspartate aminotransferase/alanine aminotransferase abnormality. The mean length of hospitalization was 6.3 ± 8.3 days (standard deviation), and 18 (32.7%) patients were discharged on the next day after chemoembolization. The tumor responses of the patients who met the Milan criteria were significantly higher (p = 0.014) than those of the patients who did not. The overall median survival was 7.1 months (95% confidence interval: 4.4-9.8 months). Even in patients with Child-Pugh class C, chemoembolization can be performed safely with a selective technique in selected cases with a small tumor burden.

  20. Infant safety during and after maternal valacyclovir therapy in conjunction with antiretroviral HIV-1 prophylaxis in a randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Alison L Drake

    Full Text Available BACKGROUND: Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs for prevention of mother-to-child HIV-1 transmission (PMTCT has not been described. METHODS: Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm(3 were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62% specimens. Fisher's Exact and Wilcoxon rank-sum tests were used for analysis. RESULTS: One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl and median creatinine (median 0.50 mg/dl and infant growth did not differ between study arms. Acyclovir was detected in 35 (80% of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6-4.19. CONCLUSIONS: Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00530777.

  1. Technical challenges in designing post-marketing eCRFs to address clinical safety and pharmacovigilance needs.

    Science.gov (United States)

    Lu, Zhengwu

    2010-01-01

    To identify key challenges and propose technical considerations in designing electronic case report form (eCRF) for post-marketing studies, the author undertakes a comprehensive literature review of peer reviewed and grey literature to assess the key aspects, processes, standards, recommendations, and best practices in designing eCRFs based on industry experience in designing and supporting electronic data capture (EDC) studies. Literature search using strings on MEDLINE and PUBMED returned few papers directly related to CRF design. Health informatics and general practice journals were searched and results reviewed. Many conference, government commission, health professional and special interests group websites provide relevant information from practical experience - summarization of this information is presented. Further, we presented a list of concrete technical considerations in dealing with EDC technology/system limitations based on literature assessment and industry implementation experience. It is recognized that cross-functional teams be involved in eCRF design process and decision making. To summarize the keys in designing eCRFs to address post-market study safety and pharmacovigilance needs, the first is to identify required data elements from the study protocol supporting data analyses and reporting requirements. Secondly, accepted best practices, CDASH & CDISC guidelines, and company internal or therapeutic unit standard should be considered and applied. Coding (MedDRA & WHODD) mapping should be managed and implemented as well when possible. Finally, we need to be on top of the EDC technologies, challenge the technologies, drive EDC improvement via working with vendors, and utilize the technologies to drive clinical effectiveness. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  2. Endovascular stroke treatment now and then-procedural and clinical effectiveness and safety of different mechanical thrombectomy techniques over time.

    Science.gov (United States)

    von Gadow, Niels; Nikoubashman, Omid; Freiherr, Jessica; Block, Frank; Reich, Arno; Fesl, Gunther; Wiesmann, Martin

    2017-02-01

    The most essential development in endovascular stroke treatment (EST) was the shift from intra-arterial thrombolysis to endovascular thrombectomy with dedicated thrombectomy devices, most notably the introduction of stent-retrievers. We evaluated procedural and clinical effectiveness and safety of different EST techniques over time. We retrospectively analyzed EST cases that were treated by the same interventionalist before (n=36) and after (n=50) stent-retrievers were established as the treatment device of first choice. EST techniques in the first cohort comprised intra-arterial thrombolysis (n=24), manual thrombus aspiration (n=15), the use of the Penumbra thrombectomy system (n=13) and the Phenox clot retriever (n=3), intracranial stenting (n=10), and EST with stent-retrievers as a salvage procedure (n=11). In the second cohort, EST with stent-retrievers was the treatment option of first choice (n=47). Intra-arterial thrombolysis (n=15) and stenting of the occluded vessel (n=1) were performed, whenever EST with stent-retrievers failed. In both cohorts, revascularization rates (TICI ≥2b) were high (91.7% and 86.0%, respectively). A significantly lower number of interventional techniques per case were required in the second cohort (mean ± SD, 1.4±0.5 vs. 2.1±0.9, P<0.001). Recanalization was achieved almost twice as fast in the second cohort (85 vs. 163 minutes on average, P<0.001). The rate of patients achieving good functional outcome (mRS ≤2) was higher in the second cohort (40.0% vs. 22.2%, P=0.083). Our findings imply that when stent-retrievers were established as first-line the treatment device a significantly lower number of interventional techniques per case were required and recanalization was achieved almost twice as fast.

  3. Effectiveness and safety of endotracheal tube cuffs filled with air versus filled with alkalinized lidocaine: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Lais Helena Camacho Navarro

    Full Text Available CONTEXT AND OBJECTIVE: High intracuff pressure in endotracheal tubes (ETs may cause tracheal lesions. The aim of this study was to evaluate the effectiveness and safety of endotracheal tube cuffs filled with air or with alkalinized lidocaine. DESIGN AND SETTING: This was a prospective clinical study at the Department of Anesthesiology, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista. METHODS: Among 50 patients, ET cuff pressures were recorded before, 30, 60, 90 and 120 minutes after starting and upon ending nitrous oxide anesthesia. The patients were randomly allocated to two groups: Air, with ET cuff inflated with air to attain a cuff pressure of 20 cmH2O; and Lido, with ET cuff filled with 2% lidocaine plus 8.4% sodium bicarbonate to attain the same pressure. ET discomfort before tracheal extubation, and sore throat, hoarseness and coughing incidence were studied at the time of discharge from the post-anesthesia care unit, and sore throat and hoarseness were studied 24 hours after anesthesia. RESULTS: Pressures in Lido cuffs were significantly lower than in Air cuffs (p < 0.05. Tracheal complaints were similar for the two groups, except for lower ET discomfort and sore throat incidence after 24 hours and lower systolic arterial pressure at the time of extubation in the Lido group (p < 0.05. CONCLUSION: ET cuffs filled with alkalinized lidocaine prevented the occurrence of high cuff pressures during N2O anesthesia and reduced ET discomfort and postoperative sore throat incidence. Thus, alkalinized lidocaine-filled ET cuffs seem to be safer than conventional air-filled ET cuffs.

  4. Clinical efficacy and safety of recruitment maneuver in patients with acute respiratory distress syndrome using low tidal volume ventilation: a multicenter randomized controlled clinical trial

    Institute of Scientific and Technical Information of China (English)

    XI Xiu-ming; JIANG Li; ZHU Bo; the RM group

    2010-01-01

    Background The recruitment maneuver (RM) has been shown to improve oxygenation in some patients with acute respiratory distress syndrome. But there is a lack of standardization and lack of clinical studies to prove the improvement on clinical outcome. We conducted this study to evaluate the clinical efficacy and safety of the RM in patients with acute respiratory distress syndrome (ARDS) using Iow tidal volume ventilation.Methods We randomly assigned 110 patients with ARDS from 14 Chinese intensive care units (ICUs) at the tertiary teaching hospitals. Patients with PaO2 ≤200 mmHg at FiO2 1.0 and PEEP ≥10 cmH2O were included in the study.Patients were randomized into two groups: control group and RM group. The tidal volume was set to 6-8 mi per kilogram of predicted body weight (PBW) in both groups. RM was performed by continuous positive airway pressure (CPAP) of 40 cmH2O maintained for 40 seconds. RMs was conducted every eight hours for the first five days, or stopped within five days if the patient reached the weaning standard.Results One hundred and ten patients had completed the requirements for the primary study goals, 55 from the RM group and 55 control patients. Baseline characteristics remained similar in the two groups. In the RM group the PaO2/FiO2 was significantly increased compared to baseline at 120 minutes after RM on day one and day two (P=0.007and P=0.001). There were no significant differences between the RM and control group in hospital mortality (41.8% vs.56.4%, P=0.13), 28-day mortality (29.1% vs. 43.6%, P=0.11) and ventilator-free days at day 28 (10.8±10.1 vs. 7.4±10.0,P=0.08). ICU mortality (32.7% vs. 52.7%, P=0.03), the rate of survival with unassisted breathing for at least 48 consecutive hours at day 28 (58.2% vs. 36.2%, P=0.02), and nonpulmonary organ failure-free days at day 28 (17.4±11.1vs. 13.0±12.0, P=0.03) favored the RM group. There was no significant difference in mean blood pressure and heart rate before RM and at 30, 60

  5. Schistosomiasis vaccine candidate Sm14/GLA-SE: Phase 1 safety and immunogenicity clinical trial in healthy, male adults.

    Science.gov (United States)

    Santini-Oliveira, Marilia; Coler, Rhea N; Parra, Juçara; Veloso, Valdilea; Jayashankar, Lakshmi; Pinto, Patricia M; Ciol, Marcia A; Bergquist, Robert; Reed, Steven G; Tendler, Miriam

    2016-01-20

    Safety and immunogenicity of a recombinant 14kDa, fatty acid-binding protein(FABP) from Schistosoma mansoni (rSm14) were evaluated through an open, non-placebo-controlled, dose-standardized trial, performed at a single research site. The vaccine was formulated with glucopyranosyl lipid A (GLA) adjuvant in an oil-in-water emulsion (SE) and investigated in 20 male volunteers from a non-endemic area for schistosomiasis in the state of Rio de Janeiro, Brazil. Fifty microgram rSm14 with 10 μg GLA-SE (rSm14/GLA-SE)/dose were given intramuscularly three times with 30-day intervals. Participants were assessed clinically, biochemically and immunologically for up to 120 days. Participants were screened for inclusion by physical examination, haematology and blood chemistry; then followed to assess adverse events and immunogenicity. Sera were tested for IgG (total and isotypes) and IgE. T cell induction of cytokines IL-2, IL-5, IL-10, IFNγ and TNFα was assessed by Milliplex kit and flow cytometry. The investigational product showed high tolerability; some self-limited, mild adverse events were observed during and after vaccine administration. Significant increases in Sm14-specific total IgG, IgG1 and IgG3 were observed 30 days after the first vaccination with specific IgG2 and IgG4 after 60 days. An increase in IgE antibodies was not observed at any time point. The IgG response was augmented after the second dose and 88% of all vaccinated subjects had developed high anti-Sm14 IgG titres 90 days after the first injection. From day 60 and onwards, there was an increase in CD4(+) T cells producing single cytokines, particularly TNFα and IL-2, with no significant increase of multi-functional TH1 cells. Clinical trial data on tolerability and specific immune responses after vaccination of adult, male volunteers in a non-endemic area for schistosomiasis with rSm14/GLA-SE, support this product as a safe, strongly immunogenic vaccine against schistosomiasis paving the way for

  6. Efficacy and safety of N-acetylcysteine in prevention of noise induced hearing loss: a randomized clinical trial.

    Science.gov (United States)

    Kopke, Richard; Slade, Martin D; Jackson, Ronald; Hammill, Tanisha; Fausti, Stephen; Lonsbury-Martin, Brenda; Sanderson, Alicia; Dreisbach, Laura; Rabinowitz, Peter; Torre, Peter; Balough, Ben

    2015-05-01

    Despite a robust hearing conservation program, military personnel continue to be at high risk for noise induced hearing loss (NIHL). For more than a decade, a number of laboratories have investigated the use of antioxidants as a safe and effective adjunct to hearing conservation programs. Of the antioxidants that have been investigated, N-acetylcysteine (NAC) has consistently reduced permanent NIHL in the laboratory, but its clinical efficacy is still controversial. This study provides a prospective, randomized, double-blinded, placebo-controlled clinical trial investigating the safety profile and the efficacy of NAC to prevent hearing loss in a military population after weapons training. Of the 566 total study subjects, 277 received NAC while 289 were given placebo. The null hypothesis for the rate of STS was not rejected based on the measured results. While no significant differences were found for the primary outcome, rate of threshold shifts, the right ear threshold shift rate difference did approach significance (p = 0.0562). No significant difference was found in the second primary outcome, percentage of subjects experiencing an adverse event between placebo and NAC groups (26.7% and 27.4%, respectively, p = 0.4465). Results for the secondary outcome, STS rate in the trigger hand ear, did show a significant difference (34.98% for placebo-treated, 27.14% for NAC-treated, p-value = 0.0288). Additionally, post-hoc analysis showed significant differences in threshold shift rates when handedness was taken into account. While the secondary outcomes and post-hoc analysis suggest that NAC treatment is superior to the placebo, the present study design failed to confirm this. The lack of significant differences in overall hearing loss between the treatment and placebo groups may be due to a number of factors, including suboptimal dosing, premature post-exposure audiograms, or differences in risk between ears or subjects. Based on secondary outcomes and post hoc

  7. Efficacy and Safety of Single Dose Zoledronic Acid for Osteoporosis in Frail Seniors: A Randomized Clinical Trial

    Science.gov (United States)

    Greenspan, Susan L.; Perera, Subashan; Ferchak, Mary Anne; Nace, David A.; Resnick, Neil M.

    2016-01-01

    Importance 85% of institutionalized elderly have osteoporosis, with fracture rates 8–9 fold higher than observed among community-dwelling elderly. Yet most are untreated and excluded from pivotal osteoporosis trials. Objective Determine the efficacy and safety of zoledronic acid in frail elderly women. Design 2-year, randomized, placebo-controlled, double-blinded study conducted between December 2007 and March 2012. Setting Nursing home and assisted living facilities. Participants 181 women ≥ age 65 with osteoporosis including those with cognitive impairment, immobility, and multimorbidity. Intervention One 5 mg dose of zoledronic acid or placebo IV and daily calcium and vitamin D. Main Outcomes (1) Hip and spine bone mineral density (BMD) at 12 and 24 months and (2) adverse events. Results There were no baseline differences in age (mean=85.4±0.6 years), BMD, or functional or cognitive status, but the treatment group included more subjects with frailty, falls history, diabetes, and anticonvulsant use. BMD was available for 87% of participants at 12 months and 73% at 24 months. BMD changes were greater in the treatment group (p< 0.01): 3.2 ± 0.7 and 3.9 ± 0.7 percentage point differences (mean ± SE) in the total hip at 12 and 24 months respectively, and 1.8 ± 0.7 and 3.6 ± 0.7 at the spine (p<0.01); adjusted analyses were similar. The treatment and placebo groups’ fracture rates were 20% and 16%, respectively (OR=1.30; 95% CI=0.61–2.78); mortality rates were 16% and 13% (OR=1.24; 95% CI=0.54–2.86). Groups did not differ in the proportion of single fallers (28% vs. 24%; OR=1.24; 95% CI=0.64–2.42; p=0.52) but more subjects in the treatment group had multiple falls (49% vs. 35%; OR=1.83; 95% CI=1.01–3.33; p=0.047); this was no longer significant when adjusted for baseline frailty. Conclusions and Relevance In this group of frail, osteoporotic women, one dose of zoledronic acid improved BMD over 2 years. The clinical importance of nonsignificant

  8. Comparison of clinical efficacy and safety between indacaterol and tiotropium in COPD: meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Jung Soo Kim

    Full Text Available Two once-daily inhaled bronchodilators, indacaterol and tiotropium, are widely used as first-line therapy in stable COPD patients. This study was performed to compare the clinical efficacy and safety between indacaterol and tiotropium in patients with moderate-to-severe COPD. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched to identify all published randomized controlled trials (RCTs. The primary outcome was trough forced expiratory volume in 1 second (FEV1 at week 12. Four RCTs were eligible for inclusion (three RCTs with moderate-to-severe COPD patients and one RCT with only severe COPD patients. Trough FEV₁ at weeks 12 and 26 were not significantly different between indacaterol and tiotropium by the standardized mean difference with 0.014 (95% CI, -0.036, 0.063, I²= 23.5% and with 0.037 (95% CI, -0.059 to 0.133, I²= 0% along with differences in means of 0.003L and 0.014L, respectively. Indacaterol and tiotropium also showed similar St. George's Respiratory Questionnaire (SGRQ total scores and percentages of patients with SGRQ improvement (≥ 4 units at week 26. The incidences of nasopharyngitis, serious cardiovascular events, and serious adverse events were not different between indacaterol and tiotropium, while those of cough (OR = 1.68, P < 0.001, and RR = 1.63 and COPD worsening (OR = 1.18, P = 0.003, and RR = 1.12 were higher for indacaterol than tiotropium. However, when one study with only severe COPD patients was removed from the meta-analysis, the difference in the incidence of COPD worsening between indacaterol and tiotropium became non-significant (OR = 1.13, P = 0.204, and RR = 1.09. The clinical efficacy and serious adverse events between indacaterol and tiotropium were equivocal in patients with moderate-to-severe COPD. Cough is a common complaint associated with indacaterol, and COPD worsening needs to be carefully monitored in severe COPD patients when treated with indacaterol.

  9. Observation the clinical effect of safety infusion sets.%分隔输液器临床应用效果观察

    Institute of Scientific and Technical Information of China (English)

    胡靖青; 沈晓霞

    2012-01-01

    Objective: To research the safety infusion sets's application and effect in clinical transfusion. Methods:To compare the working process and the time of traditional infusion sets and Safety infusion sets in clinical transfusion . Results: According to the survey, Security separated infusion sets simplify the steps of the traditional infusion. Two kinds of infusion time for comparison, the safety infusion sets can shorten the time obviously. The results of this research have statistical significance,P<0. 05. Conclusion:Compared with the traditional infusion sets, safe infusion sets have more advantages, can save time and reduce human resources costs visibly, and improve safety and efficiency of care.%目的:探讨分隔输液器在临床输液中的应用与效果.方法:对传统输液器与分隔输液器的工作过程和时间进行对比.结果:分隔输液器简化了传统输液器操作步骤,明显缩短了输液时间(P<0.05),两者比较具有统计学意义.结论:相对于传统输液器,分隔式输液器能显著节约时间,提高护理的安全性和效率.

  10. Paediatric pharmacovigilance: use of pharmacovigilance data mining algorithms for signal detection in a safety dataset of a paediatric clinical study conducted in seven African countries.

    Directory of Open Access Journals (Sweden)

    Dan K Kajungu

    Full Text Available BACKGROUND: Pharmacovigilance programmes monitor and help ensuring the safe use of medicines which is critical to the success of public health programmes. The commonest method used for discovering previously unknown safety risks is spontaneous notifications. In this study we examine the use of data mining algorithms to identify signals from adverse events reported in a phase IIIb/IV clinical trial evaluating the efficacy and safety of several Artemisinin-based combination therapies (ACTs for treatment of uncomplicated malaria in African children. METHODS: We used paediatric safety data from a multi-site, multi-country clinical study conducted in seven African countries (Burkina Faso, Gabon, Nigeria, Rwanda, Uganda, Zambia, and Mozambique. Each site compared three out of four ACTs, namely amodiaquine-artesunate (ASAQ, dihydroartemisinin-piperaquine (DHAPQ, artemether-lumefantrine (AL or chlorproguanil/dapsone and artesunate (CD+A. We examine two pharmacovigilance signal detection methods, namely proportional reporting ratio and Bayesian Confidence Propagation Neural Network on the clinical safety dataset. RESULTS: Among the 4,116 children (6-59 months old enrolled and followed up for 28 days post treatment, a total of 6,238 adverse events were reported resulting into 346 drug-event combinations. Nine signals were generated both by proportional reporting ratio and Bayesian Confidence Propagation Neural Network. A review of the manufacturer package leaflets, an online Multi-Drug Symptom/Interaction Checker (DoubleCheckMD and further by therapeutic area experts reduced the number of signals to five. The ranking of some drug-adverse reaction pairs on the basis of their signal index differed between the two methods. CONCLUSIONS: Our two data mining methods were equally able to generate suspected signals using the pooled safety data from a phase IIIb/IV clinical trial. This analysis demonstrated the possibility of utilising clinical studies safety data

  11. Enhancing quality and safety competency development at the unit level: an initial evaluation of student learning and clinical teaching on dedicated education units.

    Science.gov (United States)

    Mulready-Shick, Joann; Kafel, Kathleen W; Banister, Gaurdia; Mylott, Laura

    2009-12-01

    The need to attend to quality and safety competency development, increase capacity in nursing education programs, address the faculty and nursing shortages, and find new ways to keep step with an ever-changing health care environment has brought forth numerous creative curricular responses and collaborative efforts. To tackle these multiple needs and challenges simultaneously, a new academic-service partnership was created to collaboratively develop an innovative clinical education delivery model. The designed dedicated education unit model not only promoted student learning about quality and safety competencies via unit-based projects but also supported quality improvements in nursing care delivery. Following the initial semester of the model's implementation, a pilot study was conducted. The findings generated the evidence required to take this innovation to the next level. Moreover, the education-practice partnership, which was created to implement the clinical education delivery model, was strengthened as a result of this preliminary evaluation.

  12. [Initial Evaluation of the Efficacy and Safety of Tablets Containing Trifluridine and Tipiracil Hydrochloride--Safety Measures Devised by a Multidisciplinary Team Including a Pharmaceutical Outpatient Clinic].

    Science.gov (United States)

    Aimono, Yuka; Kamoshida, Toshiro; Sakamoto, Risa; Nemoto, Masahiko; Saito, Yoshiko; Aoyama, Yoshifumi; Maruyama, Tsunehiko

    2015-07-01

    In May 2014, tablets containing both trifluridine and tipiracil hydrochloride (Lonsurf® tablets) were launched in Japan ahead of other countries, for the treatment of advanced/relapsed unresectable colorectal cancer. The benefits of these tablets in terms of a new therapeutic option have been demonstrated. However, the manufacturer has requested healthcare professionals to help develop safety measures for the appropriate and safe use of the tablets. In this study, we evaluated the efficacy and safety of the tablets in 16 patients who received the tablets at our hospital. Among the 4 evaluable patients, none achieved a complete or partial response. One patient (25.0%) had stable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines outlined in the General Rules of the Study of Colorectal Cancer (The 8th Edition). Lonsurf® is considered to be a third-line (or later) treatment. Among the 16 cases studied, Lonsurf® was used as a third-, fourth-, and fifth-line treatment in 9, 6, and 1 cases, respectively. Therefore, Grade 3 or worse toxicities were a potential concern. Despite a high incidence of Grade 3 or worse neutropenia (7 of the 16 patients [43.8%]), none of the patients were hospitalized due to neutropenia or other treatment-related adverse events. Pharmacists have made 126 proposals to physicians regarding the use of Lonsurf®, 121 (96.0%) of which have been adopted. All of the adverse reactions experienced by our patients were resolved after supportive therapy.

  13. Safety and Efficacy of Cerebrolysin in Infants with Communication Defects due to Severe Perinatal Brain Insult: A Randomized Controlled Clinical Trial

    OpenAIRE

    Hassanein, Sahar M.A.; Deifalla, Shaymaa M.; El-Houssinie, Moustafa; Mokbel, Somaia A.

    2015-01-01

    Background and Purpose The neuroregenerative drug Cerebrolysin has demonstrated efficacy in improving cognition in adults with stroke and Alzheimer's disease. The aim of this study was to determine the efficacy and safety of Cerebrolysin in the treatment of communication defects in infants with severe perinatal brain insult. Methods A randomized placebo-controlled clinical trial was conducted in which 158 infants (age 6-21 months) with communication defects due to severe perinatal brain insul...

  14. [Clinical safety studies based on 30 026 post-marketing cases of Shenqi Fuzheng injection by intensive hospital monitoring nested NCCS].

    Science.gov (United States)

    Wang, Lian-xin; Xie, Yan-ming; Ai, Qing-hua; Xu, Wen-fu

    2015-12-01

    This study adopted a large sample, multicenter, registered hospital centralized monitoring nested prospective case-control study design. From the real world clinical application of Shenqi Fuzheng injection, monitored 30 026 cases of patients with the use of Shenqi Fuzheng injection. A total of 51 adverse drug reaction (ADR) cases was monitored, including 1 case of severe adverse reactions. ADR incidence rate was 1.7 per 1,000. Blood samples were collected from patients with allergic reactions and their matched controls. Related biological indicators of allergic reactions were unified detected and analysed in order to explore the mechanism of allergic reaction and promote the clinical safety.

  15. Comparison of the effectiveness and safety of cefpodoxime and ciprofloxacin in acute exacerbation of chronic suppurative otitis media: A randomized, open-labeled, phase IV clinical trial

    Directory of Open Access Journals (Sweden)

    Arijit Ghosh

    2012-01-01

    Full Text Available Objective : To compare the effectiveness and safety of cefpodoxime and ciprofloxacin for the treatment of mild to moderate cases of acute exacerbation of chronic suppurative otitis media (AECSOM. Materials and Methods : Adult patients diagnosed with AECSOM were screened and patients fulfilling the inclusion criteria were randomized to receive either cefpodoxime 200 mg twice daily or ciprofloxacin 500 mg twice daily orally for 7 days. The primary outcome of this randomized, open-labeled, phase IV clinical trial (Registration Number - CTRI/2011/10/002079 was clinical success rate at day 14 visit and the secondary outcome was incidence of adverse events (AEs. Forty-six patients were enrolled: 23 in the cefpodoxime group and 23 in the ciprofloxacin group. Results : The clinical success rates were 95.6% in the cefpodoxime group versus 90.9% in the ciprofloxacin group. These rates are comparable, but no statistically significant difference was observed between the groups. Few mild and self-limiting AEs were observed and the tolerability of both the drugs was also good. Conclusion : The results of this randomized, open-labeled phase IV clinical trial showed that a 7-day course of cefpodoxime is therapeutically comparable to ciprofloxacin in terms of both clinical effectiveness and safety for the treatment of patients with AECSOM.

  16. Clinical efficacy and safety of autologous stem cell transplantation for patients with ST-segment elevation myocardial infarction

    Directory of Open Access Journals (Sweden)

    Li R

    2016-08-01

    Full Text Available Rong Li,1,* Xiao-Ming Li,2,* Jun-Rong Chen,3 1Department of Intensive Care Unit, The People’s Hospital of Baoji City, 2Department of Cardiovascular Medicine, 3Department of Function, Baoji Central Hospital, Baoji, Shaanxi, People’s Republic of China *These authors contributed equally to this work Purpose: The purpose of this study is to evaluate the therapeutic efficacy and safety of stem cells for the treatment of patients with ST-segment elevation myocardial infarction (STEMI.Materials and methods: We performed a systematic review and meta-analysis of relevant published clinical studies. A computerized search was conducted for randomized controlled trials of stem cell therapy for STEMI.Results: Twenty-eight randomized controlled trials with a total of 1,938 STEMI patients were included in the present meta-analysis. Stem cell therapy resulted in an improvement in long-term (12 months left ventricular ejection fraction of 3.15% (95% confidence interval 1.01–5.29, P<0.01. The 3-month to 4-month, 6-month, and 12-month left ventricular end-systolic volume showed favorable results in the stem cell therapy group compared with the control group (P≤0.05. Significant decrease was also observed in left ventricular end-diastolic volume after 3-month to 4-month and 12-month follow-up compared with controls (P<0.05. Wall mean score index was reduced significantly in stem cell therapy group when compared with the control group at 6-month and 12-month follow-up (P=0.01. Moreover, our analysis showed a significant change of 12-month infarct size decrease in STEMI patients treated with stem cells compared with controls (P<0.01. In addition, no significant difference was found between treatment group and control in adverse reactions (P>0.05.Conclusion: Overall, stem cell therapy is efficacious in the treatment of patients with STEMI, with low rates of adverse events compared with control group patients. Keywords: ST-segment elevation myocardial

  17. Safety and usefulness of Laghu shankha prakshalana in patients with essential hypertension: A self controlled clinical study

    Directory of Open Access Journals (Sweden)

    Prakash Mashyal

    2014-01-01

    Full Text Available Background: Yoga and Ayurveda texts emphasize the role of cleansing the bowel as an important component of management of hypertension (HTN. Observations during our clinical experience and pilot studies on Laghu shankha prakshalana kriya (LSP, a yogic bowel cleansing technique, appeared to be safe and complimentary. Objective: To test the safety and effectiveness of LSP in patients with essential hypertension. Materials and Methods: This self control study recruited 32 patients with mild to moderate essential HTN admitted for a week long residential integrated yoga therapy program at the integrative health home in Bengaluru. Patients had a daily routine of 6 hours of integrated approach of yoga therapy (IAYT module for HTN that included physical postures, relaxation sessions, pranayama and meditations. LSP, an additional practice, that involved drinking of luke-warm water (with or without a herbal combination, triphala followed by a set of specific yoga postures that activates defecation reflex, was administered on 2 nd (LSP without triphala and 5 th day (LSP with triphala. Assessments (sitting blood pressure and pulse rate were done just before and after both the sessions of LSP. Secondary outcome measures such as body mass index (BMI, symptom scores, medication scores, fatigue, state and trait anxiety, general health and quality of life were assessed on 1 st and 6 th day of IAYT intervention. Results: There was significant (P < 0.001, paired t test reduction in blood pressure (systolic and diastolic and pulse rate immediately after both the sessions (LSP with and without triphala. There were no adverse effects reported during or after LSP. There was no significant difference between the two techniques (P < 0.505, independent samples t test, although the percentage change appeared to be higher after triphala LSP session. The number of visits to clear the bowel during the procedure was significantly (P < 0.001, independent samples t test higher

  18. Patients’ safety: is there a systemic release of gentamicin by gentamicin-coated tibia nails in clinical use?

    Directory of Open Access Journals (Sweden)

    Moghaddam A

    2016-09-01

    Full Text Available Arash Moghaddam,1 Viola Graeser,1 Fabian Westhauser,1 Ulrike Dapunt,1 Till Kamradt,1 Stefan M Woerner,2 Gerhard Schmidmaier1 1HTRG – Heidelberg Traume Research Group Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany; 2Department of Internal Medicine and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany Introduction: Osteitis is one of the most serious complications in orthopedic surgery. Expert Tibia Nail (ETN PROtect™ coated with a biodegradable layer of gentamicin-laden polymer was developed for prophylaxis of osteomyelitis. In systemic administration, gentamicin has only a small therapeutic index and serious side effects; it is potentially nephrotoxic as well as ototoxic. It is not yet known if relevant gentamicin concentrations are released into the systemic circulation after implantation of gentamicin-coated nails. In order to evaluate the patients’ risks profiles and increase patient safety, we measured gentamicin levels in pre- and postoperative serum samples of patients undergoing implantation of ETN PROtect.Methods: Twenty-five patients who received ETN PROtect between March 2012 and August 2014 were included in this study. Collection of blood samples occurred before the operation, at weeks 1–4, 3 and 6 months, and up to 1 year after the implantation. Measurement of gentamicin levels in serum samples was performed at the central laboratory of Heidelberg University Hospital. Additionally, laboratory parameters, C-reactive protein, leukocyte number, urea and creatinine concentrations were analyzed in routine controls before and after operating and assessed for systemic side effects.Results: Over the course of this prospective observational study, we were able to determine that gentamicin-coated nails do not release gentamicin into the systemic circulation above the lowest detectable level of 0.2 mg/dL. There were slight increases in the mean

  19. Efficacy and Safety of Ciprofloxacin Plus Fluocinolone in Otitis Media With Tympanostomy Tubes in Pediatric Patients: A Randomized Clinical Trial.

