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Sample records for replacement therapy regimens

  1. Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, Anette Tønnes; Lynge, Elsebeth

    2004-01-01

    was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle-related factors. Breast cancer cases......Epidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort...

  2. A randomized trial evaluating a block-replacement regimen during radioiodine therapy

    DEFF Research Database (Denmark)

    Bonnema, Steen J; Grupe, Peter; Boel-Jørgensen, Henrik

    2011-01-01

    Eur J Clin Invest 2010 ABSTRACT: Background  Lack of consensus regarding the antithyroid drug regimen in relation to radioiodine ((131) I) therapy of hyperthyroidism prompted this randomized trial comparing two strategies. Design  Patients with Graves' disease (GD, n = 51) or toxic nodular goitre...

  3. Future long-term trials of postmenopausal hormone replacement therapy - what is possible and what is the optimal protocol and regimen?

    Science.gov (United States)

    Purbrick, B; Stranks, K; Sum, C; MacLennan, A H

    2012-06-01

    The ideal long-term, randomized, placebo-controlled trial of hormone replacement therapy (HRT) from near menopause for up to 30 years to assess major morbidity and mortality is impractical because of high cost, participant retention, therapy compliance, and continuity of research staff and funding. Also the trial regimen may become outdated. It is nihilistic to demand such a long-term trial before endorsing HRT. However, medium-term trials using surrogate measures for long-term morbidity and mortality are possible and two are near completion. If these studies have been able to maintain reasonable participant retention, therapy compliance and minimal breach of protocol, they will set standards for trials of new HRT regimens. This paper discusses lessons learnt from past attempts at long-term trials and suggests the currently optimal protocol and cost of assessing new HRT regimens to optimize potential benefits and minimize adverse effects. A 5-7-year randomized, placebo-controlled trial of a flexible transdermal estrogen regimen ± either a selective estrogen receptor modulator, e.g. bazedoxifene, or micronized progesterone is discussed. Mild to moderately symptomatic women, 1-4 years post menopause, can be recruited via general practice and group meetings. Future trials should be funded by independent agencies and are high priority in women's health.

  4. Effects of different progestin regimens in hormone replacement therapy on blood coagulation factor VII and tissue factor pathway inhibitor

    DEFF Research Database (Denmark)

    Bladbjerg, E-M; Skouby, S O.; Andersen, L F

    2002-01-01

    BACKGROUND: Long-term hormone replacement therapy (HRT) reduces cardiovascular risk, but an early increased risk was reported in women with coronary heart disease. In such women the arterial intima can express tissue factor, and changes in coagulation factor VII (factor VII) and tissue factor...... pathway inhibitor (TFPI) may be deleterious. METHODS: We measured factor VII clotting activity, activated factor VII, and concentrations of factor VII and TFPI during 12 months in healthy post-menopausal women randomized to: (i). cyclic oral estrogen/progestin (n = 25); (ii). long-cycle oral estrogen......: No variations were observed in the reference group. There was a substantial decrease in TFPI concentrations in the HRT groups irrespective of the type of progestin. In women receiving long-cycle treatment, all factor VII measures increased during the unopposed estrogen periods, and the increase was reversed...

  5. Nicotine replacement therapy

    Science.gov (United States)

    Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Before you start using a nicotine replacement product, here are some things to know: The more cigarettes you smoke, the higher the dose you may need to ...

  6. Iron replacement therapy

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Coskun, Mehmet; Weiss, Günter

    2016-01-01

    PURPOSE OF REVIEW: Approximately, one-third of the world's population suffers from anemia, and at least half of these cases are because of iron deficiency. With the introduction of new intravenous iron preparations over the last decade, uncertainty has arisen when these compounds should...... be administered and under which circumstances oral therapy is still an appropriate and effective treatment. RECENT FINDINGS: Numerous guidelines are available, but none go into detail about therapeutic start and end points or how iron-deficiency anemia should be best treated depending on the underlying cause...... of iron deficiency or in regard to concomitant underlying or additional diseases. SUMMARY: The study points to major issues to be considered in revisions of future guidelines for the true optimal iron replacement therapy, including how to assess the need for treatment, when to start and when to stop...

  7. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  8. Antibiotic Dosing in Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Shaw, Alexander R; Mueller, Bruce A

    2017-07-01

    Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  9. Thyroid hormone replacement therapy

    NARCIS (Netherlands)

    Wiersinga, W. M.

    2001-01-01

    Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T(4)) and triiodothyronine (T(3)); serum T(3) frequently rises to supranormal values in the absorption

  10. Pancreatic enzyme replacement therapy.

    Science.gov (United States)

    Layer, P; Keller, J; Lankisch, P G

    2001-04-01

    Malabsorption due to severe pancreatic exocrine insufficiency is one of the most important late features of chronic pancreatitis. Generally, steatorrhea is more severe and occurs several years prior to malabsorption of other nutrients because synthesis and secretion of lipase are impaired more rapidly, its intraluminal survival is shorter, and the lack of pancreatic lipase activity is not compensated for by nonpancreatic mechanisms. Patients suffer not only from nutritional deficiencies but also from increased nutrient delivery to distal intestinal sites, causing symptoms by profound alteration of upper gastrointestinal secretory and motor functions. Adequate nutrient absorption requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. The following recommendations are based on modern therapeutic concepts: 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres, with dosage increases, compliance checks, and differential diagnosis in case of treatment failure. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed to optimize treatment.

  11. Hormone Replacement Therapy and Your Heart

    Science.gov (United States)

    Hormone replacement therapy and your heart Are you taking — or considering — hormone therapy to treat bothersome menopausal symptoms? Understand ... you. By Mayo Clinic Staff Long-term hormone replacement therapy used to be routinely prescribed for postmenopausal ...

  12. Hybrid Therapy Regimen for Helicobacter Pylori Eradication

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Song

    2016-01-01

    Conclusions: Hybrid therapy showed wide differences in the efficacy but consistently good compliance and safety across different regions. Dual clarithromycin and metronidazole resistance were the key factor to efficacy. Hybrid therapy was similar to sequential or concomitant therapy in the efficacy, safety, and compliance.

  13. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  14. Renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    Pippias, Maria; Stel, Vianda S; Abad Diez, José Maria

    2015-01-01

    BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). METHODS: Data provided by 45 national or regional renal...... disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp...... to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59...

  15. Hormone replacement therapy in Denmark, 1995-2004

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen; Lidegaard, Ojvind; Møller, Lisbeth Nørgaard

    2007-01-01

    Recently, the Danish National Register of Medicinal Product Statistics (NRM) was opened for research purposes, and therefore, on an individual basis, can merge with other national registers. The aim of this study was to analyse the use of hormones based on the individual data of the entire Danish...... female population, with the focus on a detailed evaluation of specific hormone regimens and factors associated with systemic hormone replacement therapy (HRT)....

  16. A meal replacement regimen improves blood glucose levels in prediabetic healthy individuals with impaired fasting glucose.

    Science.gov (United States)

    König, Daniel; Kookhan, Sadaf; Schaffner, Denise; Deibert, Peter; Berg, Aloys

    2014-01-01

    The aim of this study was to investigate the effect of a 6-wk intervention with either lifestyle intervention (increased physical activity and a low-calorie diet) or a meal replacement regimen on glycemic control in patients who are prediabetic and have impaired fasting glucose. Forty-two overweight or obese men and women (age 54 ± 8 y; weight 95.1 ± 11.9 kg; body mass index [BMI] 32.8 ± 2.89 kg/m(2)) were included in this randomized controlled clinical trial. Patients in the lifestyle group (LS; n = 14) received dietary counseling sessions (fat-restricted low-calorie diet) and instructions on how to increase physical activity. Patients in the meal replacement group (MR; n = 28) were instructed to replace two daily meals with a low-calorie, high soy-protein drink with a low glycemic index. Both interventions resulted in a significant decrease in body weight and BMI, although the reduction was more pronounced (P meal replacement is an effective intervention for rapid improvement of elevated fasting glucose and increased insulin concentrations, these being important biomarkers of the prediabetic state. The 6-wk intervention has shown that the effect of meal replacement on fasting blood glucose was comparable to the effect of lifestyle intervention. The alterations in BMI, insulin, and HOMA-IR were significantly more pronounced following the meal replacement regimen. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Hormone replacement therapy and hypercoagulability

    DEFF Research Database (Denmark)

    Sidelmann, Johannes Jakobsen; Jespersen, Jørgen; Andersen, Lars F.

    2003-01-01

    OBJECTIVE: To assess the influence of a variety of HRT regimens on the haemostatic balance using markers of fibrin turnover and inhibitors of coagulation. DESIGN: An open randomised study allocating women to either a control group or five different HRT treatment groups. SETTING: Gentofte Hospital...

  18. Preclinical Evaluations To Identify Optimal Linezolid Regimens for Tuberculosis Therapy

    Science.gov (United States)

    Drusano, George L.; Adams, Jonathan R.; Rodriquez, Jaime L.; Jambunathan, Kalyani; Baluya, Dodge L.; Brown, David L.; Kwara, Awewura; Mirsalis, Jon C.; Hafner, Richard; Louie, Arnold

    2015-01-01

    ABSTRACT Linezolid is an oxazolidinone with potent activity against Mycobacterium tuberculosis. Linezolid toxicity in patients correlates with the dose and duration of therapy. These toxicities are attributable to the inhibition of mitochondrial protein synthesis. Clinically relevant linezolid regimens were simulated in the in vitro hollow-fiber infection model (HFIM) system to identify the linezolid therapies that minimize toxicity, maximize antibacterial activity, and prevent drug resistance. Linezolid inhibited mitochondrial proteins in an exposure-dependent manner, with toxicity being driven by trough concentrations. Once-daily linezolid killed M. tuberculosis in an exposure-dependent manner. Further, 300 mg linezolid given every 12 hours generated more bacterial kill but more toxicity than 600 mg linezolid given once daily. None of the regimens prevented linezolid resistance. These findings show that with linezolid monotherapy, a clear tradeoff exists between antibacterial activity and toxicity. By identifying the pharmacokinetic parameters linked with toxicity and antibacterial activity, these data can provide guidance for clinical trials evaluating linezolid in multidrug antituberculosis regimens. PMID:26530386

  19. Menopause and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Ali Baziad

    2001-12-01

    Full Text Available The global population in the 21st century has reached 6.2 billion people, by the year 2025 it is to be around 8.3-8.5 billion, and will increase further. Elderly people are expected to grow rapidly than other groups. The fastest increase in the elderly population will take place in Asia. Life expectancy is increasing steadily throughout developed and developing countries. For many  menopausal women, increased life expectancy will accompanied by many health problems. The consequences of estrogen deficiency are the menopausal symptoms. The treatment of menopause related complaints and diseases became an  important socioeconomic and medical issue. Long term symptoms, such as the increase in osteoporosis fractures, cardio and cerebrovascular disesses and dementia, created a large financial burden on individuals and society. All these health problems can be lreated or prevented by hormone replacement therapy (HRT. Natural HRT is usually prefened. Synthetic  estrogen in oral contraceptives (oc are not recommended for HRT. Many contra-indications for oc, but now it is widely usedfor HRT. The main reasons for discontinuing HRT are unwanted bleeding, fear of cancer, and negative side effects. Until now there are sill debates about the rebrtonship between HRT and the incidence of breast cancer. Many data showed that there were no clear relationship between the use of HRT and breast cancer. ThereÎore, nwny experts advocate the use of HRTfrom the first sign of climacteric complaints until death. (Med J Indones 2001;10: 242-51Keywords: estrogen deficiency, climacteric phases, tibolone.

  20. Postmenopausal hormone replacement therapy--clinical implications

    DEFF Research Database (Denmark)

    Ravn, S H; Rosenberg, J; Bostofte, E

    1994-01-01

    The menopause is defined as cessation of menstruation, ending the fertile period. The hormonal changes are a decrease in progesterone level, followed by a marked decrease in estrogen production. Symptoms associated with these hormonal changes may advocate for hormonal replacement therapy....... This review is based on the English-language literature on the effect of estrogen therapy and estrogen plus progestin therapy on postmenopausal women. The advantages of hormone replacement therapy are regulation of dysfunctional uterine bleeding, relief of hot flushes, and prevention of atrophic changes...... in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin...

  1. Assessment of non-standard HIV antiretroviral therapy regimens at ...

    African Journals Online (AJOL)

    2016-03-06

    Mar 6, 2016 ... Most patients were transitioned to standard regimens, ... In cases of first-line regimen treatment failure, ..... tute; National Heart, Lung, and Blood Institute; National. Institute of Dental & Craniofacial Research; National Insti-.

  2. Enzyme Replacement Therapy for Fabry Disease

    Directory of Open Access Journals (Sweden)

    Maria Dolores Sanchez-Niño PhD

    2016-11-01

    Full Text Available Fabry disease is a rare X-linked disease caused by the deficiency of α-galactosidase that leads to the accumulation of abnormal glycolipid. Untreated patients develop potentially lethal complications by age 30 to 50 years. Enzyme replacement therapy is the current standard of therapy for Fabry disease. Two formulations of recombinant human α-galactosidase A (agalsidase are available in most markets: agalsidase-α and agalsidase-β, allowing a choice of therapy. However, the US Food and Drug Administration rejected the application for commercialization of agalsidase-α. The main difference between the 2 enzymes is the dose. The label dose for agalsidase-α is 0.2 mg/kg/2 weeks, while the dose for agalsidase-β is 1.0 mg/kg/2 weeks. Recent evidence suggests a dose-dependent effect of enzyme replacement therapy and agalsidase-β is 1.0 mg/kg/2 weeks, which has been shown to reduce the occurrence of hard end points (severe renal and cardiac events, stroke, and death. In addition, patients with Fabry disease who have developed tissue injury should receive coadjuvant tissue protective therapy, together with enzyme replacement therapy, to limit nonspecific progression of the tissue injury. It is likely that in the near future, additional oral drugs become available to treat Fabry disease, such as chaperones or substrate reduction therapy.

  3. of surfactant replacement therapy at Johannesburg Hospital ...

    African Journals Online (AJOL)

    To assess the impact of surfactant replacement therapy (SRl) on the outcome of ... oxygen requirements) was compared with that of a historical control group of ... The use of SRT added to the total cost of treating a patient ventilated for HMD.

  4. Hormone replacement therapy and risk of glioma

    DEFF Research Database (Denmark)

    Andersen, Lene; Friis, Søren; Hallas, Jesper

    2013-01-01

    Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma...

  5. Renal replacement therapy in healthy adult horses.

    Science.gov (United States)

    Wong, D M; Witty, D; Alcott, C J; Sponseller, B A; Wang, C; Hepworth, K

    2013-01-01

    Renal replacement therapy (RRT) has been implemented extensively in people to facilitate recovery from acute renal failure (ARF). RRT has not been explored in horses, but might provide a further treatment option in horses with ARF. To investigate efficacy and safety of RRT in horses. Five healthy adult horses. A prospective study was performed on horses restrained in stocks and intravenously connected to a commercial RRT machine to allow continuous venovenous hemodiafiltration to be performed for 6 hours. The RRT machine was set at the following flow rates: blood flow rate 250 mL/min; dialysate rate 3,000 mL/h; prefilter replacement pump 3,000 mL/h; and postfilter replacement pump rate 2,000 mL/h. Balanced electrolyte solution was used as dialysate and replacement fluid. Heart rate, respiratory rate, body temperature, direct arterial blood pressure, urine output, and various clinicopathologic parameters were measured over the study period. Renal replacement therapy was successfully performed in horses, resulting in a mean creatinine clearance of 0.127 mL/kg/min (68.9 mL/min) and urea reduction ratio of 24%. No adverse effects were detected although a significant decrease in rectal temperature was observed (P ≤ .007). A significant increase in serum phosphorus (P ≤ .001) and decrease in BUN (P replacement therapy can safely and effectively be used in adult horses. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  6. Transdermal testosterone replacement therapy in men

    Directory of Open Access Journals (Sweden)

    Ullah MI

    2014-01-01

    Full Text Available M Iftekhar Ullah,1 Daniel M Riche,1,2 Christian A Koch1,31Department of Medicine, University of Mississippi Medical Center, 2Department of Pharmacy Practice, The University of Mississippi, 3GV (Sonny Montgomery VA Medical Center, Jackson, MS, USAAbstract: Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.Keywords: hypogonadism, transdermal, testosterone, sexual function, testosterone replacement therapy, estradiol

  7. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

    Directory of Open Access Journals (Sweden)

    Lars Rejnmark

    2015-12-01

    Full Text Available Hypoparathyroidism (HypoPT is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH. Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84 as well as therapy with the N-terminal PTH fragment (rhPTH(1-34 have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.

  8. HIV Therapy Simulator: a graphical user interface for comparing the effectiveness of novel therapy regimens.

    Science.gov (United States)

    Lim, Huat Chye; Curlin, Marcel E; Mittler, John E

    2011-11-01

    Computer simulation models can be useful in exploring the efficacy of HIV therapy regimens in preventing the evolution of drug-resistant viruses. Current modeling programs, however, were designed by researchers with expertise in computational biology, limiting their accessibility to those who might lack such a background. We have developed a user-friendly graphical program, HIV Therapy Simulator (HIVSIM), that is accessible to non-technical users. The program allows clinicians and researchers to explore the effectiveness of various therapeutic strategies, such as structured treatment interruptions, booster therapies and induction-maintenance therapies. We anticipate that HIVSIM will be useful for evaluating novel drug-based treatment concepts in clinical research, and as an educational tool. HIV Therapy Simulator is freely available for Mac OS and Windows at http://sites.google.com/site/hivsimulator/. jmittler@uw.edu. Supplementary data are available at Bioinformatics online.

  9. Anticoagulation After Biological Aortic Valve Replacement: Is There An Optimal Regimen?

    Science.gov (United States)

    Owais, Tamer; Rouman, Mina; Breuer, Martin; Hüter, Lars; Fuchs, Jürgen; Lauer, Bernward; Kuntze, Thomas

    2016-03-01

    The anticoagulation of biological heart valves remains a 'hot spot' of discussion in various domains due to the risk of developing valve thrombosis and arterial thromboembolism. The situation has always been controversial, especially during the early postoperative phase. The American College of Cardiology/ American Heart Association and European Society of Cardiology guidelines recommend the use of warfarin for the first three months after biological aortic valve replacement (BAVR), although the American College of Chest Physicians guidelines suggest that these recommendations are experience-based and that the risk/benefit is unclear. The aim of the present study was to compare the efficacy of aspirin and warfarin in patients after BAVR. A total of 863 patients who underwent BAVR between 2008 and 2015 was allocated to two groups. Each group was managed with a specific anticoagulation regimen, with 430 patients receiving warfarin during the first three postoperative months, and 433 receiving aspirin. The major study end points were bleeding, cerebral ischemic events, and survival. In total, 10 and 15 postoperative cerebral ischemic events occurred between 24 h and three months after surgery in patients treated with aspirin and warfarin, respectively. After three months the incidence of cerebral ischemic events did not differ greatly between the two groups. The rate of major bleeding events and rates of stroke-free survival and overall survival were not statistically significant between the warfarin and aspirin groups. Plasma anticoagulation with warfarin during the early postoperative phase was shown statistically to be inferior to platelet aggregation inhibition by aspirin with regards to postoperative bleeding risk, cerebral ischemic events, and survival.

  10. Improving compliance to meal-replacement food regimens. Forming implementation intentions (conscious IF-THEN plans) increases compliance.

    Science.gov (United States)

    Zandstra, E H; den Hoed, W; van der Meer, N; van der Maas, A

    2010-12-01

    Creating and changing habits around dieting behaviour can be a way to help consumers to consume more healthy products and to control their weight. Previous studies suggested that implementation intentions - deliberate plans on when, where and how - increase the likelihood that consumers perform the intended behaviour (Armitage, 2004; Gollwitzer & Sheeran, 2006; Jackson et al., 2005). This study investigated the effect of forming implementation intentions on compliance to a regimen based on a range of meal-replacement food products and snacks. Participants (n = 57) were allocated to one of two groups, either: (1) an implementation-intention group, who formed deliberate plans (implementation intentions) to consume the products - these implementation intentions were formed only once at the beginning of the study -, or (2) a control group who formed no implementation intentions. Participants were then instructed to follow a daily regimen, which included the consumption of foods from a range of meal-replacement products and snacks provided gratis for four weeks. Results showed that the implementation-intention group consumed significantly more meal-replacement food products per week (p intentions was apparent for 18 days. These findings indicate that forming implementation intentions may assist individuals in their compliance to a meal-replacement product regimen. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Transdermal testosterone replacement therapy in men

    Science.gov (United States)

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

  12. Neonatal varicella pneumonia, surfactant replacement therapy

    Directory of Open Access Journals (Sweden)

    Mousa Ahmadpour-kacho

    2015-12-01

    Full Text Available Background: Chickenpox is a very contagious viral disease that caused by varicella-zoster virus, which appears in the first week of life secondary to transplacental transmission of infection from the affected mother. When mother catches the disease five days before and up to two days after the delivery, the chance of varicella in neonate in first week of life is 17%. A generalized papulovesicular lesion is the most common clinical feature. Respiratory involvement may lead to giant cell pneumonia and respiratory failure. The mortality rate is up to 30% in the case of no treatment, often due to pneumonia. Treatment includes hospitalization, isolation and administration of intravenous acyclovir. The aim of this case report is to introduce the exogenous surfactant replacement therapy after intubation and mechanical ventilation for respiratory failure in neonatal chickenpox pneumonia and respiratory distress. Case Presentation: A seven-day-old neonate boy was admitted to the Neonatal Intensive Care Unit at Amirkola Children’s Hospital, Babol, north of Iran, with generalized papulovesicular lesions and respiratory distress. His mother has had a history of Varicella 4 days before delivery. He was isolated and given supportive care, intravenous acyclovir and antibiotics. On the second day, he was intubated and connected to mechanical ventilator due to severe pneumonia and respiratory failure. Because of sever pulmonary involvement evidenced by Chest X-Ray and high ventilators set-up requirement, intratracheal surfactant was administered in two doses separated by 12 hours. He was discharged after 14 days without any complication with good general condition. Conclusion: Exogenous surfactant replacement therapy can be useful as an adjunctive therapy for the treatment of respiratory failure due to neonatal chickenpox.

  13. Hormone Replacement Therapy: MedlinePlus Health Topic

    Science.gov (United States)

    ... of hormone therapy (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Hormone Replacement Therapy ... Estrogen overdose Types of hormone therapy Related Health Topics Menopause National Institutes of Health The primary NIH ...

  14. Avascular necrosis of bone complicating corticosteroid replacement therapy.

    OpenAIRE

    Williams, P L; Corbett, M

    1983-01-01

    Two patients who developed widespread severe avascular necrosis of bone while on steroid replacement therapy are described. One, a diabetic, underwent yttrium-90 pituitary ablation for retinopathy and developed avascular necrosis within 18 months of starting prednisolone. The other, who had Addison's disease, developed avascular necrosis within 14 months of starting cortisol replacement therapy. Both cases came to bilateral total hip replacement.

  15. Hormone replacement therapy in cancer survivors: Utopia?

    Science.gov (United States)

    Angioli, Roberto; Luvero, Daniela; Armento, Grazia; Capriglione, Stella; Plotti, Francesco; Scaletta, Giuseppe; Lopez, Salvatore; Montera, Roberto; Gatti, Alessandra; Serra, Giovan Battista; Benedetti Panici, Pierluigi; Terranova, Corrado

    2018-04-01

    As growing of old women population, menopausal women will also increase: an accurate estimation of postmenopausal population is an essential information for health care providers considering that with aging, the incidence of all cancers is expected to increase. Hormone replacement therapy (HRT) has proven to be highly effective in alleviating menopausal symptoms such as hot flashes, night sweats, dyspareunia, sexual disorders, and insomnia and in preventing osteoporosis. According to preclinical data, estrogen and progesterone are supposed to be involved in the induction and progression of breast and endometrial cancers. Similarly, in epithelial ovarian cancer (EOC), the pathogenesis seems to be at least partly hormonally influenced. Is HRT in gynecological cancer survivors possible? The literature data are controversial. Many clinicians remain reluctant to prescribe HRT for these patients due to the fear of relapse and the risk to develop coronary heart disease or breast cancer. Before the decision to use HRT an accurate counselling should be mandatory in order to individualizing on the basis of potential risks and benefits, including a close follow-up. Nevertheless, we do believe that with strong informed consent doctors may individually consider to prescribe some course of HRT in order to minimize menopausal symptoms and disease related to hormonal reduction. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. 3D Model of Surfactant Replacement Therapy

    Science.gov (United States)

    Grotberg, James; Tai, Cheng-Feng; Filoche, Marcel

    2015-11-01

    Surfactant Replacement Therapy (SRT) involves instillation of a liquid-surfactant mixture directly into the lung airway tree. Though successful in neonatal applications, its use in adults had early success followed by failure. We present the first mathematical model of 3D SRT where a liquid plug propagates through the tree from forced inspiration. In two separate modeling steps, the plug first deposits a coating film on the airway wall which subtracts from its volume, a ``coating cost''. Then the plug splits unevenly at the airway bifurcation due to gravity. The steps are repeated until a plug ruptures or reaches the tree endpoint alveoli/acinus. The model generates 3D images of the resulting acinar distribution and calculates two global indexes, efficiency and homogeneity. Simulating published literature, the earlier successful adult SRT studies show comparatively good index values, while the later failed studies do not. Those unsuccessful studies used smaller dose volumes with higher concentration mixtures, apparently assuming a well mixed compartment. The model shows that adult lungs are not well mixed in SRT due to the coating cost and gravity effects. Returning to the higher dose volume protocols could save many thousands of lives annually in the US. Supported by NIH Grants HL85156, HL84370 and Agence Nationale de la Recherche, ANR no. 2010-BLAN-1119-05.

  17. Hormone replacement therapy: changes in frequency and type of prescription by Dutch GPs during the last decade of the millenium.

    NARCIS (Netherlands)

    Donker, G.A.; Spreeuwenberg, P.; Bartelds, A.I.M.; Velden, K. van der; Foets, M.

    2000-01-01

    Objective: The present study was conducted in order to determine the change of frequency and type of hormone replacement therapy (HRT) regimen newly prescribed by Dutch GPs. Methods: A comparison was made of two data sets (multi-stage random samples) collected in 1987/88 and from 1995 to 1998

  18. Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

    DEFF Research Database (Denmark)

    Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh

    2004-01-01

    We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

  19. Discontinuation of nicotine replacement therapy among smoking-cessation attempters.

    Science.gov (United States)

    Burns, Emily K; Levinson, Arnold H

    2008-03-01

    Nicotine replacement therapy (NRT) doubles successful quitting, but more than half of NRT users do not comply with optimal treatment regimens. From the 2005 Colorado state tobacco survey, quit attempters who utilized NRT (N=366) were analyzed in spring 2007. Descriptive and regression analyses were used to examine reasons for discontinuing NRT, length of time on NRT, and quit intentions. The reasons for discontinuing NRT were resuming smoking (34%), side effects (17%), NRT not helping with quitting (14%), quitting smoking (10%), and cost (5%). Poverty, age, and non-Latino minority status were associated with reasons for discontinuation other than quitting smoking. Having side effects was associated with a short duration of NRT use and 95% lower odds of intending to quit in the next month. In the first population-level study examining reasons for discontinuing NRT, general-population smokers who initiate NRT use when attempting to quit are highly likely to discontinue NRT prematurely. Age and culturally-appropriate medication management interventions may increase NRT compliance and improve cessation outcomes.

