... Careers at LLS Language English Spanish Canadian English French Canadian I am a Patient looking for Disease/ ... other treatments you've used. Your doctor may speak to you about participating in a clinical trial. ...
Cihoric, Nikola; Tsikkinis, Alexandros; van Rhoon, Gerard; Crezee, Hans; Aebersold, Daniel M.; Bodis, Stephan; Beck, Marcus; Nadobny, Jacek; Budach, Volker; Wust, Peter; Ghadjar, Pirus
Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. The records of 175,538 clinical trials registered at ClinicalTrials.gov were
Reekie, J; Mocroft, A; J, Neaton
and knowledge of HIV led to short-term trials using surrogate outcomes such as viral load and CD4 count. This established a faster drug approval process that complimented the rapid need to evaluate and provide access to drugs based on short-term trials. However, no treatment has yet been found that eradicates......Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...
Reekie, J; Mocroft, A; J, Neaton
Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...
Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...
Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be ...
Full Text Available ... Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, ... required to have an IRB. Office for Human Research Protections The U.S. Department of Health and Human ...
Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... care providers might be part of your treatment team. They will monitor your health closely. You may ...
Full Text Available ... need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in ... Maryland, runs clinical trials. Many other clinical trials take place in medical centers and ... trial can have many benefits. For example, you may gain access to new treatments before ...
Full Text Available ... Blood Institute (NHLBI) sponsored a trial of two different combinations of asthma treatments. The trial found that ... ways, taking part in a clinical trial is different from having regular care from your own doctor. ...
Full Text Available ... to the strategies and treatments that work best. How Clinical Trials Work If you take part in ... a protocol (PRO-to-kol). This plan explains how the trial will work. The trial is led ...
Jakobsen, Jan Nyrop; Sørensen, Jens Benn
Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all...... clinical trials evaluating the effect of targeted treatments in MM....
Full Text Available ... treatment, or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research ... are required to have an IRB. Office for Human Research Protections The U.S. Department of Health and ...
Full Text Available ... Clinical trials produce the best data available for health care decisionmaking. The purpose of clinical trials is research, ... and advance medical care. They also can help health care decisionmakers direct resources to the strategies and treatments ...
Full Text Available ... medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a key research tool for ... other for moderate persistent asthma. The results provided important treatment information for doctors and patients. The results ...
Clinical trials are research studies that test how well new medical approaches work in people. Each study answers ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...
Full Text Available ... are needed focusing on children's health with the goal to develop treatments, drugs, and devices specific to ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...
Full Text Available ... and treatments that work best. How Clinical Trials Work If you take part in a clinical trial, ... Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute of Health ...
Full Text Available ... are research studies that explore whether a medical strategy, treatment, or device is safe and effective for ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...
Full Text Available ... Health Topics / About Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical strategy, treatment, ... tool for advancing medical knowledge and patient care. Clinical research is done only if doctors don't know ...
Zhe He; Zhiwei Chen; George, Thomas J; Lipori, Gloria; Bian
The generalizability (external validity) of clinical trials has long been a concern for both clinical research community as well as the general public. Results of trials that do not represent the target population may not be applicable to the broader patient population. In this study, we used a previously published metric Generalizability Index for Study Traits (GIST) to assess the population representativeness of colorectal cancer (CRC) treatment trials. Our analysis showed that the quantitative eligibility criteria of CRC trials are in general not restrictive. However, the qualitative eligibility criteria in these trials are with moderate or strict restrictions, which may impact their population representativeness of the real-world patient population.
Full Text Available ... small groups of people for safety and side effects. Phase II clinical trials look at how well ... confirm how well treatments work, further examine side effects, and compare new treatments with other available treatments. ...
Full Text Available ... proven to work and you're in the group getting it, you might be among the first to benefit. If you're in a clinical trial and ... health closely. In late-phase clinical trials, possible benefits or ... trials have large groups of similar patients taking the same treatment the ...
Full Text Available ... Back To Health Topics / About Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a ... is safe and effective for humans. What Are Clinical Trials? Clinical trials are research studies that explore ...
Full Text Available ... you may get tests or treatments in a hospital, clinic, or doctor's office. In some ways, taking ... people will need to travel or stay in hospitals to take part in clinical trials. For example, ...
Full Text Available ... Clinical trials are research studies that explore whether a medical strategy, treatment, or device is safe and ... drugs, and devices specific to children. Resources for a Wide Range of Audiences The Children and Clinical ...
Full Text Available ... and how often they will get them; what type of data will be collected during the clinical trial; and detailed information about the treatment plan. Eligibility Criteria A clinical ...
Full Text Available ... of research. Sometimes, when no accepted standard treatment exists for a condition, people in one group may ... medical centers, and hospitals. ClinicalTrials.gov View a database of clinical studies (past and present) funded or ...
Full Text Available ... care providers might be part of your treatment team. They will monitor your health closely. You may ... taking part in a clinical trial. Your treatment team also may ask you to do other tasks. ...
Full Text Available ... questions and clinical trials. Optimizing our Clinical Trials Enterprise NHLBI has a strong tradition of supporting clinical ... multi-pronged approach to Optimize our Clinical Trials Enterprise that will make our clinical trials enterprise even ...
Full Text Available ... health closely. In late-phase clinical trials, possible benefits or risks of a treatment can be identified earlier than they would be in general medical practice. This is because late-phase trials have large groups of similar patients taking the same treatment ...
Korn, E L; Baumrind, S
The standard design for randomised clinical trials may be inappropriate when the clinician believes that one of the treatments being tested is superior for the patient, or when the clinician has a preference for one of the treatments. For such instances the suggestion is that the patient is randomly allocated to treatment only when there is clinical disagreement about treatment of choice for that patient, and then the patient is assigned to a clinician who had thought that the regimen allocated is the one most appropriate for that patient.
Jakobsen, Jan Nyrop; Sørensen, Jens Benn
Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all...
Full Text Available ... clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a ... purpose is to ensure that clinical trials are ethical and that the participants' rights are protected. The ...
Full Text Available ... issues arise. Participation and Eligibility Each clinical trial defines who is eligible to take part in the ... the strategy or treatment is having harmful effects. Food and Drug Administration In the United States, the ...
Full Text Available ... benefits of lowering high blood pressure in the elderly outweighed the risks. Other examples of clinical trials ... treatment is or how well it works. Children (aged 18 and younger) get special protection as research ...
Full Text Available ... Usually, a computer program makes the group assignments. Masking The term "masking" refers to not telling the clinical trial participants which treatment they're getting. Masking, or "blinding," helps avoid bias. For this reason, ...
Full Text Available ... as gene therapy or new biological treatments. Health insurance and health care providers don't always cover ... oversight for clinical trials that are testing new medicines or medical devices. The FDA reviews applications for ...
Full Text Available ... or treatment is having harmful effects. Food and Drug Administration In the United States, the Food and ... in clinical trials at the NIH. The NHLBI conducts a large number of research studies at the ...
Full Text Available ... look at the best age and frequency for doing screening tests, such as mammography; and compare two ... available treatments. Steps To Avoid Bias The researchers doing clinical trials take steps to avoid bias. "Bias" ...
Full Text Available ... treatment is having harmful effects. Food and Drug Administration In the United States, the Food and Drug Administration (FDA) provides oversight for clinical trials that are ...
Full Text Available ... has had certain treatments or has other health problems. Eligibility criteria ensure that new approaches are tested ... review data from a clinical trial for safety problems or differences in results among different groups. The ...
Full Text Available ... or treatment is having harmful effects. Food and Drug Administration In the United States, the Food and Drug Administration (FDA) provides oversight for clinical trials that ...
Full Text Available ... III clinical trial is required to have a Data and Safety Monitoring Board (DSMB). This board consists of a group of research and study topic experts. The NIH also requires DSMBs for large trials comparing alternative strategies for diagnosis or treatment. In addition, the NIH ...
Full Text Available ... phase II clinical trials. The risk of side effects might be even greater for trials with cutting-edge approaches, such as gene therapy or new biological treatments. Health insurance and health care providers don't always ...
Full Text Available ... how these studies should be done. Patient Rights Informed Consent Informed consent is the process of giving clinical trial participants ... part and during the course of the trial. Informed consent includes details about the treatments and tests you ...
Full Text Available ... Back To Health Topics / About Clinical Trials About Clinical Trials Clinical trials are research studies that explore whether a medical ... is safe and effective for humans. What Are Clinical Trials? Clinical trials are research studies that explore whether ...
Full Text Available ... study results. Clinical Trial Protocol Each clinical trial has a master plan called a protocol (PRO-to-kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...
Full Text Available ... patients. The results from other clinical trials show what doesn't work or may cause harm. For example, the NHLBI ... had to accept medicines and treatments based on what is known to work in adults. To improve clinical care of children, ...
Full Text Available ... examples of clinical trials that test principles or strategies include studies that explore whether surgery or other medical treatments ... board consists of a group of research and study topic experts. The NIH also ... alternative strategies for diagnosis or treatment. In addition, the NIH ...
Full Text Available ... and doctors' offices around the country. Benefits and Risks Possible Benefits Taking part in a clinical trial can have many benefits. For example, you may gain access to new treatments before they're widely available. If a new treatment is proven to work and you're in the group getting it, ...
Full Text Available ... people and is safe and which treatments or strategies work best for certain illnesses or groups of people. Some clinical trials show a positive ... available. If a new treatment is proven to work and you're in the group getting ... get the new strategy being tested, you may receive the current standard ...
Full Text Available ... or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research studies ... parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, doctors, nurses, ...
Full Text Available ... groups of people. Some clinical trials show a positive result. For example, the National Heart, Lung, and ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find ...
Full Text Available ... possible benefits. Clinical Trial Phases Clinical trials of new medicines or medical devices are done in phases. These ... provides oversight for clinical trials that are testing new medicines or medical devices. The FDA reviews applications for ...
Full Text Available ... clinical trials. The NIH may partner with these companies or groups to help sponsor some trials. All types of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical trials are a key research tool for advancing medical knowledge and patient ...
Full Text Available Abstract Background Magnesium (Mg deficiency is common among alcoholics. Earlier research suggests that Mg treatment may help to normalize elevated enzyme activities and some other clinically relevant parameters among alcoholics but the evidence is weak. Methods The effect of Mg was studied in a randomized, parallel group, double-blind trial. The patients were first treated for alcohol withdrawal symptoms and then received for 8 weeks either 500 mg of Mg divided into two tablets or matching placebo. Measurements were made at the beginning and in the end of the Mg treatment period. The primary outcome was serum gamma-glutamyltransferase (S-GGT activity; secondary outcomes included aspartate-aminotransferase (S-AST and alanine-aminotransferase (S-ALT activity. Results The number of randomized patients (completers was 64 (27 in the treatment and 54 (31 in the control group. In intention-to-treat-analyses and in most analyses of study completers, there were no significant differences between the Mg-treated and placebo groups in the outcome variables. When baseline serum Mg level, coffee intake, and the number of unused Mg tablets were controlled for in a multivariate regression model, after-treatment serum Mg levels were found to be higher among the Mg-treated group than in the placebo group (t-test 3.334, df = 53, p = 0.002. After controlling for age, body weight, baseline alcohol intake, subsequent change in alcohol intake and baseline S-AST, the after-treatment S-AST levels were found to be lower among the Mg-treated group than in the placebo group (t-test 2.061, df = 49, p = 0.045. Conclusion Mg treatment may speed up the S-AST decrease in compliant patients. This might decrease the risk of death from alcoholic liver disease. Trial Registration ClinicalTrials.gov ID NCT00325299
Robert G. Gish
Full Text Available Despite its place as the third leading cause of cancer deaths worldwide, there are currently no approved chemotherapeutic agents, devices or techniques to treat hepatocellular carcinoma. Importantly, there have been no phase III studies demonstrating survival benefit, nor any randomized studies of treatment except for transarterial chemoembolization and most recently sorafenib. The importance of well-designed clinical trials of agents to treat HCC has never been greater. However, general clinical study design issues, combined with HCC-specific issues pose significant challenges in structuring such studies. HCC-related challenges include the heterogeneity of this cancer and the fact that it is frequently accompanied by significant comorbidities at diagnosis, such as active hepatitis B or C virus replication, substantial past or on-going alcohol use, and cirrhosis, itself often a fatal disease. The recently published comparison of a newer treatment, nolatrexed to doxorubicin, and comments about this study’s initial HCC diagnostic criteria, staging system, comparator therapy and choice of endpoints have provided a platform to discuss the challenges unique to the design of HCC clinical trials. The difficulty in accurately framing study results obtained from the constantly changing HCC clinical landscape and approaches to meet these challenges will be reviewed.
Full Text Available ... protocol affect the trial's results. Comparison Groups In most clinical trials, researchers use comparison groups. This means ... study before you agree to take part. Randomization Most clinical trials that have comparison groups use randomization. ...
Full Text Available ... more information about eligibility criteria, go to "How Do Clinical Trials Work?" Some trials enroll people who ... for adults. For more information, go to "How Do Clinical Trials Protect Participants?" For more information about ...
Maria do Carmo Santos Araújo
Full Text Available Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide, were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.
Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa
Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma-Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.
Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L.; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa
Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut) in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide), were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer. PMID:22811748
Full Text Available ... moderate persistent asthma. The results provided important treatment information for doctors and patients. The results from other clinical trials show what doesn't work or may cause harm. For example, the NHLBI Women's Health Initiative tested whether hormone ...
Full Text Available ... treatments produce better results for certain illnesses or groups of people; look at the best age and frequency for doing screening tests, such as mammography; and compare two or more screening tests to see which test ... Some companies and groups sponsor clinical trials that test the safety of ...
Full Text Available ... safe a treatment is or how well it works. Children (aged 18 and younger) get special protection as research subjects. Almost always, parents must give legal consent for their child to take part in a clinical trial. When ...
Full Text Available ... under way. For example, some trials are stopped early if benefits from a strategy or treatment are ... stop a trial, or part of a trial, early if the strategy or treatment is having harmful ...
Full Text Available ... Working at the NHLBI Contact and FAQs Accessible Search Form Search the NHLBI, use the drop down list to ... to learn more about clinical research and to search for clinical trials: NHLBI Clinical Trials Browse a ...
Full Text Available ... these results are important because they advance medical knowledge and help improve patient care. Sponsorship and Funding ... All types of clinical trials contribute to medical knowledge and practice. Why Clinical Trials Are Important Clinical ...
Fariba Sadeghi movahhed
Full Text Available Background & Objectives: Insomnia is one of the most common sleep disorders in the world. It causes disruption in daily activities and increases the risk of major depression. Hence, clinically the appropriate and persistent treatment of insomnia is very important. Using of hypnotic drugs such as benzodiazepines is the common treatment for insomnia but they show several side effects and it seems that new medications should be used for treatment of sleep disorders. The aim of this study was comparison between the effects of electromagnetic therapy and conventional drug usage in the treatment of insomnia. Methods: In a blind randomized clinical trial study, 60 people referred to the private office of the psychiatrist and experienced more than 3 months extended primary insomnia were selected. They were diagnosed by DSM-IV criteria and had no other underlying problems. The subjects were divided in two groups: 30 people in each and treated electromagnetically or with Alprazolam for 3 weeks. Before treatment, immediately and one month after treatment, quality of sleep and severity of the insomnia were evaluated by using the standard questionnaires and finally, the results were analyzed statistically. Results : In this study, 60 individuals participated from whom 28 were male (46.7% and 32 patients were female (53.3%.The mean age was 37.3 years old in a range of 17- 65. The mean point of each questionnaire, before and immediately after treatment significantly didn't show any difference but one month after treatment, there was a significant difference in both groups. Conclusion : To treat insomnia, electromagnetic therapy appears to be used as a replacement for sedative medicines. It also has more stability in comparison with other sedative medicines and no side effects have been reported yet.
Full Text Available ... list of NHLBI-sponsored clinical trials. NIH Clinical Research Studies Search for studies conducted within other Institutes at the NIH, including trials performed on our campus or trials NIH has sponsored at universities, medical centers, and hospitals. ClinicalTrials.gov View a ...
Full Text Available ... about your health or fill out forms about how you feel. Some people will need to travel or stay in hospitals to take part in clinical trials. For example, the National Institutes of Health Clinical Center in Bethesda, Maryland, runs clinical trials. Many other clinical trials take place ...
Full Text Available ... trial participants. Children and Clinical Studies Learn about the importance of children in clinical studies and get answers to common questions. NIH Clinical Research Trials and You Get additional guidance on participating in clinical trials at the NIH. The NHLBI conducts a large number of ...
Full Text Available ... and Centers sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include ... U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers ( ...
Full Text Available ... clinical trials. An IRB is an independent committee created by the institution that sponsors a clinical trial. ... have not only shaped medical practice around the world, but have improved the health of millions of ...
Full Text Available ... Entire Site NHLBI Entire Site Health Topics News & Resources Intramural Research ... or device is safe and effective for humans. What Are Clinical Trials? Clinical trials are research ...
Full Text Available ... quickly show this information if safety issues arise. Participation and Eligibility Each clinical trial defines who is ... to Expect During a clinical trial, doctors, nurses, social workers, and other health care providers might be ...
Full Text Available ... are doctors, statisticians, and community members. The IRB's purpose is to ensure that clinical trials are ethical ... enrolling in a clinical trial: What is the purpose of the study? Who is sponsoring the study, ...
Full Text Available ... quickly show this information if safety issues arise. Participation and Eligibility Each clinical trial defines who is ... parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, doctors, nurses, ...
Full Text Available ... best data available for health care decisionmaking. The purpose of clinical trials is research, so the studies ... Thus, research in humans is needed. For safety purposes, clinical trials start with small groups of patients ...
Full Text Available ... providers don't always cover all patient care costs for clinical trials. If you're thinking about ... clinical trial, find out ahead of time about costs and coverage. You should learn about the risks ...
Full Text Available ... and groups sponsor clinical trials that test the safety of products, such as medicines, and how well they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. ...
Full Text Available ... whether a new approach causes any harm. In later phases of clinical trials, researchers learn more about ... other National Institutes of Health (NIH) Institutes and Centers sponsor clinical trials. Many other groups, companies, and ...
Full Text Available ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ... lung, and blood disorders. By engaging the research community and a broad group of stakeholders and advisory ...
Full Text Available ... Clinical Trials Are Important Clinical trials are a key research tool for advancing medical knowledge and patient ... that does the study uses the same protocol. Key information in a protocol includes how many patients ...
Full Text Available ... sponsor clinical trials. Many other groups, companies, and organizations also sponsor clinical trials. Examples include Government Agencies, ... and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including the NHLBI) usually ...
Full Text Available ... Events About NHLBI About NHLBI Home Mission and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...
Full Text Available ... team also may ask you to do other tasks. For example, you may have to keep a ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...
Full Text Available ... at the smallest dose and for the shortest time possible. Clinical trials, like the two described above, ... in a clinical trial, find out ahead of time about costs and coverage. You should learn about ...
Full Text Available ... comparison groups by chance, rather than choice. This method helps ensure that any differences observed during a ... a Clinical Trial If you're interested in learning more about, or taking part in, clinical trials, ...
Full Text Available ... for health-related questions and clinical trials. Optimizing our Clinical Trials Enterprise NHLBI has a strong tradition of supporting clinical trials that have not only shaped medical practice around the world, but have improved the health of millions of ...
Full Text Available ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find out ahead of time about costs and coverage. You should learn about the risks and benefits of any clinical trial before you agree to ...
Full Text Available ... harm. In later phases of clinical trials, researchers learn more about the new approach's risks and benefits. ... Clinical Studies Web page. Children and Clinical Studies Learn more about Children and Clinical Studies Importance of ...
Full Text Available ... sponsored a trial of two different combinations of asthma treatments. The trial found that one of the ... much better than the other for moderate persistent asthma. The results provided important treatment information for doctors ...
Full Text Available ... trials are research studies that explore whether a medical strategy, treatment, or device is safe and effective ... trials are research studies that explore whether a medical strategy, treatment, or device is safe and effective ...
Pacik, Peter T; Geletta, Simon
pain-free intercourse as noted by patient communications and serial female sexual function studies. Further studies are indicated to better understand the individual components of this multimodal treatment program. Pacik PT, Geletta S. Vaginismus Treatment: Clinical Trials Follow Up 241 Patients. Sex Med 2017;5:e114-e123. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Full Text Available ... the same scientific safeguards as clinical trials for adults. For more information, go to "How Do Clinical ... based on what is known to work in adults. To improve clinical care of children, more studies ...
Full Text Available ... participants. Children and Clinical Studies Learn about the importance of children in clinical studies and get answers to common questions. NIH Clinical Research Trials and You Get additional guidance on participating ...
Full Text Available ... you to explore NIH Clinical Center for patient recruitment and clinical trial information. For more information, please email the NIH Clinical Center Office of Patient Recruitment at email@example.com or call ...
Full Text Available ... Studies Learn more about Children and Clinical Studies Importance of Children in Clinical Studies Children have often ... or vulnerable patients (such as children). A DSMB's role is to review data from a clinical trial ...
Full Text Available ... and devices specific to children. Resources for a Wide Range of Audiences The Children and Clinical Studies ... medical centers, and hospitals. ClinicalTrials.gov View a database of clinical studies (past and present) funded or ...
Full Text Available Carmen Rosa, Udi Ghitza, Betty TaiCenter for the Clinical Trials Network, National Institute on Drug Abuse, Bethesda, MD, USAAbstract: Based on recommendations from a US Institute of Medicine report, the National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN in 1999, to accelerate the translation of science-based addiction treatment research into community-based practice, and to improve the quality of addiction treatment, using science as the vehicle. One of the CTN's primary tasks is to serve as a platform to forge bi-directional communications and collaborations between providers and scientists, to enhance the relevance of research, which generates empirical results that impact practice. Among many obstacles in moving research into real-world settings, this commentary mainly describes challenges and iterative experiences in regard to how the CTN develops its research protocols, with focus on how the CTN study teams select and utilize assessment instruments, which can reasonably balance the interests of both research scientists and practicing providers when applied in CTN trials. This commentary also discusses the process by which the CTN further selects a core set of common assessment instruments that may be applied across all trials, to allow easier cross-study analyses of comparable data.Keywords: addiction, assessment, drug abuse treatment, drug dependence, NIDA Clinical Trials Network, substance use disorder
Full Text Available ... or strategies work best for certain illnesses or groups of people. Some clinical trials show a positive result. For example, the National Heart, Lung, and Blood Institute (NHLBI) sponsored a trial of two different ...
Full Text Available ... education for parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, ... be identified earlier than they would be in general medical practice. This is because late-phase trials ...
Full Text Available ... the past, clinical trial participants often were White men. Researchers assumed that trial results were valid for ... different ethnic groups sometimes respond differently than White men to the same medical approach. As a result, ...
Full Text Available ... trials produce the best data available for health care decisionmaking. The purpose of clinical trials is research, ... they advance medical knowledge and help improve patient care. Sponsorship and Funding The National Heart, Lung, and ...
Full Text Available ... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... the past, clinical trial participants often were White men. Researchers assumed that trial results were valid for ...
Full Text Available ... Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including ... our campus or trials NIH has sponsored at universities, medical centers, and hospitals. ClinicalTrials.gov View a ...
Full Text Available ... help produce reliable study results. Clinical trials are one of the final stages of a long and ... trials that test principles or strategies. For example, one NHLBI study explored whether the benefits of lowering ...
Full Text Available ... groups, companies, and organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments ... sponsor trials that test principles or strategies. For example, one NHLBI study explored whether the benefits of ...
Full Text Available ... In the past, clinical trial participants often were White men. Researchers assumed that trial results were valid ... in different ethnic groups sometimes respond differently than White men to the same medical approach. As a ...
Full Text Available ... including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study explored ... risks. Other examples of clinical trials that test principles or strategies include studies that explore whether surgery ...
Full Text Available ... Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s Health All Science A-Z Grants & ... or groups to help sponsor some trials. All types of clinical trials contribute to medical knowledge and ...
Full Text Available ... well they work. The U.S. Food and Drug Administration (FDA) oversees these clinical trials. The NIH may partner with these companies or groups to help sponsor some trials. All ...
After decades of basic science research involving the testing of regenerative strategies in animal models of retinal degenerative diseases, a number of clinical trials are now underway, with additional trials set to begin shortly. These efforts will evaluate the safety and preliminary efficacy of cell-based products in the eyes of patients with a number of retinal conditions, notably including age-related macular degeneration, retinitis pigmentosa and Stargardt's disease. This review considers the scientific work and early trials with fetal cells and tissues that set the stage for the current clinical investigatory work, as well the trials themselves, specifically those either now completed, underway or close to initiation. The cells of interest include retinal pigment epithelial cells derived from embryonic stem or induced pluripotent stem cells, undifferentiated neural or retinal progenitors or cells from the vascular/bone marrow compartment or umbilical cord tissue. Degenerative diseases of the retina represent a popular target for emerging cell-based therapeutics and initial data from early stage clinical trials suggest that short-term safety objectives can be met in at least some cases. The question of efficacy will require additional time and testing to be adequately resolved.
Full Text Available ... doing screening tests, such as mammography; and compare two or more screening tests to see which test ... and Blood Institute (NHLBI) sponsored a trial of two different combinations of asthma treatments. The trial found ...
Full Text Available ... for trials with cutting-edge approaches, such as gene therapy or new biological treatments. Health insurance and ... trials that involve high-risk procedures (such as gene therapy) or vulnerable patients (such as children). A ...
Full Text Available ... trial's results apply. These criteria also are a safety measure. They ensure a trial excludes any people for whom the protocol has known risks that outweigh any possible ... groups of people for safety and side effects. Phase II clinical trials look ...
Full Text Available ... rights that help protect them. Scientific Oversight Institutional Review Board Institutional review boards (IRBs) help provide scientific ... ClinicalTrials.gov View a database of clinical studies (past and present) funded or sponsored by the NIH ...
Mayer, Tom G; Gatchel, Robert J; Keeley, Janice; McGeary, Don; Dersh, Jeffrey; Anagnostis, Christopher
A randomized single-blind clinical trial of facet injections plus exercise, versus exercise alone, in chronic disabling work-related lumbar spinal disorders (CDWRLSD), accompanied by pilot interrater reliability and facet syndrome prevalence studies. To systematically investigate the use of facet injections as an adjunct to supervised lumbar stretching exercises in regaining lumbar range of motion (ROM) following prolonged deconditioning after work-related lumbar injuries. To assess interrater reliability of visual assessment of segmental rigidity (SR), and to evaluate the prevalence of facet syndrome in cases of lumbar SR. Corticosteroid joint injections have often been used to reduce musculoskeletal inflammation to facilitate joint mobilization in the presence of degenerative arthritis. Lumbar segmental rigidity is a recently described entity usually associated with painful chronic spinal disorders and postoperative spine surgery. Previous work has shown that SR and lumbar ROM improves with a brief intervention consisting of facet injections followed by specific stretching exercises. No systematic study has investigated the potential benefits of a combination of facet injections and exercise over supervised exercises alone to treat lumbar SR. Similarly, no study has assessed the association between SR and the facet syndrome. From a group of consecutive patients (n = 421) with CDWRLSD referred for tertiary rehabilitation between November 1999 and January 2001, 70 were noted to have SR on intake physical examination. The first part of this study assessed interrater reliability for detecting SR, and intrarater reliability for 3-segment true lumbar ROM measurements. Patients randomly assigned to participate in supervised stretching exercises with the addition of fluoroscopically guided bilateral facet injections at the involved levels (Group A, n = 36) also underwent facet syndrome prevalence assessment at the time of injection. They were compared to a randomly
Full Text Available ... harmful. However, an approach that works well in the lab or animals doesn't always work well in people. Thus, research in humans is needed. For safety purposes, clinical trials start ... more about the new approach's risks and benefits. A clinical trial ...
Bonouvrié, Laura A; Becher, Jules G; Vles, Johannes S H; Boeschoten, Karin; Soudant, Dan; de Groot, Vincent; van Ouwerkerk, Willem J R; Strijers, Rob L M; Foncke, Elisabeth; Geytenbeek, Joke; van de Ven, Peter M; Teernstra, Onno; Vermeulen, R Jeroen
Dystonic cerebral palsy is primarily caused by damage to the basal ganglia and central cortex. The daily care of these patients can be difficult due to dystonic movements. Intrathecal baclofen treatment is a potential treatment option for dystonia and has become common practice. Despite this widespread adoption, high quality evidence on the effects of intrathecal baclofen treatment on daily activities is lacking and prospective data are needed to judge the usefulness and indications for dystonic cerebral palsy. The primary aim of this study is to provide level one clinical evidence for the effects of intrathecal baclofen treatment on the level of activities and participation in dystonic cerebral palsy patients. Furthermore, we hope to identify clinical characteristics that will predict a beneficial effect of intrathecal baclofen in an individual patient. A double blind placebo-controlled multi-center randomized clinical trial will be performed in 30 children with dystonic cerebral palsy. Patients aged between 4 and 25 years old with a confirmed diagnosis of dystonic cerebral palsy, Gross Motor Functioning Classification System level IV or V, with lesions in the cerebral white matter, basal ganglia or central cortex and who are eligible for intrathecal baclofen treatment will be included. Group A will receive three months of continuous intrathecal baclofen treatment and group B will receive three months of placebo treatment, both via an implanted pump. After this three month period, all patients will receive intrathecal baclofen treatment, with a follow-up after nine months. The primary outcome measurement will be the effect on activities of and participation in daily life measured by Goal Attainment Scaling. Secondary outcome measurements on the level of body functions include dystonia, spasticity, pain, comfort and sleep-related breathing disorders. Side effects will be monitored and we will study whether patient characteristics influence outcome. The results of
van de Wall Bryan JM
Full Text Available Abstract Background Persisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses. Both conservative and operative management of patients with persisting abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management. We, therefore, constructed a randomised clinical trial comparing these two treatment strategies. Methods/design The DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management. Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used. The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, Short-Form 36, EQ-5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and total costs. The total follow-up will be three years. Discussion Considering the high incidence and the
Full Text Available ... involve animal testing. This shows how the approach affects a living body and whether it's harmful. However, ... or other factors not related to the protocol affect the trial's results. Comparison Groups In most clinical ...
... of Personal Stories Peers Celebrating Art Peers Celebrating Music Be Vocal Support Locator DBSA In-Person Support ... by participating in a clinical trial is to science first and to the patient second. More About ...
Full Text Available ... symptoms. It also was increasingly being used for prevention of heart disease.) The study found that HT ... enroll healthy people to test new approaches to prevention, diagnosis, or screening. In the past, clinical trial ...
Full Text Available ... States, the Food and Drug Administration (FDA) provides oversight for clinical trials that are testing new medicines or medical devices. The FDA reviews applications for new medicines ...
Full Text Available ... always, parents must give legal consent for their child to take part in a clinical trial. When ... minimal, both parents must give permission for their child to enroll. Also, children aged 7 and older ...
Full Text Available ... Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s ... always, parents must give legal consent for their child to take part in a clinical trial. When ...
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Full Text Available ... final stages of a long and careful research process. The process often begins in a laboratory (lab), where scientists ... part in clinical trials are vital to the process of improving medical care. Many people volunteer because ...
Full Text Available ... as gene therapy) or vulnerable patients (such as children). A DSMB's role is to review data from a clinical trial for safety problems or differences in results among different groups. The DSMB also reviews research results ...
Full Text Available ... seems promising, the next step may involve animal testing. This shows how the approach affects a living ... FDA) provides oversight for clinical trials that are testing new medicines or medical devices. The FDA reviews ...
Full Text Available ... combination of estrogen and progestin, the risk of breast cancer also increased. As a result, the U.S. Food ... healthy people to test new approaches to prevention, diagnosis, or screening. In the past, clinical trial participants ...
Full Text Available ... Events About NHLBI About NHLBI Home Mission and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory ... offer a variety of funding mechanisms tailored to planning and conducting clinical trials at all phases, including ...
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Full Text Available ... work best for certain illnesses or groups of people. Clinical trials produce the best data available for ... or animals doesn't always work well in people. Thus, research in humans is needed. For safety ...
Full Text Available ... records can quickly show this information if safety issues arise. Participation and Eligibility Each clinical trial defines ... and materials, and offer advice on research-related issues. Data Safety Monitoring Board Every National Institutes of ...
Full Text Available ... sponsor clinical trials that test the safety of products, such as medicines, and how well they work. ... placebo (plah-SE-bo). This is an inactive product that looks like the test product. You'll ...
Full Text Available ... medical centers and doctors' offices around the country. Benefits and Risks Possible Benefits Taking part in a clinical trial can have many benefits. For example, you may gain access to new ...
Full Text Available ... materials, and offer advice on research-related issues. Data Safety Monitoring Board Every National Institutes of Health ( ... III clinical trial is required to have a Data and Safety Monitoring Board (DSMB). This board consists ...
Full Text Available ... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... patients to find out whether a new approach causes any harm. In later phases of clinical trials, ...
Full Text Available ... issues arise. Participation and Eligibility Each clinical trial defines who is eligible to take part in the ... and Usage No FEAR Act Grants and Funding Customer Service/Center for Health Information Email Alerts Jobs ...
Full Text Available ... organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and ... how you feel. Some people will need to travel or stay in hospitals to take part in ...
Full Text Available ... Government Agencies, such as the U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit ... public health. We offer a variety of funding mechanisms tailored to planning and conducting clinical trials at ...
Full Text Available ... at the smallest dose and for the shortest time possible. Clinical trials, like the two described above, ... how you feel. Some people will need to travel or stay in hospitals to take part in ...
Full Text Available ... patients to find out whether a new approach causes any harm. In later phases of clinical trials, ... device improves patient outcomes; offers no benefit; or causes unexpected harm All of these results are important ...
Full Text Available ... and evaluated to fill an important gap in information and education for parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, ...
Full Text Available Skip to main content U.S. Department of Health & Human Services Health Topics Health Topics A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ...
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Full Text Available ... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... always, parents must give legal consent for their child to take part in a clinical trial. When ...
Full Text Available ... results. Clinical trials are one of the final stages of a long and careful research process. The ... a patient's age and gender, the type and stage of disease, and whether the patient has had ...
Full Text Available ... study explored whether the benefits of lowering high blood pressure in the elderly outweighed the risks. Other examples of clinical trials that test principles or strategies include studies that explore whether ...
Full Text Available ... questions to ask your doctor and the research staff, go to "How Do Clinical Trials Protect Participants?" ... in Bethesda, Maryland. The physicians, nurses, scientists and staff of the NHLBI encourage you to explore NIH ...
Full Text Available ... research process. The process often begins in a laboratory (lab), where scientists first develop and test new ... healthy people to test new approaches to prevention, diagnosis, or screening. In the past, clinical trial participants ...
Full Text Available ... studies. View funding information for clinical trials optimization . Building 31 31 Center Drive Bethesda, MD 20892 Learn ... and Usage No FEAR Act Grants and Funding Building 31 31 Center Drive Bethesda, MD 20892 Learn ...
Full Text Available ... and organizations also sponsor clinical trials. Examples include Government Agencies, such as the U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and ...
Full Text Available ... risk of heart disease in the first few years, and HT also increased the risk of stroke ... the shortest time possible. Clinical trials, like the two described above, help improve and advance medical care. ...
Faurschou, A.; Wulf, Hans Chr.
Objective: To examine the effect of topical corticosteroid treatment on acute sunburn. Design: Randomized, double-blind clinical trial. Setting: University dermatology department. Patients: Twenty healthy volunteers with Fitzpatrick skin types I (highly sensitive, always burns easily, tans...... in the acute sunburn reaction when applied 6 or 23 hours after UV exposure. Clinical Trial Registry: clinicaltrials. gov Identifier: NCT00206882 Udgivelsesdato: 2008/5...
Full Text Available ... for trials with cutting-edge approaches, such as gene therapy or new biological treatments. Health insurance and health ... trials that involve high-risk procedures (such as gene therapy) or vulnerable patients (such as children). A DSMB's ...
Full Text Available ... NIH also requires DSMBs for large trials comparing alternative strategies for diagnosis or treatment. In addition, the NIH requires DSMBs for some earlier phase trials that involve high-risk procedures (such as gene therapy) or vulnerable patients (such as children). A DSMB's ...
Full Text Available ... the strategy or treatment is having harmful effects. Food and Drug Administration In the United States, the ... part in the study? How might this trial affect my daily life? Will I have to be ...
Full Text Available ... the NHLBI Women's Health Initiative tested whether hormone therapy (HT) reduced the risk of heart disease in ... trials with cutting-edge approaches, such as gene therapy or new biological treatments. Health insurance and health ...
Full Text Available ... as gene therapy or new biological treatments. Health insurance and health care providers don't always cover ... study? How might this trial affect my daily life? Will I have to be in the hospital? ...
Full Text Available ... treatment is having harmful effects. Food and Drug Administration In the United States, the Food and Drug ... life? Will I have to be in the hospital? How long will the trial last? Who will ...
Full Text Available ... Initiative tested whether hormone therapy (HT) reduced the risk of heart disease in postmenopausal women. (When the trial began, HT was already in common use for the treatment of menopausal symptoms. It also ...
Full Text Available ... Masking, or "blinding," helps avoid bias. For this reason, researchers also may not be told which treatments ... from a study at any time, for any reason. Also, during the trial, you have the right ...
Full Text Available ... trials are research studies that explore whether a medical strategy, treatment, or device is safe and effective ... IRBs, develop educational programs and materials, and offer advice on research-related issues. Data Safety Monitoring Board ...
Full Text Available ... Wide Range of Audiences The Children and Clinical Studies Program has been successfully developed and evaluated to fill an important gap in information and education for parents, clinicians, researchers, children, and the general public. What to Expect During a clinical trial, doctors, ...
Harris-Hayes, Marcie; McDonough, Christine M; Leunig, Michael
Patient-reported outcome measures are an important component of outcomes assessment in clinical trials to assess the treatment of femoroacetabular impingement (FAI). This review of disease-specific measures and instruments used to assess the generic quality of life and physical activity levels...... developed recently and have not been established in the literature. Although currently used generic and activity-level measures have limitations, as well, they should be considered, depending on the specific goals of the study. Additional research is needed to assess the properties of these measures fully...
Tur, Carmen; Moccia, Marcello; Barkhof, Frederik; Chataway, Jeremy; Sastre-Garriga, Jaume; Thompson, Alan J; Ciccarelli, Olga
Increasing numbers of drugs are being developed for the treatment of multiple sclerosis (MS). Measurement of relevant outcomes is key for assessing the efficacy of new drugs in clinical trials and for monitoring responses to disease-modifying drugs in individual patients. Most outcomes used in trial and clinical settings reflect either clinical or neuroimaging aspects of MS (such as relapse and accrual of disability or the presence of visible inflammation and brain tissue loss, respectively). However, most measures employed in clinical trials to assess treatment effects are not used in routine practice. In clinical trials, the appropriate choice of outcome measures is crucial because the results determine whether a drug is considered effective and therefore worthy of further development; in the clinic, outcome measures can guide treatment decisions, such as choosing a first-line disease-modifying drug or escalating to second-line treatment. This Review discusses clinical, neuroimaging and composite outcome measures for MS, including patient-reported outcome measures, used in both trials and the clinical setting. Its aim is to help clinicians and researchers navigate through the multiple options encountered when choosing an outcome measure. Barriers and limitations that need to be overcome to translate trial outcome measures into the clinical setting are also discussed.
Full Text Available ... go to the NHLBI's Children and Clinical Studies Web page. Children and Clinical Studies Learn more about Children and Clinical Studies Importance of Children in Clinical Studies Children have often had to accept medicines and treatments based on what is known to work in adults. To improve ...
Jedrzejewska, T; Bałczewska, E; Peterson, R; Urbaniak, B; Ostrowska, B
The effect of Solcoseryl on the clinical state of the parodontium was assessed in 26 patients aged from 18 to 57 years with the diagnosis of deep parodontopathies. Each patient received 30 ampoules of 2 ml of Solcoseryl for one course of the treatment. Submucous injections of the drug near the teeth 13, 23, 33 and 43 were done as follows: during the first 10 days one ampoule daily, then 10 injections every other day, and 10 injections at three-day intervals. The condition of the parodontium was assessed before and after the treatment by means of the PI, GI, GBI and teeth mobility indices, and measurements of the depth of gingival pouches--K, and volume of fluid in pouches SFFR according to Brill. The therapeutic method applied in these cases had a good effect on reduction of gingivitis, bleeding and volume of secreted pouch fluid but had only a small effect on teeth mobility and depth of gingival pouches.
Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M
Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.