    Science.gov (United States)

    Spektor, Zorik; Pumarola, Felix; Ismail, Khaleed; Lanier, Brent; Hussain, Iftikhar; Ansley, John; Butehorn, Henry F; Esterhuizen, Kenneth; Byers, John; Douglis, Franklin; Lansford, Bryan; Hernández, F Javier

    2017-04-01

    Acute otitis media with tympanostomy tubes (AOMT) in children commonly presents with otorrhea and negatively affects their daily activities. To evaluate the efficacy and safety of topical ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution relative to ciprofloxacin, 0.3%, otic solution alone and fluocinolone acetonide, 0.025%, otic solution alone in the treatment of AOMT in children. Two twin multicenter, randomized, double-blind clinical trials with identical designs were conducted from June 24, 2011, through June 23, 2014, at ear, nose, and throat pediatric practices, general practices, hospitals, and clinical research centers. The study population comprised 662 children (331 in each trial) with AOMT in at least 1 ear who presented with moderate or severe purulent otorrhea for 3 weeks or less. Data analyses were performed on an intention-to-treat basis. Patients were randomly assigned to receive ciprofloxacin plus fluocinolone, ciprofloxacin alone, or fluocinolone alone twice daily for 7 days and were evaluated on days 1 (baseline), 3 to 5 (undergoing therapy), 8 to 10 (end of therapy), and 18 to 22 (test of cure). The primary efficacy measure was time to cessation of otorrhea. The principal secondary end point was sustained microbiological cure, defined as eradication or presumed eradication at end-of-therapy and test-of-cure visits. A total of 662 children participating in the 2 studies were randomized to receive ciprofloxacin plus fluocinolone (n = 223), ciprofloxacin alone (n = 221), or fluocinolone alone (n = 218). The median age was 2.5 years (range, 0.6-12.7 years). The median time to cessation of otorrhea was 4.23 days (95% CI, 3.65-4.95 days) in patients receiving ciprofloxacin plus fluocinolone compared with 6.95 days (95% CI, 5.66-8.20 days) in those receiving ciprofloxacin and not estimable findings in those receiving fluocinolone alone (P ciprofloxacin plus fluocinolone group, 67.4% in the ciprofloxacin group

  20. THE EFFICACY AND SAFETY OF CARMOLIS GEL IN THE COMBINATION THERAPY OF KNEE OSTEOARTHRITIS: RESULTS OF A MULTICENTER CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    I. N. Denisov

    2015-01-01

    Full Text Available Osteoarthritis (OA is one of the most common rheumatic diseases. Knee OA is particularly frequently encountered among all forms of OA, the prevalence of knee OA being about 25% in the general population. Despite multiple guidelines for the management of knee OA, which have been prepared by the European League Against Rheumatism (EULAR, the American College of Rheumatology (ACR, and the Osteoarthritis Research Society International (OARSI, many problems of its treatment policy remain to be solved. The same holds true for not only the symptomatic and disease-modifying effects of chondroprotectors, but also topical therapy options.Objective: to evaluate the clinical efficacy and safety of Carmolis gel in patients with knee OA.Subjects and methods.The trial included 280 patients with knee OA (a study group consisted of 190 patents; a control group comprised 90 patients. The mean age was 58.3±9.3 years in the study group and 59±10.5 years in the control group. The disease duration was 10.3±5.5 and 10.1±4.1 years, respectively. Carmolis gel was applied to the region of the most painful knee joint up to 4–5 times daily, followed by massage of this skin area. The treatment cycle lasted for 2 weeks. No therapy was performed in the control patients. The clinical efficacy was determined by the changes in joint pains at rest or on movement and palpation, according to a visual analogue scale (VAS, WOMAC questionnaire, the synovitis intensity (assessed by ultrasonography, patient and physician global assessments of disease activity (Likert scale, and the possibility of reducing the daily dosage of nonsteroidal anti-inflammatory drugs (NSAIDs. The onset the therapeutic effect of the gel and the duration of its action were recorded.Results and discussion. The topical application of Carmolis gel caused a statistically significant reduction in joint pain at rest and on movement from 57.7±6.8 to 12±1.8 mm (р < 0.01 and from 52±5.3 to 17±2.7 mm

  1. 临床护理人员安全文化的现状与对策%Status Quo of Safety Culture of Clinical Nursing Staff and Strategies

    Institute of Scientific and Technical Information of China (English)

    许乐; 姜贺

    2011-01-01

    Objective To understand the status of safety culture of clinical nursing staff, and to analyze potential problems in nursing safety management, and provide reasonable measures for managers. Methods A total of 580 clinical nursing staff were investigated with a self-designed questionnaire with convenience sampling. The problem percent response (PPR) towards every item and dimension were calculated to reflect the status of safety culture. Results The score of safety culture was 35.9%, which was in positive level, however, the PPR of the fear of blame, the frequency of adverse event and the executive force of nurses were slightly high, and all of them were in negative level. Conclusion The results show an overall positive safety culture exists, but some aspects need to be strengthened. In order to promote the development of safety culture, it is necessary to transfer current management concepts, establish an adverse event reporting system and safety culture measurement system.%目的 了解临床护理人员的安全文化现状,分析安全管理中存在的问题,提出相应的管理对策.方法 采用方便抽样法,以自行编制的"安全文化测评问卷"对580 名临床护理人员进行调查,统计分析各条目及维度的问题应答率以反映安全文化现状.结果 临床护士安全文化的问题应答率与中立值之和为35.9%,处于正向水平,但惩罚性感受、不良事件报告和护士执行力3 个维度问题应答率与中立值之和较高,均处于负向水平.结论临床护士的安全文化总体表现较为理想,但部分领域仍需改进.转变当前的管理理念,建立完善的不良事件报告系统和安全文化测评机制将有助于安全文化氛围的积极转变.

  2. Clinical efficacy of nursing safety intervention mechanism in the operation room safety management%手术室实施护理安全管理的效果分析

    Institute of Scientific and Technical Information of China (English)

    冉俊辉

    2014-01-01

    Objective:To observe the clinical efficacy of nursing safety intervention mechanism in the operation room safety management. Methods:A total of 1280 patients who received nursing safety management were selected into the observation group,another 1000 patients before the implementation of nursing safe-ty management were selected into the control group,the nursing qualities of the two groups were compared. Results:The score of nursing quality,the satisfaction degree of nursing job of the patients and doctors in the observation group were significantly higher than that in the control group (P<0. 05 ). The incidence of nursing errors in the observation group were shorter than that in the control group (P<0. 05 ). Conclusions:Nursing safety intervention mechanism can effective-ly reduce the incidence rate of safety risk and medical errors accident in operating room and can raise the satisfaction of patients.%目的:分析研究手术室实施护理安全管理的临床效果。方法:将我院实施护理安全管理的1280例手术的患者作为观察组,另选实施护理安全管理以前的1000例患者作为对照组,比较两组患者的手术室护理质量。结果:与对照组比较,观察组护理质量评分、患者和医生对护理工作的满意度明显增高(P<0.05);观察组护理差错发生率少于对照组,两组比较差异有统计学意义(P<0.05)。结论:在手术室的安全管理中,有效应用护理干预机制,可对手术室护理的安全质量起到提高效果,预防和减少风险事件的发生,提高手术配合质量。

  3. A new liposomal liver-specific contrast agent for CT: first human phase-I clinical trial assessing efficacy and safety

    Energy Technology Data Exchange (ETDEWEB)

    Leander, P. [Dept. of Diagnostic Radiology, Malmoe University Hospital (Sweden); Hoeglund, P. [Dept. of Clinical Pharmacology, Lund University Hospital (Sweden); Boerseth, A.; Kloster, Y.; Berg, A. [Nycomed Amersham Imaging, Oslo (Norway)

    2001-04-01

    In this first clinical trial liposome-encapsulated iodixanol, CT particles (CTP) were studied. The aims of the present trial were to assess the efficacy of CTP in CT and to determine the safety of different doses of CTP. A total of 47 healthy volunteers were enrolled in the present study. The CTP was administered at doses 10, 30, 70 and 100 mg encapsulated I/kg bw. Efficacy was assessed using single-slice CT of the abdomen and evaluated by dose-response attenuation curves over time in liver, spleen, and abdominal vessels. Safety was assessed by blood tests, clinical examinations and recording of subjective adverse events (AE). The attenuations in liver tissue increased with the dose and maximal values above baseline were 20, 39 and 45 HU at the doses 30, 70 and 100 mg encapsulated I/kg bw, respectively. Maximal increases were seen 12.5 min after contrast administration. As for liver, the attenuations in spleen increased with the dose, but higher attenuations were obtained. In early images clinically significant enhancement was seen in abdominal vessels. Mild and moderate subjective AE were encountered at the doses 70 and 100 mg encapsulated I/kg bw. The CTP is efficacious in enhancing hepatic and splenic tissues and in early imaging of abdominal vessels. Adverse event precludes a clinical use of CTP in the current formulation. (orig.)

  4. Safety and efficacy of a novel tartar control dentifrice containing 3.3% pyrophosphate: a controlled six-month clinical trial.

    Science.gov (United States)

    Segreto, V A; Stevens, D P; Schulte, M C; Fortna, R H; Gerlach, R W

    1998-01-01

    This study was undertaken to establish the tartar control efficacy and long-term safety of a new tartar control dentifrice that was formulated to enhance aesthetics and consumer acceptability. In a partially randomized, examiner-blind clinical trial, the experimental dentifrice, Crest MultiCare with 3.3% pyrophosphate, was compared to two currently marketed control dentifrices, Crest Regular Paste or Crest Tartar Protection Paste with 5.0% pyrophosphate. The eight-month trial model included a two-month pretest period to establish calculus formation after prophylaxis, followed by a six-month test period to evaluate efficacy and safety. Following the pretest period, 456 subjects were allocated to one of the three treatment groups and then monitored for calculus accumulation. After three and six months' test product use, the Crest MultiCare group experienced reductions in calculus accumulation of 28.9% and 32.3%, respectively compared to the regular control dentifrice. Over the six-month observation period, the experimental tartar control and the marketed tartar control dentifrices were comparable on adverse event frequency, type or severity, and no subject discontinued treatment due to an oral soft tissue adverse event. In this partially randomized and controlled six-month clinical trial, this new dentifrice exhibited tartar control efficacy, with a comparable overall safety profile to a marketed tartar control dentifrice.

  5. Randomized Clinical Trial of the Innovative Bilayered Wound Dressing Made of Silk and Gelatin: Safety and Efficacy Tests Using a Split-Thickness Skin Graft Model

    Directory of Open Access Journals (Sweden)

    Sukhontha Hasatsri

    2015-01-01

    Full Text Available We developed the novel silk fibroin-based bilayered wound dressing for the treatment of partial thickness wounds. And it showed relevant characteristics and accelerated the healing of full-thickness wounds in a rat model. This study is the clinical evaluation of the bilayered wound dressing to confirm its safety and efficacy for the treatment of split-thickness skin donor sites. The safety test was performed using a patch model and no evidence of marked and severe cutaneous reactions was found. The efficacy test of the bilayered wound dressing was conducted on 23 patients with 30 split-thickness skin graft donor sites to evaluate healing time, pain score, skin barrier function, and systemic reaction in comparison to Bactigras. We found that the healing time of donor site wounds treated with the bilayered wound dressing (11 ± 6 days was significantly faster than those treated with Bactigras (14 ± 6 days (p=10-6. The wound sites treated with the bilayered wound dressing showed significantly less pain and more rapid skin functional barrier recovery than those treated with Bactigras (p=10-5. Therefore, these results confirmed the clinical safety and efficacy of the bilayered wound dressing for the treatment of split-thickness skin graft donor sites.

  6. Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

    Science.gov (United States)

    Nagpal, Anjali; Choy, Fong Chan; Howell, Stuart; Hillier, Susan; Chan, Fiona; Hamilton-Bruce, Monica A; Koblar, Simon A

    2017-08-30

    Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

  7. Four-hour quantitative real-time polymerase chain reaction-based comprehensive chromosome screening and accumulating evidence of accuracy, safety, predictive value, and clinical efficacy.

    Science.gov (United States)

    Treff, Nathan R; Scott, Richard T

    2013-03-15

    Embryonic comprehensive chromosomal euploidy may represent a powerful biomarker to improve the success of IVF. However, there are a number of aneuploidy screening strategies to consider, including different technologic platforms with which to interrogate the embryonic DNA, and different embryonic developmental stages from which DNA can be analyzed. Although there are advantages and disadvantages associated with each strategy, a series of experiments producing evidence of accuracy, safety, clinical predictive value, and clinical efficacy indicate that trophectoderm biopsy and quantitative real-time polymerase chain reaction (qPCR)-based comprehensive chromosome screening (CCS) may represent a useful strategy to improve the success of IVF. This Biomarkers in Reproductive Medicine special issue review summarizes the accumulated experience with the development and clinical application of a 4-hour blastocyst qPCR-based CCS technology. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals; availability. Notice.

    Science.gov (United States)

    2010-01-21

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.'' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance, which is a revision of an existing guidance, discusses the types of nonclinical studies, their scope and duration, and their relation to the conduct of human clinical trials and marketing authorization for pharmaceuticals. The guidance is intended to facilitate the timely conduct of clinical trials and reduce the unnecessary use of animals and other drug development resources.

  9. Clinical efficacy and safety of the Shugan Jieyu capsule in patients with acute myocardial infarction and depression.

    Science.gov (United States)

    Liu, Wei; Qin, Jun

    2016-08-01

    Objective The aim is to comparatively study Shugan Jieyu capsule and sertraline for non-inferiority in the treatment of patients with acute myocardial infarction and depression (observing the curative effects and safety) by the randomized controlled experiment. Methods A total of 149 patients with acute myocardial infarction and depression were randomly divided into two groups, the Shugan Jieyu group (76 cases) and the sertraline group (73 cases), and received treatments for 24 weeks. Depression states were assessed by the rote diagnostic checklist, and effects were evaluated by the Hamilton depression scale. Drug safety for heart was assessed by left ventricular ejection fraction (reduced by 5%), blood pressure, heart rate, P-wave and R wave interval, Q-R-S complex wave, and corrected Q-T interval after 12 weeks of treatment. Results There were no significant differences in the effective rates of Shugan Jieyu and sertraline groups. Significantly lower adverse event rate was observed in the Shugan Jieyu group. Two groups had a similar cardiac safety. Conclusion Shugan Jieyu capsule has a reliable effect and high safety in patients with acute myocardial infarction and depression.

  10. Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs.

    Science.gov (United States)

    Tipold, A; Keefe, T J; Löscher, W; Rundfeldt, C; de Vries, F

    2015-04-01

    The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  11. Heparin-induced extracorporeal LDL-precipitation(HELP):Mode of action,safety and clinical experience(3)

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ Safety and practicability of the HELP procedure Compared to standard plasma exchange, HELP-apheresis is much better tolerated, primarily be-cause heparin rather than citrate is used for anti-coagulation and therefore problems due to hypercalce-mia do not play a role.

  12. Clinical efficacy, safety and pharmacokinetics of a newly developed controlled release morphine sulphate suppository in patients with cancer pain

    NARCIS (Netherlands)

    Moolenaar, F.; Meijler, W.J.; Frijlink, H.W.; Visser, Jan; Proost, J.H.

    2000-01-01

    Objective: To compare the efficacy, safety and pharmacokinetics of a newly developed controlled-release suppository (MSR) with MS Contin tablets (MSC) in cancer patients with pain. Methods: In a double-blind, randomised, two-way crossover trial, 25 patients with cancer pain were selected with a morp

  13. Clinical efficacy, safety and pharmacokinetics of a newly developed controlled release morphine sulphate suppository in patients with cancer pain

    NARCIS (Netherlands)

    Moolenaar, F.; Meijler, W.J.; Frijlink, H.W.; Visser, Jan; Proost, J.H.

    Objective: To compare the efficacy, safety and pharmacokinetics of a newly developed controlled-release suppository (MSR) with MS Contin tablets (MSC) in cancer patients with pain. Methods: In a double-blind, randomised, two-way crossover trial, 25 patients with cancer pain were selected with a

  14. 临床病人安全用药的管理方法与效果%Methods and effects of enhancing clinical meditation safety management

    Institute of Scientific and Technical Information of China (English)

    霍世英; 黄叶莉; 蔡伟萍; 黄海燕; 田宇红; 董媛媛

    2012-01-01

    目的 探讨临床病人安全用药的管理方法与效果,从而减少给药差错发生,保障病人安全用药.方法 对38例发生给药差错病例进行分析,采取举办给药差错案例分析讨论会、强化护士给药安全意识、加强查对制度的督查、加强有效沟通的培训与督查等安全管理措施.结果 实施临床病人安全用药管理后降低了给药差错发生率(P<0.01).结论 加强临床病人安全用药管理,可有效减少给药差错的发生.%Objective To explore the methods and effects of clinical meditation safety management, then to reduce meditation errors and ensure patients safety. Methods Thirty - eight cases of meditation errors were retrospectively analyzed and the countermeasures were developed according to the causes,including strengthening the meditation safety awareness of nurses, reinforcing the supervision systems and training skills to improve communication, and so on. Results The incidence of meditation errors was reduced significantly (P < 0.01). Conclusion Enhancing the management of clinical meditation safety can effectively reduce the incidence of meditation errors.

  15. 临床护士安全自我管理现状调查分析%Survey on safety self-management in clinical nursing staff

    Institute of Scientific and Technical Information of China (English)

    秦霞; 王素云; 盛素巧; 张文静

    2012-01-01

    目的 了解临床护士安全自我管理行为现状及其影响因素,以期对医院护理安全管理工作提供借鉴.方法 根据Vincent临床事件分析系统,采用自制安全问卷调查表对378护士进行现场调查.结果 护士安全自我管理得分最高的条目是首次执行药疗时询问过敏史,熟练掌握护理不良事件应急预案及处理程序;得分最低的是主动向护士长报告自己工作中的失误.职称与工龄是影响护士安全自我管理得分的主要因素(均P<0.01).结论 临床护士安全自我管理现状不容乐观,其影响因素是多方面的;应主要关注低年资护士,加强教育,以培养护士安全自我管理意识,提高工作安全性.%Objective To investigate status of safety self-management in clinical nurses and the influencing factors, and to provide information for nursing safety management. Methods A total of 378 nurses were investigated by filling out a self-designed questionnaire which was developed based on the Vincent clinical events analysis system. Results Nurses scored highest on the items of 'asking drug allergy history at the first medication' and 'mastering procedures of handling adverse events', and they scored lowest on the item of 'reporting work errors to head nurses voluntarily'. Professional title and length of service were predictive factors of safety self-management in nurses (P<0. 01 for both). Conclusion The status of safety self-management among nurses is not satisfactory, and it is affected by many factors. Managers should pay more attention to nurses with low professional title and short length of service, and strengthen education to culture nurses' safety awareness and to improve nursing safety.

  16. Vaccine Safety

    Science.gov (United States)

    ... Vaccine Safety Shingles (Herpes Zoster) Vaccine Safety Smallpox Vaccine Safety Common Concerns Adjuvants Autism CDC Statement: 2004 Pediatrics Paper on MMR and Autism Fainting (Syncope) Febrile ...

  17. Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort.

    Science.gov (United States)

    Calleja, Jose Luis; Crespo, Javier; Rincón, Diego; Ruiz-Antorán, Belén; Fernandez, Inmaculada; Perelló, Christie; Gea, Francisco; Lens, Sabela; García-Samaniego, Javier; Sacristán, Begoña; García-Eliz, María; Llerena, Susana; Pascasio, Juan Manuel; Turnes, Juan; Torras, Xavier; Morillas, Rosa Maria; Llaneras, Jordi; Serra, Miguel A; Diago, Moises; Rodriguez, Conrado Fernández; Ampuero, Javier; Jorquera, Francisco; Simon, Miguel A; Arenas, Juan; Navascues, Carmen Alvarez; Bañares, Rafael; Muñoz, Raquel; Albillos, Agustin; Mariño, Zoe

    2017-06-01

    Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/ritonavir plus dasabuvir (OMV/PTV/r+DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice. Data from HCV genotype 1 patients treated with either OMV/PTV/r+DSV±ribavirin (RBV) (n=1567) or LDV/SOF±RBV (n=1758) in 35 centers across Spain between April 1, 2015 and February 28, 2016 were recorded in a large national database. Demographic, clinical and virological data were analyzed. Details of serious adverse events (SAEs) were recorded. The two cohorts were not matched with respect to baseline characteristics and could not be compared directly. The SVR12 rate was 96.8% with OMV/PTVr/DSV±RBV and 95.8% with LDV/SOF±RBV. No significant differences were observed in SVR according to HCV subgenotype (p=0.321 [OMV/PTV/r+DSV±RBV] and p=0.174 [LDV/SOF]) or degree of fibrosis (c0.548 [OMV/PTV/r/DSV±RBV] and p=0.085 [LDV/SOF]). Only baseline albumin level was significantly associated with failure to achieve SVR (pOMV/PTV/r+DSV subcohort and 5.5% and 1.5% in the LDV/SOF subcohort, respectively. Hepatocellular carcinoma (HCC) recurred in 30% of patients with a complete response to therapy for previous HCC. Incident HCC was reported in 0.93%. In this large cohort of patients managed in the real-world setting in Spain, OMV/PTV/r+DSV and LDV/SOF achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with similarly good safety profiles. In clinical trials, second-generation direct-acting antiviral agents (DAAs) have been shown to cure over 90% of patients chronically infected with the genotype 1 hepatitis C virus and have been better tolerated than previous treatment

  18. Development, preclinical safety, formulation, and stability of clinical grade bevacizumab-800CW, a new near infrared fluorescent imaging agent for first in human use.

    Science.gov (United States)

    Ter Weele, Eva J; Terwisscha van Scheltinga, Anton G T; Linssen, Matthijs D; Nagengast, Wouter B; Lindner, Ingo; Jorritsma-Smit, Annelies; de Vries, Elisabeth G E; Kosterink, Jos G W; Lub-de Hooge, Marjolijn N

    2016-07-01

    There is a dire need for better visualization of cancer and analysis of specific targets in vivo. Molecular imaging with fluorescence is gaining more and more attention, as it allows detection of these targets and has advantages over radioactivity, such as no radiation dose, and lower costs. A key challenge in optical imaging however, is translation of the newly developed tracers from pre-clinical phase to clinical application. We describe the development and safety testing of clinical grade bevacizumab-800CW, an antibody-based targeted agent for non-invasive imaging of vascular endothelial growth factor A (VEGF-A). Development included implementing the manufacturing process and analytical methods according to current Good Manufacturing Practice (cGMP), formulation studies, extended characterization and stability testing. For safety pharmacology an extended single dose toxicity study in mice was performed. Bevacizumab-800CW was formulated in isotonic phosphate buffered sodium chloride solution at pH 7. The production was robust and showed a reproducible labeling efficiency, and no impurities. The binding affinity to VEGF-A remained intact. The optimized product meets all release specifications, is stable up to at least 3months and its characteristics did not significantly differ from the unlabeled bevacizumab. Toxicity testing in mice showed no remarkable findings. In conclusion, sterile bevacizumab-800CW (6mg=6ml) can be produced in stock according to current Good Manufacturing Practice. It is ready for first-in-human use.

  19. Surgical and clinical safety and effectiveness of robot-assisted laparoscopic hysterectomy compared to conventional laparoscopy and laparotomy for cervical cancer: A systematic review and meta-analysis.

    Science.gov (United States)

    Park, D A; Yun, J E; Kim, S W; Lee, S H

    2017-06-01

    This study aimed to evaluate the surgical safety and clinical effectiveness of RH versus LH and laparotomy for cervical cancer. We searched Ovid-Medline, Ovid-EMBASE, and the Cochrane library through May 2015, and checked references of relevant studies. We selected the comparative studies reported the surgical safety (overall; peri-operative; and post-operative complications; death within 30 days; and specific morbidities), and clinical effectiveness (survival; recurrence; length of stay [LOS]; estimated blood loss [EBL]; operative time [OT]) and patient-reported outcomes. Fifteen studies comparing RH with OH and 11 comparing RH with LH were identified. No significant differences were found in survival outcomes. The LOS was shorter and transfusion rate was lower with RH compared to OH or LH. EBL was significantly reduced with RH compared to OH. Compared to OH, overall complications, urinary infection, wound infection, and fever were significantly less frequent with RH. The overall, peri-operative, and post-operative complications were similar in other comparisons. Several patient-reported outcomes were improved with RH, though each outcome was reported in only one study. RH appears to have a positive effect in reducing overall complications, individual adverse events including wound infection, fever, urinary tract infection, transfusion, LOS, EBL, and time to diet than OH for cervical cancer patients. Compared to LH, the current evidence is not enough to clearly determine its clinical safety and effectiveness. Further rigorous prospective studies with long-term follow-up that overcome the many limitations of the current evidence are needed. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  20. The LVIS Jr. microstent to assist coil embolization of wide-neck intracranial aneurysms: clinical study to assess safety and efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Moehlenbruch, M.; Herweh, C.; Behrens, L.; Jestaedt, L.; Bendszus, M.; Pham, M. [University of Heidelberg Medical Center, Department of Neuroradiology, Heidelberg (Germany); Amiri, H.; Ringleb, P.A. [University of Heidelberg Medical Center, Department of Neurology, Heidelberg (Germany)

    2014-05-15

    This study was aimed to assess clinical safety and efficacy of the LVIS Jr. microstent in stent-assisted coil embolization of wide-neck intracranial aneurysms. IRB approved single-center interventional clinical study in 22 patients (10 females, 12 males, mean age 55, age range 33-74 years) for the endovascular treatment of wide-neck aneurysms. After obtaining informed consent, patients were included according to the following criteria: aneurysm fundus-to-neck ratio < 2 or neck diameter > 4 mm, and a parent vessel diameter of ≤3.5 mm. Primary end point for clinical safety was absence of death, absence of major or minor stroke, and absence of transient ischemic attack. Primary end point for treatment efficacy was complete angiographic occlusion according to the Raymond-Roy Occlusion Classification (RROC) immediately after the procedure and at follow-up after 3 and 6 months on magnetic resonance imaging (MRI). In 20/22 (91 %) of patients, the primary end point of safety was reached; in the two remaining patients, transient ischemic attack, but no permanent deficit was observed; in 16/22 (73 %), efficient occlusion (RROC1) was reached, and in 6/22 (27 %), a residual neck remained (RROC2). Single [seven with antegrade, two in crossover configuration, and four with ''first-balloon-then-stent'' (FBTS) technique] or double-stent (eight patients with Y configuration and one patient with X configuration) deployment was technically successful in all cases. Deployment of the LVIS Jr. microstent in various single- or double-stent configurations is safe and effective to assist the treatment of intracranial wide-neck aneurysms. (orig.)

  1. The efficacy and safety of preoperative chemotherapy with triweekly abraxane and cyclophosphamide followed by 5-Fluorouracil, epirubicin, and cyclophosphamide therapy for resectable breast cancer: a multicenter clinical trial.

    Science.gov (United States)

    Shigematsu, Hideo; Kadoya, Takayuki; Masumoto, Norio; Sasada, Tatsunari; Emi, Akiko; Ohara, Masahiro; Kajitani, Keiko; Okada, Morihito

    2015-04-01

    It has been reported that tri-weekly Abraxane therapy has better outcomes in recurrent breast cancer than tri-weekly Cremophor-based taxol therapy, and that cyclophosphamide combined with taxane shows an enhanced antitumor effect. We conducted a phase II clinical trial of preoperative chemotherapy with a combination of TRI-ABC. From September 2011 to September 2013, 4 cycles of preoperative chemotherapy with TRI-ABC followed by 4 cycles of FEC were administered in patients with resectable breast cancer. In patients with HER2-positive breast cancer, tri-weekly Trastuzumab was administered with TRI-ABC. The primary end point was the pathological complete response (pCR) rate in the breasts and lymph nodes. The treatment outcomes and safety were evaluated in 54 patients who received at least 1 dose of chemotherapy. All patients underwent radical surgery, and the overall pCR rate of 37% (20 of 54) was achieved. The pCR rates according to each subtype were 8% (2 of 24) in hormone receptor (HR)-positive HER2-negative breast cancer, 56% (5 of 9) in HR-positive HER2-positive breast cancer, 63% (5 of 8) in HR-negative HER2-positive breast cancer, and 62% (8 of 13) in triple-negative breast cancer. Multivariate analysis revealed that HR negativity and HER2 positivity were predictive factors of pCR. Clinical response was observed in 49 patients (91%). The safety profile was acceptable. Preoperative chemotherapy with TRI-ABC followed by FEC showed high efficacy and excellent safety. Further clinical studies should be conducted to compare the efficacy of TRI-ABC followed by FEC with conventional taxane-anthracycline regimens. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Glucagon-Like Peptide-1 Receptor Agonists for Type 2 Diabetes:A Clinical Update of Safety and Efficacy

    OpenAIRE

    Drab, Scott R.

    2016-01-01

    Abstract: Introduction Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly being used for the treatment of type 2 diabetes mellitus, but consideration of benefits and potential adverse events is required. This review examines the state of glycemic control, weight loss, blood pressure, and tolerability, as well as the current debate about the safety of GLP-1 RAs, including risk of pancreatitis, pancreatic cancer, and thyroid cancer. Methods A MEDLINE search (2010-2015) ident...

  3. Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women

    OpenAIRE

    Jones, CE; Munoz, FM; Spiegel, HML; Heininger, U; Zuber, PLF; Edwards, KM; Lambach, P.; Neels, P; Kohl, KS; Gidudu, J; Hirschfeld, S; Oleske, JM; Khuri-Bulos, N.; Bauwens, J.; Eckert, LO

    2016-01-01

    Vaccination during pregnancy is increasingly being used as an effective approach for protecting both young infants and their mothers from serious infections. Drawing conclusions from published studies in this area can be difficult because of the inability to compare vaccine trial results across different studies and settings due to the heterogeneity in the definitions of terms used to assess the safety of vaccines in pregnancy and the data collected in such studies.\\ud \\ud The guidelines prop...