  20. Enzyme replacement therapy for infantile-onset Pompe disease.

    Science.gov (United States)

    Chen, Min; Zhang, Lingli; Quan, Shuyan

    2017-11-20

    Infantile-onset Pompe disease is a rare and progressive autosomal-recessive disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Current treatment involves enzyme replacement therapy (with recombinant human alglucosidase alfa) and symptomatic therapies (e.g. to control secretions). Children who are cross-reactive immunological material (CRIM)-negative require immunomodulation prior to commencing enzyme replacement therapy.Enzyme replacement therapy was developed as the most promising therapeutic approach for Pompe disease; however, the evidence is lacking, especially regarding the optimal dose and dose frequency. To assess the effectiveness, safety and appropriate dose regimen of enzyme replacement therapy for treating infantile-onset Pompe disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, which is compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the Cochrane Central Register of Controlled Trials (CENTRAL), Embase (Ovid), PubMed and LILACS, and CBM, CNKI, VIP, and WANFANG for literature published in Chinese. In addition, we searched three online registers: WHO International Clinical Trials Registry Platform ClinicalTrials.gov, and www.genzymeclinicalresearch.com. We also searched the reference lists of relevant articles and reviews.Date of last search of the Group's Inborn Errors of Metabolism Trials Register: 24 November 2016. Randomized and quasi-randomized controlled trials of enzyme replacement therapy in children with infantile-onset Pompe disease. Two authors independently selected relevant trials, assessed the risk of bias and extracted data. We contacted investigators to obtain important missing information. We found no trials comparing the effectiveness and safety of enzyme replacement therapy to another intervention, no intervention or placebo.We found one trial (18 participants

  1. Surfactant replacement therapy--economic impact.

    Science.gov (United States)

    Pejaver, R K; al Hifzi, I; Aldussari, S

    2001-06-01

    Surfactant replacement is an effective treatment for neonatal respiratory distress syndrome. (RDS). As widespread use of surfactant is becoming a reality, it is important to assess the economic implications of this new form of therapy. A comparison study was carried out at the Neonatal Intensive Care Unit (NICU) of Northwest Armed Forces Hospital, Saudi Arabia. Among 75 infants who received surfactant for RDS and similar number who were managed during time period just before the surfactant was available, but by set criteria would have made them eligible for surfactant. All other management modalities except surfactant were the same for all these babies. Based on the intensity of monitoring and nursing care required by the baby, the level of care was divided as: Level IIIA, IIIB, Level II, Level I. The cost per day per bed for each level was calculated, taking into account the use of hospital immovable equipment, personal salaries of nursing, medical, ancillary staff, overheads and maintenance, depreciation and replacement costs. Medications used, procedures done, TPN, oxygen, were all added to individual patient's total expenditure. 75 infants in the Surfactant group had 62 survivors. They spent a total of 4300 days in hospital. (av 69.35) Out of which 970 d (av 15.65 per patient) were ventilated days. There were 56 survivors in the non-surfactant group of 75. They had spent a total of 5023 days in the hospital (av 89.69/patient) out of which 1490 were ventilated days (av 26.60 d). Including the cost of surfactant (two doses), cost of hospital stay for each infant taking the average figures of stay would be SR 118, 009.75 per surfactant treated baby and SR 164, 070.70 per non-surfactant treated baby. The difference of 46,061 SR is 39.03% more in non-surfactant group. One Saudi rial = 8 Rs (approx at the time study was carried out.) Medical care cost varies from place to place. However, it is definitely cost-effective where surfactant is concerned. Quality adjusted

  2. Continuous renal replacement therapy for critically ill infants and children

    DEFF Research Database (Denmark)

    Pedersen, Ole; Jepsen, Søren Bruun; Toft, Palle

    2012-01-01

    Continuous renal replacement therapy (CRRT) is an important treatment in critically ill children with acute kidney injury (AKI). Over the past decade, CRRT has been the preferred method of renal replacement therapy. We compared children with CRRT-treated adults with AKI in terms of return of kidney...

  3. Hormone replacement therapy increases the risk of cranial meningioma

    DEFF Research Database (Denmark)

    Andersen, Lene; Friis, Søren; Hallas, Jesper

    2013-01-01

    We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting.......We investigated the influence of hormone replacement therapy (HRT) use on the risk of meningioma in a population-based setting....

  4. Improving compliance with hormonal replacement therapy in primary osteoporosis prevention

    DEFF Research Database (Denmark)

    Vestergaard, P; Hermann, A P; Gram, J

    1997-01-01

    To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule.......To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule....

  5. Internal Fat and Cardiometabolic Risk Factors Following a Meal-Replacement Regimen vs. Comprehensive Lifestyle Changes in Obese Subjects.

    Science.gov (United States)

    König, Daniel; Zdzieblik, Denise; Deibert, Peter; Berg, Aloys; Gollhofer, Albert; Büchert, Martin

    2015-12-01

    The aim of the present study was to investigate the effect of a meal-replacement regimen vs. comprehensive lifestyle changes in overweight or obese subjects on intra-abdominal fat stores (Magnetic Resonance Imaging (MRI) measurements) and cardiometabolic risk factors. Forty-two obese men (n = 18) and women (n = 24) (age 49 ± 8 years; weight 96.3 ± 12.1 kg; BMI 32.7 ± 2.3 kg/m2) were selected for this randomized parallel-group design investigation. Subjects in the lifestyle group (LS-G; n = 22) received dietary counselling sessions and instructions how to increase physical activity. In the meal replacement group (MR-G; n = 20) meals were replaced by a low-calorie drink high in soy protein. After six months, subjects in the LS-G lost 8.88 ± 6.24 kg and subjects in the MR-G lost 7.1 ± 2.33 kg; p meal replacement group suggesting an additional effect of soy protein components.

  6. Citrate Anticoagulation during Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Ricci, Davide; Panicali, Laura; Facchini, Maria Grazia; Mancini, Elena

    2017-01-01

    During extracorporeal dialysis, some anticoagulation strategy is necessary to prevent the coagulation of blood. Heparin has historically been used as an anticoagulant because of its efficacy combined with low cost. However, a variable incidence of hemorrhagic complications (5-30%) has been documented in patients undergoing continuous renal replacement therapy (CRRT) with heparin as an anticoagulant. Citrate has anticoagulation properties secondary to its ability to chelate calcium, which is necessary for the coagulation cascade. Citrate may thus be used in a regional anticoagulation (RCA), limited to the extracorporeal circuit of CRRT, to avoid systemic anticoagulation. Recent meta-analysis confirmed the advantage of RCA over heparin in terms of incidence of bleeding during CRRT. Moreover, an increase in filter lifespan is documented, with a secondary advantage in reaching the prescribed dialysis dose. In our experience, we could confirm this positive effect. In fact, with a progressive increase in the proportion of CRRT with citrate as RCA, we obtained a reduction in the number of filters used for every 72 h of treatment (from 2.4 in 2011 to 1.3 in 2015), and most importantly, a reduction in the difference between the prescribed and delivered dialysis doses (from 22 to 7%). Citrate has an intense effect on the acid-base balance as well, if fully metabolized through the Krebs cycle, due to the production of bicarbonate. Even more severely ill patients, such as those with liver dysfunction, may be treated with RCA without severe complications, because modern machines for CRRT are equipped with simple systems that are able to manage the citrate infusion and control the calcium levels, with minimal risks of metabolic derangements. © 2017 S. Karger AG, Basel.

  7. Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens

    CERN Document Server

    Vittorino Gaddi, A; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

    2014-01-01

    Objectives: To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. Study design: This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). Methods: Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and swi...

  8. Nursing procedures during continuous renal replacement therapies: a national survey.

    Science.gov (United States)

    Ricci, Zaccaria; Benelli, Sonia; Barbarigo, Fabio; Cocozza, Giulia; Pettinelli, Noemi; Di Luca, Emanuela; Mettifogo, Mariangela; Toniolo, Andrea; Ronco, Claudio

    2015-01-01

    The current role of nurses in the management of critically ill patients needing continuous renal replacement therapies is clearly fundamental. The care of these complex patients is typically shared by critical care and dialysis nurses: their precise duties may vary from country to country. To clarify this issue we conducted a national-level survey at a recent Italian course on nursing practices during continuous renal replacement therapies. A total of 119 questionnaires were analysed. The participants, who were equally divided between critical care and dialysis nurses, came from 44 different hospitals and 35 Italian cities. Overall, 23% of participants answered that "the dialysis staff" were responsible for continuous renal replacement therapies in the Intensive Care Unit, while 39% answered "the critical care nurse", and 38% "a shared organization". Interestingly, less than the half of participants claimed specific continuous renal replacement therapies training was provided to employees before handling an acute dialysis machine. Finally, about 60% of participants had experience of extra-corporeal membrane oxygenation machines used in conjunction with continuous renal replacement therapies. Workload coordination and management of critically ill patients undergoing continuous renal replacement therapies in Italy is not standardized. At present, the duties of critical care and dialysis nurses vary significantly across the country. They frequently overlap or leave gaps in the assistance received by patients. The role of nurses involved in the care of continuous renal replacement therapies patients in Italy currently requires better organization, possibly starting with intensive standardized training and educational programs.

  9. A cost-effectiveness analysis of hormone replacement therapy in the menopause.

    Science.gov (United States)

    Cheung, A P; Wren, B G

    1992-03-02

    To evaluate the cost-effectiveness of hormone replacement therapy in the menopause with particular reference to osteoporotic fracture and myocardial infarction. The multiple-decrement form of the life table was the mathematical model used to follow women of age 50 through their lifetime under the "no hormone replacement" and "hormone replacement" assumptions. Standard demographic and health economic techniques were used to calculate the corresponding lifetime differences in direct health care costs (net costs in dollars) and health effects ("net effectiveness" in terms of life expectancy and quality, in "quality-adjusted life-years"). This was then expressed as a cost-effectiveness ratio or the cost ($) per quality-adjusted life-year (QALY) for each of the chosen hormone replacement regimens. All women of age 50 in New South Wales, Australia (n = 27,021). The analysis showed that the lifetime net increments in direct medical care costs were largely contributed by hormone drug and consultation costs. Hormone replacement was associated with increased quality-adjusted life expectancy, a large percentage of which was attributed to a relief of menopausal symptoms. Cost-effectiveness ratios ranged from under 10,000 to over a million dollars per QALY. Factors associated with improved cost-effectiveness were prolonged treatment duration, the presence of menopausal symptoms, minimum progestogen side effects (in the case of oestrogen with progestogen regimens), oestrogen use after hysterectomy and the inclusion of cardiac benefits in addition to fracture prevention. Hormone replacement therapy for symptomatic women is cost-effective when factors that enhance its efficiency are considered. Short-term treatment of asymptomatic women for prevention of osteoporotic fractures and myocardial infarction is an inefficient use of health resources. Cost-effectiveness of hormone replacement in asymptomatic women is dependent on the magnitude of cardiac benefits associated with hormone

  10. Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism?

    Science.gov (United States)

    Biondi, Bernadette; Wartofsky, Leonard

    2012-07-01

    Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic. We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action. The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients. Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.

  11. [Effects of growth hormone replacement therapy on bone metabolism].

    Science.gov (United States)

    Yamamoto, Masahiro; Sugimoto, Toshitsugu

    2014-06-01

    Growth hormone (GH) as well as insulin like growth factor-1 (IGF-1) are essential hormones to maintain homeostasis of bone turnover by activating osteoblastogenesis and osteoclastogenesis. Results from GH replacement therapy for primary osteoporosis and adult-onset GH deficiency (AGHD) suggest that one year or more treatment period by this agent is required to gain bone mineral density (BMD) over the basal level after compensating BMD loss caused by dominant increase in bone resorption which was observed at early phase of GH treatment. A recent meta-analysis demonstrates the efficacy of GH replacement therapy on increases in BMD in male patients with AGHD. Additional analyses are needed to draw firm conclusions in female patients with AGHD, because insufficient amounts of GH might be administrated to them without considerations of influence of estrogen replacement therapy on IGF-1 production. Further observational studies are needed to clarify whether GH replacement therapy prevent fracture risk in these patients.

  12. QUALITY OF LIFE, COUNSELLING AND HORMONE REPLACEMENT THERAPY

    Directory of Open Access Journals (Sweden)

    Nena Kopčavar Guček

    2008-12-01

    Quality of life in menopause is a result of many factors and therefore it is very individual.Hormone replacement therapy is one of the possibilities of improvement. Therefore, it isessential that a woman is adequately informed about all the advantages and risks of thehormonal replacement therapy. Only an informed patient can be a partner in shareddecision making about the improvement of quality of life

  13. Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

    Directory of Open Access Journals (Sweden)

    George L Drusano

    Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

  14. Spontaneous Coronary Artery Dissection following Topical Hormone Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Alexander L. Pan

    2012-01-01

    Full Text Available Spontaneous coronary artery dissection is a rare condition, usually presenting as an acute coronary syndrome, and is often seen in states associated with high systemic estrogen levels such as pregnancy or oral contraceptive use. While topical hormonal replacement therapy may result in increased estrogen levels similar to those documented with oral contraceptive use, there are no reported cases of spontaneous coronary dissection with topical hormonal replacement therapy. We describe a 53-year-old female who developed two spontaneous coronary dissections while on topical hormonal replacement therapy. The patient had no other risk factors for coronary dissection. After withdrawal from topical hormonal therapy, our patient has done well and has not had recurrent coronary artery dissections over a one-year follow-up period. The potential contributory role of topical hormonal therapy as a cause of spontaneous coronary dissection should be recognized.

  15. Economic impact of simplified de Gramont regimen in first-line therapy in metastatic colorectal cancer.

    Science.gov (United States)

    Limat, Samuel; Bracco-Nolin, Claire-Hélène; Legat-Fagnoni, Christine; Chaigneau, Loic; Stein, Ulrich; Huchet, Bernard; Pivot, Xavier; Woronoff-Lemsi, Marie-Christine

    2006-06-01

    The cost of chemotherapy has dramatically increased in advanced colorectal cancer patients, and the schedule of fluorouracil administration appears to be a determining factor. This retrospective study compared direct medical costs related to two different de Gramont schedules (standard vs. simplified) given in first-line chemotherapy with oxaliplatin or irinotecan. This cost-minimization analysis was performed from the French Health System perspective. Consecutive unselected patients treated in first-line therapy by LV5FU2 de Gramont with oxaliplatin (Folfox regimen) or with irinotecan (Folfiri regimen) were enrolled. Hospital and outpatient resources related to chemotherapy and adverse events were collected from 1999 to 2004 in 87 patients. Overall cost was reduced in the simplified regimen. The major factor which explained cost saving was the lower need for admissions for chemotherapy. Amount of cost saving depended on the method for assessing hospital stay. In patients treated by the Folfox regimen the per diem and DRG methods found cost savings of Euro 1,997 and Euro 5,982 according to studied schedules; in patients treated by Folfiri regimen cost savings of Euro 4,773 and Euro 7,274 were observed, respectively. In addition, travel costs were also reduced by simplified regimens. The robustness of our results was showed by one-way sensitivity analyses. These findings demonstrate that the simplified de Gramont schedule reduces costs of current first-line chemotherapy in advanced colorectal cancer. Interestingly, our study showed several differences in costs between two costing approaches of hospital stay: average per diem and DRG costs. These results suggested that standard regimen may be considered a profitable strategy from the hospital perspective. The opposition between health system perspective and hospital perspective is worth examining and may affect daily practices. In conclusion, our study shows that the simplified de Gramont schedule in combination with

  16. Revisiting Dosing Regimen Using Pharmacokinetic/Pharmacodynamic Mathematical Modeling: Densification and Intensification of Combination Cancer Therapy.

    Science.gov (United States)

    Meille, Christophe; Barbolosi, Dominique; Ciccolini, Joseph; Freyer, Gilles; Iliadis, Athanassios

    2016-08-01

    Controlling effects of drugs administered in combination is particularly challenging with a densified regimen because of life-threatening hematological toxicities. We have developed a mathematical model to optimize drug dosing regimens and to redesign the dose intensification-dose escalation process, using densified cycles of combined anticancer drugs. A generic mathematical model was developed to describe the main components of the real process, including pharmacokinetics, safety and efficacy pharmacodynamics, and non-hematological toxicity risk. This model allowed for computing the distribution of the total drug amount of each drug in combination, for each escalation dose level, in order to minimize the average tumor mass for each cycle. This was achieved while complying with absolute neutrophil count clinical constraints and without exceeding a fixed risk of non-hematological dose-limiting toxicity. The innovative part of this work was the development of densifying and intensifying designs in a unified procedure. This model enabled us to determine the appropriate regimen in a pilot phase I/II study in metastatic breast patients for a 2-week-cycle treatment of docetaxel plus epirubicin doublet, and to propose a new dose-ranging process. In addition to the present application, this method can be further used to achieve optimization of any combination therapy, thus improving the efficacy versus toxicity balance of such a regimen.

  17. Enzyme replacement therapy in Fabry disease, towards individualized treatment

    NARCIS (Netherlands)

    Arends, M.

    2017-01-01

    Fabry disease is a very heterogeneous disorder for which expensive enzyme replacement therapy is available since more than 15 years. Because of the variety of symptoms and disease course, individual choices need to be made to improve the appropriate use of therapy. Supported by ZONWM, we have been

  18. Intrinsic imperfections of endocrine replacement therapy

    NARCIS (Netherlands)

    Romijn, J. A.; Smit, J. W. A.; Lamberts, S. W. J.

    2003-01-01

    Hormonal substitution therapy has been extremely successful, with respect to morbidity and mortality, in the treatment of the major syndromes of endocrine insufficiency. However, many patients treated for endocrine insufficiencies still suffer from more or less vague complaints and a decreased

  19. EXPERIMENTAL CONFIRMATION FOR SELECTION OF IRRADIATION REGIMENS FOR INTRAPERITONEAL PHOTODYNAMIC THERAPY WITH PORPHYRIN AND PHTHALOCYANINE PHOTOSENSITIZERS

    Directory of Open Access Journals (Sweden)

    A. A. Pankratov

    2017-01-01

    Full Text Available Optimized irradiation regimens for intraperitoneal photodynamic therapy with porphyrin and phthalocyanine photosensitizers are determined in in vitro and in vivo studies.The experimental  study on НЕр2 cell line showed that reduce of power density for constant  light dose increased significantly the efficacy of photodynamic therapy (the reduce of power density from 20-80 mW/cm2 to 10 mW/cm2 had the same results (90% cell death for half as much concentration of the photosensitizer.The obtained results were confirmed in vivo in mice with grafted tumor S-37. For light dose of 90 J/cm2  and power density of 25 mW/cm2 none of animals in the experimental  group had total resorption of the tumor. For the same light dose and decrease  of power density to 12 mW/cm2  total tumor resorption was achieved in 34% of animals, 66% of animals died from phototoxic  shock. For twofold decrease  of light dose – to 45 J/cm2  with the same low-intensity power density (12 mW/cm2 we managed total tumor resorption in 100% of animals.In the following studies of optimized irradiation regimen for intrapleural photodynamic therapy the reaction of intact peritoneum of rats on photodynamic exposure was assessed and optimized parameters of laser irradiation, which did not cause necrosis and intense inflammatory reaction of peritoneum, were determined – light dose of 10 J/cm2  with power density of mW/cm2.Thus, the reasonability for use of low-intensity regimens of irradiation for intraperitoneal photodynamic therapy was confirmed experimentally with possibility of high efficacy of treatment without inflammatory reactions of peritoneum.

  20. Gene replacement therapy for genetic hepatocellular jaundice.

    Science.gov (United States)

    van Dijk, Remco; Beuers, Ulrich; Bosma, Piter J

    2015-06-01

    Jaundice results from the systemic accumulation of bilirubin, the final product of the catabolism of haem. Inherited liver disorders of bilirubin metabolism and transport can result in reduced hepatic uptake, conjugation or biliary secretion of bilirubin. In patients with Rotor syndrome, bilirubin (re)uptake is impaired due to the deficiency of two basolateral/sinusoidal hepatocellular membrane proteins, organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3. Dubin-Johnson syndrome is caused by a defect in the ATP-dependent canalicular transporter, multidrug resistance-associated protein 2 (MRP2), which mediates the export of conjugated bilirubin into bile. Both disorders are benign and not progressive and are characterised by elevated serum levels of mainly conjugated bilirubin. Uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) is responsible for the glucuronidation of bilirubin; deficiency of this enzyme results in unconjugated hyperbilirubinaemia. Gilbert syndrome is the mild and benign form of inherited unconjugated hyperbilirubinaemia and is mostly caused by reduced promoter activity of the UGT1A1 gene. Crigler-Najjar syndrome is the severe inherited form of unconjugated hyperbilirubinaemia due to mutations in the UGT1A1 gene, which can cause kernicterus early in life and can be even lethal when left untreated. Due to major disadvantages of the current standard treatments for Crigler-Najjar syndrome, phototherapy and liver transplantation, new effective therapeutic strategies are under development. Here, we review the clinical features, pathophysiology and genetic background of these inherited disorders of bilirubin metabolism and transport. We also discuss the upcoming treatment option of viral gene therapy for genetic disorders such as Crigler-Najjar syndrome and the possible immunological consequences of this therapy.

  1. Enzyme replacement therapy for murine hypophosphatasia.

    Science.gov (United States)

    Millán, José Luis; Narisawa, Sonoko; Lemire, Isabelle; Loisel, Thomas P; Boileau, Guy; Leonard, Pierre; Gramatikova, Svetlana; Terkeltaub, Robert; Camacho, Nancy Pleshko; McKee, Marc D; Crine, Philippe; Whyte, Michael P

    2008-06-01

    Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5'-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6-dependent seizures. There is no established medical treatment. Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2-/-), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, microCT, and histomorphometry. Akp2-/- mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2-/- mice.

  2. Enzyme Replacement Therapy for Murine Hypophosphatasia*

    Science.gov (United States)

    Millán, José Luis; Narisawa, Sonoko; Lemire, Isabelle; Loisel, Thomas P; Boileau, Guy; Leonard, Pierre; Gramatikova, Svetlana; Terkeltaub, Robert; Camacho, Nancy Pleshko; McKee, Marc D; Crine, Philippe; Whyte, Michael P

    2008-01-01

    Introduction Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5`-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6-dependent seizures. There is no established medical treatment. Materials and Methods Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2−/−), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, μCT, and histomorphometry. Results Akp2−/− mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Conclusions Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2−/− mice. PMID:18086009

  3. Seeking optimal renal replacement therapy delivery in intensive care units.

    Science.gov (United States)

    Kocjan, Marinka; Brunet, Fabrice P

    2010-01-01

    Globally, critical care environments within health care organizations strive to provide optimal quality renal replacement therapy (RRT), an artificial replacement for lost kidney function. Examination of RRT delivery model literature and a case study review of the multidisciplinary-mixed RRT delivery model utilized within a closed medical surgical intensive care unit illustrates the organizational and clinical management of specialized resource and multidisciplinary roles. The successful utilization of a specific RRT delivery model is dependent upon resource availability.

  4. Colostrum replacer feeding regimen, addition of sodium bicarbonate, and milk replacer: the combined effects on absorptive efficiency of immunoglobulin G in neonatal calves.

    Science.gov (United States)

    Cabral, R G; Cabral, M A; Chapman, C E; Kent, E J; Haines, D M; Erickson, P S

    2014-01-01

    Eighty Holstein and Holstein cross dairy calves were blocked by birth date and randomly assigned to 1 of 8 treatments within each block to examine the effect of a colostrum replacer (CR) feeding regimen, supplementation of CR with sodium bicarbonate (NaHCO3), and provision of a milk replacer (MR) feeding on IgG absorption. Calves were offered a CR containing 184.5g/L of IgG in either 1 feeding at 0h (within 30 min of birth), with or without 30g of NaHCO3, with or without a feeding of MR at 6h of age, or 2 feedings of CR (123g of IgG at 0h with or without 20g of NaHCO3 and 61.5g of IgG at 6h with or without 10g of NaHCO3), with or without a MR feeding at 12h. Therefore, treatments were (1) 1 feeding of CR; (2) 2 feedings of CR; (3) 1 feeding of CR + 30g of NaHCO3; (4) 2 feedings of CR + 30g of NaHCO3; (5) 1 feeding of CR + MR feeding; (6) 2 feedings of CR + MR feeding; (7) 1 feeding of CR + 30g NaHCO3 + MR feeding; and (8) 2 feedings of CR + 30g NaHCO3 + MR feeding. Blood samples were obtained at 0, 6, 12, 18, and 24h after birth and were analyzed for IgG via radial immunoassay. Results indicated that CR feeding schedule, MR feeding, and the interactions CR × Na, CR × MR, and CR × Na × MR were similar for 24-h serum IgG, apparent efficiency of absorption, or area under the curve. Serum IgG at 24h, apparent efficiency of absorption, and area under the curve were decreased with addition of NaHCO3 compared with calves not supplemented with NaHCO3. These data indicate that supplementation of CR with NaHCO3 is not beneficial to IgG absorption and feeding MR within 6h of CR feeding does not affect IgG absorption. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Risk of fracture in adults on renal replacement therapy

    DEFF Research Database (Denmark)

    Hansen, Ditte; Olesen, Jonas B; Gislason, Gunnar H

    2016-01-01

    BACKGROUND: Patients on dialysis treatment or living with a transplanted kidney have several risk factors for bone fracture, especially disturbances in mineral metabolism and immunosuppressive therapy. We describe the incidence of fracture in this retrospective national Danish cohort study and ex....... Differences in age, gender, drug use and comorbidity only partly explain this increased risk. Further studies are warranted to explore the reason for this increased fracture risk in patients on renal replacement therapy....

  6. Renal Replacement Therapy Resources in Africa | Matri | Arab ...

    African Journals Online (AJOL)

    However, there is a general impression that it is at least three to four times more frequent than in more developed countries Methods: a survey on renal replacement therapy in Africa was conducted in the context of the African Association of Nephrology (AFRAN) Congress 2007. A questionnaire was sent to leading African ...

  7. The secondary hypothyroidism after radioiodine therapy and the replacement treatment

    International Nuclear Information System (INIS)

    Xu Ying; Xu Xiaohui

    2004-01-01

    The secondary hypothyroidism is the most important intercurrent disease after radioiodine therapy. The early hypothyroidism and the late hypothyroidism are incompletely different in pathogenesis. It needs researching further. there has not yet been an affirmable answer to choose the distillates from animal hypothyroid extract or complex preparation of levo-thyroxine in replacement treatment. (authors)

  8. Lifetime risk of renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    van den Brand, Jan A J G; Pippias, Maria; Stel, Vianda S

    2017-01-01

    Background: Upcoming KDIGO guidelines for the evaluation of living kidney donors are expected to move towards a personal risk-based evaluation of potential donors. We present the age and sex-specific lifetime risk of renal replacement therapy (RRT) for end-stage renal disease in 10 European...

  9. A Critical Evaluation of Nicotine Replacement Therapy for Teenage Smokers.

    Science.gov (United States)

    Patten, Christi A.