Poole-Wilson, Philip A.; Kirwan, Bridget-Anne; Voko, Zoltan; de Brouwer, Sophie; Dunselman, Peter H. J. M.; van Dalen, Frederik J.; Lubsen, Jacobus
Background and Objective: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data. Methods: Data from a trial comparing long-acting nifedipine
Zvonareva, Olga; Engel, Nora; Martsevich, Sergey; de Wert, Guido; Horstman, Klasien
The issue of balance between research and treatment in clinical trials conduct has been surrounded by controversies. Scientific characteristics of trials may compromise medical care available to participants, while conceiving research participation as having therapeutic value may foster the therapeutic misconception. However, it has also been questioned whether research can and should always be separated from medical care provision. In this paper we analyze how these concerns played out in practice settings of the three trial sites in Russia, specialized in trials in cardiovascular diseases. Using in-depth interviews with participants of phase II and III trials (n = 21) and discussions with physician-investigators (n = 7), we found that trial enrollment allowed participants to establish continuous supportive relationships with the physician-investigators. In the context of unresponsive health care, chronically ill participants received regular monitoring, treatment recommendations and help in case of problems and emergencies through such relationships. The trial designs in the three sites did not preclude the provision of individualized treatment. We suggest that debates about the research/treatment interface in trials need to become more attuned to the conditions in locations of their conduct, views and experiences of actors involved and evolving trial methodologies. Too much focus on categorical differentiation of research and treatment may obscure the fact that globalizing clinical trials proceed amidst profound health disparities, dismiss diverse concerns of people on the ground and risk attenuating responsibilities of trial organizers, sponsors and investigators towards research participants. Copyright © 2015 Elsevier Ltd. All rights reserved.
Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Studies Women’s Health All Science A-Z Grants & Training Grants and Training Home Policies and Guidelines Funding ...
Full Text Available ... clinical trials that have not only shaped medical practice around the world, but have improved the health of millions of people suffering from heart, lung, and blood disorders. By engaging the research community and a broad group of stakeholders and advisory ...
Full Text Available ... This shows how the approach affects a living body and whether it's harmful. However, an approach that works well in the lab or animals doesn't always work well in people. Thus, research in humans is needed. For safety purposes, clinical trials start ...
Full Text Available ... educational programs and materials, and offer advice on research-related issues. Data Safety Monitoring Board Every National Institutes of Health ( ... III clinical trial is required to have a Data and Safety Monitoring Board ... of a group of research and study topic experts. The NIH also requires ...
Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders and Blood Safety Sleep ... Activity Population and Epidemiology Studies Women’s Health All Science A-Z Grants & Training Grants and Training Home Policies and Guidelines Funding ...
Full Text Available ... protect patients and help produce reliable study results. Clinical trials are one of the final stages of a long and careful research process. The process often begins in a laboratory (lab), where scientists first develop and test new ...
Full Text Available ... In the United States, the Food and Drug Administration (FDA) provides oversight for clinical trials that are testing new medicines or medical devices. The FDA reviews applications for new medicines and devices before any testing on humans is done. They check to make sure that ...
Full Text Available ... taking the same treatment the same way. These patients are closely watched by Data and Safety Monitoring Boards. Even if you don't directly ... risk procedures (such as gene therapy) or vulnerable patients (such as ... trial for safety problems or differences in results among different groups. ...
Clinical trials testing infertility treatments often do not report on the major outcomes of interest to patients and clinicians and the public (such as live birth) nor on the harms, including maternal risks during pregnancy and fetal anomalies. This is complicated by the multiple participants in infertility trials which may include a woman (mother), a man (father), and a third individual if successful, their offspring (child), who is also the desired outcome of treatment. The primary outcome of interest and many adverse events occur after cessation of infertility treatment and during pregnancy and the puerperium, which creates a unique burden of follow-up for clinical trial investigators and participants. In 2013, because of the inconsistencies in trial reporting and the unique aspects of infertility trials not adequately addressed by existing Consolidated Standards of Reporting Trials (CONSORT) statements, we convened a consensus conference in Harbin, China, with the aim of planning modifications to the CONSORT checklist to improve the quality of reporting of clinical trials testing infertility treatment. The consensus group recommended that the preferred primary outcome of all infertility trials is live birth (defined as any delivery of a live infant after ≥20 weeks' gestation) or cumulative live birth, defined as the live birth per women over a defined time period (or number of treatment cycles). In addition, harms to all participants should be systematically collected and reported, including during the intervention, any resulting pregnancy, and the neonatal period. Routine information should be collected and reported on both male and female participants in the trial. We propose to track the change in quality that these guidelines may produce in published trials testing infertility treatments. Our ultimate goal is to increase the transparency of benefits and risks of infertility treatments to provide better medical care to affected individuals and couples
Martinez, Ana Maria Blanco; Goulart, Camila de Oliveira; Ramalho, Bruna Dos Santos; Oliveira, Júlia Teixeira; Almeida, Fernanda Martins
Mesenchymal stem cell (MSC) therapy has attracted the attention of scientists and clinicians around the world. Basic and pre-clinical experimental studies have highlighted the positive effects of MSC treatment after spinal cord and peripheral nerve injury. These effects are believed to be due to their ability to differentiate into other cell lineages, modulate inflammatory and immunomodulatory responses, reduce cell apoptosis, secrete several neurotrophic factors and respond to tissue injury, among others. There are many pre-clinical studies on MSC treatment for spinal cord injury (SCI) and peripheral nerve injuries. However, the same is not true for clinical trials, particularly those concerned with nerve trauma, indicating the necessity of more well-constructed studies showing the benefits that cell therapy can provide for individuals suffering the consequences of nerve lesions. As for clinical trials for SCI treatment the results obtained so far are not as beneficial as those described in experimental studies. For these reasons basic and pre-clinical studies dealing with MSC therapy should emphasize the standardization of protocols that could be translated to the clinical set with consistent and positive outcomes. This review is based on pre-clinical studies and clinical trials available in the literature from 2010 until now. At the time of writing this article there were 43 and 36 pre-clinical and 19 and 1 clinical trials on injured spinal cord and peripheral nerves, respectively.
Full Text Available ... the strategy or treatment is having harmful effects. Food and Drug Administration In the United States, the Food and Drug Administration (FDA) provides oversight for clinical ...
...] Design of Clinical Trials of Aerosolized Antimicrobials for the Treatment of Cystic Fibrosis; Public... development of aerosolized antimicrobials for the management and/or treatment of patients with cystic fibrosis... respiratory symptoms in patients with cystic fibrosis. This public workshop is intended to provide information...
Haynes, L. F.; Korte, J. E.; Holmes, B. E.; Gooden, L.; Matheson, T.; Feaster, D. J.; Leff, J. A.; Wilson, L.; Metsch, L. R.; Schackman, B. R.
The Substance Abuse Mental Health Services Administration has promoted HIV testing and counseling as an evidence-based practice. Nevertheless, adoption of HIV testing in substance abuse treatment programs has been slow. This article describes the experience of a substance abuse treatment agency where, following participation in a clinical trial,…
Day, Simon; Machin, David; Green, Sylvan B
... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1 The Development of Clinical Trials Simon...
Lawton, Julia; White, David; Rankin, David; Elliott, Jackie; Taylor, Carolin; Cooper, Cindy; Heller, Simon; Hallowell, Nina
The ending of a clinical trial may be challenging, particularly if staff are required to withdraw the investigated treatment(s); however, this aspect of trial work is surprisingly under-researched. To address this gap, we explored the experiences of staff involved in closing out a trial that entailed withdrawal of treatment (insulin pumps) from some patients. Interviews were conducted with n = 22 staff, recruited from seven trial sites. Data were analysed thematically. Staff described a myriad of ethical and emotional challenges at closeout, many of which had been unforeseen when the trial began. A key challenge for staff was that, while patients gave their agreement to participate on the understanding that pump treatment could be withdrawn, they often found themselves benefitting from this regimen in ways they could not have foreseen. Hence, as the trial progressed, patients became increasingly anxious about withdrawal of treatment. This situation forced staff to consider whether the consent patients had given at the outset remained valid; it also presented them with a dilemma at closeout because many of those who had wanted to remain on a pump did not meet the clinical criteria required for post-trial funding. When deciding whether to withdraw treatment, staff not only had to take funding pressures and patient distress into account, but they also found themselves caught between an ethic of Hippocratic individualism and one of utilitarianism. These conflicting pressures and ethical considerations resulted in staff decision-making varying across the sites, an issue that some described as a further source of ethical unease. Staff concluded that, had there been more advanced planning and discussion, and greater accountability to an ethics committee, some of the challenges they had confronted at closeout could have been lessened or even prevented. The same kinds of ethical issues that may vex staff at the beginning of a trial (e.g. patients having unrealistic
Full Text Available ... criteria differ from trial to trial. They include factors such as a patient's age and gender, the ... bias. "Bias" means that human choices or other factors not related to the protocol affect the trial's ...
Full Text Available Many chiropractors believe that chiropractic treatments are effective for gastrointestinal disorders. The aim of the present systematic review was to critically evaluate the evidence from controlled clinical trials supporting or not supporting this notion. Six electronic databases were searched for relevant studies. No limits were applied to language or publication date. Prospective, controlled, clinical trials of any type of chiropractic treatment for any type of gastrointestinal problem, except infant colic, were included. Only two trials were found – one was a pilot study, and the other had reached a positive conclusion; however, both had serious methodological flaws. There is no supportive evidence that chiropractic is an effective treatment for gastrointestinal disorders.
Ritto, Ana Paula; Juste, Fabiola Staróbole; Stuart, Andrew; Kalinowski, Joseph; de Andrade, Claudia Regina Furquim
Background: Numerous studies have demonstrated the benefit of devices delivering altered auditory feedback (AAF) as a therapeutic alternative for those who stutter. Aims: The effectiveness of a device delivering AAF (SpeechEasy®) was compared with behavioural techniques in the treatment of stuttering in a randomized clinical trial. Methods &…
Legro, Richard S; Wu, Xiaoke; Barnhart, Kurt T; Farquhar, Cynthia; Fauser, Bart C J M; Mol, Ben
Clinical trials testing infertility treatments often do not report on the major outcomes of interest to patients and clinicians and the public (such as live birth) nor on the harms, including maternal risks during pregnancy and fetal anomalies. This is complicated by the multiple participants in infertility trials which may include a woman (mother), a man (father), and result in a third individual if successful, their offspring (child), who is also the desired outcome of treatment. The primary outcome of interest and many adverse events occur after cessation of infertility treatment and during pregnancy and the puerperium, which create a unique burden of follow-up for clinical trial investigators and participants. In 2013, because of the inconsistencies in trial reporting and the unique aspects of infertility trials not adequately addressed by existing Consolidated Standards of Reporting Trials (CONSORT) statements, we convened a consensus conference in Harbin, China, with the aim of planning modifications to the CONSORT checklist to improve the quality of reporting of clinical trials testing infertility treatment. The consensus group recommended that the preferred primary outcome of all infertility trials is live birth (defined as any delivery of a live infant ≥20 weeks gestations) or cumulative live birth, defined as the live birth per women over a defined time period (or number of treatment cycles). In addition, harms to all participants should be systematically collected and reported, including during the intervention, any resulting pregnancy, and during the neonatal period. Routine information should be collected and reported on both male and female participants in the trial. We propose to track the change in quality that these guidelines may produce in published trials testing infertility treatments. Our ultimate goal is to increase the transparency of benefits and risks of infertility treatments to provide better medical care to affected individuals and
Full Text Available ... trials show what doesn't work or may cause harm. For example, the NHLBI Women's Health Initiative tested whether hormone therapy (HT) reduced the risk of heart disease in postmenopausal women. (When the trial began, HT ...
Kleijnen, J; Knipschild, P; ter Riet, G
OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800
Dworkin, R.H.; Turk, D.C.; Wyrwich, K.W.
for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression Inventory...... and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures...
Full Text Available There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Vitamin D is actively under investigation as a potential intervention for epilepsy. Vitamin D is fat soluble steroid which shows promise in animal models of epilepsy. Basic research has shed light on the possible mechanisms by which Vitamin D may reduce seizures, and animal data support the efficacy of Vitamin D in rat and mouse models of epilepsy. Very little clinical data exists to support the treatment of human epilepsy with Vitamin D, but positive findings from preliminary clinical trials warrant larger Phase I and II clinical trials in order to more rigorously determine the potential therapeutic value of Vitamin D as a treatment for human epilepsy.
Ducharme, Lori J; Knudsen, Hannah K; Roman, Paul M; Johnson, J Aaron
Researchers and policymakers are increasingly focusing on factors that facilitate or impede the diffusion of evidence-based treatment techniques into routine clinical practice. One potentially fruitful avenue of research is the influence of involvement in research networks as a predictor of organizational innovation. The Clinical Trials Network (CTN) is examining a number of behavioral and pharmacological treatment techniques in controlled multisite studies. Using data from participating CTN treatment programs and large samples of programs outside the CTN, these analyses examine the influence of exposure to clinical trials on the subsequent adoption of buprenorphine and voucher-based motivational incentives. The analyses show that, controlling for a variety of organizational characteristics, direct exposure to buprenorphine clinical trials in the CTN significantly increased the odds of subsequent adoption. By contrast, the adoption of motivational incentives was entirely explained by organizational characteristics. The findings suggest that adoption of treatment innovations is a function of exposure, organizational resources, nature of innovations, and stage of the diffusion process.
... HUMAN SERVICES Food and Drug Administration Design of Clinical Trials for Systemic Antibacterial Drugs for the Treatment of Acute Otitis Media; Public Workshop AGENCY: Food and Drug Administration, HHS... workshop regarding the design of Clinical Trials for Systemic Antibacterial Agents for the Treatment of...
Full Text Available The semi-parametric proportional hazards model is widely adopted in randomized clinical trials with time-to-event outcomes, and the log-rank test is frequently used to detect a potential treatment effect. Immuno-oncology therapies pose unique challenges to the design of a trial as the treatment effect may be delayed, which violates the proportional hazards assumption, and the log-rank test has been shown to markedly lose power under the non-proportional hazards setting. A novel design and analysis approach for immuno-oncology trials is proposed through a piecewise treatment effect function, which is capable of detecting a potentially delayed treatment effect. The number of events required for the trial will be determined to ensure sufficient power for both the overall log-rank test without a delayed effect and the test beyond the delayed period when such a delay exists. The existence of a treatment delay is determined by a likelihood ratio test with resampling. Numerical results show that the proposed design adequately controls the Type I error rate, has a minimal loss in power under the proportional hazards setting and is markedly more powerful than the log-rank test with a delayed treatment effect.
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Full Text Available Abstract Background Patellofemoral pain syndrome is a highly prevalent musculoskeletal overuse condition that has a significant impact on participation in daily and physical activities. A recent systematic review highlighted the lack of high quality evidence from randomised controlled trials for the conservative management of patellofemoral pain syndrome. Although foot orthoses are a commonly used intervention for patellofemoral pain syndrome, only two pilot studies with short term follow up have been conducted into their clinical efficacy. Methods/design A randomised single-blinded clinical trial will be conducted to investigate the clinical efficacy and cost effectiveness of foot orthoses in the management of patellofemoral pain syndrome. One hundred and seventy-six participants aged 18–40 with anterior or retropatellar knee pain of non-traumatic origin and at least six weeks duration will be recruited from the greater Brisbane area in Queensland, Australia through print, radio and television advertising. Suitable participants will be randomly allocated to receive either foot orthoses, flat insoles, physiotherapy or a combined intervention of foot orthoses and physiotherapy, and will attend six visits with a physiotherapist over a 6 week period. Outcome will be measured at 6, 12 and 52 weeks using primary outcome measures of usual and worst pain visual analogue scale, patient perceived treatment effect, perceived global effect, the Functional Index Questionnaire, and the Anterior Knee Pain Scale. Secondary outcome measures will include the Lower Extremity Functional Scale, McGill Pain Questionnaire, 36-Item Short-Form Health Survey, Hospital Anxiety and Depression Scale, Patient-Specific Functional Scale, Physical Activity Level in the Previous Week, pressure pain threshold and physical measures of step and squat tests. Cost-effectiveness analysis will be based on treatment effectiveness against resource usage recorded in treatment logs and
Full Text Available ... long and careful research process. The process often begins in a laboratory (lab), where scientists first develop ... IRB reviews the trial's protocol before the study begins. An IRB will only approve research that deals ...
Full Text Available ... are ethical and that the participants' rights are protected. The IRB reviews the trial's protocol before the ... may know about studies going on in your area. You can visit the following website to learn ...
Full Text Available ... or groups of people; look at the best age and frequency for doing screening tests, such as ... trial. They include factors such as a patient's age and gender, the type and stage of disease, ...
Full Text Available ... Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s Health All Science A- ... assumed that trial results were valid for other populations as well. Researchers now realize that women and ...
Full Text Available ... Form Search the NHLBI, use the drop down list to select: the entire site, the Health Topics ... specific trials you're interested in. For a list of questions to ask your doctor and the ...
Full Text Available ... a laboratory (lab), where scientists first develop and test new ideas. If an approach seems promising, the ... Centers (including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study ...
Full Text Available ... risk of heart disease in the first few years, and HT also increased the risk of stroke ... master plan called a protocol (PRO-to-kol). This plan explains how the trial will work. The ...
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Full Text Available ... medicines, and how well they work. The U.S. Food and Drug Administration (FDA) oversees these ... trials are a key research tool for advancing medical knowledge and patient care. ...
de Glas, N. A.; Hamaker, M. E.; Kiderlen, M.; de Craen, A. J. M.; Mooijaart, S. P.; van de Velde, C. J. H.; van Munster, B. C.; Portielje, J. E. A.; Liefers, G. J.; Bastiaannet, E.
With the ongoing ageing of western societies, the proportion of older breast cancer patients will increase. For several years, clinicians and researchers in geriatric oncology have urged for new clinical trials that address patient-related endpoints such as functional decline after treatment of
Looareesuwan, S; Chulay, J D; Canfield, C J; Hutchinson, D B
The continuing spread of drug-resistant malaria emphasizes the need for new antimalarial drugs. Atovaquone is a broad-spectrum antiprotozoal drug with a novel mechanism of action, via inhibition of parasite mitochondrial electron transport, and a favorable safety profile. Early studies with atovaquone alone for treatment of malaria demonstrated good initial control of parasitemia but an unacceptable rate of recrudescent parasitemia. Parasites isolated during recrudescence after treatment with atovaquone alone were resistant to atovaquone in vitro. The combination of atovaquone and proguanil is synergistic in vitro, and clinical studies demonstrated enhanced efficacy of the combination compared to either drug alone for treatment of malaria. Malarone, a fixed-dose combination of 250 mg of atovaquone and 100 mg of proguanil hydrochloride, is available in many countries for treatment of acute, uncomplicated malaria caused by Plasmodium falciparum. At the recommended dose (in adults, four tablets once a day for three days), the overall cure rate was > 98% in more than 500 patients with falciparum malaria. In four randomized, controlled clinical trials, treatment with atovaquone and proguanil hydrochloride was significantly more effective than mefloquine (Thailand), amodiaquine (Gabon), chloroquine (Peru and the Philippines) or chloroquine plus pyrimethamine/sulfadoxine (Philippines). In clinical trials where the comparator drug was highly effective, treatment with atovaquone and proguanil hydrochloride was equally effective. Parasites isolated during recrudescence after treatment with the combination of atovaquone and proguanil were not resistant to atovaquone in vitro. The most commonly reported adverse events in clinical trials (abdominal pain, anorexia, nausea, vomiting, diarrhea and coughing) occurred with similar frequency in patients treated with a comparator drug. Malarone is a safe and effective new agent for treatment of malaria.
Friedman, Lawrence M; DeMets, David L; Reboussin, David M; Granger, Christopher B
This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise. Most chapters have been revised considerably from the fourth edition. A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded. Many contemporary clinical trial examples have been added. There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing, and international trials. This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of ...
VISHAL KUMAR S. MODI; TARASHANKAR BASURI; VIRAG A. SHAH; ISHVAR PARMAR; SIDDIQUE SHABABANO
Breast cancer is the most common cancer in women in both developed and undeveloped countries, and the second most frequent cause of cancer deaths after lung cancer. Although there have been many chemotherapeutic agents like 5-fluorouracil, taxol, tamoxifen, doxorubicin, cisplatin, and camptothecin and hormones are used to treat breast cancer. This review focuses on the causes of breast cancer, latest diagnostic techniques and various molecules under clinical trials for the treatment of breast...
Gregersen, Trine Ammentorp; Birkelund, Regner; Ammentorp, Jette
Title: Clinical trial or standard treatment? Shared decision making at the department of oncology. Authors: Ph.d. student, Trine A. Gregersen. Trine.firstname.lastname@example.org. Department of Oncology. Health Services Research Unit Lillebaelt Hospital / IRS University of Southern Denmark. Professor, Regner...... Analyzing field notes: • How to write useful field notes? • How to analyze field notes systematically? • Using Nvivo when analyzing field notes and interviews?...
Ahmed A. Al-Mohammadi; Adil A. Noaimi; Khalifa E. Sharquie; Khalil I. Al-Hamdi
Thallium poisoning is usually associated with typical dermatological features simulating that of zinc deficiency. The aim of this study was to evaluate the role of oral zinc sulphate in the treatment of patients with thallium poisoning.Materials and methods: This clinical therapeutic trial study was conducted in Departments of Dermatology of Baghdad and Basrah Teaching Hospitals from February 2008 - February 2010, where a total of 37 patients with thallium poisoning were enrolled.A detailed h...
Roberts, Chris; Roberts, Stephen A
Where patients receive therapy as a group, there are good theoretical reasons to believe that variation in the outcome will be smaller for patients treated in the same group than for patients treated in different groups. Similarly, where different therapists treat different groups of patients, outcome for patients treated by the same therapist may differ less than outcome for patients treated by different therapists. Clinical trials evaluating such therapies need to consider this potential lack of independence. As with cluster-randomized trials, this has implications for the precision of treatment effects estimates and statistical power. There are nevertheless differences between clustering due to the organization of treatment and that due to randomization. In cluster-randomized trials the distribution of cluster sizes in each treatment arm should be similar as a consequence of randomization unless there is differential loss to follow-up. With clustering due to therapy group or therapist, cluster size may differ systematically between treatment arms, due to size of therapy groups or differing health professional caseload. Intra-cluster correlation may also differ between treatment arms. The implications of differential cluster size and intracluster correlation for design and analysis will be illustrated by data from two trials, the first comparing nurse practitioner care with general practitioner care, and the second comparing a group therapy with individual treatment as usual. The special case where a group therapy or therapist is compared with an unclustered treatment is examined in detail using a simulation study. The implications of differential clustering effects for sample size and power are addressed. It is argued that the design and analysis of this type of trial should take account of possible heterogeneity in cluster size and intracluster correlation.
Gilbert, Peter B.; Shepherd, Bryan E.; Hudgens, Michael G.
Summary Assessing per-protocol treatment effcacy on a time-to-event endpoint is a common objective of randomized clinical trials. The typical analysis uses the same method employed for the intention-to-treat analysis (e.g., standard survival analysis) applied to the subgroup meeting protocol adherence criteria. However, due to potential post-randomization selection bias, this analysis may mislead about treatment efficacy. Moreover, while there is extensive literature on methods for assessing causal treatment effects in compliers, these methods do not apply to a common class of trials where a) the primary objective compares survival curves, b) it is inconceivable to assign participants to be adherent and event-free before adherence is measured, and c) the exclusion restriction assumption fails to hold. HIV vaccine efficacy trials including the recent RV144 trial exemplify this class, because many primary endpoints (e.g., HIV infections) occur before adherence is measured, and nonadherent subjects who receive some of the planned immunizations may be partially protected. Therefore, we develop methods for assessing per-protocol treatment efficacy for this problem class, considering three causal estimands of interest. Because these estimands are not identifiable from the observable data, we develop nonparametric bounds and semiparametric sensitivity analysis methods that yield estimated ignorance and uncertainty intervals. The methods are applied to RV144. PMID:24187408
Struyf, F; Nijs, J; Mollekens, S; Jeurissen, I; Truijen, S; Mottram, S; Meeusen, R
The purpose of this clinical trial is to compare the effectiveness of a scapular-focused treatment with a control therapy in patients with shoulder impingement syndrome. Therefore, a randomized clinical trial with a blinded assessor was used in 22 patients with shoulder impingement syndrome. The primary outcome measures included self-reported shoulder disability and pain. Next, patients were evaluated regarding scapular positioning and shoulder muscle strength. The scapular-focused treatment included stretching and scapular motor control training. The control therapy included stretching, muscle friction, and eccentric rotator cuff training. Main outcome measures were the shoulder disability questionnaire, diagnostic tests for shoulder impingement syndrome, clinical tests for scapular positioning, shoulder pain (visual analog scale; VAS), and muscle strength. A large clinically important treatment effect in favor of scapular motor control training was found in self-reported disability (Cohen's d = 0.93, p = 0.025), and a moderate to large clinically important improvement in pain during the Neer test, Hawkins test, and empty can test (Cohen's d 0.76, 1.04, and 0.92, respectively). In addition, the experimental group demonstrated a moderate (Cohen's d = 0.67) improvement in self-experienced pain at rest (VAS), whereas the control group did not change. The effects were maintained at three months follow-up.
Full Text Available ... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... the NHLBI's Children and Clinical Studies Web page. Children and Clinical Studies Learn more about Children and ...
Full Text Available ... go to the NHLBI's Children and Clinical Studies Web page. Children and Clinical Studies Learn more about ... Protections The U.S. Department of Health and Human Services’ (HHS’) Office for Human Research Protections (OHRP) oversees ...
Full Text Available ... U.S. Departments of Defense and Veterans Affairs; private companies; universities; and nonprofit organizations. NIH Institutes and Centers (including the NHLBI) usually sponsor trials that test principles or strategies. For example, one NHLBI study explored whether the ...
Full Text Available ... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... include factors such as a patient's age and gender, the type and stage of disease, ... helps ensure that any differences observed during a trial are due to the ...
... Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies ... include factors such as a patient's age and gender, the type and stage of disease, ... helps ensure that any differences observed during a trial are due to the ...
Khedr, Eman Mohamed; Badry, Reda; Ali, Anwer Mohamed; Abo El-Fetoh, Noha; El-Hammady, Dina Hatem; Ghandour, Abeer Mohamed; Abdel-Haleem, Ahmed
A large number of patients with Bell's palsy fail to recover facial function completely after steroid therapy. Only a few small trials have been conducted to test whether outcomes can be improved by the addition of antiviral therapy. To evaluate the efficacy of treatment with steroid alone versus steroid + antiviral in a group of patients with moderately severe to severe acute Bell's palsy. Fifty eligible patients out of a total of 65 with acute onset Bell's palsy were randomized to receive the two treatments. Evaluation was performed before starting treatment, after 2 weeks of treatment and 3 months after onset, using the House and Brackmann facial nerve grading system (HB) and the Sunnybrook grading system.This study was registered with ClinicalTrials.gov, number NCT02328079. Both treatments had comparable demographics and clinical scores at baseline. There was greater improvement in the mean HB and Sunnybrook scores of the steroid + antiviral group in comparison to steroid group at 3 months. At the end of the 3rd month, 17 patients (68%) had good recovery and 8 patients (32%) had poor recovery in the steroid group compared with 23 patients (92%) and 2 (8%) respectively in the steroid and antiviral group (p = 0.034). The combination of steroid and antiviral treatment increases the possibility of recovery in moderately severe to complete acute Bell's palsy.
Full Text Available ... have many benefits. For example, you may gain access to new treatments before they're widely available. ... strategy or treatment are obvious. That way, wider access to the new strategy can occur sooner. Sponsors ...
Full Text Available ... research studies that explore whether a medical strategy, treatment, or device is safe and effective for humans. ... research studies that explore whether a medical strategy, treatment, or device is safe and effective for humans. ...
Full Text Available ... the strategy or treatment is having harmful effects. Food and Drug Administration In the United States, the ... treatment options. Together, you can make the best choice for you. Other Rights The informed consent document ...
Full Text Available ... are research studies that explore whether a medical strategy, treatment, or device is safe and effective for ... are research studies that explore whether a medical strategy, treatment, or device is safe and effective for ...
Full Text Available ... care. They also can help health care decisionmakers direct resources to the strategies and treatments that work ... strategies. For example, one group may get the current standard treatment for a condition, while another group ...
Full Text Available ... strategies. For example, one group may get the current standard treatment for a condition, while another group ... new strategy being tested, you may receive the current standard care for your condition. This treatment might ...
Background Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B). Methods We assessed the one-year-natural course of dysferlinopathy, and the safety and efficacy of deflazacort treatment in a double-blind, placebo-controlled cross-over trial. After one year of natural course without intervention, 25 patients with genetically defined dysferlinopathy were randomized to receive deflazacort and placebo for six months each (1 mg/kg/day in month one, 1 mg/kg every 2nd day during months two to six) in one of two treatment sequences. Results During one year of natural course, muscle strength declined about 2% as measured by CIDD (Clinical Investigation of Duchenne Dystrophy) score, and 76 Newton as measured by hand-held dynamometry. Deflazacort did not improve muscle strength. In contrast, there is a trend of worsening muscle strength under deflazacort treatment, which recovers after discontinuation of the study drug. During deflazacort treatment, patients showed a broad spectrum of steroid side effects. Conclusion Deflazacort is not an effective therapy for dysferlinopathies, and off-label use is not warranted. This is an important finding, since steroid treatment should not be administered in patients with dysferlinopathy, who may be often misdiagnosed as polymyositis. Trial registration This clinical trial was registered at http://www.ClincalTrials.gov, identifier: NCT00527228, and was always freely accessible to the public. PMID:23406536
Choi, Tae-Young; Lee, Myeong Soo; Ernst, Edzard
The purpose of this study is to assess the efficacy of moxibustion as a treatment of chemotherapy-induced leukopenia. Twelve databases were searched from their inception through June 2014, without a language restriction. Randomized clinical trials (RCTs) were included if moxibustion was used as the sole treatment or as a part of a combination therapy with conventional drugs for leukopenia induced by chemotherapy. Cochrane criteria were used to assess the risk of bias. Six RCTs with a total of 681 patients met our inclusion criteria. All of the included RCTs were associated with a high risk of bias. The trials included patients with various types of cancer receiving ongoing chemotherapy or after chemotherapy. The results of two RCTs suggested the effectiveness of moxibustion combined with chemotherapy vs. chemotherapy alone. In four RCTs, moxibustion was more effective than conventional drug therapy. Six RCTs showed that moxibustion was more effective than various types of control interventions in increasing white blood cell counts. There is low level of evidence based on these six trials that demonstrates the superiority of moxibustion over drug therapies in the treatment of chemotherapy-induced leukopenia. However, the number of trials, the total sample size, and the methodological quality are too low to draw firm conclusions. Future RCTs appear to be warranted.
Cardona Velásquez, Santiago; Guzmán Vivares, Laura; Cardona-Arias, Jaiberth Antonio
Despite the clinical, epidemiological, and economic significance of metabolic syndrome, the profile of clinical trials on this disease is unknown. To characterize the clinical trials related to treatment of metabolic syndrome during the 1980-2015 period. Systematic review of the literature using an ex ante search protocol which followed the phases of the guide Preferred Reporting Items for Systematic Reviews and Meta-Analyses in four multidisciplinary databases with seven search strategies. Reproducibility and methodological quality of the studies were assessed. One hundred and six trials were included, most from the United States, Italy, and Spain, of which 63.2% evaluated interventions effective for several components of the syndrome such as diet (40.6%) or physical activity (22.6%). Other studies assessed drugs for a single factor such as hypertension (7.5%), hypertriglyceridemia (11.3%), or hyperglycemia (9.4%). Placebo was used as control in 54.7% of trials, and outcome measures included triglycerides (52.8%), HDL (48.1%), glucose (29.2%), BMI (33.0%), blood pressure (27.4%), waist circumference (26.4%), glycated hemoglobin (11.3%), and hip circumference (7.5%). It was shown that studies ob efficacy of treatment for metabolic syndrome are scarce and have mainly been conducted in the last five years and in high-income countries. Trials on interventions that affect three or more factors and assess several outcome measures are few, and lifestyle interventions (diet and physical activity) are highlighted as most important to impact on this multifactorial syndrome. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.
Full Text Available Betty Tai, Steven Sparenborg, David Liu, Michele StrausCenter for the Clinical Trials Network, National Institute on Drug Abuse, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, USAAbstract: The National Drug Abuse Treatment Clinical Trials Network (CTN has faced many challenges over its first eleven years. This review explores some of these challenges and the paths the CTN took to meet these challenges, including: designing clinical trials that reflect the CTN’s mission and changing public health needs, finding the synergies in the varied expertise of clinical treatment providers and academic researchers, promoting evidence-based practices and expanding the Network into mainstream medical practices to reach a broader patient population. Included in this exploration are specific examples from CTN clinical trials.Keywords: Clinical Trials Network, drug abuse, addiction
Lebwohl, Mark G; Papp, Kim A; Marangell, Lauren B; Koo, John; Blauvelt, Andrew; Gooderham, Melinda; Wu, Jashin J; Rastogi, Shipra; Harris, Susan; Pillai, Radhakrishnan; Israel, Robert J
Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody. Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Baccetti, Tiziano; Franchi, Lorenzo; Giuntini, Veronica; Masucci, Caterina; Vangelisti, Andrea; Defraia, Efisio
The aim of this prospective clinical trial was to compare the outcomes of prepubertal vs pubertal treatment of deepbite patients with a protocol including biteplane and fixed appliances. A sample of 58 subjects with deepbite completed the study. A total of 34 subjects received treatment with removable biteplane appliances in the mixed dentition at a prepubertal stage of skeletal maturation (early treatment group), and 24 subjects were treated at a pubertal stage of skeletal maturation in the permanent dentition (late treatment group). All subjects of both groups were reevaluated after an average period of 15 months after the completion of fixed appliance therapy. Treatment outcomes were assessed statistically after a phase with removable biteplane appliances and at the posttreatment observation. Treatment duration was significantly shorter in the early treatment group than in the late treatment group. Overbite reduction was significantly greater in the late treatment group (-3.1 mm) than in the early treatment group (-1.4 mm). In the late treatment group, 92% of the patients had a corrected overbite 1 year after therapy. Treatment of deepbite at puberty in the permanent dentition leads to significantly more favorable outcomes than treatment before puberty in the mixed dentition. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.
Reddy, Rishindra M., E-mail: email@example.com [Medical Center, University of Michigan, 1500 E. Medical Center Drive, 2120 Taubman Center, Ann Arbor, MI 48109 (United States); Kakarala, Madhuri; Wicha, Max S. [Comprehensive Cancer Center, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109 (United States)
The cancer stem cell model introduces new strategies for the prevention and treatment of cancers. In cancers that appear to follow the stem cell model, pathways such as Wnt, Notch and Hedgehog may be targeted with natural compounds such as curcumin or drugs to reduce the risk of initiation of new tumors. Disease progression of established tumors could also potentially be inhibited by targeting the tumorigenic stem cells alone, rather than aiming to reduce overall tumor size. These new approaches mandate a change in the design of clinical trials and biomarkers chosen for efficacy assessment for preventative, neoadjuvant, adjuvant, and palliative treatments. Cancer treatments could be evaluated by assessing stem cell markers before and after treatment. Targeted stem cell specific treatment of cancers may not result in “complete” or “partial” responses radiologically, as stem cell targeting may not reduce the tumor bulk, but eliminate further tumorigenic potential. These changes are discussed using breast, pancreatic, and lung cancer as examples.
Roy, Nelson; Weinrich, Barbara; Gray, Steven D; Tanner, Kristine; Stemple, Joseph C; Sapienza, Christine M
Voice problems are a common occupational hazard of teaching school, yet few studies exist that have objectively evaluated treatment approaches aimed at rehabilitating these occupation-related voice disorders. This randomized clinical trial used patient-based treatment outcome measures to evaluate the effectiveness of three treatment programs. Sixty-four teachers with voice disorders were randomly assigned to 1 of 3 treatment groups: voice amplification using the ChatterVox portable amplifier (VA; n = 25), resonance therapy (RT; n = 19), and respiratory muscle training (RMT; n = 20). Before and after a 6-week treatment phase, all teachers completed (a) the Voice Handicap Index (VHI; B. H. Jacobson et al., 1997), an instrument designed to appraise the self-perceived psychosocial consequences of voice disorders, and (b) a voice severity self-rating scale. Both intention-to-treat and as-treated analyses revealed that only the VA and RT groups reported significant reductions in mean VHI scores and in voice severity self-ratings following treatment. Furthermore, results from a posttreatment questionnaire regarding the perceived benefits of treatment showed that compared to RT and RMT, teachers in the VA group reported significantly more overall voice improvement, greater vocal clarity, and greater ease of speaking and singing voice following treatment. These findings replicate previous results from an earlier clinical trial confirming the efficacy of VA and provide new evidence to support RT as an effective treatment alternative for voice problems in teachers. The results are discussed in the context of uneven levels of self-reported compliance and disparate dropout rates among the treatment groups.
Hoffman, Jessica; Frerichs, Leah; Story, Mary; Jones, Jason; Gaskin, Kiah; Apple, Annie; Skinner, Asheley; Armstrong, Sarah
Effective treatment of childhood obesity remains elusive. Integration of clinical and community systems may achieve effective and sustainable treatment. However, the feasibility and effectiveness of this integrated model are unknown. We conducted a randomized clinical trial among children aged 5 to 11 presenting for obesity treatment. We randomized participants to clinical care or clinical care plus community-based programming at a local parks and recreation facility. Primary outcomes were the change in child BMI at 6 months and the intensity of the program in treatment hours. Secondary outcomes included health behaviors, fitness, attrition, and quality of life. We enrolled 97 children with obesity, and retention at 6 months was 70%. Participants had a mean age of 9.1 years and a mean baseline BMI z score of 2.28, and 70% were living in poverty. Intervention participants achieved more treatment hours than controls (11.4 vs 4.4, SD: 15.3 and 1.6, respectively). We did not observe differences in child BMI z score or percent of the 95th percentile at 6 months. Intervention participants had significantly greater improvements in physical activity ( P = .010) and quality of life ( P = .008). An integrated clinic-community model of child obesity treatment is feasible to deliver in a low-income and racially diverse population. As compared with multidisciplinary treatment, the integrated model provides more treatment hours, improves physical activity, and increases quality of life. Parks and recreation departments hold significant promise as a partner agency to deliver child obesity treatment. Copyright © 2018 by the American Academy of Pediatrics.
Full Text Available ... preexisting differences between the patients. Usually, a computer program makes the group assignments. Masking The term "masking" ... Range of Audiences The Children and Clinical Studies Program has been successfully developed and evaluated to fill ...
Full Text Available ... and devices specific to children. Resources for a Wide Range of Audiences The Children and Clinical Studies ... have not only shaped medical practice around the world, but have improved the health of millions of ...