  4. Observation on the safety:clinical trail on intracoronary autologus bone marrow mononuclear cells transplantation for acute myocardiol infarction

    Institute of Scientific and Technical Information of China (English)

    姚康

    2006-01-01

    Objective To investigate the safety of autologous bone marrow mononuclear cell (BM-MNCs) transplantation by intracoronary infusion in patients with acute myocardial infarction (AMI). Methods One hundred and eighty-four patients with AMI treated with percutaneous coronary intervention (PCI) were randomized in a 1:1 way to either intracoronary transplantation of autologous BM-MNCs (n =92) right after PCI or to sodium chloride concluding heparin (controlled, n=92) via a micro

  5. Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial

    Science.gov (United States)

    Demarin, Vida; Bašić Kes, Vanja; Trkanjec, Zlatko; Budišić, Mislav; Bošnjak Pašić, Marija; Črnac, Petra; Budinčević, Hrvoje

    2017-01-01

    Objectives The aim of this randomized, double-blind, placebo-controlled trial was to determine the efficacy and safety of Ginkgo biloba extract in patients diagnosed with vascular cognitive impairment (VCI). Methods A total of 90 patients (aged 67.1±8.0 years; 59 women) were randomly allocated (1:1:1) to receive G. biloba 120 mg, G. biloba 60 mg, or placebo during a 6-month period. Assessment was made for efficacy indicators, including neuropsychological tests scores (Sandoz Clinical Assessment Geriatric Scale, Folstein Mini-Mental State Examination, Mattis Dementia Rating Scale, and Clinical Global Impression) and transcranial Doppler ultrasound findings. Safety indicators included laboratory findings, reported adverse reactions, and clinical examination. Results At the end of 6-month study period, G. biloba 120 and 60 mg showed a statistically significant positive effect in comparison with placebo only on the Clinical Global Impression score (2.6±0.8 vs 3.1±0.7 vs 2.8±0.7, respectively; P=0.038). The Clinical Global Impression score showed a significant deterioration from the baseline values in the placebo group (−0.3±0.5; P=0.021) as opposed to G. biloba groups. No significant differences were found in the transcranial Doppler ultrasound findings. Adverse reactions were significantly more common and serious in the placebo group (16 subjects) than in either of the two G. biloba extract groups (eight and nine subjects, respectively), whereas laboratory findings and clinical examinations revealed no differences between the groups receiving G. biloba extract and placebo. Conclusion According to our results, G. biloba seemed to slow down the cognitive deterioration in patients with VCI, but the effect was shown in only one of the four neuropsychological tests administered. However, because of this mild effect in combination with a few adverse reactions, we cannot say that it is ineffective or unsafe either. Further studies are still needed to provide

  6. Hurricane Safety

    Science.gov (United States)

    ... English Hurricane Safety Checklist - Arabic Hurricane Safety Checklist - Chinese Hurricane Safety Checklist - French Hurricane Safety Checklist - Haitian ... Cross serves in the US, its territories and military installations around the world. Please try again. Your ...

  7. Prevalence of Substance Use in an HIV Primary Care Safety Net Clinic: A Call for Screening.

    Science.gov (United States)

    Dawson-Rose, Carol; Draughon, Jessica E; Zepf, Roland; Cuca, Yvette P; Huang, Emily; Freeborn, Kellie; Lum, Paula J

    Substance use complicates HIV care and prevention. Primary care clinics are an ideal setting to screen for and offer interventions for unhealthy alcohol and drug use; however, few HIV clinics routinely screen for substance use. We enrolled 208 clinic patients at an urban underserved HIV primary care clinic. We screened the patients for substance use with the Alcohol, Smoking, and Substance Involvement Score Test and measured urine toxicology. Of the 168 participants who completed screening, the majority reported tobacco or nonprescribed substance use in the previous 3 months. More African American participants reported low or no risk amphetamine use compared to Hispanic, White, or Other race participants (p < .001). Implementing standard clinic practice for screening and assessing substance use in HIV primary care clinics is needed.

  8. Applying the Plan-Do-Study-Act (PDSA) approach to a large pragmatic study involving safety net clinics

    OpenAIRE

    Coury, Jennifer; Schneider, Jennifer L.; Rivelli, Jennifer S.; Petrik, Amanda F.; Seibel, Evelyn; D?Agostini, Brieshon; Taplin, Stephen H.; Green, Beverly B; Coronado, Gloria D

    2017-01-01

    Background The Plan-Do-Study-Act (PDSA) cycle is a commonly used improvement process in health care settings, although its documented use in pragmatic clinical research is rare. A recent pragmatic clinical research study, called the Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC), used this process to optimize the research implementation of an automated colon cancer screening outreach program in intervention clinics. We describe the process of using this P...

  9. Clinical evaluation of the efficacy and safety of combined bipolar radiofrequency and optical energies vs. optical energy alone for the treatment of aging hands.

    Science.gov (United States)

    Verner, Ines; Kutscher, Tuvia Dror

    2017-08-01

    Different treatment modalities are used for the treatment and esthetic improvement of aging hands. This study evaluated the efficacy and safety of a novel technology, which combines bipolar radio frequency (RF) and optical energies for the cosmetic treatment of aging hands. The objective of the study was to assess the efficacy, safety, tolerability, and patient satisfaction of combined bipolar radiofrequency and optical energies vs. optical energy alone for the treatment of aging hands. Thirteen female patients with solar lentigines on the back of the hands were enrolled. Participants received three treatments: combined RF and intense pulsed light (IPL) on one hand and IPL treatment alone on the other. Standardized clinical photographs were taken, and patient and investigator improvement assessment (Global Esthetic Improvement (GAI) scale), patient satisfaction, and tolerability were evaluated. At the 1 and 3 months follow-up, skin laxity and pigmentation, investigator and patient improvement assessments, and satisfaction were significantly better in the hand treated with combined bipolar RF and IPL. This study demonstrates the safety and efficacy of combining RF and optical energies for the esthetic improvement of aging hands. Combined RF and IPL treatment was more efficient than IPL alone in improving skin pigmentation, skin laxity, and texture.

  10. An approach to 'dynamic--DDD (defined daily dose) monitoring' to reduce adverse clinical outcomes and increase patient safety: information repositories and event triggers in clinical practice.

    Science.gov (United States)

    Eryilmaz, Esat N

    2011-01-01

    The goal of every effort and actions/interventions in almost all healthcare settings throughout the world's health systems -primary care, inpatient, outpatient encounters, diagnostic and therapeutic interventions, peri-operative settings- is and has been to achieve a well defined outcome (a kind of improvement in health status of the patient under consideration, an observable and significant change(s) in selected set(s) of clinical parameters confirmed by laboratory results and pathology findings, improvements in clinical outcomes). Clinical inefficiencies, in this context, should be addressed very systematically and scientifically. This is achieved through a continuously monitoring approach to adverse drug events based on information repositories and evidence-based rule sets. For monitoring drug-related outcomes and clinical outcomes in general, the concept of DDD (Defined Daily Dose) compliance is explained in this article to eliminate and avoid adverse clinical outcomes.

  11. Safety, immune and clinical responses in metastatic melanoma patients vaccinated with a long peptide derived from indoleamine 2,3-dioxygenase in combination with ipilimumab

    DEFF Research Database (Denmark)

    Bjoern, Jon; Iversen, Trine Zeeberg; Nitschke, Nikolaj Juul;

    2016-01-01

    BACKGROUND AIM: Indoleamine 2,3-dioxygenase (IDO) is an emerging new target in cancer therapy that can be targeted with active immunotherapy (e.g. through peptide vaccination). Furthermore, IDO has been identified as a key mechanism underlying resistance to treatment with the checkpoint blocking...... antibody ipilimumab (ipi). METHODS: Ten patients with metastatic melanoma participated in a phase I first-in-human clinical study assessing safety of combining ipi with a 21-mer synthetic peptide vaccine from IDO denoted IDOlong. Secondary and tertiary end points included vaccine and clinical response....... RESULTS: Treatment was generally safe and well tolerated. Vaccine related adverse reactions included grade I and II erythema, oedema and pruritus at the vaccination site, which were manageable with mild topical corticosteroids. One patient developed presumed ipi-induced colitis. It initially responded...

  12. Pooled analysis of clinical trial data evaluating the safety and effectiveness of diclofenac epolamine topical patch 1.3% for the treatment of acute ankle sprain

    Directory of Open Access Journals (Sweden)

    Lionberger DR

    2011-07-01

    Full Text Available David R Lionberger1, Eric Joussellin2, Jillmarie Yanchick3, Merrell Magelli3,4, Arturo Lanzarotti51Southwest Orthopedic Group, LLP, Houston, TX, USA; 2Institut National du Sport, Paris, France; 3Formerly Alpharma Pharmaceuticals LLC, Piscataway, NJ, USA; 4GTx, Inc., Memphis, TN, USA; 5Institut Biochimique SA, SwitzerlandAbstract: This pooled analysis assessed the efficacy and safety of the diclofenac epolamine topical patch 1.3% (DETP for the treatment of acute mild-to-moderate ankle sprain. Data from 2 randomized, double-blind, placebo-controlled studies enrolling 274 male and female patients aged 18 to 65 years with acute ankle sprain were pooled and evaluated. The primary end point was pain reduction on movement assessed using a 100 mm visual analog scale (VAS. Safety and tolerability were also assessed. Beginning approximately 3 hours after initial treatment, DETP-treated patients experienced statistically significant and sustained lower mean VAS scores in pain intensity on movement (mean ± SD, 54.1 ± 20.0 mm versus 60.3 ± 16.8 mm compared with placebo-treated patients, representing a 20% versus 13% reduction in VAS pain scores from baseline (P = 0.012. This statistically significant difference in mean VAS score was maintained through day 7 (9.4 ± 14.4 mm versus 18.4 ± 18.2 mm, P < 0.0001. The DETP and placebo patches were well tolerated. These results further confirm the efficacy and safety of DETP for the treatment of acute pain from ankle sprains.Keywords: soft tissue injury, acute pain, visual analog scale, clinical trial, double-blind, safety

  13. Progress of Clinical Application and Safety of Tetanus Antitoxin%破伤风抗毒素临床应用及安全性研究进展

    Institute of Scientific and Technical Information of China (English)

    余超; 徐玉茗; 徐瑾; 万凯化; 袁兴东; 李穗; 周鹃

    2016-01-01

    目的了解破伤风抗毒素(tetanus antitoxin, TAT)的临床应用现状及其安全性研究进展,为开展上市后安全性评估提供参考。方法检索国内外研究TAT临床应用安全性相关的文献,对其进行归类分析研究。结果目前TAT在临床上主要应用于破伤风被动免疫和破伤风治疗;大量安全性研究显示,其皮试阳性率较高,主要与患者体质、药物因素、操作因素及其他原因造成假阳性过高有关。其不良反应主要有过敏性休克、血清病及其他类型不良反应。结论 TAT仍是国内为外伤患者预防破伤风的首选注射药物,建议在临床应用中应重视过敏,注意观察,并尽快制定适合我国的破伤风预防指南和规范,促进合理用药。%Objective To understand the progress of the clinical utilization status and safety of tetanus antitoxin (TAT), and to provide references for post-marketing safety evaluation.Methods Domestic and foreign literatures on the clinical application and safety of TAT were reviewed for further analysis and comparison.Results Now TAT has been mainly used for passive immunity and tetanus therapeutics in clinic. Intensive safety studies showed that higher false-positive rate of its skin test mainly related to patients’ physique, medicine factor, infusion operation factor, and so on. Its main adverse effects included anaphylactic shock, erum sickness, and other kinds of adverse reactions.Conclusion TAT is still the ifrst choice against tetanus of trauma patients in China, the paper suggests that medical workers must put emphasis on anaphylaxis and close observation, along with our country should expeditiously enact a speciifc against tetanus guidelines and standards of Chinese style, and promoting rational drug use.

  14. Long-term safety evaluation of bimatoprost ophthalmic solution 0.03%: a pooled analysis of six double-masked, randomized, active-controlled clinical trials

    Directory of Open Access Journals (Sweden)

    Wirta D

    2011-06-01

    Full Text Available David Wirta1, Amanda M VanDenburgh2, Emily Weng3, Scott M Whitcup4, Sef Kurstjens5, Frederick C Beddingfield III4,61Private Practice, Newport Beach, CA, USA; 2Clinical Development, 3Biostatistics, 4Research and Development, 5Global Drug Development, Allergan, Inc, Irvine, CA, USA; 6Department of Medicine, Division of Dermatology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USABackground: Bimatoprost ophthalmic solution 0.03% was approved in the US for reducing intraoccular pressure (IOP based on two double-masked, active-controlled clinical trials. Four additional long-term studies (≥ 12months were conducted; however, the aggregate safety profile of the six studies has not been reported.Methods: Adverse events (AEs were pooled from six double-masked, active-controlled, long-term clinical trials in which subjects received bimatoprost 0.03% once daily (QD or twice daily (BID as an eyedrop. AE terms were converted to MedDRA (V.11.0 Preferred Terms and analyzed.Results: In total, 1409 patients received more than one dose of bimatoprost 0.03% QD or BID. Most AEs were mild in severity and reported by 86.7% (QD and 94.8% (BID of subjects (≤ 12 months of treatment. AEs reported through month 12 (aggregate incidence of ≥ 5% were conjunctival hyperemia, increased eyelash growth, eye pruritus, periocular skin hyperpigmentation, eye irritation, dry eye, and hypertrichosis. AE onset was generally reported within four months of treatment. The cumulative incidence of common AEs in the QD treatment group at 24–48 months was similar to that measured at 12 months of treatment.Conclusion: Bimatoprost 0.03% has a favorable safety and tolerability profile as characterized by six long-term studies. Common AEs were due to the known pharmacological activity of bimatoprost and reversible with treatment cessation.Keywords: intraocular pressure, eyelids, pharmacology, clinical trial, medical treatment

  15. BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety.

    Science.gov (United States)

    Maas Enriquez, Monika; Thrift, John; Garger, Stephen; Katterle, Yvonne

    2016-11-01

    BAY 81-8973 is a full-length, unmodified recombinant human factor VIII (FVIII) approved for the treatment of hemophilia A. BAY 81-8973 has the same amino acid sequence as the currently marketed sucrose-formulated recombinant FVIII (rFVIII-FS) product and is produced using additional advanced manufacturing technologies. One of the key manufacturing advances for BAY 81-8973 is introduction of the gene for human heat shock protein 70 (HSP70) into the rFVIII-FS cell line. HSP70 facilitates proper folding of proteins, enhances cell survival by inhibiting apoptosis, and potentially impacts rFVIII glycosylation. HSP70 expression in the BAY 81-8973 cell line along with other manufacturing advances resulted in a higher-producing cell line and improvements in the pharmacokinetics of the final product as determined in clinical studies. HSP70 protein is not detected in the harvest or in the final BAY 81-8973 product. However, because this is a new process, clinical trial safety assessments included monitoring for anti-HSP70 antibodies. Most patients, across all age groups, had low levels of anti-HSP70 antibodies before exposure to the investigational product. During BAY 81-8973 treatment, 5% of patients had sporadic increases in anti-HSP70 antibody levels above a predefined threshold (cutoff value, 239 ng/mL). No clinical symptoms related to anti-HSP70 antibody development occurred. In conclusion, addition of HSP70 to the BAY 81-8973 cell line is an innovative technology for manufacturing rFVIII aimed at improving protein folding and expression. Improved pharmacokinetics and no effect on safety of BAY 81-8973 were observed in clinical trials in patients with hemophilia A. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Tocilizumab use in pregnancy: Analysis of a global safety database including data from clinical trials and post-marketing data.

    Science.gov (United States)

    Hoeltzenbein, Maria; Beck, Evelin; Rajwanshi, Richa; Gøtestam Skorpen, Carina; Berber, Erhan; Schaefer, Christof; Østensen, Monika

    2016-10-01

    Analyze the cumulative evidence for pregnancy outcomes after maternal exposure to tocilizumab, an anti-interleukin-6-receptor monoclonal antibody used for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. At present, published experience on tocilizumab use during pregnancy is very limited. We have analyzed all pregnancy-related reports documented in the Roche Global Safety Database until December 31, 2014 (n = 501). After exclusion of ongoing pregnancies, duplicates, and cases retrieved from the literature, 399 women were found to have been exposed to tocilizumab shortly before or during pregnancy, with pregnancy outcomes being reported in 288 pregnancies (72.2%). Of these 288 pregnancies, 180 were prospectively reported resulting in 109 live births (60.6%), 39 spontaneous abortions (21.7%), 31 elective terminations of pregnancy (17.2%), and 1 stillbirth. The rate of malformations was 4.5%. Co-medications included methotrexate in 21.1% of the prospectively ascertained cases. Compared to the general population, an increased rate of preterm birth (31.2%) was observed. Retrospectively reported pregnancies (n = 108) resulted in 55 live births (50.9%), 31 spontaneous abortions (28.7%), and 22 elective terminations (20.4%). Three infants/fetuses with congenital anomalies were reported in this group. No increased risks for adverse pregnancy outcomes were observed after paternal exposure in 13 pregnancies with known outcome. No indication for a substantially increased malformation risk was observed. Considering the limitations of global safety databases, the data do not yet prove safety, but provide information for physicians and patients to make informed decisions. This is particularly important after inadvertent exposure to tocilizumab, shortly before or during early pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Clinical study to evaluate the safety and effectiveness of the Aesculap Activ-L™ artificial disc in the treatment of degenerative disc disease

    Directory of Open Access Journals (Sweden)

    Mo Fred F

    2010-04-01

    Full Text Available Abstract Background The objective of this clinical study is to evaluate the safety and effectiveness of the Activ-L Artificial Disc for treatment of single-level degenerative disc disease of the lumbar spine in patients who have been unresponsive to at least six months of prior conservative care. The hypothesis of the study is that the Activ-L Disc is non-inferior to the control (the Charité® Artificial Disc [DePuy Spine] or ProDisc-L® Total Disc Replacement [Synthes Spine] with respect to the rate of individual subject success at 24 months. Individual subject success is a composite of effectiveness and safety. Methods/Design The study proposed is a prospective, randomized, single-masked, controlled, multi-center clinical trial consisting of an estimated 414 subjects with single-level DDD of the lumbar spine (L4/L5, or L5/S1 who have failed to improve with conservative treatment for at least six months prior to enrollment. After enrollment, subjects will be randomized in a 2:1 ratio to either the Activ-L Disc (investigational device or the control (Charité or ProDisc-L. Radiographic endpoints will be evaluated by an independent reviewer at an imaging core laboratory. Each subject will be followed for 5 years post-treatment. Discussion The safety and effectiveness of the Activ-L Artificial Disc for treatment of single-level degenerative disc disease of the lumbar spine will be equivalent to Charité® Artificial Disc [DePuy Spine] or ProDisc-L® Total Disc Replacement [Synthes Spine] at 24 months. Trial Registration Current Controlled Trials NCT00589797.

  18. First Human Implantation of a Bioresorbable Polymer Scaffold for Acute Traumatic Spinal Cord Injury: A Clinical Pilot Study for Safety and Feasibility.

    Science.gov (United States)

    Theodore, Nicholas; Hlubek, Randall; Danielson, Jill; Neff, Kristin; Vaickus, Lou; Ulich, Thomas R; Ropper, Alexander E

    2016-08-01

    A porous bioresorbable polymer scaffold has previously been tested in preclinical animal models of spinal cord contusion injury to promote appositional healing, spare white matter, decrease posttraumatic cysts, and normalize intraparenchymal tissue pressure. This is the first report of its human implantation in a spinal cord injury patient during a pilot study testing the safety and feasibility of this technique (ClinicalTrials.gov Identifier: NCT02138110). A 25-year-old man had a T11-12 fracture dislocation sustained in a motocross accident that resulted in a T11 American Spinal Injury Association Impairment Scale (AIS) grade A traumatic spinal cord injury. He was treated with acute surgical decompression and spinal fixation with fusion, and enrolled in the spinal scaffold study. A 2 × 10 mm bioresorbable scaffold was placed in the spinal cord parenchyma at T12. The scaffold was implanted directly into the traumatic cavity within the spinal cord through a dorsal root entry zone myelotomy at the caudal extent of the contused area. By 3 months, his neurological examination improved to an L1 AIS grade C incomplete injury. At 6-month postoperative follow-up, there were no procedural complications or apparent safety issues related to the scaffold implantation. Although longer-term follow-up and investigation are required, this case demonstrates that a polymer scaffold can be safely implanted into an acutely contused spinal cord. This is the first human surgical implantation, and future outcomes of other patients in this clinical trial will better elucidate the safety and possible efficacy profile of the scaffold. AIS, American Spinal Injury Association Impairment ScaleSCI, spinal cord injurytSCI, traumatic spinal cord injury.

  19. Clinical safety and outcomes of laparoscopic surgery versus open surgery for palliative resection of primary tumors in patients with stage IV colorectal cancer: a meta-analysis.

    Science.gov (United States)

    Zhou, Min-Wei; Gu, Xiao-Dong; Xiang, Jian-Bin; Chen, Zong-You

    2016-05-01

    This study was performed to compare the clinical safety and outcomes of laparoscopic versus open surgery for primary tumors in patients with stage IV colorectal cancer. Pertinent studies were selected from the MEDLINE, EMBASE, and Cochrane Library databases; references from published articles; and reviews. Both prospective and retrospective studies were included for the meta-analysis. Clinical outcomes included safety, complications, mortality, and survival. Six trials involving 1802 patients were included. The operative time was longer for laparoscopic than for open surgery (mean difference (MD) = 44.20, 95 % confidence interval (CI) 17.31-71.09, Z = 3.22, P = 0.001). Laparoscopic surgery was also associated with fewer postoperative complications (odds ratio 0.53, 95 % CI 0.37-0.78, Z = 3.29, P = 0.001) and less operative blood loss (MD = -65.40, 95 % CI -102.37 to -28.42, Z = 3.47, P = 0.0005). Median survival ranged from 11.4 to 30.1 months. The total hospital stay was 1.68 days shorter for laparoscopic than for open surgery (95 % CI -1.83 to -1.53, Z = 21.64, P < 0.00001). Laparoscopic surgery for palliative resection of stage IV colorectal cancer is associated with better perioperative outcomes than open surgery.

  20. Letter to the editor regarding "Clinical effectiveness and safety of powered exoskeleton-assisted walking in patients with spinal cord injury: systematic review with meta-analysis"

    Directory of Open Access Journals (Sweden)

    Dijkers MP

    2016-11-01

    Full Text Available Marcel P Dijkers,1 Katherine G Akers,2 Sujay S Galen,3 Diane E Patzer,4 Phuong T Vu41Department of Physical Medicine and Rehabilitation, Wayne State University, Detroit, 2Shiffman Medical Library, Wayne State University, Detroit, 3Physical Therapy Program, Wayne State University, Detroit, 4Center for Spinal Cord Injury Recovery, Rehabilitation Institute of Michigan, Detroit, MI, USAIn the article “Clinical effectiveness and safety of powered exoskeleton-assisted walking in patients with spinal cord injury: systematic review with meta-analysis”, published in the March issue of Medical Devices: Evidence and Research, Miller et al1 present a meta-analysis of the clinical effectiveness and safety of powered exoskeletons for spinal cord injury (SCI patients. A close examination of this article shows surprising coincidences, in that two primary studies (references 25 and 33 in the reference list report the same proportions and 95% confidence intervals (CIs of subjects able to ambulate with an exoskeleton without assistance (Figure 2 of the study, and two different primary studies (references 26 and 28 report the same mean and 95% CIs for the distance (in meters walked in a 6-minute walk test (Figure 4 of the study.View the original paper by Miller and colleagues.

  1. A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen (Ambrosia artemisiifolia)

    Science.gov (United States)

    Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante

    2017-01-01

    Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed (Ambrosia artemisiifolia) is on the rise throughout Europe, having a significant negative impact on the patients’ and their family’s quality of life. Allergen-specific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success.

  2. Understanding the digital divide in the clinical setting: the technology knowledge gap experienced by US safety net patients during teleretinal screening.

    Science.gov (United States)

    George, Sheba; Moran, Erin; Fish, Allison; Ogunyemi, Lola

    2013-01-01

    Differential access to everyday technology and healthcare amongst safety net patients is associated with low technological and health literacies, respectively. These low rates of literacy produce a complex patient "knowledge gap" that influences the effectiveness of telehealth technologies. To understand this "knowledge gap", six focus groups (2 African-American and 4 Latino) were conducted with patients who received teleretinal screenings in U.S. urban safety-net settings. Findings indicate that patients' "knowledge gap" is primarily produced at three points: (1) when patients' preexisting personal barriers to care became exacerbated in the clinical setting; (2) through encounters with technology during screening; and (3) in doctor-patient follow-up. This "knowledge gap" can produce confusion and fear, potentially affecting patients' confidence in quality of care and limiting their disease management ability. In rethinking the digital divide to include the consequences of this knowledge gap faced by patients in the clinical setting, we suggest that patient education focus on both their disease and specific telehealth technologies deployed in care delivery.

  3. Switching to biosimilar infliximab (CT-P13): Evidence of clinical safety, effectiveness and impact on public health.

    Science.gov (United States)

    Braun, Jürgen; Kudrin, Alex

    2016-07-01

    CT-P13, the biosimilar of infliximab, has been recently approved in the EU, Australia, Canada, Japan and many other countries. Thus, it was the first biosimilar approved in the field of rheumatology, dermatology and gastroenterology. Since there has been debate about the issue of switching from RMP to the biosimilar and some national societies have expressed concerns, this review was written with the following objectives: The review concludes that whilst prudent switching practices should be employed, growing safety experience accumulated thus far with CT-P13 and other biosimilars is favorable and does not raise any specific concerns.

  4. SAFETY OF CELL-DERIVED SUBUNIT ADJUVANTED INFLUENZA VACCINE FOR CHILDREN VACCINATION: DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    S.M. Kharit

    2010-01-01

    Full Text Available This article presents the safety data for cell-derived inactivated subunit adjuvanted influenza vaccine «Grippol Neo» in children 3–17 years old in comparison with reference egg-derived inactivated subunit vaccine «Grippol plus». Good test vaccine tolerability and high efficacy profile is demonstrated. Based on the results obtained vaccine «Grippol Neo» is recommended for mass influenza prophylaxis in pediatry, including National Immunization Schedule.Key words: children, influenza, vaccination, «Grippol Neo».(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:44-49

  5. Clinical Efficacy and Safety of Gubitong Recipe (骨痹通方) in Treating Osteoarthritis of Knee Joint

    Institute of Scientific and Technical Information of China (English)

    陶庆文; 徐愿; 金笛儿; 阎小萍

    2009-01-01

    Objective:To observe the therapeutic efficacy and safety of Gubitong Recipe(骨痹通方,GBT) in treating osteoarthritis(OA) of knee joint.Methods:Ninety patients with knee osteoarthritis were equally assigned, according to a randomizing digital table,to the treatment group and the control group.The treatment group was treated with GBT Decoction one dose every day and the control group with glucosamine sulfate 500 mg thrice a day,respectively,for eight successive weeks.Besides,diclofenac sodium could be given as...

  6. Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in "real-world" clinical practice

    DEFF Research Database (Denmark)

    Li, Xiaoyan; Deitelzweig, Steve; Keshishian, Allison

    2017-01-01

    ) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate...... to warfarin treatment. This is the largest "real-world" study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various...

  7. Leflunomide : a manageable safety profile

    NARCIS (Netherlands)

    Riel, P.L.C.M. van; Smolen, J.S.; Emery, P.; Kalden, J.R.; Dougados, M.; Strand, C.V.; Breedveld, F.C.

    2004-01-01

    The safety profile of leflunomide in the treatment of rheumatoid arthritis has been well documented in clinical trials, postmarketing surveillance, and epidemiological studies. Both postmarketing surveillance and epidemiological study results are consistent with the safety profile of leflunomide rep

  8. Over 25 Years of Clinical Experience With Ivermectin: An Overview of Safety for an Increasing Number of Indications.

    Science.gov (United States)

    Kircik, Leon H; Del Rosso, James Q; Layton, Alison M; Schauber, Jürgen

    2016-03-01

    Although the broad-spectrum anti-parasitic effects of the avermectin derivative ivermectin are well documented, its anti-inflammatory activity has only recently been demonstrated. For over 25 years, ivermectin has been used to treat parasitic infections in mammals, with a good safety profile that may be attributed to its high affinity to invertebrate neuronal ion channels and its inability to cross the blood-brain barrier in humans and other mammals. Numerous studies report low rates of adverse events, as an oral treatment for parasitic infections, scabies and head lice. Ivermectin has been used off-label to treat diseases associated with Demodex mites, such as blepharitis and demodicidosis. New evidence has linked Demodex mites to rosacea, a chronic inflammatory disease. Ivermectin has recently received FDA and EU approval for the treatment of adult patients with inflammatory lesions of rosacea, a disease in which this agent has been shown to be well tolerated. After more than 25 years of use, ivermectin continues to provide a high margin of safety for a growing number of indications based on its anti-parasitic and anti-inflammatory activities.

  9. Efficacy, Safety, and Tolerability of Desvenlafaxine 50 mg/d for the Treatment of Major Depressive Disorder:A Systematic Review of Clinical Trials

    Science.gov (United States)

    Tourian, Karen A.

    2010-01-01

    Objective: Desvenlafaxine is the third serotonin-norepinephrine reuptake inhibitor (SNRI) approved by the US Food and Drug Administration for major depressive disorder (MDD). This article summarizes data on the clinical pharmacology, efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) for MDD with a focus on the 50-mg/d therapeutic dose. Additionally, the article discusses clinical practice considerations and future directions in desvenlafaxine research. Data sources: Data relating to desvenlafaxine 50 mg/d were identified through searches of MEDLINE and publication databases of Pfizer for articles in English published before January 2009. Keywords were desvenlafaxine, O-desmethylvenlafaxine, ODV, and 50 mg. Study selection: Three randomized, placebo- and/or active comparator–controlled, 8-week clinical trials reported the efficacy of desvenlafaxine 50 mg/d for the treatment of MDD. The third of these studies included a post hoc pooled analysis of data from all 3 of these trials. In addition, the search retrieved an article examining pooled data from 9 trials, including 50-mg data from 2 of the 3 retrieved trials. Data synthesis: Desvenlafaxine is the major active metabolite of the SNRI venlafaxine. Significant improvements compared with placebo were observed on the primary efficacy measure (17-item Hamilton Depression Rating Scale total score) and most secondary measures in 2 of 3 clinical trials. An integrated analysis of registration data from 9 randomized, double-blind, placebo-controlled, 8-week studies of desvenlafaxine (50 to 400 mg/d) for MDD demonstrated no evidence of greater efficacy with doses higher than 50 mg/d. Safety results indicate that desvenlafaxine treatment is generally safe and well tolerated; findings were consistent with those for the SNRI class. The 50-mg/d dose of desvenlafaxine was associated with low rates of discontinuation due to treatment-emergent adverse events, which were similar to

  10. An emerging playbook for antibody-drug conjugates: lessons from the laboratory and clinic suggest a strategy for improving efficacy and safety.

    Science.gov (United States)

    Drake, Penelope M; Rabuka, David

    2015-10-01

    Antibody-drug conjugates (ADCs) have become de rigueur for pharmaceutical oncology drug development pipelines. There are more than 40 ADCs undergoing clinical trials and many more in preclinical development. The field has rushed to follow the initial successes of Kadcyla™ and Adcetris™, and moved forward with new targets without much pause for optimization. In some respects, the ADC space has become divided into the clinical realm-where the proven technologies continue to represent the bulk of clinical candidates with a few exceptions-and the research realm-where innovations in conjugation chemistry and linker technologies have suggested that there is much room for improvement in the conventional methods. Now, two and four years after the approvals of Kadcyla™ and Adcetris™, respectively, consensus may at last be building that these two drugs rely on rather unique target antigens that enable their success. It is becoming increasingly clear that future target antigens will require additional innovative approaches. Next-generation ADCs have begun to move out of the lab and into the clinic, where there is a pressing need for continued innovation to overcome the twin challenges of safety and efficacy.

  11. Safety aspects of Chinese herbal medicine in pregnancy-re-evaluation of experimental data of two animal studies and the clinical experience.