    2000-01-01

    Evaluates the appropriateness and feasibility of nicotine replacement therapy (NRT) in teenage smokers. Available forms of NRT, theoretical rationale and efficacy of NRT, ethical considerations, and the feasibility of NRT in teenage smokers are addressed. Several characteristics similar to adult nicotine dependent smokers have been found in teen…

  10. RANDOMIZED EUROPEAN MULTICENTER TRIAL OF SURFACTANT REPLACEMENT THERAPY FOR SEVERE NEONATAL RESPIRATORY-DISTRESS SYNDROME - SINGLE VERSUS MULTIPLE DOSES OF CUROSURF

    NARCIS (Netherlands)

    SPEER, CP; ROBERTSON, B; CURSTEDT, T; HALLIDAY, HL; COMPAGNONE, D; GEFELLER, O; HARMS, K; HERTING, E; MCCLURE, G; REID, M; TUBMAN, R; HERIN, P; NOACK, G; KOK, J; KOPPE, J; VANSONDEREN, L; LAUFKOTTER, E; KOHLER, W; BOENISCH, H; ALBRECHT, K; HANSSLER, L; HAIM, M; OETOMO, SB; Okken, Albert; ALTFELD, PC; GRONECK, P; KACHEL, W; RELIER, JP; WALTI, H

    There is now convincing evidence that the severity of neonatal respiratory distress syndrome can be reduced by surfactant replacement therapy; however, the optimal therapeutic regimen has not been defined. This randomized European multicenter trial was designed to determine whether the beneficial

  11. Enzyme replacement and substrate reduction therapy for Gaucher disease.

    Science.gov (United States)

    Shemesh, Elad; Deroma, Laura; Bembi, Bruno; Deegan, Patrick; Hollak, Carla; Weinreb, Neal J; Cox, Timothy M

    2015-03-27

    Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four treatments are currently approved by various regulatory authorities for use in routine clinical practice. Hitherto, because of the relatively few people affected worldwide, many of whom started therapy during a prolonged period when there were essentially no alternatives to imiglucerase, these treatments have not been systematically evaluated in studies such as randomized controlled trials now considered necessary to generate the highest level of clinical evidence. To summarize all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Additional searches were conducted on ClinicalTrials.gov for any ongoing studies with potential interim results, and through PubMed. We also searched the reference lists of relevant articles and reviews.Date of last search: 07 August 2014. All randomized and quasi-randomized controlled studies (including open-label studies and cross-over studies) assessing enzyme replacement therapy or substrate reduction therapy, or both, in all types of Gaucher disease were included. Two authors independently assessed the risk of bias in the included studies, and extracted relevant data. Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized.Four studies reported the responses to enzyme replacement therapy of previously

  12. Current regimen of pulse therapy for pemphigus: Minor modifications, improved results

    Directory of Open Access Journals (Sweden)

    Pasricha J

    2008-01-01

    Full Text Available Background: If administered properly, dexamethasone cyclophosphamide pulse (DCP therapy has the potential to effect lifelong recovery from pemphigus. Aims: The objective of this paper is to highlight various parameters of DCP therapy and also, to report the effects of a few modifications in the regimen. Methods: An analysis of 123 patients treated with the DCP/DP regimen over a period of five years (1998 to 2002 is presented here. Seventeen patients who did not start/continue the treatment and three patients who died during the treatment have been excluded from the analysis. Twenty patients who had not yet started families were given only dexamethasone pulses (DPs while 103 patients received DCPs. Low dose (50 mg/day cyclophosphamide was used as in the standard regimen. The three modifications introduced into the regimen were: (1 an additional daily dose of oral betamethasone sufficient to control the disease activity during phase I, which was progressively tapered off completely as the patient recovered, (2 use of systemic antibiotics if the patient had skin lesions, and oral anti-candida drugs if the patient had oral ulcers until complete healing, and (3 insistence on thorough cleaning of the skin and scalp with a normal soap and shampoo, and proper maintenance of oral hygiene in spite of skin/mucosal lesions. The regimen consisted of DCP/DP repeated in exactly 28-day cycles, along with 50 mg cyclophosphamide per day, insistence on completing the treatment and avoiding irregular pulses in all patients. The number of DCPs/DPs during phase I varied in different patients depending upon the dose of betamethasone used and the rate of recovery, but phase II (nine DCPs/DPs in exactly 28-day cycles along with 50 mg cyclophosphamide per day and phase III (only 50 mg cyclophosphamide per day was fixed at nine months each. This was followed by posttreatment follow-up (phase IV. Results: At present, all the patients are in complete remission. The

  13. Hormone replacement therapy and the risk of endometrial cancer

    DEFF Research Database (Denmark)

    Sjögren, Lea L; Mørch, Lina Steinrud; Løkkegaard, Ellen

    2016-01-01

    BACKGROUND: In 1975, estrogen only was found to be associated with an increased risk of endometrial cancer. In November 2015, NICE guidelines on hormone therapy were published that did not take this risk into account. AIM: This systematic literature review assesses the safety of estrogen plus...... progestin therapy according to the risk of endometrial cancer, while considering both regimen and type of progestin. METHODS: PubMed, EMBASE and the Cochrane Library were searched, resulting in the identification of 527 published articles on menopausal women with intact uteri treated with estrogen only......, estrogen plus progestin or tibolone for a minimum of one year. Risk of endometrial cancer was compared to placebo or never users and measured as relative risk, hazard or odds ratio. RESULTS: 28 studies were included. The observational literature found an increased risk among users of estrogen alone...

  14. Antithyroid drug regimens before and after 131I-therapy for hyperthyroidism: evidence-based?

    Science.gov (United States)

    Mijnhout, G S; Franken, A A M

    2008-06-01

    In view of the new national guideline on thyroid dysfunction, the evidence base for current practice as well as the new guideline is assessed with regard to the use of antithyroid drugs (ATDs) before and after radioiodine (131I) therapy. In December 2006, we surveyed 16 hospitals by telephone about different aspects of their antithyroid drug regimen: all eight academic centres and eight nonacademic teaching hospitals. The literature was searched for an evidence-based answer to each question in the inquiry. 13 of 16 hospitals (81%) use antithyroid drugs for pretreatment before 131I. ATDs are discontinued on average four days before 131I or diagnostic scan. However, 27% stop only three days beforehand, which may diminish the effect of 131I. Propylthiouracil (PTU) is also withdrawn four days before 131I, although the literature shows that PTU diminishes the effect of 131I even if it is stopped 15 days beforehand. Resumption of ATDs after 131I to prevent thyrotoxicosis is common practice (81%). One hospital (6%) never restarts ATDs, two (13%) only by indication. Adjunctive treatment consists of combination therapy in 93%, is usually resumed within two days after 131I therapy, and then continued for two to six months. Routine adjunctive treatment is not evidence-based and may be limited to a high-risk subset, especially elderly patients (>70 years) and patients with cardiac comorbidity. Resumption of ATDs within five to seven days after 131I may diminish the effect of 131I. Antithyroid drug regimens in the Netherlands are heterogeneous. The evidence base of current practice and the new guideline are discussed.

  15. Therapy of Hypoparathyroidism by Replacement with Parathyroid Hormone

    Directory of Open Access Journals (Sweden)

    Lars Rejnmark

    2014-01-01

    Full Text Available Hypoparathyroidism (HypoPT is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH. HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (QoL seems impaired and patients are at increased risk of renal complications. A number of studies have suggested subcutaneous injections with PTH as an alternative therapy. By replacement with the missing hormone, urinary calcium may be lowered and QoL may improve. PTH replacement therapy (PTH-RT possesses, nevertheless, a number of challenges. If PTH is injected only once a day, fluctuations in calcium levels may occur resulting in hypercalcemia in the hours following an injection. Twice-a-day injections seem to cause less fluctuation in plasma calcium but do stimulate bone turnover to above normal. Most recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range. Further studies are needed to assess the long-term effects. If beneficial, it seems likely that standard treatment of HypoPT in the future will change into replacement therapy with the missing hormone.

  16. Involved field radiation therapy for Hodgkin's disease autologous bone marrow transplantation regimens

    International Nuclear Information System (INIS)

    Pezner, Richard D.; Nademanee, Auayporn; Niland, Joyce C.; Vora, Nayana; Forman, Stephen J.

    1995-01-01

    From 1986 through 1992, involved-field radiation therapy (IF-RT) was administered to 29 of 86 patients with recurrent Hodgkin's disease (HD) who received a high-dose cyclophosphamide/etoposide regimen with autologous bone marrow transplantation (A-BMT). Patients without a significant history of prior RT received total body irradiation (TBI), initially as a single dose 5-7.5 Gy, and subsequently with fractionated TBI (F-TBI) delivering 12 Gy. Previously irradiated patients received a high-dose BCNU regimen instead of TBI. IF-RT was employed selectively, usually for sites of bulky disease (> 5 cm). IF-RT doses were typically 20 Gy at 2 Gy per fraction for TBI patients and 30-40 Gy at 1.8-2.0 Gy per fraction for non-TBI Patients. Fatal complications developed in four patients while second malignancies have developed in two. The region which received IF-RT was the site of first recurrence in only two cases (7%). With a median follow-up of 28 months, the two-year disease-free survival rate was 44%. For the 22 patients treated by either F-TBI or high-dose BCNU, the 2-year disease-free survival rate was 50% with a median follow up of 29 months. Selective use of IF-RT may increase the chances of complete remission and disease free survival in HD patients with a history of bulky disease

  17. Pancreatic enzyme replacement therapy for people with cystic fibrosis.

    Science.gov (United States)

    Somaraju, Usha Rani; Solis-Moya, Arturo

    2016-11-23

    Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One

  18. Estrogen replacement therapy, Alzheimer's disease, and mild cognitive impairment.

    Science.gov (United States)

    Mulnard, Ruth A; Corrada, Marìa M; Kawas, Claudia H

    2004-09-01

    This article highlights the latest findings regarding estrogen replacement therapy in the treatment and prevention of Alzheimer's disease (AD) and mild cognitive impairment in women. Despite considerable evidence from observational studies, recent randomized clinical trials of conjugated equine estrogens, alone and in combination with progestin, have shown no benefit for either the treatment of established AD or for the short-term prevention of AD, mild cognitive impairment, or cognitive decline. Based on the evidence, there is no role at present for estrogen replacement therapy in the treatment or prevention of AD or cognitive decline, despite intriguing results from the laboratory and from observational studies. However, numerous questions remain about the biologic effects of estrogens on brain structure and function. Additional basic and clinical investigations are necessary to examine different forms and dosages of estrogens, other populations, and the relevance of timing and duration of exposure.

  19. The Effect of Nicotine Replacement Therapy Advertising on Youth Smoking

    OpenAIRE

    Henry Saffer; Melanie Wakefield; Yvonne Terry-McElrath

    2007-01-01

    This paper examines the effect of nicotine replacement therapy (NRT) advertising on youth smoking. NRT advertising could decrease smoking by informing smokers that the product can make quitting easier and thus inducing more smokers to try and quit. However, a moral hazard is created because NRT advertising increases the expectation that cessation is relatively easy. NRT advertising could thus induce youth to smoke, to smoke more and/or to delay quit attempts. Data from Nielsen Media Research ...

  20. High Phenobarbital Clearance During Continuous Renal Replacement Therapy

    Science.gov (United States)

    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-01-01

    Abstract Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring. A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure. Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus. The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed. Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring. PMID:25101986

  1. Comparison of Sequential Regimen and Standard Therapy for Helicobacter pylori Eradication in Patients with Dyspepsia

    Directory of Open Access Journals (Sweden)

    Gh. Roshanaei

    2013-10-01

    Full Text Available Introduction & Objective: Some studies have reported successful eradication rates using se-quential therapy but more recent studies performed in Asia did not find a similar benefit. Due to inconsistencies in the comparison of standard triple drugs therapy and sequential regimen, in the previous researches we decided to compare these treatments in Persian patients. Materials & Methods: This study is a randomized clinical trial, performed in one hundred and forty patients suffering from dyspepsia with indication for H. pylori eradication between No-vember 2010 and March 2012.Patients were randomized in two equal groups. The patients in the first group (standard were treated by omeprazole capsule 20 mg BID, amoxicillin cap-sule 1 gr BID, clarithromycin tablet 500mg BID for 14 days; while the patients in the second group (sequential were treated by omeprazole capsule 20 mg for 10 days, amoxicillin cap-sule 1 gr BID for 5 days, then clarithromycin tablet 500 mg and tinidazole tablet 500 mg BID for other 5 days. 4-6 weeks after the treatment, we compared the eradication of H.pylori be-tween the two groups by urease breathe test with C14. Results: H. pylori infection was successfully cured in 57/70 (81.43% with a 10-day sequen-tial therapy, in 60/70 (85.75% with the standard fourteen-day triple therapy, respectively. Conclusion: We detected no significant differences between the 10-day sequential eradication therapy for H. pylori and 14-day standard triple treatment among the patients. (Sci J Hamadan Univ Med Sci 2013; 20 (3:184-193

  2. Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Gérald E. Piérard

    2013-01-01

    Full Text Available Menopause is a key point moment in the specific aging process of women. It represents a universal evolution in life. Its initiation is defined by a 12-month amenorrhea following the ultimate menstrual period. It encompasses a series of different biologic and physiologic characteristics. This period of life appears to spot a decline in a series of skin functional performances initiating tissue atrophy, withering, and slackness. Any part of the skin is possibly altered, including the epidermis, dermis, hypodermis, and hair follicles. Hormone replacement therapy (oral and nonoral and transdermal estrogen therapy represent possible specific managements for women engaged in the climacteric phase. All the current reports indicate that chronologic aging, climacteric estrogen deficiency, and adequate hormone therapy exert profound effects on various parts of the skin.

  3. Discontinuation of continuous renal replacement therapy: A post hoc analysis of a prospective multicenter observational study

    NARCIS (Netherlands)

    Uchino, Shigehiko; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Oudemans-van Straaten, Heleen; Ronco, Claudio; Kellum, John A.

    2009-01-01

    Objectives: To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes.

  4. Neuronal replacement therapy: previous achievements and challenges ahead

    Science.gov (United States)

    Grade, Sofia; Götz, Magdalena

    2017-10-01

    Lifelong neurogenesis and incorporation of newborn neurons into mature neuronal circuits operates in specialized niches of the mammalian brain and serves as role model for neuronal replacement strategies. However, to which extent can the remaining brain parenchyma, which never incorporates new neurons during the adulthood, be as plastic and readily accommodate neurons in networks that suffered neuronal loss due to injury or neurological disease? Which microenvironment is permissive for neuronal replacement and synaptic integration and which cells perform best? Can lost function be restored and how adequate is the participation in the pre-existing circuitry? Could aberrant connections cause malfunction especially in networks dominated by excitatory neurons, such as the cerebral cortex? These questions show how important connectivity and circuitry aspects are for regenerative medicine, which is the focus of this review. We will discuss the impressive advances in neuronal replacement strategies and success from exogenous as well as endogenous cell sources. Both have seen key novel technologies, like the groundbreaking discovery of induced pluripotent stem cells and direct neuronal reprogramming, offering alternatives to the transplantation of fetal neurons, and both herald great expectations. For these to become reality, neuronal circuitry analysis is key now. As our understanding of neuronal circuits increases, neuronal replacement therapy should fulfill those prerequisites in network structure and function, in brain-wide input and output. Now is the time to incorporate neural circuitry research into regenerative medicine if we ever want to truly repair brain injury.

  5. The influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate triple therapy regimens for Helicobacter pylori infection

    NARCIS (Netherlands)

    Van der Wouden, EJ; Thijs, JC; Van Zwet, AA; Kooy, A; Kleibeuker, JH

    Aim: To assess the influence of metronidazole resistance on the efficacy of ranitidine bismuth citrate-based triple therapy regimens in two consecutive studies. Methods: In the first study, patients with a culture-proven Helicobacter pylori infection were treated with ranitidine bismuth citrate 400

  6. Hormone replacement therapy and risk of non-fatal stroke

    DEFF Research Database (Denmark)

    Pedersen, A T; Lidegaard, O; Kreiner, S

    1997-01-01

    haemorrhage, 846 thromboembolic infarction, 321 transient ischaemic attack) and 3171 controls. FINDINGS: After adjustment for confounding variables and correction for the trend in sales of HRT preparations, no significant associations were detected between current use of unopposed oestrogen replacement...... influence on the risk of subarachnoid haemorrhage (1.22 [0.79-1.89]), intracerebral haemorrhage (1.17 [0.64-2.13]), or thromboembolic infarction (1.17 [0.92-1.47]). A significantly increased incidence of transient ischaemic attacks among former users of HRT and among current users of unopposed oestrogen may...... to some extent be explained by selection--HRT users being more aware of symptoms than non-users. INTERPRETATION: Unopposed oestrogen and combined oestrogen-progestagen replacement therapy have no influence on the risk of non-fatal thromboembolic or haemorrhagic stroke in women aged 45-64 years....

  7. Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy.

    Science.gov (United States)

    Etiebet, Mary-Ann A; Shepherd, James; Nowak, Rebecca G; Charurat, Man; Chang, Harry; Ajayi, Samuel; Elegba, Olufunmilayo; Ndembi, Nicaise; Abimiku, Alashle; Carr, Jean K; Eyzaguirre, Lindsay M; Blattner, William A

    2013-02-20

    In resource-limited settings, HIV-1 drug resistance testing to guide antiretroviral therapy (ART) selection is unavailable. We retrospectively conducted genotypic analysis on archived samples from Nigerian patients who received targeted viral load testing to confirm treatment failure and report their drug resistance mutation patterns. Stored plasma from 349 adult patients on non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens was assayed for HIV-1 RNA viral load, and samples with more than 1000 copies/ml were sequenced in the pol gene. Analysis for resistance mutations utilized the IAS-US 2011 Drug Resistance Mutation list. One hundred and seventy-five samples were genotyped; the majority of the subtypes were G (42.9%) and CRF02_AG (33.7%). Patients were on ART for a median of 27 months. 90% had the M184V/I mutation, 62% had at least one thymidine analog mutation, and 14% had the K65R mutation. 97% had an NNRTI resistance mutation and 47% had at least two etravirine-associated mutations. In multivariate analysis tenofovir-based regimens were less likely to have at least three nucleoside reverse transcriptase inhibitor (NRTI) mutations after adjusting for subtype, previous ART, CD4, and HIV viral load [P < 0.001, odds ratio (OR) 0.04]. 70% of patients on tenofovir-based regimens had at least two susceptible NRTIs to include in a second-line regimen compared with 40% on zidovudine-based regimens (P = 0.04, OR = 3.4). At recognition of treatment failure, patients on tenofovir-based first-line regimens had fewer NRTI drug-resistant mutations and more active NRTI drugs available for second-line regimens. These findings can inform strategies for ART regimen sequencing to optimize long-term HIV treatment outcomes in low-resource settings.

  8. The benefits and risks of testosterone replacement therapy: a review

    Directory of Open Access Journals (Sweden)

    Nazem Bassil

    2009-06-01

    Full Text Available Nazem Bassil1, Saad Alkaade2, John E Morley1,31Division of Geriatric Medicine; 2Internal Medicine, Saint Louis University Health Sciences Center, St. Louis, Missouri, USA; 3GRECC, VA Medical Center, St. Louis, Missouri, USAAbstract: Increased longevity and population aging will increase the number of men with late onset hypogonadism. It is a common condition, but often underdiagnosed and undertreated. The indication of testosterone-replacement therapy (TRT treatment requires the presence of low testosterone level, and symptoms and signs of hypogonadism. Although controversy remains regarding indications for testosterone supplementation in aging men due to lack of large-scale, long-term studies assessing the benefits and risks of testosterone-replacement therapy in men, reports indicate that TRT may produce a wide range of benefits for men with hypogonadism that include improvement in libido and sexual function, bone density, muscle mass, body composition, mood, erythropoiesis, cognition, quality of life and cardiovascular disease. Perhaps the most controversial area is the issue of risk, especially possible stimulation of prostate cancer by testosterone, even though no evidence to support this risk exists. Other possible risks include worsening symptoms of benign prostatic hypertrophy, liver toxicity, hyperviscosity, erythrocytosis, worsening untreated sleep apnea or severe heart failure. Despite this controversy, testosterone supplementation in the United States has increased substantially over the past several years. The physician should discuss with the patient the potential benefits and risks of TRT. The purpose of this review is to discuss what is known and not known regarding the benefits and risks of TRT.Keywords: hypogonadism, testosterone replacement therapy, erectile dysfunction, osteoporosis, cardiovascular disease

  9. Modern iron replacement therapy: clinical and pathophysiological insights.

    Science.gov (United States)

    Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa

    2018-01-01

    Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

  10. Renal replacement therapy in sepsis-induced acute renal failure

    Directory of Open Access Journals (Sweden)

    Rajapakse Senaka

    2009-01-01

    Full Text Available Acute renal failure (ARF is a common complication of sepsis and carries a high mortality. Renal replacement therapy (RRT during the acute stage is the mainstay of therapy. Va-rious modalities of RRT are available. Continuous RRT using convective methods are preferred in sepsis-induced ARF, especially in hemodynamically unstable patients, although clear evidence of benefit over intermittent hemodialysis is still not available. Peritoneal dialysis is clearly inferior, and is not recommended. Early initiation of RRT is probably advantageous, although the optimal timing of dialysis is yet unknown. Higher doses of RRT are more likely to be beneficial. Use of bio-compatible membranes and bicarbonate buffer in the dialysate are preferred. Anticoagulation during dialysis must be carefully adjusted and monitored.

  11. Patient and regimen characteristics associated with self-reported nonadherence to antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Patrick S Sullivan

    Full Text Available BACKGROUND: Nonadherence to antiretroviral therapy (ARVT is an important behavioral determinant of the success of ARVT. Nonadherence may lead to virological failure, and increases the risk of development of drug resistance. Understanding the prevalence of nonadherence and associated factors is important to inform secondary HIV prevention efforts. METHODOLOGY/PRINCIPAL FINDINGS: We used data from a cross-sectional interview study of persons with HIV conducted in 18 U.S. states from 2000-2004. We calculated the proportion of nonadherent respondents (took or=4 medications; living in a shelter or on the street; and feeling "blue" >or=14 of the past 30 days. We found weaker associations with having both male-male sex and injection drug use risks for HIV acquisition; being prescribed ARVT for >or=21 months; and being prescribed a protease inhibitor (PI-based regimen not boosted with ritonavir. The median proportion of doses missed was 50%. The most common reasons for missing doses were forgetting and side effects. CONCLUSIONS/SIGNIFICANCE: Self-reported recent nonadherence was high in our study. Our data support increased emphasis on adherence in clinical settings, and additional research on how providers and patients can overcome barriers to adherence.

  12. How much elderly people of Isfahan are adherent to their drug therapy regimens?

    Science.gov (United States)

    Abazari, Parvaneh; Jafari, Tayebe Arab; Sabzghabaee, Ali Mohammad

    2017-01-01

    The need for a correct follow-up for medical advices of health givers is the cornerstone for avoiding drug-related complications in especial period of elderly people life. There isn't any data about drug therapy regimens adherence of elderly people of Isfahan. In this study, we aimed to cover this deficit. In this cross-sectional study which was carried out in Isfahan (Iran) in 2013 senior citizens (aged 65 or more) who were taking at least one medication and had no record of residency in nursing homes were included. We used Morisky medication adherence scale (after validation and reliability assessment for using this questionnaire in Persian language) to evaluate the level of adherence in the study population. A total of 200 elderly participants were fully studied ( n = 200, 61% females), and 52% of them had poor medication adherence. 77.5% of participants were suffered from at least four medical illnesses, and 18.5% of them were taking more than eight medications per day. We have not found any significant statistical relationship between vision or hearing loss disorders and the medication adherence of the participants). There was a significant positive relationship between the level of education and medication adherence ( P = 0.001), ( χ 2 = 0.29). Low Medication adherence is a common and important drug issue in the elderly in Isfahan. This issue can lead to medical complications and huge cost if it is not addressed appropriately.

  13. Language Profile in Congenital Hypothyroid Children Receiving Replacement Therapy.

    Science.gov (United States)

    Soliman, Hend; Abdel Hady, Aisha Fawzy; Abdel Hamid, Asmaa; Mahmoud, Heba

    2016-01-01

    The aim of this work was to evaluate receptive and expressive language skills in children with congenital hypothyroidism receiving early hormonal replacement treatment before the age of 3 months and to identify any subtle areas of weaknesses in their language development to check the necessity for future language intervention. The study was conducted on 30 hypothyroid children receiving hormonal replacement. They were subdivided into group I (5-8 years 11 months; 12 cases) and group II (9-12 years 11 months; 18 cases). All patients were subjected to a protocol of assessment applied in the Diabetes, Endocrine and Metabolism Pediatric Unit (DEMPU) and evaluation of language skills by the REAL scale. The younger group reached average Arabic language scores, while the older group showed moderate language delay. Early replacement therapy supports language development in young children. However, longitudinal and follow-up studies are required to identify difficulties presenting at older ages that may affect children in the academic settings. © 2016 S. Karger AG, Basel.

  14. Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia

    2007-01-01

    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...... (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1...... January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance...

  15. Continuous Renal Replacement Therapy Applications on Extracorporeal Membrane Oxygenation Circuit.

    Science.gov (United States)

    Yetimakman, Ayse Filiz; Tanyildiz, Murat; Kesici, Selman; Kockuzu, Esra; Bayrakci, Benan

    2017-06-01

    Continuous venovenous hemofiltration or hemodiafiltration is used frequently in pediatric patients, but experience of continuous renal replacement therapy (CRRT) application on extracorporeal membrane oxygenation (ECMO) circuit is still limited. Among several methods used for applying CRRT on ECMO patients, we aim to share our experience on inclusion of a CRRT device in the ECMO circuit which we believe is easier and safer to apply. The data were collected on demographics, outcomes, and details of the treatment of ECMO patients who had CRRT. During the study period of 3 years, venous cannula of ECMO circuit before pump was used for CRRT access for both the filter inlet and outlet of CRRT machine to minimize the thromboembolic complications. The common indication for CRRT was fluid overload. CRRT was used in 3.68% of a total number of patients admitted and 43% of patients on ECMO. The patients have undergone renal replacement therapy for periods of time ranging between 24 h and 25 days (260 h mean). The survival rate of this group of patients with multiorgan failure was 33%. Renal recovery occurred in all of the survivors. Complications such as electrolyte imbalance, hypothermia, and bradykinin syndrome were easily managed. Adding a CRRT device on ECMO circuit is a safe and effective technique. The major advantages of this technique are easy to access, applying CRRT without extra anticoagulation process, preventing potential hemodynamic disturbances, and increased clearance of solutes and fluid overload using larger hemofilter.

  16. Systematic review of hormone replacement therapy in the infertile man

    Directory of Open Access Journals (Sweden)

    Amr El Meliegy

    2018-03-01

    Full Text Available Objectives: To highlight alternative treatment options other than exogenous testosterone administration for hypogonadal men with concomitant infertility or who wish to preserve their fertility potential, as testosterone replacement therapy (TRT inhibits spermatogenesis, representing a problem for hypogonadal men of reproductive age. Materials and methods: We performed a comprehensive literature review for the years 1978–2017 via PubMed. Also abstracts from major urological/surgical conferences were reviewed. Review was consistent with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA criteria. We used Medical Subject Heading terms for the search including ‘testosterone replacement therapy’ or ‘TRT’ and ‘male infertility’. Results: In all, 91 manuscripts were screened and the final number used for the review was 56. All studies included were performed in adults, were written in English and had an abstract available. Conclusions: Exogenous testosterone inhibits spermatogenesis. Hypogonadal men wanting to preserve their fertility and at the same time benefiting from TRT effects can be prescribed selective oestrogen receptor modulators or testosterone plus low-dose human chorionic gonadotrophin (hCG. Patients treated for infertility with hypogonadotrophic hypogonadism can be prescribed hCG alone at first followed by or in combination from the start with follicle-stimulating hormone preparations. Keywords: Gonadotrophins, Hypogonadism, Infertility, Systematic review, Testosterone therapy

  17. Functional and molecular neuroimaging of menopause and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Erika eComasco

    2014-12-01

    Full Text Available The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. This review summarizes the findings of thirty-four studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women’s brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal

  18. Comparison of Effectiveness between Rifampicin Ofloxin-Minocycline Regimen and Multidrug Therapy-World Health Organization in Multibacillary Leprosy Patients

    Directory of Open Access Journals (Sweden)

    Octawyana Moestopo

    2016-12-01

    Full Text Available Background: Multidrug therapy (MDT which is recommended by the World Health Organization (WHO for multibacillary (MB leprosy patients has some side effects; it is given in 12 doses over 12-18 months. Patients who refuse or are contraindicated in undertaking MDT-WHO can be given alternative rifampicin-ofloxacin-minocycline (ROM regimen for 24 months, whose side effects are less but more expensive. This study was conducted to compare the effectiveness between ROM and MDT-WHO regimen in the first 12 months based on the derivation in morphological index (MI of acid-fast bacilli (AFB in MB leprosy patient. Methods: This was an observational analytical study with retrospective cohort method. Data was collected from medical records of MB leprosy patients in the Medical Record Installation and Morbus Hansen Clinic, Dr. Hasan Sadikin General Hospital Bandung. The overall derivation in MI in 12 months was assessed according to the type of therapy undertaken by the patient. Data was analyzed by Mann-Whitney U Test. Results: A total of 59 data were selected out of 800 data of new leprosy patients based on the inclusion and exclusion criteria. Among those, 20 patients were treated by ROM and 39 by MDT-WHO. Derivation of MI occurred among both groups, but ROM regimen had higher percentage (94.83% compared with MDT-WHO regimen (79.57% with p value=0.003 (p <0.05. Conclusions: ROM regimen has better effectiveness than MDT-WHO regimen in the first 12 months in MB leprosy patients.