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Leanna M. Delhey
Full Text Available Autism spectrum disorder (ASD affects about 1 in 45 individuals in the United States, yet effective treatments are yet to be defined. There is growing evidence that ASD is associated with abnormalities in several metabolic pathways, including the inter-connected folate, methylation and glutathione pathways. Several treatments that can therapeutically target these pathways have been tested in preliminary clinical trials. The combination of methylcobalamin (mB12 with low-dose folinic acid (LDFA and sapropterin, a synthetic form of tetrahydrobiopterin (BH4 have been studied in open-label trials while high-dose folinic acid has been studied in a double-blind placebo controlled trial. All of these treatments have the potential to positively affect folate, methylation and glutathione pathways. Although the effect of mB12/LDFA and BH4 on methylation and glutathione metabolism have been examined in the open-label studies, these changes have not been compared to controls who received a placebo in order to account for the natural variation in the changes in these pathways. Furthermore, the recent study using high-dose folinic acid (HDFA did not analyze the change in metabolism resulting from the treatment. Thus, we compared changes in methylation and glutathione metabolism and biomarkers of chronic oxidative stress as a result of these three treatments to individuals receiving placebo. In general, mB12/LDFA treatment had a significant effect on glutathione and cysteine metabolism with a medium effect size while BH4 had a significant effect on methylation and markers of chronic oxidative stress with a large effect size. HDFA treatment did not significantly influence biomarkers of methylation, glutathione or chronic oxidative stress. One caveat was that participants in the mB12/LDFA and BH4 studies had significantly worse markers of glutathione metabolism and chronic oxidative stress at baseline, respectively. Thus, the participants selected in these two
Delhey, Leanna M; Tippett, Marie; Rose, Shannon; Bennuri, Sirish C; Slattery, John C; Melnyk, Stepan; James, S Jill; Frye, Richard E
Autism spectrum disorder (ASD) affects about 1 in 45 individuals in the United States, yet effective treatments are yet to be defined. There is growing evidence that ASD is associated with abnormalities in several metabolic pathways, including the inter-connected folate, methylation and glutathione pathways. Several treatments that can therapeutically target these pathways have been tested in preliminary clinical trials. The combination of methylcobalamin (mB12) with low-dose folinic acid (LDFA) and sapropterin, a synthetic form of tetrahydrobiopterin (BH4) have been studied in open-label trials while high-dose folinic acid has been studied in a double-blind placebo controlled trial. All of these treatments have the potential to positively affect folate, methylation and glutathione pathways. Although the effect of mB12/LDFA and BH4 on methylation and glutathione metabolism have been examined in the open-label studies, these changes have not been compared to controls who received a placebo in order to account for the natural variation in the changes in these pathways. Furthermore, the recent study using high-dose folinic acid (HDFA) did not analyze the change in metabolism resulting from the treatment. Thus, we compared changes in methylation and glutathione metabolism and biomarkers of chronic oxidative stress as a result of these three treatments to individuals receiving placebo. In general, mB12/LDFA treatment had a significant effect on glutathione and cysteine metabolism with a medium effect size while BH4 had a significant effect on methylation and markers of chronic oxidative stress with a large effect size. HDFA treatment did not significantly influence biomarkers of methylation, glutathione or chronic oxidative stress. One caveat was that participants in the mB12/LDFA and BH4 studies had significantly worse markers of glutathione metabolism and chronic oxidative stress at baseline, respectively. Thus, the participants selected in these two clinical trials
Full Text Available Abstract Background The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin (Selective Serotonin Reuptake Inhibitors – SSRIs and noradrenaline (Noradrenaline Reuptake Inhibitors – NaRIs into the presynaptic terminal. There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action. Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs, there are patients who respond to one class of compounds and not another. This suggests that treatment response could be predicted by genetic and/or clinical characteristics. Firstly, this study aims to investigate the influence of a polymorphism (SLC6A4 in the 5HT transporter in altering response to SSRI medication. Secondly, the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs. Methods/design The GenPod trial is a multi-centre randomised controlled trial. GPs referred patients aged between 18–74 years presenting with a new episode of depression, who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse. Patients were interviewed to ascertain their suitability for the study. Eligible participants (with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory (BDI score > 14 were randomised to receive one of two antidepressant treatments, either the SSRI Citalopram or the NaRI Reboxetine, stratified according to severity. The final number randomised to the trial was 601. Follow-up assessments took place at 2, 6 and 12 weeks following randomisation. Primary outcome was measured at 6 weeks by the BDI. Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments
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Viswanathan, Chandra; Sarang, Shabari
Rapidly increasing number of diabetic patients across the world is a great challenge to the current therapeutic approach. Although the traditional method of rendering exogenous insulin is an established method of treatment, it is not sufficient and often causes lethal hypoglycemia. There is also a good amount of success with whole organ transplantation or Islet cells' transplantation. But this technique is limited with regards the availability of donors. Currently, many clinicians and researchers are involved in clinical studies using various different stem cells from embryonic as well as adult sources for the treatment of diabetes. In this review we have tried to discuss the results of various clinical trials using stem cells. We have also tried to look at various stem cell types and the routes of injections that are currently being followed world wide.
Meineche-Schmidt, V.; Christensen, E.; Bytzer, P.
Background: Response to proton pump inhibitor (PPI) treatment in dyspepsia is unpredictable. Aim: To identify symptoms associated with response to esomeprazole in order to target patients for empirical treatment. Methods: Eight hundred and five uninvestigated, primary care patients with upper GI....... Conclusions In patients with uninvestigated dyspepsia, PPI responders can be reliably identified by a simple pocket chart using symptoms and patient characteristics (ClinicalTrials.gov NCT00318968)....
Ana Luiza Soares Rodrigues
Full Text Available OBJECTIVE: to assess the effectiveness of 2% papain gel compared to 2% carboxymethyl cellulose in the treatment of chronic venous ulcer patients.METHOD: randomized controlled clinical trial with 12-week follow-up. The sample consisted of 18 volunteers and 28 venous ulcers. In the trial group, 2% papain gel was used and, in the control group, 2% carboxymethyl cellulose gel.RESULTS: the trial group showed a significant reduction in the lesion area, especially between the fifth and twelfth week of treatment, with two healed ulcers and a considerable increase in the amount of epithelial tissue in the wound bed.CONCLUSION: 2% papain gel demonstrated greater effectiveness in the reduction of the lesion area, but was similar to 2% carboxymethyl cellulose gel regarding the reduction in the amount of exudate and devitalized tissue. Multicenter research is suggested to evidence the effectiveness of 2% papain gel in the healing of venous ulcers. UTN number: U1111-1157-2998
Tolentino, Michael John; Dennrick, Abrahan; John, Elizabeth; Tolentino, Michael Steven
The clinical development of anti-VEGF therapies for the treatment of exudative age-related macular degeneration (wet AMD) has revolutionized ophthalmology. Indeed, it has provided clinicians and patients with treatments that lessen visual loss from in a disease that once was uniformly blinding. Although blindness is yet to be eradicated from AMD, repeated intraocular anti-VEGF injections are required to preserve a patient's vision. Therefore, further advances in this field are necessary. This review provides an overview of the agents that are in mid-stage phase trials for both exudative (wet AMD) and nonexudative macular degeneration (dry AMD). For wet AMD, new agents intend to enhance efficacy, develop alternative delivery such as eye drops, investigate alternate targets and construct sustained release strategies. For advanced dry AMD, the goal is to develop a strategy to slow or stop progressive loss of retinal tissue seen in geographic atrophy, the hallmark of advanced dry AMD. It is important to develop better more sensitive biomarkers, validating different approvable clinical trial endpoints and stratifying patients on their genetic polymorphisms. These developments should help to progress the already rapidly developing field of macular degeneration therapy.
López-de-Celis, Carlos; Barra-López, Martin-Eusebio; González-Rueda, Vanessa; Bueno-Gracia, Elena; Rodríguez-Rubio, Pere-Ramón; Tricás-Moreno, José-Miguel
To assess the end of treatment and three months after treatment effects of diacutaneous fibrolysis as adjuvant of physical therapy for chronic lateral epicondylalgia. Double-blind (patient and evaluator) randomized controlled trial. Primary Care Center of the Spanish NHS. A total of 54 people with 60 elbows affected with chronic lateral epicondylalgia, 33 women, mean (SD) age was 48.43 (8.69) years. All three groups (Intervention, Placebo and Control) received three weeks of physical therapy treatment and in addition Intervention Group received six sessions of real diacutaneous fibrolysis and Placebo Group received six sessions of sham diacutaneous fibrolysis. Pain intensity, pressure pain threshold, pain free grip strength, function and subjective assessment were assessed at baseline, at the end of treatment and three months after treatment. Between-group results at three months after treatment showed a statistically significant improvement of the Intervention Group in pain free grip strength (mean, 7.91 km/cm 2 ; SD, 9.23) compared to the Placebo Group (mean, 1.47 km/cm 2 ; SD, 7.86) and to the Control Group (mean, 2.09 km/cm 2 ; SD, 4.45) ( P values Diacutaneous fibrolysis added to physical therapy provides better results in the treatment of chronic lateral epicondylalgia, with greater clinical satisfaction among patients.
Stochkendahl, Mette J; Christensen, Henrik W; Vach, Werner
We have previously reported short-term follow-up from a pragmatic randomized clinical trial comparing 2 treatments for acute musculoskeletal chest pain: (1) chiropractic treatment and (2) self-management. Results indicated a positive effect in favor of the chiropractic treatment after 4 and 12...
McClure, Erin A; Campbell, Aimee N C; Pavlicova, Martina; Hu, Meichen; Winhusen, Theresa; Vandrey, Ryan G; Ruglass, Lesia M; Covey, Lirio S; Stitzer, Maxine L; Kyle, Tiffany L; Nunes, Edward V
The majority of patients enrolled in treatment for substance use disorders (SUDs) also use tobacco. Many will continue to use tobacco even during abstinence from other drugs and alcohol, often leading to smoking-related illnesses. Despite this, little research has been conducted to assess the influence of being a smoker on SUD treatment outcomes and changes in smoking during a treatment episode. In this secondary analysis, cigarette smoking was evaluated in participants completing outpatient SUD treatment as part of a multi-site study conducted by the National Drug Abuse Treatment Clinical Trials Network. Analyses included the assessment of changes in smoking and nicotine dependence via the Fagerström Test for Nicotine Dependence during the 12-week study among all smokers (aim #1), specifically among those in the experimental treatment group (aim #2), and the moderating effect of being a smoker on treatment outcomes (aim #3). Participants generally did not reduce or quit smoking throughout the course of the study. Among a sub-set of participants with higher baseline nicotine dependence scores randomized to the control arm, scores at the end of treatment were lower compared to the experimental arm, though measures of smoking quantity did not appear to decrease. Further, being a smoker was associated with poorer treatment outcomes compared to non-smokers enrolled in the trial. This study provides evidence that patients enrolled in community-based SUD treatment continue to smoke, even when abstaining from drugs and alcohol. These results add to the growing literature encouraging the implementation of targeted, evidence-based interventions to promote abstinence from tobacco among SUD treatment patients. Copyright © 2015 Elsevier Inc. All rights reserved.
Thomas L. Sevier
Full Text Available Introduction. Patients with chronic lateral elbow (LE tendinopathy, commonly known as tennis elbow, often experience prolonged symptoms and frequent relapses. Astym treatment, evidenced in animal studies to promote the healing and regeneration of soft tissues, is hypothesized to improve outcomes in LE tendinopathy patients. This study had two objectives: (1 to compare the efficacy of Astym treatment to an evidence-based eccentric exercise program (EE for patients with chronic LE tendinopathy, and (2 to quantify outcomes of subjects non-responsive to EE who were subsequently treated with Astym treatment.Study Design. Prospective, two group, parallel, randomized controlled trial completed at a large orthopedic center in Indiana. Inclusion criteria: age range of 18–65 years old, with clinical indications of LE tendinopathy greater than 12 weeks, with no recent corticosteriod injection or disease altering comorbidities.Methods. Subjects with chronic LE tendinopathy (107 subjects with 113 affected elbows were randomly assigned using computer-generated random number tables to 4 weeks of Astym treatment (57 elbows or EE treatment (56 elbows. Data collected at baseline, 4, 8, 12 weeks, 6 and 12 months. Primary outcome measure: DASH; secondary outcome measures: pain with activity, maximum grip strength and function. The treating physicians and the rater were blinded; subjects and treating clinicians could not be blinded due to the nature of the treatments.Results. Resolution response rates were 78.3% for the Astym group and 40.9% for the EE group. Astym subjects showed greater gains in DASH scores (p = 0.047 and in maximum grip strength (p = 0.008 than EE subjects. Astym therapy also resolved 20/21 (95.7% of the EE non-responders, who showed improvements in DASH scores (p < 0.005, pain with activity (p = 0.002, and function (p = 0.004 following Astym treatment. Gains continued at 6 and 12 months. No adverse effects were reported.Conclusion. This study
Zhao, Zuo-Tao; Ji, Chun-Mei; Yu, Wen-Jun; Meng, Ling; Hawro, Tomasz; Wei, Ji-Fu; Maurer, Marcus
Chronic spontaneous urticaria (CSU) is defined by itchy hives, angioedema, or both for at least 6 weeks. Omalizumab, an anti-IgE antibody that affects mast cell and basophil function, is a promising new treatment option. As of now, however, the efficacy and safety of different doses of omalizumab used in clinical trials for CSU have not been systematically analyzed and summarized. We sought to assess the efficacy and safety of different doses of omalizumab for the treatment of CSU in a meta-analysis of clinical trial results. Suitable trials were identified by searching PubMed, Medline, Embase, and Web of Science databases and with the help of omalizumab's manufacturers. Only double-blind, randomized, placebo-controlled studies with omalizumab-treated versus placebo-treated patients with CSU were included in this analysis. We identified 7 randomized, placebo-controlled studies with 1312 patients with CSU. Patients treated with omalizumab (75-600 mg every 4 weeks) had significantly reduced weekly itch and weekly wheal scores compared with the placebo group. Omalizumab's effects were dose dependent, with the strongest reduction in weekly itch and weekly wheal scores observed with 300 mg. Rates of complete response were significantly higher in the omalizumab group (relative risk, 4.55; P omalizumab and placebo groups. This meta-analysis provides high-quality evidence for the efficacy and safety of omalizumab in patients with CSU and for treating these patients with 300 mg of omalizumab every 4 weeks. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Viele, Kert; Berry, Scott; Neuenschwander, Beat; Amzal, Billy; Chen, Fang; Enas, Nathan; Hobbs, Brian; Ibrahim, Joseph G.; Kinnersley, Nelson; Lindborg, Stacy; Micallef, Sandrine; Roychoudhury, Satrajit; Thompson, Laura
Clinical trials rarely, if ever, occur in a vacuum. Generally, large amounts of clinical data are available prior to the start of a study, particularly on the current study’s control arm. There is obvious appeal in using (i.e., ‘borrowing’) this information. With historical data providing information on the control arm, more trial resources can be devoted to the novel treatment while retaining accurate estimates of the current control arm parameters. This can result in more accurate point estimates, increased power, and reduced type I error in clinical trials, provided the historical information is sufficiently similar to the current control data. If this assumption of similarity is not satisfied, however, one can acquire increased mean square error of point estimates due to bias and either reduced power or increased type I error depending on the direction of the bias. In this manuscript, we review several methods for historical borrowing, illustrating how key parameters in each method affect borrowing behavior, and then, we compare these methods on the basis of mean square error, power and type I error. We emphasize two main themes. First, we discuss the idea of ‘dynamic’ (versus ‘static’) borrowing. Second, we emphasize the decision process involved in determining whether or not to include historical borrowing in terms of the perceived likelihood that the current control arm is sufficiently similar to the historical data. Our goal is to provide a clear review of the key issues involved in historical borrowing and provide a comparison of several methods useful for practitioners. PMID:23913901
Chaibub Neto, Elias
Clinical trials traditionally employ blinding as a design mechanism to reduce the influence of placebo effects. In practice, however, it can be difficult or impossible to blind study participants and unblinded trials are common in medical research. Here we show how instrumental variables can be used to quantify and disentangle treatment and placebo effects in randomized clinical trials comparing control and active treatments in the presence of confounders. The key idea is to use randomization to separately manipulate treatment assignment and psychological encouragement conversations/interactions that increase the participants’ desire for improved symptoms. The proposed approach is able to improve the estimation of treatment effects in blinded studies and, most importantly, opens the doors to account for placebo effects in unblinded trials.
Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.
Peace, Karl E; Chen, Ding-Geng
"Now viewed as its own scientific discipline, clinical trial methodology encompasses the methods required for the protection of participants in a clinical trial and the methods necessary to provide...
Berghmans, L C; Hendriks, H J; De Bie, R A; van Waalwijk van Doorn, E S; Bø, K; van Kerrebroeck, P E
To assess the efficacy of physical therapies for first-line use in the treatment of urge urinary incontinence (UUI) in women, using a systematic review of randomized clinical trials (RCTs). A computer-aided and manual search was carried out for RCTs published between 1980 and 1999 investigating the treatment of UUI defined by the keywords 'physical therapies', e.g. bladder (re)training (including 'behavioural' treatment), pelvic floor muscle (PFM) exercises, with or without biofeedback and/or electrical stimulation. The methodological quality of the included trials was assessed using methodological criteria, based on generally accepted principles of interventional research. Fifteen RCTs were identified; the methodological quality of the studies was moderate, with a median (range) score of 6 (3-8.5) (maximum possible 10). Eight RCTs were considered of sufficient quality, i.e. an internal validity score of >/= 5.5 points on a scale of 0-10, and were included in a further analysis. Based on levels-of-evidence criteria, there is weak evidence to suggest that bladder (re)training is more effective than no treatment (controls), and that bladder (re)training is better than drug therapy. Stimulation types and parameters in the studies of electrical stimulation were heterogeneous. There is insufficient evidence that electrical stimulation is more effective than sham electrical simulation. To date there are too few studies to evaluate effects of PFM exercise with or without biofeedback, and of toilet training for women with UUI. Although almost all studies included reported positive results in favour of physical therapies for the treatment of UUI, more research of high methodological quality is required to evaluate the effects of each method in the range of physical therapies.
Solís García del Pozo, Julián; Solera, Javier
Background Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance. Methods and Findings A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05–4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81–4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63–2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future. Conclusions Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current
Menzies, Ross; O'Brian, Sue; Lowe, Robyn; Packman, Ann; Onslow, Mark
CBTPsych is an individualized, fully automated, standalone Internet treatment program that requires no clinical contact or support. It is designed specifically for those who stutter. Two preliminary trials demonstrated that it may be efficacious for treating the social anxiety commonly associated with stuttering. However, both trials involved pre- and post-treatment assessment at a speech clinic. This contact may have increased compliance, commitment and adherence with the program. The present study sought to establish the effectiveness of CBTPsych in a large international trial with no contact of any kind from researchers or clinicians. Participants were 267 adults with a reported history of stuttering who were given a maximum of 5 months access to CBTPsych. Pre- and post-treatment functioning was assessed within the online program with a range of psychometric measures. Forty-nine participants (18.4%) completed all seven modules of CBTPsych and completed the post-treatment online assessments. That compliance rate was far superior to similar community trials of self-directed Internet mental health programs. Completion of the program was associated with large, statistically and clinically significant reductions for all measures. The reductions were similar to those obtained in earlier trials of CBTPsych, and those obtained in trials of in-clinic CBT with an expert clinician. CBTPsych is a promising individualized treatment for social anxiety for a proportion of adults who stutter, which requires no health care costs in terms of clinician contact or support. The reader will be able to: (a) discuss the reasons for investigating CBTPsych without any clinical contact; (b) describe the main components of the CBTPsych treatment; (c) summarize the results of this clinical trial; (d) describe how the results might affect clinical practice, if at all. Copyright © 2016 Elsevier Inc. All rights reserved.
Mocroft, A; Neaton, J; Bebchuk, J
the assumptions used in designing ESPRIT, a large randomized clinical trial assessing the clinical benefit of interleukin-2 treatment in patients with HIV infection, to use EuroSIDA to mimic the inclusion criterion of ESPRIT in order to compare the observed event rate in ESPRIT with the projected rate in Euro......BACKGROUND: Planning clinical-endpoint trials in patients with HIV remain difficult as long-term follow-up of many patients is required. Cohort studies of patients with HIV can provide key estimates of the likely disease progression, required sample size and follow-up. OBJECTIVES: To verify...... to observational studies or clinical trials cannot always be adjusted for. CONCLUSIONS: Event rates in EuroSIDA were similar in the first two years to those used in the design of ESPRIT, but did not increase over time, leading to an increase in the expected duration of ESPRIT. Clinical endpoint trials in HIV...
Neul, Jeffrey L; Glaze, Daniel G; Percy, Alan K; Feyma, Tim; Beisang, Arthur; Dinh, Thuy; Suter, Bernhard; Anagnostou, Evdokia; Snape, Mike; Horrigan, Joseph; Jones, Nancy E
Rett syndrome is a genetically based neurodevelopmental disorder. Although the clinical consequences of Rett syndrome are profound and lifelong, currently no approved drug treatments are available specifically targeted to Rett symptoms. High quality outcome measures, specific to the core symptoms of a disorder are a critical component of well-designed clinical trials for individuals with neurodevelopmental disorders. The Clinical Global Impression Scale is a measure of global clinical change with strong face validity that has been widely used as an outcome measure in clinical trials of central nervous system disorders. Despite its favorable assay sensitivity in clinical trials, as a global measure, the Clinical Global Impression Scale is not specific to the signs and symptoms of the disorder under study. Development of key anchors for the scale, specific to the disorder being assessed, holds promise for enhancing the validity and reliability of the measure for disorders such as Rett syndrome. © The Author(s) 2015.
Pérez-Palomares, Sara; Oliván-Blázquez, Bárbara; Pérez-Palomares, Ana; Gaspar-Calvo, Elena; Pérez-Benito, Marina; López-Lapeña, Elena; de la Torre-Beldarraín, Maria Luisa; Magallón-Botaya, Rosa
Study Design Multicenter, parallel randomized clinical trial. Background Myofascial trigger points (MTrPs) are implicated in shoulder pain and functional limitations. An intervention intended to treat MTrPs is dry needling. Objectives To investigate the effectiveness of dry needling in addition to evidence-based personalized physical therapy treatment in the treatment of shoulder pain. Methods One hundred twenty patients with nonspecific shoulder pain were randomly allocated into 2 parallel groups: (1) personalized, evidencebased physical therapy treatment; and (2) trigger point dry needling in addition to personalized, evidence-based physical therapy treatment. Patients were assessed at baseline, posttreatment, and 3-month follow-up. The primary outcome measure was pain assessed by a visual analog scale at 3 months, and secondary variables were joint range-of-motion limitations, Constant-Murley score for pain and function, and number of active MTrPs. Clinical efficacy was assessed using intention-to-treat analysis. Results Of the 120 enrolled patients, 63 were randomly assigned to the control group and 57 to the intervention group. There were no significant differences in outcome between the 2 treatment groups. Both groups showed improvement over time. Conclusion Dry needling did not offer benefits in addition to personalized, evidencebased physical therapy treatment for patients with nonspecific shoulder pain. Level of Evidence Therapy, level 1b. Registered February 11, 2009 at www.isrctn.com (ISRCTN30907460). J Orthop Sports Phys Ther 2017;47(1):11-20. Epub 9 Dec 2016. doi:10.2519/jospt.2017.6698.
Rizik, David G; Hermiller, James B; Kereiakes, Dean J
The permanent metal prosthesis common to bare metal stents (BMS) as well as both first- and second-generation drug-eluting stents (DES) following treatment of coronary artery disease represents a long-lasting substrate for late adverse coronary events including restenosis, thrombosis, and neoatherosclerosis. Following resorbtion, bioresorbable scaffolds (BRS) may eliminate this nidus and improve late outcomes through restoration of the vessel to more normal vascular structure and function. BRS represents a single platform which incorporates the mechanical features of metallic stents to provide safe and effective revascularization, suppression of restenosis and prevention of constrictive remodeling with long-term restoration of the treated vessel to a more natural state. The landscape of BRS is rapidly evolving with new materials which target various performance goals for the duration of vascular support and polymer resorption time. The Absorb bioresorbable vascular scaffold (Absorb BVS), recently approved by United States Food and Drug Administration, has extensive clinical evidence to date in support of its clinical efficacy and safety. Recently published data from well-executed randomized clinical trials (RCTs) as part of the ABSORB Clinical development program along with other investigator-initiated trials provide insights into the safety and performance of this device in patients with de novo coronary lesions as well in the setting of ST-segment elevation myocardial infarction (STEMI). This review provides a comprehensive, outcomes based understanding of the available evidence from RCTs that offer head-to-head comparisons of Absorb BVS with metallic everolimus-eluting stents (EES). © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Amparo, Francisco; Dastjerdi, Mohammad H; Okanobo, Andre; Ferrari, Giulio; Smaga, Leila; Hamrah, Pedram; Jurkunas, Ula; Schaumberg, Debra A; Dana, Reza
The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy. To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction. Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial. Seventy-five patients with refractory DED. Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks. Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality. Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P < .001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P
Neul, Jeff; Glaze, Daniel; Percy, Alan; Feyma, Tim; Beisang, Arthur; Dinh, Thuy; Suter, Bernhard; Anagnostou, Evdokia; Snape, Mike; Horrigan, Joseph; Jones, Nancy E.
Rett syndrome is a genetically based neurodevelopmental disorder. While the clinical consequences of Rett syndrome are profound and life-long, currently no approved drug treatments are available specifically targeted to Rett symptoms. High quality outcome measures, specific to the core symptoms of a disorder are a critical component to well-designed clinical trials for individuals with neurodevelopmental disorders. The Clinical Global Impression Scale is a measure of global clinical change wi...
Steiner, Hans; Saxena, Kirti S.; Carrion, Victor; Khanzode, Leena A.; Silverman, Melissa; Chang, Kiki
We examined the efficacy of divalproex sodium (DVP) for the treatment of PTSD in conduct disorder, utilizing a previous study in which 71 youth were enrolled in a randomized controlled clinical trial. Twelve had PTSD. Subjects (all males, mean age 16, SD 1.0) were randomized into high and low dose conditions. Clinical Global Impression (CGI)…
Smolen, Josef S.; Collaud Basset, Sabine; Boers, Maarten; Breedveld, Ferdinand; Edwards, Christopher J.; Kvien, Tore K.; Miossec, Pierre; Sokka-Isler, Tuulikki; van Vollenhoven, Ronald F.; Abadie, Eric C.; Bruyère, Olivier; Cooper, Cyrus; Mäkinen, Heidi; Thomas, Thierry; Tugwell, Peter; Reginster, Jean-Yves
The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft 'Guideline on clinical investigation of medicinal products for
Hartmann, Andreas; Müllner, Julia; Meier, Niklaus; Hesekamp, Helke; van Meerbeeck, Priscilla; Habert, Marie-Odile; Kas, Aurélie; Tanguy, Marie-Laure; Mazmanian, Merry; Oya, Hervé; Abuaf, Nissen; Gaouar, Hafida; Salhi, Sabrina; Charbonnier-Beaupel, Fanny; Fievet, Marie-Hélène; Galanaud, Damien; Arguillere, Sophie; Roze, Emmanuel; Degos, Bertrand; Grabli, David; Lacomblez, Lucette; Hubsch, Cécile; Vidailhet, Marie; Bonnet, Anne-Marie; Corvol, Jean-Christophe; Schüpbach, Michael
In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. ClinicalTrials.gov NCT
Berghmans, L C; Hendriks, H J; Bo, K; Hay-Smith, E J; de Bie, R A; van Waalwijk van Doorn, E S
To assess the efficacy of physical therapies for first-line use in the treatment and prevention of stress urinary incontinence (SUI) in women, using a systematic review of randomized clinical trials (RCTs). A computer-aided and manual search for published RCTs investigating treatment and prevention of SUI using physical therapies, e.g. pelvic floor muscle (PFM) exercises, with or without other treatment modalities, were carried out. The methodological quality of the included trials was assessed using criteria based on generally accepted principles of interventional research. Twenty-four RCTs (22 treatment and two prevention) were identified; the methodological quality of the studies included was moderate and 11 RCTs were of sufficient quality to be included in further analysis. Based on levels-of-evidence criteria, there is strong evidence to suggest that PFM exercises are effective in reducing the symptoms of SUI. There is limited evidence for the efficacy of high-intensity vs a low-intensity regimen of PFM exercises. Despite significant effects of biofeedback after testing as an adjunct to PFM exercises, there is no evidence that PFM exercises with biofeedback are more effective than PFM exercises alone. There is little consistency (of stimulation types and parameters) in the studies of electrical stimulation, but when the results are combined there is strong evidence to suggest that electrostimulation is superior to sham electrostimulation, and limited evidence that there is no difference between electrostimulation and other physical therapies. In the prevention of SUI the efficacy of PFM exercises, with or without other adjuncts, is uncertain.
Holmes, Jonathan M.
Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. PMID:25752747
Prajna, N Venkatesh; Krishnan, Tiruvengada; Rajaraman, Revathi; Patel, Sushila; Srinivasan, Muthiah; Das, Manoranjan; Ray, Kathryn J; O'Brien, Kieran S; Oldenburg, Catherine E; McLeod, Stephen D; Zegans, Michael E; Porco, Travis C; Acharya, Nisha R; Lietman, Thomas M; Rose-Nussbaumer, Jennifer
To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. The Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis. Study participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%. The primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use. A total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup analyses comparing treatment effects among organism subgroups, there was some
Full Text Available Abstract Background Depressive disorders are the most common form of mental disorders in community and health care settings. Unfortunately, the treatment of Major Depressive Disorder (MDD is far from satisfactory. Vagus nerve stimulation (VNS is a relatively new and promising physical treatment for depressive disorders. One particularly appealing element of VNS is the long-term benefit in mood regulation. However, because this intervention involves surgery, perioperative risks, and potentially significant side effects, this treatment has been limited to those patients with treatment-resistant depression who have failed medication trials and exhausted established somatic treatments for major depression, due to intolerance or lack of response. This double-blinded randomized clinical trial aims to overcome these limitations by introducing a novel method of stimulating superficial branches of the vagus nerve on the ear to treat MDD. The rationale is that direct stimulation of the afferent nerve fibers on the ear area with afferent vagus nerve distribution should produce a similar effect as classic VNS in reducing depressive symptoms without the burden of surgical intervention. Design One hundred twenty cases (60 males of volunteer patients with mild and moderate depression will be randomly divided into transcutaneous vagus nerve stimulation group (tVNS and sham tVNS group. The treatment period lasts 4 months and all clinical and physiological measurements are acquired at the beginning and the end of the treatment period. Discussion This study has the potential to significantly extend the application of VNS treatment for MDD and other disorders (including epilepsy, bipolar disorder, and morbid obesity, resulting in direct benefit to the patients suffering from these highly prevalent disorders. In addition, the results of this double-blinded clinical trial will shed new light on our understanding of acupuncture point specificity, and development of
Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn
OBJECTIVE: To determine, using research on duloxetine for major depressive disorder as an example, if there are inconsistencies between protocols, clinical study reports, and main publicly available sources (journal articles and trial registries), and within clinical study reports themselves......, with respect to benefits and major harms. DESIGN: Data on primary efficacy analysis and major harms extracted from each data source and compared. SETTING: Nine randomised placebo controlled trials of duloxetine (total 2878 patients) submitted to the European Medicines Agency (EMA) for marketing approval.......gov and the manufacturer's online clinical trial registry were searched for trial results. RESULTS: Clinical study reports fully described the primary efficacy analysis and major harms (deaths (including suicides), suicide attempts, serious adverse events, and discontinuations because of adverse events). There were minor...
Long, Timothy E; Williams, Justin T
Healthcare-associated infections caused by multi-drug resistant bacteria remain a major cause of worldwide mortality. With the recent approval of agents such as hetero-resistant cocci (i.e., ceftaroline, ceftobiprole, telavancin) for the treatment of Gram-positive infections by and drugs like fidaxomicin for treating Clostridium difficile, present-day research on antibacterials has largely shifted to developing interventions for diseases caused by Gram-negative bacilli. Cephalosporins have gained significant interest as antipseudomonals to be used in hospitals for treating device- and procedure-associated infections. With extended-spectrum activity against many enterobacterial pathogens, the introduction of new antipseudomonal cephalosporin-based treatments will mark a significant advancement in the management of hospital-borne diseases. The following review examines the present-day status of investigational cephalosporins currently in preclinical, Phase I and Phase II stage development. The article focuses specifically on treatments used for healthcare-associated infections due to Gram-negative bacteria. There is an urgent need for new antimicrobials to treat nosocomial infections due to multi-drug resistant Gram-negative bacteria. The impending approvals of antipseudomonal cephalosporins co-formulated with a β-lactamase inhibitor will allow clinicians to treat more hetero-resistant infections with cephalosporins, while avoiding the use of more toxic agents such as colistin. The growing interest in developing new β-lactamase inhibitor combinatorial treatments with approved β-lactam antibiotics is anticipated to decrease the number of novel cephalosporins entering clinical trials this decade.
Chen, Fa-Ming; Gao, Li-Na; Tian, Bei-Min; Zhang, Xi-Yu; Zhang, Yong-Jie; Dong, Guang-Ying; Lu, Hong; Chu, Qing; Xu, Jie; Yu, Yang; Wu, Rui-Xin; Yin, Yuan; Shi, Songtao; Jin, Yan
Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry. We conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss(®)) or the Control group (treatment with GTR and Bio-oss(®) without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure. A total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p 0.05). This study
Ahmed A. Al-Mohammadi
Full Text Available Thallium poisoning is usually associated with typical dermatological features simulating that of zinc deficiency. The aim of this study was to evaluate the role of oral zinc sulphate in the treatment of patients with thallium poisoning.Materials and methods: This clinical therapeutic trial study was conducted in Departments of Dermatology of Baghdad and Basrah Teaching Hospitals from February 2008 - February 2010, where a total of 37 patients with thallium poisoning were enrolled.A detailed history was taken from all patients and complete clinical examination was performed. All patients received zinc sulphate in a dose of 5 mg/kg three times a day few days before confirming the diagnosis of thallium poisoning. Thallium in urine had been measured using the colorimetric method and was positive in all patients. After confirming the diagnosis of thallium poisoning, thallium antidotes Prussian blue was given to 32 patients.Results: Age range of 37 patients was 5-33 (24±5.3 years. The dermatological findings were mainly: anagen hair loss affected the scalp and limbs. Also, dusky ecchymotic red dermatitis like rash was observed on the face and dorsum of hands and legs, while neurological manifestations were mainly of peripheral neuropathy, were reported in 21 (55% patients. All patients but two responded promptly to a trial of zinc sulphate within few days.Conclusion: Oral Zinc sulphate appears to be an effective and safe treatment for thallium poisoning particularly for skin and hair features and in reducing its lethal progression and complications. J Clin Exp Invest 2011;2(2:133-7
Cowan, Marie J; Freedland, Kenneth E; Burg, Matthew M; Saab, Patrice G; Youngblood, Marston E; Cornell, Carol E; Powell, Lynda H; Czajkowski, Susan M
To determine whether the 'dose' of treatment exposure, delivery of specific components of cognitive behavior therapy (CBT), patient adherence and/or use of antidepressants predict favorable depression and social support outcomes after 6 months of cognitive behavioral treatment. Secondary analyses of the intervention arm of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial involving persons with acute myocardial infarction (MI): n = 641 for the depression outcomes and n = 523 for the social support outcomes. The outcome measures were, for depression: the Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAM-D); for social support: the ENRICHD Social Support Instrument (ESSI) and Perceived Social Support Scale (PSSS). Better depression outcomes (measured by the BDI) were receiving a high number of depression-specific intervention components, p depression outcomes (measured by the HAM-D) were receiving a high number of the social communication and assertiveness components of the intervention, p social support outcomes (measured by the ESSI and PSSS) were predicted by membership in a racial or ethnic minority group, p social communication and assertiveness components of the intervention was an independent predictor of a worse social support outcome, p depression are useful in treating comorbid depression in post-MI patients. Working on communication skills may help to improve depression but not necessarily social support outcomes in this patient population, while adherence to cognitive-behavioral homework assignments is important for both outcomes. Other components of the ENRICHD intervention that were designed to improve social support had no discernible effects on outcomes. Intervention refinements may be needed in order to achieve better results in future post-MI clinical trials. A greater emphasis on CBT homework adherence could improve both depression and social support outcomes. 2008 S. Karger AG, Basel
Horigian, Viviana E; Marín-Navarrete, Rodrigo A; Verdeja, Rosa E; Alonso, Elizabeth; Perez, María A; Fernández-Mondragón, José; Berlanga, Carlos; Medina-Mora, María Elena; Szapocznik, José
Low- and middle-income countries (LMIC) lack the research infrastructure and capacity to conduct rigorous substance abuse and mental health effectiveness clinical trials to guide clinical practice. A partnership between the Florida Node Alliance of the United States National Drug Abuse Treatment Clinical Trials Network and the National Institute of Psychiatry in Mexico was established in 2011 to improve substance abuse practice in Mexico. The purpose of this partnership was to develop a Mexican national clinical trials network of substance abuse researchers and providers capable of implementing effectiveness randomized clinical trials in community-based settings. A technology transfer model was implemented and ran from 2011-2013. The Florida Node Alliance shared the "know how" for the development of the research infrastructure to implement randomized clinical trials in community programs through core and specific training modules, role-specific coaching, pairings, modeling, monitoring, and feedback. The technology transfer process was bi-directional in nature in that it was informed by feedback on feasibility and cultural appropriateness for the context in which practices were implemented. The Institute, in turn, led the effort to create the national network of researchers and practitioners in Mexico and the implementation of the first trial. A collaborative model of technology transfer was useful in creating a Mexican researcher-provider network that is capable of changing national practice in substance abuse research and treatment. Key considerations for transnational technology transfer are presented.
Full Text Available Neonatal sepsis, a life-threatening condition, presents with non-specific clinical manifestations and needs immediate empirical antimicrobial therapy. Choosing an appropriate antibiotic regimen covering the most probable pathogens is an important issue. In this study we compared the effectiveness of ceftizoxime and amikacin in the treatment of neonatal sepsis both in combination with ampicillin. In a randomized clinical trial, all term neonates with suspected sepsis referred to Bahrami hospital during March 2008 to March 2010 were evaluated. Patients were randomly recruited into two groups; one group receiving ampicillin and amikacin and the other ampicillin and ceftizoxime. Blood, urine and cerebrospinal fluid cultures, leukocyte count and C-reactive protein level were measured in all neonates. A total of 135 neonates were evaluated, 65 in amikacin group and 70 in ceftizoxime group. 60 neonates (85.7% in ceftizoxime group and 54 neonates (83.1% in amikacin group responded to the treatment (P= 0.673 and χ2 = 0.178. Only 24 (18% blood samples had a report of positive blood culture. The most frequent pathogen was coagulase negative staphylococcus with the frequency of 58.32% of all positive blood samples. Ceftizoxime in combination with ampicillin is an appropriate antimicrobial regimen for surrogating the combination of ampicillin and amikacin to prevent bacterial resistance against them.
Van Acker, Heleen H; Anguille, Sébastien; Willemen, Yannick; Smits, Evelien L; Van Tendeloo, Viggo F
A growing body of evidence points toward an important anti-cancer effect of bisphosphonates, a group of inexpensive, safe, potent, and long-term stable pharmacologicals that are widely used as osteoporosis drugs. To date, they are already used in the prevention of complications of bone metastases. Because the bisphosphonates can also reduce mortality in among other multiple myeloma, breast, and prostate cancer patients, they are now thoroughly studied in oncology. In particular, the more potent nitrogen-containing bisphosphonates have the potential to improve prognosis. The first part of this review will elaborate on the direct and indirect anti-tumoral effects of bisphosphonates, including induction of tumor cell apoptosis, inhibition of tumor cell adhesion and invasion, anti-angiogenesis, synergism with anti-neoplastic drugs, and enhancement of immune surveillance (e.g., through activation of γδ T cells and targeting macrophages). In the second part, we shed light on the current clinical position of bisphosphonates in the treatment of hematological and solid malignancies, as well as on ongoing and completed clinical trials investigating the therapeutic effect of bisphosphonates in cancer. Based on these recent data, the role of bisphosphonates is expected to further expand in the near future outside the field of osteoporosis and to open up new avenues in the treatment of malignancies. Copyright © 2015 Elsevier Inc. All rights reserved.
Emily K Tarleton
Full Text Available Current treatment options for depression are limited by efficacy, cost, availability, side effects, and acceptability to patients. Several studies have looked at the association between magnesium and depression, yet its role in symptom management is unclear. The objective of this trial was to test whether supplementation with over-the-counter magnesium chloride improves symptoms of depression. An open-label, blocked, randomized, cross-over trial was carried out in outpatient primary care clinics on 126 adults (mean age 52; 38% male diagnosed with and currently experiencing mild-to-moderate symptoms with Patient Health Questionnaire-9 (PHQ-9 scores of 5-19. The intervention was 6 weeks of active treatment (248 mg of elemental magnesium per day compared to 6 weeks of control (no treatment. Assessments of depression symptoms were completed at bi-weekly phone calls. The primary outcome was the net difference in the change in depression symptoms from baseline to the end of each treatment period. Secondary outcomes included changes in anxiety symptoms as well as adherence to the supplement regimen, appearance of adverse effects, and intention to use magnesium supplements in the future. Between June 2015 and May 2016, 112 participants provided analyzable data. Consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in PHQ-9 scores of -6.0 points (CI -7.9, -4.2; P<0.001 and net improvement in Generalized Anxiety Disorders-7 scores of -4.5 points (CI -6.6, -2.4; P<0.001. Average adherence was 83% by pill count. The supplements were well tolerated and 61% of participants reported they would use magnesium in the future. Similar effects were observed regardless of age, gender, baseline severity of depression, baseline magnesium level, or use of antidepressant treatments. Effects were observed within two weeks. Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated
Vuchinich, Rudy; Wallace, Dennis; Milby, Jesse B; Schumacher, Joseph E; Mennemeyer, Stephen; Kertesz, Stefan
Clinical trials with cocaine-dependent outpatients have found a strong relation between in-treatment and follow-up abstinence, and the strength of this relation is constant across treatment conditions with variable efficacy in generating abstinence. The authors conducted secondary analyses of data from 3 clinical trials to determine whether this relation generalizes to cocaine-dependent homeless persons. The 3 trials (total N = 543) were conducted in a community health care facility for homeless people. The 7 treatment arms across the 3 trials were combinations of day treatment, abstinence-contingent housing, and vocational training. Drug use was measured with urine toxicology testing. Consecutive weeks of abstinence during treatment were strongly related to abstinence at the 12-month follow-up, whether or not missing 12-month data were included in the analysis. The treatment arms differed in their efficacy in generating abstinence, but the relation between in-treatment and follow-up abstinence did not differ across treatment arms. These results replicate earlier reports of these relations and extend them to a population of homeless people. The lack of differences between treatment arms in the in-treatment-follow-up abstinence relation implies that that relation is independent of the treatment-specific intervention components that generate group differences in abstinence.