    Science.gov (United States)

    Wiebrecht, Axel; Gaus, Wilhelm; Becker, Simon; Hummelsberger, Josef; Kuhlmann, Kirsten

    2014-10-01

    Chinese herbal medicine is an increasingly popular worldwide medical therapy which also has an impact in pregnancy. However, the question of its drug safety during pregnancy remains unresolved. Potential problems include teratogenicity, abortion, perinatal toxicity, pre- and postnatal developmental abnormalities, and eventually an increased risk for carcinomas in the offspring. Standard Materia Medica textbooks contain unreliable information when it comes to risks during pregnancy. Wang and co-workers conducted an experimental study (WS) on mice in which they investigated the effects of 17 Chinese medicinals regarding embryotoxicity and fetotoxicity. All these drugs seemed to exhibit multiple significant toxic effects. Another study by Li and co-workers (LS) investigated the reproductive toxicity of Atractylodis macrocephalae Rhizoma in mice, rats and rabbits. They described an increased pre- and postnatal mortality and, at high doses, congenital malformations. In an attempt to identify the risks of the tested medicinals during pregnancy, we analysed these two experimental studies and compared their results with possible safety data for humans from two reviews of clinical studies on threatened miscarriage (AR and CR). We re-evaluated WS and LS in relation to accordance with internationally accepted rules, equivalence to human dose, biometric accuracy, plausibility, and coherence. Eligible studies of the two reviews on threatened miscarriage were evaluated for specific pregnancy risks concerning the 17 medicinals tested in WS and LS. We found that WS does not conform to international ICH guidelines and includes many inconsistencies, implausibilities and several severe biometrical flaws. It reported a total of 364 significant events out of which 145 false significant results are expected. The data-handling pointed to irregularities. Analysis of LS exhibited also many inconsistencies. The results regarding congenital malformations were statistically insignificant and

  12. Safety of magnetic resonance imaging of patients with a new Medtronic EnRhythm MRI SureScan pacing system: clinical study design

    Directory of Open Access Journals (Sweden)

    Jenniskens Inge

    2008-12-01

    Full Text Available Abstract Background Magnetic Resonance Imaging (MRI of patients with implanted cardiac devices is currently considered hazardous due to potential for electromagnetic interference to the patient and pacemaker system. With approximately 60 million MRI scans performed worldwide per year, an estimated majority of pacemaker patients may develop an indication for an MRI during the lifetime of their pacemakers, suggesting that safe use of pacemakers in the MRI environment would be clinically valuable. A new pacing system (Medtronic EnRhythm MRI™ SureScan™ and CapSureFix MRI™ leads has been designed and pre-clinically tested for safe use in the MRI environment. The EnRhythm MRI study is designed to confirm the safety and efficacy of this new pacing system. Methods The EnRhythm MRI study is a prospective, randomized controlled, unblinded clinical trial to confirm the safety and efficacy of MRI at 1.5 Tesla in patients implanted with a specifically designed pacemaker and lead system. The patients have standard indications for dual chamber pacemaker implantation. Successfully implanted patients are randomized in a 2:1 ratio to undergo MRI (MRI group or to have no MRI scan (control group at 9–12 weeks after pacemaker system implantation. Magnetic resonance (MR scanning includes 14 head and lumbar scan sequences representing clinically relevant scans while maximizing the gradient slew rate up to 200 T/m/s, and/or the transmitted radiofrequency (RF power up to SAR (specific absorption rate levels of 2 W/kg body weight (upper limit of normal operating mode. Full interrogation of all device information and sensing and capture function are measured at device implantation, every follow-up and before and immediately after MRI in the MRI group and at the same time points in the control group. Complete pacemaker and lead evaluations are also done at one week and one month after the scan for the MRI and control group patients. The primary endpoint is safe and

  13. Safety of magnetic resonance imaging of patients with a new Medtronic EnRhythm MRI SureScan pacing system: clinical study design

    Science.gov (United States)

    Sutton, Richard; Kanal, Emanuel; Wilkoff, Bruce L; Bello, David; Luechinger, Roger; Jenniskens, Inge; Hull, Michael; Sommer, Torsten

    2008-01-01

    Background Magnetic Resonance Imaging (MRI) of patients with implanted cardiac devices is currently considered hazardous due to potential for electromagnetic interference to the patient and pacemaker system. With approximately 60 million MRI scans performed worldwide per year, an estimated majority of pacemaker patients may develop an indication for an MRI during the lifetime of their pacemakers, suggesting that safe use of pacemakers in the MRI environment would be clinically valuable. A new pacing system (Medtronic EnRhythm MRI™ SureScan™ and CapSureFix MRI™ leads) has been designed and pre-clinically tested for safe use in the MRI environment. The EnRhythm MRI study is designed to confirm the safety and efficacy of this new pacing system. Methods The EnRhythm MRI study is a prospective, randomized controlled, unblinded clinical trial to confirm the safety and efficacy of MRI at 1.5 Tesla in patients implanted with a specifically designed pacemaker and lead system. The patients have standard indications for dual chamber pacemaker implantation. Successfully implanted patients are randomized in a 2:1 ratio to undergo MRI (MRI group) or to have no MRI scan (control group) at 9–12 weeks after pacemaker system implantation. Magnetic resonance (MR) scanning includes 14 head and lumbar scan sequences representing clinically relevant scans while maximizing the gradient slew rate up to 200 T/m/s, and/or the transmitted radiofrequency (RF) power up to SAR (specific absorption rate) levels of 2 W/kg body weight (upper limit of normal operating mode). Full interrogation of all device information and sensing and capture function are measured at device implantation, every follow-up and before and immediately after MRI in the MRI group and at the same time points in the control group. Complete pacemaker and lead evaluations are also done at one week and one month after the scan for the MRI and control group patients. The primary endpoint is safe and successful

  14. How safe is our "place of safety"? Clinical guidance promoting safer medical care of patients detained under section 136 of the Mental Health Act.

    Science.gov (United States)

    Mouko, Josie; Goddard, Aurielle; Nimmo-Smith, Victoria

    2015-01-01

    A new four-bed unit was opened in Bristol, UK, in 2014, for people detained under section 136 of the Mental Health Act. Police bring individuals posing a risk to themselves or others to a Place of Safety (PoS) in order to receive a mental health assessment. Individuals may be held for up to 72 hours, but cannot receive treatment against their will, unless assessed as lacking the capacity to refuse treatment. Issues requiring medical input arose in more than a third of patients, yet there was little guidance for trainees around the PoS. We conducted a survey which confirmed that robust clinical guidance was needed for junior doctors around medical assistance in this unique environment. We identified specific concerns around patient safety in relation to alcohol withdrawal, uncertainties around legislation and lack of clarity of who to call out of hours. Trainees felt they were working outside of their expertise. We collaborated with a variety of professionals to produce clinical guidance in line with best evidence, and made this easily accessible. We also gained a consensus that more experienced core trainees (SHOs) in Psychiatry should be the first point of contact. We then conducted a survey in June 2015, and found that doctors covering the PoS now felt there was sufficient guidance on most clinical scenarios, 100% consensus on who to contact and improved confidence in their ability to manage issues arising. In August 2015 we held an informal training session for the new intake of trainees on the rota. A subsequent survey revealed similarly positive results. Through this project, we were able to identify defects in a system, provide needed guidance to enable safer and more equitable care to a vulnerable group, and foster closer collaboration between junior doctors and managers in the design and use of services.

  15. Comparative efficacy and safety of nortriptyline and fluoxetine in the treatment of major depression: a clinical study.

    Science.gov (United States)

    Fabre, L F; Scharf, M B; Itil, T M

    1991-06-01

    The safety and efficacy of nortriptyline and fluoxetine were compared in a double-blind, randomized, multicenter 5-week trial involving 205 outpatients with acute major depression of moderate severity. Seventy-two nortriptyline and 84 fluoxetine patients completed at least 2 weeks of medication and were included in the efficacy analysis; all patients were evaluated for side effects. Average total scores on the Hamilton Rating Scale for Depression (HAM-D) for both treatment groups declined from 22-23 at baseline to 11.5 at the conclusion of the 5-week period. At Week, 5, 71% of nortriptyline patients and 65% of fluoxetine patients were much or very much improved. Fluoxetine was associated more frequently with nausea (p less than .05), while nortriptyline was associated more frequently with dry mouth (p less than .05). These results are discussed in the context of selecting between nortriptyline and fluoxetine for a particular depressed patient.

  16. Safety of fondaparinux for prevention of postoperative venous thromboembolism in urological malignancy: A prospective randomized clinical trial.

    Science.gov (United States)

    Hata, Kenichi; Kimura, Takahiro; Tsuzuki, Shunsuke; Ishii, Gen; Kido, Masahito; Yamamoto, Toshihiro; Sasaki, Hiroshi; Miki, Jun; Yamada, Hiroki; Furuta, Akira; Miki, Kenta; Egawa, Shin

    2016-11-01

    To prospectively evaluate the safety of postoperative fondaparinux in comparison with low molecular weight heparin in patients undergoing uro-oncological surgery. The present study was a prospective, single-blind, non-inferiority randomized trial. A total of 359 patients undergoing surgery for urological malignancy were enrolled from January 2011 to December 2012. A total of 298 of these patients (fondaparinux group, 152; low molecular weight heparin group, 146) were evaluable for the intention-to-treat-analysis. Patients were randomly assigned to low-dose unfractionated heparin, 5000 units twice daily until postoperative day 1 plus either fondaparinux 2.5 mg once daily or low molecular weight heparin 2000 units twice daily until postoperative day 5. The primary end-point was postoperative bleeding as by independent review, and the study was powered to show the non-inferiority of fondaparinux versus low molecular weight heparin. The other adverse events were evaluated. D-dimer and soluble fibrin monomer complex levels were measured perioperatively. Bleeding occurred in 21 patients (12 in the fondaparinux group and 9 in low molecular weight heparin group, respectively). No significant differences were detected in the incidence of postoperative bleeding and the other adverse events between the two groups. The D-dimer was elevated on postoperative day 1 in one patient (16.6 μg/mL). In another patient, the soluble fibrin monomer complex was elevated (109 μg/mL). Fondaparinux is non-inferior to low molecular weight heparin with respect to risk of bleeding. The favorable safety profile of fondparinux supports its prophylactic use as an alternative to low molecular weight heparin after surgery for urological malignancy. © 2016 The Japanese Urological Association.

  17. [Postoperative Adjuvant Chemotherapy for Stage III Colon Cancer--Drug Selection, Tolerability, and Safety in Clinical Practice].

    Science.gov (United States)

    Okada, Kazutake; Sadahiro, Sotaro; Saito, Gota; Tanaka, Akira; Suzuki, Toshiyuki

    2016-05-01

    In the National Comprehensive Cancer Network (NCCN) guidelines, oxaliplatin (L-OHP)-based chemotherapeutic regimens, including 5-fluorouracil, Leucovorin (LV), and L-OHP (FOLFOX); capecitabine and L-OHP (CapeOX); and 5-fluorouracil, folinic acid, and L-OHP (FLOX) are designated as category 1 recommendations for postoperative adjuvant chemotherapy in Stage III colon cancer, followed by capecitabine and 5-fluorouracil plus LV as category 2A recommendations. We studied the selection of drugs for adjuvant chemotherapy and assessed the tolerability and safety of CapeOX and tegafur-uracil (UFT) plus LV (UFT/LV) in patients with Stage III colon cancer. The study group included 104 consecutive patients with Stage III colon cancer who underwent curative surgery. One patient changed hospitals immediately after surgery. Among the remaining 103 patients, 82 (80%) received adjuvant chemotherapy and 21 (20%) did not. CapeOX was administered to 32 patients (31%), UFT/LV to 49 patients (48%), and capecitabine to 1 patient (1%). In 59 patients, the treatment choice was determined according to the patient's preference; 32 patients (54%) selected CapeOX, 26 (44%) selected UFT/LV, and 1 (2%) selected no chemotherapy. The treatment completion rate was 80% for CapeOX and 84% for UFT/LV. Among patients who completed chemotherapy, dose reduction and drug withdrawal were not required in 22% of patients who received CapeOX and 80% of those who received UFT/LV. Neither CapeOX nor UFT/LV was associated with any serious adverse events. The tolerability and safety of CapeOX and UFT/LV were acceptable. However, CapeOX dose had to be carefully adjusted according to each patient's condition.

  18. What can providers learn from childhood body mass index trajectories: a study of a large, safety-net clinical population.

    Science.gov (United States)

    McCormick, Emily V; Dickinson, L Miriam; Haemer, Matthew A; Knierim, Shanna D; Hambidge, Simon J; Davidson, Arthur J

    2014-01-01

    To describe childhood weight gain using body mass index (BMI) z-score trajectories in a low-income urban safety-net population and identify among gender- and race/ethnicity-specific groups any trends for increased risk. A retrospective cohort study was conducted among 2- to 12-year-old patients (2006-2013) visiting a safety-net provider. BMI z-score trajectories were calculated overall, for gender- and race/ethnicity-specific groups, and for peak BMI percentile subgroups to describe weight gain longitudinally. From 2006 to 2013, a total of 26,234 eligible children were followed for an average of 3.7 years. At baseline (mean age, 4.2 years), 74% of patients were at a normal weight compared to 65% at most recent observation (mean age, 7.8 years). All gender and race/ethnicity subgroups showed increasing average BMI z-scores during childhood. Children consistently under the 50th percentile and those of white race had the most stable BMI z-score trajectories. BMI z-score increased with increasing age in all subgroups. Hispanic boys and black girls had the most significant increase in BMI z-score during this observation period. Children observed in early childhood and whose BMI exceeded the 95th percentile at any time were often already overweight (20%) or obese (36%) by 3 years of age. The entire population demonstrated an upward trend in BMI z-score trajectory. This trend was most notable among black girls and Hispanic boys. Many obese children were already overweight by age 3, and persistence of obesity after 3 years of age was high, suggesting that intervention before age 3 may be essential to curbing unhealthy weight trajectories. Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  19. Safety and Efficacy of Trifluridine/Tipiracil Monotherapy in Clinical Practice for Patients With Metastatic Colorectal Cancer: Experience at a Single Institution.

    Science.gov (United States)

    Kotani, Daisuke; Shitara, Kohei; Kawazoe, Akihito; Fukuoka, Shota; Kuboki, Yasutoshi; Bando, Hideaki; Okamoto, Wataru; Kojima, Takashi; Doi, Toshihiko; Ohtsu, Atsushi; Yoshino, Takayuki

    2016-09-01

    The combination drug TAS-102 is a novel oral nucleoside antitumor agent containing trifluridine and tipiracil hydrochloride, which prevents the degradation of trifluridine. The global phase III RECOURSE trial (Study of TAS-102 in Patients With Metastatic Colorectal Cancer Refractory to Standard Chemotherapies) demonstrated that TAS-102 prolonged the survival of patients with metastatic colorectal cancer (mCRC) whose disease progressed after standard therapies. TAS-102 was first approved in Japan in March 2014, and little is known about its safety and efficacy in clinical practice, especially for mCRC patients with previous regorafenib treatment. We investigated the safety and efficacy of TAS-102 monotherapy in clinical practice for patients with mCRC refractory to standard therapies who were treated from May 2014 to January 2015. A total of 55 patients received TAS-102. The Eastern Cooperative Oncology Group performance status was 0, 1, and 2 in 41.8%, 47.3%, and 10.9% of patients. Of the 55 patients, 32 (58.2%) had been treated with regorafenib before receiving TAS-102. The median progression-free survival and overall survival was 2.0 months and 5.3 months, respectively. Emergency hospitalization was required for 23.6% of the patients during TAS-102 treatment, although most of the events (76.9%) were disease-related. The most common grade 3 or 4 adverse events were neutropenia (41.8%), leukopenia (27.2%), anemia (23.6%), febrile neutropenia (5.5%), and fatigue (3.6%). The frequency of grade ≥ 3 events was not significantly increased among the patients who had compared with those who had not received regorafenib. The progression-free survival (median 2.1 vs. 2.0 months) and overall survival (median 6.2 vs. 4.7 months) were similar for the 2 subgroups. The safety and efficacy of TAS-102 monotherapy in clinical practice were maintained, irrespective of previous regorafenib treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Vernakalant (RSD1235) in the management of atrial fibrillation: a review of pharmacological properties, clinical efficacy and safety

    DEFF Research Database (Denmark)

    Weeke, Peter; Andersson, Charlotte; Brendorp, Bente;

    2008-01-01

    Vernakalant (RSD1235) is a novel antiarrhythmic agent for conversion of rapid onset atrial fibrillation (AF). It is an atria-selective multichannel ion blocker (blocks I(Kur), I(Na), I(Ca, L), I(to) and I(Kr)), with a small effect on ventricular repolarization. In clinical Phase II and III studie...

  1. Applying the Plan-Do-Study-Act (PDSA) approach to a large pragmatic study involving safety net clinics.

    Science.gov (United States)

    Coury, Jennifer; Schneider, Jennifer L; Rivelli, Jennifer S; Petrik, Amanda F; Seibel, Evelyn; D'Agostini, Brieshon; Taplin, Stephen H; Green, Beverly B; Coronado, Gloria D

    2017-06-19

    The Plan-Do-Study-Act (PDSA) cycle is a commonly used improvement process in health care settings, although its documented use in pragmatic clinical research is rare. A recent pragmatic clinical research study, called the Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC), used this process to optimize the research implementation of an automated colon cancer screening outreach program in intervention clinics. We describe the process of using this PDSA approach, the selection of PDSA topics by clinic leaders, and project leaders' reactions to using PDSA in pragmatic research. STOP CRC is a cluster-randomized pragmatic study that aims to test the effectiveness of a direct-mail fecal immunochemical testing (FIT) program involving eight Federally Qualified Health Centers in Oregon and California. We and a practice improvement specialist trained in the PDSA process delivered structured presentations to leaders of these centers; the presentations addressed how to apply the PDSA process to improve implementation of a mailed outreach program offering colorectal cancer screening through FIT tests. Center leaders submitted PDSA plans and delivered reports via webinar at quarterly meetings of the project's advisory board. Project staff conducted one-on-one, 45-min interviews with project leads from each health center to assess the reaction to and value of the PDSA process in supporting the implementation of STOP CRC. Clinic-selected PDSA activities included refining the intervention staffing model, improving outreach materials, and changing workflow steps. Common benefits of using PDSA cycles in pragmatic research were that it provided a structure for staff to focus on improving the program and it allowed staff to test the change they wanted to see. A commonly reported challenge was measuring the success of the PDSA process with the available electronic medical record tools. Understanding how the PDSA process can be applied to pragmatic

  2. A randomized, double-blind, placebo-controlled clinical study to assess safety and clinical activity of OTO-104 given as a single intratympanic injection in patients with unilateral Ménière's disease.

    Science.gov (United States)

    Lambert, Paul R; Nguyen, Shaun; Maxwell, Kenneth S; Tucci, Debara L; Lustig, Lawrence R; Fletcher, Malcolm; Bear, Moraye; Lebel, Carl

    2012-09-01

    To evaluate the safety, tolerability, and clinical activity of a single intratympanic injection of OTO-104, sustained-release dexamethasone formulation, in patients with unilateral Ménière's disease. Prospective, double-blind, randomized, placebo-controlled, dose-escalation study of 16 weeks' (4-wk lead-in before dosing; 12-wk follow-up after dosing) duration for each patient. Fifteen centers (physician offices and academic or tertiary referral centers). Forty-four patients aged 22 to 75 years. Single intratympanic injection of OTO-104 (3 or 12 mg) or placebo. Safety and tolerability were assessed via adverse event reports, otoscopy, audiometry, and tympanometry. Clinical activity was assessed primarily as changes in vertigo frequency. OTO-104 was well tolerated, with no impact on hearing function. Plasma levels were observed in a few patients and were barely quantifiable. The most frequently reported adverse event considered related to investigational product was tympanic membrane perforation; no clinical sequelae were associated with these perforations and all were graded mild or moderate. At Month 3, the observed mean ± standard deviation (SD) change from baseline in vertigo frequency was -0.124 ± 0.153, -0.147 ± 0.166, and -0.211 ± 0.153 for the placebo, 3-mg OTO-104, and 12-mg OTO-104 groups, respectively; corresponding to 42%, 56% and 73% reductions in vertigo frequency, respectively. Similar results were observed for tinnitus, measured by the Tinnitus Handicap Inventory (THI-25). OTO-104 was safe and well tolerated. Although the sample size was small, the data suggest 12 mg of OTO-104 was associated with a clinically meaningful reduction in vertigo frequency compared to placebo 3 months after treatment.

  3. Results from a large multinational clinical trial (guardian™3) using prophylactic treatment with turoctocog alfa in paediatric patients with severe haemophilia A: safety, efficacy and pharmacokinetics.

    Science.gov (United States)

    Kulkarni, R; Karim, F A; Glamocanin, S; Janic, D; Vdovin, V; Ozelo, M; Rageliene, L; Carboni, E; Laguna, P; Dobaczewski, G; Seremetis, S; Lindblom, A; Santagostino, E

    2013-09-01

    Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open-label, non-controlled trial investigated the safety, efficacy and pharmacokinetics (PK) of turoctocog alfa, a new rFVIII product, in a paediatric population. The primary objective was to evaluate safety. A total of 31 younger children (0-5 years) and 32 older children (6-11 years), with ≥ 50 exposure days to any factor VIII (FVIII) product and no history of inhibitors, received prophylaxis with turoctocog alfa (25-50 IU kg(-1) every second day or 25-60 IU kg(-1) three times weekly). PK assessments of turoctocog alfa and the patients' previous FVIII product were performed in 28 patients. Mean exposure to turoctocog alfa was 60 exposure days per patient. This corresponds to approximately 4.5 months in the trial. None of the patients developed inhibitors (≥ 0.6 BU) and no safety concerns were raised. A total of 120 bleeding episodes (95%) were controlled with 1-2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as 'excellent' or 'good' haemostatic response) for treatment of bleeding episodes was 92%. Overall, the median annualized bleeding rate was 3.0 (interquartile range: 8.5) bleeds patient(-1) year(-1) . PK parameters were comparable between the two age groups. In conclusion, the present large global clinical trial showed that turoctocog alfa was safe, effective in treatment of bleeding episodes and had a prophylactic effect in paediatric patients. © 2013 John Wiley & Sons Ltd.

  4. Effect of crisis response planning vs. contracts for safety on suicide risk in U.S. Army Soldiers: A randomized clinical trial.

    Science.gov (United States)

    Bryan, Craig J; Mintz, Jim; Clemans, Tracy A; Leeson, Bruce; Burch, T Scott; Williams, Sean R; Maney, Emily; Rudd, M David

    2017-04-01

    To evaluate the effectiveness of crisis response planning for the prevention of suicide attempts. Randomized clinical trial of active duty Army Soldiers (N=97) at Fort Carson, Colorado, presenting for an emergency behavioral health appointment. Participants were randomly assigned to receive a contract for safety, a standard crisis response plan, or an enhanced crisis response plan. Incidence of suicide attempts during follow-up was assessed with the Suicide Attempt Self-Injury Interview. Inclusion criteria were the presence of suicidal ideation during the past week and/or a lifetime history of suicide attempt. Exclusion criteria were the presence of a medical condition that precluded informed consent (e.g., active psychosis, mania). Survival curve analyses were used to determine efficacy on time to first suicide attempt. Longitudinal mixed effects models were used to determine efficacy on severity of suicide ideation and follow-up mental health care utilization. From baseline to the 6-month follow-up, 3 participants receiving a crisis response plan (estimated proportion: 5%) and 5 participants receiving a contract for safety (estimated proportion: 19%) attempted suicide (log-rank χ(2)(1)=4.85, p=0.028; hazard ratio=0.24, 95% CI=0.06-0.96), suggesting a 76% reduction in suicide attempts. Crisis response planning was associated with significantly faster decline in suicide ideation (F(3,195)=18.64, pcrisis response plan conditions. Crisis response planning was more effective than a contract for safety in preventing suicide attempts, resolving suicide ideation, and reducing inpatient hospitalization among high-risk active duty Soldiers. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Safety data on 19 vehicles for use in 1 month oral rodent pre-clinical studies: administration of hydroxypropyl-ß-cyclodextrin causes renal toxicity.

    Science.gov (United States)

    Healing, Guy; Sulemann, Tabassum; Cotton, Peter; Harris, Jayne; Hargreaves, Adam; Finney, Rowena; Kirk, Sarah; Schramm, Carolin; Garner, Clare; Pivette, Perrine; Burdett, Lisa

    2016-01-01

    Potential new drugs are assessed in pre-clinical in vivo studies to determine their safety profiles. The drugs are formulated in vehicles suitable for the route of administration and the physicochemical properties of the drug, aiming to achieve optimal exposure in the test species. The availability of safety data on vehicles is often limited (incomplete data, access restricted/private databases). Nineteen potentially useful vehicles that contained new and/or increased concentrations of excipients and for which little safety data have been published were tested. Vehicles were dosed orally once daily to HanWistar rats for a minimum of 28 days and a wide range of toxicological parameters were assessed. Only 30% (w/v) hydroxypropyl-ß-cyclodextrin was found unsuitable owing to effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased salivation and hence this vehicle should be used with caution. As 40% (v/v) tetraethylene glycol affected urinary parameters, its use should be carefully considered, particularly for compounds suspected to impact the renal system and studies longer than 1 month. There were no toxicologically significant findings with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v) Miglyol®812, 20% (w/v) Kolliphor®RH40, 10% (w/v) Poloxamer 407, 5% (w/v) polyvinylpyrrolidone K30 or 10% (v/v) Labrafil®M1944. All other vehicles tested caused isolated or low magnitude effects which would not prevent their use. The aim of sharing these data, including adverse findings, is to provide meaningful information for vehicle selection, thereby avoiding repetition of animal experimentation.

  6. Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Guo Hua

    2010-04-01

    Full Text Available Abstract Background In a previous pooled analysis of 12 double-blind clinical studies that included data on 6,139 patients with type 2 diabetes, treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4 inhibitor, was shown to be generally well tolerated compared with treatment with control agents. As clinical development of sitagliptin continues, additional studies have been completed, and more patients have been exposed to sitagliptin. The purpose of the present analysis is to update the safety and tolerability assessment of sitagliptin by pooling data from 19 double-blind clinical studies. Methods The present analysis included data from 10,246 patients with type 2 diabetes who received either sitagliptin 100 mg/day (N = 5,429; sitagliptin group or a comparator agent (placebo or an active comparator (N = 4,817; non-exposed group. The 19 studies from which this pooled population was drawn represent the double-blind, randomized studies that included patients treated with the usual clinical dose of sitagliptin (100 mg/day for between 12 weeks and 2 years and for which results were available as of July 2009. These 19 studies assessed sitagliptin taken as monotherapy, initial combination therapy with metformin or pioglitazone, or as add-on combination therapy with other antihyperglycemic agents (metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin. Patients in the non-exposed group were taking placebo, metformin, pioglitazone, a sulfonylurea ± metformin, insulin ± metformin, or rosiglitazone + metformin. The analysis used patient-level data from each study to evaluate between-group differences in the exposure-adjusted incidence rates of adverse events. Results Summary measures of overall adverse events were similar in the sitagliptin and non-exposed groups, except for an increased incidence of drug-related adverse events in the non-exposed group. Incidence rates of specific adverse events were

  7. Renal safety in pediatric imaging: randomized, double-blind phase IV clinical trial of iobitridol 300 versus iodixanol 270 in multidetector CT

    Energy Technology Data Exchange (ETDEWEB)

    Zo' o, Martin; Dosseur, Patrick Le [CHU Charles Nicolle, Radiology Department, Rouen (France); Hoermann, Marcus; Balassy, Csilla [AKH, Radiology Department, Vienna (Austria); Brunelle, Francis [Necker Hospital, Radiopediatry Department, Paris (France); Azoulay, Robin [Robert Debre Hospital, Radiopediatry Department, Paris (France); Pariente, Daniele [Kremlin-Bicetre Hospital, Radiopediatry Department, Kremlin-Bicetre (France); Panuel, Michel [Nord Hospital, Medical Imaging Department, Marseille (France)

    2011-11-15

    It is debated whether iso-osmolar and low-osmolar contrast media are associated with different incidences of contrast medium-induced nephropathy (CIN) in patients with renal insufficiency. To compare the incidence of CIN in children undergoing contrast-enhanced multidetector computer tomography (MDCT) with intravenous injection of low-osmolar (iobitridol, Xenetix {sup registered} 300) or an iso-osmolar (iodixanol, Visipaque {sup registered} 270) iodinated contrast medium. One hundred forty-six children with normal renal function were included in this multicenter trial and underwent contrast-enhanced MDCT. The primary endpoint was the relative change in creatinine clearance from 48 h pre- to 72 h postcontrast medium administration using a noninferiority analysis in the intent-to-treat (ITT, n = 128) and per protocol (n = 68) populations. Secondary endpoints were incidence of CIN, global image quality, diagnostic efficacy and clinical safety. In the ITT population, the noninferiority of iobitridol over iodixanol was demonstrated. CIN incidence was 4.8% (three cases) with iobitridol and 10.6% (seven cases) with iodixanol (not significant). No statistically significant differences were observed for the secondary endpoints. Comparable satisfactory safety profiles were confirmed for both contrast media, with no significant difference in the incidence of CIN in children with normal renal function. (orig.)

  8. Decreasing Turnaround Time and Increasing Patient Satisfaction in a Safety Net Hospital-Based Pediatrics Clinic Using Lean Six Sigma Methodologies.

    Science.gov (United States)

    Jayasinha, Yasangi

    2016-01-01

    Increasingly, health care quality indicators are focusing on patient-centeredness as an indicator of performance. The National Quality Forum lists assessment of patient experience, often conducted using patient surveys, as a top priority. We developed a patient-reported time stamp data collection tool that was used to collect cycle times in a safety net hospital-based outpatient pediatrics clinic. Data were collected using patient-reported survey to obtain cycle times in Pediatric clinic, as well as qualitative and quantitative patient satisfaction data. Several rapid-cycle improvements were performed using Lean Six Sigma methodologies to reduce cycle time by eliminating waste and revise unnecessary processes to improve operational effectiveness and patient and staff satisfaction. A total of 94 surveys were collected and revealed average cycle time of 113 minutes. Our measured patient satisfaction rating was 87%. Discharge and check-in processes were identified as the least efficient and were targeted for intervention. Following implementation, the overall cycle time was decreased from 113 to 90 minutes. Patient satisfaction ratings increased from 87% to 95%. We demonstrate that using Lean Six Sigma tools can be invaluable to clinical restructuring and redesign and results in measurable, improved outcomes in care delivery.