  19. JCL Roundtable: enzyme replacement therapy for lipid storage disorders.

    Science.gov (United States)

    Brown, W Virgil; Desnick, Robert J; Grabowski, Gregory A

    2014-01-01

    There are several inherited disorders that involve abnormal storage of lipids in tissues leading to severe compromise of organs. Sadly, these are often accompanied by lifelong morbidity and early mortality. Disorders such as Gaucher, Fabry, and lysosomal acid lipase deficiencies (Wolman and cholesteryl ester storage diseases) have been known for many years, and provide a difficult and frustrating set of problems for patients, their families, and their physicians. With recombinant methods of protein synthesis, it is now possible to literally replace the defective enzymes that underlie the basic pathophysiology of many such disorders. The delivery of these enzymes into the affected cells is possible because of their location in the lysosomes where the natural degradation of their lipid substrates occurs. I have asked 2 well-known investigators to join us for this Roundtable. These are professors who have been involved with the research that has made this type of therapy possible and who have participated in the clinical trials that demonstrated the value of enzyme replacement therapy. They are Dr. Robert Desnick, dean of Genetic and Genomic Medicine and professor and chairman emeritus of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai in New York City, and Dr. Gregory Grabowski, professor of Microbiology, Biochemistry, and Pediatrics, at the University of Cincinnati College of Medicine. Dr. Grabowski recently retired from that school to become the chief science officer of Synageva, a company involved in producing enzymes for this type of therapy. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  20. Interruption of enzyme replacement therapy in Gaucher disease.

    Science.gov (United States)

    Goldblatt, J; Fletcher, J M; McGill, J; Szer, J; Wilson, M

    2016-05-25

    In Australia, 58 patients with Gaucher disease were managed by a Gaucher Disease Advisory Committee (GDAC) through a centrally adminis-tered national programme, the Life Savings Drug Program (LSDP). In June 2009, Genzyme Corporation, which manufactures imiglucerase (Cerezyme), the only enzyme replacement therapy (ERT) registered for the treatment of Gaucher disease in Australia at that time, announced that due to a viral contamination problem there would be no further shipments of Cerezyme to Australia prior to the end of 2009. The GDAC allocated available drug supplies in order to maintain treatment to those most in need on a hierarchal clinical severity basis. A cohort of 24 patients with Type 1 Gaucher disease was withdrawn from therapy, 22 of whom had no discernible clinically significant adverse effects when reviewed off therapy for up to 6 months. In this paper, we review the course of 20 of the patients who have been on imiglucerase for periods of at least 24 months after the end of their 'drug holiday'. No patient experienced a bone crisis nor clinical nor magnetic resonance imaging evidence of new avascular necrosis events during this period. Two years after recommencing ERT after a 6-month drug holiday, no patient had developed an overt irreversible complication of their Gaucher disease, with the majority returning to their previous clinical status.

  1. Parental experience of enzyme replacement therapy for Hunter syndrome.

    Science.gov (United States)

    Buraczewska, M; O'Leary, D; Walsh, O; Monavari, A; Crushell, E

    2013-04-01

    We aimed to establish the profile of Irish patients with Hunter Syndrome (Mucopolysaccharidosis type II, MPS II) receiving weekly intravenous Enzyme Replacement Therapy (ERT) with recombinant iduronate-2-sulfatase and to assess the social impact and parental opinion of ERT through the use of a parental questionnaire. Nine patients aged 3.5- 14 years have received a mean of 2 (range 0.5-3.5) years of ERT. Treatment was associated with clinical improvements from baseline in hepatosplenomegaly in 6/7 (85%) respiratory manifestations in 4/6 (67%) and a mean reduction in urinary glycosaminoglycan excretion of 62%. Changes noted by parents included increased energy 3/9 (33%) and softening of skin, hair and facial features 8/9 (89%). Parents report that seven hours weekly were spent on hospitalizations for ERT. Parental employment was adversely affected in 8 (89%) families. One day of school/preschool (20%) was lost every week for 8 (89%) children. All parents believed the benefits of ERT out-weigh the difficulties involved. All families would welcome the introduction of home based therapy. In conclusion the social and educational burden of hospital-based ERT on these children and their families is significant. The introduction of home-based therapy is likely to improve overall quality of life for MPSII patients and their families.

  2. Cerebral magnetic resonance findings during enzyme replacement therapy in mucopolysaccharidosis

    International Nuclear Information System (INIS)

    Matsubara, Yoshiko; Miyazaki, Osamu; Nosaka, Shunsuke; Kosuga, Motomichi; Okuyama, Torayuki

    2017-01-01

    Although enzyme replacement therapy (ERT) is an effective treatment for mucopolysaccharidosis (MPS) types I, II, IVA and VI, its effectiveness in children with central nervous system (CNS) disorders is said to be poor because the blood-brain barrier cannot be penetrated by ERT drugs. To assess CNS involvement in mucopolysaccharidosis at the start of enzyme replacement therapy and to investigate the time course of ERT in the central nervous system. We performed brain MRI in 17 children and young adults who underwent ERT. The clinical severity was classified as attenuated or severe by a specialist pediatrician, based on the clinical symptoms and genotypes. At the start of ERT, we scored nine parameters using two- or three-point scales based on the severity of the disease revealed on MRI scans. After the start of ERT, we compared the initial and follow-up MRI scans, and classified the findings as no change, improved or worse. We then compared the results with the changes in clinical findings. At the start of ERT, comparison of the clinical symptoms and image scores revealed differences between severe and attenuated mucopolysaccharidosis. The scores in patients with severe MPS ranged from 9 to 16 (mean 12.2); for patients with attenuated MPS, they ranged from 2 to 11 (mean 6.4). Images of the four patients with severe MPS showed ventricular dilation and brain atrophy. Such findings were made in only 2 of 13 patients with attenuated MPS. The results after the start of ERT showed that 11/17 (65%) patients manifested improvement or no change. All five patients with MPS I experienced improvement in some regions. There were no new lesions. One patient with MPS II experienced worsening of his CNS symptoms, and his MRI findings revealed more severe ventricular dilation, brain atrophy and white matter lesions. Ventricular dilation and brain atrophy on imaging studies might represent useful markers in predicting the severity of mucopolysaccharidosis and worsening of CNS

  3. Cerebral magnetic resonance findings during enzyme replacement therapy in mucopolysaccharidosis

    Energy Technology Data Exchange (ETDEWEB)

    Matsubara, Yoshiko [Division of Radiology, National Center for Child Health and Development, Tokyo (Japan); Hiroshima University, Department of Diagnostic Radiology, Hiroshima (Japan); Miyazaki, Osamu; Nosaka, Shunsuke [Division of Radiology, National Center for Child Health and Development, Tokyo (Japan); Kosuga, Motomichi [Division of Medical Genetics, National Center for Child Health and Development, Tokyo (Japan); Okuyama, Torayuki [Department of Clinical Laboratory Medicine, National Center for Child Health and Development, Tokyo (Japan)

    2017-11-15

    Although enzyme replacement therapy (ERT) is an effective treatment for mucopolysaccharidosis (MPS) types I, II, IVA and VI, its effectiveness in children with central nervous system (CNS) disorders is said to be poor because the blood-brain barrier cannot be penetrated by ERT drugs. To assess CNS involvement in mucopolysaccharidosis at the start of enzyme replacement therapy and to investigate the time course of ERT in the central nervous system. We performed brain MRI in 17 children and young adults who underwent ERT. The clinical severity was classified as attenuated or severe by a specialist pediatrician, based on the clinical symptoms and genotypes. At the start of ERT, we scored nine parameters using two- or three-point scales based on the severity of the disease revealed on MRI scans. After the start of ERT, we compared the initial and follow-up MRI scans, and classified the findings as no change, improved or worse. We then compared the results with the changes in clinical findings. At the start of ERT, comparison of the clinical symptoms and image scores revealed differences between severe and attenuated mucopolysaccharidosis. The scores in patients with severe MPS ranged from 9 to 16 (mean 12.2); for patients with attenuated MPS, they ranged from 2 to 11 (mean 6.4). Images of the four patients with severe MPS showed ventricular dilation and brain atrophy. Such findings were made in only 2 of 13 patients with attenuated MPS. The results after the start of ERT showed that 11/17 (65%) patients manifested improvement or no change. All five patients with MPS I experienced improvement in some regions. There were no new lesions. One patient with MPS II experienced worsening of his CNS symptoms, and his MRI findings revealed more severe ventricular dilation, brain atrophy and white matter lesions. Ventricular dilation and brain atrophy on imaging studies might represent useful markers in predicting the severity of mucopolysaccharidosis and worsening of CNS

  4. Predictors of Renal Replacement Therapy in Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Michael J. Koziolek

    2012-09-01

    Full Text Available Backgrounds: Criteria that may guide early renal replacement therapy (RRT initiation in patients with acute kidney injury (AKI currently do not exist. Methods: In 120 consecutive patients with AKI, clinical and laboratory data were analyzed on admittance. The prognostic power of those parameters which were significantly different between the two groups was analyzed by receiver operator characteristic curves and by leave-1-out cross validation. Results: Six parameters (urine albumin, plasma creatinine, blood urea nitrogen, daily urine output, fluid balance and plasma sodium were combined in a logistic regression model that estimates the probability that a particular patient will need RRT. Additionally, a second model without daily urine output was established. Both models yielded a higher accuracy (89 and 88% correct classification rate, respectively than the best single parameter, cystatin C (correct classification rate 74%. Conclusions: The combined models may help to better predict the necessity of RRT using clinical and routine laboratory data in patients with AKI.

  5. Factors predicting successful discontinuation of continuous renal replacement therapy.

    Science.gov (United States)

    Katayama, S; Uchino, S; Uji, M; Ohnuma, T; Namba, Y; Kawarazaki, H; Toki, N; Takeda, K; Yasuda, H; Izawa, J; Tokuhira, N; Nagata, I

    2016-07-01

    This multicentre, retrospective observational study was conducted from January 2010 to December 2010 to determine the optimal time for discontinuing continuous renal replacement therapy (CRRT) by evaluating factors predictive of successful discontinuation in patients with acute kidney injury. Analysis was performed for patients after CRRT was discontinued because of renal function recovery. Patients were divided into two groups according to the success or failure of CRRT discontinuation. In multivariate logistic regression analysis, urine output at discontinuation, creatinine level and CRRT duration were found to be significant variables (area under the receiver operating characteristic curve for urine output, 0.814). In conclusion, we found that higher urine output, lower creatinine and shorter CRRT duration were significant factors to predict successful discontinuation of CRRT.

  6. History of renal replacement therapy in Baltic countries.

    Science.gov (United States)

    Kuzminskis, Vytautas; Rosenberg, Mai; Cernevskis, Harijs; Bumblyte, Inga Arūne

    2011-01-01

    The history of renal replacement therapy (RRT) in the 3 Baltic countries can be divided into 2 periods: the Soviet period (1944-1991) with strict central regulation and isolation from Western countries, and the period of independence (1991 to the present). Between 1963 and 1967, hemodialysis was used in cases of acute kidney injury and later in chronic renal failure, but only for patients suitable for kidney transplantation. The first renal transplant was performed in 1968, in Tartu, Estonia, and shortly thereafter, in Lithuania and Latvia. During the period of independence, development of RRT has been extremely rapid, and now this field of the health system has no major differences from that in other developed countries.

  7. Primary prevention of cardiovascular disease with hormone replacement therapy

    DEFF Research Database (Denmark)

    Schierbeck, L

    2015-01-01

    Many peri- and postmenopausal women suffer from a reduced quality of life due to menopausal symptoms and preventable diseases. The importance of cardiovascular disease in women must be emphasized, as it is the leading cause of mortality and morbidity in women. It is well known that female hormones...... contribute to the later onset of cardiovascular disease in women. The effect of estrogens has for decades been understood from observational studies of postmenopausal women treated with hormone replacement therapy (HRT). Later, treatment with HRT was disregarded due to the fear of side......-effects and an ambiguity of the cardiovascular advantages. Accumulating knowledge from the large number of trials and studies has elucidated the cause for the disparity in results. In this paper, the beneficial effects of HRT, with emphasis on cardiovascular disease are explained, and the relative and absolute risks...

  8. Being a long-term user of nicotine replacement therapy

    DEFF Research Database (Denmark)

    Borup, Gitte; Nørgaard, Lotte Stig; Tønnesen, Philip

    Background During recent years a gradual shift in the application of nicotine replacement therapy (NRT) has taken place from NRT-products only being recommended to achieve smoking cessation, to now including smoking reduction, and long-term substitution of tobacco with NRT has taken place. This has...... been promoted as a way of achieving harm-reduction in highly nicotine dependent smokers who are unwilling or incapable of quitting all nicotine products, as continued use of NRT is widely accepted as being far less hazardous than continued smoking. To our knowledge no previous research has been done...... of feeling addicted, cost of NRT products and fear of adverse health consequences. Aim of study • To get a thorough understanding of the lived experiences of nicotine dependent long-term NRT users. • To investigate what motivates or discourages quitting NRT. Method Semi-structured interviews with long...

  9. Demographics of paediatric renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    Chesnaye, Nicholas; Bonthuis, Marjolein; Schaefer, Franz

    2014-01-01

    BACKGROUND: The ESPN/ERA-EDTA Registry collects data on European children with end-stage renal disease receiving renal replacement therapy (RRT) who are listed on national and regional renal registries in Europe. In this paper we report on the analysis of demographic data collected from 2009...... to 2011. METHODS: Data on primary renal disease, incidence, prevalence, 4-year survival, transplantation rate and causes of death in paediatric patients receiving RRT were extracted from the ESPN/ERA-EDTA Registry for 37 European countries. RESULTS: The incidence of RRT in paediatric patients in Europe...... during the study period was 5.5 cases per million age-related population (pmarp) in patients aged 0-14 years and varied markedly between countries (interquartile range 3.4-7.0 years). The prevalence of RRT was 27.9 pmarp and increased with age, with 67 % of prevalent patients living with a functioning...

  10. Renouncement of renal replacement therapy: withdrawal and refusal

    Directory of Open Access Journals (Sweden)

    José Andrade Moura Neto

    Full Text Available Abstract Renouncement of renal replacement therapy (RRT is a medical dilemma. This review covers the concept, the magnitude, the prognosis, and discusses strategies and management approaches about this subject in patients with CKD and AKI. Evidence suggests that refusal is more frequent and carries a more guarded prognosis than withdrawal of RRT. When RRT is not expected to be beneficial in terms of survival or quality of life, conservative treatment and palliative care are alternatives. We review the historical evolution of guidelines about renouncement of RRT and palliative care, and highlight the absence of specific recommendations in Brazil. However renouncement of RRT may be ethically and legally accepted in Brazil, as the right to a dignified death. Longer life expectancy, economic pressures, and greater awareness will require a more detailed discussion about indications and sustainable use of RRT, and possibly the elaboration of national guidelines.

  11. Functional and molecular neuroimaging of menopause and hormone replacement therapy

    DEFF Research Database (Denmark)

    Comasco, Erika; Frøkjær, Vibe; Sundström-Poromaa, Inger

    2014-01-01

    The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuat......The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone...... fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. The present review summarizes the findings of thirty-five studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri......-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal variations on the brain....

  12. Precision Fluid Management in Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Murugan, Raghavan; Hoste, Eric; Mehta, Ravindra L; Samoni, Sara; Ding, Xiaoqiang; Rosner, Mitchell H; Kellum, John A; Ronco, Claudio

    2016-01-01

    Fluid management during continuous renal replacement therapy (CRRT) in critically ill patients is a dynamic process that encompasses 3 inter-related goals: maintenance of the patency of the CRRT circuit, maintenance of plasma electrolyte and acid-base homeostasis and regulation of patient fluid balance. In this article, we report the consensus recommendations of the 2016 Acute Disease Quality Initiative XVII conference on 'Precision Fluid Management in CRRT'. We discuss the principles of fluid management, describe various prescription methods to achieve circuit integrity and introduce the concept of integrated fluid balance for tailoring fluid balance to the needs of the individual patient. We suggest that these recommendations could serve to develop the best clinical practice and standards of care for fluid management in patients undergoing CRRT. Finally, we identify and highlight areas of uncertainty in fluid management and set an agenda for future research. © 2016 S. Karger AG, Basel.

  13. A Cost Analysis of Kidney Replacement Therapy Options in Palestine

    Directory of Open Access Journals (Sweden)

    Mustafa Younis Ph.D.

    2015-03-01

    Full Text Available This study provides a cost analysis of kidney replacement therapy options in Palestine. It informs evidence-based resource allocation decisions for government-funded kidney disease services where transplant donors are limited, and some of the common modalities, i.e., peritoneal dialysis (PD and home hemodialysis (HD, are not widely available due to shortages of qualified staff, specialists, and centers to follow the patient cases, provide training, make home visits, or provide educational programs for patients. The average cost of kidney transplant was US$16 277 for the first year; the estimated cost of HD per patient averaged US$16 085 per year—nearly as much as a transplant. Consistent with prior literature and experience, while live, related kidney donors are scarce, we found that kidney transplant was more adequate and less expensive than HD. These results have direct resource allocation implications for government-funded kidney disease services under Palestinian Ministry of Health. Our findings strongly suggest that investing in sufficient qualified staff, equipment, and clinical infrastructure to replace HD services with transplantation whenever medically indicated and suitable kidney donors are available, as well as deploying PD programs and Home HD programs, will result in major overall cost savings. Our results provide a better understanding of the costs of kidney disease and will help to inform Ministry of Health and related policy makers as they develop short- and long-term strategies for the population, in terms of both cost savings and enhanced quality of life.

  14. [Survival in acute renal failure with conventional therapy or continuous replacement therapy].

    Science.gov (United States)

    Santibáñez-Velázquez, Martín; Sánchez-Montoya, Felipe; Alvirde-Gutiérrez, Luis

    2014-01-01

    To know the survival rate in patients with RIFLE I and II stages on acute renal failure, treated with supportive care or continuous renal replacement therapy with PRISMA machine, at an intensive care unit. There were included patients of both sexes, aged 16 to 69 years, with acute renal failure in RIFLE I and II stages and score of scale APACHE II lower than 36 points. The sample studied was divided in two groups: a group was treated with supportive care, and the other group received continuous renal replacement therapy via PRISMA machine. We compared mortality between both groups and the association with the RIFLE stages with Pearson's chi-squared test. The average score of the scale APACHE I was 14 points, and the probability of death was 15 %. The patients with acute renal failure RIFLE I were 54.5 % and RIFLE II 45.5 %, with mortality of 30.4 % and 38.8 %, respectively. Patients in RIFLE I stage who received supportive care and continuous replacement therapy had non-statistical differences in mortality (p = 0.356). The mortality in patients with acute renal failure in RIFLE II stage treated with continuous replacement therapy was higher (p = 0.000). Because of its accessibility and lower mortality, supportive care should be the initial procedure in patients with acute renal failure in RIFLE I and II stages.

  15. Estrogen replacement therapy and cardioprotection: mechanisms and controversies

    Directory of Open Access Journals (Sweden)

    M.T.R. Subbiah

    2002-03-01

    Full Text Available Epidemiological and case-controlled studies suggest that estrogen replacement therapy might be beneficial in terms of primary prevention of coronary heart disease (CHD. This beneficial effect of estrogens was initially considered to be due to the reduction of low density lipoproteins (LDL and to increases in high density lipoproteins (HDL. Recent studies have shown that estrogens protect against oxidative stress and decrease LDL oxidation. Estrogens have direct effects on the arterial tissue and modulate vascular reactivity through nitric oxide and prostaglandin synthesis. While many of the effects of estrogen on vascular tissue are believed to be mediated by estrogen receptors alpha and ß, there is evidence for `immediate non-genomic' effects. The role of HDL in interacting with 17ß-estradiol including its esterification and transfer of esterified estrogens to LDL is beginning to be elucidated. Despite the suggested positive effects of estrogens, two recent placebo-controlled clinical trials in women with CHD did not detect any beneficial effects on overall coronary events with estrogen therapy. In fact, there was an increase in CHD events in some women. Mutations in thrombogenic genes (factor V Leiden, prothrombin mutation, etc. in a subset of women may play a role in this unexpected finding. Thus, the cardioprotective effect of estrogens appears to be more complicated than originally thought and requires more research.

  16. Role of telehealth in renal replacement therapy education.

    Science.gov (United States)

    Malkina, Anna; Tuot, Delphine S

    2018-03-01

    The prevalence of end-stage renal disease is rising in the United States, which bears high financial and public health burden. The most common modality of renal replacement therapy (RRT) in the United States is in-center hemodialysis. Many patients report lack of comprehensive and timely education about their treatment options, which may preclude them from participating in home-based dialysis therapies and kidney transplantation evaluation. While RRT education has traditionally been provided in-person, the rise of telehealth has afforded new opportunities to improve upon the status quo. For example, technology-augmented RRT education has recently been implemented into telehealth nephrology clinics, informational websites and mobile applications maintained by professional organizations, patient-driven forums on social media, and multimodality programs. The benefits of technology in RRT education are increased access for geographically isolated and/or medically frail patients, versatility of content delivery, information repetition to enhance knowledge retention, and interpersonal connection for educational content and emotional support. Challenges center around privacy and accuracy of information sharing, in addition to differential access to technology due to age and socioeconomic status. A review of available scholarly and social media resources suggests that technology-aided delivery of education about treatment options for end-stage renal disease provides an important alternative and/or supplemental resource for patients and families. © 2018 Wiley Periodicals, Inc.

  17. Optimising glucocorticoid replacement therapy in severely adrenocorticotropin (ACTH) deficient hypopituitary male patients.

    LENUS (Irish Health Repository)

    Behan, Lucy-Ann

    2011-04-18

    Context:  The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15mg to 30mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. Objective:  Primarily to define the hydrocortisone regimen which results in a 24hour cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). Design:  10 male hypopituitary patients with severe ACTH deficiency (basal cortisol <100nM and peak response to stimulation <400nM) were enrolled in a prospective, randomised, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24hour serum cortisol sampling and QoL assessment with the Short Form 36 and the Nottingham Health Profile questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. Results:  CBG was significantly lower across all dose regimens compared to controls (p<0.05). The lower dose regimen C(10mg mane\\/5mg tarde) produced a 24hour free cortisol profile which most closely resembled that of controls. Both regimen A(20mg mane\\/10mg tarde) and B(10mg mane\\/10mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (p<0.001). Conclusions:  The lower dose of HC(10mg\\/5mg) produces a more physiological cortisol profile, without compromising quality of life, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

  18. Optimizing glucocorticoid replacement therapy in severely adrenocorticotropin-deficient hypopituitary male patients.

    LENUS (Irish Health Repository)

    Behan, Lucy-Ann

    2012-02-01

    BACKGROUND: The optimal replacement regimen of hydrocortisone in adults with severe ACTH deficiency remains unknown. Management strategies vary from treatment with 15-30 mg or higher in daily divided doses, reflecting the paucity of prospective data on the adequacy of different glucocorticoid regimens. OBJECTIVE: Primarily to define the hydrocortisone regimen which results in a 24 h cortisol profile that most closely resembles that of healthy controls and secondarily to assess the impact on quality of life (QoL). DESIGN: Ten male hypopituitary patients with severe ACTH deficiency (basal cortisol <100 nm and peak response to stimulation <400 nm) were enrolled in a prospective, randomized, crossover study of 3 hydrocortisone dose regimens. Following 6 weeks of each regimen patients underwent 24 h serum cortisol sampling and QoL assessment with the Short Form 36 (SF36) and the Nottingham Health Profile (NHP) questionnaires. Free cortisol was calculated using Coolen\\'s equation. All results were compared to those of healthy, matched controls. RESULTS: Corticosteroid binding globulin (CBG) was significantly lower across all dose regimens compared to controls (P < 0.05). The lower dose regimen C (10 mg mane\\/5 mg tarde) produced a 24 h free cortisol profile (FCP) which most closely resembled that of controls. Both regimen A(20 mg mane\\/10 mg tarde) and B(10 mg mane\\/10 mg tarde) produced supraphysiological post-absorption peaks. There was no significant difference in QoL in patients between the three regimens, however energy level was significantly lower across all dose regimens compared to controls (P < 0.001). CONCLUSIONS: The lower dose of hydrocortisone (10 mg\\/5 mg) produces a more physiological cortisol profile, without compromising QoL, compared to higher doses still used in clinical practice. This may have important implications in these patients, known to have excess cardiovascular mortality.

  19. Elevated hair cortisol concentrations in children with adrenal insufficiency on hydrocortisone replacement therapy.

    Science.gov (United States)

    Noppe, G; van Rossum, E F C; Vliegenthart, J; Koper, J W; van den Akker, E L T

    2014-12-01

    Glucocorticoid replacement therapy in patients with adrenal insufficiency needs to be tailored to the individual patient based on body composition and clinical signs and symptoms as no objective method for assessment of treatment adequacy is available. Current treatment regimens are often not satisfactory, which is shown by the adverse metabolic profile and doubled mortality rates in treated adrenal insufficiency patients. Measurement of cortisol concentrations in hair reflect the long-term systemic cortisol exposure and may be of use in refinement of hydrocortisone treatment. We aimed to study whether long-term cortisol (hydrocortisone) levels, as measured in scalp hair, are similar in children with adrenal insufficiency and healthy children. We set up a case control study, measuring anthropometric characteristics and hair cortisol concentrations (HCC) in 54 hydrocortisone substituted children with adrenal insufficiency (AI patients) in the age of 4-18 years and 54 healthy children matched for gender and age. Mean HCC were significantly higher in AI patients compared with healthy controls (mean 13·3 vs 8·2 pg/mg, P = 0·02). AI patients also had a higher BMI (P < 0·001) and waist circumference (WC) (P = 0·02). HCC was significantly associated with BMI (P = 0·002) and WC (P = 0·002). HCC explained 13% of the difference in BMI and 29% of the difference in WC between AI patients and controls. Hydrocortisone-treated AI patients have increased HCC and adverse anthropometric characteristics compared with healthy controls. HCC measurement may be of value in identifying overtreatment and thereby improve hydrocortisone replacement therapy. © 2014 John Wiley & Sons Ltd.

  20. Risks and benefits of citrate anticoagulation for continuous renal replacement therapy.

    Science.gov (United States)

    Shum, H P; Yan, W W; Chan, T M

    2015-04-01

    Heparin, despite its significant side-effects, is the most commonly used anticoagulant for continuous renal replacement therapy in critical care setting. In recent years, citrate has gained much popularity by improving continuous renal replacement therapy circuit survival and decreasing blood transfusion requirements. However, its complex metabolic consequences warrant modification in the design of the citrate-based continuous renal replacement therapy protocol. With thorough understanding of the therapeutic mechanism of citrate, a simple and practicable protocol can be devised. Citrate-based continuous renal replacement therapy can be safely and widely used in the clinical setting with appropriate clinical staff training.