López-Carvajal, Liliana; Cardona-Arias, Jaiberth Antonio; Zapata-Cardona, María Isabel; Sánchez-Giraldo, Vanesa; Vélez, Iván Darío
Cryotherapy is a local treatment for cutaneous leishmaniasis with variable efficacy and greater safety than conventional treatment. The objective of this study is to evaluate the efficacy and safety of cryotherapy for the treatment of cutaneous leishmaniasis and to compare it with pentavalent antimonials. A meta-analysis based on a search of nine databases with eight strategies was conducted. Inclusion and exclusion criteria were applied, the methodological quality of each article was evaluated, and the reproducibility of the study selection and information extraction from each clinical trial was assured. The per lesion and per patient efficacy was calculated, and a meta-analysis of relative risks with the random effects model and the Dersimonian and Laird's, Begg, and Egger tests, along with a sensitivity analysis, were performed. A meta-regression based on the methodological quality of the trials included was also performed. Eight studies were included in which respective per lesion efficacies of 67.3 % and 67.7 % were reported for cryotherapy and pentavalent antimonials. In 271 patients treated with cryotherapy and in 199 with pentavalent antimonials, respective per protocol and intent to treat efficacies of 63.6 % and 54.2 % were found in the first group, and per protocol and intent to treat efficacies of 74.7 % and 68.3 % were found in the second group. The relative risk for the comparison of efficacy in the two groups was 0.73 (0.42-1.29). The results of the sensitivity analysis and the meta-regression analysis of relative risks were statistically equal to the overall results. This investigation provides evidence in favor of the use of cryotherapy given that its efficacy is similar to that of pentavalent antimonials.
Hartmann, Andreas; Müllner, Julia; Meier, Niklaus; Hesekamp, Helke; van Meerbeeck, Priscilla; Habert, Marie-Odile; Kas, Aurélie; Tanguy, Marie-Laure; Mazmanian, Merry; Oya, Hervé; Abuaf, Nissen; Gaouar, Hafida; Salhi, Sabrina; Charbonnier-Beaupel, Fanny; Fievet, Marie-Hélène; Galanaud, Damien; Arguillere, Sophie; Roze, Emmanuel; Degos, Bertrand; Grabli, David; Lacomblez, Lucette; Hubsch, Cécile; Vidailhet, Marie; Bonnet, Anne-Marie
In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease. Trial Registration
Roman, Paul M; Abraham, Amanda J; Rothrauff, Tanja C; Knudsen, Hannah K
The National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) to conduct trials of promising substance abuse treatment interventions in diverse clinical settings and to disseminate results of these trials. This article focuses on three dimensions of CTN's organizational functioning. First, a longitudinal dataset is used to examine CTN's formation as a network of interorganizational interaction among treatment practitioners and researchers. Data indicate strong relationships of interaction and trust, but a decline in problem-centered interorganizational interaction over time. Second, adoption of buprenorphine and motivational incentives among CTN's affiliated community treatment programs (CTPs) is examined over three waves of data. Although adoption is found to increase with CTPs' CTN participation, there is only modest evidence of widespread penetration and implementation. Third, CTPs' pursuit of the CTN's dissemination goals are examined, indicating that such organizational outreach activities are underway and likely to increase innovation diffusion in the future.
Cerritelli, Francesco; Ginevri, Liana; Messi, Gabriella; Caprari, Emanuele; Di Vincenzo, Marcello; Renzetti, Cinzia; Cozzolino, Vincenzo; Barlafante, Gina; Foschi, Nicoletta; Provinciali, Leandro
To assess the effectiveness of OMT on chronic migraineurs using HIT-6 questionnaire, drug consumption, days of migraine, pain intensity and functional disability. 3-Armed randomized controlled trial setting: all patients admitted in the Department of Neurology of Ancona's United Hospitals, Italy, with a diagnosis of migraine and without chronic illness, were considered eligible for the study. Patients were randomly divided into three groups: (1) OMT+medication therapy, (2) sham+medication therapy and (3) medication therapy only. Patients received 8 treatments in a study period of 6 months. Changing from baseline HIT-6 score. 105 subjects were included. At the end of the study, ANOVA showed that OMT significantly reduced HIT-6 score (mean change scores OMT-conventional care: -8.74; 95% confidence interval (CI) -12.96 to -4.52; p<0.001 and OMT-sham: -6.62; 95% CI -10.85 to -2.41; p<0.001), drug consumption (OMT-sham: RR=0.22, 95% CI 0.11-0.40; OMT-control: RR=0.20, 95% CI 0.10-0.36), days of migraine (OMT-conventional care: M=-21.06; 95% CI -23.19 to -18.92; p<0.001 and OMT-sham: -17.43; 95% CI -19.57 to -15.29; p<0.001), pain intensity (OMT-sham: RR=0.42, 95% CI 0.24-0.69; OMT-control: RR=0.31, 95% CI 0.19-0.49) and functional disability (p<0.001). These findings suggest that OMT may be considered a valid procedure for the management of migraineurs. The present trial was registered on www.ClinicalTrials.gov (identifier: NCT01851148). Copyright © 2015 Elsevier Ltd. All rights reserved.
Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn
, with respect to benefits and major harms. DESIGN: Data on primary efficacy analysis and major harms extracted from each data source and compared. SETTING: Nine randomised placebo controlled trials of duloxetine (total 2878 patients) submitted to the European Medicines Agency (EMA) for marketing approval...... inconsistencies in the population in the primary efficacy analysis between the protocol and clinical study report and within the clinical study report for one trial. Furthermore, we found contradictory information within the reports for seven serious adverse events and eight adverse events that led......OBJECTIVE: To determine, using research on duloxetine for major depressive disorder as an example, if there are inconsistencies between protocols, clinical study reports, and main publicly available sources (journal articles and trial registries), and within clinical study reports themselves...
Mosley, Scott A; Hicks, J Kevin; Portman, Diane G; Donovan, Kristine A; Gopalan, Priya; Schmit, Jessica; Starr, Jason; Silver, Natalie; Gong, Yan; Langaee, Taimour; Clare-Salzler, Michael; Starostik, Petr; Chang, Young D; Rajasekhara, Sahana; Smith, Joshua E; Soares, Heloisa P; George, Thomas J; McLeod, Howard L; Cavallari, Larisa H
Pain is one of the most burdensome symptoms associated with cancer and its treatment, and opioids are the cornerstone of pain management. Opioid therapy is empirically selected, and patients often require adjustments in therapy to effectively alleviate pain or ameliorate adverse drug effects that interfere with quality of life. There are data suggesting CYP2D6 genotype may contribute to inter-patient variability in response to opioids through its effects on opioid metabolism. Therefore, we aim to determine if CYP2D6 genotype-guided opioid prescribing results in greater reductions in pain and symptom severity and interference with daily living compared to a conventional prescribing approach in patients with cancer. Patients with solid tumors with metastasis and a self-reported pain score ≥ 4/10 are eligible for enrollment and randomized to a genotype-guided or conventional pain management strategy. For patients in the genotype-guided arm, CYP2D6 genotype information is integrated into opioid prescribing decisions. Patients are asked to complete questionnaires regarding their pain, symptoms, and quality of life at baseline and 2, 4, 6, and 8 weeks after enrollment. The primary endpoint is differential change in pain severity by treatment strategy (genotype-guided versus conventional pain management). Secondary endpoints include change in pain and symptom interference with daily living. Pharmacogenetic-guided opioid selection for cancer pain management has potential clinical utility, but current evidence is limited to retrospective and observational studies. Precision Medicine Guided Treatment for Cancer Pain is a pragmatic clinical trial that seeks to determine the utility of CYP2D6 genotype-guided opioid prescribing in patients with cancer. Copyright © 2018 Elsevier Inc. All rights reserved.
Rompalo, A.; Taylor, S.; Seña, A. C.; Martin, D. H.; Lopez, L. M.; Lensing, S.; Lee, J. Y.
Background. Nongonococcal urethritis (NGU) is a common chlamydia-associated syndrome in men; however, Trichomonas vaginalis and Mycoplasma genitalium are associated with its etiology and should be considered in approaches to therapy. We sought to determine whether the addition of tinidazole, an anti-trichomonal agent, to the treatment regimen would result in higher cure rates than those achieved with treatment with doxycycline or azithromycin alone. A secondary aim was to compare the efficacy of doxycycline therapy and with that of azithromycin therapy. Methods. Randomized, controlled, double-blinded phase IIB trial of men with NGU. Participants were randomized to receive doxycycline plus or minus tinidazole or azithromycin plus or minus tinidazole and were observed for up to 45 days. Results. The prevalences of Chlamydia trachomatis, M. genitalium, and T. vaginalis were 43%, 31%, and 13%, respectively. No pathogens were identified in 29% of participants. Clinical cure rates at the first follow-up visit were 74.5% (111 of 149 patients) for doxycycline-containing regimens and 68.6% (107 of 156 patients) for azithromycin-containing regimens. By the final visit, cure rates were 49% (73 of 149 patients) for doxycycline-containing regimens and 43.6% (68 of 156 patients) for azithromycin-containing regimens. There were no significant differences in clinical response rates among the treatment arms. However, the chlamydia clearance rate was 94.8% (55 of 58 patients) for the doxycycline arm and 77.4% (41 of 53 patients) for the azithromycin arm (P = .011), and the M. genitalium clearance rate was 30.8% (12 of 39 patients) for the doxycycline arm and 66.7% (30 of 45 patients) for the azithromycin arm (P = .002). Conclusions. Addition of tinidazole to the treatment regimen did not result in higher cure rates but effectively eradicated trichomonas. Clinical cure rates were not significantly different between patients treated with doxycycline and those treated
Tfelt-Hansen, Peer; Lindqvist, Janus Kaufmann; Do, Thien Phu
Background In 2008, the International Headache Society published guidelines on the "evaluation and registration of adverse events in clinical drug trials on migraine". They listed seven recommendations for reporting adverse events in randomized controlled trials on migraine. The present study aimed to evaluate adherence to these recommendations, and based on the results, to recommend improvements. Methods We searched the PubMed/MEDLINE database to identify controlled trials on migraine drugs published from 2010 to 2015. For each trial, we noted whether five of the recommended parameters were presented. In addition, we noted whether adverse events were reported in abstracts. Results We identified 73 trials; 51 studied acutely administered drugs and 22 studied prophylactic drugs for migraine. The number of patients with any adverse events were reported in 74% of acute-administration and 86% of prophylactic drug trials. Only 30 (41%) of the 73 studies reported adverse events with data in the abstracts, and 27 (37%) abstracts did not mention adverse events. Conclusion Adverse events, both frequency and symptoms, should be reported to allow a fair judgement of benefit/tolerability ratio when randomized controlled trials in migraine treatment are published. Clinically significant adverse events should be included in the abstract of every randomized controlled trial in migraine treatment.
Full Text Available Abstract Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation.
Nordentoft, Merete; Thorup, Anne; Petersen, Lone
Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms.......Only a few randomized clinical trials have tested the effect on transition rates of intervention programs for patients with sub-threshold psychosis-like symptoms....
Bagiella, Emilia; Novack, Thomas A; Ansel, Beth; Diaz-Arrastia, Ramon; Dikmen, Sureyya; Hart, Tessa; Temkin, Nancy
Traumatic brain injury (TBI) involves several aspects of a patient's condition, including physical, mental, emotional, cognitive, social, and functional changes. Therefore, a clinical trial with individuals with TBI should consider outcome measures that reflect their global status. We present the work of the National Institute of Child Health and Development-sponsored Traumatic Brain Injury Clinical Trials Network Outcome Measures subcommittee and its choice of outcome measures for a phase III clinical trial of patients with complicated mild to severe TBI. On the basis of theoretical and practical considerations, the subcommittee recommended the adoption of a core of 9 measures that cover 2 different areas of recovery: functional and cognitive. These measures are the Extended Glasgow Outcome Scale; the Controlled Oral Word Association Test; the Trail Making Test, Parts A and B; the California Verbal Learning Test-II; the Wechsler Adult Intelligence Scale-III Digit Span subtest; the Wechsler Adult Intelligence Scale-III Processing Speed Index; and the Stroop Color-Word Matching Test, Parts 1 and 2. The statistical methods proposed to analyze these measures using a global test procedure, along with research and methodological and regulatory issues involved with the use of multiple outcomes in a clinical trial, are discussed.
Califf, R.M.; Zarin, D.A.; Kramer, J.M.; Sherman, R.E.; Aberle, L.H.; Tasneem, A.
CONTEXT: Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials
ter Riet, G.; Kessels, A. G.; Knipschild, P. G.
The objective of this study was to assess the effects of ascorbic acid supplementation, 500 mg twice daily in the treatment of pressure ulcers as an adjunct to standardized treatment. The design consisted of a multicenter blinded randomized trial. The control group received 10 mg of ascorbic acid
Faghihi, Gita; Khosravani, Parastoo; Nilforoushzadeh, Mohammad Ali; Hosseini, Sayyed Mohsen; Assaf, Fatemeh; Zeinali, Naser; Smiley, Abbas
We aimed to evaluate the effects of 5% dapsone gel compared with 0.75% metronidazole gel in the treatment of papulopustular rosacea. In a double-blind randomized clinical trial, 56 adult patients with papulopustular rosacea were enrolled. The severity of disorder was determined by the patient according to visual analogue score (VAS). Investigator's global assessment (IGA) scores and number of inflammatory lesions were recorded. 5% dapsone gel was administered for group D and 0.75% metronidazole gel was administered for group M. Systemic doxycycline was administered for all patients. Follow-up assessments were done at 4, 8, and 12 weeks. Changes in VAS, IGA scores and number of lesions were evaluated. Intention to treat analysis was carried out using SPSS version 17 (Chicago, IL). There was no significant difference in sex and age distribution between the two groups. Mean (SD) IGA score before and after intervention in group D was 3.9 (0.9) and 3.3 (0.9), respectively (PDapsone gel was as effective as metronidazole gel in the treatment of papulopustular rosacea.
Wanke, M M; Delpino, M V; Baldi, P C
To date, no totally effective antibiotic for the eradication of canine brucellosis has been found. The purpose of this study was to evaluate the efficacy of enrofloxacin in a kennel infected with Brucella canis. Twelve dogs, 2 males and 10 females (including 1 in estrus, 3 pregnant, and 6 in anestrus) infected with B. canis were given 5 mg/kg of enrofloxacin orally every 12 h for 30 days. Females received additional courses of enrofloxacin during the estral and luteal phases of the subsequent cycles (0-2 cycles). They were repeatedly mated by infected males. A serological follow-up was carried out for 38 months. The clinical, serological and bacteriological findings were recorded. In a trial carried out 14 months after the beginning of this study, all dogs were negative on the Rapid Slide Agglutination Test (RSAT). No abortions were observed. All mated female dogs conceived and gave birth to healthy puppies. Cultures of postpartum vaginal discharges (lochia) were negative for B. canis. Similar to other treatments, although enrofloxacin was not completely efficacious in treating canine brucellosis, it maintained fertility and avoided the recurrence of abortions, transmission of the disease to the puppies and dissemination of microorganisms during parturition. We inferred that enrofloxacin could be used as an alternative drug for the treatment of canine brucellosis.
Le Grange, Daniel; Hughes, Elizabeth K; Court, Andrew; Yeo, Michele; Crosby, Ross D; Sawyer, Susan M
There have been few randomized clinical trials (RCTs) for adolescents with anorexia nervosa (AN). Most of these posit that involving all family members in treatment supports favorable outcomes. However, at least 2 RCTs suggest that separate parent and adolescent sessions may be just as effective as conjoint treatment. This study compared the relative efficacy of family-based treatment (FBT) and parent-focused treatment (PFT). In PFT, the therapist meets with the parents only, while a nurse monitors the patient. Participants (N = 107) aged 12 to 18 years and meeting DSM 4(th)Edition criteria for AN or partial AN were randomized to either FBT or PFT. Participants were assessed at baseline, end of treatment (EOT), and at 6 and 12 months posttreatment. Treatments comprised 18 outpatient sessions over 6 months. The primary outcome was remission, defined as ≥95% of median body mass index and Eating Disorder Examination Global Score within 1 SD of community norms. Remission was higher in PFT than in FBT at EOT (43% versus 22%; p = .016, odds ratio [OR] = 3.03, 95% CI = 1.23-7.46), but did not differ statistically at 6-month (PFT 39% versus FBT 22%; p = .053, OR = 2.48, CI = 0.989-6.22), or 12-month (PFT 37% versus FBT 29%; p = .444, OR = 1.39, 95% CI = 0.60-3.21) follow-up. Several treatment effect moderators of primary outcome were identified. At EOT, PFT was more efficacious than FBT in bringing about remission in adolescents with AN. However, differences in remission rates between PFT and FBT at follow-up were not statistically significant. A Randomised Controlled Trial of Two Forms of Family-Based Treatment and the Effect on Percent Ideal Body Weight and Eating Disorders Symptoms in Adolescent Anorexia Nervosa; http://www.anzctr.org.au/; ACTRN12610000216011. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
Sun, Hong; Bretz, Frank; Gerke, Oke
idea of selecting the subset with minimal p-value when testing the subset-specific treatment effects. We present a framework to compare this approach with other approaches to select subsets by introducing three performance measures. The results of a comprehensive simulation study are presented...
-mediated dilation did not significantly change in the carbocysteine group.Oral carbocysteine slightly improves sleep disorders by attenuating oxidative stress in patients with moderate to severe OSAS. Carbocysteine may have a role in the treatment of OSAS patients with poor compliance with CPAP treatment. However, the efficiency and feasibility of carbocysteine treatment for OSAS needs further evaluation.ClinicalTrials.gov NCT02015598.
Full Text Available In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20. The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease.ClinicalTrials
Full Text Available Abstract Background Gastric ulcers are a frequent problem in the United States. Proton pump inhibitors have been shown to increase healing rates and improve clinical symptoms. The objective of this study is to compare gastric ulcer healing rates for patients treated with a proton pump inhibitor (PPI (omeprazole, rabeprazole, pantoprazole, or lansoprazole, an histamine 2- receptor antagonist (ranitidine or placebo. Methods A literature search was conducted to identify randomized, controlled clinical trials that included a PPI in at least one treatment arm and assessed the gastric ulcer healing rates endoscopically. The healing rates were estimated for each treatment at specific time points, and Rate Ratios (RR and 95% confidence intervals (CI were estimated for each trial. Results Sixteen trials met the inclusion criteria: four compared a PPI versus placebo, nine compared a PPI versus ranitidine (no trials of rabeprazole versus ranitidine met the inclusion criteria, and three compared a newer PPI (lansoprazole, pantoprazole or rabeprazole versus omeprazole. In relation to ranitidine, the pooled RR of PPIs (lansoprazole, omeprazole and pantoprazole was 1.33 (95% CI 1.24 to 1.42 at four weeks. In each trial, greater improvement in the studied clinical symptoms was found with the newer PPIs (rabeprazole, pantoprazole and lansoprazole when compared to omeprazole. Conclusion In this study treatment with PPIs resulted in higher healing rates than ranitidine or placebo. This evidence suggests that the first choice for gastric ulcer treatment for the greater relief of symptoms is one of the newer PPIs.
Maiti, Rituparna; M, Raghavendra
The concept of outsourcing for the development and global studies on new drugs has become widely accepted in the pharmaceutical industry due to its cost and uncertainty. India is going to be the most preferred location for contract pharma research and development due to its huge treatment naïve population, human resources, technical skills, adoption/amendment/implementation of rules/laws by regulatory authorities, and changing economic environment. But still 'miles to go' to fulfill the pre-requisites to ensure India's success. In spite of all the pitfalls, the country is ambitious and optimist to attract multinational pharmaceutical companies to conduct their clinical trials in India.
Wang, Chi; Tan, Zhiqiang; Louis, Thomas A
Evaluating the effect of a treatment on a time-to-event outcome is the focus of many randomized clinical trials. It is often observed that the treatment effect is heterogeneous, where only a subgroup of the patients may respond to the treatment due to some unknown mechanism such as genetic polymorphism. In this paper, we propose a semiparametric exponential tilt mixture model to estimate the proportion of patients who respond to the treatment and to assess the treatment effect. Our model is a natural extension of parametric mixture models to a semiparametric setting with a time-to-event outcome. We propose a nonparametric maximum likelihood estimation approach for inference and establish related asymptotic properties. Our method is illustrated by a randomized clinical trial on biodegradable polymer-delivered chemotherapy for malignant gliomas patients.
Dunning, Jake; Sahr, Foday; Rojek, Amanda
BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD...... of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429....
McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John
The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, prelationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. Copyright © 2015 Elsevier Inc. All rights reserved.
Johnson, Dawn M.; Zlotnick, Caron; Perez, Sara
Objective: This study was designed to explore the acceptability, feasibility, and initial efficacy of a new shelter-based treatment for victims of intimate partner violence (IPV; i.e., Helping to Overcome PTSD through Empowerment [HOPE]). Method: A Phase I randomized clinical trial comparing HOPE (n = 35) with standard shelter services (SSS) (n =…
Padberg, M.; de Bruijn, S. F. T. M.; de Haan, R. J.; Tavy, D. L. J.
Botulinum toxin is increasingly advocated as effective treatment in chronic tension-type headache. We conducted a randomized, placebo-controlled clinical trial to prove efficacy of botulinum toxin in chronic tension-type headache. Patients were randomly assigned to receive botulinum toxin (maximum
Gordon, Michael S.; Kinlock, Timothy W.; Couvillion, Kathryn A.; Schwartz, Robert P.; O'Grady, Kevin
The present report is an intent-to-treat analysis involving secondary data drawn from the first randomized clinical trial of prison-initiated methadone in the United States. This study examined predictors of treatment entry and completion in prison. A sample of 211 adult male prerelease inmates with preincarceration heroin dependence were randomly…
Steunebrink, Mirjam; Zwerver, Johannes; Brandsema, Ruben; Groenenboom, Petra; van den Akker-Scheek, Inge; Weir, Adam
Objectives To assess if continuous topical glyceryl trinitrate (GTN) treatment improves outcome in patients with chronic patellar tendinopathy when compared with eccentric training alone. Methods Randomised double-blind, placebo-controlled clinical trial comparing a 12-week programme of using a GTN
.... Clinical Trials in Neurology aims to improve the efficiency of clinical trials and the development of interventions in order to enhance the development of new treatments for neurologic diseases...
Wu, H; Zhang, Y; Huang, J; Zhang, Y; Liu, G; Sun, N; Yu, Z; Zhou, Y
To compare the effects of an alpha, beta blocker, arotinolol, in the treatment of essential hypertension between patients with a dipper and those with a non-dipper profile by means of 24-h ambulatory blood pressure monitoring (ABPM), a multicenter single blind parallel trial was carried out in five clinical centers. After a one-week single blind placebo run-in period, the patients underwent ABPM if their clinic diastolic blood pressure (DBP) ranged from 90-109 mmHg and their clinic systolic blood pressure (SBP) was or =10% of daytime BP. ABPM was measured again at the end of the active treatment phase. All patients were given Arotinolol 10-20 mg twice daily for 4 weeks. Twenty four-hour systolic and diastolic average BPs (MSBP, MDBP), 24-h systolic and diastolic blood pressure load (LS BP, LDBP), daytime systolic and diastolic average BPs (dMSBP, dMDBP), daytime systolic and diastolic blood pressure load (dLSBP, dLDBP), nighttime systolic and diastolic average BPs (nMSBP, nMDBP) and nighttime systolic and diastolic blood pressure load (nLSBP, nLDBP) were calculated. Arotinolol was effective in 78.2% of dippers and 54.2% of non-dippers, but the difference in effectiveness between these groups was not statistically significant. After treatment, SBP and DBP-including 24-h, daytime and nighttime systolic and diastolic BPs- were significantly reduced in both groups. During the daytime period, the systolic and diastolic blood pressures were significantly reduced in both dippers and non-dippers, while nighttime systolic and diastolic blood pressures were significantly reduced only in the non-dipper group. No significant changes were found in the dipper group over this period. In conclusion, Arotinolol, which can be dosed twice daily, is an effective antihypertensive agent which effectively lowers blood pressure during the day while reducing nighttime blood pressure more in non-dippers than in dippers, without excessive lowering blood pressure in the latter.
Mao, Jun J; Xie, Sharon X; Keefe, John R; Soeller, Irene; Li, Qing S; Amsterdam, Jay D
Generalized Anxiety Disorder (GAD) is one of the most common anxiety disorders treated in primary care, yet current therapies have limited efficacy and substantial side effects. To evaluate long-term chamomile (Matricaria chamomilla L.) use for prevention of GAD symptom relapse. Outpatients from primary care practices and local communities with a primary diagnosis of moderate-to-severe GAD were enrolled for this two-phase study at a large US academic medical center. During Phase 1, eligible participants received 12 weeks of open-label therapy with chamomile pharmaceutical grade extract 1500mg (500mg capsule 3 times daily). During Phase 2, treatment responders were randomized to either 26 weeks of continuation chamomile therapy or placebo in a double-blinded, placebo-substitution design. The primary outcome was time to relapse during continuation therapy, analyzed using Cox proportional hazards. Secondary outcomes included the proportion who relapsed, treatment-emergent adverse events, and vital sign changes. This study is registered at ClinicalTrials.gov, identifier NCT01072344. Between March 1, 2010, and June 30, 2015, we enrolled 179 participants. Of those, 93 (51.9%) were responders and agreed to continue in the double-blind randomized controlled trial. A numerically greater number of placebo-switched (n=12/47; 25.5%) versus chamomile-continuation (n = 7/46; 15.2%) participants relapsed during follow-up. Mean time to relapse was 11.4 ± 8.4 weeks for chamomile and 6.3 ± 3.9 weeks for placebo. Hazard of relapse was non-significantly lower for chamomile (hazard ratio, 0.52; 95% CI, 0.20-1.33; P = 0.16). During follow-up, chamomile participants maintained significantly lower GAD symptoms than placebo (P = 0.0032), with significant reductions in body weight (P = 0.046) and mean arterial blood pressure (P = 0.0063). Both treatments had similar low adverse event rates. Long-term chamomile was safe and significantly reduced moderate
Sabzghabaee, Ali Mohammad; Dianatkhah, Mehrnoush; Sarrafzadegan, Nizal; Asgary, Sedigheh; Ghannadi, Alireza
Natural products are proved to play a good role as an alternative to synthetic chemicals in many clinical conditions. Hypercholesterolemia is the most important risk factor for atherosclerosis. Previous studies showed that Nigella sativa L. has both antioxidant and lipid lowering potentials. To evaluate the efficacy of the seeds of Nigella sativa on the treatment of hyperlipidemia. In this randomized, placebo controlled clinical trial which was conducted in Isfahan city (Iran), 88 subjects aged > or =18 years with a total cholesterol concentration >200 mg/dl were included. According to the patients" profiles number, they were randomized to receive either N. sativa capsules or the matching placebo. Each N sativa capsule contained 500 +/- 10 mg N. sativa crushed seeds, and patients had to take 2 g N. sativa per day for 4 weeks. Fasting baseline laboratory values (fasting blood sugar, total cholesterol, low density lipoprotein, high density lipoprotein and triglyceride) were obtained for all parameters on each subject prior to the start of the study and at the end of 4 weeks. In our study a significant decrease was observed in the concentration of total cholesterol (4.78%), Low density lipoprotein (7.6%) and Triglyceride (16.65%), and this decrease was more significant for TG concentration. N. sativa had not any beneficial effects on Fasting blood sugar and High density lipoprotein. According to the results of our present study it seems that N. sativa may have some beneficial therapeutic effects in the treatment of hyperlipidemia. However, further investigations with a larger sample size are necessary.
Jensen, Rikke Krüger; Leboeuf-Yde, Charlotte; Wedderkopp, Niels
ABSTRACT: BACKGROUND: Clinical experience suggests that many patients with Modic changes have relatively severe and persistent low back pain (LBP), which typically appears to be resistant to treatment. Exercise therapy is the recommended treatment for chronic LBP, however due to their underlying...... on any outcome. CONCLUSIONS: No differences were found between the two treatment approaches, 'rest and reduced load' and 'exercise and staying active', in patients with persistent LBP and Modic changes. Trial registration: ClinicalTrials.gov NCT00454792....... pathology, Modic changes might be a diagnostic subgroup that does not benefit from exercise. The objective of this study was to compare the current state-of-the art treatment approach (exercise and staying active) with a new approach (load reduction and daily rest) for people with Modic changes using...
Weiss, Roger D; Potter, Jennifer Sharpe; Griffin, Margaret L; Provost, Scott E; Fitzmaurice, Garrett M; McDermott, Katherine A; Srisarajivakul, Emily N; Dodd, Dorian R; Dreifuss, Jessica A; McHugh, R Kathryn; Carroll, Kathleen M
Despite the growing prevalence of prescription opioid dependence, longitudinal studies have not examined long-term treatment response. The current study examined outcomes over 42 months in the Prescription Opioid Addiction Treatment Study (POATS). POATS was a multi-site clinical trial lasting up to 9 months, examining different durations of buprenorphine-naloxone plus standard medical management for prescription opioid dependence, with participants randomized to receive or not receive additional opioid drug counseling. A subset of participants (N=375 of 653) enrolled in a follow-up study. Telephone interviews were administered approximately 18, 30, and 42 months after main-trial enrollment. Comparison of baseline characteristics by follow-up participation suggested few differences. At Month 42, much improvement was seen: 31.7% were abstinent from opioids and not on agonist therapy; 29.4% were receiving opioid agonist therapy, but met no symptom criteria for current opioid dependence; 7.5% were using illicit opioids while on agonist therapy; and the remaining 31.4% were using opioids without agonist therapy. Participants reporting a lifetime history of heroin use at baseline were more likely to meet DSM-IV criteria for opioid dependence at Month 42 (OR=4.56, 95% CI=1.29-16.04, p<.05). Engagement in agonist therapy was associated with a greater likelihood of illicit-opioid abstinence. Eight percent (n=27/338) used heroin for the first time during follow-up; 10.1% reported first-time injection heroin use. Long-term outcomes for those dependent on prescription opioids demonstrated clear improvement from baseline. However, a subset exhibited a worsening course, by initiating heroin use and/or injection opioid use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Gao, Tina Y; Anstice, Nicola; Babu, Raiju J; Black, Joanna M; Bobier, William R; Dai, Shuan; Guo, Cindy X; Hess, Robert F; Jenkins, Michelle; Jiang, Yannan; Kearns, Lisa; Kowal, Lionel; Lam, Carly S Y; Pang, Peter C K; Parag, Varsha; South, Jayshree; Staffieri, Sandra Elfride; Wadham, Angela; Walker, Natalie; Thompson, Benjamin
Optical treatment alone can improve visual acuity (VA) in children with amblyopia, thus clinical trials investigating additional amblyopia therapies (such as patching or videogames) for children require a preceding optical treatment phase. Emerging therapies for adult patients are entering clinical trials. It is unknown whether optical treatment is effective for adults with amblyopia and whether an optical correction phase is required for trials involving adults. We examined participants who underwent optical treatment in the Binocular Treatment for Amblyopia using Videogames (BRAVO) clinical trial (ANZCTR ID: ACTRN12613001004752). Participants were recruited in three age groups (7 to 12, 13 to 17, or ≥18 years), and had unilateral amblyopia due to anisometropia and/or strabismus, with amblyopic eye VA of 0.30-1.00 logMAR (6/12 to 6/60, 20/40 to 20/200). Corrective lenses were prescribed based on cycloplegic refraction to fully correct any anisometropia. VA was assessed using the electronic visual acuity testing algorithm (e-ETDRS) test and near stereoacuity was assessed using the Randot Preschool Test. Participants were assessed every four weeks up to 16 weeks, until either VA was stable or until amblyopic eye VA improved to better than 0.30 logMAR, rendering the participant ineligible for the trial. Eighty participants (mean age 24.6 years, range 7.6-55.5 years) completed four to 16 weeks of optical treatment. A small but statistically significant mean improvement in amblyopic eye VA of 0.05 logMAR was observed (S.D. 0.08 logMAR; paired t-test p < 0.0001). Twenty-five participants (31%) improved by ≥1 logMAR line and of these, seven (9%) improved by ≥2 logMAR lines. Stereoacuity improved in 15 participants (19%). Visual improvements were not associated with age, presence of strabismus, or prior occlusion treatment. Two adult participants withdrew due to intolerance to anisometropic correction. Sixteen out of 80 participants (20%) achieved better than 0
Trivedi, Madhukar H; Thase, Michael E; Osuntokun, Olawale; Henley, David B; Case, Michael; Watson, Susan B; Campbell, Giedra M; Corya, Sara A
To evaluate the efficacy of olanzapine/fluoxetine combination (OFC) versus olanzapine or fluoxetine monotherapy across all clinical trials of treatment-resistant depression sponsored by Eli Lilly and Company. Efficacy and safety data from 1146 patients with a history of nonresponse during the current depressive episode who subsequently exhibited nonresponse during a 6- to 8-week antidepressant open-label lead-in phase and were randomly assigned to OFC (N = 462), fluoxetine (N = 342), or olanzapine (N = 342) for double-blind treatment were analyzed. All patients had a diagnosis of major depressive disorder as defined by DSM-III or DSM-IV criteria. The dates in which the trials were conducted ranged from May 1997 to July 2005. After 8 weeks, OFC patients demonstrated significantly greater Montgomery-Asberg Depression Rating Scale improvement (mean change = -13.0) than fluoxetine (-8.6, p or= 10% of OFC patients were weight gain, increased appetite, dry mouth, somnolence, fatigue, headache, and peripheral edema. Random glucose mean change (mg/dL) was +7.92 for the OFC group, +1.62 for the fluoxetine group (p = .020), and +9.91 for the olanzapine group (p = .485). Random cholesterol mean change (mg/dL) was +12.4 for OFC, +2.3 for fluoxetine (p or= 240 subsequently) was significantly higher for the OFC group (10.2%) than for the fluoxetine group (3.1%, p = .017) but not the olanzapine group (8.0%, p = .569). Mean weight change (kg) was +4.42 for OFC, -0.15 for fluoxetine (p or= 7% body weight (vs. olanzapine: 42.9%, p = .515; fluoxetine: 2.3%, p < .001). Results of this analysis showed that OFC-treated patients experienced significantly improved depressive symptoms compared with olanzapine- or fluoxetine-treated patients following failure of 2 or more antidepressants within the current depressive episode. Safety results for OFC were generally consistent with those for its component monotherapies. The total cholesterol increase associated with OFC was more pronounced
Sahebnasagh, Adeleh; Ghasemi, Arash; Akbari, Jafar; Alipour, Abbas; Lashkardoost, Hossein; Ala, Shahram; Salehifar, Ebrahim
Acute radiation proctitis (ARP) is a common side-effect that affects up to 50% of patients receiving radiotherapy. The aim of this study was to evaluate the role of a topical preparation of Aloe vera in the treatment of ARP induced by radiotherapy of pelvic area. In this double-blind placebo-controlled trial, 20 consecutive patients with ARP after external-beam radiation therapy (46-72 Gy) of pelvic malignancies were randomized to receive either Aloe vera 3% or placebo ointment, 1 g twice daily for 4 weeks. These patients presented with at least two of the following symptoms: rectal bleeding, abdominal/rectal pain, diarrhea, or fecal urgency. These symptoms were rated by the patients in terms of their severity (grade 0-4) for each of the symptoms mentioned earlier at baseline and then weekly for 4 weeks. A symptom index was calculated by the addition of the scores (16 most symptomatic). Radiation Therapy Oncology Group (RTOG) acute toxicity criteria and psychosocial status of the patients were also recorded weekly. The lifestyle impact of the symptoms was assessed by questionnaire grading from 0 (no effect on daily activity) to 4 (afraid to leave home). There was a significant (p Aloe vera) for diarrhea (median score: 0.67 vs. 0.11), fecal urgency (median score: 0.89 vs. 0.11), clinical presentation total (median score: 4.33 vs. 1.22), RTOG total (median score: 2.89 vs. 0.89), and lifestyle (median score: 1.1 vs. 0.33). Hemorrhage and abdominal/rectal pain did not improve significantly. The odds ratios for advantage of Aloe vera over placebo for "clinical presentation total" and "RTOG total" were 3.97 (1.3-11.9) and 5.9 (1.6-21.6), respectively. A substantial number of patients with radiation proctitis seem to benefit from therapy with Aloe vera 3% ointment.
Smith-Lock, Karen M.; Leitão, Suze; Prior, Polly; Nickels, Lyndsey
Purpose: This study compared the effectiveness of two grammar treatment procedures for children with specific language impairment. Method: A double-blind superiority trial with cluster randomization was used to compare a cueing procedure, designed to elicit a correct production following an initial error, to a recasting procedure, which required…
Hall, Jacqueline A; Daidone, Maria Grazia; Peters, Godefridus J; Harbeck, Nadia; Lacombe, Denis; Sleijfer, Stefan
Access to biospecimens and their derivatives, that is, human biological materials (HBM), for translational research (TR) is considered a major bottleneck hindering successful bench to bedside translation. Clinical trials offer a unique opportunity to collect HBM in a specialized setting that allows prospectively designed, high-quality TR that would be difficult to fulfill from community- or population-based HBM collections alone. Increasingly, as the field advances toward personalized treatment of cancer patients, access to HBM is becoming a necessity for patient enrollment in a new generation of clinical studies that are designed and driven by molecular hypotheses. The European Organization for Research and Treatment of Cancer (EORTC) is one of the largest networks for clinical trials in oncology. The EORTC is re-focusing its strategy, building on experiences and expertise gained over the years from specific initiatives such as EORTC Group activities and the EORTC Virtual Tumour Bank, by developing new mechanisms to support investigators with the practical aspects of HBM collection as part of EORTC clinical studies. Due to the complex, multidisciplinary nature of HBM collection and TR, integration of HBM collection into clinical trials warrants careful upfront planning and input from a range of expertise. To simplify HBM collection in clinical studies, the EORTC has developed a simple checklist containing the key elements of HBM collection setup and combines these into a simple tool for practical use. Through identifying and managing key risk areas, this can maximize the HBM collection success while achieving efficient clinical trial development. This article focuses on the key elements of HBM collection and the approaches of the EORTC for efficiently integrating this collection into clinical trial development.
Baccetti, Tiziano; Mucedero, Manuela; Leonardi, Maria; Cozza, Paola
Our aim in this prospective randomized clinical study was to assess the prevalence rate of eruption of palatally displaced canines, diagnosed at an early developmental stage with posteroanterior radiographs and consequently treated by rapid maxillary expansion. A sample of 60 subjects in the early mixed dentition with palatally displaced canines diagnosed on posteroanterior radiographs was enrolled in the trial. Their age range at the first observation (T1) was 7.6 to 9.6 years, with a prepubertal stage of skeletal maturity (CS1 or CS2). The 60 subjects were randomly allocated to the treatment group (TG, 35 subjects) or the no-treatment group (NTG, 25 subjects). The TG was treated with a banded rapid maxillary expander; after expansion, all patients were retained with the expander in place for 6 months. Thereafter, the expander was removed, and the patients wore a retention plate at night for a year. The NTG received no treatment. All subjects were reevaluated in the early permanent dentition (T2) (postpubertal CS4). The number of dropouts was recorded. The main outcome recorded at T2 was successful or unsuccessful eruption of the maxillary permanent canines. The starting forms at T1 for measurements on posteroanterior and panoramic films were compared in the 2 groups with the Mann-Whitney U test (P <0.05). The prevalence rates of successful and unsuccessful treatments in the TG were compared with those in NTG with chi-square tests (P <0.05). From T1 to T2, there were 3 dropouts in each group. The final sample comprised 32 subjects in the TG and 22 subjects in the NTG. No statistically significant differences were found for any variable at T1. The prevalence rates of successful eruption of the maxillary canines were 65.7% (21 subjects) in the TG and 13.6% (3 subjects) in the NTG. The comparison was statistically significant (chi-square = 12.4; P <0.001). Subjects with palatally displaced canines in the early mixed dentition do not have transverse deficiency of the
Approaches to the treatment of endometriosis vary worldwide, but studies comparing endometriosis medications in different ethnic groups are rare. A systematic literature search identified two studies directly comparing dienogest (DNG) versus gonadotropin-releasing hormone (GnRH) analogues in European and Japanese populations. Meta-analysis of visual analogue scale scores revealed no heterogeneity in response between the trials, indicating equivalent efficacy of DNG and GnRH analogues for endometriosis-related pain across populations. DNG was significantly superior to GnRH analogues for bone mineral density change in both trials, but significant heterogeneity between the studies may indicate ethnic differences in physiology. PMID:22515510
Full Text Available Abstract Approaches to the treatment of endometriosis vary worldwide, but studies comparing endometriosis medications in different ethnic groups are rare. A systematic literature search identified two studies directly comparing dienogest (DNG versus gonadotropin-releasing hormone (GnRH analogues in European and Japanese populations. Meta-analysis of visual analogue scale scores revealed no heterogeneity in response between the trials, indicating equivalent efficacy of DNG and GnRH analogues for endometriosis-related pain across populations. DNG was significantly superior to GnRH analogues for bone mineral density change in both trials, but significant heterogeneity between the studies may indicate ethnic differences in physiology.