  9. Safety culture

    Energy Technology Data Exchange (ETDEWEB)

    Keen, L.J. [Canadian Nuclear Safety Commission, Ottawa, Ontario (Canada)

    2003-07-01

    Safety culture has become a topic of increasing interest for industry and regulators as issues are raised on safety problems around the world. The keys to safety culture are organizational effectiveness, effective communications, organizational learning, and a culture that encourages the identification and resolution of safety issues. The necessity of a strong safety culture places an onus on all of us to continually question whether the safety measures already in place are sufficient, and are being applied. (author)

  10. Clinical Research of the Efficacy and the Safety of Dioscoreae Rhizoma (Sanyak Pharmacopuncture Therapy for Peripheral Facial Paralysis Patients

    Directory of Open Access Journals (Sweden)

    Sung In-Soo

    2012-12-01

    Full Text Available Objectives: The aim of this study is to evaluate the efficacy and the safety of Sanyak pharmacopuncture therapy for the treatment of peripheral facial paralysis patients. Methods: This study was a retrospective investigation of a total of 70 patients who were inpatients of the Oriental Hospital of Daejeon University between January 1, 2011, and May 31, 2012, and who were diagnosed as having peripheral facial paralysis by physical examination, the patients received three different interventions. Eleven (11 patients were treated with acupuncture and alcohol Dioscorea rhizoma pharmacopuncture (ADG, 25 patients with acupuncture and distillation Dioscorea rhizoma pharmacopuncture (DDG, and 34 patients with acupuncture and non-Dioscorea rhizoma pharmacopuncture (NDG. The resulting data were analyzed. Results: The changed H-B grades indicated significant improvements in all three groups, and the ADG and the DDG groups showed significant results after two weeks of treatment when compared to the NDG group. The changed y-Scores indicated significant improvements in all three groups, and the ADG group showed significant results after 10 and 15 days of treatment when compared to the NDG group. Dioscorea rhizoma pharmacopuncture may be safe for the human body because in most cases, the only abnormal finding was the pain could by the application of pharmacopuncture. Conclusions: The results of this study suggest that Oriental medical treatment with dioscoreae Rhizoma (Sanyak pharmacopuncture complex therapy may be effective and safe in patient with peripheral facial paralysis

  11. Safety and tolerability of Panax ginseng root extract: a randomized, placebo-controlled, clinical trial in healthy Korean volunteers.

    Science.gov (United States)

    Lee, Nam-Hun; Yoo, Sa-Ra; Kim, Hyeong-Geug; Cho, Jung-Hyo; Son, Chang Gue

    2012-11-01

    Panax ginseng has been extensively used as an adaptogen and is among the top 10 selling herbal supplements in the United States over the past decade. However, there have been few reports about the toxicity of P. ginseng in human studies. Given the lack of toxicological studies in human, this study investigated whether P. ginseng administration causes any noticeable toxic effects in healthy volunteers. This study was designed as a randomized, double-blind, placebo-controlled, and parallel group trial in healthy volunteers. The subjects were required to be healthy, free from any significant disease, as assessed at screening by physical examination, medical history, and laboratory (hematological and biochemical) tests. Eligible subjects received P. ginseng extract (1 g/day or 2 g/day) or placebo over a 4-week period. Although mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation, were reported in both P. ginseng and placebo group, no serious untoward reactions were reported following P. ginseng administration. Nonsignificant changes were observed in hematological and biochemical tests. P. ginseng administration for 4 weeks was shown to be safe, tolerable, and free of any untoward toxic effect in healthy male and female volunteers. Future results from ongoing multicenter collaborative efforts to evaluate short- and long-term effects of P. ginseng may contribute to our current understanding of safety and tolerability of this herbal product.

  12. Safety and Tolerability of Panax ginseng Root Extract: A Randomized, Placebo-Controlled, Clinical Trial in Healthy Korean Volunteers

    Science.gov (United States)

    Lee, Nam-Hun; Yoo, Sa-Ra; Kim, Hyeong-Geug; Cho, Jung-Hyo

    2012-01-01

    Abstract Objectives Panax ginseng has been extensively used as an adaptogen and is among the top 10 selling herbal supplements in the United States over the past decade. However, there have been few reports about the toxicity of P. ginseng in human studies. Given the lack of toxicological studies in human, this study investigated whether P. ginseng administration causes any noticeable toxic effects in healthy volunteers. Methods This study was designed as a randomized, double-blind, placebo-controlled, and parallel group trial in healthy volunteers. The subjects were required to be healthy, free from any significant disease, as assessed at screening by physical examination, medical history, and laboratory (hematological and biochemical) tests. Eligible subjects received P. ginseng extract (1 g/day or 2 g/day) or placebo over a 4-week period. Results Although mild adverse events, such as dyspepsia, hot flash, insomnia, and constipation, were reported in both P. ginseng and placebo group, no serious untoward reactions were reported following P. ginseng administration. Nonsignificant changes were observed in hematological and biochemical tests. Conclusions P. ginseng administration for 4 weeks was shown to be safe, tolerable, and free of any untoward toxic effect in healthy male and female volunteers. Future results from ongoing multicenter collaborative efforts to evaluate short- and long-term effects of P. ginseng may contribute to our current understanding of safety and tolerability of this herbal product. PMID:22909282

  13. Advances in levodopa therapy for Parkinson disease: Review of RYTARY (carbidopa and levodopa) clinical efficacy and safety.

    Science.gov (United States)

    Dhall, Rohit; Kreitzman, David L

    2016-04-01

    Parkinson disease (PD) is a slowly progressive, incurable, neurodegenerative disorder with progressive motor symptoms that can be managed with treatments. Levodopa is generally recognized as the most effective and widely used treatment for PD. It improves function and quality of life, morbidity, and mortality, and therefore reduces individual and societal costs. Levodopa has a relatively short half-life, however, and is quickly metabolized in the plasma, leading to fluctuations, including wearing-off of effect and inconsistent symptomatic relief as well as development of dyskinesias, with both wearing off and dyskinesias worsening with advancing disease. Immediate-release and controlled-release formulations have been used with success, but motor fluctuations remain a problem. RYTARY (levodopa and carbidopa, IPX066) is an oral extended-release therapy composed of carbidopa-levodopa microbeads designed to dissolve at various rates that allows for quick absorption and sustained levodopa release over an extended period. In development studies, RYTARY improved symptoms in patients with both early and advanced PD and offered significantly improved Unified Parkinson Disease Rating Scale scores and "on" times, without worsening troublesome dyskinesias when compared to other levodopa formulations. Tolerability and safety were comparable to other formulations. This section reviews the data that support the use of RYTARY in the treatment of PD.

  14. Clinical research of the efficacy and the safety of dioscoreae rhizoma (sanyak) pharmacopuncture therapy for peripheral facial paralysis patients.

    Science.gov (United States)

    Sung, In-Soo; Hong, Kwon-Eui; Kim, Min-Jung; Song, In

    2012-12-01

    The aim of this study is to evaluate the efficacy and the safety of Sanyak pharmacopuncture therapy for the treatment of peripheral facial paralysis patients. This study was a retrospective investigation of a total of 70 patients who were inpatients of the Oriental Hospital of Daejeon University between January 1, 2011, and May 31, 2012, and who were diagnosed as having peripheral facial paralysis by physical examination, the patients received three different interventions. Eleven (11) patients were treated with acupuncture and alcohol Dioscorea rhizoma pharmacopuncture (ADG), 25 patients with acupuncture and distillation Dioscorea rhizoma pharmacopuncture (DDG), and 34 patients with acupuncture and non-Dioscorea rhizoma pharmacopuncture (NDG). The resulting data were analyzed. The changed H-B grades indicated significant improvements in all three groups, and the ADG and the DDG groups showed significant results after two weeks of treatment when compared to the NDG group. The changed y-Scores indicated significant improvements in all three groups, and the ADG group showed significant results after 10 and 15 days of treatment when compared to the NDG group. Dioscorea rhizoma pharmacopuncture may be safe for the human body because in most cases, the only abnormal finding was the pain could by the application of pharmacopuncture. The results of this study suggest that Oriental medical treatment with dioscoreae Rhizoma (Sanyak) pharmacopuncture complex therapy may be effective and safe in patient with peripheral facial paralysis.

  15. CLINICAL EFFECTIVENESS AND SAFETY OF IVABRADINE USE IN PATIENTS WITH UNSTABLE ANGINA AND DIABETES MELLITUS TYPE 2

    Directory of Open Access Journals (Sweden)

    A. I. Kondratiev

    2011-01-01

    Full Text Available Aim – to estimate the clinical and pharmacological effects of ivabradine in complex treatment of patients with acute coronary syndrome anddiabetes mellitus type 2 (DM 2.Materials and methods. The study included 36 patients with acute coronary insufficiency (unstable angina and acute left ventricular failure(Killip class I–III during concomitant type 2 diabetes.Results. Prescribing ivabradine in treatment of unstable angina pectoris complicated by type 2 diabetes led to decrease in clinical symptoms,heart rate and reduce in number of myocardial ischemia episodes. Patients treated with ivabradine, showed a significant tendency to increase left ventricular ejection fraction (12.3 %. Mo adverse reactions were recorded, including hypotensive complications.Conclusion. Ivabradine therapy was characterized by high ischemic and antianginal efficacy, good tolerability, did not lead to the developmentof tolerance and was not accompanied by the appearance of withdrawal syndrome.

  16. CLINICAL EFFECTIVENESS AND SAFETY OF IVABRADINE USE IN PATIENTS WITH UNSTABLE ANGINA AND DIABETES MELLITUS TYPE 2

    Directory of Open Access Journals (Sweden)

    A. I. Kondratiev

    2014-07-01

    Full Text Available Aim – to estimate the clinical and pharmacological effects of ivabradine in complex treatment of patients with acute coronary syndrome anddiabetes mellitus type 2 (DM 2.Materials and methods. The study included 36 patients with acute coronary insufficiency (unstable angina and acute left ventricular failure(Killip class I–III during concomitant type 2 diabetes.Results. Prescribing ivabradine in treatment of unstable angina pectoris complicated by type 2 diabetes led to decrease in clinical symptoms,heart rate and reduce in number of myocardial ischemia episodes. Patients treated with ivabradine, showed a significant tendency to increase left ventricular ejection fraction (12.3 %. Mo adverse reactions were recorded, including hypotensive complications.Conclusion. Ivabradine therapy was characterized by high ischemic and antianginal efficacy, good tolerability, did not lead to the developmentof tolerance and was not accompanied by the appearance of withdrawal syndrome.

  17. Efficacy and safety of entecavir treatment in a heterogeneous CHB population from a ‘real-world’ clinical practice setting in China.

    Science.gov (United States)

    Hou, J-L; Jia, J-D; Wei, L; Zhao, W; Wang, Y M; Cheng, M; Tang, X; Tan, D-M; Ren, H; Tang, H; Cohen, D; Llamoso, C

    2013-11-01

    Chronic hepatitis B infection is an important cause of liver-related mortality in China. This study assessed the efficacy and safety of entecavir in a heterogeneous patient population from a ‘real-world’ clinical practice setting in China. This prospective, observational cohort provides 48-week data on 2600 patients from 50 sites in China who received entecavir (0.5 or 1.0 mg) and were assessed for virologic, serologic and biochemical responses. Patients were nucleos(t)ide-na€ıve or -experienced and had compensated or decompensated liver function. At Week 48, 1545/2424 (64%) patients with compensated liver disease and 30/44 (68%) patients with decompensated liver disease achieved HBV DNAworld’ setting, entecavir was efficacious and well tolerated throughout 48 weeks in a heterogeneous Chinese CHB population.

  18. Reducing wound pain in venous leg ulcers with Biatain Ibu: A randomized, controlled double-blind clinical investigation on the performance and safety

    DEFF Research Database (Denmark)

    Gottrup, F.; Jorgensen, B.; Karlsmark, T.

    2008-01-01

    Six out of 10 patients with chronic wounds suffer from persistent wound pain. A multinational and multicenter randomized double-blind clinical investigation of 122 patients compared two moist wound healing dressings: a nonadhesive foam dressing with ibuprofen (62 patients randomized to Biatain Ibu...... Nonadhesive Coloplast A/S) and a nonadhesive foam without ibuprofen (60 patients to Biatain Non-Adhesive-comparator). Patients were recruited from September 2005 to April 2006. The ibuprofen foam was considered successful if the pain relief on a five-point Verbal Rating Scale was higher than the comparator...... without compromising safety including appropriate healing rate. Additional endpoints were change in persistent wound pain between dressing changes and pain at dressing change on days 1-5 (double blind) and days 43-47 (single blind). The primary response variable, persistent pain relief, was significantly...

  19. Efficacy and safety of acupuncture for chronic pain caused by gonarthrosis: A study protocol of an ongoing multi-centre randomised controlled clinical trial [ISRCTN27450856

    Directory of Open Access Journals (Sweden)

    Krämer Jürgen

    2004-03-01

    Full Text Available Abstract Background Controlled clinical trials produced contradictory results with respect to a specific analgesic effect of acupuncture. There is a lack of large multi-centre acupuncture trials. The German Acupuncture Trial represents the largest multi-centre study of acupuncture in the treatment of chronic pain caused by gonarthrosis up to now. Methods 900 patients will be randomised to three treatment arms. One group receives verum acupuncture, the second sham acupuncture, and the third conservative standard therapy. The trial protocol is described with eligibility criteria, detailed information on the treatment definition, blinding, endpoints, safety evaluation, statistical methods, sample size determination, monitoring, legal aspects, and the current status of the trial. Discussion A critical discussion is given regarding the considerations about standardisation of the acupuncture treatment, the choice of the control group, and the blinding of patients and observers.

  20. A Comparative Randomized Controlled Clinical Trial on the Effectiveness, Safety, and Tolerability of a Homeopathic Medicinal Product in Children with Sleep Disorders and Restlessness.

    Science.gov (United States)

    Jong, Miek C; Ilyenko, Lydia; Kholodova, Irina; Verwer, Cynthia; Burkart, Julia; Weber, Stephan; Keller, Thomas; Klement, Petra

    2016-01-01

    A prospective, multicenter, randomized, open-label, controlled clinical trial was performed to evaluate the effectiveness and safety of the homeopathic product ZinCyp-3-02 in children with sleep disorders for ≥ one month compared to glycine. Children ≤ six years old received either ZinCyp-3-02 (N = 89) or comparator glycine (N = 90). After treatment for 28 days, total sleep-disorder-associated complaints severity scores decreased in both groups from median 7.0 (out of maximum 11.0) points to 2.0 (ZinCyp-3-02) and 4.0 (glycine) points, respectively, with overall higher odds of showing improvement for ZinCyp-3-02 (odds ratio: 4.45 (95% CI: 2.77-7.14), p product ZinCyp-3-02 was found to be safe and superior to the comparator glycine in the treatment of sleep disorders in children.

  1. A questionnaire study regarding local anesthesia in dentistry and safety measures in dental clinics among dental students

    OpenAIRE

    オオケ, ハナコ; クドウ, マサル; シンヤ, ノボル; Hanako, OHKE; Masaru, KUDO; Noboru, SHINYA

    2005-01-01

    This reports the results of a questionnaire study of dental students on the awareness of "local anesthesia" and "use of patient monitoring systems" in dental clinics. Subjects participated in the present study included 96 sixth year dental students (D6) and 93 first year dental students (D1). The results indicate that the majority of respondents including both D6 and D1 support the notion that a "dentist" is the most suitable person to perform local anesthesia in dental treatment. With respec...

  2. Using Interactive Web-Based Screening, Brief Intervention and Referral to Treatment in an Urban, Safety-Net HIV Clinic.

    Science.gov (United States)

    Dawson Rose, Carol; Cuca, Yvette P; Kamitani, Emiko; Eng, Shannon; Zepf, Roland; Draughon, Jessica; Lum, Paula

    2015-06-01

    Substance use among people living with HIV is high, and screening, brief intervention, and referral to treatment (SBIRT) is an evidence-based approach to addressing the issue. We examined whether patients would participate in a technology-based SBIRT program in an urban HIV clinic. An SBIRT intervention was programmed into the clinic's web-based patient portal linked to their personal health record. We examined: demographic, health, HIV, and substance use characteristics of participants who completed the web-based intervention compared to those who did not. Fewer than half of the 96 participants assigned to the web-based SBIRT completed it (n = 39; 41 %). Participants who completed the web-based intervention had significantly higher amphetamine SSIS scores than those who did not complete the intervention. Participants whose substance use is more harmful may be more motivated to seek help from a variety of sources. In addition, it is important that technology-based approaches to behavioral interventions in clinics take into consideration feasibility, client knowledge, and comfort using technology.

  3. Using clinical and computer simulations to reason about the impact of context on system safety and technology-induced error.

    Science.gov (United States)

    Kushniruk, Andre W; Borycki, Elizabeth M; Anderson, James; Anderson, Marilyn; Nicoll, James; Kannry, Joseph

    2013-01-01

    This paper describes how simulations can be used to reason about the impact of user interface design features in exploring the effect of different contexts of use on the occurrence of technology-induced errors. The paper describes our approach in several phases, using an example from the analysis of technology-induced errors in medication administration. In the initial phase a clinical simulation is conducted to gather baseline data on the occurrence of technology-induced error using the technology under study. In this phase of the study, data arising from the clinical simulation are collected and then analyzed using qualitative and quantitative approaches to assess the relationship between aspects of interface design (i.e. usability problems) and rates of technology-induced error. In the next phase, the base rates for error associated with specific types of usability problems (from the initial phase) form the input into computer-based mathematical simulations. This approach links clinical simulations with computer-based simulations and demonstrates the potential impact of aspects of interface design and contextual factors upon medical error along with the implications for correcting interface design issues.

  4. Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Demarin V

    2017-02-01

    Full Text Available Vida Demarin,1,2 Vanja Bašić Kes,1 Zlatko Trkanjec,1 Mislav Budišić,1 Marija Bošnjak Pašić,3,4 Petra Črnac,5 Hrvoje Budinčević4,5 1Department of Neurology, University Hospital Center “Sestre Milosrdnice”, 2International Institute for Brain Health, 3Department of Neurology, University Hospital Center Zagreb, Zagreb, 4Department of Neurology, School of Medicine, University Josip Juraj Strossmayer, Osijek, 5Department of Neurology, Stroke and Intensive Care Unit, University Hospital “Sveti Duh”, Zagreb, Croatia Objectives: The aim of this randomized, double-blind, placebo-controlled trial was to determine the efficacy and safety of Ginkgo biloba extract in patients diagnosed with vascular cognitive impairment (VCI. Methods: A total of 90 patients (aged 67.1±8.0 years; 59 women were randomly allocated (1:1:1 to receive G. biloba 120 mg, G. biloba 60 mg, or placebo during a 6-month period. Assessment was made for efficacy indicators, including neuropsychological tests scores (Sandoz Clinical Assessment Geriatric Scale, Folstein Mini-Mental State Examination, Mattis Dementia Rating Scale, and Clinical Global Impression and transcranial Doppler ultrasound findings. Safety indicators included laboratory findings, reported adverse reactions, and clinical examination. Results: At the end of 6-month study period, G. biloba 120 and 60 mg showed a statistically significant positive effect in comparison with placebo only on the Clinical Global Impression score (2.6±0.8 vs 3.1±0.7 vs 2.8±0.7, respectively; P=0.038. The Clinical Global Impression score showed a significant deterioration from the baseline values in the placebo group (-0.3±0.5; P=0.021 as opposed to G. biloba groups. No significant differences were found in the transcranial Doppler ultrasound findings. Adverse reactions were significantly more common and serious in the placebo group (16 subjects than in either of the two G. biloba extract groups (eight and nine subjects

  5. Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Yu Chih-Chieh

    2012-05-01

    Full Text Available Abstract Background Reducing low-density lipoprotein cholesterol (LDL-C is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83 to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026 and total cholesterol (20.8% vs 12.2%, p = 0.0003. Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6% vs doubling statin (41.2%, but the difference was not statistically significant (p = 0.1675. The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327

  6. Ready-made allogeneic ABO-specific serum eye drops: production from regular male blood donors, clinical routine, safety and efficacy.

    Science.gov (United States)

    Harritshøj, Lene Holm; Nielsen, Connie; Ullum, Henrik; Hansen, Morten Bagge; Julian, Hanne Olsen

    2014-12-01

    To overcome problems and delays of the preparation of autologous serum eye drops, a production line of ABO-specific allogeneic serum eye drops from male blood donors was set up in a blood bank. Feasibility, clinical routine, safety and efficacy were evaluated in a cohort of patients with severe ocular surface disorders. Serum was derived from 450 ml whole-blood donations from regular male blood donors, produced and tested according to good manufacturing practice and legislation regulating blood products in Denmark. Serum was diluted to 20% (v/v) with NaCl 0.9%, filtered, bottled, registered and stored at -30°C in the blood bank. Upon request, frozen ABO-identical serum drops in lots of 14 bottles could be provided immediately. Safety and efficacy were evaluated in 34 patients with severe ocular surface disease refractory to conventional medical therapy. Patients were treated six times daily for minimum 2-4 weeks. Objective findings and subjective symptoms were compared between day 0 and after 4 weeks of treatment using the Wilcoxon signed-rank test. Clinically, no side-effects were observed. In total, 59% of the patients with ocular surface changes improved objectively (slit-lamp examination). Partial or full healing of corneal changes, as well as subjective relief of symptoms, was observed in 16 of 20 patients with keratoconjunctivitis sicca (p ABO-identical allogeneic serum eye drops were straightforwardly produced, quality-assured and registered as a safe standard blood product for the treatment of certain cases of severe dry eye disease. Therapeutic efficacy was comparable to previous reports on autologous serum drops. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  7. Pancreatic safety in Japanese patients with type 2 diabetes treated with once weekly dulaglutide 0.75 mg up to 52 weeks in phase 3 clinical trials.

    Science.gov (United States)

    Emoto, Masanori; Oura, Tomonori; Matsui, Akiko; Kazama, Hirotaka; Iwamoto, Noriyuki

    2017-02-27

    The effects of incretin therapies on pancreatic safety are currently being evaluated. In 3 phase 3 clinical studies of once weekly dulaglutide 0.75 mg (dulaglutide) in Japanese patients with type 2 diabetes (T2D), symptoms suggestive of acute pancreatitis as well as pancreatic enzymes were assessed and the risk of acute pancreatitis was evaluated. Patients who met any of the predefined criteria (clinical signs/symptoms of acute pancreatitis, confirmed amylase or lipase level ≥3 times the upper limit of normal [ULN], abdominal imaging of the pancreas) were adjudicated for acute pancreatitis by a blinded external committee. A total of 43 events in 40 patients (dulaglutide, 35/917 patients; liraglutide, 2/137 patients; insulin glargine, 2/180 patients; and placebo, 2/70 patients) were adjudicated (1 patient had events adjudicated during both placebo and dulaglutide treatment); 2 patients treated with dulaglutide had acute pancreatitis confirmed (2/917 [0.2%]; 2.651 patients/1,000 patient-years). One of these patients was diagnosed by the investigator with acute pancreatitis related to dulaglutide, but there was no typical abdominal pain. The event in the other patient occurred following an endoscopic ultrasound-guided fine needle aspiration. Transient increases in lipase ≥3×ULN were observed in 2% of patients in both the dulaglutide and liraglutide groups; the incidence in dulaglutide-treated patients was not significantly different from the incidences in liraglutide, placebo-, or insulin glargine-treated patients. Results of systematic assessments of pancreatic safety in 3 phase 3 studies for up to 52 weeks do not suggest an increased risk of acute pancreatitis in Japanese patients treated with dulaglutide.

  8. Safety, pharmacokinetic, and functional effects of the nogo-a monoclonal antibody in amyotrophic lateral sclerosis: a randomized, first-in-human clinical trial.

    Directory of Open Access Journals (Sweden)

    Vincent Meininger

    Full Text Available The neurite outgrowth inhibitor, Nogo-A, has been shown to be overexpressed in skeletal muscle in amyotrophic lateral sclerosis (ALS; it is both a potential biomarker and therapeutic target. We performed a double-blind, two-part, dose-escalation study, in subjects with ALS, assessing safety, pharmacokinetics (PK and functional effects of ozanezumab, a humanized monoclonal antibody against Nogo-A. In Part 1, 40 subjects were randomized (3∶1 to receive single dose intravenous ozanezumab (0.01, 0.1, 1, 5, or 15 mg/kg or placebo. In Part 2, 36 subjects were randomized (3∶1 to receive two repeat doses of intravenous ozanezumab (0.5, 2.5, or 15 mg/kg or placebo, approximately 4 weeks apart. The primary endpoints were safety and tolerability (adverse events [AEs], vital signs, electrocardiogram (ECG, and clinical laboratory tests. Secondary endpoints included PK, immunogenicity, functional endpoints (clinical and electrophysiological, and biomarker parameters. Overall, ozanezumab treatment (0.01-15 mg/kg was well tolerated. The overall incidence of AEs in the repeat dose 2.5 mg/kg and 15 mg/kg ozanezumab groups was higher than in the repeat dose placebo group and repeat dose 0.5 mg/kg ozanezumab group. The majority were considered not related to study drug by the investigators. Six serious AEs were reported in three subjects receiving ozanezumab; none were considered related to study drug. No study drug-related patterns were identified for ECG, laboratory, or vital signs parameters. One subject (repeat dose 15 mg/kg ozanezumab showed a weak, positive anti-ozanezumab-antibody result. PK results were generally consistent with monoclonal antibody treatments. No apparent treatment effects were observed for functional endpoints or muscle biomarkers. Immunohistochemical staining showed dose-dependent co-localization of ozanezumab with Nogo-A in skeletal muscle. In conclusion, single and repeat dose ozanezumab treatment was well tolerated and demonstrated

  9. Evaluation of the efficacy and safety of lanreotide in combination with targeted therapies in patients with neuroendocrine tumours in clinical practice: a retrospective cross-sectional analysis.

    Science.gov (United States)

    Capdevila, Jaume; Sevilla, Isabel; Alonso, Vicente; Antón Aparicio, Luís; Jiménez Fonseca, Paula; Grande, Enrique; Reina, Juan José; Manzano, José Luís; Alonso Lájara, Juan Domingo; Barriuso, Jorge; Castellano, Daniel; Medina, Javier; López, Carlos; Segura, Ángel; Carrera, Sergio; Crespo, Guillermo; Fuster, José; Munarriz, Javier; García Alfonso, Pilar

    2015-07-04

    Based on the mechanism of action, combining somatostatin analogues (SSAs) with mTOR inhibitors or antiangiogenic agents may provide synergistic effects for the treatment of patients with neuroendocrine tumours (NETs). Herein, we investigate the use of these treatment combinations in clinical practice. This retrospective cross-sectional analysis of patients with NETs treated with the SSA lanreotide and targeted therapies at 35 Spanish hospitals evaluated the efficacy and safety of lanreotide treatment combinations in clinical practice. The data of 159 treatment combinations with lanreotide in 133 patients was retrospectively collected. Of the 133 patients, with a median age of 59.4 (16-83) years, 70 (52.6%) patients were male, 64 (48.1%) had pancreatic NET, 23 (17.3%) had ECOG PS ≥ 2, 41 (30.8%) had functioning tumours, 63 (47.7%) underwent surgery of the primary tumour, 45 (33.8%) had received prior chemotherapy, and 115 (86.5%) had received prior SSAs. 115 patients received 1 lanreotide treatment combination and 18 patients received between 2 and 5 combinations. Lanreotide was mainly administered in combination with everolimus (73 combinations) or sunitinib (61 combinations). The probability of being progression-free was 78.5% (6 months), 68.6% (12 months) and 57.0% (18 months) for patients who only received everolimus plus lanreotide (n = 57) and 89.3% (6 months), 73.0% (12 months), and 67.4% (18 months) for patients who only received sunitinib and lanreotide (n = 50). In patients who only received everolimus plus lanreotide the median time-to-progression from the initiation of lanreotide combination treatment was 25.8 months (95% CI, 11.3, 40.3) and it had not yet been reached among the subgroup of patients only receiving sunitinib plus lanreotide. The safety profile of the combination treatment was comparable to that of the targeted agent alone. The combination of lanreotide and targeted therapies, mainly everolimus and sunitinib, is widely used in clinical

  10. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies

    Directory of Open Access Journals (Sweden)

    Zlateva Gergana

    2010-11-01

    Full Text Available Abstract Background Older patients are typically underrepresented in clinical trials of medications for chronic pain. A post hoc analysis of multiple clinical studies of pregabalin in patients with painful diabetic peripheral neuropathy (DPN or postherpetic neuralgia (PHN was conducted to evaluate the efficacy and safety of pregabalin in older patients. Methods Data from 11 double-blind, randomized, placebo-controlled clinical studies of pregabalin in patients with DPN or PHN were pooled. Efficacy outcomes included change in Daily Pain Rating Scale score, ≥30% and ≥50% responders, and endpoint pain score ≤3. Safety was based on adverse events (AEs. Primary efficacy was analyzed by analysis of covariance with terms for treatment, age category, protocol, baseline pain, and treatment-by-age category interaction. Results 2516 patients (white, n = 2344 [93.2%]; men, n = 1347 [53.5%]; PHN, n = 1003 [39.9%]; pregabalin, n = 1595 were included in the analysis. Patients were grouped by age: 18 to 64 years (n = 1236, 65 to 74 years (n = 766, and ≥75 years (n = 514. Baseline mean pain and sleep interference scores were comparable across treatment and age groups. Significant improvements in endpoint mean pain were observed for all pregabalin dosages versus placebo in all age groups (p ≤ 0.0009, except for the lowest dosage (150 mg/day in the youngest age group. Clinically meaningful pain relief, defined as ≥30% and ≥50% pain response, was observed in all age groups. The most common AEs were dizziness, somnolence, peripheral edema, asthenia, dry mouth, weight gain, and infections. The relative risks for these AEs increased with pregabalin dose, but did not appear related to older age or type of neuropathic pain. Conclusions Pregabalin (150-600 mg/day significantly reduced pain in older patients (age ≥65 years with neuropathic pain and improvements in pain were comparable to those observed in younger patients. Titration of pregabalin to the

  11. Safety and efficacy of pneumatic lithotripters versus holmium laser in management of ureteral calculi: a randomized clinical trial.

    Science.gov (United States)

    Razzaghi, Mohammad Reza; Razi, Abdollah; Mazloomfard, Mohammad Mohsen; Golmohammadi Taklimi, Amin; Valipour, Reza; Razzaghi, Zahra

    2013-01-01

    To compare efficacy and safety of holmium:YAG laser and pneumatic lithotripter in the management of ureteral stones. One hundred and twelve patients with 1 to 2 cm ureteral calculi were selected for pneumatic or holmium:YAG laser transurethral ureterolithotripsy (56 patients in each group). Ultrasonography and plain abdominal x-ray were performed for all the patients before the operation. The pneumatic lithoclast was Swiss LithoClast, while in laser lithotripsy, holmium:YAG laser frequency was used, which was usually set between 5 and 10 Hz at a power of 10 to 15 Watt. Intravenous urography was performed for all the patients at 3 months to assess functional status and to delineate the ureteral anatomy. The mean patients' age and stones' size were the same in both groups, and there were no statistical differences. Mean duration of lithotripsy was 13.7 ± 12.6 minutes in laser group and 7.9 ± 4.2 minutes in pneumatic lithotripsy group. Immediate stone-free rate was 100% and 82.1% in the laser and pneumatic groups, respectively (P = .001). Stone pushing back occurred only in 10 (17.9%) patients in pneumatic group. In terms of complications, such as perforation, mucosal injury, and bleeding, there were no differences between the two groups. No intravenous pyelography related complication was seen at 3-month follow-up. Laser lithotripsy is a superior approach for the management of upper ureteral stones of 1 to 2 cm in size due to its higher rate of stone clearance.