  1. Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence

    NARCIS (Netherlands)

    Schallig, Henk D. F. H.; Tinto, Halidou; Sawa, Patrick; Kaur, Harparkash; Duparc, Stephan; Ishengoma, Deus S.; Magnussen, Pascal; Alifrangis, Michael; Sutherland, Colin J.

    2017-01-01

    Management of uncomplicated Plasmodium falciparum malaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia and changing parasite susceptibility to ACT

  2. The outcome of clinical parameters in adults with severe Type I Gaucher disease using very low dose enzyme replacement therapy.

    Science.gov (United States)

    Wilson, Callum; Spearing, Ruth; Teague, Lochie; Robertson, Patsy; Blacklock, Hilary

    2007-01-01

    Enzyme replacement therapy is now well established as the treatment of choice in Type I Gaucher disease. Historically higher dosage regimens have been used in preference to lower doses despite the little clinical evidence in the way of large controlled clinical trials to support this. Moreover, the extraordinary cost of therapy means that not all eligible patients are able to be treated at the higher dose. Twelve type I adult patients with relatively severe disease were commenced on a very low dose of 7.5U of alglucerase/imiglucerase per kg every two weeks (initially given thrice weekly and later weekly). Follow-up 5 year data reveal a good visceral and haematological response with outcomes consistent with recently published treatment guidelines. Satisfactory clinical and radiological skeletal improvement was also demonstrated in most patients. Three patients had an inadequate overall skeletal response to therapy. Biomarkers also steadily improved although perhaps not quite at the same rate as that seen in higher doses. Very low dose enzyme replacement therapy may be appropriate for adult type I Gaucher patients with mild-moderate skeletal disease.

  3. The effect of hormonal replacement therapy on breast

    International Nuclear Information System (INIS)

    Jeong, Mi Gyoung; Oh, Ki Keun; Kim, Mi Hye

    1995-01-01

    To evaluate mammographic and sonographic breast parenchymal changes and the risk of breast cancer in women on hormonal replacement therapy (HRT). The study group consisted of 50 patients examined with serial mammograms and/or ultrasonograms during HRT. The control group consisted of 50 patients examined with serial mammogram for a routine health check. Mammographic parenchymal changes in both the study and control groups and sonographic findings of 27/50 patients in study group were evaluated. Follow-up mammogram of the control group showed no interval change or slight evolution of parenchyma with increasing age, but the study group showed increasing parenchymal densities. Most frequently encountered finding on sonogram in 11 women treated by estrogen alone, was ductal dilatation (7 cases; 64%), whereas in 16 women treated by estrogen and progesteron it was ductal epithelial hyperplasia (8 cases; 50%). Overall, four breast cancers developed; one infiltrating ductal carcinoma and three ductal carcinoma in situ. HRT causes the changes of breast parenchyma on mammogram and sonogram of postmenopausal women, and increases the risk of developing breast cancer. Therefore, careful and regular examination should be followed in those on postmenopausal HRT

  4. Bone benefits of testosterone replacement therapy in male hypogonadism.

    Science.gov (United States)

    Tirabassi, G; Biagioli, A; Balercia, G

    2014-06-01

    Osteoporosis is an asymptomatic, systemic bone disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in increased bone fragility. Such condition is often underdiagnosed and undertreated, especially in men, therefore considerably increasing the fracture risk. Of note, fracture-related morbidity and mortality is generally higher in men, partly due to greater frailty. On the other hand, male hypogonadism is defined as the failure of the testes to produce androgens, sperm, or both and it is often due to the ageing process. This disorder, in turn, causes many systemic disorders, and it is the condition mainly associated with male osteoporosis. Testosterone replacement therapy (TRT) is usually prescribed to restore optimal hormone levels, but conflicting data are available about the efficacy of TRT treatment on bone mineral density. In this review we extensively examined literature data about the usefulness of TRT in improving hypogonadism-associated low bone mineral density. Furthermore, we considered the complex relationship between male osteoporosis and hypogonadism, by specifically addressing the role of androgens in male bone physiology and the diagnostic approach to male osteoporosis and hypogonadism and also by dealing with some new related aspects such as the new endocrine pathways between bone and testis and the role of androgen receptor CAG polymorphism on bone density.

  5. Technological advances in renal replacement therapy: five years and beyond.

    Science.gov (United States)

    Rastogi, Anjay; Nissenson, Allen R

    2009-12-01

    The worldwide epidemic of chronic kidney disease shows no signs of abating in the near future. Current dialysis forms of renal replacement therapy (RRT), even though successful in sustaining life and improving quality of life somewhat for patients with ESRD, have many limitations that result in still unacceptably high morbidity and mortality. Transplantation is an excellent option but is limited by the scarcity of organs. An ideal form of RRT would mimic the functions of natural kidneys and be transparent to the patient, as well as affordable to society. Recent advances in technology, although generally in early stages of development, might achieve these goals. The application of nanotechnology, microfluidics, bioreactors with kidney cells, and miniaturized sorbent systems to regenerate dialysate makes clinical reality seem closer than ever before. Finally, stem cells hold much promise, both for kidney disease and as a source of tissues and organs. In summary, nephrology is at an exciting crossroad with the application of innovative and novel technologies to RRT that hold considerable promise for the near future.

  6. The ethics of aggregation and hormone replacement therapy.

    Science.gov (United States)

    Lyerly, A D; Myers, E R; Faden, R R

    2001-01-01

    The use of aggregated quality of life estimates in the formation of public policy and practice guidelines raises concerns about the moral relevance of variability in values in preferences for health care. This variability may reflect unique and deeply held beliefs that may be lost when averaged with the preferences of other individuals. Feminist moral theories which argue for attention to context and particularity underline the importance of ascertaining the extent to which differences in preferences for health states reveal information which is morally relevant to clinicians and policymakers. To facilitate these considerations, we present an empirical study of preferences for the timing and occurrence of health states associated with hormone replacement therapy (HRT). Sixteen women between the ages of 45 and 55 were enrolled in this pilot study. Their preferences regarding five health states associated with HRT (menopausal symptoms. side effects of HRT, breast cancer, myocardial infarction, and osteoporosis) were assessed in quantitative terms known as utilities. Two standard methods, the visual analog scale (VAS) and the standard gamble (SG), were used to assess utility and time preference (calculated as a discount rate). The wide variability of responses underlines the importance of tailoring health care to individual women's preferences. Policy guidelines which incorporate utility analysis must recognize the normative limitations of aggregated preferences, and the moral relevance of individual conceptions of health.

  7. The impact of advertising on nicotine replacement therapy demand.

    Science.gov (United States)

    Tauras, John A; Chaloupka, Frank J; Emery, Sherry

    2005-05-01

    While much is known about the economic determinants of tobacco use, very little is known about the economic determinants of nicotine replacement therapy (NRT) use. This paper is the first econometric study to examine the impact of advertising on NRT demand. Pooled cross-sectional time-series scanner-based data for 50 major metropolitan markets in the USA covering the period between the second quarter of 1996 and the second quarter of 2002 are used in the analysis. Fixed-effects modeling is employed to estimate the NRT demand equation. The estimates indicate that increased advertising of Nicoderm CQ transdermal patches and Nicotrol transdermal patches increases per-capita sales of established Nicoderm CQ and Nicotrol products, respectively. However, increased advertising of Nicorette polacrilex (gum) was found not to significantly increase sales of established Nicorette products. Moreover, decreases in the price of NRT and increases in the price of cigarettes were found to increase per-capita sales of NRT products. Given the documented efficacy of NRT, measures to increase peoples' awareness of NRT products through advertising, measures to decrease the price of NRT, and measures to increase the price of cigarettes would be effective means to increase the use of NRT, likely leading to decreased cigarette smoking and reductions in the future public health burden caused by tobacco use.

  8. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis.

    Science.gov (United States)

    de la Iglesia-García, Daniel; Huang, Wei; Szatmary, Peter; Baston-Rey, Iria; Gonzalez-Lopez, Jaime; Prada-Ramallal, Guillermo; Mukherjee, Rajarshi; Nunes, Quentin M; Domínguez-Muñoz, J Enrique; Sutton, Robert

    2017-08-01

    The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, pregression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Kunka, Megan E; Cady, Elizabeth A; Woo, Heejung C; Thompson Bastin, Melissa L

    2015-01-01

    Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient's actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

  10. Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Megan E. Kunka

    2015-01-01

    Full Text Available Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours, which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient’s actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

  11. Applying lean principles to continuous renal replacement therapy processes.

    Science.gov (United States)

    Benfield, C Brett; Brummond, Philip; Lucarotti, Andrew; Villarreal, Maria; Goodwin, Adam; Wonnacott, Rob; Talley, Cheryl; Heung, Michael

    2015-02-01

    The application of lean principles to continuous renal replacement therapy (CRRT) processes in an academic medical center is described. A manual audit over six consecutive weeks revealed that 133 5-L bags of CRRT solution were discarded after being dispensed from pharmacy but before clinical use. Lean principles were used to examine the workflow for CRRT preparation and develop and implement an intervention. An educational program was developed to encourage and enhance direct communication between nursing and pharmacy about changes in a patient's condition or CRRT order. It was through this education program that the reordering workflow shifted from nurses to pharmacy technicians. The primary outcome was the number of CRRT solution bags delivered in the preintervention and postintervention periods. Nurses and pharmacy technicians were surveyed to determine their satisfaction with the workflow change. After implementation of lean principles, the mean number of CRRT solution bags dispensed per day of CRRT decreased substantially. Respondents' overall satisfaction with the CRRT solution preparation process increased during the postintervention period, and the satisfaction scores for each individual component of the workflow after implementation of lean principles. The decreased solution waste resulted in projected annual cost savings exceeding $70,000 in product alone. The use of lean principles to identify medication waste in the CRRT workflow and implementation of an intervention to shift the workload from intensive care unit nurses to pharmacy technicians led to reduced CRRT solution waste, improved efficiency of CRRT workflow, and increased satisfaction among staff. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  12. An experience of renal replacement therapy in children

    International Nuclear Information System (INIS)

    Jamal, A.; Ramzan, A.

    2002-01-01

    Objective: To determine the prevalence of renal failure in children requiring renal replacement therapy (RRT), the types of RRT being performed, problems encountered during the procedure and the outcome of the RRT in pediatric age group. Design: It was a retrospective study on pediatric patients with renal failure undergoing RRT. Place and Duration of Study: The study was carried out at National Institute of Child Health (N. I. C. H) covering a period of four years. Subjects and Methods: The study included all pediatric patients of acute renal failure, chronic renal failure and end stage renal disease who underwent RRT at N. I. C. H. Results: 17% of the patients with renal disease came in renal failure. A total of 65. 04 % patients received RT. Out of these, 84.7% underwent peritoneal dialysis (PD) while 15.3 % required hemodialysis and 2 were successfully transplanted. High cost of the RRT was the most commonly encountered problem during the procedure. Peritonitis was the commonest complication faced during the peritoneal dialysis while hypotension and complications related to vascular access were commonest during hemodialysis. About 50% of the patients undergoing peritoneal dialysis were left with persistent renal impairment while hemodialysis revealed a mortality of 37%. The two transplanted patients were doing well. Conclusion: The study showed that renal failure was a fairly common problem in pediatric age group and the prospects of successful RRT in Pakistan were quite high with a little effort on the part of medical professionals along with some financial assistance from the affluent of the country. (author)

  13. Patient perspectives on the optimal start of renal replacement therapy.

    Science.gov (United States)

    Henry, Shayna L; Munoz-Plaza, Corrine; Garcia Delgadillo, Jazmine; Mihara, Nichole K; Rutkowski, Mark P

    2017-09-01

    Healthcare systems and providers are encouraged to prepare their patients with advanced chronic kidney disease (CKD) for a planned start to renal replacement therapies (RRT). Less well understood are the socioemotional experiences surrounding the optimal start of RRT versus suboptimal haemodialysis (HD) starts with a central catheter. To characterise the experiences of patients beginning RRT. Qualitative, semi-structured phone interviews. A total of 168 patients with stage 5 CKD initiating RRT in an integrated, capitated learning healthcare system. Qualitative data from patients were collected as part of a quality improvement initiative to better understand patient-reported themes concerning preparation for RRT, patients' perceptions of their transition to dialysis and why sub-optimal starts for RRT occur within our healthcare system. Dual review and verification was used to identify key phrases and themes within and across each domain, using both deductive a priori codes generated by the interview guide and grounded discovery of emergent themes. From the patient perspective, preparing for RRT is an experience rooted in deep feelings of fear. In addition, a number of key factors contributed to patients' preparation (or failure to prepare) for RRT. While the education provided by our system was viewed as adequate overall, patients often felt that their emotional and psychosocial needs went unmet, regardless of whether or not, they experienced an optimal dialysis start. Future efforts should incorporate additional strategies for helping patients with advanced CKD achieve emotional and psychological safety while preparing for RRT. © 2017 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  14. Factors associated with poor outcomes of continuous renal replacement therapy.

    Directory of Open Access Journals (Sweden)

    Chih-Chin Kao

    Full Text Available Continuous renal replacement therapy (CRRT is one of the dialysis modalities for critically ill patients. Despite intensive dialysis care, a high mortality rate is found in these patients. Our objective was to investigate the factors associated with poor outcomes in these patients. We conducted a retrospective cohort study using the National Health Insurance Research Database. Records of critically ill patients who received CRRT between 2007 and 2011 were retrieved, and the patients were categorized into two groups: those with acute kidney injury (AKI and those with history of end-stage renal disease (ESRD. Our primary and secondary outcomes were in-hospital mortality and long-term survival and non-renal recovery (long-term dialysis dependence, respectively, in the AKI group. We enrolled 15,453 patients, with 13,204 and 2249 in the AKI and ESRD groups, respectively. Overall, 66.5% patients died during hospitalization. In-hospital mortality did not differ significantly between groups (adjusted odds ratio, 0.93; 95% CI, 0.84-1.02. Age, chronic liver disease, and cancer history were identified as independent risk factors for in-hospital mortality in both groups. Hypertension was associated with higher risk of in-hospital mortality in patients with AKI. Age, coronary artery disease, and admission to the medical intensive care unit (MICU were risk factors for long-term dialysis dependence in patients with AKI. Patients with AKI and ESRD have similarly poor outcomes after CRRT. Older age and presence of chronic liver disease and cancer were associated with higher mortality. Older age, presence of coronary artery disease, and admission to MICU were associated with lower renal recovery rate in patients with AKI.

  15. The integrated management for renal replacement therapy in Portugal.

    Science.gov (United States)

    Coelho, Anabela P; Sá, Helena O; Diniz, José A; Dussault, Gilles

    2014-01-01

    Portugal was the first European country to introduce an integrated management of end-stage renal disease (IM ESRD). This new program integrates various dialysis services and products, which are reimbursed at a fixed rate/patient/week called "comprehensive price payment." This initiative restructured the delivery of dialysis services, the monitoring of outcomes, and the funding of renal replacement therapy. This article described the implementation of a new model of comprehensive provision of hemodialysis (HD) services and aimed to assess its impact on dialysis care. Quality assessments and reports of patient satisfaction, produced by the Ministry of Health since 2008, as well as national registries and reports, provided the data for this review. Indicators of HD services in all continental facilities show positive results that have successively improved along the period of 2009-2011, in spite of an average annual growth of 3% of the population under HD treatment. Mortality rates for HD patients were 12.7%, 12%, and 11%, respectively in 2009, 2010, and 2011; annual hospitalization rates were 4.9%, 3.8%, and 4.4% for the same years; key performance indicators showed averages above the reference values such as hemoglobin, serum phosphorus, eKt/V, water quality, number of days of hospitalization per patient per year, and number of weekly dialysis sessions. The financing analysis of IM ESRD demonstrates a sustained control of global costs, without compromising quality. The IM ERSD program is an innovative and quality-driven approach that benefits both dialysis patients and providers, contributing toward the rationalization of service provision and the efficient use of resources. © 2013 International Society for Hemodialysis.

  16. AB19. Testosterone replacement therapy: how safe is it?

    Science.gov (United States)

    Goldenberg, Larry

    2014-01-01

    controversies surrounding testosterone replacement therapy (TRT) have been addressed in the past few years. Although the androgenic effects of TRT on normal and malignant prostate cells have been studied for over 70 years, little clinical prospective research exists on the physiological responses of prostate tissues to a wide range of serum testosterone levels. The early, well-designed in vivo studies formed the basis of the concept that testosterone has a threshold or saturation level in all types of androgen-dependent prostate cells. That is, the stimulatory effects of androgens on the prostate reach a point within physiological serum levels above which they no longer have any proliferative effect and serum levels of testosterone and dihydrotestosterone can decrease substantially in both the eugonadal and hypogonadal states without affecting the amount of androgen within the nucleus of the cell. At a certain threshold level (possibly ‘castrate’ level), the intranuclear level of androgen will begin to decrease and the appropriate physiological changes will be triggered. Questions remain as to whether results from experimental studies in the rat can be extrapolated to the situation in humans. Is the human prostate subject to the same homeostatic constraints as has been so well defined in animal experiments, and if so, what is the threshold or saturation level for maximal intracellular androgens and physiological responses in man? The sensitivity of an individual to varying levels of testosterone is also influenced by his genetic makeup, particularly polymorphisms in the androgen receptor, and other upstream signaling and downstream metabolic events, including diabetes mellitus and obesity. Despite decades of research, no compelling evidence exists that increasing testosterone beyond this threshold level has a causative role in prostate cancer, or indeed changes the biology of the disease. Notwithstanding this, the reluctance to utilize testosterone replacement has been

  17. Responsiveness to a Physiological Regimen of GnRH Therapy and Relation to Genotype in Women With Isolated Hypogonadotropic Hypogonadism

    Science.gov (United States)

    Abel, Brent S.; Shaw, Natalie D.; Brown, Jenifer M.; Adams, Judith M.; Alati, Teresa; Martin, Kathryn A.; Pitteloud, Nelly; Seminara, Stephanie B.; Plummer, Lacey; Pignatelli, Duarte; Crowley, William F.; Welt, Corrine K.

    2013-01-01

    Context: Isolated hypogonadotropic hypogonadism (IHH) is caused by defective GnRH secretion or action resulting in absent or incomplete pubertal development and infertility. Most women with IHH ovulate with physiological GnRH replacement, implicating GnRH deficiency as the etiology. However, a subset does not respond normally, suggesting the presence of defects at the pituitary or ovary. Objectives: The objective of the study was to unmask pituitary or ovarian defects in IHH women using a physiological regimen of GnRH replacement, relating these responses to genes known to cause IHH. Design, Setting, and Subjects: This study is a retrospective analysis of 37 IHH women treated with iv pulsatile GnRH (75 ng/kg per bolus). Main Outcome Measures: Serum gonadotropin and sex steroid levels were measured, and 14 genes implicated in IHH were sequenced. Results: During their first cycle of GnRH replacement, normal cycles were recreated in 60% (22 of 37) of IHH women. Thirty percent of women (12 of 37) demonstrated an attenuated gonadotropin response, indicating pituitary resistance, and 10% (3 of 37) exhibited an exaggerated FSH response, consistent with ovarian resistance. Mutations in CHD7, FGFR1, KAL1, TAC3, and TACR3 were documented in IHH women with normal cycles, whereas mutations were identified in GNRHR, PROKR2, and FGFR1 in those with pituitary resistance. Women with ovarian resistance were mutation negative. Conclusions: Although physiological replacement with GnRH recreates normal menstrual cycle dynamics in most IHH women, hypogonadotropic responses in the first week of treatment identify a subset of women with pituitary dysfunction, only some of whom have mutations in GNRHR. IHH women with hypergonadotropic responses to GnRH replacement, consistent with an additional ovarian defect, did not have mutations in genes known to cause IHH, similar to our findings in a subset of IHH men with evidence of an additional testicular defect. PMID:23341491

  18. Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with lopinavir/ritonavir plus lamivudine for initial ART in HIV infected adults.

    Science.gov (United States)

    Gatell Artigas, Josep María; Arribas López, José Ramón; Lázaro Y de Mercado, Pablo; Blasco Bravo, Antonio Javier

    2016-01-01

    The National AIDS Plan and the Spanish AIDS study group (GESIDA) proposes "preferred regimens" (PR) of antiretroviral treatment (ART) as initial therapy in HIV-infected patients. In 2013, the recommended regimens were all triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy ratios. Decision tree models were built. probability of having viral load cost: costs of ART, adverse effects, and drug resistance tests during the first 48 weeks. Cost/efficacy ratios varied between 5,817 and 13,930 euros per responder at 48 weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir, respectively. Taking into account the official Spanish prices of ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple therapy with non-nucleoside containing regimens. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  19. Hormone replacement therapy in postmenopause - where we stand?

    Directory of Open Access Journals (Sweden)

    Damir Franić

    2007-02-01

    Full Text Available Background: The findings of most relevant randomized clinical studies such as HERS, WHI and MWS, performed in the last decade have shown that hormonal replacement therapy (HRT users are at increased risk for the development of breast cancer, stroke and pulmonary edema. On the other hand they are at a lower risk for the development of large bowel cancer and for hip and vertebral fractures; the incidences of endometrial cancer and coronary heart disease have not been proved to be significantly affected by HRT. As for the prevention of cardiovascular diseases, the findings of these studies differed from those provided by observational studies, it became an imperative to find the causes of these discrepancies. The major criticism of randomized clinical studies was aimed at the inclusion criteria, as the mean women’s age in HERS and in WHI study was 63 years. The women of that age may no longer be healthy, and are particularly exposed to cardiovascular diseases. In all studies the same type of HRT was used, i.e. conjugated equine estrogen alone or in combination with medroxyprogesterone acetate. In Europe, this combination is rarely prescribed; we do not prescribe it in Slovenia either. The same type of HRT used in randomized clinical studies was further criticized, the basic idea of HRT being an individual approach to each woman requiring HRT. For rather sensational and often misinterpreted findings of randomized studies, the largest menopause societies worldwide, the International Menopause Society (IMS, the European Menopause and Andropause Society (EMAS and the North American Menopause Society (NAMS, have revised the guidelines for HRT use in postmenopause. These guidelines have been adopted by the Slovene Menopause Society as well.Conclusions: The indications for HRT remain to be markedly expressed and severe climacteric symptoms, prevention and treatment of osteoporosis, urogenital syndrome and premature menopause. However, the

  20. Temporal changes in clinic and ambulatory blood pressure during cyclic post-menopausal hormone replacement therapy

    DEFF Research Database (Denmark)

    Sørensen, M B; Rasmussen, Verner; Jensen, Gorm Boje

    2000-01-01

    OBJECTIVE: Post-menopausal hormone replacement (HRT) might protect against cardiovascular disease, possibly by arterial vasodilation and reduced blood pressure. Progestogens are needed to avoid endometrial disease but vascular effects are controversial. The objective was to assess temporal changes...... in blood pressure (BP) by two measurement techniques during a cyclic hormone replacement regimen. DESIGN AND METHODS: Sixteen healthy and normotensive post-menopausal women (age 55 +/- 3 years) were studied in a placebo-controlled, randomized crossover study, and were randomized to 17beta-oestradiol plus...

  1. Replacement

    Directory of Open Access Journals (Sweden)

    S. Radhakrishnan

    2014-03-01

    Full Text Available The fishmeal replaced with Spirulina platensis, Chlorella vulgaris and Azolla pinnata and the formulated diet fed to Macrobrachium rosenbergii postlarvae to assess the enhancement ability of non-enzymatic antioxidants (vitamin C and E, enzymatic antioxidants (superoxide dismutase (SOD and catalase (CAT and lipid peroxidation (LPx were analysed. In the present study, the S. platensis, C. vulgaris and A. pinnata inclusion diet fed groups had significant (P < 0.05 improvement in the levels of vitamins C and E in the hepatopancreas and muscle tissue. Among all the diets, the replacement materials in 50% incorporated feed fed groups showed better performance when compared with the control group in non-enzymatic antioxidant activity. The 50% fishmeal replacement (best performance diet fed groups taken for enzymatic antioxidant study, in SOD, CAT and LPx showed no significant increases when compared with the control group. Hence, the present results revealed that the formulated feed enhanced the vitamins C and E, the result of decreased level of enzymatic antioxidants (SOD, CAT and LPx revealed that these feeds are non-toxic and do not produce any stress to postlarvae. These ingredients can be used as an alternative protein source for sustainable Macrobrachium culture.

  2. Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM

    NARCIS (Netherlands)

    Brussaard, H.E.; Gevers Leuven, J.A.; Frölich, M.; Kluft, C.; Krans, H.M.J.

    1997-01-01

    Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin- dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for

  3. Clarithromycin vs. Gemifloxacin in Quadruple Therapy Regimens for Empiric Primary Treatment of Helicobacter pylori Infection: A Randomized Clinical Trial

    Science.gov (United States)

    Masoodi, Mohsen; Talebi-Taher, Mahshid; Tabatabaie, Khadijeh; Khaleghi, Siamak; Faghihi, Amir-Hossein; Agah, Shahram; Asadi, Reyhaneh

    2015-01-01

    BACKGROUND Eradication of Helicobacter pylori infection plays a crucial role in the treatment of peptic ulcer. Clarithromycin resistance is a major cause of treatment failure. This randomized clinical trial aimed at evaluating the efficacy of a clarithromycin versus gemifloxacin containing quadruple therapy regimen in eradication of H.pylori infection. METHODS In this randomized double blind clinical trial (RCT 2012102011054N2), a total of 120 patients were randomized to two groups of 60 patients each. Patients with proven H.pylori infection were consecutively assigned into two groups to receive OBAG or OBAC in gastroenterology clinic in Rasoul-e- Akram General Hospital in Tehran, Iran. The patients in the OBAG group received omeprazole (20 mg) twice daily, bismuth subcitrate (240 mg) twice daily, amoxicillin (1 gr) twice daily, and gemifloxacin (320 mg) once daily, and those in the OBAC group received omeprazole (20 mg) twice daily, 240 mg of bismuth subcitrate twice daily, amoxicillin (1 gr) twice daily, and clarithromycin (500 mg) twice daily for 10 days. RESULTS Five patients from each group were excluded from the study because of poor compliance, so 110 patients completed the study. The intention-to-treat eradication rate was 61.6% and 66.6% for the OBAC and OBAG groups, respectively. According to the per protocol analysis, the success rates of eradication of H.pylori infection were 67.2% and 72.7% for OBAC and OBAG groups, respectively (p=0.568). CONCLUSION The results of this study suggest that gemifloxacin containing regimen is at least as effective as clarithromycin regimen; hence, this new treatment could be considered as an alternative for the patients who cannot tolerate clarithromycin. PMID:26106468

  4. Combined miglustat and enzyme replacement therapy in two patients with type 1 Gaucher disease: two case reports.

    Science.gov (United States)

    Amato, Dominick; Patterson, Mary Anne

    2018-01-27

    Intravenous enzyme replacement therapy is a first-line therapy for Gaucher disease type 1, and substrate reduction therapy represents an oral treatment alternative. Both enzyme replacement therapy and substrate reduction therapy are generally used as monotherapies in Gaucher disease. However, one randomized study and several case reports have described combination therapy over short time periods. We report two female Gaucher disease type 1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement therapy and miglustat substrate reduction therapy were administered to overcome refractory clinical symptoms. The first patient was diagnosed at age 17 and developed Gaucher disease-related bone manifestations that worsened despite starting imiglucerase enzyme replacement therapy. After switching to miglustat substrate reduction therapy, her bone symptoms improved, but she developed tremors and eventually switched back to enzyme replacement therapy. Miglustat was later recommenced in combination with ongoing enzyme replacement therapy due to continued bone pain, and her bone symptoms improved along with maintained visceral manifestations. Enzyme replacement therapy was subsequently tapered off and the patient has since been successfully maintained on miglustat. The second patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement therapy aged 15. After 9 years on enzyme replacement therapy she switched to miglustat substrate reduction therapy and her core symptoms were maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later added as a boost to therapy and her symptoms were subsequently maintained over a 2.3-year period. However, miglustat was discontinued due to her relocation, necessitating an increase in enzyme replacement therapy dose. Overall, both patients benefited from combination therapy. While the majority of Gaucher disease type 1 patients will not need treatment with both substrate reduction therapy

  5. Toward a noncytotoxic glioblastoma therapy: blocking MCP-1 with the MTZ Regimen

    Directory of Open Access Journals (Sweden)

    Salacz ME

    2016-04-01

    Full Text Available Michael E Salacz,1,2 Richard E Kast,3 Najmaldin Saki,4 Ansgar Brüning,5 Georg Karpel-Massler,6 Marc-Eric Halatsch6 1Department of Internal Medicine, 2Department of Neurosurgery, University of Kansas, Kansas City, KS, USA; 3IIAIGC Study Center, Burlington, VT, USA; 4Health Research Institute, Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 5Molecular Biology Laboratory, University Hospital Munich, Munich, Germany; 6Department of Neurosurgery, University of Ulm, Ulm, Germany Abstract: To improve the prognosis of glioblastoma, we developed an adjuvant treatment directed to a neglected aspect of glioblastoma growth, the contribution of nonmalignant monocyte lineage cells (MLCs (monocyte, macrophage, microglia, dendritic cells that infiltrated a main tumor mass. These nonmalignant cells contribute to glioblastoma growth and tumor homeostasis. MLCs comprise of approximately 10%–30% of glioblastoma by volume. After integration into the tumor mass, these become polarized toward an M2 immunosuppressive, pro-angiogenic phenotype that promotes continued tumor growth. Glioblastoma cells initiate and promote this process by synthesizing 13 kDa MCP-1 that attracts circulating monocytes to the tumor. Infiltrating monocytes, after polarizing toward an M2 phenotype, synthesize more MCP-1, forming an amplification loop. Three noncytotoxic drugs, an antibiotic – minocycline, an antihypertensive drug – telmisartan, and a bisphosphonate – zoledronic acid, have ancillary attributes of MCP-1 synthesis inhibition and could be re-purposed, singly or in combination, to inhibit or reverse MLC-mediated immunosuppression, angiogenesis, and other growth-enhancing aspects. Minocycline, telmisartan, and zoledronic acid – the MTZ Regimen – have low-toxicity profiles and could be added to standard radiotherapy and temozolomide. Re-purposing older drugs has advantages of established safety and low

  6. Calculating evidence-based renal replacement therapy - Introducing an excel-based calculator to improve prescribing and delivery in renal replacement therapy - A before and after study.