Kraus, V B; Blanco, F J; Englund, M
The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from...... both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials...... and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety...
Full Text Available OBJECTIVE To evaluate the efficacy of Calendula officinalis in relation to Essential Fatty Acids for the prevention and treatment of radiodermatitis. METHOD This is a randomized double-blind controlled clinical trial with 51 patients with head and neck cancer in radiotherapy treatment divided into two groups: control (27 and experimental (24. RESULTS There is statistically significant evidence (p-value = 0.0120 that the proportion of radiodermatitis grade 2 in Essential Fatty Acids group is higher than Calendula group. Through the Kaplan-Meier survival curve we observed that Essential Fatty Acids group has always remained below the Calendula group survival curve, due to the lower risk of developing radiodermatitis grade 1, which makes the usage of Calendula more effective, with statistical significance (p-value = 0.00402. CONCLUSION Calendula showed better therapeutic response than the Essential Fatty Acids in the prevention and treatment of radiodermatitis. Brazilian Registry of Clinical Trials: RBR-237v4b.
Schneider, Franciane; Danski, Mitzy Tannia Reichembach; Vayego, Stela Adami
To evaluate the efficacy of Calendula officinalis in relation to Essential Fatty Acids for the prevention and treatment of radiodermatitis. This is a randomized double-blind controlled clinical trial with 51 patients with head and neck cancer in radiotherapy treatment divided into two groups: control (27) and experimental (24). There is statistically significant evidence (p-value = 0.0120) that the proportion of radiodermatitis grade 2 in Essential Fatty Acids group is higher than Calendula group. Through the Kaplan-Meier survival curve we observed that Essential Fatty Acids group has always remained below the Calendula group survival curve, due to the lower risk of developing radiodermatitis grade 1, which makes the usage of Calendula more effective, with statistical significance (p-value = 0.00402). Calendula showed better therapeutic response than the Essential Fatty Acids in the prevention and treatment of radiodermatitis. Brazilian Registry of Clinical Trials: RBR-237v4b.
Lazar, Ann A.; Bonetti, Marco; Cole, Bernard F.; Yip, Wai-ki; Gelber, Richard D.
Background Investigators conducting randomized clinical trials (RCTs) often explore treatment effect heterogeneity to assess whether treatment efficacy varies according to patient characteristics. Identifying heterogeneity is central to making informed personalized health care decisions. Treatment effect heterogeneity can be investigated using subpopulation treatment effect pattern plot (STEPP), a non-parametric graphical approach that constructs overlapping patient subpopulations with varying values of a characteristic. Procedures for statistical testing using STEPP when the endpoint of interest is survival remain an area of active investigation. Motivating Data A STEPP analysis was used to explore patterns of absolute and relative treatment effects for varying levels of a breast cancer biomarker, Ki-67, in the phase III BIG (Breast International Group) 1-98 RCT, comparing letrozole to tamoxifen as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer. Absolute treatment effects were measured by differences in 4-year cumulative incidence of breast cancer recurrence, while relative effects were measured by the subdistribution hazard ratio in the presence of competing risks using O − E (observed-minus-expected) methodology, an intuitive non-parametric method. While estimation of hazard ratio values based on O − E methodology has been shown, a similar development for the subdistribution hazard ratio has not. Furthermore, we observed that the STEPP analysis, may not produce results, even with 100 patients within each subpopulation. After further investigation through simulation studies, we observed inflation of the type I error rate of the traditional test statistic and sometimes singular variance-covariance matrix estimates that may lead to results not being produced. This is due to the lack of a sufficient number of events within the subpopulations, which we refer to as instability of a STEPP analysis. Methods We introduce
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.
Chen, Fa-Ming; Gao, Li-Na; Tian, Bei-Min; Zhang, Xi-Yu; Zhang, Yong-Jie; Dong, Guang-Ying; Lu, Hong; Chu, Qing; Xu, Jie; Yu, Yang; Wu, Rui-Xin; Yin, Yuan; Shi, Songtao; Jin, Yan
Background Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem ce...
Wang, Jiazhou; Chen, Wenzhou; Studenski, Matthew; Cui, Yunfeng; Xiao, Ying; Lee, Andrew J
The goal of this work is to develop a plan-quality evaluation program for clinical routine and multi-institutional clinical trials so that the overall evaluation efficiency is improved. In multi-institutional clinical trials evaluating the plan quality is a time-consuming and labor-intensive process. In this note, we present a semi-automated plan-quality evaluation program which combines MIMVista, Java/MATLAB, and extensible markup language (XML). More specifically, MIMVista is used for data visualization; Java and its powerful function library are implemented for calculating dosimetry parameters; and to improve the clarity of the index definitions, XML is applied. The accuracy and the efficiency of the program were evaluated by comparing the results of the program with the manually recorded results in two RTOG trials. A slight difference of about 0.2% in volume or 0.6 Gy in dose between the semi-automated program and manual recording was observed. According to the criteria of indices, there are minimal differences between the two methods. The evaluation time is reduced from 10–20 min to 2 min by applying the semi-automated plan-quality evaluation program. (note)
Wang, Jiazhou; Chen, Wenzhou; Studenski, Matthew; Cui, Yunfeng; Lee, Andrew J.; Xiao, Ying
The goal of this work is to develop a plan-quality evaluation program for clinical routine and multi-institutional clinical trials so that the overall evaluation efficiency is improved. In multi-institutional clinical trials evaluating the plan quality is a time-consuming and labor-intensive process. In this note, we present a semi-automated plan-quality evaluation program which combines MIMVista, Java/MATLAB, and extensible markup language (XML). More specifically, MIMVista is used for data visualization; Java and its powerful function library are implemented for calculating dosimetry parameters; and to improve the clarity of the index definitions, XML is applied. The accuracy and the efficiency of the program were evaluated by comparing the results of the program with the manually recorded results in two RTOG trials. A slight difference of about 0.2% in volume or 0.6 Gy in dose between the semi-automated program and manual recording was observed. According to the criteria of indices, there are minimal differences between the two methods. The evaluation time is reduced from 10-20 min to 2 min by applying the semi-automated plan-quality evaluation program.
... Questions to Ask about Your Treatment Research Cancer Clinical Trials at the National Institutes of Health Clinical Center ... they are eligible for a clinical trial . NCI Clinical Trials at the NIH Clinical Center Cancer research at ...
Wismeijer, D; van Waas, MAJ; Mulder, J; Vermeeren, JIJF; Kalk, W
In a randomized controlled clinical trial carried out at the Ignatius teaching hospital in Breda, The Netherlands, 110 edentulous patients with severe mandibular bone loss were treated with implants of the ITI(R) Dental Implant System using 3 different treatment strategies: a mandibular overdenture
Cowley, Benjamin; Holmström, Édua; Juurmaa, Kristiina; Kovarskis, Levas; Krause, Christina M.
Background: We report a randomized controlled clinical trial of neurofeedback therapy intervention for ADHD/ADD in adults. We focus on internal mechanics of neurofeedback learning, to elucidate the primary role of cortical self-regulation in neurofeedback. We report initial results; more extensive analysis will follow. Methods: Trial has two phases: intervention and follow-up. The intervention consisted of neurofeedback treatment, including intake and outtake measurements, using a waiting-list control group. Treatment involved ~40 h-long sessions 2–5 times per week. Training involved either theta/beta or sensorimotor-rhythm regimes, adapted by adding a novel “inverse-training” condition to promote self-regulation. Follow-up (ongoing) will consist of self-report and executive function tests. Setting: Intake and outtake measurements were conducted at University of Helsinki. Treatment was administered at partner clinic Mental Capital Care, Helsinki. Randomization: We randomly allocated half the sample then adaptively allocated the remainder to minimize baseline differences in prognostic variables. Blinding: Waiting-list control design meant trial was not blinded. Participants: Fifty-four adult Finnish participants (mean age 36 years; 29 females) were recruited after screening by psychiatric review. Forty-four had ADHD diagnoses, 10 had ADD. Measurements: Symptoms were assessed by computerized attention test (T.O.V.A.) and self-report scales, at intake and outtake. Performance during neurofeedback trials was recorded. Results: Participants were recruited and completed intake measurements during summer 2012, before assignment to treatment and control, September 2012. Outtake measurements ran April-August 2013. After dropouts, 23 treatment and 21 waiting-list participants remained for analysis. Initial analysis showed that, compared to waiting-list control, neurofeedback promoted improvement of self-reported ADHD symptoms, but did not show transfer of learning to T
Sosa, Carlos; Lorenzo Calvo, Alberto; Jiménez, Sergio L.; Bonfanti, Noelia
Chronic patellar tendinopathy is a common pathology in sporting population. To date, there is no agreed upon protocol as election treatment. Eccentric exercises have been used with satisfactory outcomes. The purpose of this trial is compare the effects of two eccentric exercise protocols. 0.146 SJR (2014) Q4, 199/231 Health (social science), 131/169 Physical therapy, sports therapy and rehabilitation, 119/128 Sports sciences UEM
de Wit G Ardine
Full Text Available Abstract Background Fatigue is a major problem of cancer patients. Thirty percent of cancer survivors report serious fatigue three years after finishing treatment. There is evidence that physical exercise during cancer treatment reduces fatigue. This may also lead to an improvement of quality of life. Such findings may result in a decrease of healthcare related expenditures and societal costs due to sick leave. However, no studies are known that investigated these hypotheses. Therefore, the primary aim of our study is to assess the effect of exercise during cancer treatment on reducing complaints of fatigue and on reducing health service utilisation and sick leave. Methods/Design The Physical Activity during Cancer Treatment study is a multicentre randomised controlled trial in 150 breast and 150 colon cancer patients undergoing cancer treatment. Participants will be randomised to an exercise or a control group. In addition to the usual care, the exercise group will participate in an 18-week supervised group exercise programme. The control group will be asked to maintain their habitual physical activity pattern. Study endpoints will be assessed after 18 weeks (short term and after 9 months (long term. Validated questionnaires will be used. Primary outcome: fatigue (Multidimensional Fatigue Inventory and Fatigue Quality List and cost-effectiveness, health service utilisation and sick leave. Secondary outcome: health related quality of life (European Organisation Research and Treatment of Cancer-Quality of Life questionnaire-C30, Short Form 36 healthy survey, impact on functioning and autonomy (Impact on functioning and autonomy questionnaire, anxiety and depression (Hospital Anxiety and Depression Scale, physical fitness (aerobic peak capacity, muscle strength, body composition and cognitive-behavioural aspects. To register health service utilisation and sick leave, participants will keep diaries including the EuroQuol-5D. Physical activity level
... participating in was reviewed by an IRB. Further reading For more information about research protections, see: Office ... information and decide whether the results have medical importance. Results from clinical trials are often published in ...
U.S. Department of Health & Human Services — Provides patients, family members, health care professionals, and members of the public easy access to information on clinical trials for a wide range of diseases...
Tamm, Leanne; Denton, Carolyn A; Epstein, Jeffery N; Schatschneider, Christopher; Taylor, Heather; Arnold, L Eugene; Bukstein, Oscar; Anixt, Julia; Koshy, Anson; Newman, Nicholas C; Maltinsky, Jan; Brinson, Patricia; Loren, Richard E A; Prasad, Mary R; Ewing-Cobbs, Linda; Vaughn, Aaron
This trial compared attention-deficit/hyperactivity disorder (ADHD) treatment alone, intensive reading intervention alone, and their combination for children with ADHD and word reading difficulties and disabilities (RD). Children (n = 216; predominantly African American males) in Grades 2-5 with ADHD and word reading/decoding deficits were randomized to ADHD treatment (medication + parent training), reading treatment (reading instruction), or combined ADHD + reading treatment. Outcomes were parent and teacher ADHD ratings and measures of word reading/decoding. Analyses utilized a mixed models covariate-adjusted gain score approach with posttest regressed onto pretest. Inattention and hyperactivity/impulsivity outcomes were significantly better in the ADHD (parent Hedges's g = .87/.75; teacher g = .67/.50) and combined (parent g = 1.06/.95; teacher g = .36/41) treatment groups than reading treatment alone; the ADHD and Combined groups did not differ significantly (parent g = .19/.20; teacher g = .31/.09). Word reading and decoding outcomes were significantly better in the reading (word reading g = .23; decoding g = .39) and combined (word reading g = .32; decoding g = .39) treatment groups than ADHD treatment alone; reading and combined groups did not differ (word reading g = .09; decoding g = .00). Significant group differences were maintained at the 3- to 5-month follow-up on all outcomes except word reading. Children with ADHD and RD benefit from specific treatment of each disorder. ADHD treatment is associated with more improvement in ADHD symptoms than RD treatment, and reading instruction is associated with better word reading and decoding outcomes than ADHD treatment. The additive value of combining treatments was not significant within disorder, but the combination allows treating both disorders simultaneously. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Busse, Jason W; Bhandari, Mohit; Einhorn, Thomas A; Schemitsch, Emil; Heckman, James D; Tornetta, Paul; Leung, Kwok-Sui; Heels-Ansdell, Diane; Makosso-Kallyth, Sun; Della Rocca, Gregory J; Jones, Clifford B; Guyatt, Gordon H
Objective?To determine whether low intensity pulsed ultrasound (LIPUS), compared with sham treatment, accelerates functional recovery and radiographic healing in patients with operatively managed tibial fractures. Design?A concealed, randomized, blinded, sham controlled clinical trial with a parallel group design of 501 patients, enrolled between October 2008 and September 2012, and followed for one year. Setting?43 North American academic trauma centers. Participants?Skeletally mature men or...
Cano Stefan J
Full Text Available Abstract Background The Anti-Clot Treatment Scale (ACTS is a 15-item patient-reported instrument of satisfaction with anticoagulant treatment. It includes a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. Its role in clinical trials and other settings should be supported by evidence that it is both clinically meaningful and scientifically sound. The aim of the study was to evaluate the measurement performance of the ACTS (Dutch, Italian, French, German and English language versions in patients with venous thromboembolism based on traditional psychometric methods. Methods ACTS Burdens and Benefits scale data from a large clinical trial (EINSTEIN DVT involving 1336 people with venous thromboembolism were analysed at both the scale and item level. Five key psychometric properties were examined using traditional psychometric methods: acceptability, scaling assumptions, reliability (including internal consistency reliability, test-retest reproducibility; validity (including known groups and discriminant validity; and responsiveness. These methods of examination underpin the US Food and Drug Administration recommendations for patient-reported outcome instrument evaluation. Results Overall, the 12-item ACTS Burdens scale and 3-item ACTS Benefits scale met the psychometric criteria evaluated at both item and scale levels, with the exception of some relatively minor issues in the Dutch language version, which were just below reliability criteria (i.e. alpha = 0.72, test-retest intraclass correlation = 0.79. A consistent finding from item-level evaluations of aggregate endorsement frequencies and skewness suggested that response scales may be improved by reducing the number of response options from five to four. Conclusions Both the ACTS Burdens and ACTS Benefits scales consistently satisfied traditional reliability and validity criteria across multiple language datasets, supporting it as a clinically useful patient
Brown, M S; Hayes, M J; Thornton, L M
Compare duration of treatment of neonatal abstinence syndrome between methadone and morphine. A prospective, double-masked, randomized trial at a single site. Randomization of methadone or morphine was stratified for maternal treatment with methadone or buprenorphine. Inclusion criteria were (i) maternal treatment with prescribed methadone or buprenorphine, (ii) withdrawal treatment criteria, (iii) adjusted gestational age ⩾35(0/7) weeks and (iv) medically stable. Primary outcome was length of opioid treatment. From January 2011 through October 2012, 78 infants were eligible for the study: 41 methadone-exposed and 37 buprenorphine-exposed. Consent was obtained from 31 mothers, 13/41 (32%) methadone-treated and 18/37 (49%) buprenorphine-treated. Length of opioid treatment was significantly shorter for methadone than morphine treatment, median 14 versus 21 days (P=0.008). Methadone had a shorter length of neonatal withdrawal treatment compared with morphine. Owing to the smaller sample size and single site, a larger randomized study is needed.
Full Text Available Abstract Background The hospital treatment of heart failure frequently does not follow published guidelines, potentially contributing to the high morbidity, mortality and economic cost of this disorder. Consequently the development of clinical pathways has the potential to reduce the current variability in care, enhance guideline adherence, and improve outcomes for patients. Despite enthusiasm and diffusion, the widespread acceptance of clinical pathways remain questionable because very little prospective controlled data demonstrated their effectiveness. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was designed in order to conduct a rigorous evaluation of clinical pathways in hospital treatment of acute heart failure. The primary objective of the trial was to evaluate the effectiveness of the implementation of clinical pathways for hospital treatment of heart failure in Italian hospitals. Methods/design Two-arm, cluster-randomized trial. 14 community hospitals were randomized either to arm 1 (clinical pathway: appropriate use of practice guidelines and supplies of drugs and ancillary services, new organization and procedures, patient education, etc. or to arm 2 (no intervention, usual care. 424 patients sample (212 in each group, 80% of power at the 5% significance level (two-sided. The primary outcome measure is in-hospital mortality. We will also analyze the impact of the clinical pathways comparing the length and the appropriateness of the stay, the rate of unscheduled readmissions, the customers' satisfaction and the costs treating the patients with the pathways and with the current practice along all the observation period. The quality of the care will be assessed by monitoring the use of diagnostic and therapeutic procedures during hospital stay and by measuring key quality indicators at discharge. Discussion This paper examines the design of the evaluation of a complex
Jian, Wen-Jia; Shi, Jing; Tian, Jin-Zhou; Ni, Jing-Nian
Chinese herbal medicine has been extensively used in the treatment of vascular dementia (VaD), but lacked systematic review on its efficacy and safety. So we conducted a systematic review to assess the efficacy and safety of Chinese herbal medicine in treating VaD. CNKI, CBM, PubMed, and Wiley Online Library were retrieved for randomized trials (RCTs) on Chinese herbal medicine treating VaD patients. Randomized parallel control trials by taking Chinese herbal medicine as one treatment method and placebos/cholinesterase inhibitors/Memantine hydrochloride as the control were included. Quality rating and data extraction were performed. RevMan5.2.0 Software was used for meta-analysis. Standardized mean difference (SMD) at 95% confidence interval (CI) was used to indicate effect indicators of results. Seven RCTs met the inclusive criteria. Totally 677 VaD patients were randomly assigned to the treatment group and the control group. Descriptive analyses were performed in inclusive trials. The cognitive function was assessed in all trials. Results showed Mini-Mental state examination (MMSE) score was better in the Chinese herbal medicine group than in the placebo group, but with no significant difference when compared with the donepezil group (P > 0.05). Adverse reactions were mainly manifested as gastrointestinal symptoms such as abdominal pain in the Chinese herbal medicine group. But they occurred more in the donepezil group than in the Chinese herbal medicine group. The methodological quality of included trials was poor with less samples. Results of different trials were lack of consistency. Present evidence is not sufficient to prove or disapprove the role of Chinese herbal medicine in improving clinical symptoms and outcome indicators of VaD patients. Their clinical efficacy and safety need to be supported by more higher quality RCTs.
Design paper: The CapOpus trial: a randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis
Hjorthøj, Carsten; Fohlmann, Allan; Larsen, Anne-Mette
: The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. DESIGN: The trial is designed as a randomized, parallel-group, observer-blinded clinical...... trial. Patients are primarily recruited through early-psychosis detection teams, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1) specialized addiction treatment plus treatment as usual or 2......) treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case manager of the patient.The primary outcome measure will be changes in amount...
Şener, Hülya Özlem; Malkoç, Mehtap; Ergin, Gülbin; Karadibak, Didem; Yavuzşen, Tuğba
The aim of the present study was to compare the effects of clinical Pilates exercises with those of the standard lymphedema exercises on lymphedema developing after breast cancer treatment. The study comprised 60 female patients with a mean age of 53.2±7.7 years who developed lymphedema after having breast cancer treatment. The patients were randomized into two groups: the clinical Pilates exercise group (n=30), and the control group (n=30). Before, and at the 8th week of treatment, the following parameters were measured: the severity of lymphedema, limb circumferences, body image using the Social Appearance Anxiety Scale, quality of life with the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-BR23), and upper extremity function using the Disabilities of the Arm, Shoulder and Hand (DASH) outcome measure. Both groups performed one-hour exercises three days a week for 8 weeks. After treatment, the symptoms recovered significantly in both groups. Reductions in the severity of lymphedema, improvements in the social appearance anxiety scale scores, quality of life scores, and upper extremity functions scores in the clinical Pilates exercise group were greater than those in the control group. Clinical Pilates exercises were determined to be more effective on the symptoms of patients with lymphedema than were standard lymphedema exercises. Clinical Pilates exercises could be considered a safe model and would contribute to treatment programs.
Full Text Available Akira Ueda, Ayumu Hosokawa, Kohei Ogawa, Hiroki Yoshita, Takayuki Ando, Shinya Kajiura, Haruka Fujinami, Kengo Kawai, Jun Nishikawa, Kazuto Tajiri, Masami Minemura, Toshiro SugiyamaDepartment of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama, Toyama, JapanObjective: The aim of this study was to evaluate the outcome of patients with advanced pancreatic cancer in clinical practice, and assess whether chemotherapy provided a clinical benefit for patients who did not meet the eligibility criteria of the clinical trial.Methods: We retrospectively analyzed the medical records of 75 patients who received first-line chemotherapy for pancreatic cancer between April 2006 and September 2011. Patients were treated with gemcitabine (GEM alone, S-1 (tegafur, gimeracil, and oteracil potassium alone, or GEM plus S-1. Patients were divided into the clinical trial eligible group (arm eligible or the ineligible group (arm ineligible. We evaluated the efficacy and the safety of the chemotherapy.Results: A total of 23 patients out of 75 (31% belonged to the ineligible group, for the following reasons: 20 patients had poor performance status, eight had massive ascites, one had synchronous malignancy, and one had icterus. The median progression-free survival (PFS was 3.5 months, and the median overall survival (OS was 6.7 months in all patients. In arm eligible, median PFS was 4.5 months, and median OS was 10.5 months. In arm ineligible, median PFS was 1.1 months, and median OS was 2.9 months.Conclusion: The outcome of the patients who did not meet the eligibility criteria was very poor. It is important to select the patients that could benefit from either chemotherapy or optimal supportive care.Keywords: gemcitabine, S-1, clinical practice
Latimer, Nicholas R; Abrams, Keith R; Lambert, Paul C; Morden, James P; Crowther, Michael J
When patients randomised to the control group of a randomised controlled trial are allowed to switch onto the experimental treatment, intention-to-treat analyses of the treatment effect are confounded because the separation of randomised groups is lost. Previous research has investigated statistical methods that aim to estimate the treatment effect that would have been observed had this treatment switching not occurred and has demonstrated their performance in a limited set of scenarios. Here, we investigate these methods in a new range of realistic scenarios, allowing conclusions to be made based upon a broader evidence base. We simulated randomised controlled trials incorporating prognosis-related treatment switching and investigated the impact of sample size, reduced switching proportions, disease severity, and alternative data-generating models on the performance of adjustment methods, assessed through a comparison of bias, mean squared error, and coverage, related to the estimation of true restricted mean survival in the absence of switching in the control group. Rank preserving structural failure time models, inverse probability of censoring weights, and two-stage methods consistently produced less bias than the intention-to-treat analysis. The switching proportion was confirmed to be a key determinant of bias: sample size and censoring proportion were relatively less important. It is critical to determine the size of the treatment effect in terms of an acceleration factor (rather than a hazard ratio) to provide information on the likely bias associated with rank-preserving structural failure time model adjustments. In general, inverse probability of censoring weight methods are more volatile than other adjustment methods.
Charytoniuk, Tomasz; Drygalski, Krzysztof; Konstantynowicz-Nowicka, Karolina; Berk, Klaudia; Chabowski, Adrian
Nonalcoholic fatty liver disease (NAFLD) is considered to be one of the most common liver pathologies that occur widely among societies with a predominance of the Western dietary pattern. NAFLD may progress from hepatic steatosis to nonalcoholic steatohepatitis (NASH), subsequently leading to cirrhosis and becoming a major cause of hepatocellular carcinoma. Thus its prevention and therapy play an important role in hepatology. To our knowledge, there is no effective treatment for patients with NAFLD. The aim of this review was to summarize the results of recent alternative treatment studies conducted both on cell cultures and in vivo that concern molecular effects of resveratrol (3,5,4'-trihydroxystilbene) in the treatment of NAFLD. The precise metabolism, pharmacology, and clinical trials with different concentrations of resveratrol were described. The review also presents a brief summary of other alternative treatment methods of NAFLD and their mechanisms compared with current clinical understanding. Copyright © 2016 Elsevier Inc. All rights reserved.
Takada, Michihiro; Sozu, Takashi; Sato, Tosiya
Crossover designs have some advantages over standard clinical trial designs and they are often used in trials evaluating the efficacy of treatments for infertility. However, clinical trials of infertility treatments violate a fundamental condition of crossover designs, because women who become pregnant in the first treatment period are not treated in the second period. In previous research, to deal with this problem, some new designs, such as re-randomization designs, and analysis methods including the logistic mixture model and the beta-binomial mixture model were proposed. Although the performance of these designs and methods has previously been evaluated in large-scale clinical trials with sample sizes of more than 1000 per group, the actual sample sizes of infertility treatment trials are usually around 100 per group. The most appropriate design and analysis for these moderate-scale clinical trials are currently unclear. In this study, we conducted simulation studies to determine the appropriate design and analysis method of moderate-scale clinical trials for irreversible endpoints by evaluating the statistical power and bias in the treatment effect estimates. The Mantel-Haenszel method had similar power and bias to the logistic mixture model. The crossover designs had the highest power and the smallest bias. We recommend using a combination of the crossover design and the Mantel-Haenszel method for two-period, two-treatment clinical trials with irreversible endpoints. Copyright © 2015 John Wiley & Sons, Ltd.
Background Sufficient evidence is lacking to draw final conclusions on the efficiency of medical and psychological treatments of traumatized refugees with PTSD. The pharmacological treatments of choice today for post-traumatic stress disorder are antidepressants from the subgroup selective serotonin reuptake inhibitors, especially Sertraline. The evidence for the use of selective serotonin reuptake inhibitors in the treatment of complex post-traumatic stress disorder in traumatized refugees is very limited. Venlafaxine is a dual-action antidepressant that works on several pathways in the brain. It influences areas in the brain which are responsible for the enhanced anxiety and hyper-arousal experienced by traumatized refugees and which some studies have found to be enlarged among patients suffering from post-traumatic stress disorder. Design This study will include approximately 150 patients, randomized into two different groups treated with either Sertraline or Venlafaxine. Patients in both groups will receive the same manual-based cognitive behavioral therapy, which has been especially adapted to this group of patients. The treatment period will be 6 to 7 months. The trial endpoints will be post-traumatic stress disorder and depressive symptoms and social functioning, all measured on validated ratings scales. Furthermore the study will examine the relation between a psycho-social resources and treatment outcome based on 15 different possible outcome predictors. Discussion This study is expected to bring forward new knowledge on treatment and clinical evaluation of traumatized refugees and the results are expected to be used in reference programs and clinical guidelines. Trial registration ClinicalTrials.gov NCT01569685 PMID:23663588
Morgado, Luciano Ferreira; Trávolo, Ana Regina Franchi; Muehlmann, Luís Alexandre; Narcizo, Paulo Souza; Nunes, Rodrigo Barbosa; Pereira, Pedro Alencar Gomes; Py-Daniel, Karen Rapp; Jiang, Cheng-Shi; Gu, Jinsong; Azevedo, Ricardo Bentes; Longo, João Paulo Figueiró
The conventional treatment of onychomycosis, a common fungal infection, consists in the use of local and systemic drugs for 4-6 months. This long protocol is often ineffective due to patient compliance, and usually promotes important collateral effects such as liver and kidney failure. As the alternative, Photodynamic Therapy (PDT) has been used as a noninvasive alternative local treatment for onychomycosis due to the reduction of systemic side effects, fact indicates their use for patients undergoing other systemic treatments. In the present article, we evaluated the effectiveness, as well as the safety of PDT mediated by Aluminium-Phthalocyanine Chloride, entrapped in nanoemulsions, as a drug carrier, to treat onychomycosis in a proof of concept clinical trial. To the date, this is the first published clinical trial that uses PDT mediated by nanomedicines to treat onychomycosis. As main results, we can highlight the safety of the clinical protocol and the antifungal effectiveness similar to the conventional treatments. We observed the (1) clinical cure of 60% of treated lesions; (2) the absence of local and systemic adverse effects; (3) from these clinically healed lesions, 40% were negative for fungal infection in laboratorial exams; and (4) nails that presented negative fungal culture were kept without fungal infection for at least four weeks. The innovation of this approach is the absence of collateral effects, due to the local therapeutically treatment, and the possibility to repeat the treatment without inducing fungal resistance, a fact that indicates this approach as a possible alternative protocol for onychomycosis management. Copyright © 2017 Elsevier B.V. All rights reserved.
Mirroring everyday clinical practice in clinical trial design: a new concept to improve the external validity of randomized double-blind placebo-controlled trials in the pharmacological treatment of major depression
Full Text Available Abstract Background Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection. Discussion To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population. Summary We propose a list of measures to be taken to improve the external validity of double-blind, placebo-controlled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself.
improved when compared to a control group which received a sham protocol of NET. Chronic neck pain sufferers may benefit from NET treatment in the relief of trigger point sensitivity. Further research including long-term randomised controlled trials for the effect of NET on chronic neck pain, and other chronic pain syndromes are recommended. Trial Registration This trial has been registered and allocated the Australian Clinical Trials Registry (ACTR number ACTRN012607000358448. The ACTR has met the requirements of the ICMJE's trials registration policy and is an ICMJE acceptable registry.
Design paper: The CapOpus trial: a randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis
Hjorthøj, Carsten; Fohlmann, Allan; Larsen, Anne-Mette
BACKGROUND: A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis. OBJECTIVES......: The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. DESIGN: The trial is designed as a randomized, parallel-group, observer-blinded clinical...... of cannabis consumption over time. Other outcome measures will be psychosis symptoms, cognitive functioning, quality of life, social functioning, and cost-benefit analyses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00484302....
Branco, Marcelo; Rêgo, Neiva N; Silva, Paulo H; Archanjo, Ingrid E; Ribeiro, Mirian C; Trevisani, Virgínia F
Osteoarthritis is a degenerative disease associated with pain, reduced range of motion, and impaired function. Balneotherapy or bathing in thermal or mineral waters is used as a non-invasive treatment for various rheumatic diseases. To evaluate the effectiveness of hot sulfurous and non-sulfurous waters in the treatment of knee osteoarthritis. A randomized, assessor-blind, controlled trial. A spa resort. One hundred and forty patients of both genders, mean age of 64.8±8.9 years, with knee osteoarthritis and chronic knee pain. Patients were randomized into three groups: the sulfurous water (SW) group (N.=47), non-sulfurous water (NSW) group (N.=50), or control group (N.=43) who received no treatment. Patients were not blinded to treatment allocation. Treatment groups received 30 individual thermal baths (three 20-minute baths a week for 10 weeks) at 37-39 °C. The outcome measures were pain (visual analog scale, VAS), physical function (Western Ontario and McMaster Universities Osteoarthritis Index, WOMAC; Lequesne Algofunctional Index, LAFI; Stanford Health Assessment Questionnaire, HAQ), and use of pain medication. Patients were assessed before treatment (T1), at treatment endpoint (T2), and two months post-intervention (T3). Intra- and intergroup comparisons were performed at a significance level of 0.05 (Ptreatment groups (Ptreatment groups at T2 and T3 (Ptreatment groups at T2, but patients in the SW group reported less pain and better functional status than those in the NSW group at T3, showing a lasting effect of sulfurous water baths. Both therapeutic methods were effective in the treatment of knee osteoarthritis; however, sulfurous baths yielded longer-lasting effects than non-sulfurous water baths. Baths in thermal waters, especially those in sulfurous waters, are effective in reducing pain and improving physical function in patients with knee osteoarthritis.
Jensen Rikke K
Full Text Available Abstract Background Clinical experience suggests that many patients with Modic changes have relatively severe and persistent low back pain (LBP, which typically appears to be resistant to treatment. Exercise therapy is the recommended treatment for chronic LBP, however, due to their underlying pathology, Modic changes might be a diagnostic subgroup that does not benefit from exercise. The objective of this study was to compare the current state-of-the art treatment approach (exercise and staying active with a new approach (load reduction and daily rest for people with Modic changes using a randomized controlled trial design. Methods Participants were patients from an outpatient clinic with persistent LBP and Modic changes. They were allocated using minimization to either rest therapy for 10 weeks with a recommendation to rest for two hours daily and the option of using a flexible lumbar belt or exercise therapy once a week for 10 weeks. Follow-up was at 10 weeks after recruitment and 52 weeks after intervention and the clinical outcome measures were pain, disability, general health and global assessment, supplemented by weekly information on low back problems and sick leave measured by short text message (SMS tracking. Results In total, 100 patients were included in the study. Data on 87 patients at 10 weeks and 96 patients at one-year follow-up were available and were used in the intention-to-treat analysis. No statistically significant differences were found between the two intervention groups on any outcome. Conclusions No differences were found between the two treatment approaches, 'rest and reduced load' and 'exercise and staying active', in patients with persistent LBP and Modic changes. Trial Registration ClinicalTrials.gov: NCT00454792
Chi, John H; Gokaslan, Ziya; McCormick, Paul; Tibbs, Phillip A; Kryscio, Richard J; Patchell, Roy A
Randomized clinical trial. OBJECTIVE.: To determine if age affects outcomes from differing treatments in patients with spinal metastases. Recently, class I data were published supporting surgery with radiation over radiation alone for patients with malignant epidural spinal cord compression (MESCC). However, the criteria to properly select candidates for surgery remains controversial and few independent variables which predict success after treatment have been identified. Data for this study was obtained in a randomized clinical trial comparing surgery versus radiation for MESCC. Hazard ratios were determined for the effect of age and the interaction between age and treatment. Age estimates at which prespecified relative risks could be expected were calculated with greater than 95% confidence to suggest possible age cut points for further stratification. Multivariate models and Kaplan-Meier curves were tested using stratified cohorts for both treatment groups in the randomized trial each divided into 2 age groups. Secondary data analysis with age stratification demonstrated a strong interaction between age and treatment (hazard ratio = 1.61, P = 0.01), such that as age increases, the chances of surgery being equal to radiation alone increases. The best estimate for the age at which surgery is no longer superior to radiation alone was calculated to be between 60 and 70 years of age (95% CI), using sequential prespecified relative risk ratios. Multivariate modeling and Kaplan-Meier curves for stratified treatment groups showed that there was no difference in outcome between treatments for patients >or=65 years of age. Ambulation preservation was significantly prolonged in patients variable in predicting preservation of ambulation and survival for patients being treated for spinal metastases. Our results provide compelling evidence for the first time that particular age cut points may help in selecting patients for surgical or nonsurgical intervention based on outcome.
Design paper: The CapOpus trial: A randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis
Full Text Available Abstract Background A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders. There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis. Objectives The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual. Design The trial is designed as a randomized, parallel-group, observer-blinded clinical trial. Patients are primarily recruited through early-psychosis detection teams, community mental health centers, and assertive community treatment teams. Patients are randomized to one of two treatment arms, both lasting six months: 1 specialized addiction treatment plus treatment as usual or 2 treatment as usual. The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy, and incorporates both the family and the case manager of the patient. The primary outcome measure will be changes in amount of cannabis consumption over time. Other outcome measures will be psychosis symptoms, cognitive functioning, quality of life, social functioning, and cost-benefit analyses. Trial registration ClinicalTrials.gov NCT00484302.
Jackson, V Margaret; Price, David A; Carpino, Philip A
The discovery of new antiobesity agents has attracted considerable interest over the past decade, but many of the investigational agents that have advanced into human clinical trials have shown unacceptable adverse events and/or efficacy profiles. This review summarizes the available preclinical and clinical data of antiobesity drugs currently in Phase II clinical trials. It also provides a brief summary of the mechanisms underlying the regulation of energy homeostasis. New approaches to solving the obesity epidemic are needed, exemplified in part by some of the agents currently in Phase II clinical trials. Weight loss treatments could be tailored to specific subpopulations such as morbidly obese individuals with a high risk for complications or obese patients with a specific genotype. Fixed dose combinations of drugs that target multiple complementary pathways could be developed to deliver durable, 10% or greater weight loss. A shift away from pharmacological agents that act on pathways in the CNS could lead to drugs with fewer side effects and more favorable risk/benefit ratios.
Shmueli-Blumberg, Dikla; Hu, Lian; Allen, Colleen; Frasketi, Michael; Wu, Li-Tzy; Vanveldhuisen, Paul
There are many benefits of data sharing, including the promotion of new research from effective use of existing data, replication of findings through re-analysis of pooled data files, meta-analysis using individual patient data, and reinforcement of open scientific inquiry. A randomized controlled trial is considered as the 'gold standard' for establishing treatment effectiveness, but clinical trial research is very costly, and sharing data is an opportunity to expand the investment of the clinical trial beyond its original goals at minimal costs. We describe the goals, developments, and usage of the Data Share website (http://www.ctndatashare.org) for the National Drug Abuse Treatment Clinical Trials Network (CTN) in the United States, including lessons learned, limitations, and major revisions, and considerations for future directions to improve data sharing. Data management and programming procedures were conducted to produce uniform and Health Insurance Portability and Accountability Act (HIPAA)-compliant de-identified research data files from the completed trials of the CTN for archiving, managing, and sharing on the Data Share website. Since its inception in 2006 and through October 2012, nearly 1700 downloads from 27 clinical trials have been accessed from the Data Share website, with the use increasing over the years. Individuals from 31 countries have downloaded data from the website, and there have been at least 13 publications derived from analyzing data through the public Data Share website. Minimal control over data requests and usage has resulted in little information and lack of control regarding how the data from the website are used. Lack of uniformity in data elements collected across CTN trials has limited cross-study analyses. The Data Share website offers researchers easy access to de-identified data files with the goal to promote additional research and identify new findings from completed CTN studies. To maximize the utility of the website
McAlindon, T. E.; Driban, J. B.; Henrotin, Y.
The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct......, and reporting of clinical trials for knee OA we initially drafted recommendations through an iterative process. Members of the working group included representatives from industry and academia. After the working group members reviewed a final draft, they scored the appropriateness for recommendations. After...... and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials...
Haas, Alex Nogueira; Silva-Boghossian, Carina Maciel; Colombo, Ana Paula; Albandar, Jasim; Oppermann, Rui Vicente; Rösing, Cassiano Kuchenbecker; Susin, Cristiano
Little is known about the factors that may be used in clinical practice to predict the therapeutic response of aggressive periodontitis patients. The aim of this study was to determine predictors of clinical outcomes after non-surgical treatment of aggressive periodontitis. A total of 24 patients (aged 13-26 years) received oral hygiene instructions, as well as subgingival scaling and root planing. Twelve subjects received systemic azithromycin at random. Clinical variables were assessed at baseline, 3, 6, 9, and 12 months. Baseline microbiological assessment was performed by checkerboard DNA-DNA hybridization. Multivariable models used generalized estimating equations. There were significant improvements in the entire sample in regard to pocket depth, clinical attachment level and bleeding on probing. Significant predictors of a reduction in mean pocket depth were: use of azithromycin, non-molar teeth, generalized disease and baseline pocket depth. Absence of plaque predicted a 0.22 mm higher attachment gain, whereas a baseline pocket depth ≥7 mm predicted a 1.36 mm higher attachment loss. Azithromycin, plaque, and baseline pocket depth were significant predictors of bleeding on probing. The concomitant presence of all three red complex species predicted a 0.78 mm higher attachment loss. It may be concluded that dental plaque, tooth type, disease extent, baseline pocket depth, and use of azithromycin were significant predictors of the clinical response to treatment for aggressive periodontitis in young individuals. Moreover, the presence of multiple periodontal pathogens may predict challenges in achieving a favorable outcome for aggressive periodontitis.