  12. Safety and efficacy of electrospun polycarbonate-urethane vascular graft for early hemodialysis access: first clinical results in man.

    Science.gov (United States)

    Wijeyaratne, Serosha M; Kannangara, Lushanthi

    2011-01-01

    The purpose of this study was to assess the safety and efficacy of an electrospun multilayered, self-sealing polycarbonate-urethane graft for early hemodialysis access in patients. Seventeen eligible consenting patients had a polycarbonate-urethane graft (AVflo™) implanted and followed up prospectively for 12 months or to the end of secondary patency. Performance measures included graft patency, complications, time to first cannulation, and hemostasis times after needle withdrawal. All patients were of Asian origin (mean age 57 years, range 29-78). Diabetes mellitus was the most common cause of renal failure (52.9%). There were no systemic or local reactions to the graft. Five patients (29.4%) died due to medical complications unrelated to the device. There was 1 pseudoaneurysm, 3 infected grafts that subsequently thrombosed, and 1 primary thrombosis associated with thrombophilia. One venous stenosis needed balloon angioplasty. Primary and secondary patency rates at 6 months were 72.7% and 81.8%, and at 12 months, 54.5% and 72.7%, respectively. Postimplantation vascular access needs were met entirely by the graft in every instance and prevented the need for venous catheters. Fifty-six percent were accessed within 8 days, the earliest being 48 hours. Finally, all arterial punctures and 98% of venous punctures had sealed in less than 5 minutes, with two thirds sealing off within 3 minutes of needle withdrawal. The electrospun polycarbonate-urethane graft is safe in humans, permits early access obviating the need for venous catheters, and has equivalent patency to other prosthetic grafts at 1 year.

  13. Patients’ safety: is there a systemic release of gentamicin by gentamicin-coated tibia nails in clinical use?

    Science.gov (United States)

    Moghaddam, Arash; Graeser, Viola; Westhauser, Fabian; Dapunt, Ulrike; Kamradt, Till; Woerner, Stefan M; Schmidmaier, Gerhard

    2016-01-01

    Introduction Osteitis is one of the most serious complications in orthopedic surgery. Expert Tibia Nail (ETN) PROtect™ coated with a biodegradable layer of gentamicin-laden polymer was developed for prophylaxis of osteomyelitis. In systemic administration, gentamicin has only a small therapeutic index and serious side effects; it is potentially nephrotoxic as well as ototoxic. It is not yet known if relevant gentamicin concentrations are released into the systemic circulation after implantation of gentamicin-coated nails. In order to evaluate the patients’ risks profiles and increase patient safety, we measured gentamicin levels in pre- and postoperative serum samples of patients undergoing implantation of ETN PROtect. Methods Twenty-five patients who received ETN PROtect between March 2012 and August 2014 were included in this study. Collection of blood samples occurred before the operation, at weeks 1–4, 3 and 6 months, and up to 1 year after the implantation. Measurement of gentamicin levels in serum samples was performed at the central laboratory of Heidelberg University Hospital. Additionally, laboratory parameters, C-reactive protein, leukocyte number, urea and creatinine concentrations were analyzed in routine controls before and after operating and assessed for systemic side effects. Results Over the course of this prospective observational study, we were able to determine that gentamicin-coated nails do not release gentamicin into the systemic circulation above the lowest detectable level of 0.2 mg/dL. There were slight increases in the mean inflammation and renal retention markers, but no gentamicin-associated side effects could be linked to implantation. Furthermore, no allergic reactions could be detected during our study. Conclusion Our findings suggest that there is no relevant release of gentamicin into the systemic circulation causing a systemic effect, and serious side effects due to gentamicin-coated tibia nails should not be feared

  14. Preclinical pharmacology, efficacy, and safety of varenicline in smoking cessation and clinical utility in high risk patients

    Directory of Open Access Journals (Sweden)

    Zheng-Xiong Xi

    2010-04-01

    Full Text Available Zheng-Xiong XiNational Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, USAAbstract: Smoking is still the most prominent cause of preventable premature death in the United States and an increasing cause of morbidity and mortality throughout the world. Although the current treatments such as nicotine replacement therapy (NRT and bupropion are effective, long-term abstinence rates are low. Mechanism studies suggest that the pleasurable effects of smoking are mediated predominantly by nicotine, which activates the brain reward system by activation of brain α4β2 nicotinic acetylcholine receptors (nAChRs. Varenicline is a novel α4β2 nAChR partial agonist and has been found to be even more effective than NRT or bupropion in attenuating smoking satisfaction and in relieving craving and withdrawal symptoms after abstinence. Thus, varenicline has been recently approved to be a first-line medication for smoking cessation in the United States and European countries. Varenicline is generally well tolerated in healthy adult smokers, with the most commonly reported adverse effects being nausea, insomnia, and headache. However, growing postmarketing data has linked varenicline to an increase in neuropsychiatric symptoms such as seizures, suicidal attempts, depression, and psychosis as well as serious injuries potentially relating to unconsciousness, dizziness, visual disturbances, or movement disorders. Therefore, new safety warnings are issued to certain high risk populations, such as patients with mental illness and operators of commercial vehicles and heavy machinery. In particular, pilots, air traffic controllers, truck and bus drivers have been banned from taking varenicline.Keywords: nicotine, varenicline, α4β2 nicotinic acetylcholine receptor, nAChRs, partial agonist, smoking cessation

  15. Clinical experience with the first 40 cases with femtosecond laser cataract surgery technology: safety of the learning curve

    Directory of Open Access Journals (Sweden)

    Joao Crispim

    2015-10-01

    Full Text Available ABSTRACT Objective: To evaluate the introduction of the femtosecond laser (FSL to perform the key steps of the traditional cataract surgery process and the operational difficulties and safety of this new technology during routine use in an operating room in Brazil. Methods A retrospective study was conducted using the first cases operated on at a single center using the laser platform LenSx/Alcon with a soft contact lens patient interface.All patients underwent a detailed preoperative assessment.The anterior capsulotomy, nuclear fragmentation, and corneal incisions were created with the FSL; then, the surgery was completed following the standard phacoemulsification procedure. The main outcome measurements were difficulties and complications related to the learning curve and an analysis of postoperative uncorrected distance visual acuity (UDVA. Results: Of 31 patients (40 eyes, 9 patients had FSL cataract surgery in both eyes.The mean age was 64 ± 12 years (ranging from 42 to 82, the mean cataract nuclear sclerosis was grading 2 ± 0.6 (ranging from 1 to 4, and the preoperative mean UDVA in logMAR was 0.4 ± 0.2 (ranging from 0.1 to 1.3. Anterior capsulotomy was complete in all patients, and scissors were not needed to cut off any intact portion. The postoperative corneal incisions were not completely linear and showed some irregularities. Laser phaco-fragmentation was effective, with the division of the nucleus into smaller segments easily performed before phacoemulsification.After 1 month, the postoperative mean UDVA in logMAR was 0.1 ± 0.1 (ranging from 0.0 to 0.4 (P < 0.0001. Conclusion: With increasing surgical cases and experience, the phacoemulsification steps are performed precisely and effectively with FSL pretreatment, resulting in a safe learning curve.

  16. Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized, Comparator-Controlled, International Phase 3 Clinical Trial.

    Directory of Open Access Journals (Sweden)

    Gabriele Pohlig

    2016-02-01

    Full Text Available Sleeping sickness (human African trypanosomiasis [HAT] is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days and stage 1 HAT patients (for up to 10 days, and demonstrated efficacy comparable to pentamidine.This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included. The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673.The overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to

  17. Analgesic Effects and Safety of Desmopressin, Tramadol and Indomethacin in Patients with Acute Renal Colic; A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Mehdi Shirazi

    2015-04-01

    Full Text Available Objective: To compare the efficacy of desmopressin (DDAVP, tramadol and indomethacin on pain intensity of patients with acute renal colic caused by urolithiasis. Methods: This prospective, randomized clinical trial was conducted between July 2005 and July 2006 including 120 patients (70 men and 50 women, mean age 38.2±5.8 years referring to emergency room of Shahid Faghihi hospital with renal colic caused by urolithiasis without any previous treatment. The patients were randomly assigned to three groups: group A received tramadol 50mg intramuscularly (n=40, group B received desmopressin 40 µg intranasally (n=40 and group C received indomethacin 100mg rectally (n=40. The pain was assessed both on admission and 30 minutes after the intervention. The pain intensity and the side effects were compared between two study groups. Results: There was no significant difference between two study groups regarding the baseline characteristics. The intensity of pain of presentation was almost similar in all groups. In group A, 30 patients (75%, in group B, 15 patients (37.5% and in group C, 19 patients (47.5% had complete pain relief. The pain intensity decreased significantly after the intervention within all three groups ( p<0.001. Conclusion: According to the results of the current study, rectal indomethacin, intramuscular tramadol and intranasal desmopressin are effective and safe routs of controlling pain in acute renal colic secondary to urolithiasis. Tramadol was the most effective agent in controlling the pain. Clinical Trial Registry: The current study is registered with Iranian Registry for Clinical Trials (www.irct.ir; IRCT2015030919470N18

  18. Immediate and long-term efficacy and safety of photodynamic therapy with Photolon (Fotolon): a seven-year clinical experience

    Science.gov (United States)

    Istomin, Yuri P.; Kaplan, Michael A.; Shliakhtsin, Siarhei V.; Lapzevich, Tatsiana P.; Cerkovsky, Dmitriy A.; Marchanka, Ludmila N.; Fedulov, Alexander S.; Trukhachova, Tatsiana V.

    2009-06-01

    The purpose of the present study was to summarize data on the long-term efficacy of photodynamic therapy (PDT) with Photolon in patients with malignant tumors of various types and localizations. The data obtained show that PDT with Photolon is a highly effective therapeutic modality for the treatment of skin tumors, cervical intraepithelial neoplasias, lung cancers, disseminated forms of melanoma, primary and metastatic brain tumors, several ophthalmologic diseases. This paper provides a review of most illustrative studies of the application of PDT with Photolon for the treatment of different oncological and non-oncological diseases performed in leading clinical centers of the Republic of Belarus and Russia.

  19. Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (Ferinject from clinical trial reports and published trial data

    Directory of Open Access Journals (Sweden)

    Gaskell Helen

    2011-09-01

    Full Text Available Abstract Background Recommendations given for intravenous iron treatment are typically not supported by a high level of evidence. This meta-analysis addressed this by summarising the available date from clinical trials of ferric carboxymaltose using clinical trial reports and published reports. Methods Clinical trial reports were supplemented by electronic literature searches comparing ferric carboxymaltose with active comparators or placebo. Various outcomes were sought for efficacy (attainment of normal haemoglobin (Hb, increase of Hb by a defined amount, for example, together with measures of harm, including serious adverse events and deaths. Results Fourteen studies were identified with 2,348 randomised patients exposed to ferric carboxymaltose, 832 to oral iron, 762 to placebo, and 384 to intravenous iron sucrose. Additional data were available from cohort studies. Intravenous ferric carboxymaltose was given up to the calculated iron deficit (up to 1,000 mg in one week for iron deficiency anaemia secondary to chronic kidney disease, blood loss in obstetric and gynaecological conditions, gastrointestinal disease, and other conditions like heart failure. The most common comparator was oral iron, and trials lasted 1 to 24 weeks. Intravenous ferric carboxymaltose improved mean Hb, serum ferritin, and transferrin saturation levels; the mean end-of-trial increase over oral iron was, for Hb 4.8 (95% confidence interval 3.3 to 6.3 g/L, for ferritin 163 (153 to 173 μg/L, and for transferrin saturation 5.3% (3.7 to 6.8%. Ferric carboxymaltose was significantly better than comparator in achievement of target Hb increase (number needed to treat (NNT 6.8; 5.3 to 9.7 and target Hb NNT (5.9; 4.7 to 8.1. Serious adverse events and deaths were similar in incidence in ferric carboxymaltose and comparators; rates of constipation, diarrhoea, and nausea or vomiting were lower than with oral iron. Conclusions This review examined the available trials of

  20. Comparison of Peritendinous Hyaluronan Injections Versus Extracorporeal Shock Wave Therapy in the Treatment of Painful Achilles' Tendinopathy: A Randomized Clinical Efficacy and Safety Study.

    Science.gov (United States)

    Lynen, Nils; De Vroey, Thierry; Spiegel, Imke; Van Ongeval, Frederik; Hendrickx, Niels-Jan; Stassijns, Gaëtane

    2017-01-01

    To compare the safety and efficacy of hyaluronan (HA) injections with standard extracorporeal shock wave therapy (ESWT) in the treatment of painful midportion Achilles' tendinopathy. Multinational, prospective, randomized controlled, blinded-observer trial. Ambulatory care. Adults (N=62) with Achilles' midportion tendinopathy for ≥6 weeks and a pain score of at least 40mm (Huskisson visual analog scale [VAS], 100mm) were randomized, and 59 were analyzed in the intention-to-treat data set. There were no withdrawals because of adverse effects. Two peritendinous HA injections versus 3 ESWT applications at weekly intervals. Primary efficacy criterion was changed from the Victorian Institute of Sports Assessment-Achilles' questionnaire (VISA-A) score to the percent change in pain (VAS) at 3 months posttreatment, compared with baseline values. Main secondary parameters were VISA-A, Clinical Global Impression (CGI), and clinical parameters. HA treatment provided a clinically relevant improvement in Achilles' midportion tendinopathy. A large superiority of the HA group, compared with ESWT application, was observed for percent change in pain (VAS), and this superiority was proven to be statistically significant (Mann-Whitney statistic [MW]=.7507 with P=.0030 lower than required α=.025 significance level 1-sided; Mann-Whitney U test) at 3 months posttreatment. Similar findings for HA were also observed at 4 weeks (MW=.6425, P=.0304) and 6 months (MW=.7172, P=.0018). Advantage of HA treatment was confirmed by VISA-A questionnaire, CGI, and clinical parameters. Ten adverse events, 4 in the HA group and 6 in the ESWT group, were reported, but none were classified as serious. Two peritendinous HA injections showed greater treatment success in Achilles' midportion tendinopathy compared with standard ESWT. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  1. Improving immunogenicity, efficacy and safety of vaccines through innovation in clinical assay development and trial design: the Phacilitate Vaccine Forum, Washington D.C. 2011.

    Science.gov (United States)

    Moldovan, Ioana R; Tary-Lehmann, Magdalena

    2011-06-01

    The 9th Annual Vaccine Forum organized by Phacilitate in Washington D.C. 2011 brought together 50+ senior level speakers and over 400 participants representing all the key stakeholders concerning vaccines. The main focus of the meeting was to define priorities in the global vaccines sector from funding to manufacturing and evaluation of vaccine efficacy. A special session was devoted to improving immunogenicity, efficacy and safety of vaccines through innovation in clinical assay development and trial design. The current regulatory approach to clinical assay specification, validation and standardization that enable more direct comparisons of efficacy between trials was illustrated by the success in meningococcal vaccine development. The industry approach to validation strategies was exemplified by a new serologic test used on the diagnostic of pneumococcal pneumonia. The application of the Animal Rule to bridge clinical and non-clinical studies in botulism has allowed significant progress in developing one of the first vaccines to seek approval under the FDA Animal Efficacy Rule. An example of pushing the boundaries in the correlation of immunological responses and efficacy points was represented by a recent cell-based influenza vaccine for which the same correlates of protection apply as for the traditional, egg-based flue vaccine. In the field of HIV phase 2b studies are underway, based on promising results obtained with some vaccine candidates. The conclusion of this session was that creativity in vaccine design and evaluation is beneficial and can lead to innovative new vaccine designs as well as to validated assays to assess vaccine efficacy.

  2. Cardiac safety of tiotropium in patients with COPD: a combined analysis of Holter-ECG data from four randomised clinical trials.

    Science.gov (United States)

    Hohlfeld, J M; Furtwaengler, A; Könen-Bergmann, M; Wallenstein, G; Walter, B; Bateman, E D

    2015-01-01

    Tiotropium is generally well tolerated; however, there has been debate whether antimuscarinics, particularly tiotropium administered via Respimat(®) Soft Mist(™) Inhaler, may induce cardiac arrhythmias in a vulnerable subpopulation with cardiovascular comorbidity. The aim of this study was to provide evidence of the cardiac safety of tiotropium maintenance therapy. Combined analysis of Holter electrocardiogram (ECG) data from clinical trials of tiotropium in chronic obstructive pulmonary disease (COPD). Trials in the Boehringer Ingelheim clinical trials database conducted between 2003 and 2012, involving tiotropium HandiHaler(®) 18 μg and/or tiotropium Respimat(®) (1.25-, 2.5-, 5.0- and 10-μg doses) were reviewed. All trials involving Holter-ECG monitoring during this period were included in the analysis. Men and women aged ≥ 40 years with a smoking history of ≥ 10 pack-years, and a clinical diagnosis of COPD were included. Holter ECGs were evaluated for heart rate (HR), supraventricular premature beats (SVPBs), ventricular premature beats (VPBs) and pauses. Quantitative and categorical end-points were derived for each of the Holter monitoring days. Four trials (n = 727) were included in the analysis. Respimat(®) (1.25-10 μg) or HandiHaler(®) (18 μg) was not associated with changes in HR, SVPBs, VPBs and pauses compared with placebo or the pretreatment baseline period. In terms of cardiac arrhythmia end-points, there was no evidence for an exposure-effect relationship. In this analysis, tiotropium maintenance therapy administered using Respimat(®) (1.25-10 μg) or HandiHaler(®) (18 μg) once daily for periods of up to 48 weeks was well tolerated with no increased risk of cardiac arrhythmia in patients with COPD. © 2014 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

  3. Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man.

    Science.gov (United States)

    Youssef, Nagy A; Sidhom, Emad

    2017-11-01

    Current pulse amplitude used in clinical ECT may be higher than needed. Reducing pulse amplitude may improve focality of the electric field and thus cognitive adverse effects. Here we examine the feasibility, safety, and whether Low Pulse Amplitude Seizure Therapy (LAP-ST, 0.5-0.6A) minimizes cognitive adverse effects while retaining efficacy. Patients with treatment-resistant primary mood (depressive episodes) or psychotic disorders who were clinically indicated to undergo ECT were offered to be enrolled in an open-label study. The study consisted of a full acute course of LAP-ST under standard anesthesia and muscle relaxation. The primary outcome was feasibility of seizure induction. Clinical outcome measures were: time to reorientation (TRO), Mini Mental State Examination, Montgomery Aberg Depression Scale, and Brief Psychiatric Rating Scale, and Clinical Global Impression Scale. Twenty-two patients consented for enrollment in the study. LAP-ST was feasible, and all patients had seizures in the first session. Participants had a quick orientation with median TRO of 4.5min. Treatment was efficacious for both depressive and psychotic symptoms. Relatively small sample size, non-blinded, and no randomization was performed in this initial proof of concept study. This first human preliminary data of a full course of focal LAP-ST demonstrates that seizure induction is feasible. These results, although preliminary, suggest that the LAP-ST compared to the standard ECT techniques may result in less cognitive side effects, but comparable efficacy. Larger studies are needed to replicate these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Clinical efficacy and safety of surface imaging guided radiosurgery (SIG-RS) in the treatment of benign skull base tumors.

    Science.gov (United States)

    Lau, Steven K M; Patel, Kunal; Kim, Teddy; Knipprath, Erik; Kim, Gwe-Ya; Cerviño, Laura I; Lawson, Joshua D; Murphy, Kevin T; Sanghvi, Parag; Carter, Bob S; Chen, Clark C

    2017-04-01

    Frameless, surface imaging guided radiosurgery (SIG-RS) is a novel platform for stereotactic radiosurgery (SRS) wherein patient positioning is monitored in real-time through infra-red camera tracking of facial topography. Here we describe our initial clinical experience with SIG-RS for the treatment of benign neoplasms of the skull base. We identified 48 patients with benign skull base tumors consecutively treated with SIG-RS at a single institution between 2009 and 2011. Patients were diagnosed with meningioma (n = 22), vestibular schwannoma (n = 20), or nonfunctional pituitary adenoma (n = 6). Local control and treatment-related toxicity were retrospectively assessed. Median follow-up was 65 months (range 61-72 months). Prescription doses were 12-13 Gy in a single fraction (n = 18), 8 Gy × 3 fractions (n = 6), and 5 Gy × 5 fractions (n = 24). Actuarial tumor control rate at 5 years was 98%. No grade ≥3 treatment-related toxicity was observed. Grade ≤2 toxicity was associated with symptomatic lesions (p = 0.049) and single fraction treatment (p = 0.005). SIG-RS for benign skull base tumors produces clinical outcomes comparable to conventional frame-based SRS techniques while enhancing patient comfort.

  5. Topical imiquimod treatment of cutaneous vascular disorders in pediatric patients: clinical evaluation on the efficacy and safety

    Institute of Scientific and Technical Information of China (English)

    Xiao-hong MAO; Jian-you WANG; Jian-liang YAN

    2012-01-01

    Objective:To evaluate the clinical effect of topical imiquimod treatment on cutaneous vascular disorders in pediatric patients.Methods:A retrospective investigation was conducted in 25 pediatric patients with cutaneous vascular disorders,including 19 infantile hemangiomas (IHs) (12 superficial/7 mixed type),5 nevus flammeus (NF),and 1 pyogenic granuloma (PG).Imiquimod 5% cream was applied every other day for 4 to 16 weeks (average 9.6weeks).Results:Of the 19 IHs treated,an overall efficacy of 52.6% was achieved,with a clinical resolution rate of 15.8%,excellent rate of 26.3%,and moderate rate of 10.5%.The superficial type responded the best at 66.7%,while the mixed type showed only 28.6% effectiveness,which was predominantly from their superficial parts.No obvious response was noted in the 5 patients with NF.Side effects were observed in 78.9% of the patients,mostly mild to moderate local irritations and occasionally severe reactions such as thick crusting and ulceration.Systemic side events were observed in 4 IH patients including fever and digestive tract reactions.No recurrence was observed during the follow-up examination.Conclusions:Topical imiquimod could be an alternative option for the treatment of uncomplicated superficial IHs with satisfactory tolerability.

  6. Clinical study on safety of adult-to-adult living donor liver transplantation in both donors and recipients

    Institute of Scientific and Technical Information of China (English)

    Bin Liu; Ji-Chun Zhao; Yu-Kui Ma; Jiang-Wen Liu; Hong Wu; Lu-Nan Yan; Wen-Tao Wang; Bo Li; Yong Zeng; Tian-Fu Wen; Ming-Qing Xu; Jia-Yin Yang; Zhe-Yu Chen

    2007-01-01

    AIM: To investigate the safety of adult-to-adult living donor liver transplantation (A-A LDLT) in both donors and recipients.METHODS: From January 2002 to July 2006, 50 cases of A-A LDLT were performed at West China Hospital, Sichuan University, consisting of 47 cases using right lobe graft without middle hepatic vein (MHV), and 3 cases using dual grafts (one case using two left lobe, 2 using one right lobe and one left lobe). The most common diagnoses were hepatitis B liver cirrosis, 30 (60%) cases; and hepatocellular carcinoma, 15 (30%) cases in adult recipients. Among them, 10 cases had the model of end-stage liver disease (MELD) with a score of more than 25. Donor screening consisted of reconstruction of the hepatic blood vessels and biliary system with 3-dimension computed tomography and volumetry of whole liver and right liver volume. Various improved surgical techniques were adopted in the procedures for both donors and recipients .RESULTS: Forty-nine right lobes and 3 left lobes (2 left lobe grafts for 1 recipient, 1 left lobe graft for 1 recipient who had received right lobe graft donated by relative living donor) were obtained from 52 living donors. The 49 right lobe grafts, without MHV, weighed 400 g-850 g (media 550 g), and the ratio of graft volume to recipient standard liver volume (GV/SLV) ranged from 31.74% to 71.68% (mean 45.35%). All donors' remnant liver volume was over 35% of the whole liver volume. There was no donor mortality. With a follow-up of 2-52 mo (media 9 mo), among 50 adult recipients, complications occurred in 13 (26%) cases and 4 (8%) died postoperatively within 3 mo. Their 1-year actual survival rate was 92%.CONCLUSION: When preoperative CT volumetry shows volume of remnant liver is more than 35%, the ratio of right lobe graft to recipients standard liver volume exceeding 40%, A-A LDLT using right lobe graft without MHV should be a very safe procedure for both donors and recipients, otherwise dual grafts liver transplantation

  7. [Clinical safety research of penetrating acupuncture at the head points for cerebral hemorrhage at the acute stage].

    Science.gov (United States)

    Yuan, Ping; Bao, Chun-Ling; Dong, Gui-Rong

    2012-07-01

    To verify the safety of penetrating acupuncture at the head points for cerebral hemorrhage at the acute stage. Sixty cases of cerebral hemorrhage at the acute stage were selected and randomized into a western medication group and a head-point group, 30 cases in each one. In the western medication group, the anti-cranial pressure and anti-blood pressure program was administered with the conventional intravenous infusion of Sodium Nitroprusside, Mannite, etc. In the head-point group, on the basis of the treatment as the western medication group, the penetrating acupuncture at the head points was supplemented. For consciousness disturbance, Taiyang (EX-HN 5), Benshen (GB 13) and penetrating needling from Shenting (GV 24) to Shangxing (GV 23) were selected. For headache, the penetrating needling was adopted from Shangxing (GV 23) to Yintang (EX-HN 3) and from Fengchi (GB 20) to Fengchi (GB 20). For disturbance of urination and defecation, the penetrating needling was adopted from Baihui (GV 20) to Sishencong (EX-HN 1). For aphasia, the penetrating needling was adopted from Fengfu (GV 16) to Yamen (GV 15), etc. For facial paralysis, the penetrating needling from Dicang (ST 4) to Jiache (ST 6) and Xiaguan (ST 7) were selected. For paralysis, the penetrating needling was adopted from Baihui (GV 20) to Taiyang (EX-HN 5), etc. Before and after treatment, the changes in cerebral hemorrhagic volume, the results of blood, urine and stool routine examination, the situations of the life indices such as heart, liver and kidney functions, blood pressure, respiration and heart rate were observed, as well as the impacts on ECG. The cranial CT sania cn indicated that the rate of the basic and significant absorption of hematoma was 80.0% (24/30) in the head-point group, which was superior to 56.7% (17/30) in the western medication group (P 0.05). There were no any abnormal changes in liver and kidney functions. In the head-point group, the abnormality rate of ECG was lower obviously

  8. Principles of safety pharmacology.

    Science.gov (United States)

    Pugsley, M K; Authier, S; Curtis, M J

    2008-08-01

    Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.).

  9. Clinical efficacy and safety of Ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Alessandro Battaggia

    Full Text Available Randomized clinical trials (RCTs about Ezetimibe's efficacy on patient-oriented outcomes have given discordant results. The aim of this study was to determine the net effect of Ezetimibe and of the widely marketed combination, Ezetimibe+simvastatin, on mortality and morbidity outcomes.We searched for RCT on Ezetimibe using MEDLINE, CCTR, EMBASE, ClinicalTrials.gov databases up to December 2013, Merck and Novartis online registers, and personal communications. Two authors independently selected trials fulfilling these criteria: RCTs comparing Ezetimibe±statin or another lipid-lowering drug against placebo, or against the same lipid-lowering drug at the same dosage, with a follow-up at least 24 weeks and one or more of these outcomes: all-cause mortality, cardiovascular (CV mortality, stroke, myocardial infarction (MI, cancer, serious adverse events (SAEs; we assessed the risk of bias using the Cochrane checklist. We extracted the data for major clinical events as a dichotomous measure, with the patient the unit of analysis. Pooled analysis was done with random and fixed effect based models. Trials comparing Ezetimibe plus a lipid-lowering drug against the same lipidlowering drug representing the net effect of Ezetimibe, showed a nonsignificant tendency toward damage for cancer, MI, stroke and SAEs. Ezetimibe+simvastatin vs. simvastatin alone showed a stronger tendency towards a higher risk for all-cause death (2.52; 0.65-9.74, CV death (3.04; 0.48-19.21, non-CV death (3.03; 0.12-73.50, MI (1.91; 0.42-8.70, stroke (2.38; 0.46-12.35, cancer (RR 11.11; 0.62-198.29, and SAEs (1.45; 0.95-2.23. Limitations include small numbers of events and inadequate power of the pooling. Trials comparing Ezetimibe+simvastatin vs placebo showed non-significant effects: MI (0.81; 0.66-1.00 p = 0.051, all-cause death (1.02; 0.95-1.09, CV death (0.91; 0.80-1.04, non-CV death (108; 0.99-1.18, stroke (0.86; 0.72-1.04, cancer (1.18; 0.80-1.74, SAEs (1.01; 0

  10. Topical alprostadil (PGE1) for the treatment of female sexual arousal disorder: in-clinic evaluation of safety and efficacy.

    Science.gov (United States)

    Heiman, Julia R; Gittelman, Marc; Costabile, Raymond; Guay, Andre; Friedman, Alice; Heard-Davison, Amy; Peterson, Craig; Dietrich, John; Stephens, Darby

    2006-03-01

    This multi-center, randomized, placebo-controlled, crossover design study evaluated the effects of a topical alprostadil solution for the treatment of female sexual arousal disorder (FSAD). A total of 79 naturally or surgically post menopausal women with FSAD were treated with either 100 or 400 micrograms of alprostadil solution and placebo, delivered on separate clinic visits in random order. Study drug was applied to the external genitalia and was followed by 30 minutes of visual sexual stimulation. Study evaluations included investigator assessments of genital vasocongestion and patient assessments of physical and emotional sexual arousal, and sexual satisfaction. Genital vasocongestion in response to PGE1 was significantly greater than placebo (p alprostadil. Topical alprostadil was well tolerated with no reports of significant systemic side effects. The most common adverse event was mild, transient genital burning typically alprostadil should be further researched as a potentially appropriate on-demand therapeutic choice for women experiencing FSAD.

  11. Clinical Efficacy and Safety of Liquid Pelargonium sidoides Preparation (EPs 7630 in Children with Acute Non-Streptococcal Tonsillopharyngitis

    Directory of Open Access Journals (Sweden)

    V. Berezhnoi

    2016-11-01

    Full Text Available Background Acute tonsillopharyngitis is amongst the most common reasons for children, adolescents and young adults to consult with a physician. Despite extensive prescription, antibiotic therapy is indicated in less than one-fifth of these cases. New treatment strategies for patients with non-group-A-streptococcal acute tonsillopharyngitis are therefore required. Objectives EPs 7630 is an extract from the roots of Pelargonium sidoides DC. After positive clinical study results in children with acute bronchitis, the present study was conducted to demonstrate the efficacy of EPs 7630 in the treatment of acute tonsillopharyngitis in children. Methods In this double-blind placebo-controlled clinical trial with a group sequential design, the efficacy and tolerability of EPs 7630 were investigated in 6- to 10-year-old patients with acute tonsillopharyngitis, who showed no evidence of group A β-hemolytic streptococcus. Treatment duration was 6 days. Primary efficacy variable was change in the sum score of the tonsillitis severity score (TSS on day 4 compared to baseline. Results Overall, data on the change of the TSS measured for the EPs 7630 and placebo group were available for 60 and 64 children, respectively. After 4 days of treatment, the TSS had decreased from 9.6 ± 1.2 to 2.8 ± 2.6 points in the active medication group and from 9.5 ± 1.3 to 6.1 ± 4.1 points in the placebo group (P < 0.001, indicating superiority of EPs 7630 over placebo. Conclusions EPs 7630 was found to be efficacious in the treatment of acute tonsillopharyngitis in children and was very well tolerated.