    Science.gov (United States)

    Cottle, Daniel; Mousdale, Stephen; Waqar-Uddin, Haroon; Tully, Redmond; Taylor, Benjamin

    2016-02-01

    Transferring the theoretical aspect of continuous renal replacement therapy to the bedside and delivering a given "dose" can be difficult. In research, the "dose" of renal replacement therapy is given as effluent flow rate in ml kg -1  h -1 . Unfortunately, most machines require other information when they are initiating therapy, including blood flow rate, pre-blood pump flow rate, dialysate flow rate, etc. This can lead to confusion, resulting in patients receiving inappropriate doses of renal replacement therapy. Our aim was to design an excel calculator which would personalise patient's treatment, deliver an effective, evidence-based dose of renal replacement therapy without large variations in practice and prolong filter life. Our calculator prescribes a haemodialfiltration dose of 25 ml kg -1  h -1 whilst limiting the filtration fraction to 15%. We compared the episodes of renal replacement therapy received by a historical group of patients, by retrieving their data stored on the haemofiltration machines, to a group where the calculator was used. In the second group, the data were gathered prospectively. The median delivered dose reduced from 41.0 ml kg -1  h -1 to 26.8 ml kg -1  h -1 with reduced variability that was significantly closer to the aim of 25 ml kg -1 .h -1 ( p  < 0.0001). The median treatment time increased from 8.5 h to 22.2 h ( p  = 0.00001). Our calculator significantly reduces variation in prescriptions of continuous veno-venous haemodiafiltration and provides an evidence-based dose. It is easy to use and provides personal care for patients whilst optimizing continuous veno-venous haemodiafiltration delivery and treatment times.

  7. Exploring the bio-psychosocial effects of renal replacement therapy ...

    African Journals Online (AJOL)

    2011-05-25

    May 25, 2011 ... This article described a qualitative study that investigated the bio-psychosocial effects of renal replacement ... of the exodus of health professionals affecting the medical fraternity, as .... and interpret the meanings and effects of specific phenomena. ... as an early indicator of topic and location selection by.

  8. Decreased plasma cholesterol esterification and cholesteryl ester transfer in hypopituitary patients on glucocorticoid replacement therapy

    NARCIS (Netherlands)

    Beentjes, JAM; Van Tol, A; Sluiter, WJ; Dullaart, RPF

    Cardiovascular risk is increased in hypopituitary patients. No data are available with respect to the effect of glucocorticoid replacement therapy on high density lipoproteins (HDL) metabolism in such patients. Plasma lecithin:choresterol acyl transferase (LCAT), cholesteryl ester transfer protein

  9. Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease

    NARCIS (Netherlands)

    Smans, L.; Lentjes, E.G.W.M.; Hermus, A.R.; Zelissen, P.M.J.

    2013-01-01

    OBJECTIVE: Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects.

  10. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease

    DEFF Research Database (Denmark)

    Biegstraaten, Marieke; Arngrímsson, Reynir; Barbey, Frederic

    2015-01-01

    INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed ...

  11. [Investigation of the medical and social situation of patients managed by opiate replacement regimens for over 10 years by their GP].

    Science.gov (United States)

    Messaadi, Nassir; Favre, Jonathan; Rolland, Benjamin; Cottencin, Olivier; Calafiore, Matthieu; Stalnikiewicz, Bertrand; Berkhout, Christophe

    2016-10-01

    Management with opiate replacement regimens (ORRs) of patients presenting to primary care settings with opiate addiction has become a long-term follow-up. The aim of this survey study was to describe patients who had been prescribed ORRs for at least 10 years by their general practitioner (GP). In 2011, two questionnaires were sent to a sample of 38 GPs prescribing ORRs in Northern France. Doctors' questionnaires collected their typology and opinions on their patients receiving opiate substitution treatments for over 10 years. Patients' questionnaires were completed in the presence of the patient. Twenty-three doctors' and 83 patients' questionnaires were suitable for analysis. The average number of listed ORR patients was 14.2 and 3.6 had been managed for 10 years or more. Misuse persisted: 30.5% of GPs considered that it was carried out by at least by 15% of patients. Average dosages were 60.3 mg for methadone and 7.0 mg for buprenorphine. Employment (46.3% of patients had a salary), dwelling and family live (46.3% of patients were in charge of children) were favored. Nevertheless, precariousness persisted: 32% of patients were indebted and help of social workers was not systematically searched. One third of the patients were alcohol and cannabis misusers, 70% were smoking and 34.5% multiple drug misusers. An important number of patients were taking anxiolytics (37.8%) and hypnotics (30.5%). After 10 years of follow-up for an ORR by a GP, the social situation of patients seems to have stabilized, but psychoactive drugs consumption remains important. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  12. Renal Replacement Therapy Modality in the ICU and Renal Recovery at Hospital Discharge.

    Science.gov (United States)

    Bonnassieux, Martin; Duclos, Antoine; Schneider, Antoine G; Schmidt, Aurélie; Bénard, Stève; Cancalon, Charlotte; Joannes-Boyau, Olivier; Ichai, Carole; Constantin, Jean-Michel; Lefrant, Jean-Yves; Kellum, John A; Rimmelé, Thomas

    2018-02-01

    Acute kidney injury requiring renal replacement therapy is a major concern in ICUs. Initial renal replacement therapy modality, continuous renal replacement therapy or intermittent hemodialysis, may impact renal recovery. The aim of this study was to assess the influence of initial renal replacement therapy modality on renal recovery at hospital discharge. Retrospective cohort study of all ICU stays from January 1, 2010, to December 31, 2013, with a "renal replacement therapy for acute kidney injury" code using the French hospital discharge database. Two hundred ninety-one ICUs in France. A total of 1,031,120 stays: 58,635 with renal replacement therapy for acute kidney injury and 25,750 included in the main analysis. None. PPatients alive at hospital discharge were grouped according to initial modality (continuous renal replacement therapy or intermittent hemodialysis) and included in the main analysis to identify predictors of renal recovery. Renal recovery was defined as greater than 3 days without renal replacement therapy before hospital discharge. The main analysis was a hierarchical logistic regression analysis including patient demographics, comorbidities, and severity variables, as well as center characteristics. Three sensitivity analyses were performed. Overall mortality was 56.1%, and overall renal recovery was 86.2%. Intermittent hemodialysis was associated with a lower likelihood of recovery at hospital discharge; odds ratio, 0.910 (95% CI, 0.834-0.992) p value equals to 0.0327. Results were consistent across all sensitivity analyses with odds/hazards ratios ranging from 0.883 to 0.958. In this large retrospective study, intermittent hemodialysis as an initial modality was associated with lower renal recovery at hospital discharge among patients with acute kidney injury, although the difference seems somewhat clinically limited.

  13. Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, H.E.; Ott, Peter

    2007-01-01

    Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.......Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

  14. Use of Monte Carlo Simulations to Determine Optimal Carbapenem Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Lewis, Susan J; Kays, Michael B; Mueller, Bruce A

    2016-10-01

    Pharmacokinetic/pharmacodynamic analyses with Monte Carlo simulations (MCSs) can be used to integrate prior information on model parameters into a new renal replacement therapy (RRT) to develop optimal drug dosing when pharmacokinetic trials are not feasible. This study used MCSs to determine initial doripenem, imipenem, meropenem, and ertapenem dosing regimens for critically ill patients receiving prolonged intermittent RRT (PIRRT). Published body weights and pharmacokinetic parameter estimates (nonrenal clearance, free fraction, volume of distribution, extraction coefficients) with variability were used to develop a pharmacokinetic model. MCS of 5000 patients evaluated multiple regimens in 4 different PIRRT effluent/duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis or hemofiltration) occurring at the beginning or 14-16 hours after drug infusion. The probability of target attainment (PTA) was calculated using ≥40% free serum concentrations above 4 times the minimum inhibitory concentration (MIC) for the first 48 hours. Optimal doses were defined as the smallest daily dose achieving ≥90% PTA in all PIRRT combinations. At the MIC of 2 mg/L for Pseudomonas aeruginosa, optimal doses were doripenem 750 mg every 8 hours, imipenem 1 g every 8 hours or 750 mg every 6 hours, and meropenem 1 g every 12 hours or 1 g pre- and post-PIRRT. Ertapenem 500 mg followed by 500 mg post-PIRRT was optimal at the MIC of 1 mg/L for Streptococcus pneumoniae. Incorporating data from critically ill patients receiving RRT into MCS resulted in markedly different carbapenem dosing regimens in PIRRT from those recommended for conventional RRTs because of the unique drug clearance characteristics of PIRRT. These results warrant clinical validation. © 2016, The American College of Clinical Pharmacology.

  15. Hormone Replacement Therapy: Can It Cause Vaginal Bleeding?

    Science.gov (United States)

    ... hormone therapy for menopause symptoms, and my monthly menstrual periods have returned. Is this normal? Answers from ... Advertising and sponsorship opportunities Reprint Permissions A single copy of these materials may be reprinted for noncommercial ...

  16. The cost and effectiveness of surfactant replacement therapy at ...

    African Journals Online (AJOL)

    S Atr Med J 1995; 85; 646-649. Department of Paediatrics and Child Health, Johannesburg Hospital ..... infants is small - of the order of 1% - as in this study. ... effects of surfactant therapy for neonatal respiratory distress syndrome. J Pediatr.

  17. The effect of a high-protein, high-sodium diet on calcium and bone metabolism in postmenopausal women stratified by hormone replacement therapy use

    DEFF Research Database (Denmark)

    Harrington, M.; Bennett, T.; Jakobsen, Jette

    2004-01-01

    The objective of this study was to investigate the influence of a high-sodium, high-protein diet on bone metabolism in postmenopausal women ( aged 49 - 60 y) stratified by hormone replacement therapy (HRT) use. In a crossover trial, 18 women (n = 8 HRT users (+HRT) and n = 10 nonusers (-HRT)) were...... randomly assigned to a diet high in protein ( 90 g/day) and sodium (180 mmol/day) ( calciuric diet) or a diet moderate in protein ( 70 g/day) and low in sodium ( 65 mmol/day) for 4 weeks followed by crossover to alternative dietary regimen for a further 4 weeks. The calciuric diet significantly (P...

  18. Evening versus morning dosing regimen drug therapy for chronic kidney disease patients with hypertension in blood pressure patterns: a systematic review and meta-analysis.

    Science.gov (United States)

    Wang, Caixia; Ye, Yuqiu; Liu, Chunyong; Zhou, Yongming; Lv, Linsheng; Cheng, Cailian; Li, Shaomin; Lou, Tanqi; Liu, Xun

    2017-08-01

    Evening dosing regimen drug therapy on blood pressure (BP) control is used widely, but its clinical benefits and preservation or re-establishment of the normal 24-h BP dipping pattern in chronic kidney disease (CKD) patients is not known. To investigate the effect of an evening dosing regimen of antihypertensive drugs on BP patterns of CKD patients with hypertension. A systematic review was conducted by searching PUBMED, EMBASE, ASN-ONLINE, the Cochrane Library and the reference lists of relevant articles of published papers. All trials designed to evaluate the effects of evening versus morning dosing regimen drug therapy for CKD patients with hypertension were included. Meta-analysis was performed using random or fixed effects models. Five randomised controlled trials and one comparative study, including 3732 patients, met the inclusion criteria. Compared with morning dosing regimen drug therapy, evening administration of antihypertensive medication was associated with a significant reduction of 40% in non-dipper BP patterns (risk ratio (RR), 95% CI, (0.43, 0.84)). We noted a significant decrease in nocturnal systolic blood pressure (SBP) (MD -3.17 mmHg, 95% CI (-5.41, -0.94)), a significant reduction in nocturnal diastolic blood pressure (DBP) (MD -1.37 mmHg, 95% CI (-2.05, -0.69)) and a significant increase in awake SBP (MD 1.15 mmHg, 95% CI (0.10, 2.19)) in patients assigned to the evening dosing regimen drug therapy group. Patients showed no significant differences for all-cause mortality and cardiovascular mortality. This review shows that evening dosing regimen drug therapy could reverse non-dipper BP patterns in hypertensive CKD patients. © 2017 Royal Australasian College of Physicians.

  19. Microvascular blood flow dynamics associated with photodynamic therapy, pulsed dye laser irradiation and combined regimens

    OpenAIRE

    Smith, TK; Choi, B; Ramirez-San-Juan, JC; Nelson, JS; Osann, K; Kelly, KM

    2006-01-01

    Background and Objectives: Previous in vitro studies demonstrated the potential utility of benzoporphyrin derivative monoacid ring A (BPD) photodynamic therapy (PDT) for vascular destruction. Moreover, the effects of PDT were enhanced when this intervention was followed immediately by pulsed dye laser (PDL) irradiation (PDT/ PDL). We further evaluate vascular effects of PDT alone, PDL alone and PDT/PDL in an in vivo rodent dorsal skinfold model. Study Design/Materials and Methods: A dorsal sk...

  20. The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties.

    Science.gov (United States)

    Iung, Bernard; Rodés-Cabau, Josep

    2014-11-07

    Anti-thrombotic therapy after valve replacement encompasses a number of different situations. Long-term anticoagulation of mechanical prostheses uses vitamin K antagonists with a target international normalized ratio adapted to the characteristics of the prosthesis and the patient. The association of low-dose aspirin is systematic in the American guidelines and more restrictive in the European guidelines. Early heparin therapy is frequently used early after mechanical valve replacement, although there are no precise recommendations regarding timing, type, and dose of drug. Direct oral anticoagulants are presently contraindicated in patients with mechanical prosthesis. The main advantage of bioprostheses is the absence of long-term anticoagulant therapy. Early anticoagulation is indicated after valve replacement for mitral bioprostheses, whereas aspirin is now favoured early after bioprosthetic valve replacement in the aortic position. Early dual antiplatelet therapy is indicated after transcatheter aortic valve implantation, followed by single antiplatelet therapy. However, this relies on low levels of evidence and optimization of anti-thrombotic therapy is warranted in these high-risk patients. Although guidelines are consistent in most instances, discrepancies and the low-level of evidence of certain recommendations highlight the need for further controlled trials, in particular with regard to the combination of antiplatelet therapy with oral anticoagulant and the early post-operative anti-thrombotic therapy following the procedure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  1. Radiosynoviorhesis after total knee replacement: effective therapy of ''polythylene disease''

    International Nuclear Information System (INIS)

    Moedder, G.; Moedder-Reese, R.

    2001-01-01

    Radiosynoviorthesis is an adequate therapy to remove the effects of polyethylene wear: β-emission reduces growth of the foreign body granulomas and means an overkill for bacterias in penetration depth. This is a report about experience with 107 patients. (orig.) [de

  2. The physician's role in selecting a factor replacement therapy.

    Science.gov (United States)

    Pipe, S W

    2006-03-01

    Over the past 20 years, transmissions of human immunodeficiency virus (HIV), hepatitis B virus or hepatitis C virus have been virtually eliminated from plasma-derived or recombinant therapy in the USA, a record that can be largely attributed to the use of effective screening and inactivation technologies for known pathogens. The next significant threat will likely come from the emergence of a new, blood-borne infectious disease, perhaps one transmitted by a non-lipid-enveloped virus or prion, for which current inactivation methods are ineffective. Following the HIV crisis of the 1980s, government, patient advocacy groups, medical and scientific communities and the manufacturers of clotting therapies can learn from the past and approach potential threats from emerging pathogens in a proactive and productive manner. For clinicians, this includes actively engaging patients in a dialogue about all the factors that may influence their choice of clotting factor therapies, including emerging pathogens, patient convenience, consistency and reliability of supply, relative cost/benefit ratios, reimbursement issues (where applicable), patient preference and brand loyalty. It is our obligation as healthcare providers to understand potential risks and help make proactive decisions with our patients, decisions that often must be made in an environment of scientific uncertainty. Threats from infectious agents that were once deemed theoretical can, and often do, ultimately become real, with serious implications for morbidity and mortality.

  3. Therapy of hypoparathyroidism by replacement with parathyroid hormone

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Underbjerg, Line; Sikjaer, Tanja

    2014-01-01

    Hypoparathyroidism (HypoPT) is a state of hypocalcemia due to inappropriate low levels of parathyroid hormone (PTH). HypoPT is normally treated by calcium supplements and activated vitamin D analogues. Although plasma calcium is normalized in response to conventional therapy, quality of life (Qo...... recently, continuous delivery of PTH by pump has appeared as a feasible alternative to injections. Plasma calcium levels do not fluctuate, urinary calcium is lowered, and bone turnover is only stimulated modestly (into the normal range). Further studies are needed to assess the long-term effects...

  4. Testosterone Replacement Therapy and Polycythemia in HIV-infected Patients

    Science.gov (United States)

    Vorkas, Charles Kyriakos; Vaamonde, Carlos M.; Glesby, Marshall J.

    2013-01-01

    We conducted a case-control study to assess testosterone use as a primary risk factor for polycythemia in 21 HIV-infected men. Any testosterone use within two months of first elevated hemoglobin was associated with polycythemia (matched odds ratio 6.55; 95% CI 1.83-23.4; P=0.004) and intramuscular administration demonstrated a stronger association than topical use. No adverse cardiovascular or thrombotic events were observed. HIV-infected patients taking testosterone should undergo routine hematologic monitoring with adjustment of therapy when appropriate. PMID:22008652

  5. Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy

    International Nuclear Information System (INIS)

    Chen Bin; Pogue, Brian W.; Hoopes, P. Jack; Hasan, Tayyaba

    2005-01-01

    Purpose: Photodynamic therapy (PDT) can be designed to target either tumor vasculature or tumor cells by varying the drug-light interval. Photodynamic therapy treatments with different drug-light intervals can be combined to increase tumor response by targeting both tumor vasculature and tumor cells. The sequence of photosensitizer and light delivery can influence the effect of combined treatments. Methods and materials: The R3327-MatLyLu rat prostate tumor model was used in this study. Photosensitizer verteporfin distribution was quantified by fluorescence microscopy. Tumor blood flow changes were monitored by laser-Doppler system and tumor hypoxia was quantified by the immunohistochemical staining for the hypoxic marker EF5. The therapeutic effects of PDT treatments were evaluated by the histologic examination and tumor regrowth assay. Results: Fluorescence microscopic studies indicated that tumor localization of verteporfin changed from predominantly within the tumor vasculature at 15 min after injection, to being throughout the tumor parenchyma at 3 h after injection. Light treatment (50 J/cm 2 ) at 15 min after verteporfin injection (0.25 mg/kg, i.v.) induced significant tumor vascular damage, as manifested by tumor blood flow reduction and increase in the tumor hypoxic fraction. In contrast, the vascular effect observed after the same light dose (50 J/cm 2 ) delivered 3 h after administration of verteporfin (1 mg/kg, i.v.) was an initial acute decrease in blood flow, followed by recovery to the level of control. The EF5 staining revealed no significant increase in hypoxic fraction at 1 h after PDT using 3 h drug-light interval. The combination of 3-h interval PDT and 15-min interval PDT was more effective in inhibiting tumor growth than each individual PDT treatment. However, it was found that the combined treatment with the sequence of 3-h interval PDT before 15-min interval PDT led to a superior antitumor effect than the other combinative PDT treatments

  6. Associations between the number of natural teeth in postmenopausal women and hormone replacement therapy.

    Science.gov (United States)

    Han, Kyungdo; Ko, Youngkyung; Park, Yong-Gyu; Park, Jun-Beom

    2016-12-01

    Increasing research suggests that periodontal status is associated with hormone replacement therapy in postmenopausal women. This study was performed to assess the relationship between the number of natural teeth and ever use of hormone replacement therapy in postmenopausal women using nationally representative Korean data. Data from the Korea National Health and Nutrition Examination Survey between 2010 and 2012 were used, and the analysis in this study was confined to a total of 4869 respondents over 19 years old who had gone through menopause and who had no missing data for the reproductive factors and outcome variables in that study. The total number of natural teeth was then calculated after excluding third molars. The time of day when tooth brushing was done was recorded as representative oral health behavior. Multiple logistic regression analyses were used to assess association between the number of natural teeth and the use of hormone replacement therapy. Among participants who had ever used hormone replacement therapy, the proportions (percentage and standard error) with no teeth, 1-9 teeth, 10-19 teeth, 20-27 teeth, and 28 teeth were 5.0±2.4%, 6.7±1.4%, 12.5±1.7%, 18.9±1.0%, and 20.7±1.6%, respectively (Preplacement therapy, after adjustments. The analysis revealed that the use of hormone replacement therapy by postmenopausal women showed positive effects for retention of natural teeth. Lack of hormone replacement therapy may be considered to be an independent risk indicator for tooth loss in Korean postmenopausal women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Temporal changes in clinic and ambulatory blood pressure during cyclic post-menopausal hormone replacement therapy

    DEFF Research Database (Denmark)

    Sørensen, M B; Rasmussen, Verner; Jensen, Gorm Boje

    2000-01-01

    OBJECTIVE: Post-menopausal hormone replacement (HRT) might protect against cardiovascular disease, possibly by arterial vasodilation and reduced blood pressure. Progestogens are needed to avoid endometrial disease but vascular effects are controversial. The objective was to assess temporal changes...... in blood pressure (BP) by two measurement techniques during a cyclic hormone replacement regimen. DESIGN AND METHODS: Sixteen healthy and normotensive post-menopausal women (age 55 +/- 3 years) were studied in a placebo-controlled, randomized crossover study, and were randomized to 17beta-oestradiol plus...... and in the ninth weeks of treatment in both periods. RESULTS: Clinic systolic and diastolic BP were reduced after 10 days of oestradiol (-5.1 and -3.2 mmHg respectively, P

  8. Positive impact of hormone replacement therapy on the fibrinolytic system

    DEFF Research Database (Denmark)

    Madsen, J S; Kristensen, S R; Gram, J

    2003-01-01

    be of importance. OBJECTIVES: To investigate the prolonged effect of HRT on the fibrinolytic system and to determine whether two common polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) genes modulate this effect. Methods: Healthy postmenopausal women (n...... = 248) were randomized to HRT (n = 122) or no substitution (n = 126) 5 years prior to investigation. RESULTS: Significantly higher values of t-PA activity and lower values of PAI-1 activity and PAI-1 antigen were found in the HRT group compared with the control group. This effect was independent...... of smoking and without influence from the two common polymorphisms PAI-1 -675(4G/5G) and t-PA intron8ins311. Furthermore, no difference between opposed estrogen (with norethisterone acetate as the gestagen component) and unopposed estrogen therapy was found. Both an intention-to-treat and a per...

  9. Kidney transplantation in the context of renal replacement therapy.

    Science.gov (United States)

    Pesavento, Todd E

    2009-12-01

    Kidney transplantation has dramatically evolved from a life-saving yet unproven therapy for patients with renal failure to a mature field that is the preferred treatment for those suffering from ESRD. Patients who receive a transplant experience a 68% lower risk of death compared with those waiting on dialysis for a transplant. This benefit is afforded to all patient subgroups including the elderly (> or =70 yr), and diabetics, who can gain 11 yr of extra life with transplantation. Prolonged transplant wait times result in a higher risk of death but this can be ameliorated with preemptive transplantation. Future challenges will focus on appropriate organ allocation and addressing long-term renal function and comorbid conditions so patients can enjoy the full benefits of transplantation.

  10. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    Science.gov (United States)

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

  11. Postoperative Radiation Therapy for Prostate Cancer: Comparison of Conventional Versus Hypofractionated Radiation Regimens.