Carei, T Rain; Fyfe-Johnson, Amber L; Breuner, Cora C; Brown, Margaret A
This was a pilot project designed to assess the effect of individualized yoga treatment on eating disorder outcomes among adolescents receiving outpatient care for diagnosed eating disorders (anorexia nervosa, bulimia nervosa, eating disorder not otherwise specified). A total of 50 girls and 4 boys aged 11-21 years were randomized to an 8-week trial of standard care vs. individualized yoga plus standard care. Of these, 27 were randomized to standard care and 26 to yoga plus standard care (attrition: n = 4). Standard care (every other week physician and/or dietician appointments) was required to meet ethical guidelines. The No Yoga group was offered yoga after study completion as an incentive to maintain participation. Outcomes evaluated at baseline, end of trial, and 1-month follow-up included Eating Disorder Examination (EDE), Body Mass Index (BMI), Beck Depression Inventory, State-Trait Anxiety Inventory, and Food Preoccupation questionnaire. The Yoga group demonstrated greater decreases in eating disorder symptoms. Specifically, the EDE scores decreased over time in the Yoga group, whereas the No Yoga group showed some initial decline but then returned to baseline EDE levels at week 12. Food preoccupation was measured before and after each yoga session, and decreased significantly after all sessions. Both groups maintained current BMI levels and decreased in anxiety and depression over time. Individualized yoga treatment decreased EDE scores at 12 weeks, and significantly reduced food preoccupation immediately after yoga sessions. Yoga treatment did not have a negative effect on BMI. Results suggest that individualized yoga therapy holds promise as adjunctive therapy to standard care. Copyright 2010 Society for Adolescent Medicine. Published by Elsevier Inc. All rights reserved.
Gonzalez-Quesada, Carlos J; Giugliano, Robert P
Although vitamin K antagonists (VKAs) have been the backbone of thromboprophylaxis in nonvalvular atrial fibrillation, their limitations have encouraged the development of a new generation of oral anticoagulants. This review compares the different designs and procedures used to conduct four phase III trials that tested dabigatran, rivaroxaban, apixaban, and edoxaban versus VKAs. Although pharmacologic characteristics and results of the main trials are briefly discussed, this review mainly focuses on study designs, enrollment criteria, populations studied, quality metrics, and transition strategies between oral anticoagulants. While each of the trials was of high quality, performed independently, and led by independent academic groups, substantial differences exist in terms of drug pharmacology and trial characteristics. Caution is advised when comparing results across trials as practicing clinicians strive to personalize anticoagulation treatments for their individual patients. We believe that the differences in the pharmacokinetic and pharmacodynamic profiles of the available novel oral anticoagulants (NOACs), coupled with substantial heterogeneity in the trial populations and designs and procedures used to conduct the trials, support an important role for each of the NOACs dependent upon the specific clinical scenario faced by the practicing clinician.
Maserejian, Nancy N.; Trachtenberg, Felicia L.; Hauser, Russ; McKinlay, Sonja; Shrader, Peter; Bellinger, David C.
Background Resin-based dental restorations may intra-orally release their components and bisphenol A. Gestational bisphenol A exposure has been associated with poorer executive functioning in children. Objectives To examine whether exposure to resin-based composite restorations is associated with neuropsychological development in children. Methods Secondary analysis of treatment level data from the New England Children’s Amalgam Trial, a 2-group randomized safety trial conducted from 1997–2006. Children (N=534) aged 6–10 y with >2 posterior tooth caries were randomized to treatment with amalgam or resin-based composites (bisphenol-A-diglycidyl-dimethacrylate-composite for permanent teeth; urethane dimethacrylate-based polyacid-modified compomer for primary teeth). Neuropsychological function at 4- and 5-year follow-up (N=444) was measured by a battery of tests of executive function, intelligence, memory, visual-spatial skills, verbal fluency, and problem-solving. Multivariable generalized linear regression models were used to examine the association between composite exposure levels and changes in neuropsychological test scores from baseline to follow-up. For comparison, data on children randomized to amalgam treatment were similarly analyzed. Results With greater exposure to either dental composite material, results were generally consistent in the direction of slightly poorer changes in tests of intelligence, achievement or memory, but there were no statistically significant associations. For the four primary measures of executive function, scores were slightly worse with greater total composite exposure, but statistically significant only for the test of Letter Fluency (10-surface-years β= −0.8, SE=0.4, P=0.035), and the subtest of color naming (β= −1.5, SE=0.5, P=0.004) in the Stroop Color-Word Interference Test. Multivariate analysis of variance confirmed that the negative associations between composite level and executive function were not
Triviño, Mónica; Ródenas, Estrella; Lupiáñez, Juan; Arnedo, Marisa
Confabulators consistently generate false memories without intention to deceive and with great feelings of rightness. However, to our knowledge, there is currently no known effective treatment for them. In order to fill this gap, our aim was to design a neuropsychological treatment based on current theoretical models and test it experimentally in 20 confabulators sequentially allocated to two groups: an experimental and a control group. The experimental group received nine sessions of treatment for three weeks (three sessions per week). The sessions consisted of some brief material that participants had to learn and recall at both immediate and delayed time points. After this, patients were given feedback about their performance (errors and correct responses). Pre- and post-treatment measurements were recorded. Confabulators in the control group were included in a waiting list for three weeks, performed the pre- and post- measurements without treatment, and only then received the treatment, after which a post-treatment measurement was recorded. This applied to only half of the participants; the other half quit the study prematurely. Results showed a significant decrease in confabulations and a significant increase in correct responses in the experimental group; by contrast, patients in the control group did not improve during the waiting list period. Only control group patients who subsequently received the treatment after serving as controls improved. The effects of the treatment were generalized to patients’ everyday lives, as reported by relatives, and persisted over time. This treatment seems to be effective and easy to implement and consequently of clinical interest. Moreover, it also has theoretical implications regarding the processes related to the genesis and/or maintenance of confabulations. In particular, results point to a deficit in early stages of memory retrieval with the preservation of later strategic monitoring processes. Specifically, some of
Full Text Available Confabulators consistently generate false memories without intention to deceive and with great feelings of rightness. However, to our knowledge, there is currently no known effective treatment for them. In order to fill this gap, our aim was to design a neuropsychological treatment based on current theoretical models and test it experimentally in 20 confabulators sequentially allocated to two groups: an experimental and a control group. The experimental group received nine sessions of treatment for three weeks (three sessions per week. The sessions consisted of some brief material that participants had to learn and recall at both immediate and delayed time points. After this, patients were given feedback about their performance (errors and correct responses. Pre- and post-treatment measurements were recorded. Confabulators in the control group were included in a waiting list for three weeks, performed the pre- and post- measurements without treatment, and only then received the treatment, after which a post-treatment measurement was recorded. This applied to only half of the participants; the other half quit the study prematurely. Results showed a significant decrease in confabulations and a significant increase in correct responses in the experimental group; by contrast, patients in the control group did not improve during the waiting list period. Only control group patients who subsequently received the treatment after serving as controls improved. The effects of the treatment were generalized to patients' everyday lives, as reported by relatives, and persisted over time. This treatment seems to be effective and easy to implement and consequently of clinical interest. Moreover, it also has theoretical implications regarding the processes related to the genesis and/or maintenance of confabulations. In particular, results point to a deficit in early stages of memory retrieval with the preservation of later strategic monitoring processes
Sloan, Denise M; Unger, William; Gayle Beck, J
Despite significant advances in individual treatment approaches for PTSD, knowledge of group approaches has lagged behind. Much of the reason knowledge about group treatment for PTSD has been limited is due to the complexity of conducting randomized controlled trials in the group treatment context. This limited empirical knowledge is unfortunate given the frequency with which group treatment for PTSD is used in clinical settings, including the Department of Veteran Affairs. The goal of this study is to examine the efficacy of a group cognitive-behavioral treatment (GCBT) for PTSD relative to group supportive counseling approach (i.e. group present centered treatment; GPCT). The sample consists of 196 veterans diagnosed with PTSD who are randomly assigned to either GCBT (n=98) or GPCT (n=98). Both treatments are administered by two therapists over the course of 14 sessions. Assessments take place at baseline, mid-treatment, post-treatment and 3-, 6-, and 12-month follow-up. The primary outcome measure is the PTSD symptom severity assessed with a semi-structured diagnostic instrument. Given the substantial rise of veterans presenting for PTSD treatment services, identifying an efficacious group treatment approach is invaluable. Copyright © 2016 Elsevier Inc. All rights reserved.
Gellatly, Judith; Bower, Peter; McMillan, Dean; Roberts, Christopher; Byford, Sarah; Bee, Penny; Gilbody, Simon; Arundel, Catherine; Hardy, Gillian; Barkham, Michael; Reynolds, Shirley; Gega, Lina; Mottram, Patricia; Lidbetter, Nicola; Pedley, Rebecca; Peckham, Emily; Connell, Janice; Molle, Jo; O'Leary, Neil; Lovell, Karina
UK National Institute of Health and Clinical Excellence guidelines for obsessive compulsive disorder (OCD) specify recommendations for the treatment and management of OCD using a stepped care approach. Steps three to six of this model recommend treatment options for people with OCD that range from low-intensity guided self-help (GSH) to more intensive psychological and pharmacological interventions. Cognitive behavioural therapy (CBT), including exposure and response prevention, is the recommended psychological treatment. However, whilst there is some preliminary evidence that self-managed therapy packages for OCD can be effective, a more robust evidence base of their clinical and cost effectiveness and acceptability is required. Our proposed study will test two different self-help treatments for OCD: 1) computerised CBT (cCBT) using OCFighter, an internet-delivered OCD treatment package; and 2) GSH using a book. Both treatments will be accompanied by email or telephone support from a mental health professional. We will evaluate the effectiveness, cost and patient and health professional acceptability of the treatments. This study will provide more robust evidence of efficacy, cost effectiveness and acceptability of self-help treatments for OCD. If cCBT and/or GSH prove effective, it will provide additional, more accessible treatment options for people with OCD. Current Controlled Trials: ISRCTN73535163. Date of registration: 5 April 2011.
Kirsten L. White
Full Text Available The integrase (IN strand transfer inhibitors (INSTIs, raltegravir (RAL, elvitegravir (EVG and dolutegravir (DTG, comprise the newest drug class approved for the treatment of HIV-1 infection, which joins the existing classes of reverse transcriptase, protease and binding/entry inhibitors. The efficacy of first-line regimens has attained remarkably high levels, reaching undetectable viral loads in 90% of patients by Week 48; however, there remain patients who require a change in regimen due to adverse events, virologic failure with emergent resistance or other issues of patient management. Large, randomized clinical trials conducted in antiretroviral treatment-naive individuals are required for drug approval in this population in the US, EU and other countries, with the primary endpoint for virologic success at Week 48. However, there are differences in the definition of virologic failure and the evaluation of drug resistance among the trials. This review focuses on the methodology and tabulation of resistance to INSTIs in phase 3 clinical trials of first-line regimens and discusses case studies of resistance.
White, Kirsten L.; Raffi, Francois; Miller, Michael D.
The integrase (IN) strand transfer inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG), comprise the newest drug class approved for the treatment of HIV-1 infection, which joins the existing classes of reverse transcriptase, protease and binding/entry inhibitors. The efficacy of first-line regimens has attained remarkably high levels, reaching undetectable viral loads in 90% of patients by Week 48; however, there remain patients who require a change in regimen due to adverse events, virologic failure with emergent resistance or other issues of patient management. Large, randomized clinical trials conducted in antiretroviral treatment-naive individuals are required for drug approval in this population in the US, EU and other countries, with the primary endpoint for virologic success at Week 48. However, there are differences in the definition of virologic failure and the evaluation of drug resistance among the trials. This review focuses on the methodology and tabulation of resistance to INSTIs in phase 3 clinical trials of first-line regimens and discusses case studies of resistance. PMID:25054884
Peul Wilco C
Full Text Available Abstract Background The objective is to present the design of randomised clinical trial (RCT on the effectiveness of physical therapy added to general practitioners management compared to general practitioners management only in patients with an acute lumbosacral radicular syndrome (also called sciatica. Methods/Design Patients in general practice diagnosed with an acute (less than 6 weeks lumbosacral radicular syndrome and an age above 18 years are eligible for participation. The general practitioners treatment follows their clinical guideline. The physical therapy treatment will consist of patient education and exercise therapy. The primary outcome measure is patients reported global perceived effect. Secondary outcome measures are severity of complaints, functional status, health status, fear of movement, medical consumption, sickness absence, costs and treatment preference. The follow-up is 52 weeks. Discussion Treatment by general practitioners and physical therapists in this study will be transparent and not a complete "black box". The results of this trial will contribute to the decision of the general practitioner regarding referral to physical therapy in patients with an acute lumbosacral radicular syndrome.
Bründl, Elisabeth; Böhm, Christina; Lürding, Ralf; Schödel, Petra; Bele, Sylvia; Hochreiter, Andreas; Scheitzach, Judith; Zeman, Florian; Brawanski, Alexander; Schebesch, Karl-Michael
Few studies have addressed the effect of treatment of unruptured intracranial aneurysm (UIA) on cognitive function. Neuropsychological assessment after UIA treatment is underreported, and prospective trials have repeatedly been demanded. In 2014, we conducted a prospective controlled study to evaluate the differences in cognitive processing caused by the treatment of anterior circulation UIAs. Thirty patients were enrolled until September 2015. Ten patients received endovascular aneurysm occlusion (EV), 10 patients were treated microsurgically (MS), and 10 patients with surgically treated degenerative lumbar spine disease (LD) served as control. All patients underwent extended standardized neuropsychological assessment before (t 1 ) and 6 weeks after treatment (t 2 ). Tests included verbal, visual, and visuospatial memory, psychomotor functioning, executive functioning, and its subdomains verbal fluency and cognitive flexibility. We statistically evaluated intragroup and intergroup changes. Intragroup comparisons and group-rate analysis showed no significant impairment in overall neuropsychological performance, either postinterventionally or postoperatively. However, the postoperative performance in cognitive processing speed, cognitive flexibility, and executive functioning was significantly worse in the MS group than in the EV (P = 0.038) and LD group (P = 0.02). Compared with the EV group, patients with MS showed significant postoperative impairment in a subtest for auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. EV P = 0.011). The MS group trended toward posttreatment impairment in subtests for verbal fluency and semantic memory (Regensburg Word Fluency Test; MS vs. EV P = 0.083) and in auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. LD P = 0.06). Our preliminary data showed no effect of anterior circulation UIA treatment on overall neuropsychological function but impaired
Full Text Available BackgroundWe report a randomised controlled clinical trial of neurofeedback therapy intervention for ADHD/ADD in adults. We focus on internal mechanics of neurofeedback learning, to elucidate the primary role of cortical self-regulation in neurofeedback. We report initial results; more extensive analysis will follow.MethodsTrial has two phases: intervention and follow-up. The intervention consisted of neurofeedback treatment, including intake and outtake measurements, using a waiting-list control group. Treatment involved $sim$40 hour-long sessions 2-5 times per week. Training involved either theta/beta or sensorimotor-rhythm regimes, adapted by adding a novel 'inverse-training' condition to promote self-regulation. Follow-up (ongoing will consist of self-report and executive function tests.SettingIntake and outtake measurements were conducted at University of Helsinki. Treatment was administered at partner clinic Mental Capital Care, Helsinki.RandomisationWe randomly allocated half the sample then adaptively allocated the remainder to minimise baseline differences in prognostic variables.BlindingWaiting-list control design meant trial was not blinded.Participants54 adult Finnish participants (mean age 36 years; 29 females were recruited after screening by psychiatric review. 44 had ADHD diagnoses, 10 had ADD.MeasurementsSymptoms were assessed by computerised attention test (T.O.V.A. and self-report scales, at intake and outtake. Performance during neurofeedback trials was recorded.ResultsParticipants were recruited and completed intake measurements during summer 2012, before assignment to treatment and control, September 2012. Outtake measurements ran April-August 2013. After dropouts, 23 treatment and 21 waiting-list participants remained for analysis.Initial analysis showed that, compared to waiting-list control, neurofeedback promoted improvement of self-reported ADHD symptoms, but did not show transfer of learning to T.O.V.A. Comprehensive
SANT’ANA, Adriana Campos Passanezi; de CAMPOS, Marinele R.; PASSANEZI, Selma Campos; de REZENDE, Maria Lúcia Rubo; GREGHI, Sebastião Luiz Aguiar; PASSANEZI, Euloir
Objectives The aim of this study was to evaluate the effects of non-surgical treatment of periodontal disease during the second trimester of gestation on adverse pregnancy outcomes. Material and Methods Pregnant patients during the 1st and 2nd trimesters at antenatal care in a Public Health Center were divided into 2 groups: NIG – "no intervention" (n=17) or IG- "intervention" (n=16). IG patients were submitted to a non-surgical periodontal treatment performed by a single periodontist consisting of scaling and root planning (SRP), professional prophylaxis (PROPH) and oral hygiene instruction (OHI). NIG received PROPH and OHI during pregnancy and were referred for treatment after delivery. Periodontal evaluation was performed by a single trained examiner, blinded to periodontal treatment, according to probing depth (PD), clinical attachment level (CAL), plaque index (PI) and sulcular bleeding index (SBI) at baseline and 35 gestational weeks-28 days post-partum. Primary adverse pregnancy outcomes were preterm birth (0.05) at IG and worsening of all periodontal parameters at NIG (ppregnancy outcomes was 47.05% in NIG and 6.25% in IG. Periodontal treatment during pregnancy was associated to a decreased risk of developing adverse pregnancy outcomes [OR=13.50; CI: 1.47-123.45; p=0.02]. Conclusions Periodontal treatment during the second trimester of gestation contributes to decrease adverse pregnancy outcomes. PMID:21552714
Cooper Nicholas J
Full Text Available Abstract Background Clinically useful treatment moderators of Major Depressive Disorder (MDD have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators. Methods/Design The International Study to Predict Optimized Treatment - in Depression (iSPOT-D is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65 from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls. Study-eligible patients are antidepressant medication (ADM naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary. Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm. Discussion First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide. Trial registration International Study to Predict Optimised Treatment - in Depression (iSPOT-D ClinicalTrials.gov Identifier
Bablis, Peter; Pollard, Henry; Bonello, Rod
Trigger points have been shown to be active in many myofascial pain syndromes. Treatment of trigger point pain and dysfunction may be explained through the mechanisms of central and peripheral paradigms. This study aimed to investigate whether the mind/body treatment of Neuro Emotional Technique (NET) could significantly relieve pain sensitivity of trigger points presenting in a cohort of chronic neck pain sufferers. Sixty participants presenting to a private chiropractic clinic with chronic cervical pain as their primary complaint were sequentially allocated into treatment and control groups. Participants in the treatment group received a short course of Neuro Emotional Technique that consists of muscle testing, general semantics and Traditional Chinese Medicine. The control group received a sham NET protocol. Outcome measurements included pain assessment utilizing a visual analog scale and a pressure gauge algometer. Pain sensitivity was measured at four trigger point locations: suboccipital region (S); levator scapulae region (LS); sternocleidomastoid region (SCM) and temporomandibular region (TMJ). For each outcome measurement and each trigger point, we calculated the change in measurement between pre- and post- treatment. We then examined the relationships between these measurement changes and six independent variables (i.e. treatment group and the above five additional participant variables) using forward stepwise General Linear Model. The visual analog scale (0 to 10) had an improvement of 7.6 at S, 7.2 at LS, 7.5 at SCM and 7.1 at the TMJ in the treatment group compared with no improvement of at S, and an improvement of 0.04 at LS, 0.1 at SCM and 0.1 at the TMJ point in the control group, (P algometer recordings of four trigger point locations in a cohort of chronic neck pain sufferers were significantly improved when compared to a control group which received a sham protocol of NET. Chronic neck pain sufferers may benefit from NET treatment in the relief
McClure, Erin A; King, Jacqueline S; Wahle, Aimee; Matthews, Abigail G; Sonne, Susan C; Lofwall, Michelle R; McRae-Clark, Aimee L; Ghitza, Udi E; Martinez, Melissa; Cloud, Kasie; Virk, Harvir S; Gray, Kevin M
Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment: Episodes Data Set - Admissions. Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings. Copyright © 2017 Elsevier B.V. All rights reserved.
Jensen, Rikke K; Leboeuf-Yde, Charlotte; Wedderkopp, Niels; Sorensen, Joan S; Manniche, Claus
Clinical experience suggests that many patients with Modic changes have relatively severe and persistent low back pain (LBP), which typically appears to be resistant to treatment. Exercise therapy is the recommended treatment for chronic LBP, however, due to their underlying pathology, Modic changes might be a diagnostic subgroup that does not benefit from exercise. The objective of this study was to compare the current state-of-the art treatment approach (exercise and staying active) with a new approach (load reduction and daily rest) for people with Modic changes using a randomized controlled trial design. Participants were patients from an outpatient clinic with persistent LBP and Modic changes. They were allocated using minimization to either rest therapy for 10 weeks with a recommendation to rest for two hours daily and the option of using a flexible lumbar belt or exercise therapy once a week for 10 weeks. Follow-up was at 10 weeks after recruitment and 52 weeks after intervention and the clinical outcome measures were pain, disability, general health and global assessment, supplemented by weekly information on low back problems and sick leave measured by short text message (SMS) tracking. In total, 100 patients were included in the study. Data on 87 patients at 10 weeks and 96 patients at one-year follow-up were available and were used in the intention-to-treat analysis. No statistically significant differences were found between the two intervention groups on any outcome. No differences were found between the two treatment approaches, 'rest and reduced load' and 'exercise and staying active', in patients with persistent LBP and Modic changes. ClinicalTrials.gov: NCT00454792.
Gregg, Robert H., II
Formation of dystrophic calcification deposits within the root canal of a tooth, have historically been difficult clinical endodontic complications. Presently, removal of such tissue, mineralized through the deposition of calcareous materials in a root canal (a 'calcified canal'), remains resistant to conventional endodontic techniques. The subsequent treatment primarily involves undesirable surgical procedures and/or loss of the tooth. Described in this clinical trial is a technique using free running (RF) pulsed, Nd:YAG laser energy to ablate hard calcified tissue which obstructed mechanical access of the root canal and root apex--a technique employed after conventional endodontic methods failed. This paper discusses the 'plasma' effect, 'spallation', canal illumination and transillumination using the helium-neon (HeNe) aiming beam. A free running pulsed, FR Nd:YAG dental laser was successfully used at 20 pulses per second and 1.75 watts to photovaporize and photodisrupt enough calcified tissue obstruction, to allow a conventional endodontic file to pass the canal blockage, and access the root apex. This clinical trial achieved the immediate, short term objective of endodontic hard tissue removal via photovaporization and photodisruption. The pulsed FR Nd:YAG dental laser used as described in this clinical report appears to be a very safe and very effective technique; offers a treatment alternative to traditional therapy that suggests high patient acceptance; and is significantly less stressful for the doctor and staff than traditional treatment options. Long-term, controlled scientific and clinical studies are necessary to establish the safety and efficacy of both the helium-neon energy for visualization and the low- watt pulsed FR Nd:YAG energy for photovaporization and photodisruption of hard calcified tissue within the root canal. Research is especially needed to understand the effects of low- watt, pulsed FR, Nd:YAG laser on the activity of osteoclasts and
Anisimov, Vladimir V; Yeung, Wai Y; Coad, D Stephen
Randomisation schemes are rules that assign patients to treatments in a clinical trial. Many of these schemes have the common aim of maintaining balance in the numbers of patients across treatment groups. The properties of imbalance that have been investigated in the literature are based on two treatment groups. In this paper, their properties for K > 2 treatments are studied for two randomisation schemes: centre-stratified permuted-block and complete randomisation. For both randomisation schemes, analytical approaches are investigated assuming that the patient recruitment process follows a Poisson-gamma model. When the number of centres involved in a trial is large, the imbalance for both schemes is approximated by a multivariate normal distribution. The accuracy of the approximations is assessed by simulation. A test for treatment differences is also considered for normal responses, and numerical values for its power are presented for centre-stratified permuted-block randomisation. To speed up the calculations, a combined analytical/approximate approach is used. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Farajzadeh, Saeedeh; Heshmatkhah, Amireh; Vares, Behrooz; Mohebbi, Elham; Mohebbi, Azadeh; Aflatoonian, Mahin; Eybpoosh, Sana; Sharifi, Iraj; Aflatoonian, Mohammad Reza; Shamsi Meymandi, Simin; Fekri, Ali Reza; Mostafavi, Mahshid
Leishmaniasis is a spectrum of disease condition with considerable health impacts, caused by different species of Leishmania . This disease is currently endemic in 98 countries and territories in the world. There are many treatment modalities for cutaneous leishmaniasis. The use of topical terbinafine in the treatment of cutaneous leishmaniasis has recently been considered. Eighty-eight participants more than two years old with proven acute CL by a positive direct smear were randomly allocated to one of the two study arms: first group received meglumine antimoniate (Glucantime) 20 mg/kg/day intramuscular injection (IM) plus a placebo ointment (Mahan Vaseline) for 20 days. The second group received meglumine antimoniate (Glucantime) 20 mg/kg/day IM plus topical terbinafine, for 20 days and were monitored closely by dermatologist during the course of the study. Crude regression analysis showed that there was no significant difference between placebo and intervention group regarding partial or complete treatment (partial treatment: HR crude = 1.1, CI 95 % = 0.7-1.7; complete treatment: HR crude = 1.1, CI 95 % = 0.8-1.7). Although, there was no statistically significant different between the two treatment groups, but clinically it seems that the treatment rate in those who receive glucantime plus terbinafine was more effective than the other group. However this rate depended on the type of lesions. As data indicated ulcerated nodules, papules and plaque in experimental group have been completely improved two times faster than placebo group. Ulcerated nodules, nodules and plaque were partially improved faster in those used tebinafine than placebo ointment.
Jose M Trigo
Full Text Available The current lack of pharmacological treatments for cannabis use disorder (CUD warrants novel approaches and further investigation of promising pharmacotherapy. We previously showed that nabiximols (27 mg/ml Δ9-tetrahydrocannabinol (THC/ 25 mg/ml cannabidiol (CBD, Sativex® can decrease cannabis withdrawal symptoms. Here, we assessed in a pilot study the tolerability and safety of self-titrated nabiximols vs. placebo among 40 treatment-seeking cannabis-dependent participants.Subjects participated in a double blind randomized clinical trial, with as-needed nabiximols up to 113.4 mg THC/105 mg CBD or placebo daily for 12 weeks, concurrently with Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT. Primary outcome measures were tolerability and abstinence, secondary outcome measures were days and amount of cannabis use, withdrawal, and craving scores. Participants received up to CDN$ 855 in compensation for their time.Medication was well tolerated and no serious adverse events (SAEs were observed. Rates of adverse events did not differ between treatment arms (F1,39 = 0.205, NS. There was no significant change in abstinence rates at trial end. Participants were not able to differentiate between subjective effects associated with nabiximols or placebo treatments (F1,40 = 0.585, NS. Cannabis use was reduced in the nabiximols (70.5% and placebo groups (42.6%. Nabiximols reduced cannabis craving but no significant differences between the nabiximols and placebo groups were observed on withdrawal scores.Nabiximols in combination with MET/CBT was well tolerated and allowed for reduction of cannabis use. Future clinical trials should explore the potential of high doses of nabiximols for cannabis dependence.
Maruyama, Y; VanNagell, J R; Yoneda, J; Donaldson, E; Gallion, H; Rowley, K; Kryscio, R; Beach, J L
Intracavitary Californium-252 combined with whole-pelvis photon radiotherapy was tested as the sole form of treatment for 22 patients with Stage IB carcinoma of the cervix. Californium-252 (Cf) is a fast neutron-emitting radioisotope currently being tested in trials of neutron brachytherapy (NT). The outcomes of the treated group of patients were traced for local tumor control, survival, patterns of failure, and complications. The Cf intracavitary therapy combined with whole-pelvis photon radiotherapy resulted in 95% 2-year and 91% 5-year actuarial survival. There were 9% Grade II-III complications by the Stockholm scale and 4% local failures. These results were obtained in an early clinical trial with a group of largely poor-risk patients with tumors of mean diameter of 4.3 cm.
Escolar, D M; Zimmerman, A; Bertorini, T; Clemens, P R; Connolly, A M; Mesa, L; Gorni, K; Kornberg, A; Kolski, H; Kuntz, N; Nevo, Y; Tesi-Rocha, C; Nagaraju, K; Rayavarapu, S; Hache, L P; Mayhew, J E; Florence, J; Hu, F; Arrieta, A; Henricson, E; Leshner, R T; Mah, J K
To determine whether pentoxifylline (PTX) slows the decline of muscle strength and function in ambulatory boys with Duchenne muscular dystrophy (DMD). This was a multicenter, randomized, double-blinded, controlled trial comparing 12 months of daily treatment with PTX or placebo in corticosteroid-treated boys with DMD using a slow-release PTX formulation (~20 mg/kg/day). The primary outcome was the change in mean total quantitative muscle testing (QMT) score. Secondary outcomes included changes in QMT subscales, manual muscle strength, pulmonary function, and timed function tests. Outcomes were compared using Student t tests and a linear mixed-effects model. Adverse events (AEs) were compared using the Fisher exact test. A total of 64 boys with DMD with a mean age of 9.9 ± 2.9 years were randomly assigned to PTX or placebo in 11 participating Cooperative International Neuromuscular Research Group centers. There was no significant difference between PTX and the placebo group in total QMT scores (p = 0.14) or in most of the secondary outcomes after a 12-month treatment. The use of PTX was associated with mild to moderate gastrointestinal or hematologic AEs. The addition of PTX to corticosteroid-treated boys with DMD at a moderate to late ambulatory stage of disease did not improve or halt the deterioration of muscle strength and function over a 12-month study period. This study provides Class I evidence that treatment with PTX does not prevent deterioration in muscle function or strength in corticosteroid-treated boys with DMD.
Palter, S F
The modern clinical trial is a form of human experimentation. There is a long history of disregard for individual rights of the patient in this context, and special attention must be paid to ethical guidelines for these studies. Clinical trials differ in basic ways from clinical practice. Foremost is the introduction of outside interests, beyond those of the patient's health, into the doctor-patient therapeutic alliance. Steps must be taken to protect the interests of the patient when such outside influence exists. Kantian moral theory and the Hippocratic oath dictate that the physician must respect the individual patient's rights and hold such interests paramount. These principles are the basis for informed consent. Randomization of patients is justified when a condition of equipoise exists. The changing nature of health care delivery in the United States introduces new outside interests into the doctor-patient relationship.
Menon, Navya P.; Varma, Balagopal R.; Janardhanan, Sureshkumar; Kumaran, Parvathy; Xavier, Arun Mamachan; Govinda, Bhat Sangeetha
Aim: To clinically and radiographically evaluate the reparative dentin formation in indirect pulp treatment (IPT) using mineral trioxide aggregate (MTA) and light cured calcium silicate (TheraCal) in primary molars over a period of 6 months. Materials and Methods: A clinical trial on IPT on 43 primary molars in 21 patients between the age of 4–7 years, divided into two groups: 22 teeth in MTA group and 21 in TheraCal group. Measurement of the variation in dentin thickness was done on the digi...
Mehmood, A.; Usmanghani, K.; Mohiuddin, E.; Akram, M.
Helicobacter pylori induces chronic inflammation of the underlying gastric mucosa and is strongly linked to the development of duodenal and gastric carcinoma. A study was conducted to evaluate the efficacy of Pylorex, a herbal formulation, for treatment of H. pylori infection as compared to triple allopathic therapy (Omeprazole, Amoxicillin, Metronidazole). The therapeutic evaluations of these medicines were conducted on 97 clinically and immunologically diagnosed cases of H. pylori infection. H. pylori was eradicated in 16 (32.6%) out of 49 patients by the use of triple allopathic therapy (Control drugs), and in 9 (18.7%) out of 48 patients by the use of Pylorex (Test drug). Pylorex possesses a therapeutic value for the treatment of H. pylori associated symptoms but the eradication rate is superior in triple allopathic therapy. (author)
The aim of this study was to compare the therapeutic effect of topical Myrtus communis (myrtle solution with topical triamcinolone (Adcortyle in the treatment of minor apotheosis. Materials & Methods: This clinical-trial study was conducted at Kurdistan University of Medical Sciences in 2009. 100 patients were randomly assigned into 2 groups. The 1st group received topical myrtle solution. The 2nd group received topical trimcinolone (Adcortyle. After one week, patients' declaration about time of the recovery of the pain and deterioration of oral lesion was recorded. The gathered data was then analyzed using the SPSS statistical software using t-test and chi-square. Results: After treatment, both groups showed response to topical medications with no significant difference between them (p>0.05. Conclusion: results of this study showed that topical myrtle solution is effective in the treatment of minor aphthous stomatitis and its therapeutic effect is comparable with topical triamcinolone (Adcortyle.
Adriana Campos Passanezi Sant'Ana
Full Text Available OBJECTIVES: The aim of this study was to evaluate the effects of non-surgical treatment of periodontal disease during the second trimester of gestation on adverse pregnancy outcomes. MATERIAL AND METHODS: Pregnant patients during the 1st and 2nd trimesters at antenatal care in a Public Health Center were divided into 2 groups: NIG - "no intervention" (n=17 or IG- "intervention" (n=16. IG patients were submitted to a non-surgical periodontal treatment performed by a single periodontist consisting of scaling and root planning (SRP, professional prophylaxis (PROPH and oral hygiene instruction (OHI. NIG received PROPH and OHI during pregnancy and were referred for treatment after delivery. Periodontal evaluation was performed by a single trained examiner, blinded to periodontal treatment, according to probing depth (PD, clinical attachment level (CAL, plaque index (PI and sulcular bleeding index (SBI at baseline and 35 gestational weeks-28 days post-partum. Primary adverse pregnancy outcomes were preterm birth (0.05 at IG and worsening of all periodontal parameters at NIG (p<0.0001, except for PI. Signifcant differences in periodontal conditions of IG and NIG were observed at 2nd examination (p<0.001. The rate of adverse pregnancy outcomes was 47.05% in NIG and 6.25% in IG. Periodontal treatment during pregnancy was associated to a decreased risk of developing adverse pregnancy outcomes [OR=13.50; CI: 1.47-123.45; p=0.02]. CONCLUSIONS: Periodontal treatment during the second trimester of gestation contributes to decrease adverse pregnancy outcomes.
McEvoy, Joseph P; Byerly, Matthew; Hamer, Robert M; Dominik, Rosalie; Swartz, Marvin S; Rosenheck, Robert A; Ray, Neepa; Lamberti, J Steven; Buckley, Peter F; Wilkins, Tania M; Stroup, T Scott
Long-acting injectable antipsychotics are used to reduce medication nonadherence and relapse in schizophrenia-spectrum disorders. The relative effectiveness of long-acting injectable versions of second-generation and older antipsychotics has not been assessed. To compare the effectiveness of the second-generation long-acting injectable antipsychotic paliperidone palmitate with the older long-acting injectable antipsychotic haloperidol decanoate. Multisite, double-blind, randomized clinical trial conducted from March 2011 to July 2013 at 22 US clinical research sites. Randomized patients (n = 311) were adults diagnosed with schizophrenia or schizoaffective disorder who were clinically assessed to be at risk of relapse and likely to benefit from a long-acting injectable antipsychotic. Intramuscular injections of haloperidol decanoate 25 to 200 mg or paliperidone palmitate 39 to 234 mg every month for as long as 24 months. Efficacy failure, defined as a psychiatric hospitalization, a need for crisis stabilization, a substantial increase in frequency of outpatient visits, a clinician's decision that oral antipsychotic could not be discontinued within 8 weeks after starting the long-acting injectable antipsychotics, or a clinician's decision to discontinue the assigned long-acting injectable due to inadequate therapeutic benefit. Key secondary outcomes were common adverse effects of antipsychotic medications. There was no statistically significant difference in the rate of efficacy failure for paliperidone palmitate compared with haloperidol decanoate (adjusted hazard ratio, 0.98; 95% CI, 0.65-1.47). The number of participants who experienced efficacy failure was 49 (33.8%) in the paliperidone palmitate group and 47 (32.4%) in the haloperidol decanoate group. On average, participants in the paliperidone palmitate group gained weight and those in the haloperidol decanoate group lost weight; after 6 months, the least-squares mean weight change for those taking
Gregory S. Alexander
Full Text Available Abstract Background Pembrolizumab is a monoclonal antibody that is designed against programmed cell death protein 1 (PD-1. Pembrolizumab and other immunocheckpoint-blocking monoclonal antibodies work by modulating a patient’s own immune system to increase anti-tumor activity. While immunocheckpoint blockade has shown promising results, only 20–40 % of patients experience objective clinical benefit. Differences in individual tumor biology and the presence multiple immune checkpoints present a challenge for treatment. Because radiotherapy has immunomodulatory effects on the tumor microenvironment, it has the potential to synergize with immunotherapy and augment tumor response. NCT02318771 is a phase 1 clinical trial designed to investigate the immunomodulatory effects of radiation therapy in combination with pembrolizumab. Case presentation The patient is a 64-year-old male with metastatic clear cell renal cell carcinoma, Fuhrman grade 4, pathologically staged as T3 N0. Metastatic disease was well controlled for several years with sunitinib. Following disease progression, he was switched to axitinib. When disease progression continued, the patient was enrolled in NCT02318771, a phase 1 clinical trial combining radiotherapy and pembrolizumab. The patient experienced unusually rapid disease progression during treatment, which was confirmed by repeated CT scans to rule out pseudoprogression. Tissue biopsies and peripheral blood draws were obtained before, during, and after treatment. Samples were analyzed to provide plausible rationale for rapid treatment failure. Conclusions Biomarker analysis demonstrated an absence of TILs, which may be a cause of treatment failure as pembrolizumab works through T cell-dependent mechanisms. Furthermore, the presence of other non-redundant immune checkpoints in the periphery and tumor microenvironment presents a treatment challenge. Additionally, the radiation dose and fractionation schedule may have played a
Dijkstra, Boukje A G; De Jong, Cor A J; Wensing, Michel; Krabbe, Paul F M; van der Staak, Cees P F
Controlled clinical trials have high internal validity but suffer from difficulties in external validity. This study evaluates the generalizability of the results of a controlled clinical trial on rapid detoxification in the everyday clinical practice of two addiction treatment centers. The results
S Ashraffodin Ghoshegir
Full Text Available Background: We aimed to evaluate the effects of Pimpinella anisum (anise from Apiaceae family on relieving the symptoms of postprandial distress syndrome (PDS in this double-blind randomized clinical trial. Materials and Methods: Totally, 107 patients attending the gastroenterology clinic, aged 18-65 years, diagnosed with PDS according to ROME III criteria and signed a written consent form were enrolled. They were randomized to receive either anise or placebo, blindly, for 4 weeks. Anise group included 47 patients and received anise powders, 3 g after each meal (3 times/day. Control group involved 60 patients and received placebo powders (corn starch, 3 gafter each meal (3 times/day. The severity of Functional dyspepsia (FD symptoms was assessed by FD severity scale. Assessments were done at baseline and by the end of weeks 2, 4 and 12. Mean scores of severity of FD symptoms and the frequency distribution of patients across the study period were compared. Results: The age, sex, body mass index, smoking history, and coffee drinking pattern of the intervention and control groups were not significantly different. Mean (standard deviation total scores of FD severity scale before intervention in the anise and control groups were 10.6 (4.1 and 10.96 (4.1, respectively (P = 0.6. They were 7.04 (4.1 and 12.30 (4.3 by week 2, respectively (P = 0.0001, 2.44 (4.2 and 13.05 (5.2 by week 4, respectively (P = 0.0001, and 1.08 (3.8 and 13.30 (6.2 by week 12, respectively (P = 0.0001. Conclusion: This study showed the effectiveness of anise in relieving the symptoms of postpartum depression. The findings were consistent across the study period at weeks 2, 4 and 12.
Dogramaci, Yunus; Kalaci, Aydiner; Savaş, Nazan; Duman, I Gokhan; Yanat, A Nedim
To determine the effectiveness of three different local injection modalities in the treatment of lateral epicondilitis. In a prospective randomized study on lateral epicondilitis, 75 patients were divided into three equal groups A, B and C (n = 25) and were treated using three different method of local injection. The patients in group A were treated with local injection of a steroid (1 mL triamcinolone) combined with local anaesthetic (1 mL lidocaine), those in group B were treated with injection of local anaesthetic (1 mL lidocaine) combined with peppering technique and those in group C with local injection of a steroid (1 mL triamcinolone) combined with local anaesthetic (1 mL lidocaine) and peppering technique. The outcome was defined by measuring the elbow pain during the activity using a 10-cm visual analogue scale (VAS) and satisfaction with the treatment using a scoring system based on the criteria of the Verhaar et al. at 3 weeks and 6 months after the injection and compared with the pre-treatment condition. There were significant (P = 0.006) differences in the successful outcomes between the three groups at 6 months. In group C in which local steroid + peppering injection technique were used; excellent results were obtained in 84% of patients comparing to 36% and 48% for patients in groups A and B, respectively. The successful outcomes were statistically higher in group C comparing to group A (P = 0.002) and group B (P = 0.011). In all groups, there was a significantly lower pain (VAS) at the 3-week and 6-month follow-ups comparing to the pre-treatment condition. VAS measured at 6-month follow-up were significantly lower in group C comparing to other groups (P = 0.002). In the treatment of lateral epicondilitis, combination of corticosteroid injections with peppering is more effective than corticosteroid injections or peppering injections alone and produces better clinical results.