  12. Clinical efficacy and safety of moxifloxacin versus levofloxacin plus metronidazole for community-acquired pneumonia with aspiration factors

    Institute of Scientific and Technical Information of China (English)

    Sun Tieying; Sun Li; Wang Rongmei; Ren Xiaoping; Sui Dong-jiang; Pu Chun; Ren Yajuan

    2014-01-01

    Background Community-acquired pneumonia (CAP) is a common infectious disease throughout the world and the incidence continues to grow as the population ages.Aspiration is an important pathogenic mechanism for pneumonia in the elderly and the management of patients with community-acquired pneumonia with aspiration factors is a major medical problem.Our study aimed to assess whether moxifloxacin in comparison to levofloxacin plus metronidazole are effective and safe in the treatment of community-acquired pneumonia with aspiration factors.Methods In this prospective,multicenter,open-label,randomized controlled trial,77 patients with mild-to-moderate community-acquired pneumonia with aspiration factors were enrolled and randomly assigned to receive moxifloxacin or levofloxacin plus metronidazole.The primary efficacy variables were clinical outcomes in evaluable patients at a follow-up visit 7 to 14 days after the end of therapy.Results Seven days after the end of therapy a clinical cure was achieved for 76.7% (23 of 37) of efficacy-evaluable patients in the moxifloxacin group and 51.7% (15 of 40) of patients in the levofloxacin plus metronidazole group.There was a significant difference between the two groups (x2=4.002,P <0.05).Bacteriological success rates were similar in the moxifloxacin group (93.3%) and levofloxacin plus metronidazole group (96.4%),there was no significant difference between the two groups (P >0.05).The overall adverse event rate was 10.8% (4/37) in the moxifloxacin group versus 17.5% (7/40) in the levofloxacin plus metronidazole group,there was no significant difference between the two groups (P>0.05).No serious adverse events were observed.Conclusions Moxifloxacin is effective and safe for treatment of community-acquired pneumonia with aspiration factors.And the regimen of moxifloxacin monotherapy is more convenient compared with levofloxacin plus metronidazole.

  13. A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine for use in the prevention of visceral leishmaniasis.

    Science.gov (United States)

    Chakravarty, Jaya; Kumar, Subodh; Trivedi, Sonali; Rai, Vijay K; Singh, Anup; Ashman, Jill A; Laughlin, Elsa M; Coler, Rhea N; Kahn, Stuart J; Beckmann, Anna Marie; Cowgill, Karen D; Reed, Steven G; Sundar, Shyam; Piazza, Franco M

    2011-04-27

    Healthy Indian adult volunteers, with or without a history of leishmaniasis, were evaluated for evidence of previous infection with Leishmania donovani based on the direct agglutination test (DAT). Three cohorts of 6 DAT-negative and 6 DAT-positive subjects were enrolled in an open-label, dose-escalating, uncontrolled clinical trial and received three injections of the LEISH-F1+MPL-SE vaccine (consisting of 5μg, 10μg, or 20μg recombinant Leishmania polyprotein LEISH-F1 antigen+25μg MPL®-SE adjuvant). The study injections were given subcutaneously on days 0, 28, and 56, and the subjects were followed through day 168 for safety and immunological endpoints. The vaccine was safe and well-tolerated in DAT-negative and DAT-positive subjects and induced T-cell production of IFN-γ and other cytokines in response to stimulation with the LEISH-F1 antigen. This clinical trial shows that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without history of previous infection with Leishmania donovani. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. A clinical trial of safety and tolerability for the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease.

    Science.gov (United States)

    Khasnavis, Tanya; Reiner, Gail; Sommerfeld, Barbara; Nyhan, William L; Chipkin, Richard; Jinnah, H A

    2016-04-01

    Lesch-Nyhan disease (LND) is an inherited metabolic disorder characterized by the overproduction of uric acid and distinct behavioral, cognitive, and motor abnormalities. The most challenging clinical problem is self-injurious behavior (SIB), which includes self-biting, self-hitting, self-abrasion, and other features. Currently, these behaviors are managed by behavioral extinction, sedatives, physical restraints, and removal of teeth. More effective treatments are needed. Pre-clinical studies have led to the hypothesis that D1-dopamine receptor antagonists may provide useful treatments for SIB in LND. Ecopipam is one such selective D1-dopamine receptor antagonist. This report summarizes results of a dose-escalation study of the safety and tolerability of ecopipam in 5 subjects with LND. The results suggest that ecopipam is well tolerated, with sedation being the most common dose-limiting event. Several exploratory measures also suggest ecopipam might reduce SIB in this population. These results support the hypothesis that D1-dopamine receptor antagonists may be useful for suppressing SIB in LND, and encourage further studies of efficacy. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Appraising the safety and efficacy profile of left atrial appendage closure in 2016 and the future clinical perspectives. Results of the EAPCI LAAC survey.

    Science.gov (United States)

    Santucci, Andrea; Byrne, Robert A; Baumbach, Andreas; Colleran, Roisin; Haude, Michael; Windecker, Stephan; Valgimigli, Marco

    2016-05-17

    The aim of this study was to determine the opinion of the scientific community regarding percutaneous left atrial appendage closure (LAAC). The main focus of the survey was on concerns and expectations regarding the safety and efficacy profile of LAAC in clinical practice and on current and future clinical perspectives. A voluntary web-based survey was distributed by the European Association of Percutaneous Coronary Interventions (EAPCI) to all individuals registered on the EuroIntervention mailing list (n=21,800). A total of 724 physicians responded to the survey, of whom 31.8% had first operator experience with LAAC. Exclusive use of the Amulet (34.4%) or WATCHMAN (30.3%) was similar, but the former was the most frequently used device in Europe. The majority of respondents (59.3%) deemed LAAC to be as effective as, but safer than oral anticoagulants (OAC) in reducing stroke risk. Periprocedural complications (40.3%) and cost (28.8%) were the major concerns. Most practitioners did not consider novel oral anticoagulants (NOACs) to be a deterrent for performing LAAC procedures. Moreover, a history of serious haemorrhage was not deemed necessary to justify LAAC for 59.8% of physicians. The results of this survey reveal a high level of confidence in percutaneous LAAC amongst surveyed interventional cardiologists, with the majority believing it to be as effective as OAC in terms of stroke prevention and safer in terms of bleeding risk.

  16. Clinical evaluation of efficacy and safety of cyclosporine (Imusporin in renal transplant patients with stable graft function maintained on neoral or bioral

    Directory of Open Access Journals (Sweden)

    Mrigank S Jha

    2007-01-01

    Full Text Available Objective: Previous pharmacokinetic studies have demonstrated bioequivalence of Imusporin (microemulsion preparation of cyclosporine, Cipla to the innovator product Neoral (Novartis, Switzerland. This study was done to evaluate the clinical efficacy and safety of Imusporin in patients who have already undergone renal transplant and have stable graft function maintained on cyclosporine preparation other than Imusporin. Materials and Methods: Twenty-two renal allograft recipients (mean age of 31.77 years, range 18-53 years, with stable graft function, previously on Neoral or Bioral were switched over to Imusporin after recording their relevant baseline clinical and biochemical parameters. These were repeated on 1, 4, 7, 15, 30 and 90 days after the start of therapy. Change in dosage required to maintain C2 levels at each visit were analyzed by paired sample t -test. Safety of the drug was assessed by the type and severity of adverse events developed during the therapy. Cost analysis was done assuming an average maintenance immunosuppression dose of 150 mg/day of cyclosporine. Results: Twenty-one patients completed the study. One patient was lost to follow-up. Mean C2 value before switchover was 894 ± 208 ng/ml, which was not significantly different from the mean values of C2 after switchover therapy ( P >0.30. Change in dosage required to maintain C2 levels was not significantly different from the baseline dose of 2.34 mg/ kg body weight ( P >0.1. No patient developed graft rejection after switchover therapy at a median follow-up of 16 months (14-18 months. Mean baseline SCr was similar to SCr at day 90 (1.38 vs. 1.37 mg/dl, P =0.930. No severe adverse events were reported. Mild side-effects included headache (4, somnolence (2, dry mouth (5 and generalized fatigue (6. Use of Imusporin (Cipla, India results in an annual savings of Rs. 19892 over Neoral (Novartis, Switzerland and Rs. 2263 over Bioral (Panacea Biotech, India. Conclusions: Imusporin

  17. First Phase I human clinical trial of a killed whole-HIV-1 vaccine: demonstration of its safety and enhancement of anti-HIV antibody responses.

    Science.gov (United States)

    Choi, Eunsil; Michalski, Chad J; Choo, Seung Ho; Kim, Gyoung Nyoun; Banasikowska, Elizabeth; Lee, Sangkyun; Wu, Kunyu; An, Hwa-Yong; Mills, Anthony; Schneider, Stefan; Bredeek, U Fritz; Coulston, Daniel R; Ding, Shilei; Finzi, Andrés; Tian, Meijuan; Klein, Katja; Arts, Eric J; Mann, Jamie F S; Gao, Yong; Kang, C Yong

    2016-11-28

    Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus. This genetically modified virus (gmHIV-1NL4-3) was inactivated and formulated as a killed whole-HIV vaccine, and then used for a Phase I human clinical trial (Trial Registration: Clinical Trials NCT01546818). The gmHIV-1NL4-3 was propagated in the A3.01 human T cell line followed by virus purification and inactivation with aldrithiol-2 and γ-irradiation. Thirty-three HIV-1 positive volunteers receiving cART were recruited for this observer-blinded, placebo-controlled Phase I human clinical trial to assess the safety and immunogenicity. Genetically modified and killed whole-HIV-1 vaccine, SAV001, was well tolerated with no serious adverse events. HIV-1NL4-3-specific PCR showed neither evidence of vaccine virus replication in the vaccine virus-infected human T lymphocytes in vitro nor in the participating volunteers receiving SAV001 vaccine. Furthermore, SAV001 with adjuvant significantly increased the pre-existing antibody response to HIV-1 proteins. Antibodies in the plasma of vaccinees were also found to recognize HIV-1 envelope protein on the surface of infected cells as well as showing an enhancement of broadly neutralizing antibodies inhibiting tier I and II of HIV-1 B, D, and A subtypes. The killed whole-HIV vaccine, SAV001, is safe and triggers anti-HIV immune responses. It remains to be determined through an appropriate trial whether this immune response prevents HIV

  18. THE SAFETY AND EXPEDIENCY OF USING A TRANSPERITONEAL LAPAROSCOPIC ACCESS TO RADICAL NEPHRECTOMY FOR CLINICALLY LOCALIZED KIDNEY CANCER

    Directory of Open Access Journals (Sweden)

    V. B. Matveev

    2013-01-01

    Full Text Available Objective: to compare immediate, oncological, and functional results, as well as quality of life in patients undergoing open and laparoscopic transperitoneal radical nephrectomy (RNE for clinically localized kidney cancer (KC.Subjects and methods. Data from 426 cT1-2N0M0 KC patients after radical nephrectomy in 1991 to 2011 were retrospectively selected. Their median age was 57 years. The male/female ratio was 1.1:1. The median highest tumor diameter was 5.0±2.2 cm. RNE was carried out in all 426 patients: in 211 (49.5 % patients through open access and in 215 (50.5 % through transperitoneal laparoscopic one. The patient groups operated on via different accesses were matched for major signs; however, the laparoscopy group displayed a preponderance of cT1a tumors. The median follow-up was 50.0±12.3 months.Results. There were no significant differences in the frequency of intraoperative and postoperative complications of laparoscopic and open nephrectomies. The five-year overall, specific, and relapse-free survival rates in the patients who had undergone open nephrectomy were 95.4, 98.4, and 92.2 %, respectively; those in the patients who had laparoscopic nephrectomy were 94.5, 100.0, and 93.6 %, respectively (p > 0.05 for all. The incidence of acute renal dysfunction and its distribution according to the RIFLE classes, the rate of acute dialysis and that of a decrease and a continued reduction in glomerular filtration rate, as well as the distribution of patients according to the stages of chronic kidney disease after RNE did not depend on the surgical access (p > 0.05 for all. The QLQ-30 survey data show that the laparoscopic access versus the laparotomic one improves quality of life within 1 month after RNE.Conclusion. Laparoscopic transperitoneal RNE is a safe alternative to open surgery that can improve quality of life in the patients with clinically localized kidney cancer within one month after surgical intervention.

  19. Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

    Directory of Open Access Journals (Sweden)

    Thomas B Campbell

    Full Text Available Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.1,571 HIV-1-infected persons (47% women from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV, atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC, or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF (EFV+FTC-TDF. ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18% among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74. Safety endpoints occurred in 243 (46% participants assigned to EFV+FTC-TDF versus 313 (60% assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001 and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01. Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21% among 526 participants assigned to ATV+DDI+FTC and 76 (15% among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007.EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are

  20. Adherence to treatment with denosumab, its efficacy and safety in women with postmenopausal osteoporosis in clinical practice

    Directory of Open Access Journals (Sweden)

    N. V. Toroptsova

    2015-01-01

    Full Text Available Adherence to treatment with antiosteoporotic drugs is one of the most important factors contributing to their efficacy during longterm therapy. The adherence is assessed by two main lines: firstly, how long a drug is taken and, secondly, whether its dosage regimen is adhered.Subjects and methods. The paper gives the data of a 12-month prospective follow-up study of 40 women with postmenopausal osteoporosis (OP who initiated treatment with the biological agent denosumab.Results and discussion. After the 12-month follow-up, the significant bone mineral density increase was 4.9% in the lumbar spine, 3.2% in the femoral neck, and 3.0% in the total hip. The previous administration of other antiosteoporotic drugs did not lower the efficiency of denosumab therapy. There were no cases of osteoporotic fractures during 1-year follow-up. 95% of the patients received two denosumab injections (an annual cycle; moreover, 90% of the women were noted to adhere to the dosage regimen. Age, marital status, level of education, time taken to reach the clinic, parental femoral fractures, a history of fractures, duration of OP, and previous therapy had no impact on treatment adherence during 12 months.Conclusion. The one-year prospective follow-up study of the outpatients demonstrated that denosumab was an effective and safe agent for the treatment of patients with postmenopausal OP and its dosage regimen implying its rare subcutaneous administration (twice yearly ensured the high patient adherence to therapy.

  1. The Clinical Efficacy and Safety of Acepromazine and Propofol Anesthesia for the Cesarean Section in the Cat

    Directory of Open Access Journals (Sweden)

    Mohammad O. Kalim

    2012-08-01

    Full Text Available A 3-year-old crossbred cat was presented at the clinics. History revealed that the cat had sustained frequent straining for the last 12 hrs. One kitten was found stuck in the birth canal. The cat was premedicated with atropine sulphate @ 0.04 mg/kg b.wt and tranquilized with acepromazine maleate @ 0.1mg/kg b.wt. I/M, and anesthetized with propofol @ 4 mg/kg b.wt. I/V. via the cephalic vein. The abdominal region was aseptically prepared from the umbilicus to the pubis region. A ventral mid line incision of approximately 3.5 cm was made in linea alba between the umbilicus and pubis, caudally. The gravid uterus was exposed through the surgical wound. A longitudinal incision was placed on the uterine body and kittens were taken out slowly one by one. One of the kittens, which was stuck in the vaginal orifice, was taken out slowly by gently manipulating its presentation. A total of four kittens were born. The use of acepromazine and propofol anesthesia for the cesarean section in the cat proved to be an easy and excellent method without any complications. [Arch Clin Exp Surg 2012; 1(4.000: 258-260

  2. Clinical efficacy and safety of Vitaros©/Virirec© (Alprostadil cream) for the treatment of erectile dysfunction.

    Science.gov (United States)

    Moncada, Ignacio; Cuzin, Béatrice

    2015-01-01

    Erectile dysfunction (ED) is a very common disorder with a deep impact on patients and their partners. Several options are now available for treating ED; oral pharmacotherapy with phosphodiesterase-5 (PDE5) inhibitors currently represents the first-line option for many ED patients. Vitaros©/Virirec© is new topical, non-invasive treatment for ED that offers the combination of an active drug (alprostadil, a synthetic PGE1) with a skin enhancer that improves its local absorption directly at the site of action. Vitaros©/Virirec© has a favorable pharmacodynamic profile and is poorly absorbed in systemic circulation. This makes it suitable in any circumstances and results in a reduced risk of adverse events (AEs), being systemic AEs reported in only 3% of the treated population. Its clinical efficacy has been demonstrated in both phase II and III trials, showing a global efficacy up to 83% with the 300 μg dose in patients with severe ED significantly better than placebo. Its fast onset of action together with its favorable toxicity profile and lack of interactions with other drugs makes Vitaros©/Virirec© a first-line therapeutic option for patients with ED, particularly for individuals who are reluctant to take systemic treatments or with AEs. It may also have an important role in patients not responding to PDE5 inhibitors, particularly those with ED after radical prostatectomy.

  3. [The long-term safety of use of the stainless steel IUD: over 20 years use. Clinical and pathological analysis].

    Science.gov (United States)

    Yang, B Y

    1988-05-01

    635 women with stainless steel rings retained in utero for 20 years or more and 724 women of similar age without IUDs as controls were under investigation. Comparison of incidences of clinical symptoms of paired wearers and controls by age in premenopausal women and by postmenopausal duration in postmenopausal women showed that the tinged vaginal discharge in the study group was 4.87% higher than the controls (P0.05). There was no difference in menorrhagia, irregular bleeding, or other main effects. No cancerous changes were found in the uterine curettage specimens of 374 IUD users in the study group. Special attention was paid to the epithelium at the site in contact with the IUD and its adjacent areas showed no apparent dysplasia. There were 9 cases (2.41%) with mild hyperplasia of the endometrium. The incidence had no correlation with the prolongation of insertion duration. Among the 315 relatively intact endometrium specimens, there were 32 cases of inflammation (10.15%). The incidence had no correlation with duration. 3 endometritis cases were actinomyces infection. Among 374 removals, the removal difficulties did not apparently relate with their IUD insertion duration but did correlate to duration of menopause. Hysterograms of 23 cases showed that atrophy of uterine cavities progressed with the increase of menopausal years; the longer the duration, the deeper incarceration of the IUD. (author's)

  4. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

    Science.gov (United States)

    Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P’Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St. Ledger, Katie

    2016-01-01

    Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. PMID:27330001

  5. A new patient safety smartphone application for prevention of "forgotten" ureteral stents: results from a clinical pilot study in 194 patients.

    Science.gov (United States)

    Molina, Wilson R; Pessoa, Rodrigo; Donalisio da Silva, Rodrigo; Kenny, McCabe C; Gustafson, Diedra; Nogueira, Leticia; Leo, Mark E; Yu, Michael K; Kim, Fernando J

    2017-01-01

    Approximately 12% of all ureteral stents placed are retained or "forgotten." Forgotten stents are associated with significant safety concerns as well as increased costs and legal issues. Retained ureteral stents (RUS) often occur due to lack of clinical follow-up, communication or language barriers, and economic concerns. We describe a multiplatform application that facilitates data collection to prevent RUS. The "Stent Tracker" application can be installed on mobile devices and computers. The encrypted and password-protected information is accessible from any device and provides information about each procedure, stent placement and removal dates, as well as product description. This multicenter retrospective study included 194 patients who underwent stent placement between July and October 2015. Nominal data was tallied and ordinal data was divided into quartiles of 25, 50, and 75%. A total of 194 patients from three institutions underwent ureteral stent placement. Reasons for stent placement include 122 cases post ureteroscopy (63%), 8 cases post percutaneous nephrolithotomy (PCNL) (4%), 14 cases post extracorporeal shock wave lithotripsy (SWL) (7%), 18 cases of cancer-related ureteral obstruction (9%), 21 cases of hydronephrosis (11%), and 11 for other reasons (6%). Of these patients, only one patient was lost to follow-up (0.5%). On average, ureteral stents were removed within 14 days of placement (IQR: 8-26 days). The "Stent Tracker" is a patient safety application that provides a secure and simplified interface, which can significantly reduce the incidence of RUS. Further developments could include automated notifications to patients and staff, color-coding, and integrated information with electronic patient charts.

  6. A randomized clinical evaluation of the safety of Systane® Lubricant Eye Drops for the relief of dry eye symptoms following LASIK refractive surgery

    Directory of Open Access Journals (Sweden)

    Daniel Durrie

    2008-12-01

    Full Text Available Daniel Durrie, Jason StahlDurrie Vision, Overland Park, Kansas, USAPurpose: To evaluate the safety of Systane® Lubricant Eye Drops in relieving the symptoms of dry eye following laser-assisted in situ keratomileusis (LASIK surgery.Methods: This was a randomized, double-masked, single-center, placebo-controlled, contralateral eye study of 30 patients undergoing LASIK surgery. The mean age of patients was 42.4 ± 10.7 years, and the mean spherical equivalent was −3.29 (range, +1.75 to −7.38. Patients’ right and left eyes were randomized to receive either Systane® or placebo – a preserved, thimerosal-free saline solution – beginning from the day of surgery and ending 30 days following surgery. Outcome measures included tear film break up time (TFBUT, visual acuity, degree of corneal and conjunctival staining, and treatment-related adverse events.Results: Preoperatively, placebo-treated eyes had statistically significantly higher sum corneal staining score than Systane®-treated eyes (p = 0.0464; however, the difference was clinically insignificant (p = 0.27. Two weeks post operatively, the average TFBUT in the Systane®-treated eyes was 1.23 seconds longer than that of the placebo-treated eyes (p = 0.028. All other evaluated variables were comparable between the two treatments. No adverse events were reported in the study.Conclusion: Systane® Lubricant Eye Drops are safe for use following LASIK surgery to relieve the discomfort symptoms of dry eye associated with the procedure.Keywords: Systane®, safety, dry eye, LASIK

  7. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A.

    Science.gov (United States)

    Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I; Fischer, Kathelijn; Gill, Joan C; P'Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St Ledger, Katie; Pabinger, Ingrid

    2016-08-04

    Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927.

  8. The safety and efficacy of bacterial nanocellulose wound dressing incorporating sericin and polyhexamethylene biguanide: in vitro, in vivo and clinical studies.

    Science.gov (United States)

    Napavichayanun, Supamas; Yamdech, Rungnapha; Aramwit, Pornanong

    2016-03-01

    In our previous work, we have attempted to develop a novel bacterial nanocellulose wound dressing which composed of both polyhexamethylene biguanide (PHMB) as an antimicrobial agent and sericin as an accelerative wound healing component. The loading sequence and concentration of PHMB and sericin were optimized to provide the wound dressing with the most effective antimicrobial activity and enhanced collagen production. In this study, further in vitro, in vivo, and clinical studies of this novel wound dressing were performed to evaluate its safety, efficacy, and applicability. For the in vitro cytotoxic test with L929 mouse fibroblast cells, our novel dressing was not toxic to the cells and also promoted cell migration as good as the commercially available dressing, possibly due to the component of sericin released. When implanted subcutaneously in rats, the lower inflammation response was observed for the novel dressing implanted, comparing to the commercially available dressing. This might be that the antimicrobial PHMB component of the novel dressing played a role to reduce infection and inflammation reaction. The clinical trial patch test was performed on the normal skin of healthy volunteers to evaluate the irritation effect of the dressing. Our novel dressing did not irritate the skin of any volunteers, as characterized by the normal levels of erythema and melanin and the absence of edema, papule, vesicle, and bullae. Then, the novel dressing was applied for the treatment of full-thickness wounds in rats. The wounds treated with our novel dressing showed significantly lower percentage of wound size and higher extent of collagen formation mainly due to the activity of sericin. We concluded that our novel bacterial nanocellulose incorporating PHMB and sericin was a safe and efficient wound dressing material for further investigation in the wound healing efficacy in clinic.

  9. Impact on Patient Safety and Satisfaction of Implementation of an Outpatient Clinic in Interventional Radiology (IPSIPOLI-Study): A Quasi-Experimental Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Lutjeboer, Jacob, E-mail: j.lutjeboer@lumc.nl; Burgmans, Mark Christiaan, E-mail: m.c.burgmans@lumc.nl, E-mail: mburgmans@hotmail.com; Chung, Kaman, E-mail: kaman.chung10@gmail.com; Erkel, Arian Robert van, E-mail: a.r.van-erkel@lumc.nl [Leiden University Medical Center, Department of Radiology (Netherlands)

    2015-06-15

    PurposeInterventional radiology (IR) procedures are associated with high rates of preparation and planning errors. In many centers, pre-procedural consultation and screening of patients is performed by referring physicians. Interventional radiologists have better knowledge about procedure details and risks, but often only get acquainted with the patient in the procedure room. We hypothesized that patient safety (PS) and patient satisfaction (PSAT) in elective IR procedures would improve by implementation of a pre-procedural visit to an outpatient IR clinic.Material and MethodsIRB approval was obtained and informed consent was waived. PS and PSAT were measured in patients undergoing elective IR procedures before (control group; n = 110) and after (experimental group; n = 110) implementation of an outpatient IR clinic. PS was measured as the number of process deviations. PSAT was assessed using a questionnaire measuring Likert scores of three dimensions: interpersonal care aspects, information/communication, and patient participation. Differences in PS and PSAT between the two groups were compared using an independent t test.ResultsThe average number of process deviations per patient was 0.39 in the control group compared to 0.06 in the experimental group (p < 0.001). In 9.1 % patients in the control group, no legal informed consent was obtained compared to 0 % in the experimental group. The mean overall Likert score was significantly higher in the experimental group compared to the control group: 2.68 (SD 0.314) versus 2.48 (SD 0.381) (p < 0.001).ConclusionPS and PSAT improve significantly if patients receive consultation and screening in an IR outpatient clinic prior to elective IR procedures.

  10. Clinical study of the safety and effectiveness of a novel over-the-counter bleaching tray system

    Directory of Open Access Journals (Sweden)

    Ghalili KM

    2014-02-01

    Full Text Available K Michael Ghalili,1 Kamal Khawaled,2 Doran Rozen,2 Veda Afsahi3 1Department of Prosthodontics, New York University College of Dentistry, New York, NY, USA; 2Department of R&D; Department of Clinical Affairs, Syneron Beauty, Ltd, Yokneam, Israel; 3Veda Faith Afsahi Inc., Fountain Valley, CA, USA Abstract: We investigated color change, gingival irritation, and tooth sensitivity in patients undergoing at-home vital tooth bleaching with a novel over-the-counter bleaching tray system. Tooth color shade in anterior teeth, supragingival plaque and gingivitis in Ramfjord teeth, as well as visual assessment of teeth gingival tissues and mucosa were evaluated in-office prior to treatment, after two consecutive applications of the 9% hydrogen peroxide bleaching product, after eight applications (10 minutes/day for 3 days at home, and after ten applications (50 minutes exposure over 5 days. Color stability was evaluated at 3 months after completing the treatment regimen. Over-the-counter bleaching products can be used by the patient at home without dentist supervision, but are frequently associated with gingival irritation and tooth sensitivity despite low concentrations of peroxide agents. Our investigations showed that the treatment is tolerable and safe with a low incidence of adverse effects. Any adverse effects associated with use of the whitening gel and tray are temporary, easily controlled, and often disappear within minutes of treatment. Statistical analysis revealed significant improvement in teeth whitening following treatment (mean color change of seven shades and at three months after treatment. Keywords: at home tooth-whitening, hydrogen peroxide teeth whitening, over-the-counter tooth-whitening, teeth bleaching

  11. Sumatriptan transdermal iontophoretic patch (NP101-Zelrix™: review of pharmacology, clinical efficacy, and safety in the acute treatment of migraine

    Directory of Open Access Journals (Sweden)

    Vikelis M

    2012-09-01

    Full Text Available Michail Vikelis,1 Dimos D Mitsikostas,2 Alan M Rapoport31Glyfada Headache Center, Glyfada, Greece; 2Neurology Department, Athens Naval Hospital, Athens, Greece; 3The David Geffen School of Medicine at UCLA, Los Angeles, CA, USAAbstract: Migraine is a chronic, painful, and often disabling primary headache disorder, typically presenting with recurrent attacks that may be accompanied by a variety of neurological, gastrointestinal, and autonomic symptoms. Gastrointestinal symptoms in association with migraine including, nausea, vomiting, and gastroparesis, affect a large proportion of migraine sufferers. These symptoms may result in delays or inconsistencies in the absorption of oral treatments. Hence, the necessity for an innovative, non-invasive, parenteral delivery formulation for quick and effective treatment of migraine attacks is evident. Iontophoresis utilizes minimal amounts of electrical potential to support the fast transfer of ionized medication transdermally and into the general circulation. Two pharmacokinetic clinical trials have shown that iontophoretic delivery of sumatriptan through the skin produces quick and reproducible therapeutic plasma concentrations. A randomized, double-blind, multicenter, phase III study demonstrated superior efficacy versus placebo and excellent tolerability, with no triptan-related adverse events. The proportion of patients that were pain-free at 2 h post-treatment was 18% for the sumatriptan patch vs 9% for placebo (P = 0.0092; number needed to treat = 11.1. Upon approval from the Food and Drug Administration and other regulatory authorities, the iontophoretic transdermal delivery of sumatriptan will be a good choice for patients experiencing poor absorption of oral medication often associated with migraine and/or for those with intolerable triptan-related adverse events.Keywords: iontophoretic patch, migraine, migraine treatment, sumatriptan, transdermal patch

  12. Thinking on Non- clinical Safety Evaluation of Natural Plants Cosmetics%对天然药物化妆品非临床安全性评价的思考

    Institute of Scientific and Technical Information of China (English)

    朱伟; 宋健平

    2012-01-01

    From the perspective of social public safety, this paper discussed the necessity of non - clinical safety e-valuation of natural plants cosmetics. We also put forward the suggestions of non - clinical safety evaluation of natural plants cosmetics in accordance with their product characteristic.%从社会公众安全的角度出发,论述了对天然药物化妆品开展非临床安全性评价的必要性,并根据天然药物化妆品的产品特点,提出了天然药物化妆品的非临床安全性评价的建议.

  13. IMPROVING PATIENT SAFETY:

    DEFF Research Database (Denmark)

    Bagger, Bettan; Taylor Kelly, Hélène; Hørdam, Britta

    2013-01-01

    Every year millions of patients worldwide suffer injury or death due to unsafe care, thus improving patient safety is both a national and international priority. A developmental project involving University College Zealand and clinical partners in the region focused upon the improvement of patient...... safety by optimizing the theory-practice connection with respect to the development of students’ competencies and the reporting of clinical errors. Population: 2nd year nursing students at University College Zealand (N: 56). Informed consent and full anonymity. Aims: - To increase patient safety...... errors. An interesting finding though is that despite the legal requirements concerning the mandatory reporting of all clinical errors, 37% of the students participating in this study report that they perhaps would be reluctant to report an eventual clinical error. Further initiatives are thus necessary...