    Science.gov (United States)

    Tandberg, Daniel J; Oyekunle, Taofik; Lee, W Robert; Wu, Yuan; Salama, Joseph K; Koontz, Bridget F

    2018-06-01

    To compare acute/late toxicity and biochemical control in contemporaneous prostate cancer patient cohorts treated with hypofractionated postprostatectomy radiation therapy (hypoPORT) or conventional PORT (coPORT). Consecutive patients treated with intensity modulated hypoPORT (2.5 Gy per fraction, median cumulative dose 65 Gy [range, 57.5-70 Gy]) or coPORT (1.8-2.0 Gy per fraction, median cumulative dose 66 Gy [range, 60-74 Gy]) between 2005 and 2016 at 2 institutions constituted the study cohort. Acute toxicity and cumulative late grade 2 and ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity incidences were calculated for all patients using the Kaplan-Meier method and compared between cohorts. Biochemical progression-free survival (bPFS) was calculated in patients with ≥12 months' follow-up. Median follow-up for all 461 patients was 38.6 months. Of the 461 patients, 167 (36%) received hypoPORT, and 294 (64%) patients received coPORT. The hypoPORT cohort had significantly worse baseline urinary incontinence. Acute grade ≥2 GU toxicity was more common after hypoPORT (22% vs 8%) (P = .0001). Late grade ≥3 GU toxicity cumulative incidence at 6 years was 11% (hypoPORT) and 4% (coPORT) (P = .0081). However, hypoPORT was not associated with late grade ≥2 GU toxicity on multivariate analysis (hazard ratio 1.39, 95% confidence interval 0.86-2.34) (P = .18). There was no difference in acute or late GI toxicity. In the subset of patients with ≥12 month's follow-up (n = 364, median follow-up 52 months), 4-year bPFS was 78% (95% CI 69.4-85.0) after hypoPORT (P = .0038) and 65% (95% CI 57.6-71.1) after coPORT. HypoPORT was not significant for bPFS on multivariate analysis (hazard ratio 0.64, 95% CI 0.41-1.02, P = .059). HypoPORT shows promising early biochemical control. After controlling for baseline urinary function, hypoPORT was not associated with greater GU toxicity than coPORT. © 2018 Elsevier Inc. Copyright © 2018 Elsevier Inc. All

  12. Eccentric LVH healing after starting renal replacement therapy.

    Science.gov (United States)

    Vertolli, Ugo; Lupia, Mario; Naso, Agostino

    2002-01-01

    Hypertension and left ventricular hypertrophy (LVH) are commonly associated in patients with CRF starting RDT. We report a case of eccentric LVH with marked dilatation and subsequent mitral incompetence of +3/4 that disappeared after three months of standard hemodialysis. Mrs SN, 62 years old, starting HD, had an echocardiography because of dyspnoea; the echo showed: dilated left atrium (78 ml/m2), moderately dilated left ventricle with normal systolic function (TDV 81 ml/m2, EF 66%), an increased ventricular mass (120 gr/m2) and a high grade mitral incompetence +3/4. After three months standard RDT and a dry weight only 2 kg less, the patients was normotensive without therapy, a cardiac angiogram with a hemodynamic study was performed as a pre-transplant workout: a normal left ventricle was found with normal systolic function (TDV 66, TSV 17, GS 49, EF 75%), and a perfectly competent mitral valve (reflux disappeared). The coronary angiography did not reveal critical stenosis. A new echocardiography confinned the data of the hemodynamic study: hypertensive cardiomiopathy with normal systolic function. After one year the patient has been transplanted, with a good renal function and the cardiac echo unchanged. Relieving uremic toxicity ameliorated the cardiac performance in this particular patient.

  13. Testosterone Replacement Therapy: Long-Term Safety and Efficacy

    Directory of Open Access Journals (Sweden)

    Giovanni Corona

    2017-08-01

    Full Text Available Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG or late-onset hypogonadism (LOH. The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T therapy (TTh. In addition, concerns related to cardiovascular (CV safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented.

  14. Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

    Science.gov (United States)

    Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

    2015-07-01

    Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

  15. Testosterone replacement therapy and the heart: friend, foe or bystander?

    Science.gov (United States)

    Lopez, David S; Canfield, Steven; Wang, Run

    2016-12-01

    The role of testosterone therapy (TTh) in cardiovascular disease (CVD) outcomes is still controversial, and it seems will remain inconclusive for the moment. An extensive body of literature has investigated the association of endogenous testosterone and use of TTh with CVD events including several meta-analyses. In some instances, a number of studies reported beneficial effects of TTh on CVD events and in other instances the body of literature reported detrimental effects or no effects at all. Yet, no review article has scrutinized this body of literature using the magnitude of associations and statistical significance reported from this relationship. We critically reviewed the previous and emerging body of literature that investigated the association of endogenous testosterone and use of TTh with CVD events (only fatal and nonfatal). These studies were divided into three groups, "beneficial (friendly use)", "detrimental (foe)" and "no effects at all (bystander)", based on their magnitude of associations and statistical significance from original research studies and meta-analyses of epidemiological studies and of randomized controlled trials (RCT's). In this review article, the studies reporting a significant association of high levels of testosterone with a reduced risk of CVD events in original prospective studies and meta-analyses of cross-sectional and prospective studies seems to be more consistent. However, the number of meta-analyses of RCT's does not provide a clear picture after we divided it into the beneficial, detrimental or no effects all groups using their magnitudes of association and statistical significance. From this review, we suggest that we need a study or number of studies that have the adequate power, epidemiological, and clinical data to provide a definitive conclusion on whether the effect of TTh on the natural history of CVD is real or not.

  16. Electronic cigarettes: health impact, nicotine replacement therapy, regulations

    Directory of Open Access Journals (Sweden)

    Zygmunt Zdrojewicz

    2017-03-01

    Full Text Available While the adverse effects of conventional cigarettes on human health have been thoroughly examined, in the last 15 years we have witnessed the birth of electronic cigarettes. There are many types of these devices available on the market. Studies are still underway to determine their negative impact on the human body. Electronic cigarettes comprise of power supply and a vaporising system. The user inhales the aerosol produced by heating up the liquid containing nicotine. In contrast with conventional cigarettes, the tobacco is not combusted, thus the compositions of the aerosol and cigarette smoke are considerably different. Out of 93 chemical substances present in the e-cigarette smoke, the aerosol contains only acetaldehyde, acetone, acrolein, formaldehyde and nicotine. More toxic substances, such as polycyclic aromatic hydrocarbons and heavy metals, are not present. The amount of evidence suggesting electronic cigarettes’ harmful effects on the human body is constantly increasing. Some reports imply that the electronic cigarettes negatively influence pregnancy, human psyche, respiratory and cardiovascular systems. They might also be involved in oncogenesis. With electronic cigarettes constantly gaining popularity, the question about the adverse effects of passive smoking becomes increasingly more relevant. Although various methods of helping people cease smoking or delivering nicotine to their bodies without burning toxic substances are being explored, electronic cigarettes are not recommended in nicotine substitution therapy. Legal regulations regarding electronic cigarettes are still being worked on. The purpose of this paper is to evaluate the effects electronic cigarettes have on the human’s health.

  17. Deconvolution analysis of 24-h serum cortisol profiles informs the amount and distribution of hydrocortisone replacement therapy.

    Science.gov (United States)

    Peters, Catherine J; Hill, Nathan; Dattani, Mehul T; Charmandari, Evangelia; Matthews, David R; Hindmarsh, Peter C

    2013-03-01

    Hydrocortisone therapy is based on a dosing regimen derived from estimates of cortisol secretion, but little is known of how the dose should be distributed throughout the 24 h. We have used deconvolution analysis of 24-h serum cortisol profiles to determine 24-h cortisol secretion and distribution to inform hydrocortisone dosing schedules in young children and older adults. Twenty four hour serum cortisol profiles from 80 adults (41 men, aged 60-74 years) and 29 children (24 boys, aged 5-9 years) were subject to deconvolution analysis using an 80-min half-life to ascertain total cortisol secretion and distribution throughout the 24-h period. Mean daily cortisol secretion was similar between adults (6.3 mg/m(2) body surface area/day, range 5.1-9.3) and children (8.0 mg/m(2) body surface area/day, range 5.3-12.0). Peak serum cortisol concentration was higher in children compared with adults, whereas nadir serum cortisol concentrations were similar. Timing of the peak serum cortisol concentration was similar (07.05-07.25), whereas that of the nadir concentration occurred later in adults (midnight) compared with children (22.48) (P = 0.003). Children had the highest percentage of cortisol secretion between 06.00 and 12.00 (38.4%), whereas in adults this took place between midnight and 06.00 (45.2%). These observations suggest that the daily hydrocortisone replacement dose should be equivalent on average to 6.3 mg/m(2) body surface area/day in adults and 8.0 mg/m(2) body surface area/day in children. Differences in distribution of the total daily dose between older adults and young children need to be taken into account when using a three or four times per day dosing regimen. © 2012 Blackwell Publishing Ltd.

  18. The efficacy of surfactant replacement therapy in the growth restricted preterm infant: what is the evidence?

    Directory of Open Access Journals (Sweden)

    Atul eMalhotra

    2014-10-01

    Full Text Available Background: Surfactant replacement therapy (SRT is an integral part of management of preterm surfactant deficiency (respiratory distress syndrome, RDS. Its role in the management of RDS has been extensively studied. However its efficacy in the management of lung disease in preterm infants born with intrauterine growth restriction (IUGR has not been systematically studied.Objective: To evaluate the efficacy of exogenous surfactant replacement therapy in the management of preterm IUGR lung disease. Methods: A systematic search of all available randomised clinical trials (RCT of surfactant replacement therapy in preterm IUGR infants was done according to the standard Cochrane collaboration search strategy. Neonatal respiratory outcomes were compared between the preterm IUGR and appropriately-grown for gestational age (AGA preterm infant populations in eligible studies. Results: No study was identified which evaluated the efficacy or responsiveness of exogenous surfactant replacement therapy in preterm IUGR infants as compared to preterm AGA infants. The only study identified through the search strategy used small for gestational age (SGA; defined as less than 10th centile for birth weight as a proxy for IUGR. The RCT evaluated the efficacy or responsiveness of SRT in preterm SGA group as compared to AGA infants. The rate of intubation, severity of RDS, rate of surfactant administration, pulmonary air leaks and days on the ventilator did not differ between both groups. However, the requirement for prolonged nasal CPAP (p< 0.001, supplemental oxygen therapy (p <0.01 and the incidence of bronchopulmonary dysplasia at 28 days and 36 weeks (both p<0.01 was greater in SGA infants. Discussion: There is currently insufficient data available to evaluate the efficacy of SRT in preterm IUGR lung disease. A variety of research strategies will be needed to enhance our understanding of the role and rationale for use of surfactant replacement therapy in preterm

  19. The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry

    NARCIS (Netherlands)

    Pippias, Maria; Jager, Kitty J.; Kramer, Anneke; Leivestad, Torbjørn; Sánchez, Manuel Benítez; Caskey, Fergus J.; Collart, Frederic; Couchoud, Cécile; Dekker, Friedo W.; Finne, Patrik; Fouque, Denis; Heaf, James G.; Hemmelder, Marc H.; Kramar, Reinhard; de Meester, Johan; Noordzij, Marlies; Palsson, Runolfur; Pascual, Julio; Zurriaga, Oscar; Wanner, Christoph; Stel, Vianda S.

    2016-01-01

    This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe. Eighteen national or regional renal registries providing data to the European Renal Association-European

  20. Characteristics and survival of young adults who started renal replacement therapy during childhood

    NARCIS (Netherlands)

    Kramer, Anneke; Stel, Vianda S.; Tizard, Jane; Verrina, Enrico; Rönnholm, Kai; Pálsson, Runólfur; Maxwell, Heather; Jager, Kitty J.

    2009-01-01

    BACKGROUND: Little is known about the group of children on renal replacement therapy (RRT) who reach the age of 18 years and are transferred from paediatric to adult nephrology services. The aim of this study was to describe patient demographics, primary renal diseases, treatment history and

  1. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy

    DEFF Research Database (Denmark)

    Sørensen, M B; Rosenfalck, A M; Højgaard, L

    2001-01-01

    OBJECTIVE: Menopause is linked to an increase in fat mass and a decrease in lean mass exceeding age-related changes, possibly related to reduced output of ovarian steroids. In this study we examined the effect of combined postmenopausal hormone replacement therapy (HRT) on the total and regional ......, which in turn, prevents disease in the elderly....

  2. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition : A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Celine; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Kobold, Anneke C. Muller; Bandsma, Robert H.; van Hensbroek, Michael Boele; Voskuijl, Wieger P.

    Objective: To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design: We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth

  3. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Muller Kobold, Anneke C.; Bandsma, Robert H.; Boele van Hensbroek, Michael; Voskuijl, Wieger P.

    2017-01-01

    Objective To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central

  4. Stabilized incidence of diabetic patients referred for renal replacement therapy in Denmark

    DEFF Research Database (Denmark)

    Sørensen, V R; Hansen, P M; Heaf, J

    2006-01-01

    Despite an improvement in diabetes care during the last 20 years, the number of diabetic patients starting renal replacement therapy (RRT) has continued to increase in the Western world. The aim was to study the incidence of patients starting RRT in Denmark from 1990 to 2004. Data were obtained f...

  5. Hormone replacement therapy: short-term versus long-term use.

    Science.gov (United States)

    Rousseau, Mary Ellen

    2002-01-01

    Midwives manage health care of women throughout the life cycle including prescribing hormone replacement therapy (HRT). This article presents a history of research on the use of HRT, as well as risks and benefits. Older research on the effects of HRT on heart disease, osteoporosis, and breast cancer is included. The results and recommendations of the Women's Health Initiative are examined.

  6. Early stage cognitive impairment in Parkinson’s disease and the influence of dopamine replacement therapy

    NARCIS (Netherlands)

    Miah, I.P.; Olde Dubbelink, K.T.E.; Stoffers, D.; Deijen, J.B.; Berendse, H.W.

    2012-01-01

    Background and purpose: The aim of this study was to establish the cognitive profile of newly diagnosed untreated (de novo) patients with Parkinson's disease (PD) and more advanced, treated patients, and to determine the effects of dopamine (DA) replacement therapy. Methods: A cohort of 23 de novo

  7. Effect of long-term Hormone Replacement Therapy on Plasma Homocysteine in Postmenopausal Women

    DEFF Research Database (Denmark)

    Madsen, Jonna S; Kristensen, Søren R; Klitgaard, Niels A

    2002-01-01

    hormone replacement therapy had significantly lower total homocysteine concentrations than women in the control group; median total homocysteine values were 8.6 micromol/L and 9.7 micromol/L, respectively, in a per-protocol analysis (P =.02). The effect was comparable in all methylenetetrahydrofolate...

  8. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

    NARCIS (Netherlands)

    Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

    2004-01-01

    Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized,

  9. Hearing loss in adult patients with Fabry disease treated with enzyme replacement therapy

    NARCIS (Netherlands)

    Suntjens, Eefje B.; Smid, Bouwien E.; Biegstraaten, Marieke; Dreschler, Wouter A.; Hollak, Carla E. M.; Linthorst, Gabor E.

    2015-01-01

    Data on prevalence, natural history, and effect of enzyme replacement therapy (ERT) on hearing loss (HL) in Fabry disease (FD) are scarce. This is a retrospective study with cross-sectional and longitudinal analyses. Low and high-frequency HL in the Dutch FD cohort was studied in four groups:

  10. Children with Pompe disease: clinical characteristics, peculiar features and effects of enzyme replacement therapy

    NARCIS (Netherlands)

    C.I. van Capelle (Carine)

    2014-01-01

    markdownabstract__Abstract__ Pompe disease is a metabolic myopathy. Since the first description of the disease in 1932 by J.C. Pompe,1 tremendous progress has been made from discovering the biochemical and genetic basis of the disease to developing enzyme replacement therapy (ERT). With this

  11. Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain

    NARCIS (Netherlands)

    Rombach, Saskia M.; Smid, Bouwien E.; Bouwman, Machtelt G.; Linthorst, Gabor E.; Dijkgraaf, Marcel G. W.; Hollak, Carla E. M.

    2013-01-01

    Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase A deficiency leading to renal, cardiac, cerebrovascular disease and premature death. Treatment with α-galactosidase A (enzyme replacement therapy, ERT) stabilises disease in some patients, but long term effectiveness

  12. Acute renal insufficiency and renal replacement therapy after pediatric cardiopulmonary bypass surgery

    NARCIS (Netherlands)

    Kist-van Holthe tot Echten, J. E.; Goedvolk, C. A.; Doornaar, M. B.; van der Vorst, M. M.; Bosman-Vermeeren, J. M.; Brand, R.; van der Heijden, A. J.; Schoof, P. H.; Hazekamp, M. G.

    2001-01-01

    The aim of the study was to investigate renal function and renal replacement therapy after cardiopulmonary bypass surgery in children. Patient characteristics (sex, age, diagnosis), operation type, and death were listed. The study was performed retrospectively using serum creatinine level before,

  13. The epidemic of aging in renal replacement therapy: an update on elderly patients and their outcomes

    NARCIS (Netherlands)

    Jager, K. J.; van Dijk, P. C. W.; Dekker, F. W.; Stengel, B.; Simpson, K.; Briggs, J. D.

    2003-01-01

    Background: In the past 2 decades, a rapid growth has occurred in the number of patients over 65 years of age accepted for renal replacement therapy (RRT) with an increasing need for dialysis resources as a consequence. The aim of this study is to describe the trends in incidence, treatment and

  14. Renal replacement therapy registries--time for a structured data quality evaluation programme

    NARCIS (Netherlands)

    Couchoud, Cécile; Lassalle, Mathilde; Cornet, Ronald; Jager, Kitty J.

    2013-01-01

    Registries in the area of renal replacement therapy (RRT) are intended to be a tool for epidemiological research, health care planning and improvement of quality of care. In this perspective, the value of a population-based RRT registry and its ability to achieve its goals rely heavily on the

  15. Should we start and continue growth hormone (GH) replacement therapy in adults with GH deficiency?

    NARCIS (Netherlands)

    ter Maaten, JC

    2000-01-01

    During the last decade, growth hormone deficiency (GHD) in adults has been described as a clinical syndrome. Central features of this entity include increased fat mass, reduced muscle and bone mass, as well as impaired exercise capacity and quality of life. GH replacement therapy has been initiated

  16. A new machine for continuous renal replacement therapy: from development to clinical testing.

    Science.gov (United States)

    Ricci, Zaccaria; Salvatori, Gabriella; Bonello, Monica; Ratanarat, Ranistha; Andrikos, Emilios; Dan, Maurizio; Piccinni, Pasquale; Ronco, Claudio

    2005-01-01

    A new continuous renal replacement therapy machine has been designed to fulfill the expectations of nephrologists and intensivists operating in the common ground of critical care nephrology. The new equipment is called Prismaflex and it is the natural evolution of the PRISMA machine that has been utilized worldwide for continuous renal replacement therapy in the last 10 years. The authors performed a preliminary alpha-trial to establish the usability, flexibility and reliability of the new device. Accuracy was also tested by recording various operational parameters during different intermittent and continuous renal replacement modalities during 62 treatments. This article will describe our first experience with this new device and touch upon the historic and technologic background leading to its development.

  17. Prepubertal Gynecomastia Due to Indirect Exposure to Nonformulary Bioidentical Hormonal Replacement Therapy: A Case Report.

    Science.gov (United States)

    De Pinho, Joao Correia; Aghajanova, Lusine; Herndon, Christopher N

    2016-01-01

    Gynecomastia is a disorder of the endocrine system characterized by an abnormal presence of a palpable unilateral or bilateral enlargement and proliferation of glandular ductal benign breast tissue in male individuals. This case discusses the medical implications of an unregulated, indirect exposure to nonformulary, bioidentical hormone replacement therapy in male children. An 8-year-old boy presented with prepubertal gynecomastia secondary to estrogen exposure from maternal use of bioidentical hormonal replacement therapy (the Wiley protocol). We review the literature on prepubertal gynecomastia secondary to exogenous estrogen exposure, evaluation, clinical surveillance of the pubertal development, and relevant short- and long-term implications. Indirect exposure to nonformulary hormonal replacement in our case report was an etiologic factor in the development of prepubertal gynecomastia. This novel estrogen exposure source has important implications in the differential diagnosis of prepubertal gynecomastia and potential adverse effects secondary to precocious hormonal exposure.

  18. A randomized trial of three single - dose radiation therapy regimens in the treatment of metastatic bone pain

    International Nuclear Information System (INIS)

    Jeremic, Branislav; Shibamoto, Yuta; Acimovic, Ljubisa; Milicic, Biljana; Milisavljevic, Slobodan; Nikolic, Nebojsa; Aleksandrovic, Jasna; Igrutinovic, Ivan

    1998-01-01

    Purpose: To investigate efficacy of three single dose radiation therapy (RT) regimens in the treatment of painful bone metastasis. Material and Methods: Patient self-assessment by using pain chart enabled evaluation of response to treatment that consisted of either one of the three single fractions of 4 Gy (group I; n = 109), 6 Gy (group II; n = 108), or 8 Gy (group III; n = 110). Results: Patients in groups II and III had higher complete response rate than those in group I, but not significantly, and with no difference between group II and III. However, both patients in group II (73%) and group III (78%) had significantly higher overall response rates when compared to those observed in group I (59%) (I vs II, p = 0.025; I vs III, p = 0.0019), and with no difference between groups II and III (p 0.39). Patients in group III had shortest time to the occurrence of any pain relief which was significantly better than those observed in group I (Welch's t-test, p = 0.012), with no difference between group I and II and group II and III, respectively. There was no difference between the three treatment groups in duration of response and retreatment rate. No effect of histology or metastatic site treated was found. No pathological fractures or spinal cord compressions were observed during the 8 weeks post-RT. Conclusion: Results of this study seem to confirm that 8 Gy could be considered as probably 'lowest' optimal single fraction RT in the treatment of painful bone metastasis, although single fraction RT of 4 Gy should not be easily discarded due to its applicability in specific cases. Since single fraction RT of 6 Gy achieved results not different from that obtained with 8 Gy, further studies are warranted in order to get more informations about 'lowest' optimal single fraction RT in the treatment of painful bone metastasis

  19. Overweight, insulin resistance and type II diabetes in type I Gaucher disease patients in relation to enzyme replacement therapy

    NARCIS (Netherlands)

    Langeveld, M.; de Fost, M.; Aerts, J. M. F. G.; Sauerwein, H. P.; Hollak, C. E. M.

    2008-01-01

    Type I Gaucher disease, a lysosomal storage disorder is associated with metabolic abnormalities such as high resting energy expenditure, low circulating adiponectin and peripheral insulin resistance. Treatment with enzyme replacement therapy (enzyme therapy) leads to a decrease in resting energy

  20. Understanding cost of care for patients on renal replacement therapy: looking beyond fixed tariffs.

    Science.gov (United States)

    Li, Bernadette; Cairns, John A; Fotheringham, James; Tomson, Charles R; Forsythe, John L; Watson, Christopher; Metcalfe, Wendy; Fogarty, Damian G; Draper, Heather; Oniscu, Gabriel C; Dudley, Christopher; Johnson, Rachel J; Roderick, Paul; Leydon, Geraldine; Bradley, J Andrew; Ravanan, Rommel

    2015-10-01

    In a number of countries, reimbursement to hospitals providing renal dialysis services is set according to a fixed tariff. While the cost of maintenance dialysis and transplant surgery are amenable to a system of fixed tariffs, patients with established renal failure commonly present with comorbid conditions that can lead to variations in the need for hospitalization beyond the provision of renal replacement therapy. Patient-level cost data for incident renal replacement therapy patients in England were obtained as a result of linkage of the Hospital Episodes Statistics dataset to UK Renal Registry data. Regression models were developed to explore variations in hospital costs in relation to treatment modality, number of years on treatment and factors such as age and comorbidities. The final models were then used to predict annual costs for patients with different sets of characteristics. Excluding the cost of renal replacement therapy itself, inpatient costs generally decreased with number of years on treatment for haemodialysis and transplant patients, whereas costs for patients receiving peritoneal dialysis remained constant. Diabetes was associated with higher mean annual costs for all patients irrespective of treatment modality and hospital setting. Age did not have a consistent effect on costs. Combining predicted hospital costs with the fixed costs of renal replacement therapy showed that the total cost differential for a patient continuing on dialysis rather than receiving a transplant is considerable following the first year of renal replacement therapy, thus reinforcing the longer-term economic advantage of transplantation over dialysis for the health service. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  1. Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome.

    Science.gov (United States)

    Gawlik, Aneta; Hankus, Magdalena; Such, Kamila; Drosdzol-Cop, Agnieszka; Madej, Paweł; Borkowska, Marzena; Zachurzok, Agnieszka; Malecka-Tendera, Ewa

    2016-12-01

    Turner syndrome is the most common example of hypergonadotropic hypogonadism resulting from gonadal dysgenesis. Most patients present delayed, or even absent, puberty. Premature ovarian failure can be expected even if spontaneous menarche occurs. Laboratory markers of gonadal dysgenesis are well known. The choice of optimal hormone replacement therapy in children and adolescents remains controversial, particularly regarding the age at which therapy should be initiated, and the dose and route of estrogen administration. On the basis of a review of the literature, we present the most acceptable schedule of sex steroid replacement therapy in younger patients with Turner syndrome. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  2. Four-year evolution of insulin regimens, glycaemic control, hypoglycaemia and body weight after starting insulin therapy in type 2 diabetes across three continents.

    Science.gov (United States)

    Home, Philip D; Dain, Marie-Paule; Freemantle, Nick; Kawamori, Ryuzo; Pfohl, Martin; Brette, Sandrine; Pilorget, Valérie; Scherbaum, Werner A; Vespasiani, Giacomo; Vincent, Maya; Balkau, Beverley

    2015-05-01

    It is of interest to understand how insulin therapy currently evolves in clinical practice, in the years after starting insulin in people with type 2 diabetes. We aimed to describe this evolution prospectively over 4 years, to assist health care planning. People who had started any insulin were identified from 12 countries on three continents. Baseline, then yearly follow-up, data were extracted from clinical records over 4 years. Of the 2999 eligible people, 2272 were followed over 4 years. When starting insulin, mean (SD) duration of diabetes was 10.6 (7.8) years, HbA1c 9.5 (2.0)% (80 [22]mmol/mol) and BMI 29.3 (6.3)kg/m(2). Initial insulin therapy was basal 52%, premix 23%, mealtime+basal 14%, mealtime 8% and other 3%; at 4 years, 30%, 25%, 33%, 2% and 5%, respectively, with 5% not on insulin. Insulin dose was 20.2U/day at the start and 45.8U/day at year 4. There were 1258 people (55%) on their original regimen at 4 years, and this percentage differed according to baseline insulin regimen. HbA1c change was -2.0 (2.2)% (-22 [24]mmol/mol) and was similar by final insulin regimen. Hypoglycaemia prevalence was <20% in years 1-4. Body weight change was mostly in year 1, and was very variable, mean +2.7 (7.5)kg at year 4. Different insulin regimens were started in people with differing characteristics, and they evolved differently; insulin dose, hypoglycaemia and body weight change were diverse and largely independent of regimen. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal anti-vascular endothelial growth factor therapy of macular diseases.

    Science.gov (United States)

    Lanzetta, Paolo; Loewenstein, Anat

    2017-07-01

    Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is now considered the gold standard for the treatment of various retinal disorders. As therapy has evolved, so too have the treatment regimens employed by physicians in clinical practice; however, visual outcomes observed in the real world have typically not reflected those reported in clinical trials. Possible reasons for this include a lack of consensus on treatment regimens and a lack of clarity about what the aims of treatment should be. The Vision Academy Steering Committee met to discuss the principles of an ideal treatment regimen, using evidence from the literature to substantiate each point. Literature searches were performed using the MEDLINE/PubMed database (cut-off date: March 2016) and restricted to English-language publications. Studies with fewer than ten patients were excluded from this review. The Steering Committee identified the following four key principles for the ideal treatment regimen for anti-VEGF management of retinal diseases: 1. Maximize and maintain visual acuity (VA) benefits for all patients 2. Decide when to treat next, rather than whether to treat now 3. Titrate the treatment intervals to match patients' needs 4. Treat at each monitoring visit. It is proposed that the adoption of a proactive and more personalized approach in the clinic such as a treat-and-extend regimen will lead to benefits for both the patient and the physician, through a reduction in the associated treatment burden and better utilization of clinic resources. Implementation of the four principles should also lead to better VA outcomes for each patient, with a minimized risk of vision loss.

  4. Association between mortality and replacement solution bicarbonate concentration in continuous renal replacement therapy: A propensity-matched cohort study.