Bertéus Forslund, H; Klingström, S; Hagberg, H; Löndahl, M; Torgerson, J S; Lindroos, A K
To study the effect to recommend no snacks vs three snacks per day on 1-year weight loss. The hypothesis was that it is easier to control energy intake and lose weight if snacks in between meals are omitted. In total 140 patients (36 men, 104 women), aged 18-60 years and body mass index>30 kg/m(2) were randomized and 93 patients (27 men, 66 women) completed the study. A 1-year randomized intervention trial was conducted with two treatment arms with different eating frequencies; 3 meals/day (3M) or 3 meals and 3 snacks/day (3+3M). The patients received regular and individualized counseling by dieticians. Information on eating patterns, dietary intake, weight and metabolic variables was collected at baseline and after 1 year. Over 1 year the 3M group reported a decrease in the number of snacks whereas the 3+3M group reported an increase (-1.1 vs +0.4 snacks/day, respectively, Ptreatment (3M vs 3+3M=-4.1+/-6.1 vs -5.9+/-9.4 kg; P=0.31). Changes in metabolic variables did not differ between the groups, except for high-density lipoprotein that increased in the 3M group but not in 3+3M group (Psnacks or not between meals does not influence 1-year weight loss.
Jónsson, Hjalti; Arendt, Kristian Bech; Jørgensen, Lisbeth
disorders aged between 7 - 14 are expected to be included, equally divided between Psychiatric clinics (n = 48) and School Counselling services (n =48). The treatment consists of 10 2-hour group sessions with 5-6 children and their parents. Results are measured by independent diagnostic interviews......Background: The efficacy of a group cognitive behavioural therapy program (Cool Kids) of childhood anxiety has been demonstrated in a university-clinic setting in Australia (Hudson et al., 2009) and findings from a randomized controlled trial (RCT) at a University-clinic supports its efficacy...... in Denmark (Arendt & Thastum, 2013). Objective: To evaluate the outcomes of evidence based, manualized group cognitive-behavioural treatment (CBT) for children and adolescent with anxiety disorders, when delivered in an outpatient Child and Adolescent Psychiatry or in a community based School Counselling...
Auinger, Peggy; Durbin, Mary; Feldon, Steven; Garvin, Mona; Kardon, Randy; Keltner, John; Kupersmith, Mark J; Sibony, Patrick; Plumb, Kim; Wang, Jui-Kai; Werner, John S
The accepted method to evaluate and monitor papilledema, Frisén grading, uses an ordinal approach based on descriptive features. Part I showed that spectral-domain optical coherence tomography (SD-OCT) in a clinical trial setting provides reliable measurement of the effects of papilledema on the optic nerve head (ONH) and peripapillary retina, particularly if a 3-D segmentation method is used for analysis.(1) We evaluated how OCT parameters are interrelated and how they correlate with vision and other clinical features in idiopathic intracranial hypertension (IIH) patients. A total of 126 subjects in the IIH Treatment Trial (IIHTT) OCT substudy had Cirrus SD-OCT optic disc and macula scans analyzed by using a 3-D segmentation algorithm to derive retinal nerve fiber layer (RNFL) thickness, total retinal thickness (TRT), retinal ganglion cell layer plus inner plexiform layer (GCL+IPL) thickness, and ONH volume. The SD-OCT parameter values were correlated with high- and low-contrast acuity, perimetric mean deviation, Frisén grading, and IIH features. At study entry, the average RNFL thickness, TRT, and ONH volume showed significant strong correlations (r ≥ 0.90) with each other. The same OCT parameters showed a strong (r > 0.76) correlation with Frisén grade and a mild (r > 0.24), but significant, correlation with lumbar puncture opening pressure. For all eyes at baseline, neither visual acuity (high or low contrast) nor mean deviation correlated with any OCT measure of swelling or GCL+IPL thickness. In newly diagnosed IIH, OCT demonstrated alterations of the peripapillary retina and ONH correlate with Frisén grading of papilledema. At presentation, OCT measures of papilledema, in patients with newly diagnosed IIH and mild vision loss, do not correlate with clinical features or visual dysfunction. (ClinicalTrials.gov number, NCT01003639.). Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Duric Nezla S
Full Text Available Abstract Background A randomized and controlled clinical study was performed to evaluate the use of neurofeedback (NF to treat attention-deficit/hyperactivity disorder (ADHD in children and adolescents. Methods The ADHD population was selected from an outpatient clinic for Child and Adolescent Mental Health in Norway. Ninety-one of the 275 children and adolescents ranging in age from 6 to 18 years (10.5 years participated in 30 sessions of an intensive NF program. The reinforcement contingency was based on the subjects’ production of cortical beta1 activity (15–18 Hz. The ADHD participants were randomized into three groups, with 30 in the NF group, 31 controls in a group that was given methylphenidate, and 30 in a group that received NF and methylphenidate. ADHD core symptoms were reported by parents using the parent form of the Clinician’s Manual for Assessment by Russell A. Barkley. Results Ninety-one children and adolescents were effectively randomized by age, sex, intelligence and distribution of ADHD core symptoms. The parents reported significant effects of the treatments, but no significant differences between the treatment groups were observed. Conclusions NF was as effective as methylphenidate at treating the attentional and hyperactivity symptoms of ADHD, based on parental reports. Trial registration Current Controlled Trials NCT01252446
Hansen, Ditte; Brandi, Lisbet; Rasmussen, Knud
BACKGROUND: Secondary hyperparathyroidism is a common feature in patients with chronic kidney disease. Its serious clinical consequences include renal osteodystrophy, calcific uremic arteriolopathy, and vascular calcifications that increase morbidity and mortality.Reduced synthesis of active...... vitamin D contributes to secondary hyperparathyroidism. Therefore, this condition is managed with activated vitamin D. However, hypercalcemia and hyperphosphatemia limit the use of activated vitamin D.In Denmark alfacalcidol is the primary choice of vitamin D analog.A new vitamin D analog, paricalcitol...... hyperparathyroidism and the tendency towards hyperphosphatemia and hypercalcemia. METHODS/DESIGN: This is an investigator-initiated cross-over study. Nine Danish haemodialysis units will recruit 117 patients with end stage renal failure on maintenance haemodialysis therapy.Patients are randomised into two treatment...
Tania Cursino de Menezes Couceiro
Full Text Available BACKGROUND AND OBJECTIVE: Postoperative pain treatment in mastectomy remains a major challenge despite the multimodal approach. The aim of this study was to investigate the analgesic effect of intravenous lidocaine in patients undergoing mastectomy, as well as the postoperative consumption of opioids. METHODS: After approval by the Human Research Ethics Committee of the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, a randomized, blind, controlled trial was conducted with intravenous lidocaine at a dose of 3 mg/kg infused over 1 h in 45 women undergoing mastectomy under general anesthesia. One patient from placebo group was. RESULTS: Groups were similar in age, body mass index, type of surgery, and postoperative need for opioids. Two of 22 patients in lidocaine group and three of 22 patients in placebo group requested opioid (p = 0.50. Pain on awakening was identified in 4/22 of lidocaine group and 5/22 of placebo group (p = 0.50; in the post-anesthetic recovery room in 14/22 and 12/22 (p = 0.37 of lidocaine and placebo groups, respectively. Pain evaluation 24 h after surgery showed that 2/22 and 3/22 patients (p = 0.50 of lidocaine and placebo groups, respectively, complained of pain. CONCLUSION: Intravenous lidocaine at a dose of 3 mg/kg administered over a period of an hour during mastectomy did not promote additional analgesia compared to placebo in the first 24 h, and has not decreased opioid consumption. However, a beneficial effect of intravenous lidocaine in selected and/or other therapeutic regimens patients cannot be ruled out.
Davidsen, Annika Helgadóttir
English summary The aim of this thesis was twofold. First, I wanted to examine the effect of client feedback on treatment attendance and outcome in group psychotherapy for eating disorders. Second, I wanted to contribute to the relatively scarce body of research on the consequences of an eating...... disorder on functionality. Group psychotherapy of various types is widely used to treat individuals with eating disorders. Dropout is, however, an important problem in the treatment of these patients, and it is therefore important to find ways to increase attendance. One of the means to address...... disorders in group therapy. We conducted a randomized clinical trial and included 159 adult participants, 156 females and 3 males, diagnosed with bulimia nervosa, binge eating disorder, or eating disorder not otherwise specified according to DSM-IV. Eighty participants were allocated to the experimental...
Asthma is a chronic inflammatory airway disease, and its treatment is frequently challenging despite detailed national and international guidelines. While basic anti-inflammatory therapy usually consists of inhaled corticosteroids in doses adapted to the asthma severity, add-on treatment with bronchodilators is essential in more severe asthma. Only recently, the long-acting anticholinergic tiotropium was introduced into the GINA guidelines. This review reports on the studies that have been performed with tiotropium in adult asthmatic patients. Following early proof-of-concept studies, several studies with tiotropium as an add-on therapy to inhaled corticosteroids (ICS), with or without a long-acting beta agonist (LABA), demonstrated convincing clinical benefit for patients. Important lung function parameters and quality of life scores significantly improved shortly after onset of the add-on therapy with tiotropium, and some studies even demonstrated non-inferiority against salmeterol. All studies reported an excellent safety profile of tiotropium. The still growing body of tiotropium studies, both in adults and children, will help to identify the position of tiotropium in future asthma guidelines and might also indicate which patients benefit most from an add-on therapy with tiotropium. © The Author(s), 2016.
Shannon, Harriet; Stocks, Janet; Gregson, Rachael K; Dunne, Catherine; Peters, Mark J; Main, Eleanor
The study investigated treatment outcomes when respiratory physiotherapy was delivered by non-respiratory on-call physiotherapists, compared with specialist respiratory physiotherapists. Prospective, randomised crossover trial. Paediatric, tertiary care hospital in the United Kingdom. Mechanically ventilated children requiring two physiotherapy interventions during a single day were eligible. Twenty two physiotherapists (10 non-respiratory) and 93 patients were recruited. Patients received one treatment from a non-respiratory physiotherapist and another from a respiratory physiotherapist, in a randomised order. Treatments were individualised to the patients' needs, often including re-positioning followed by manual lung inflations, chest wall vibrations and endotracheal suction. The primary outcome was respiratory compliance. Secondary outcomes included adverse physiological events and clinically important respiratory changes (according to an a priori definition). Treatments delivered to 63 patients were analysed. There were significant improvements to respiratory compliance (mean increase [95% confidence intervals], 0.07 and 0.08ml·cmH2O(-1)·kg(-1) [0.01 to 0.14 and 0.04 to 0.13], prespiratory physiotherapists' treatments respectively). Case-by-case, there were fewer clinically important improvements following non-respiratory physiotherapists' treatments compared with the respiratory physiotherapists' (n=27 [43%] versus n=40 [63%], p=0.03). Eleven adverse events occurred, eight following non-respiratory physiotherapists' treatments. Significant disparities exist in treatment outcomes when patients are treated by non-respiratory on-call physiotherapists, compared with specialist respiratory physiotherapists. There is an urgent need for targeted training strategies, or alternative service delivery models, to be explored. This should aim to address the quality of respiratory physiotherapy services, both during and outside of normal working hours. Clinicaltrials
Chan, C. M. C.; Scheinman, J. I.; Roth, K. S.
As the powerful tools of molecular biology continue to delineate new concepts of pathogenesis of diseases, new molecular-level therapeutic modalities are certain to emerge. In order to design and execute clinical trials to evaluate outcomes of these new treatment modalities, we will soon need a new supply of investigators with training and experience in clinical research. The slowly-progressive nature of chronic pediatric kidney disease often results in diagnosis being made at a time remote from initial result, and the inherently slow rate of progression makes changes difficult to measure. Thus, development of molecular markers for both diagnosis and rate of progression will be critical to studies of new therapeutic modalities. We will review general aspects of clinical trials and will use current and past studies as examples to illustrate specific points, especially as these apply to chronic kidney disease associated with obstructive uropathy in children. (author)
Full Text Available Abstract Background Spirulina platensis, a cynobacterium used frequently as a dietary supplement had been found to exhibit many immune-stimulating and antiviral activities. It had been found to activate macrophages, NK cells, T cells, B cells, and to stimulate the production of Interferon gamma (IFN-γ and other cytokines. Natural substances isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells. We aimed to study whether this dietary supplement possesses any therapeutically feasible activity worthy of further larger controlled clinical evaluation. Methods Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been randomized to either Spirulina or Silymarin treated groups for a period of six months treatment. The two groups were followed up and blindly compared for early (after 3 months and end of 6 months treatment virological response. The effects of both treatments on each of alanine aminotransferase (ALT, Chronic Liver Disease Questionnaire scores (CLDQ, Arizona Sexual Experience Scale scores (ASEX and the occurrence of any attributable adverse events were also compared. Results Among the 30 patients who had been treated with Spirulina and completed the 6 months protocol, 4 patients (13.3% had a complete end of treatment virological response and 2 patients (6.7% had a partial end of treatment response defined as significant decrease of virus load of at least 2-logs10. Though the proportion of responders in Spirulina group was greater than in the Silymarin group, the difference was not statistically significant at the end of both 6 months (p = 0.12 and 3 months treatment (p = 0.22 by Exact test. Alanine aminotransferase as well as CLDQ and ASEX scores were found to be more significantly improved in Spirulina than in Silymarin treated group
Hersh, Peter S; Stulting, R Doyle; Muller, David; Durrie, Daniel S; Rajpal, Rajesh K
To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) for the treatment of corneal ectasia after laser refractive surgery. Prospective, randomized, multicenter, controlled clinical trial. One hundred seventy-nine subjects with corneal ectasia after previous refractive surgery. The treatment group underwent standard CXL, and the sham control group received riboflavin alone without removal of the epithelium. The primary efficacy criterion was the change over 1 year of topography-derived maximum keratometry (K), comparing treatment with control groups. Secondary outcomes evaluated were corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent, endothelial cell count, and adverse events. In the crosslinking treatment group, the maximum K value decreased by 0.7 diopters (D) from baseline to 1 year, whereas there was continued progression in the control group (1.3 D difference between treatment and control, P Corneal haze was the most frequently reported crosslinking-related adverse finding. Corneal collagen crosslinking was effective in improving the maximum K value, CDVA, and UDVA in eyes with corneal ectasia 1 year after treatment, with an excellent safety profile. CXL is the first approved procedure to diminish progression of this ectatic corneal process. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Lopes, Rubia Garcia; da Mota, Ana Carolina Costa; Soares, Carolina; Tarzia, Olinda; Deana, Alessandro Melo; Prates, Renato Araújo; França, Cristiane Miranda; Fernandes, Kristianne Porta Santos; Ferrari, Raquel Agnelli Mesquita; Bussadori, Sandra Kalil
Light with or without chemical agents has been used to induce therapeutic and antimicrobial effects. With photodynamic therapy, the antimicrobial effect is confined to areas covered by a photosensitive dye and irradiated with light. The aim of the present study was to evaluate the effect of photodynamic therapy for the treatment of halitosis in adolescents through the analysis of volatile sulfur compounds, especially sulfide. A controlled, clinical trial was conducted with 45 adolescents randomly allocated to three groups: group 1, photodynamic therapy administered to the dorsum of the tongue; group 2, treatment with a tongue scraper; and group 3, treatment with a tongue scraper combined with photodynamic therapy. The diagnosis of halitosis was performed using gas chromatography before and after treatment. Comparisons were made using the Kruskal-Wallis test followed by the Student-Newman-Keuls test, with the level of significance set at 5 % (p photodynamic therapy. The present study describes a novel option for the treatment of halitosis in adolescents with an immediate effect that does not involve the mechanical aggression of the lingual papillae that occurs with conventional treatment. Photodynamic Therapy in Adolescents Halitosis ( https://clinicaltrials.gov/ct2/show/NCT02007993?term=NCT02007993&rank=1 )Number: NCT02007993FUNDING:FAPESPNumber: 2013/13032-8.
Madelon Novato Ribeiro
Full Text Available The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA in the treatment of cutaneous leishmaniasis (CL, in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule; we observed 82.1% (vial return, 86.0% (monitoring card, 66.7% (Morisky test and 86.0% (modified Morisky test adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.
E.J.T. Luiten (Ernest); W.C.J. Hop (Wim); J.F. Lange (Johan); H.A. Bruining (Hajo)
textabstractOBJECTIVE: A randomized, controlled, multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality. SUMMARY BACKGROUND DATA: Secondary pancreatic
Full Text Available Abstract Background Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. Methods A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days. II A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time
Daniel R Feikin
Full Text Available BACKGROUND: Zinc treatment shortens diarrhea episodes and can prevent future episodes. In rural Africa, most children with diarrhea are not brought to health facilities. In a village-randomized trial in rural Kenya, we assessed if zinc treatment might have a community-level preventive effect on diarrhea incidence if available at home versus only at health facilities. METHODS: We randomized 16 Kenyan villages (1,903 eligible children to receive a 10-day course of zinc and two oral rehydration solution (ORS sachets every two months at home and 17 villages (2,241 eligible children to receive ORS at home, but zinc at the health-facility only. Children's caretakers were educated in zinc/ORS use by village workers, both unblinded to intervention arm. We evaluated whether incidence of diarrhea and acute lower respiratory illness (ALRI reported at biweekly home visits and presenting to clinic were lower in zinc villages, using poisson regression adjusting for baseline disease rates, distance to clinic, and children's age. RESULTS: There were no differences between village groups in diarrhea incidence either reported at the home or presenting to clinic. In zinc villages (1,440 children analyzed, 61.2% of diarrheal episodes were treated with zinc, compared to 5.4% in comparison villages (1,584 children analyzed, p<0.0001. There were no differences in ORS use between zinc (59.6% and comparison villages (58.8%. Among children with fever or cough without diarrhea, zinc use was low (<0.5%. There was a lower incidence of reported ALRI in zinc villages (adjusted RR 0.68, 95% CI 0.46-0.99, but not presenting at clinic. CONCLUSIONS: In this study, home zinc use to treat diarrhea did not decrease disease rates in the community. However, with proper training, availability of zinc at home could lead to more episodes of pediatric diarrhea being treated with zinc in parts of rural Africa where healthcare utilization is low. TRIAL REGISTRATION: ClinicalTrials.gov NCT
Lee, Gun Woo; Lee, Sun-Mi; Ahn, Myun-Whan; Kim, Ho-Joong; Yeom, Jin S
complications was significantly higher in the surgery group (31%) than the traditional care group (20%) (p=.02). Conservative treatment for young patients with spondylolysis may produce similar clinical outcomes and fewer complications over 12-month follow-up than surgical treatment with DR. Copyright © 2015 Elsevier Inc. All rights reserved.
Barbosa-Leiker, Celestina; McPherson, Sterling; Mamey, Mary Rose; Burns, G Leonard; Layton, Matthew E; Roll, John; Ling, Walter
The Clinical Opiate Withdrawal Scale (COWS) is used to assess withdrawal in clinical trials and practice. The aims of this study were to examine the inter-item correlations and factor structure of the COWS in opioid-dependent men and women. This is a secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network 0003, a randomized clinical trial that compared buprenorphine/naloxone tapering strategies. The trial included 11 sites in 10 US cities. Participants were opioid-dependent individuals (n=516) that had data on the COWS. The COWS at study baseline was analyzed in this study. Inter-item correlations showed weak to moderate relationships among the items. A 1-factor model did not fit the data for men (comparative fit index (CFI)=.801, root mean square error of approximation (RMSEA)=.073, weighted root mean square residual (WRMR)=1.132) or women (CFI=.694, RMSEA=.071, WRMR=.933), where resting pulse rate was not related to withdrawal for men, and yawning and gooseflesh skin was not related to withdrawal for women. A reduced model comprised of only the 8 items that were significantly related to the construct of withdrawal in both men and women, and an exploratory 2-factor model, were also assessed but not retained due to inconsistencies across gender. When traditional psychometric models are applied to the COWS, it appears that the scale may not relate to a single underlying construct of withdrawal. Further research testing the hypothesized factor structure in other opioid-dependent samples is needed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Fekadu, Abebaw; Teferra, Solomon; Hailu, Asrat; Gebre-Mariam, Tsige; Addissie, Adamu; Deressa, Wakgari; Yimer, Getnet; Reja, Ahmed
Low income countries like Ethiopia are underrepresented in clinical research. As a major public commitment to clinical research, Ethiopia celebrated the International Clinical Trial Day (ICTD) for the first time on 20 May 2014 under the auspices of Addis Ababa University. The motto for the day was 'Clinical Trials for Excellence in Patient Care'. The celebration offered an opportunity to inform academic staff, researchers, students and the leadership about clinical trials being conducted and to discuss the future of clinical trials in the country. Although clear challenges to the conduct of trials abound, clinical trials registered from Ethiopia in trial registration databases is increasing. Cross-country collaborations, international funding support, motivation of academic staff to conduct clinical trials and the commitment and engagement of the leadership in research are all improving. The overall impact of clinical trials is also encouraging. For example, some of the trials conducted in Ethiopia have informed treatment guidelines. However, administrative capacity, research infrastructure as well as financial support remain weak. There is a need for enhanced university-industry linkage and translation of research findings into locally relevant evidence. Ethiopia, as well as the whole of Africa, has an unparalleled opportunity to lead the way in clinical trials, given its prospect of development and the need to have locally relevant evidence for its growing population. In this commentary we reflect on the celebration of ICTD, the status and opportunities for conducting clinical trials and the way forward for facilitating clinical trials in Ethiopia and Africa.
Full Text Available SN Hashemi1, HR Ghafarian Shirazi2,3, A Mohamadi4, GH Zadeh-Bagheri5, KH Noorian5, M Malekzadeh21Department of Psychiatry, Faculty of Medicine, 2Research Center of Social Factors Affecting Health, Yasuj University of Medical Sciences, Yasuj, 3School of Public Health, Tehran University of Medical Sciences, Tehran, 4Department of Psychiatry, 5School of Medicine, Yasuj University of Medical Sciences, Yasuj, IranBackground: Depression is a common psychiatric disorder worldwide, including in Iran, and is estimated to affect 10%–15% of the population. Antidepressant drugs can have multiple side effects, so a good choice of drug is important for successful treatment. This study compared the efficacy of nortriptyline with that of fluoxetine in the treatment of patients with major depressive disorder and assessed related factors, including age, gender, and level of education.Methods: The study was a double-blind, randomized clinical trial with a six-month follow-up period. Participants were 120 patients aged 15–60 years with a diagnosis of major depressive disorder based on a psychiatry interview and the Beck depression rating scale, which were performed at the beginning, middle, and end of the study. The patients were treated with nortriptyline or fluoxetine. The paired t-test, independent t-test, and the k chi-square test were used to analyze the data.Results: Twenty-three patients dropped out and 97 remained in the trial. Before intervention, the mean depression score was 32.85 ± 6.23 in the nortriptyline group and 33.12 ± 6.50 in the fluoxetine group. The results of the independent t-test showed a significant difference between depression score means before and after treatment in both groups. Changes at the end of the trial compared with baseline scores were 13.4 ± 4.68 and 16.96 ± 4.96 for nortriptyline and fluoxetine, respectively. Paired t-testing showed a significant difference in the mean depression score for both the nortriptyline and
Ragab, A; Shreef, E; Behiry, E; Zalat, S; Noaman, M
To investigate the safety and efficacy of ozone therapy in adult patients with sudden sensorineural hearing loss. Prospective, randomised, double-blinded, placebo-controlled, parallel group, clinical trial. Forty-five adult patients presented with sudden sensorineural hearing loss, and were randomly allocated to receive either placebo (15 patients) or ozone therapy (auto-haemotherapy; 30 patients). For the latter treatment, 100 ml of the patient's blood was treated immediately with a 1:1 volume, gaseous mixture of oxygen and ozone (from an ozone generator) and re-injected into the patient by intravenous infusion. Treatments were administered twice weekly for 10 sessions. The following data were recorded: pre- and post-treatment mean hearing gains; air and bone pure tone averages; speech reception thresholds; speech discrimination scores; and subjective recovery rates. Significant recovery was observed in 23 patients (77 per cent) receiving ozone treatment, compared with six (40 per cent) patients receiving placebo (p ozone-treated patients compared with placebo-treated patients (p Ozone therapy is a significant modality for treatment of sudden sensorineural hearing loss; no complications were observed.
Salwen, Jessica K; Smith, Michael T; Finan, Patrick H
To determine the relative influence of sleep continuity (sleep efficiency, sleep onset latency, total sleep time [TST], and wake after sleep onset) on clinical pain outcomes within a trial of cognitive behavioral therapy for insomnia (CBT-I) for patients with comorbid knee osteoarthritis and insomnia. Secondary analyses were performed on data from 74 patients with comorbid insomnia and knee osteoarthritis who completed a randomized clinical trial of 8-session multicomponent CBT-I versus an active behavioral desensitization control condition (BD), including a 6-month follow-up assessment. Data used herein include daily diaries of sleep parameters, actigraphy data, and self-report questionnaires administered at specific time points. Patients who reported at least 30% improvement in self-reported pain from baseline to 6-month follow-up were considered responders (N = 31). Pain responders and nonresponders did not differ significantly at baseline across any sleep continuity measures. At mid-treatment, only TST predicted pain response via t tests and logistic regression, whereas other measures of sleep continuity were nonsignificant. Recursive partitioning analyses identified a minimum cut-point of 382 min of TST achieved at mid-treatment in order to best predict pain improvements 6-month posttreatment. Actigraphy results followed the same pattern as daily diary-based results. Clinically significant pain reductions in response to both CBT-I and BD were optimally predicted by achieving approximately 6.5 hr sleep duration by mid-treatment. Thus, tailoring interventions to increase TST early in treatment may be an effective strategy to promote long-term pain reductions. More comprehensive research on components of behavioral sleep medicine treatments that contribute to pain response is warranted. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail firstname.lastname@example.org.
Allen, Richard P; Adler, Charles H; Du, Wei; Butcher, Angelia; Bregman, David B; Earley, Christopher J
Intravenous (IV) iron has been used as a treatment to reduce Restless Legs Syndrome (RLS) symptoms, but two double-blinded trials of a frequently prescribed IV iron formulation, iron sucrose, failed to show lasting efficacy. This study evaluates efficacy and safety of a new IV iron formulation (ferric carboxymaltose, FCM) with molecular properties that may make iron more available for uptake to the brain than iron sucrose does. In this 28-day, multi-centre, randomised, placebo-controlled trial 46 RLS patients were discontinued from all RLS treatment. Twenty-four received 500 mg FCM in two doses 5 days apart and 22 received a matching placebo. At day 28, those on placebo were given a single 1000 mg IV FCM and those not responding to initial treatment were given a third dose of 500 mg FCM. Patients were followed up for 24 weeks or until needing added RLS treatment. FCM significantly improved primary and secondary outcomes compared to placebo: International Restless Legs Syndrome study group severity scale (IRLS) average (SD) decrease of 8.9 (8.52) versus 4.0 (6.11), p=0.040; Clinical Global Inventory of Change (CGI-1) very much or much improved 48.3% versus 14.3%, p=0.004. Quality of life was also significantly improved. Of the 24 with initial iron treatment 45% responded and 29% remitted (IRLS ≤ 10) at day 28, and 25% continued free of other RLS medications at 24 weeks after treatment. The single 1000 mg dose on day 28 produced the same degree of treatment response as the divided dose, but the added 500 mg dose for those not responding to the initial treatment showed little benefit. There were no significant adverse events. IV FCM provided a safe and effective treatment for RLS that lasted for at least 24 weeks for some patients. Larger studies are needed to confirm these results. Copyright © 2011 Elsevier B.V. All rights reserved.
Shaffer, H J; LaSalvia, T A; Stein, J P
As more methadone treatment programs are funded in an attempt to curb substance abuse and HIV infection among i.v. drug users, more cost effective treatment approaches are being sought. To investigate whether clients in outpatient methadone maintenance treatment who practice weekly Hatha yoga in a group setting experience more favorable treatment outcomes than those who receive conventional group psychodynamic therapy. After a 5-day assessment period, 61 patients were randomly assigned to methadone maintenance enhanced by traditional group psychotherapy (ie, conventional methadone treatment) or an alternative Hatha yoga therapy (ie, alternative methadone treatment). Patients were followed for 6 months and evaluated on a variety of psychological, sociological, and biological measures. The revised Symptom Check List provided the primary psychological measures; the Addiction Severity Index provided various indices of addictive behaviors. The evidence revealed that there were no meaningful differences between traditional psychodynamic group therapy and Hatha yoga presented in a group setting. Both treatments contributed to a treatment regimen that significantly reduced drug use and criminal activities. Psychopathology at admission was significantly related to program participation regardless of treatment group. In addition to examining the characteristics of patients who present for treatment, this study identifies unexpected staff issues that complicate the integration of alternative and traditional treatment strategies. Alternative methadone treatment is not more effective than conventional methadone treatment, as originally hypothesized. However, some patients may benefit more from alternative methadone treatment than conventional methadone treatment. Additional research is necessary to determine characteristics that identify patients who might benefit from alternative methadone treatment.
Shepshelovich, Daniel; Yelin, Dana; Gafter-Gvili, Anat; Goldman, Shira; Avni, Tomer; Yahav, Dafna
Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy. We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until 5/2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after July 1 st 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a pre-requisite for considering a trial for publication. Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (IQR 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65) , respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals. We found lower inconsistency rate of outcome reporting compared to other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
DiBiase, Andrew T; Woodhouse, Neil R; Papageorgiou, Spyridon N; Johnson, Nicola; Slipper, Carmel; Grant, James; Alsaleh, Maryam; Khaja, Yousef; Cobourne, Martyn T
A multicenter parallel 3-arm randomized clinical trial was carried out in 3 university hospitals in the United Kingdom to investigate the effect of supplemental vibratory force on space closure and treatment outcome with fixed appliances. Eighty-one subjects less than 20 years of age with mandibular incisor irregularity undergoing extraction-based fixed appliance treatment were randomly allocated to supplementary (20 minutes/day) use of an intraoral vibrational device (AcceleDent; OrthoAccel Technologies, Houston, Tex) (n = 29), an identical nonfunctional (sham) device (n = 25), or fixed-appliance only (n = 27). Space closure in the mandibular arch was measured from dental study casts taken at the start of space closure, at the next appointment, and at completion of space closure. Final records were taken at completion of treatment. Data were analyzed blindly on a per-protocol basis with descriptive statistics, 1-way analysis of variance, and linear regression modeling with 95% confidence intervals. Sixty-one subjects remained in the trial at start of space closure, with all 3 groups comparable for baseline characteristics. The overall median rate of initial mandibular arch space closure (primary outcome) was 0.89 mm per month with no difference for either the AcceleDent group (difference, -0.09 mm/month; 95% CI, -0.39 to 0.22 mm/month; P = 0.57) or the sham group (difference, -0.02 mm/month; 95% CI, -0.32 to 0.29 mm/month; P = 0.91) compared with the fixed only group. Similarly, no significant differences were identified between groups for secondary outcomes, including overall treatment duration (median, 18.6 months; P >0.05), number of visits (median, 12; P >0.05), and percentage of improvement in the Peer Assessment Rating (median, 90.0%; P >0.05). Supplemental vibratory force during orthodontic treatment with fixed appliances does not affect space closure, treatment duration, total number of visits, or final occlusal outcome. NCT02314975
Wyles, David; Dvory-Sobol, Hadas; Svarovskaia, Evguenia S; Doehle, Brian P; Martin, Ross; Afdhal, Nezam H; Kowdley, Kris V; Lawitz, Eric; Brainard, Diana M; Miller, Michael D; Mo, Hongmei; Gane, Edward J
Ledipasvir/sofosbuvir combination treatment in phase III clinical trials resulted in sustained viral suppression in 94-99% of patients. This study characterized drug resistance in treatment failures, which may help to inform retreatment options. We performed NS5A and NS5B deep sequencing of hepatitis C virus (HCV) from patients infected with genotype (GT) 1 who participated in ledipasvir/sofosbuvir phase II and III clinical trials. Fifty-one of 2144 (2.4%) (42 GT1a and 9 GT1b) treated patients met the criteria for resistance analysis due to virologic failure following the end of treatment. The majority of patients with virologic failure (38 of 51; 74.5%) had detectable ledipasvir-specific resistance-associated substitutions (RASs) at the time of virologic failure (1% deep sequencing cut-off). The percent of patients with NS5A RASs at virologic failure were 37.5%, 66.7%, 94.7% and 100% in patients treated for 6, 8, 12 and 24weeks, respectively. The common substitutions detected at failure were Q30R/H, and/or Y93H/N in GT1a and Y93H in GT1b. At failure, 35.3% (18/51) of virologic failure patients' viruses had two or more NS5A RASs and the majority of patients harbored NS5A RASs conferring a 100-1000-fold (n=10) or >1000-fold (n=23) reduced susceptibility to ledipasvir. One patient in a phase II study with a known ledipasvir RAS at baseline (L31M) developed the S282T sofosbuvir (NS5B) RAS at failure. In GT1 HCV-infected patients treated with ledipasvir/sofosbuvir±ribavirin, virologic failure was rare. Ledipasvir resistance in NS5A was selected or enhanced in most patients with virologic failure, one of whom also developed resistance to sofosbuvir. Clinical studies have shown that combination treatment with ledipasvir/sofosbuvir efficiently cures most patients with genotype 1 hepatitis C infection. For the few patients failing treatment, we show that resistance to ledipasvir was observed in most patients, whereas resistance to sofosbuvir was less common. This has
We sought to determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A. DESIGN: Randomized, controlled, double-masked trial of 225 nonsmoking patients, aged 18 to 60 years, evaluated over a 4-year interval. Patients received ...
Le Grange, Daniel; Lock, James; Agras, W Stewart; Bryson, Susan W; Jo, Booil
There is a paucity of randomized clinical trials (RCTs) for adolescents with bulimia nervosa (BN). Prior studies suggest cognitive-behavioral therapy adapted for adolescents (CBT-A) and family-based treatment for adolescent bulimia nervosa (FBT-BN) could be effective for this patient population. The objective of this study was to compare the relative efficacy of these 2 specific therapies, FBT-BN and CBT-A. In addition, a smaller participant group was randomized to a nonspecific treatment (supportive psychotherapy [SPT]), whose data were to be used if there were no differences between FBT-BN and CBT-A at end of treatment. This 2-site (Chicago and Stanford) randomized controlled trial included 130 participants (aged 12-18 years) meeting DSM-IV criteria for BN or partial BN (binge eating and purging once or more per week for 6 months). Outcomes were assessed at baseline, end of treatment, and 6 and 12 months posttreatment. Treatments involved 18 outpatient sessions over 6 months. The primary outcome was defined as abstinence from binge eating and purging for 4 weeks before assessment, using the Eating Disorder Examination. Participants in FBT-BN achieved higher abstinence rates than in CBT-A at end of treatment (39% versus 20%; p = .040, number needed to treat [NNT] = 5) and at 6-month follow-up (44% versus 25%; p = .030, NNT = 5). Abstinence rates between these 2 groups did not differ statistically at 12-month follow-up (49% versus 32%; p = .130, NNT = 6). In this study, FBT-BN was more effective in promoting abstinence from binge eating and purging than CBT-A in adolescent BN at end of treatment and 6-month follow-up. By 12-month follow-up, there were no statistically significant differences between the 2 treatments. Study of Treatment for Adolescents With Bulimia Nervosa; http://clinicaltrials.gov/; NCT00879151. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
Full Text Available TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD, but its efficacy and safety in humans has not been evaluated.In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109. Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58. TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died.Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls.Pan African Clinical Trials Registry PACTR201501000997429.
Dunning, Jake; Sahr, Foday; Rojek, Amanda; Gannon, Fiona; Carson, Gail; Idriss, Baimba; Massaquoi, Thomas; Gandi, Regina; Joseph, Sebatu; Osman, Hassan K; Brooks, Timothy J G; Simpson, Andrew J H; Goodfellow, Ian; Thorne, Lucy; Arias, Armando; Merson, Laura; Castle, Lyndsey; Howell-Jones, Rebecca; Pardinaz-Solis, Raul; Hope-Gill, Benjamin; Ferri, Mauricio; Grove, Jennifer; Kowalski, Mark; Stepniewska, Kasia; Lang, Trudie; Whitehead, John; Olliaro, Piero; Samai, Mohammed; Horby, Peter W
TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Pan African Clinical Trials Registry PACTR201501000997429.
Agarwal, Mohit; Meena, Balram; Gupta, D K; Tiwari, Anjali Dave; Jakhar, Sunil Kumar
To compare the efficacy of the 3D miniplates to standard miniplates in the osteosynthesis of mandibular symphysis and parasymphysis fractures on the basis of clinical parameters and radiographic evaluation. A prospective randomized clinical trial was conducted to treat consecutive mandibular symphysis and parasymphysis fractures. The patients were randomly divided into 2 groups. The patients underwent osteosynthesis in group A with 3D titanium miniplates and in group B with conventional titanium miniplates. The cause of trauma, the number of days from injury to surgery, average age and gender were all reviewed. The assessment of the patients was done at 1, 3, and 6 weeks and 3 months using the clinical parameters and radiographic evaluation. Eighty patients with isolated symphysis or parasymphysis fracture met the inclusion criteria. In our study, a statistically significant difference was not found in the clinical parameters such as pain, swelling, infection, paresthesia, hardware failure, and mobility between the fracture segments. Similarly Radiological evaluation did not show any statistically significant difference in reduction between the 2 groups. 3D plates are difficult to adapt and use sometimes, but operative time is less with them in treatment of symphysis and parasymphysis fractures. The use of 3D miniplates for symphysis and parasymphysis fracture fixation was efficacious enough to bear the masticatory load during osteosynthesis of the fracture. Although 3D miniplate system is difficult to adapt and difficult to use in cases of fractures involving the mental nerve, they provide the advantage of less operative time and less implant material in treatment of symphysis and parasymphysis fracture, with clinical results almost similar to those seen with conventional miniplate osteosynthesis.
Yakoot, Mostafa; Salem, Amel
Spirulina platensis, a cynobacterium used frequently as a dietary supplement had been found to exhibit many immune-stimulating and antiviral activities. It had been found to activate macrophages, NK cells, T cells, B cells, and to stimulate the production of Interferon gamma (IFN-γ) and other cytokines. Natural substances isolated from Spirulina platensis had been found to be potent inhibitors against several enveloped viruses by blocking viral absorption/penetration and some replication stages of progeny viruses after penetration into cells. We aimed to study whether this dietary supplement possesses any therapeutically feasible activity worthy of further larger controlled clinical evaluation. Sixty six patients with chronic hepatitis C virus infection and eligible for inclusion had been randomized to either Spirulina or Silymarin treated groups for a period of six months treatment.The two groups were followed up and blindly compared for early (after 3 months) and end of 6 months treatment virological response. The effects of both treatments on each of alanine aminotransferase (ALT), Chronic Liver Disease Questionnaire scores (CLDQ), Arizona Sexual Experience Scale scores (ASEX) and the occurrence of any attributable adverse events were also compared. Among the 30 patients who had been treated with Spirulina and completed the 6 months protocol, 4 patients (13.3%) had a complete end of treatment virological response and 2 patients (6.7%) had a partial end of treatment response defined as significant decrease of virus load of at least 2-logs10. Though the proportion of responders in Spirulina group was greater than in the Silymarin group, the difference was not statistically significant at the end of both 6 months (p = 0.12) and 3 months treatment (p = 0.22) by Exact test. Alanine aminotransferase as well as CLDQ and ASEX scores were found to be more significantly improved in Spirulina than in Silymarin treated group. Our results could suggest a therapeutically
van der Baan-Slootweg, Olga; Benninga, Marc A.; Beelen, Anita; van der Palen, Jacobus Adrianus Maria; Tamminga-Smeulders, Christine; Tijssen, Jan G.P.; van Aalderen, Wim M.C.
Importance Severe childhood obesity has become a major health problem, and effective, evidence-based interventions are needed. The relative effectiveness of inpatient compared with ambulatory treatment remains unknown. Objective To determine whether an inpatient treatment program is more effective
Full Text Available To compare the efficacy of gabapentin and levodopa-c (Levodopa/Carbidopa in reducing restless leg syndrome (RLS symptoms and sleep problems in hemodialysis patients with RLS in a four-week randomized clinical trial. The diagnosis of RLS was made using the criteria of the International Restless Legs Study Group. Each subject completed three questionnaires: IRLS questionnaire, Pittsburgh Sleep Quality Index and Epworth sleepiness scale. After four weeks of washout period for previous treatments for RLS, subjects were randomly assigned to four weeks of gabapentin (200 mg or levodopa-c (110 mg. After four weeks of therapy, the questionnaires administered at the outset of the study were re-administered. Both drugs were found effective for the management of RLS. But, the effect of gabapentin was more significant. Gabapentin significantly improved the IRLS total score (change from baseline to post-treatment ≈-17 compared with levodopa-c (change from baseline to post-treatment ≈-13 (P: 0.016. Regarding sleep parameters, levodopa improved sleep quality, sleep latency and sleep duration (P <0.0001. Gabapentin was also effective with respect to sleep parameters (P <0.0001. Our study shows that gabapentin is a safe effective therapy for RLS among hemodialysis patients. This medication may be considered as an alternative or additive treatment to current therapeutic remedies for hemodialysis patients with RLS.