  14. The clinical safety, biodistribution and internal radiation dosimetry of [{sup 18}F]fluciclovine in healthy adult volunteers

    Energy Technology Data Exchange (ETDEWEB)

    McParland, Brian J. [Imaging Technology Group, GE Healthcare Medical Diagnostics, Amersham, Buckinghamshire (United Kingdom); Wall, Anders; Soerensen, Jens [Uppsala University, Section of Nuclear Medicine and PET, Department of Radiology, Oncology and Radiation Sciences, Uppsala (Sweden); Johansson, Silvia [Uppsala University, Section of Oncology, Department of Radiology, Oncology and Radiation Sciences, Uppsala (Sweden)

    2013-08-15

    We report on the biodistribution and internal radiation dosimetry in humans of [{sup 18}F]fluciclovine, a synthetic L-leucine analogue being investigated as a potential diagnostic biomarker for neoplasia. Whole-body positron emission tomography (PET) scans of 6 healthy volunteers were acquired at up to 16 time points up to about 5 h after a bolus administration of [{sup 18}F]fluciclovine (153.8 {+-} 2.2 MBq). Venous blood samples were taken up to about 4 h post-injection from which {sup 18}F activity concentrations in whole blood and plasma were measured. Urine was collected as voided up to 4 h post-injection, from which the excreted {sup 18}F activity was measured. Absolute values of the {sup 18}F activity contained in up to 11 source regions (brain, salivary glands, lung, heart, pancreas, spleen, liver, red bone marrow, kidneys, uterus and urinary bladder contents) were determined directly from quantitative analysis of the images. For each source region, the {sup 18}F activity decay-corrected and normalised to that injected, as a function of time, was fit by an analytical function which was subsequently integrated to yield the cumulated activity normalised to the injected activity. These normalised cumulated activities were then used as input to the Organ Level INternal Dose Assessment/EXponential Modelling (OLINDA/EXM) package to calculate the internal radiation dosimetry of each subject following the Medical Internal Radiation Dose (MIRD) schema. An effective dose was then estimated for each subject. [{sup 18}F]Fluciclovine was clinically well tolerated in this study. Very little {sup 18}F was excreted with only a mean value of 3.3 % present in the urine at about 4 h post-injection; no activity within the intestinal contents was noted. The highest mean initial uptakes were measured in the liver (13.8 %), red bone marrow (11.1 %) and lung (7.1 %). The highest mean radiation absorbed doses per unit administered activity were received by the pancreas (102.2 {mu

  15. Efficacy and safety of integrative medical program based on blood cooling and detoxification recipe in treating patients with hepatitis B virus related acute-on-chronic liver failure:a randomized controlled clinical study

    Institute of Scientific and Technical Information of China (English)

    刘慧敏

    2014-01-01

    Objective To evaluate the clinical efficacy and safety of integrative medical program based on blood cooling and detoxification recipe(BCDR)in treating patients with hepatitis B virus related acute-on-chronic liver failure(HBV-ACLF)of heat-toxicity accumulation syndrome(HTAS).Methods Adopting randomized controlled

  16. A new algorithmic approach for the extraction of temporal associations from clinical narratives with an application to medical product safety surveillance reports.

    Science.gov (United States)

    Wang, Wei; Kreimeyer, Kory; Woo, Emily Jane; Ball, Robert; Foster, Matthew; Pandey, Abhishek; Scott, John; Botsis, Taxiarchis

    2016-08-01

    The sheer volume of textual information that needs to be reviewed and analyzed in many clinical settings requires the automated retrieval of key clinical and temporal information. The existing natural language processing systems are often challenged by the low quality of clinical texts and do not demonstrate the required performance. In this study, we focus on medical product safety report narratives and investigate the association of the clinical events with appropriate time information. We developed a novel algorithm for tagging and extracting temporal information from the narratives, and associating it with related events. The proposed algorithm minimizes the performance dependency on text quality by relying only on shallow syntactic information and primitive properties of the extracted event and time entities. We demonstrated the effectiveness of the proposed algorithm by evaluating its tagging and time assignment capabilities on 140 randomly selected reports from the US Vaccine Adverse Event Reporting System (VAERS) and the FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS). We compared the performance of our tagger with the SUTime and HeidelTime taggers, and our algorithm's event-time associations with the Temporal Awareness and Reasoning Systems for Question Interpretation (TARSQI). We further evaluated the ability of our algorithm to correctly identify the time information for the events in the 2012 Informatics for Integrating Biology and the Bedside (i2b2) Challenge corpus. For the time tagging task, our algorithm performed better than the SUTime and the HeidelTime taggers (F-measure in VAERS and FAERS: Our algorithm: 0.86 and 0.88, SUTime: 0.77 and 0.74, and HeidelTime 0.75 and 0.42, respectively). In the event-time association task, our algorithm assigned an inappropriate timestamp for 25% of the events, while the TARSQI toolkit demonstrated a considerably lower performance, assigning inappropriate timestamps in 61.5% of the same

  17. Hand Safety

    Science.gov (United States)

    ... Gardening Safety Turkey Carving Removing a Ring Español Artritis de la base del pulgar Dedo en gatillo ... Gardening Safety Turkey Carving Removing a Ring Español Artritis de la base del pulgar Dedo en gatillo ...

  18. Water Safety

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Water Safety KidsHealth > For Parents > Water Safety Print A ... best measure of protection. previous continue Making Kids Water Wise It's important to teach your kids proper ...

  19. SAFETY FIRST

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Ensuring safety while peacefully utilizing nuclear energy is a top priority for China A fter a recent earthquake in Japan caused radioactive leaks at a nuclear power plant in Tokyo, the safety of nuclear energy has again aroused public attention.

  20. Safety Plan

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Swan Lake National Wildlife Refuge Safety Plan discusses policies for the safety of the station employees, volunteers, and public. This plan seeks to identify...

  1. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Directory of Open Access Journals (Sweden)

    Pierre van Damme

    Full Text Available BACKGROUND: Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇ for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. METHODOLOGY: Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen, a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen with the polysaccharide vaccine. PRINCIPAL FINDINGS: All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. CONCLUSIONS: Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01123941 NCT01193907.

  2. Safety and performance of cohesive polydensified matrix hyaluronic acid fillers with lidocaine in the clinical setting – an open-label, multicenter study

    Directory of Open Access Journals (Sweden)

    Kühne U

    2016-10-01

    Full Text Available Ulrich Kühne,1 Jørgen Esmann,2 Dennis von Heimburg,3 Matthias Imhof,1 Petra Weissenberger,4 Gerhard Sattler,5 On behalf of the BALIA Study Group 1Aesthetische Dermatologie im Medico Palais, Bad Soden, Germany; 2Jørgen Esmann Aps, Hellerup, Denmark; 3Praxisklinik Kaiserplatz, Frankfurt am Main, Germany; 4Corporate Clinical Research, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany; 5Rosenparkklinik GmbH, Darmstadt, Germany Abstract: Cohesive polydensified matrix (CPM® hyaluronic acid fillers are now available with or without lidocaine. The aim of this study was to investigate the safety and performance of CPM® fillers with lidocaine in the clinical setting. In an open-label, prospective, postmarketing study, 108 patients from seven sites in Germany and Denmark were treated with one or more lidocaine-containing CPM® fillers. Performance was assessed using the Merz Aesthetics Scales® (MAS. Pain was rated on an 11-point visual analog scale. Patients’ and physicians’ satisfaction as well as adverse events were recorded. Improvements of ≥1-point on MAS immediately after and 17 days posttreatment were observed in ~90% of patients compared with baseline. All investigators assessed ejection force, product positioning, and performance as similar or superior to the respective nonlidocaine products. Overall, 94% of investigators were satisfied with the esthetic outcomes and were willing to continue using the products. All patients except one were satisfied with the results, and all were willing to repeat the treatment. Mean pain scores were low during (<3.0 and after injection (<0.6. Except for one case of bruising, all adverse events were mild to moderate. CPM® fillers with lidocaine are safe and effective for a wide range of esthetic facial indications. Keywords: cohesive polydensified matrix, dermal fillers, Belotero, Esthélis, Fortélis, Modélis

  3. Non-clinical safety evaluation of repeated intramuscular administration of the AS15 immunostimulant combined with various antigens in rabbits and cynomolgus monkeys.

    Science.gov (United States)

    Garçon, N; Silvano, J; Kuper, C F; Baudson, N; Gérard, C; Forster, R; Segal, L

    2016-02-01

    Combination of tumor antigens with immunostimulants is a promising approach in cancer immunotherapy. We assessed animal model toxicity of AS15 combined with various tumor antigens: WT1 (rabbits), or p501, dHER2 and recPRAME (cynomolgus monkeys), administered in seven or 20 dose regimens versus a saline control. Clinical and ophthalmological examinations, followed by extensive post-mortem pathological examinations, were performed on all animals. Blood hematology and biochemistry parameters were also assessed. Antigen-specific antibody titers were determined by enzyme-linked immunosorbent assay. Additional assessments in monkeys included electrocardiography and immunohistochemical evaluations of the p501 expression pattern. Transient increases in body temperature were observed 4 h or 24 h after injections of recPRAME + AS15 and dHER2 + AS15. Edema and erythema were observed up to 1 week after most injections of recPRAME + AS15 and all injections of dHER2 + AS15. No treatment-related effects were observed for electrocardiography parameters. Mean fibrinogen levels were significantly higher in all treated groups compared to controls, but no differences could be observed at the end of the treatment-free period. Transient but significant differences in biochemistry parameters were observed post-injection: lower albumin/globulin ratios (p501 + AS15), and higher bilirubin, urea and creatinine (dHER2 + AS15). Pathology examinations revealed significant increases in axillary lymph node mean weights (recPRAME + AS15) compared to controls. A 100% seroconversion rate was observed in all treated groups, but not in controls. p501 protein expression was observed in prostates of all monkeys from studies assessing p501 + AS15. These results suggest a favorable safety profile of the AS15-containing candidate vaccines, supporting the use of AS15 for clinical development of potential anticancer vaccines.

  4. Safety and efficacy of PDpoetin for management of anemia in patients with end stage renal disease on maintenance hemodialysis: results from a phase IV clinical trial

    Directory of Open Access Journals (Sweden)

    Abbas Norouzi Javidan

    2014-09-01

    Full Text Available Recombinant human erythropoietin (rHuEPO is available for correcting anemia. PDpoetin, a new brand of rHuEPO, has been certified by Food and Drug Department of Ministry of Health and Medical Education of Iran for clinical use in patients with chronic kidney disease. We conducted this post-marketing survey to further evaluate the safety and efficacy of PDpoetin for management of anemia in patients on maintenance hemodialysis. Patients from 4 centers in Iran were enrolled for this multicenter, open-label, uncontrolled phase IV clinical trial. Changes in blood chemistry, hemoglobin and hematocrit levels, renal function, and other characteristics of the patients were recorded for 4 months; 501 of the patients recruited, completed this study. Mean age of the patients was 50.9 (±16.2 years. 48.7% of patients were female. Mean of the hemoglobin value in all of the 4 centers was 9.29 (±1.43 g/dL at beginning of the study and reached 10.96 (±2.23 g/dL after 4 months and showed significant increase overall (P<0.001. PDpoetin dose was stable at 50-100 U/kg thrice weekly. Hemorheologic disturbancesand changes in blood electrolytes was not observed. No case of immunological reactions to PDpoetin was observed. Our study, therefore, showed that PDpoetin has significantly raised the level of hemoglobin in the hemodialysis patients (about 1.7±0.6 g/dL. Anemia were successfully corrected in 49% of patients under study. Use of this biosimilar was shown to be safe and effective for the maintenance of hemoglobin in patients on maintenance hemodialysis.

  5. A randomized, controlled clinical trial comparing efficacy, safety and cost effectiveness of Lornoxicam with Diclofenac Sodium in patients of osteoarthritis knee

    Directory of Open Access Journals (Sweden)

    Vishalkumar K. Vadgama

    2011-07-01

    Full Text Available Osteoarthritis is a chronic painful condition affecting larger joints; most commonly knee joint. Pharmacological control of pain is the mainstay of management of osteoarthritis. Many patientsfail to achieve satisfactory reduction in pain with one of the most commonly prescribed drugs, diclofenac sodium, even after maximum daily allowed doses. Lornoxicam is a newer molecule in the Indian market promising better pain relief in context of low back pain and post knee replacement surgery pain as compared to standard therapies. As per profile of lornoxicam, if it is better than diclofenac sodium then it will be helpful in managing the patients of osteoarthritis more effectively. Till date no comparative clinical trial has been done to compare these two drugs for the management of osteoarthritis knee. So, to evaluate the same we carried out this study to compare safety, efficacy and cost effectiveness of lornoxicam and diclofenac sodium in relieving pain in patients of osteoarthritis knee. This study is a randomized, open labeled, controlled clinical trial having 40 newly diagnosed patients with osteoarthritis knee. After random allocation into two groups i.e. group D and group L (each having 20 patients; group D received diclofenac sodium 50 mg 12 hourly and group L received lornoxicam 4 mg 8 hourly for a period of 3 months. All patients were assessed with visual analogue scale and 100 meter walking test before starting of therapy, at 15 days and at 1, 2 and 3 months of therapy. Adverse drug reactions and cost of therapy was monitored during the study period. Mean decrease in visual analogue scale and time of 100 meter walking test was statistically significant in lornoxicam group as compared to diclofenac sodium. Gastric irritation was reported in one patient from group L and two patients from group D. Lornoxicam significantly relieves pain of osteoarthritis knee than diclofenac sodium without adversely affecting the tolerability to the patients.

  6. Safety of closed-loop therapy during reduction or omission of meal boluses in adolescents with type 1 diabetes: a randomized clinical trial.

    Science.gov (United States)

    Elleri, D; Maltoni, G; Allen, J M; Nodale, M; Kumareswaran, K; Leelarathna, L; Thabit, H; Caldwell, K; Wilinska, M E; Calhoun, P; Kollman, C; Dunger, D B; Hovorka, Roman

    2014-11-01

    We evaluated the safety and efficacy of closed-loop therapy with meal announcement during reduction and omission of meal insulin boluses in adolescents with type 1 diabetes (T1D). Twelve adolescents with T1D [six male; mean (s.d.) age 15.9 (1.8) years; mean (s.d.) glycated haemoglobin (HbA1c) 77 (27) mmol/mol] were studied in a randomized crossover study comparing closed-loop therapy with meal announcement with conventional pump therapy over two 24-h stays at a clinical research facility. Identical meals were given on both occasions. The evening meal insulin bolus was calculated to cover half of the carbohydrate content of the meal and no bolus was delivered for lunch. Plasma glucose levels were in the target range of 3.9-10 mmol/l for a median [interquartile range (IQR)] of 74 (55,86)% of the time during closed-loop therapy with meal announcement and for 62 (49,75)% of the time during conventional therapy (p = 0.26). Median (IQR) time spent with plasma glucose levels > 10 mmol/l [23 (13,39) vs. 27 (10,50)%; p = 0.88] or meal announcement in adolescents with poorly controlled T1D who miscalculate or miss meal insulin boluses. © 2014 John Wiley & Sons Ltd.

  7. Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies

    Science.gov (United States)

    2014-01-01

    Background Canagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). The efficacy and safety of canagliflozin were evaluated in patients with T2DM canagliflozin 100 and 300 mg were analysed by age: Canagliflozin 100 and 300 mg reduced HbA1c and fasting plasma glucose relative to placebo in patients canagliflozin doses reduced body weight and systolic BP relative to placebo in patients canagliflozin 100 mg than other groups in patients ≥65 years of age. As in patients canagliflozin relative to placebo in those ≥65 years of age. Incidences of urinary tract infections (UTIs), renal-related AEs, AEs related to volume depletion, and documented hypoglycaemia episodes were similar across all treatment groups in patients ≥65 years of age; no notable trends were observed with canagliflozin 100 and 300 mg relative to placebo in these AEs among patients canagliflozin were similar in both age subsets. Conclusions Canagliflozin improved glycaemic control, body weight, and systolic BP, and was generally well tolerated in older patients with T2DM. Trial registration ClinicalTrials.gov, NCT01081834; NCT01106677; NCT01106625; NCT01106690. PMID:24742013

  8. Clinical Performance and Safety of 108 SpineJack Implantations: 1-Year Results of a Prospective Multicentre Single-Arm Registry Study

    Directory of Open Access Journals (Sweden)

    David Noriega

    2015-01-01

    Full Text Available This prospective, consecutive, multicentre observational registry aimed to confirm the safety and clinical performance of the SpineJack system for the treatment of vertebral compression fractures (VCF of traumatic origin. We enrolled 103 patients (median age: 61.6 years with 108 VCF due to trauma, or traumatic VCF with associated osteoporosis. Primary outcome was back pain intensity (VAS. Secondary outcomes were Oswestry Disability Index (ODI, EuroQol-VAS, and analgesic consumption. 48 hours after surgery, a median relative decrease in pain intensity of 81.5% was observed associated with a significant reduction in analgesic intake. Improvements in disability (91.3% decrease in ODI score and in quality of life (increase 21.1% of EQ-VAS score were obtained 3 months after surgery. All results were maintained at 12 months. A reduction in the kyphotic angulation was observed postoperatively (-5.4±6.3°; p<0.001, remained at 12 months (-4.4±6.0°, p=0.002. No adverse events were implant-related and none required device removal. Three patients (2.9% experienced procedure-related complications. The overall adjacent fracture rate up to 1 year after surgery was 2.9%. The SpineJack procedure is an effective, low-risk procedure for patients with traumatic VCF allowing a fast and sustained improvement in quality of life over 1 year after surgery.

  9. Governing board, C-suite, and clinical management perceptions of quality and safety structures, processes, and priorities in U.S. hospitals.

    Science.gov (United States)

    Vaughn, Thomas; Koepke, Mark; Levey, Samuel; Kroch, Eugene; Hatcher, Christopher; Tompkins, Christopher; Baloh, Jure

    2014-01-01

    To achieve quality improvement in hospitals requires greater attention to systems thinking than is typical at this time, including a shared understanding across different levels of the hospital of the current state of quality improvement efforts. A self-administered survey assessed the perceptions of board members, C-suite executives, and clinical managers regarding quality activities and structures. This instrument, the Hospital Leadership and Quality Assessment Tool (HLQAT), includes 13 domains in six conceptual areas that we believe are major organizational drivers of quality and safety: (1) commitment of senior leaders, (2) a vision of exemplary quality, (3) a supportive culture, (4) accountable leadership, (5) appropriate organizational structures, and (6) adaptive capability. HLQAT survey results from a convenience sample of more than 300 hospitals were linked to performance on the Centers for Medicare & Medicaid Services (CMS) Core Measures. The results show significantly different perceptions between the groups. Higher HLQAT scores for each respondent group were associated with better hospital performance on the CMS Core Measures. There is no magic bullet--no one domain dominates. Leaders in higher-performing hospitals appear to be more effective at conveying their vision of quality care and creating a culture that supports an expectation that staff and leadership will work across traditional boundaries to improve quality.

  10. Gelucire and Gelucire-PEG400 formulations; tolerability in species used for non-clinical safety testing after oral (gavage) dosing.

    Science.gov (United States)

    Elander, Mikael; Boll, Jette B; Hojman, Anne S; Rasmussen, Allan D

    2016-11-01

    The selection of a vehicle for oral formulations of compounds to be used in non-clinical safety studies is a challenge for poorly soluble compounds. Typically a compromise between solubility and tolerability has to be reached. Vehicle tolerability data are not readily available for a number of vehicles, and a series of oral tolerability studies were, therefore, conducted with Gelucire and Gelucire:PEG400 formulations in rats, dogs and minipigs in order to determine tolerable daily dose volumes in these species. Gelucire and Gelucire:PEG400 formulations were assessed in studies for up to 5 days in minipigs, 7 days in rats and up to 39 weeks in dogs. Gastrointestinal side effects in terms of soft and/or liquid faeces were noted in all species, but the sensitivity to these effects differed between species with the dog being the most sensitive. It was concluded that Gelucire:PEG400 (90:10) was tolerated in Beagle dogs when administered at 1 ml kg(-1) once daily for 39 weeks, and 100% Gelucire was tolerated in the rat and the minipig when administered once daily at 5 ml kg(-1) for 5 days. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Safety and performance of cohesive polydensified matrix hyaluronic acid fillers with lidocaine in the clinical setting – an open-label, multicenter study

    Science.gov (United States)

    Kühne, Ulrich; Esmann, Jørgen; von Heimburg, Dennis; Imhof, Matthias; Weissenberger, Petra; Sattler, Gerhard

    2016-01-01

    Cohesive polydensified matrix (CPM®) hyaluronic acid fillers are now available with or without lidocaine. The aim of this study was to investigate the safety and performance of CPM® fillers with lidocaine in the clinical setting. In an open-label, prospective, postmarketing study, 108 patients from seven sites in Germany and Denmark were treated with one or more lidocaine-containing CPM® fillers. Performance was assessed using the Merz Aesthetics Scales® (MAS). Pain was rated on an 11-point visual analog scale. Patients’ and physicians’ satisfaction as well as adverse events were recorded. Improvements of ≥1-point on MAS immediately after and 17 days posttreatment were observed in ~90% of patients compared with baseline. All investigators assessed ejection force, product positioning, and performance as similar or superior to the respective nonlidocaine products. Overall, 94% of investigators were satisfied with the esthetic outcomes and were willing to continue using the products. All patients except one were satisfied with the results, and all were willing to repeat the treatment. Mean pain scores were low during (<3.0) and after injection (<0.6). Except for one case of bruising, all adverse events were mild to moderate. CPM® fillers with lidocaine are safe and effective for a wide range of esthetic facial indications. PMID:27799807

  12. The hemorheological safety of pulsed electromagnetic fields in postmenopausal women with osteoporosis in southwest China: a randomized, placebo controlled clinical trial.

    Science.gov (United States)

    Liu, Huifang; Yang, Lin; He, Hongchen; Zhou, Jun; Liu, Ying; Wang, Chunyan; Wu, Yuanchao; He, Chengqi

    2013-01-01

    Apart from medications, pulsed electromagnetic fields (PEMFs) are used to treat osteoporosis nowadays. However studies on hemorheological safety of PEMFs were scarce. This randomized, placebo controlled clinical trial assessed whether PEMFs could lead to significant hemorheological changes. Fifty-five postmenopausal women were randomly assigned to receive placebo or PEMFs. Venous blood samples were collected at baseline and after treatment to measure 14 hemorheological determinants. Independent samples t-test, paired samples t-test and chi-squared tests were performed respectively. Relationships between variables were determined by Pearson correlation analysis. Multiple linear stepwise regression analysis was used to explore predictors of selected determinants. No significant differences existed between the placebo and PEMFs groups for any of the 14 hemorheological determinants (P>0.05) or the percentage of patients with hemorheological determinant within reference range (P>0.05). Hematocrit was found to be correlated with BMI (P=0.007). The most significant predictor of blood reduced viscosity at low shear rate was blood viscosity at low shear rate. And blood reduced viscosity at high shear rate was the most important predictor of plasma viscosity. These results showed, compared with placebo, PEMFs treatment of postmenopausal osteoporosis was not associated with adverse changes in hemorheological determinants, which may contribute to venous thromboembolism.

  13. Comparison of the Supraglottic Airway Devices Classic, Fastrach and Supreme Laryngeal Mask Airway: A Prospective Randomised Clinical Trial of Efficacy, Safety and Complications.

    Science.gov (United States)

    Kömür, Erdal; Bakan, Nurten; Tomruk, Şenay Göksu; Karaören, Gülşah; Doğan, Zelin Topaç

    2015-12-01

    This prospective randomised study was designed to compare the Laryngeal Mask Airway (LMA) Classic, LMA Fastrach and LMA Supreme regarding ease of insertion and insertion time as primary outcomes and reposition, success rate of trials, effects on haemodynamic parameters, provision of an adequate and safe airway, amount of leakage and oropharyngeal and systemic complications as secondary outcomes. In this clinical trial, 90 patients aged 18-70 years of American Society of Anesthesiologists (ASA) group I-II were randomised into three groups as providing airway via LMA Classic, LMA Fastrach or LMA Supreme instead of tracheal intubation. No muscle relaxant was used. The allocated LMA was inserted by the same anaesthetist; bispectral index (BIS) was between 40% and 60%. There was no statistical difference among the groups regarding the ease of insertion and insertion time as primary outcomes; the incidence of repositioning during placement was significantly higher in the LMA Classic group than that in other groups (p<0.05) and the rates of bloodstain on the device as well as oropharyngeal mucosal oedema were higher in the LMA Fastrach group than those in other groups (p<0.05) as secondary outcomes. We suggest that LMA Classic, LMA Supreme and LMA Fastrach had similar effectiveness regarding efficiency and airway safety. However, LMA Supreme seems to be more advantageous as it is more appropriate for fewer oropharyngeal complications and there was no repositioning.

  14. Efficacy and safety of prolonged-release melatonin for insomnia in middle-aged and elderly patients with hypertension: a combined analysis of controlled clinical trials

    Directory of Open Access Journals (Sweden)

    Lemoine P

    2012-01-01

    Full Text Available Patrick Lemoine1, Alan G Wade2, Amnon Katz3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2CPS Research, 3 Todd Campus, Glasgow, UK; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, IsraelBackground: Add-on prolonged-release melatonin (PRM in antihypertensive therapy has been shown to ameliorate nocturnal hypertension. Hypertension is a major comorbidity among insomnia patients. The efficacy and safety of PRM for primary insomnia in patients aged 55 years and older who are treated with antihypertensive drugs were evaluated.Methods: Post hoc analysis of pooled antihypertensive drug-treated subpopulations from four randomized, double-blind trials of PRM and placebo for 3 weeks (N[PRM] = 195; N[placebo] = 197 or 28 weeks (N[PRM] = 157; N[placebo] = 40. Efficacy measurements included Leeds Sleep Evaluation Questionnaire scores of quality of sleep and alertness and behavioral integrity the following morning after 3 weeks, and sleep latency (daily sleep diary and Clinical Global Impression of Improvement (CGI-I after 6 months of treatment. Safety measures included antihypertensive drug-treated subpopulations from these four and three additional single-blind and open-label PRM studies of up to 1 year (N[PRM] = 650; N[placebo] = 632.Results: Quality of sleep and behavior following wakening improved significantly with PRM compared with placebo (P < 0.0001 and P < 0.0008, respectively. Sleep latency (P = 0.02 and CGI-I (P = 0.0003 also improved significantly. No differences were observed between PRM and placebo groups in vital signs, including daytime blood pressure at baseline and treatment phases. The rate of adverse events normalized per 100 patient-weeks was lower for PRM (3.66 than for placebo (8.53.Conclusions: The findings demonstrate substantive and sustained efficacy of PRM in primary insomnia patients treated with antihypertensive drugs

  15. An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism.

    Science.gov (United States)

    Nieschlag, Eberhard; Bouloux, Pierre-Marc G; Stegmann, Barbara J; Shankar, R Ravi; Guan, Yanfen; Tzontcheva, Anjela; McCrary Sisk, Christine; Behre, Hermann M

    2017-03-07

    Hypogonadotropic hypogonadism (HH) in men results in insufficient testicular function and deficiencies in testosterone and spermatogenesis. Combinations of human chorionic gonadotropin (hCG) and recombinant follicle-stimulating hormone (recFSH) have been successful in the treatment of HH. Corifollitropin alfa is a long-acting FSH-analog with demonstrated action in women seeking infertility care. The aim of this study was to investigate the efficacy and safety of corifollitropin alfa combined with hCG to increase testicular volume and induce spermatogenesis in men with HH. This was a Phase III, multi-center, open-label, single-arm trial of corifollitropin alfa in azoospermic men aged 18 to 50 years with HH. After 16 weeks of pretreatment of 23 subjects with hCG alone, 18 subjects with normalized testosterone (T) levels who remained azoospermic entered the 52-week combined treatment phase with hCG twice-weekly and 150 μg corifollitropin alfa every other week. The increase in testicular volume (primary efficacy endpoint) and induction of spermatogenesis resulting in a sperm count ≥1 × 10(6)/mL (key secondary efficacy endpoint) during 52 weeks of combined treatment were assessed. Safety was evaluated by the presence of anti-corifollitropin alfa antibodies and the occurrence of adverse events (AEs). Mean (±SD) testicular volume increased from 8.6 (±6.09) mL to 17.8 (±8.93) mL (geometric mean fold increase, 2.30 [95% CI: 2.03, 2.62]); 14 (77.8%) subjects reached a sperm count ≥1 × 10(6)/mL. No subject developed confirmed anti-corifollitropin alfa antibodies during the trial. Treatment was generally well tolerated. Corifollitropin alfa 150 μg administrated every other week combined with twice-weekly hCG for 52 weeks increased testicular volume significantly, and induced spermatogenesis in >75% of men with HH who had remained azoospermic after hCG treatment alone. ClinicalTrials.gov: NCT01709331 .

  16. Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: A comparative prospective clinical trial.

    Science.gov (United States)

    de Souza, Camila M; Tardelli, Maria A; Tedesco, Helio; Garcia, Natalia N; Caparros, Mario P; Alvarez-Gomez, Jose A; de Oliveira Junior, Itamar S

    2015-10-01

    Renal failure affects the pharmacology of nondepolarizing neuromuscular blockers making recovery of neuromuscular function unpredictable. Sugammadex antagonises rocuronium-induced neuromuscular blockade by encapsulating rocuronium, creating a stable complex molecule that is mainly excreted by the kidneys. Previous studies suggest that sugammadex is effective in reversing moderate neuromuscular block in the presence of renal failure, but no data are available regarding reversal of profound neuromuscular block in patients with renal failure. The objective of this study is to compare the efficacy and safety of sugammadex in reversing profound neuromuscular block induced by rocuronium in patients with end-stage renal disease and those with normal renal function. A prospective clinical trial. Two university hospitals, from 1 October 2011 to 31 January 2012. Forty patients undergoing kidney transplant: 20 with renal failure [creatinine clearance (ClCr) 90 ml min). Neuromuscular monitoring was performed by acceleromyography and train-of-four (TOF) stimulation. Profound neuromuscular block (posttetanic count, one to three responses) was maintained during surgery. Sugammadex 4 mg kg was administered on completion of skin closure. Recovery of the TOF ratio to 0.9 was recorded. Monitoring of neuromuscular function continued in the postanesthesia care unit for a further 2 h. The efficacy of sugammadex was evaluated by the time taken for the TOF ratio to recover to 0.9. The safety of sugammadex was assessed by monitoring for recurrence of neuromuscular block every 15 min for 2 h. Secondary variables were time to recovery of TOF ratio to 0.7 and 0.8. After sugammadex administration, the mean time for recovery of the TOF ratio to 0.9 was prolonged in the renal failure group (5