Full Text Available Introduction: Patients with chronic renal disease (CRD deal with many potential problems with hemodialysis for all their life. Regarding the importance of preventing dialysis adverse effects, which are in close connection with lack of knowledge and report on how to train the patients? This study aims at comparing the impact of two methods of face to face training and training pamphlet on complying and informing of hemodialysis treatments. Methods: This clinical trial study was conducted on 58 hemodialysis patients who visited Shahid Rahnemun Teaching hospital, Yazd, Iran, and had required conditions of the research. Data were collected through a questionnaire including personal-social information, several questions to assess the level of compliance and to inform the treatment method. The quantitative analysis of this study used the Statistical Package for Social Sciences SPSS version 13 and descriptive (frequency, mean, standard deviation and inferential (Chi-square, paired t-test, ANOVA, ANCOVA statistics were employed. Results: The mean scores for informing both groups (face to face and training pamphlet were significantly increased. The mean score for adherence to treatments was also significant.Conclusion: In this research, face to face training was found to be more effective than training pamphlet. It seemed to have more strong effect on increasing the level of information and adherence to treatment. To train these people, face to face training should be, thus, preferred.
Stallard, Nigel; Kunz, Cornelia Ursula; Todd, Susan; Parsons, Nicholas; Friede, Tim
Seamless phase II/III clinical trials in which an experimental treatment is selected at an interim analysis have been the focus of much recent research interest. Many of the methods proposed are based on the group sequential approach. This paper considers designs of this type in which the treatment selection can be based on short-term endpoint information for more patients than have primary endpoint data available. We show that in such a case, the familywise type I error rate may be inflated if previously proposed group sequential methods are used and the treatment selection rule is not specified in advance. A method is proposed to avoid this inflation by considering the treatment selection that maximises the conditional error given the data available at the interim analysis. A simulation study is reported that illustrates the type I error rate inflation and compares the power of the new approach with two other methods: a combination testing approach and a group sequential method that does not use the short-term endpoint data, both of which also strongly control the type I error rate. The new method is also illustrated through application to a study in Alzheimer's disease. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
Rankine-Mullings, Angela E; Little, Courtney R; Reid, Marvin E; Soares, Deanne P; Taylor-Bryan, Carolyn; Knight-Madden, Jennifer M; Stuber, Susan E; Badaloo, Asha V; Aldred, Karen; Wisdom-Phipps, Margaret E; Latham, Teresa; Ware, Russell E
no permanent screen failures. Of the 43 enrolled, 37 participants have initiated study treatment. This trial investigates the effects of hydroxyurea treatment at MTD in children with conditional or abnormal TCD velocities before transfusion therapy and may represent an important advance towards establishing a suitable non-transfusion protocol for stroke prevention in children with SCA. The trial outcomes will have profound significance in developing countries where the disease burden is highest. ClinicalTrials.gov NCT02556099; https://clinicaltrials.gov/ct2/show/NCT02556099 (Archived by WebCite at http://www.webcitation.org/6k1yMAa9G).
Moore R Andrew
Full Text Available Abstract Background Benign prostatic hyperplasia affects older men. This systematic review determined efficacy and adverse effects of finasteride. Review methods PubMed, the Cochrane Library, reference lists of reports, and reviews were searched for randomised, double-blind trials of finasteride in benign prostatic hyperplasia. Outcomes included symptom score, urinary flow rate, prostate volume, discontinuation, and adverse effects. Relative risk and NNT or NNH were calculated for dichotomous data. Sensitivity analyses assessed influences of baseline symptom severity, initial prostate volume, a dominating trial, and previous interventions. Results Three trials had active controls and 19 had placebo. In placebo-controlled trials, 8820 patients received finasteride 5 mg and 5909 placebo over 3–48 months. Over 48 months finasteride produced greater improvements in total symptom score, maximum urinary flow rate, and prostate volume. Significantly more sexual dysfunction, impotence, ejaculation disorder and decreased libido occurred with finasteride at 12 months; the NNH for any sexual dysfunction at 12 months was 14. Significantly fewer men treated with finasteride experienced acute retention or had surgery at 24 or 48 months than with placebo; at 12 months the NNT was 49 (31 to 112 to avoid one acute urinary retention and 31 (21 to 61 to avoid one surgery. Sensitivity analyses showed benefit with finasteride 5 mg to be constant irrespective of the initial prostate volume. Conclusions Information from many patients in studies of high quality showed beneficial effects of finasteride in terms of symptoms, flow rate and prostate volume. More utility would result if patient centred outcomes were reported in dichotomous form.
Full Text Available BACKGROUND: Cutaneous leishmaniasis (CL is a neglected infectious disease and a major health problem in several developing countries. Despite some reasonable explanation for their potential benefits, there is only trace evidence regarding the role of dressings in the treatment of CL. METHODS: This randomized, assessor-blind, controlled, clinical trial was conducted in an endemic area for CL caused by Leishmania major in Iran to assess the efficacy of administration of weekly intralesional meglumine antimoniate (i.l.MA either alone or combined with application of a silver or a non-silver polyester dressing on their lesions for 6 weeks. After screening of 241 patients with CL lesions, 83 eligible patients with 158 lesions were randomly allocated in three arms of the study. Eligibility criteria included parasitologically confirmed CL, age of 12 to 60 years; willingness to participate, duration of lesion<3 months, number of lesions<5, largest ulcer diameter<5 cm. Pregnant or lactating women were excluded. The primary outcome was absolute risk reduction (ARR based on the proportion of complete healing, which was defined as more than 75% reduction in the size of the lesion compared with baseline in each group at the termination of treatment and 1 month later. FINDINGS: ARR (95% Confidence Interval [CI] in i.l.MA versus i.l.MA+non-silver dressing groups was 5.98% (-7.07% to 20.25%, between i.l.MA versus i.l.MA+silver dressing groups was -0.23% (-13.53% to 14.82%, and between i.l.MA+non-silver dressing versus i.l.MA+silver dressing groups was -6.21%(-18.28% to 6.52% after 6 weeks of treatment. ARR (95% CI in i.l.MA versus i.l.MA+non-silver dressing groups was -2.22% (-22.12% to 18.10%, between i.l.MA versus i.l.MA+silver dressing groups was 3.64% (-15.36% to 22.82%, and between i.l.MA+non-silver dressing versus i.l.MA+silver dressing groups was 5.86% (-12.86% to 24.31% 1 month later. CONCLUSION: It could not be demonstrated that the efficacy of i
Holmes, Clarissa S; Chen, Rusan; Mackey, Eleanor; Grey, Margaret; Streisand, Randi
To evaluate the efficacy of two office-based treatments designed to prevent deterioration in glycemic control in young adolescents with type 1 diabetes in a randomized clinical trial. An individualized, more intensive family teamwork Coping skills program was compared with a diabetes Education treatment. A baseline assessment was followed by four brief treatment sessions and immediate posttesting over the course of 1.5 years. Families of 226 early adolescents (ages 11-14) were randomized to receive either individualized coping skills education or diabetes education as adjunctive treatment to quarterly medical appointments. Continued follow-up occurred at 3.5-month intervals for a long-term follow-up of up to 3 years. A post hoc Usual Care group facilitated comparisons of glycemic control. Growth curve analysis showed that both treatment groups successfully prevented deterioration in adolescent disease care and simultaneously improved adolescent and parent quality of life that included indicators of more effective communication and reduced adherence barriers-without a concomitant increase in diabetes-related or general family conflict. However, contrary to expectation, the Education group was more efficacious than the Coping group in improvement of disease adherence and glycemic control over a 3-year follow-up. Low-intensity office-based quarterly treatment can maintain or improve disease care adherence in early adolescence when provided to adolescent/parent dyads. Better outcomes are achieved when treatment goals and techniques match the needs of the targeted population. © 2014 by the American Diabetes Association.
Fabbri, A; Magrini, N; Bianchi, G; Zoli, M; Marchesini, G
The role of oral branched-chain amino acid supplements in the prevention and treatment of chronic hepatic encephalopathy is not yet established, and conflicting opinions are expressed in authoritative textbooks. We aimed to review and pool the published controlled studies by means of meta-analytical techniques. A computerized search of published papers identified nine studies, controlled against placebo, energy, alimentary proteins, or casein. Their quality score was calculated according to the protocol of Chalmers. The value of the portal-systemic encephalopathy index was chosen as main outcome, because of lack of more significant clinical outcomes. To cope with differences in trial design and data presentation, individual data were requested to authors. After 18 months, we received the individual data of only two studies, thus precluding any meta-analysis. Two studies, accounting for over 60% of total enrolled patients, were in favor of branched-chain amino acids. Their quality score was much better than that of the remaining seven negative small studies, carrying a significant risk of type II error. Based on the results of the two largest, long-term studies, the use of oral branched-chain amino acids in the prevention and treatment of chronic encephalopathy may only be proposed for patients with advanced cirrhosis, intolerant to alimentary proteins. Large, multicenter, long-term studies, considering more important clinical outcomes, are needed to provide definite answers to an aged question.
Sauerwein, W.; Hideghety, K.; Rassow, J.; Devries, M.J.; Goetz, C.; Paquis, P.; Grochulla, F.; Wolbers, J.G.; Haselsberger, K.; Turowski, B.; Moss, R.L.; Stecher-Rasmussen, F.; Touw, D.; Wiestler, O.D.; Frankhauser, H.; Gabel, D.
Based on the pre-clinical work of the European Collaboration on Boron Neutron Capture Therapy a study protocol was prepared in 1995 to initiate Boron Neutron Capture Therapy (BNCT) in patients at the High Flux Reactor (HFR) in Petten. Bio-distribution and pharmacokinetics data of the boron drug Na 2 B 12 H 11 SH (BSH) as well as the radiobiological effects of BNCT with BSH in healthy brain tissue of dogs were considered in designing the strategy for this clinical Phase I trial. The primary goal of the radiation dose escalation study is the investigation of possible adverse events due to BNCT; i.e. to establish the dose limiting toxicity and the maximal tolerated dose. The treatment is delivered in 4 fractions at a defined average boron concentration in blood. Cohorts of 10 patients are treated per dose group. The starting dose was set at 80% of the dose at which neurological symptoms occurred in preclinical dog experiments following a single fraction. After an observation period of at least 6 months, the dose is increased by 10% for the next cohort if less then three severe side effects related to the treatment occurred. The results of the first cohort are presented here. The evaluated dose level can be considered safe. (author)
Conclusions: Adjusting only for clinical variables led to substantial precision gains (at least 5% in three of the four data sets, with a 1% precision loss in the remaining data set. These gains were unchanged or increased when sample sizes were doubled in our simulations. The precision gains due to incorporating genomic information, beyond the gains from adjusting for clinical variables, were not substantial.
Arnold, Lesley M; Emir, Birol; Pauer, Lynne; Resnick, Malca; Clair, Andrew
To determine the time to immediate and sustained clinical improvement in pain and sleep quality with pregabalin in patients with fibromyalgia. A post hoc analysis of four 8- to 14-week phase 2-3, placebo-controlled trials of fixed-dose pregabalin (150-600 mg/day) for fibromyalgia, comprising 12 pregabalin and four placebo treatment arms. A total of 2,747 patients with fibromyalgia, aged 18-82 years. Pain and sleep quality scores, recorded daily on 11-point numeric rating scales (NRSs), were analyzed to determine time to immediate improvement with pregabalin, defined as the first of ≥2 consecutive days when the mean NRS score was significantly lower for pregabalin vs placebo in those treatment arms with a significant improvement at endpoint, and time to sustained clinical improvement with pregabalin, defined as a ≥1-point reduction of the baseline NRS score of patient responders who had a ≥30% improvement on the pain NRS, sleep NRS, or Fibromyalgia Impact Questionnaire (FIQ) from baseline to endpoint, or who reported "much improved" or "very much improved" on the Patient Global Impression of Change (PGIC) at endpoint. Significant improvements in pain and sleep quality scores at endpoint vs placebo were seen in 8/12 and 11/12 pregabalin treatment arms, respectively (P pain or sleep occurred by day 1 or 2. Time to sustained clinical improvement occurred significantly earlier in pain, sleep, PGIC, and FIQ responders (P pain and sleep quality occurred faster with pregabalin vs placebo. Wiley Periodicals, Inc.
Watkins, Katherine E.; Cuellar, Alison E.; Hepner, Kimberly A.; Hunter, Sarah B.; Paddock, Susan M.; Ewing, Brett A.; de la Cruz, Erin
The authors aimed to determine the economic value of providing on-site group cognitive behavioral therapy (CBT) for depression to clients receiving residential substance use disorder (SUD) treatment. Using a quasi-experimental design and an intention-to-treat analysis, the incremental cost-effectiveness and cost-utility ratio of the intervention were estimated relative to usual care residential treatment. The average cost of a treatment episode was $908, compared to $180 for usual care. The i...
Fuchs, Joerg; Dantonello, Tobias M; Blumenstock, Gunnar; Kosztyla, Daniel; Klingebiel, Thomas; Leuschner, Ivo; Schuck, Andreas; Niggli, Felix K; Koscielniak, Ewa; Seitz, Guido
To analyze the clinical course, treatment, complications, outcome, and quality of life (QOL) in patients with perineal/perianal rhabdomyosarcoma (PRMS) treated within the CWS-86, -91, -96, and -2002P trials. Although multiple international study trials exist for the treatment of rhabdomyosarcoma, only very limited information is given on treatment, outcome, and QOL in PRMS. A total of 35 patients suffering from PRMS were treated with neoadjuvant chemotherapy. Local therapy with radiation and/or surgery was performed, followed by adjuvant chemotherapy. Functional long-term follow-up was evaluated by a gastrointestinal/QOL survey. Thirty-two patients were evaluated (exclusion n = 3). Eight patients had embryonal histology, and 24 patients had alveolar histology. The median age was 108 months (median follow-up: 5.8 years). The 5-year overall survival was 47% (95% confidence interval: 29-64). Sixteen IRS (Intergroup Rhabdomyosarcoma Study) III and IV patients had locoregional lymph node involvement at diagnosis. Seven patients were treated with chemotherapy/surgery alone [5-year event-free survival (EFS): 85.7%]. Eleven patients received only radiochemotherapy (5-year EFS: 27.3%). Combined radiochemotherapy/surgery was used in 12 patients (5-year EFS: 63.6%). Two patients were treated only with chemotherapy and they died. Patients with embryonal histology had a significantly better 5-year EFS (87.5%) than patients with alveolar histology (39.1%; P = 0.013). Some patients reported symptoms of fecal incontinence. The median Wexner fecal incontinence score was 9 (possible range: 0-20), and the median QOL score was 90.5 (applicable range: 0-144). The outcome of these patients remains unsatisfactory. Prognostic factors for a favorable outcome are tumor size of smaller than 5 cm, negative locoregional lymph nodes, age less than 10 years, low IRS group, and embryonal histology. Fecal incontinence seems to be a problem.
Di Giulio, Paola; Campagna, Sara; Dimonte, Valerio
Clinical trials are pivotal for the development of nursing knowledge. To describe the clinical trials published in nursing journals in the last two years and propose some general reflections on nursing research. A search with the key-word trial was done on PubMed (2009-2013) on Cancer Nursing, European Journal of Oncology Nursing, International Journal of Nursing Studies, Journal of Advanced Nursing, Journal of Clinical Nursing and Nursing Research. Of 228 trials identified, 104 (45.8%) were published in the last 2 years. Nurses from Asian countries published the larger number of trials. Educational and supportive interventions were the most studied (61/104 trials), followed by clinical interventions (33/104). Samples were limited and most trials are monocentric. A growing number of trials is published, on issues relevant for the nursing profession, however larger samples and multicentric studies would be necessary.
Full Text Available Introduction: In this research, researchers want to study the effectiveness of Olanzapine on reduction of substance abuse relapse among people who are dependent to opioid material, merely. Method: A randomized clinical trial was designed. The population was opioid dependence subjects (only men that were diagnosed based on DSM-IV TR criteria, and referred to national center of addiction studies clinic. Detoxification was done by using of Clonidine, Clonazepam, Disiklomin, and NSAIDS within7 through 10 days. In second stage, the Patients who were referred to the clinic those men who had satisfied criterions selected. Demographic forms, testimonial certificate, Addiction Severity Index, Beck Depression Questionnaire, Zung Self report anxiety test administered among selected sample. Sample divided to two groups (placebo and Olanzapine the research last for 8 weeks. Results: the results showed that addiction severity reduced in both groups, but there was not significant difference in reduction of addiction severity between two groups. There was significant difference in depression and anxiety among mean scores of base line and follow up in both groups but there was not significant difference between two groups in follow up measures. Conclusion: Altogether, the results did not confirm the effectiveness of Olanzapine on maintenance treatment of opioid dependence.
Feder, Adriana; Parides, Michael K.; Murrough, James W.; Perez, Andrew M.; Morgan, Julia E.; Saxena, Shireen; Kirkwood, Katherine; Aan Het Rot, Marije; Lapidus, Kyle A.B.; Wan, Le-Ben; Iosifescu, Dan; Charney, Dennis S.
IMPORTANCE Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. OBJECTIVE To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and
Harris, David M.; Nicholson, Dawn M.; McCarthy, Delwin; Yukna, Raymond A.; Reynolds, Mark A.; Greenwell, Henry; Finley, James; McCawley, Thomas K.; Xenoudi, Pinelopi; Gregg, Robert H.
Data are presented from a multi-center, prospective, longitudinal, clinical trial comparing four different treatments for periodontitis, (1) the LANAPTM protocol utilizing a FR pulsed-Nd:YAG laser; (2) flap surgery using the Modified Widman technique (MWF); (3) traditional scaling and root planing (SRP); and (4) coronal debridement (CD). Each treatment was randomized to a different quadrant. Fifty-one (54) subjects were recruited at five centers that included both private practice and university-based investigators. At 6-months and 12 months post-treatment the LANAPTM protocol and MWF yielded equivalent results based on changes in probing depths. The major difference observed between the two procedures was that patients reported significantly greater comfort following the LANAP™ procedure than following the MWF (P<0.001). There was greater reduction in bleeding in the LANAPTM quadrant than in the other three at both 6 and 12 months. Improvements following SRP were better than expected at 6 months and continued to improve, providing outcomes that were equivalent to both LANAPTM and MWF at 12 months. The improvement in the SRP quadrants suggests the hypothesis that an aspect of the LANAPTM protocol generated a significant, positive and unanticipated systemic (or trans-oral) effect on sub-gingival wound healing.
Cook, Andrea J; Wellman, Robert D; Cherkin, Daniel C; Kahn, Janet R; Sherman, Karen J
This is the first study to systematically evaluate the value of a longer treatment period for massage. We provide a framework of how to conceptualize an optimal dose in this challenging setting of nonpharmacologic treatments. The aim was to determine the optimal dose of massage for neck pain. Two-phase randomized trial for persons with chronic nonspecific neck pain. Primary randomization to one of five groups receiving 4 weeks of massage (30 minutes 2x/or 3x/wk or 60 minutes 1x, 2x, or 3x/wk). Booster randomization of participants to receive an additional six massages, 60 minutes 1x/wk, or no additional massage. A total of 179 participants from Group Health and the general population of Seattle, WA, USA recruited between June 2010 and August 2011 were included. Primary outcomes self-reported neck-related dysfunction (Neck Disability Index) and pain (0-10 scale) were assessed at baseline, 12, and 26 weeks. Clinically meaningful improvement was defined as greater than or equal to 5-point decrease in dysfunction and greater than or equal to 30% decrease in pain from baseline. Clinically meaningful improvement for each primary outcome with both follow-up times was analyzed using adjusted modified Poisson generalized estimating equations (GEEs). Secondary analyses for the continuous outcomes used linear GEEs. There were no observed differences by primary treatment group at 12 or 26 weeks. Those receiving booster dose had improvements in both dysfunction and pain at 12 weeks (dysfunction: relative risk [RR]=1.56 [1.08-2.25], p=.018; pain: RR=1.25 [0.98-1.61], p=.077), but those were nonsignificant at 26 weeks (dysfunction: RR=1.22 [0.85-1.74]; pain: RR=1.09 [0.82-1.43]). Subgroup analysis by primary and booster treatments found the booster dose only effective among those initially randomized to one of the 60-minute massage groups. "Booster" doses for those initially receiving 60 minutes of massage should be incorporated into future trials of massage for chronic neck pain
Mizrachi, Yossi; Dekalo, Ann; Gluck, Ohad; Miremberg, Hadas; Dafna, Lotem; Feldstein, Ohad; Weiner, Eran; Bar, Jacob; Sagiv, Ron
Does repeat administration of misoprostol for early pregnancy loss increase the treatment success rate? Repeat administration of misoprostol does not increase the treatment success rate, and is associated with more analgesics use. Misoprostol reduces the need for surgical evacuation and shortens the time to complete expulsion in patients with early pregnancy loss. However, the impact of repeat doses of misoprostol is not clear. A randomized clinical trial was conducted in a single tertiary hospital, recruiting women with early pregnancy loss (misoprostol vaginally on Day 1, and were then randomly assigned into two groups: Patients in the single-dose group were evaluated on Day 8. Patients in the repeat-dose group were evaluated on Day 4, when they were given a repeat dose if required, and scheduled for re-evaluation on Day 8. If complete expulsion was not achieved on Day 8 (endometrial thickness >15 mm or the presence of gestational sac on transvaginal sonography), participants underwent surgical evacuation. The primary outcome was treatment success, defined as no need for surgical intervention up to Day 8. Final analysis included 87 participants in the single-dose group and 84 participants in the repeat-dose group, out of whom 41 (48.8%) received a second dose. Treatment succeeded in 67 (77%) patients in the single-dose group and 64 (76%) patients in the repeat-dose group (RR 0.98; 95% CI 0.83-1.16; P = 0.89). Patients in the repeat-dose group reported more use of over the counter analgesics (82.1% versus 69.0%, P = 0.04). The study was not blinded and our definition of complete expulsion may be debated. Follow-up time was not equal in all participants, since some had a complete expulsion on Day 4 and some underwent emergent D&C before Day 8. This, however, should not affect the primary outcome. Our results suggest that a single-dose protocol is superior to a repeat-dose protocol due to a comparable success rate and more favorable outcomes regarding the need for
Ali Reza Jafari
Conclusion: Using of CAM visual stimulation along with conventional occlusion will further improve visual acuity and stereopsis in amblyopic children. These findings recommended the CAM visual stimulation as an accompanying and complementary method in amblyopia treatment.
Sheffer, Christine E; Bickel, Warren K; Franck, Christopher T; Panissidi, Luana; Pittman, Jami C; Stayna, Helen; Evans, Shenell
Evidence-based treatments for tobacco dependence are significantly less effective for smokers of lower socioeconomic status which contributes to socioeconomic disparities in smoking prevalence rates and health. We aimed to reduce the socioeconomic gradient in treatment outcomes by systematically adapting evidence-based, cognitive-behavioral treatment for tobacco dependence for diverse lower socioeconomic smokers. Participants were randomized to adapted or standard treatment, received six 1-h group treatment sessions, and were followed for six months. We examined the effectiveness of the adapted treatment to improve treatment outcomes for lower socioeconomic groups. Participants (n=227) were ethnically, racially, and socioeconomically diverse. The adapted treatment significantly reduced the days to relapse for the two lowest socioeconomic groups: SES1: M=76.6 (SD 72.9) vs. 38.3 (SD 60.1) days to relapse (RR=0.63 95% CI, 0.45, 0.88, p=0.0013); SES2: M=88.2 (SD 67.3) vs. 40.1 (SD 62.6 days to relapse (RR=0.57 95% CI, 0.18, 0.70, p=0.0024). Interactions between socioeconomic status and condition were significant for initial abstinence (OR=1.26, 95% CI 1.09, 1.46, p=0.002), approached significance for 3-month abstinence (OR=0.90, 95% CI 0.80, 1.01, psocioeconomic smokers and reduce inequities in days to relapse. Novel methods of providing targeted extended support are needed to improve long-term outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.
Itoh, Kazunori; Asai, Sayo; Ohyabu, Hideaki; Imai, Kenji; Kitakoji, Hiroshi
We compared the effects of trigger point acupuncture with that of sham acupuncture treatments on pain and oral function in patients with temporomandibular disorders (TMDs). This 10-week study included 16 volunteers from an acupuncture school with complaints of chronic temporomandibular joint myofascial pain for at least 6 months. The participants were randomized to one of two groups, each receiving five acupuncture treatment sessions. The trigger point acupuncture group received treatment at trigger points for the same muscle, while the other acupuncture group received sham treatment on the trigger points. Outcome measures were pain intensity (visual analogue scale) and oral function (maximal mouth opening). After treatment, pain intensity was less in the trigger point acupuncture group than in the sham treatment group, but oral function remained unchanged in both groups. Pain intensity decreased significantly between pretreatment and 5 weeks after trigger point (ptrigger point acupuncture therapy may be more effective for chronic temporomandibular joint myofascial pain. Copyright © 2012. Published by Elsevier B.V.
Full Text Available When the individual outcomes within a composite outcome appear to have different treatment effects, either in magnitude or direction, researchers may question the validity or appropriateness of using this composite outcome as a basis for measuring overall treatment effect in a randomized controlled trial. The question remains as to how to distinguish random variation in estimated treatment effects from important heterogeneity within a composite outcome. This paper suggests there may be some utility in directly testing the assumption of homogeneity of treatment effect across the individual outcomes within a composite outcome. We describe a treatment heterogeneity test for composite outcomes based on a class of models used for the analysis of correlated data arising from the measurement of multiple outcomes for the same individuals. Such a test may be useful in planning a trial with a primary composite outcome and at trial end with final analysis and presentation. We demonstrate how to determine the statistical power to detect composite outcome treatment heterogeneity using the POISE Trial data. Then we describe how this test may be incorporated into a presentation of trial results with composite outcomes. We conclude that it may be informative for trialists to assess the consistency of treatment effects across the individual outcomes within a composite outcome using a formalized methodology and the suggested test represents one option.
Full Text Available Background: Acne vulgaris is self-limiting, multifactorial disease involving sebaceous glands. Omeprazole is a proton pump inhibitor with in vitro antibacterial effects against staphylococcus aureus and anti-androgen that can be potential treatment of acne vulgaris. This study was designed to evaluate the efficacy of oral omeprazole and erythromycin 4% compared to doxycycline combination therapy in the treatment of acne vulgaris. Methods: In this clinical trial study, patients with moderate acne were referred to Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Science, Iran, during August 2014 until November 2015 and were randomized into two groups receiving topical erythromycin 4% plus omeprazole (34 patients or doxycycline (35 patients for 3 months. Moderate acne, lack of sensitivity to proton pump inhibitors, lack of warfarin, phenytoin, diazepam consumption, lack of active liver or kidney disease, being older than 12 years, were considered as inclusion criteria. Pregnant or lactating patients, patients with drug allergy history, patients taking oral contraceptives, acne topical medications (including retinoids or systemic treatment within 30 days of study, patients with oligomenorrhea, hirsutism, acne conglobata, acne fulminant or body acne alone were excluded from the study. All patients were tested for Helicobacter pylori test at the beginning of the study. Results: Both inflammatory and non-inflammatory lesions decreased in both groups with negative correlation with age (P< 0.05. There was no significant correlation between positive Helicobacter pylori test and inflammatory or non-inflammatory lesion reduction (P= 0.794, P= 0.514. Also, patient satisfaction and rate of total drug side effects was not different between two treatment groups. Rate of skin reactions was 20.58% in omeprazole treated group and 11.42% in doxycycline group. For side effects, other than skin it was 2.94% versus 14.28% respectively
Liber, Juliette M.; Van Widenfelt, Brigit M.; Utens, Elisabeth M. W. J.; Ferdinand, Robert F.; Van Der Leeden, Adelinde J. M.; Van Gastel, Willemijn; Treffers, Philip D. A.
Background: The present study compares an individual versus a group format in the delivery of manualised cognitive-behavioural therapy (FRIENDS) for children with anxiety disorders. Clinically referred children (aged 8 to 12) diagnosed with Separation Anxiety Disorder (n = 52), Generalised Anxiety Disorder (n = 37), Social Phobia (n = 22) or…
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.
Alexandre Fogaça Cristante
Full Text Available OBJECTIVES: Hydrodiscectomy is a new technique used for percutaneous spinal discectomy that employs a high-intensity stream of water for herniated disc ablation and tissue aspiration. No previous clinical study has examined the effects of percutaneous hydrodiscectomy. The aim of this study is to evaluate the outcomes of hydrodiscectomy compared to open microdiscectomy regarding pain, function, satisfaction, complications and recurrence rates. METHODS: In this randomized clinical trial, patients referred to our tertiary hospital for lumbar back pain were recruited and included in the study if they had disc protrusion or small herniation in only one level, without neurological deficits and with no resolution after six weeks of conservative treatment. One group underwent open microdiscectomy, and the other group underwent percutaneous microdiscectomy via hydrosurgery. Function was evaluated using the Oswestry Disability Index and pain was assessed using a visual analog scale. Evaluations were performed preoperatively, and then during the first week and at one, three, six and twelve months postoperatively. Personal satisfaction was verified. Clinicaltrials.gov: NCT01367860. RESULTS: During the study period, 20 patients were included in each arm and 39 completed one-year of follow-up (one patient died of unrelated causes. Both groups exhibited equal improvement on the visual analog scale and Oswestry evaluations after treatment, without any significant differences. The improvement in the lumbar visual analog scale score was not significant in the hydrodiscectomy group (p=0.138. The rates of infection, pain, recurrence and satisfaction were similar between the two groups. CONCLUSION: Percutaneous hydrodiscectomy was demonstrated to be as effective as open microdiscectomy for reducing pain. The rates of complications and recurrence of herniation were similar between groups. Patient satisfaction with the treatment was also similar between groups.
Stasinopoulos, D; Stasinopoulos, I; Johnson, M I
Our aim was to assess the efficacy of polarized polychromatic noncoherent light (Bioptron light) in the treatment of idiopathic carpal tunnel syndrome. Carpal tunnel syndrome is the most common compression neuropathy, but no satisfactory conservative treatment is available at present. An uncontrolled experimental study was conducted in patients who visited our clinic from mid-2001 to mid-2002. A total of 25 patients (22 women and three men) with unilateral idiopathic carpal tunnel syndrome, mild to moderate nocturnal pain, and paraesthesia lasting >3 months participated in the study. The average age of the patients was 47.4 years and the average duration of patients' symptoms was 5.2 months. Polarized polychromatic noncoherent light (Bioptron light) was administered perpendicular to the carpal tunnel area. The irradiation time for each session was 6 min at an operating distance of 5-10 cm from the carpal tunnel area, three times weekly for 4 weeks. Outcome measures used were the participants' global assessments of nocturnal pain and paraesthesia, respectively, at 4 weeks and 6 months. At 4 weeks, two patients (8%) had no change in nocturnal pain, six (24%) were in slightly less nocturnal pain, 12 (48%) were much better in regard to nocturnal pain and five (20%) were pain-free. At 6 months, three patients (12%) were slightly better in regard to nocturnal pain, 13 (52%) were much better regarding nocturnal pain, and nine patients (36%) were pain-free. At 4 weeks, four patients (16%) had no change in paraesthesia, five (20%) were slightly better, 13 patients (52%) were much better, and three patients (12%) were without paraesthesia. At 6 months, two patients (8%) had no change in paraesthesia, two (8%) were slightly better, 14 (56%) were much better, and seven (28%) were without paraesthesia. Nocturnal pain and paraesthesia associated with idiopathic carpal tunnel syndrome improved during polarized polychromatic noncoherent light (Bioptron light) treatment. Controlled
Elashoff, Robert M; Li, Gang; Zhou, Ying
To evaluate the biological efficacy of a treatment in a randomized clinical trial, one needs to compare patients in the treatment arm who actually received treatment with the subgroup of patients in the control arm who would have received treatment had they been randomized into the treatment arm. In practice, subgroup membership in the control arm is usually unobservable. This paper develops a nonparametric inference procedure to compare subgroup probabilities with right-censored time-to-event data and unobservable subgroup membership in the control arm. We also present a procedure to estimate the onset and duration of treatment effect. The performance of our method is evaluated by simulation. An illustration is given using a randomized clinical trial for melanoma.
Altman, Roy D; Devji, Tahira; Bhandari, Mohit
OBJECTIVES: Hyaluronic acid and corticosteroids are common intra-articular (IA) therapies widely used for the management of mild to moderate knee osteoarthritis (OA). Many trials evaluating the efficacy of IA administered therapies commonly use IA saline injections as a placebo comparator arm...... in the meta-analysis. Based on data with moderate inconsistency IA saline was found to significantly improve short-term knee pain in 32 studies involving 1705 patients (SMD = -0.68; 95% CI: -0.78 to -0.57; P injection...... with saline in 19 studies involving 1445 patients (SMD = -0.61; 95% CI: -0.76 to -0.45; P injection with saline...
M. T. Javed, A. Khan, Abid Hussain and Babar Niaz
Full Text Available The study was conducted on 24 calves of one week-age, randomly divided into four groups, of six calves each. First three groups were experimentally infected with E. coli and given treatment in various combinations, while group four was taken as uninfected untreated control. Results obtained on different parameters were, green to yellow-white diarrhoea with variable consistency from watery to semisolid. Generally in all groups during first two days, calves passed faeces around 6-10 times a day and this frequency lowered in about 2-4 days. During first 3-4 days of treatment, all calves appeared weak, dull, depressed with cold skin and wetness of the muzzle, while oral mucosa was pale and eyes were sunken. Overall mean respiration rate of treatment groups was slower (P<0.05 than control group. However, pulse rate showed no difference between treatment and control group. Overall mean rectal temperature was lower (P<0.05 in calves treated with antibiotic alone and with antibiotic + electrolytes, while body weight was higher (P<0.05 in calves treated with antibiotic but was lower along with creatinine (P<0.05 in calves treated with antibiotic + electrolytes and those treated with electrolytes alone.
Doering, S.; Ohlmeier, M.C.; de Jongh, A.; Hofmann, A.; Bisping, V.
It has been hypothesized that treatment specifically focused on resolving memories of negative dental events might be efficacious for the alleviation of anxiety in patients with dental phobia. Thirty-one medication-free patients who met the Diagnostic and Statistical Manual of Mental Disorders
Watkins, Katherine E; Cuellar, Alison E; Hepner, Kimberly A; Hunter, Sarah B; Paddock, Susan M; Ewing, Brett A; de la Cruz, Erin
The authors aimed to determine the economic value of providing on-site group cognitive behavioral therapy (CBT) for depression to clients receiving residential substance use disorder (SUD) treatment. Using a quasi-experimental design and an intention-to-treat analysis, the incremental cost-effectiveness and cost-utility ratio of the intervention were estimated relative to usual care residential treatment. The average cost of a treatment episode was $908, compared to $180 for usual care. The incremental cost effectiveness ratio was $131 for each point improvement of the BDI-II and $49 for each additional depression-free day. The incremental cost-utility ratio ranged from $9,249 to $17,834 for each additional quality adjusted life year. Although the intervention costs substantially more than usual care, the cost effectiveness and cost-utility ratios compare favorably to other depression interventions. Health care reform should promote dissemination of group CBT to individuals with depression in residential SUD treatment. © 2013 Elsevier Inc. All rights reserved.
Accrual to cancer clinical trials (CCT) is imperative to safeguard continued improvement in cancer outcomes. A retrospective chart review was performed of patients (n=140) starting a new anti-cancer agent in a north Dublin cancer centre. This review was performed over a four-month period, beginning in November 2015. Only 29% (n=41) had a CCT option. The overall accrual rate to CCT was 5% (n=7), which is comparable to internationally reported figures. The main reasons for failure to recruit to CCT included the lack of a CCT option for cancer type (n=30, 23%), stage (n=25, 19%), and line of treatment (n=23, 17%). Over the last decade, the rate of accrual to CCTs has in fact doubled and the number of trials open to recruitment has tripled. Ongoing governmental and philanthropic support is necessary to continue this trend to further expand CCT patient options with a target accrual rate of 10%.
clinical and educational professionals, and parents. Findings from this study will likely impact the fields of psychology and psychiatry. Empirical...Canisius College, Science Hall 1016C, 2001 Main Street, Buffalo, NY 14208, USA 2 Department of Counseling, Educational Psychology and Special...urement error: But how should we understand and deal with informant discrepancies? Journal of Child and Adolescent Psychology , 40(1), 80–86. doi
J. Todd Kuenstner
Conclusions: In this study, UVBI was safe and had a beneficial effect in the treatment of HCV. This device should be studied for use in psoriasis and in infectious diseases that have few treatment options. This article describes a prospective, controlled, phase II clinical trial submitted to the FDA of this device used for the treatment of HCV infection (Investigational Device Exemption (IDE #G030242.
Kappelmann, Nils; Lewis, Glyn; Dantzer, Robert; Jones, Peter Brian; Khandaker, Golam Mohammed
Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO...
Thorup, Jørgen Mogens; Mauritzen, K; Skakkebaek, N E
The effect of intranasal LH-RH on cryptorchidism was investigated in 45 prepubertal boys with 68 undescended testes. A daily dose of 1.2 mg LH-RH was given for 4 weeks. A total of 16 testes (24%) descended. Follow-up examination 5 years later showed that relapse had occurred in two cases. Fifty......-two testes did not descend during the LH-RH treatment. However, seven of these testes descended spontaneously during puberty. So far surgical treatment has been carried out in 39 of the remaining 45 testes. Anatomical anomalies (ectopic position of the testis, open processus vaginalis, abnormal epididymis......) explained the failure of LH-RH to cause descent in the majority of the surgically treated cases....
Donyavi, Zakiyeh; Ghahari, Parastoo; Esmaeilzadeh, Mohammad; Kharazifard, Mohammadjavad; Yousefi-Mashouf, Rasoul
This study compared the root canal microbial count of necrotic teeth after irrigation with 6% sodium hypochlorite (NaOCl) (single session treatment) and two-session root canal treatment with two-week application of calcium hydroxide (CH) mixed with 0.2% chlorhexidine (CHX) as intracanal medicament. In this randomized clinical trial, single-rooted necrotic teeth were divided into two groups. Root canal was irrigated with 2 mL of 6% NaOCl in one group, and a mixture of 0.2% CHX and CH powder as an intracanal medicament for two weeks, in the other group. Root canal samples were obtained before and after the intervention and number of colony forming units (CFUs) was counted in each phase. The reduction of Enterococcus faecalis CFU was not significantly different between the two groups ( P =0.233) but the CFU of aerobic and anaerobic bacteria was significantly lower in CH+CHX group ( P endodontic lesions in two sessions with intracanal medicaments to achieve predictable results.
Elhafez, Haytham M; Elhafez, Salam M
The purpose of this study was to compare axillary ultrasound, laser, and postisometric facilitation technique with standard care in the management of shoulder adhesive capsulitis. This is a randomized clinical trial study. Fifty-nine participants with shoulder adhesive capsulitis were selected and randomly assigned for eligibility. Forty-five participants were assigned into 3 equal groups of 15, and 14 participants were excluded from the study. The participants were blinded to their group allocation. Standard care group (A) received traditional physical therapy treatment in the form of pulsed ultrasound, scanning laser, supervised exercise program, and home exercise program; group B received the same physical therapy program as group A, except that the ultrasound and scanning laser were applied to the axillary region of the painful shoulder; and group C received the same modified physical therapy program as group B plus postisometric facilitation technique to the painful shoulder. All dependent variables were measured by the second author, who was blinded to the participant's intervention group. The first author administered treatment to all 3 groups. All participants received 12 sessions (3 times/wk for 4 weeks). Pain level and shoulder range of motion (ROM; flexion, abduction, and external rotation) were recorded 3 times (pretreatment, immediately posttreatment, and 4 weeks of treatment). Mixed-design multivariate analysis of variance indicated significant pain reduction with significant ROM increase in all groups posttreatment and after 4 weeks. Post hoc analysis for within groups revealed that shoulder ROM and pain levels improved significantly posttreatment compared with pretreatment ROM in all groups, with the greatest improvement in group C. Between-group analysis revealed that pain-free shoulder flexion, abduction, external rotation, and pain level improved significantly in group C compared with groups A and B immediately after treatment and after 4 weeks