    Directory of Open Access Journals (Sweden)

    Kianoush Kashani

    Full Text Available Given the known deleterious effects seen with bicarbonate supplementation for acidemia, we hypothesized that utilizing high bicarbonate concentration replacement solution in continuous venovenous hemofiltration (CVVH would be independently associated with higher mortality.In a propensity score-matched historical cohort study conducted at a single tertiary care center from December 9, 2006, through December 31, 2009, a total of 287consecutive adult critically ill patients with Stage III acute kidney injury (AKI requiring CVVH were enrolled. We excluded patients on maintenance dialysis, those who received other modalities of continuous renal replacement therapies, and patients that received a mixed of 22 and 32 mEq/L bicarbonate solution pre- and post-filter. The primary outcome was in-hospital and 90-day mortality rates.Among enrollees, 68 were used 32 mEq/L bicarbonate solution, and 219 received 22mEq/L bicarbonate solution for CVVH. Patients on 32 mEq/L bicarbonate solution were more often non-surgical, had lower pH and bicarbonate level but had higher blood potassium and phosphorus levels in comparison with those on 22 mEq/L bicarbonate solution. After adjustment for the baseline characteristics, the use of 32 bicarbonate solution was significantly associated with increased in-hospital (HR = 1.94; 95% CI 1.02-3.79 and 90-day mortality (HR = 1.50; 95% CI 1.03-2.14. There was a significant increase in the hospital (p = .03 and 90-day (p = .04 mortality between the 22 vs. 32 mEq/L bicarbonate solution groups following propensity matching.Our data showed there is a strong association between using high bicarbonate solution and mortality independent of severity of illness and comorbid conditions. These findings need to be evaluated further in prospective studies.

  5. Treatment of Medial Tibial Stress Syndrome With Radial Soundwave Therapy in Elite Athletes: Current Evidence, Report on Two Cases, and Proposed Treatment Regimen.

    Science.gov (United States)

    Saxena, Amol; Fullem, Brian; Gerdesmeyer, Ludger

    Two case reports of high-level athletes with medial tibial stress syndrome (MTSS), 1 an Olympian with an actual stress fracture, are presented. Successful treatment included radial soundwave therapy, pneumatic leg braces, relative rest using an antigravity treadmill, and temporary foot orthoses. Radial soundwave therapy has a high level of evidence for treatment of MTSS. We also present recent evidence of the value of vitamin D assessment. Both patients had a successful outcome with minimal downtime. Finally, a suggested treatment regimen for MTSS is presented. Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Does hormone replacement therapy and use of oral contraceptives increase the risk of non-melanoma skin cancer?

    DEFF Research Database (Denmark)

    Birch-Johansen, Fatima; Jensen, Allan; Olesen, Anne Braae

    2012-01-01

    We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women.......We aimed to examine whether use of hormone replacement therapy (HRT) and oral contraceptives (OC) affect the risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in women....

  7. The effect of hormone replacement therapy on serum homocysteine levels in perimenopausal women : a randomized controlled trial

    NARCIS (Netherlands)

    Hak, AE; Bak, AAA; Lindemans, J; Planellas, J; Bennink, HJTC; Hofman, A; Grobbee, DE; Witteman, JCM

    2001-01-01

    Serum homocysteine levels may be lowered by hormone replacement therapy, but randomized controlled trial data are scarce. We performed a single center randomized placebo-controlled trial to assess the 6 months effect of hormone replacement therapy compared with placebo on fasting serum homocysteine

  8. EFFECT OF ADDING AN EXERCISE REGIMEN TO DIET THERAPY IN DECREASING BODY FAT PERCENTAGE AND BODY MASS INDEX AMONG OBESE FEMALES

    Directory of Open Access Journals (Sweden)

    Rajeena Haneefa

    2017-10-01

    Full Text Available BACKGROUND Obesity is one among the leading health problems in many developing countries including India. Lifestyle modifications, which include diet therapy and regular exercises are considered as the mainstay in the management of this health issue. Brisk walking is the preferred socially and economically acceptable mode of exercise. This randomised controlled trial tries to evaluate the efficacy of adding an exercise regimen to diet therapy in reducing body fat percentage and Body Mass Index (BMI among obese females. MATERIALS AND METHODS One hundred female patients aged between 20 and 60 years with BMI greater than 25 were recruited for this study of 6 months duration. Participants were randomised into either diet therapy alone group or diet therapy with exercise group. All participants were prescribed a low-calorie diet of 1500 kcal per day. The exercise intervention group was subjected to a home-based exercise regimen; walking for 30 minutes 5 days a week. Outcomes were measured by BMI and body fat percentage, documented every month. RESULTS Both groups showed significant reduction in body fat percentage and BMI, but the reduction was more in the exercise with diet therapy group (p value <0.001. CONCLUSION Adding a simple exercise like walking to other lifestyle modification measures can more efficiently bring down BMI and body fat percentage in turn significantly reducing the cardiovascular risk, morbidity and mortality in women.

  9. Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens.

    Science.gov (United States)

    Landsburg, Daniel J; Stadtmauer, Edward; Loren, Alison; Goldstein, Steven; Frey, Noelle; Nasta, Sunita D; Porter, David L; Tsai, Donald E; Perl, Alexander E; Hexner, Elizabeth O; Luger, Selina

    2013-08-01

    While the prognosis for older adults diagnosed with acute lymphoblastic leukemia (ALL) is frequently poor, long-term survival can be achieved in patients treated with curative intent. We reviewed the outcomes of 37 patients age ≥60 treated at our institution with either DVP- or hyperCVAD-based chemotherapy regimens from 2003-2011. In this patient population, a complete response rate of 92%, relapse rate of 56% and median overall survival of 18.1 months was experienced. Univariate analysis revealed that receipt of maintenance therapy vs. no maintenance therapy was associated with a statistically-significant impact on overall survival (p = 0.001, HR 0.15 for death), while disease-related characteristics including high-risk white blood cell count at diagnosis and Philadelphia chromosome status as well as treatment-related factors including chemotherapy regimen or completion of intensive therapy were not. Many patients were unable to initiate or remain on maintenance therapy due to toxicities including infections and cytopenias. Our analysis reveals the benefit of prolonged therapy in the treatment of older adults with ALL as well as the high incidence of treatment-related toxicity experienced by these patients. Copyright © 2013 Wiley Periodicals, Inc.

  10. Calculating evidence-based renal replacement therapy – Introducing an excel-based calculator to improve prescribing and delivery in renal replacement therapy – A before and after study

    OpenAIRE

    Cottle, Daniel; Mousdale, Stephen; Waqar-Uddin, Haroon; Tully, Redmond; Taylor, Benjamin

    2015-01-01

    Background Transferring the theoretical aspect of continuous renal replacement therapy to the bedside and delivering a given “dose” can be difficult. In research, the “dose” of renal replacement therapy is given as effluent flow rate in ml kg−1 h−1. Unfortunately, most machines require other information when they are initiating therapy, including blood flow rate, pre-blood pump flow rate, dialysate flow rate, etc. This can lead to confusion, resulting in patients receiving inappropriate doses...

  11. [Analysis of costs and cost-effectiveness of preferred GESIDA/National AIDS Plan regimens for initial antiretroviral therapy in human immunodeficiency virus infected adult patients in 2013].

    Science.gov (United States)

    Blasco, Antonio Javier; Llibre, Josep M; Arribas, José Ramón; Boix, Vicente; Clotet, Bonaventura; Domingo, Pere; González-García, Juan; Knobel, Hernando; López, Juan Carlos; Lozano, Fernando; Miró, José M; Podzamczer, Daniel; Santamaría, Juan Miguel; Tuset, Montserrat; Zamora, Laura; Lázaro, Pablo; Gatell, Josep M

    2013-11-01

    The GESIDA and National AIDS Plan panel of experts have proposed "preferred regimens" of antiretroviral treatment (ART) as initial therapy in HIV infected patients for 2013. The objective of this study is to evaluate the costs and effectiveness of initiating treatment with these "preferred regimens". An economic assessment of costs and effectiveness (cost/effectiveness) was performed using decision tree analysis models. Effectiveness was defined as the probability of having viral load <50copies/mL at week48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and its consequences (adverse effects, changes of ART regime and drug resistance analyses) during the first 48weeks. The perspective of the analysis is that of the National Health System was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, resistance studies, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was performed, constructing three scenarios for each regimen: baseline, most favourable, and most unfavourable cases. In the baseline case scenario, the cost of initiating treatment ranges from 6,747euros for TDF/FTC+NVP to 12,059euros for TDF/FTC+RAL. The effectiveness ranges between 0.66 for ABC/3TC+LPV/r and ABC/3TC+ATV/r, and 0.87 for TDF/FTC+RAL and ABC/3TC+RAL. Effectiveness, in terms of cost/effectiveness, varies between 8,396euros and 13,930euros per responder at 48weeks, for TDF/FTC/RPV and TDF/FTC+RAL, respectively. Taking ART at official prices, the most effective regimen was TDF/FTC/RPV, followed by the rest of non-nucleoside containing regimens. The sensitivity analysis confirms the robustness of these findings. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  12. Mitochondrial Replacement Therapy: Halachic Considerations for Enrolling in an Experimental Clinical Trial

    Science.gov (United States)

    Tendler, Rabbi Moshe D.; Loike, John D.

    2015-01-01

    The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal. PMID:26241230

  13. Mitochondrial Replacement Therapy: Halachic Considerations for Enrolling in an Experimental Clinical Trial

    Directory of Open Access Journals (Sweden)

    Rabbi Moshe D. Tendler

    2015-07-01

    Full Text Available The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal.

  14. Better prevention than cure: optimal patient preparation for renal replacement therapy.

    Science.gov (United States)

    Huang, Xiaoyan; Carrero, Juan Jesús

    2014-03-01

    A generous proportion of end-stage renal disease patients may not be adequately prepared for initiation of renal replacement therapy (RRT). Here we review potential benefits of early patient referral to nephrologists and optimal preparation for RRT. We place this evidence in the context of the epidemiological study by Kurella Tamura et al., which shows that voluntary community kidney disease screening and education is associated with better patient preparation and, importantly, improved survival upon initiation of RRT.

  15. Knowledge and Perceptions Regarding Nicotine Replacement Therapy among Dental Students in Karnataka

    OpenAIRE

    Ajagannanavar, Sunil Lingaraj; Alshahrani, Obaid Abdullah; Jhugroo, Chitra; Tashery, Hamed Mohammed; Mathews, Jacob; Chavan, Khechari

    2015-01-01

    Background: Organized dentistry has recognized the role of oral health professionals in discouraging tobacco use. Unexplored level of knowledge regarding the benefits and prescription of nicotine replacement therapy (NRT) have aroused interest among us which initiated us to assess the knowledge and perception of dental students toward NRT among various dental colleges in Karnataka, South India. Materials and Methods: A questionnaire survey was done among 16 selected colleges in Karnataka. It ...

  16. Use of nonsteroidal anti-inflammatory drugs prior to chronic renal replacement therapy initiation

    DEFF Research Database (Denmark)

    Kristensen, Søren Lund; Fosbøl, Emil L; Kamper, Anne-Lise

    2012-01-01

    PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with severe renal complications, including acute renal failure, reduced glomerular filtration rate and interstitial nephritis. Caution against NSAIDs is therefore recommended in advanced chronic kidney disease. In this study......, we examined NSAID use, aetiology and comorbidity among a national cohort of patients before the initiation of chronic renal replacement therapy (RRT). METHODS: Patients initiated on chronic RRT in the period 1997-2006 were identified in the Danish National Registry on Regular Dialysis...

  17. Incidence of virological failure and major regimen change of initial combination antiretroviral therapy in the Latin America and the Caribbean: an observational cohort study

    Science.gov (United States)

    Cesar, Carina; Jenkins, Cathy A.; Shepherd, Bryan E.; Padgett, Denis; Mejía, Fernando; Ribeiro, Sayonara Rocha; Cortes, Claudia P.; Pape, Jean W.; Madero, Juan Sierra; Fink, Valeria; Sued, Omar; McGowan, Catherine; Cahn, Pedro

    2015-01-01

    Background Access to combination antiretroviral therapy (cART) is expanding in Latin America and the Caribbean (LAC). There is little information in this region regarding incidence of and factors associated with regimen failure and regimen change. Methods Antiretroviral-naïve adults starting cART from 2000-2014 at sites in seven countries throughout LAC were included. Cumulative incidence of virologic failure and major regimen change were estimated with death considered a competing event. Findings 14,027 cART initiators (60% male, median age 37 years, median CD4 156 cells/mm3, median HIV-RNA 5·0 log10 copies/mL, and 28% with clinical AIDS) were followed for a median of 3·9 years. 1,719 patients presented virologic failure and 1,955 had a major regimen change. Excluding GHESKIO-Haiti (which did not regularly measure HIV-RNA), cumulative incidence of virologic failure was 7·8%, 19·2%, and 25·8% at one, three, and five years after cART initiation, respectively; cumulative incidence of major regimen change was 5·9%, 12·7%, and 18·2%. Incidence of major regimen change at GHESKIO-Haiti at five years was 10·7%. Virologic failure was associated with younger age (adjusted hazard ratio[aHR]=2·03 for 20 vs. 40 years; 95% confidence interval[CI] 1·68-2·44), infection through injection-drug use (IDU) (aHR=1·60; 95%CI 1·02-2·52), initiation in earlier calendar years (aHR=1·28 for 2002 vs. 2006; 95%CI 1·13-1·46), and starting with a boosted protease inhibitor (aHR=1·17 vs. non-nucleoside reverse transcriptase inhibitor; 95%CI 1·00-1·64). Interpretation Incidence of virologic failure was generally lower than in North America/Europe. Our results suggest the need to design strategies to reduce failure and major regimen change among younger patients and those with a history of IDU. Funding US National Institutes of Health: U01 AI069923. PMID:26520929

  18. Low-dose hydrocortisone (HC) replacement therapy is associated with improved bone remodeling balance in hypopituitary subjects

    LENUS (Irish Health Repository)

    Behan, L A

    2011-06-01

    The effect of commonly used glucocorticoid replacement regimens on bone health in hypopituitary subjects is not well known. We aimed to assess the effect of 3 hydrocortisone (HC) replacement dose regimens on bone turnover in this group.10 hypopituitary men with severe ACTH deficiency were randomised in a crossover design to 3 HC dose regimens, Dose A (20mg mane, 10mg tarde), Dose B (10mg twice daily) and Dose C (10mg mane, 5mg tarde). Following 6 weeks of each regimen participants underwent fasting sampling of bone turnover markers.Data from matched controls were used to produce a Z score for subject bone formation and resorption markers and to calculate the bone remodeling balance (formation Z score-resorption Z score) and turnover index ((formation Z + resorption Z)\\/2). A positive bone remodeling balance with increased turnover is consistent with a favourable bone cycle. Data are expressed as median (range).The Pro Collagen Type 1 Peptide (PINP) bone formation Z-score was significantly increased in Dose C, (1.805 (-0.6-10.24)) compared to Dose A (0.035 (-1.0-8.1)) p<0.05 while there was no difference in the C-terminal crosslinking telopeptide (CTx) resorption Z score. The bone remodeling balance was significantly lower for dose A -0.02 (-1.05-4.12) compared to dose C 1.13 (0.13-6.4) (p<0.05). Although there was a trend to an increased bone turnover index with the lower dose regimen, this was not statistically significant.Low dose HC replacement (10mg mane\\/5 mg tarde) was associated with increased bone formation and improved bone remodeling balance which is associated with a more favourable bone cycle. This may have a long term beneficial effect on bone health.

  19. Irinotecan plus folinic acid/continuous 5-fluorouracil as simplified bimonthly FOLFIRI regimen for first-line therapy of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Höhler Thomas

    2004-07-01

    Full Text Available Abstract Background Combination therapy of irinotecan, folinic acid (FA and 5-fluorouracil (5-FU has been proven to be highly effective for the treatment of metastatic colorectal cancer. However, in light of safety and efficacy concerns, the best combination regimen for first-line therapy still needs to be defined. The current study reports on the bimonthly FOLFIRI protocol consisting of irinotecan with continuous FA/5-FU in five German outpatient clinics, with emphasis on the safety and efficiency, quality of life, management of delayed diarrhea, and secondary resection of regressive liver metastases. Methods A total of 35 patients were treated for metastatic colorectal cancer. All patients received first-line treatment according to the FOLFIRI regimen, consisting of irinotecan (180 mg/m2, L-FA (200 mg/m2 and 5-FU bolus (400 mg/m2 on day 1, followed by a 46-h continuous infusion 5-FU (2400 mg/m2. One cycle contained three fortnightly administrations. Staging was performed after 2 cycles. Dosage was reduced at any time if toxicity NCI CTC grade III/IV was observed. Chemotherapy was administered only to diarrhea-free patients. Results The FOLFIRI regimen was generally well tolerated. It was postponed for one-week in 51 of 415 applications (12.3%. Dose reduction was necessary in ten patients. Grade III/IV toxicity was rare, with diarrhea (14%, nausea/vomiting (12%, leucopenia (3%, neutropenia (9% and mucositis (3%. The overall response rate was 31% (4 CR and 7 PR, with disease control in 74%. After primary chemotherapy, resection of liver metastases was achieved in three patients. In one patient, the CR was confirmed pathologically. Median progression-free and overall survival were seven and 17 months, respectively. Conclusions The FOLFIRI regimen proved to be safe and efficient. Outpatient treatment was well tolerated. Since downstaging was possible, combinations of irinotecan and continuous FA/5-FU should further be investigated in neoadjuvant

  20. CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations.

    Science.gov (United States)

    Fogleman, Sarah; Santana, Casey; Bishop, Casey; Miller, Alyssa; Capco, David G

    2016-01-01

    Thousands of mothers are at risk of transmitting mitochondrial diseases to their offspring each year, with the most severe form of these diseases being fatal [1]. With no cure, transmission prevention is the only current hope for decreasing the disease incidence. Current methods of prevention rely on low mutant maternal mitochondrial DNA levels, while those with levels close to or above threshold (>60%) are still at a very high risk of transmission [2]. Two novel approaches may offer hope for preventing and treating mitochondrial disease: mitochondrial replacement therapy, and CRISPR/Cas9. Mitochondrial replacement therapy has emerged as a promising tool that has the potential to prevent transmission in patients with higher mutant mitochondrial loads. This method is the subject of many ethical concerns due its use of a donor embryo to transplant the patient's nuclear DNA; however, it has ultimately been approved for use in the United Kingdom and was recently declared ethically permissible by the FDA. The leading-edge CRISPR/Cas9 technology exploits the principles of bacterial immune function to target and remove specific sequences of mutated DNA. This may have potential in treating individuals with disease caused by mutant mitochondrial DNA. As the technology progresses, it is important that the ethical considerations herein emerge and become more established. The purpose of this review is to discuss current research surrounding the procedure and efficacy of the techniques, compare the ethical concerns of each approach, and look into the future of mitochondrial gene replacement therapy.

  1. Change in the use of hormone replacement therapy and the incidence of fracture in Oslo.

    Science.gov (United States)

    Meyer, H E; Lofthus, C M; Søgaard, A J; Falch, J A

    2009-05-01

    Fracture incidence in Oslo decreased from the 1970s to the 1990s in younger postmenopausal women, but not in older women or in men. Concurrently, hormone replacement therapy increased considerably. Using data from the Oslo Health Study, we estimated that roughly half the decline might be attributed hormone replacement therapy. Between the late 1970s and the late 1990s, the incidence of hip fracture and distal forearm fracture decreased in younger postmenopausal women in Oslo, but not in elderly women or in men. The purpose of this report is to evaluate whether the decreased incidence was coherent with trends in use of hormone replacement therapy (HRT). Data on estrogens were collected from official drug statistics, data on fractures from published studies and data on bone mineral density (BMD) from the Oslo Health Study. The sale of all estrogens increased 22 times from 1979 to 1999, and the sub-category estradiol combined with progestin increased 35 times. In the corresponding period the incidence of distal forearm fracture in women aged 50-64 years decreased by 33% and hip fracture by 39%. Based on differences in BMD between users and non-users of HRT, we estimated that up to half of this decline might be due to HRT. The reduction in fracture incidence in postmenopausal women in Oslo occurred in a period with a substantial increase in the use of HRT. Future surveillance will reveal whether the last years' decline in use of HRT will be translated into increasing fracture rates.

  2. Characteristics of Australian smokers using bupropion and nicotine-replacement therapies.

    Science.gov (United States)

    Doran, Christopher; Stafford, Jennifer; Shanahan, Marian; Mattick, Richard P

    2007-02-01

    Smokers were surveyed using a computer-assisted telephone interview to explore behaviors associated with the use of bupropion and nicotine-replacement therapies, using a convenient sample of Australian smokers. With assistance from the Pharmacy Guild of Australia, smokers were recruited through pharmacies and interviewed at baseline and after 3 months. A total of 508 smokers were recruited, 396 were interviewed at baseline and 318 completed a 3-month computer-assisted telephone interview. At 3 months, over two-thirds of participants were still smoking, the majority daily. However, the number of cigarettes smoked per week reduced and the time taken before smoking the first cigarette after waking increased. Nearly all participants started their medication (94%), while only 39% completed the full course. The main reasons for not completing the full course were adverse side effects, such as abnormal dreams and sleep disturbance. Despite Australian guidelines for bupropion and nicotine-replacement therapies to be used within a comprehensive treatment program, only 11% of patients were recommended behavioral support for nicotine dependence by their doctor or pharmacist. The results of the study shed light on patient utilization of the medication in terms of uptake and completion, possible side effects experienced and use of adjuncts. A better understanding of the use and experience of bupropion and nicotine-replacement therapies, and the lack of behavioral support offered with these, provides policy makers with a stronger evidence base to refine and improve the use of such pharmacotherapies.

  3. High phenobarbital clearance during continuous renal replacement therapy: a case report and pharmacokinetic analysis.

    Science.gov (United States)

    Rosenborg, Staffan; Saraste, Lars; Wide, Katarina

    2014-08-01

    Phenobarbital is an old antiepileptic drug used in severe epilepsy. Despite this, little is written about the need for dose adjustments in renal replacement therapy. Most sources recommend a moderately increased dose guided by therapeutic drug monitoring.A 14 year old boy with nonketotic hyperglycinemia, a rare inborn error of metabolism, characterized by high levels of glycine, epilepsy, spasticity, and cognitive impairment, was admitted to the emergency department with respiratory failure after a few days of fever and cough. The boy was unconscious at admittance and had acute renal and hepatic failure.Due to the acute respiratory infection, hypoxic hepatic and renal failure occurred and the patient had a status epilepticus.The patient was intubated and mechanically ventilated. Continuous renal replacement therapy was initiated. Despite increased phenobarbital doses, therapeutic levels were not reached until the dose was increased to 500 mg twice daily. Therapeutic drug monitoring was performed in plasma and dialysate. Calculations revealed that phenobarbital was almost freely dialyzed.Correct dosing of drugs in patients on renal replacement therapy may need a multidisciplinary approach and guidance by therapeutic drug monitoring.

  4. Third-line rescue therapy with bismuth-containing quadruple regimen after failure of two treatments (with clarithromycin and levofloxacin) for H. pylori infection.

    Science.gov (United States)

    Gisbert, J P; Perez-Aisa, A; Rodrigo, L; Molina-Infante, J; Modolell, I; Bermejo, F; Castro-Fernández, M; Antón, R; Sacristán, B; Cosme, A; Barrio, J; Harb, Y; Gonzalez-Barcenas, M; Fernandez-Bermejo, M; Algaba, A; Marín, A C; McNicholl, A G

    2014-02-01

    Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. Prospective multicenter study of patients in whom 1st treatment with PPI-clarithromycin-amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by (13)C-urea-breath-test 4-8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58-72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies.

  5. Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease

    DEFF Research Database (Denmark)

    Fox, Ira J; Daley, George Q; Goldman, Steven A

    2014-01-01

    Pluripotent stem cells (PSCs) directed to various cell fates holds promise as source material for treating numerous disorders. The availability of precisely differentiated PSC-derived cells will dramatically affect blood component and hematopoietic stem cell therapies and should facilitate......, and industry is critical for generating new stem cell-based therapies....... treatment of diabetes, some forms of liver disease and neurologic disorders, retinal diseases, and possibly heart disease. Although an unlimited supply of specific cell types is needed, other barriers must be overcome. This review of the state of cell therapies highlights important challenges. Successful...

  6. A proof-of-concept study of short-cycle intermittent antiretroviral therapy with a once-daily regimen of didanosine, lamivudine, and efavirenz for the treatment of chronic HIV infection

    NARCIS (Netherlands)

    Dybul, M; Nies-Kraske, E; Dewar, R; Maldarelli, F; Hallahan, CW; Daucher, M; Piscitelli, SC; Ehler, L; Weigand, A; Palmer, S; Metcalf, JA; Davey, RT; Kress, DMR; Powers, A; Beck, [No Value; Frenkel, L; Baseler, M; Coffin, J; Fauci, AS

    2004-01-01

    Background. We previously demonstrated that short-cycle structured intermittent therapy ( SIT; 7 days without therapy followed by 7 days with antiretroviral therapy [ART]) with a ritonavir-boosted, indinavir-based, twice-daily regimen maintained suppression of plasma HIV viremia while reducing serum

  7. Development of a men's Preference for Testosterone Replacement Therapy (P-TRT instrument

    Directory of Open Access Journals (Sweden)

    Szeinbach SL

    2012-08-01

    Full Text Available Sheryl L Szeinbach,1 Enrique Seoane-Vazquez,2 Kent H Summers31Ohio State University, College of Pharmacy, Columbus, OH, USA; 2International Center for Pharmaceutical Economics and Policy, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, 3Endo Health Solutions, Chadds Ford, PA, USABackground: This study used a standard research approach to create a final conceptual model and the Preference for the Testosterone Replacement Therapy (P-TRT instrument.Methods: A discussion guide was developed from a literature review and expert opinion to direct one-on-one interviews with participants who used testosterone replacement therapy and consented to participate in the study. Data from telephone interviews were transcribed for theme analysis using NVivo 9 qualitative analysis software, analyzed descriptively from a saturation grid, and used to evaluate men's P-TRT. Data from cognitive debriefing for five participants were used to evaluate the final conceptual model and validate the initial P-TRT instrument.Results: Item saturation and theme exhaustion was achieved by 58 male participants of mean age 55.0 ± 10.0 (22–69 years who had used testosterone replacement therapy for a mean of 175.0 ± 299.2 days. The conceptual model was developed from items and themes obtained from the participant interviews and saturation grid. Items comprising eight dimensions were used for instrument development, ie, ease of use, effect on libido, product characteristics, physiological impact, psychological impact, side effects, treatment experience, and preference. Results from the testosterone replacement therapy preference evaluation provide a detailed insight into why most men preferred a topical gel product over an injection or patch.Conclusion: Items and themes relating to use of testosterone replacement therapy were in concordance with the final conceptual model and 29-item P-TRT instrument. The standard research approach used in this study produced the

  8. Trends in Testosterone Replacement Therapy Use from 2003 to 2013 among Reproductive-Age Men in the United States.

    Science.gov (United States)

    Rao, Pravin Kumar; Boulet, Sheree L; Mehta, Akanksha; Hotaling, James; Eisenberg, Michael L; Honig, Stanton C; Warner, Lee; Kissin, Dmitry M; Nangia, Ajay K; Ross, Lawrence S

    2017-04-01

    Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men. This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy. Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

    Science.gov (United States)

    Darcy, Justin; Fang, Yimin; Hill, Cristal M; McFadden, Sam; Sun, Liou Y; Bartke, Andrzej

    2016-10-01

    Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice. © 2016 by the Society for Experimental Biology and Medicine.

  10. An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.

    Science.gov (United States)

    Whitaker, Martin; Debono, Miguel; Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J

    2014-04-01

    It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure. © 2013 John Wiley & Sons Ltd.

  11. An oral multi-particulate, modified release, hydrocortisone replacement therapy that provides physiological cortisol exposure

    Science.gov (United States)

    Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J.

    2013-01-01

    Objective It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multi-particulate technology. Design and Measurements Screening by in-vitro dissolution profiles, pharmacokinetic testing in dexamethasone suppressed dogs and humans, and comparison to a reference population. Setting Field laboratories and clinical research facility. Results Formulations were generated using an enteric (delayed-release) design configuration with an extended (sustained-release) dissolution profile. In-vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained release functionality. Pharmacokinetic characterisation of DIURF-006 showed that, despite absence of a sustained release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n=16) receiving a twice daily ‘toothbrush’ regimen (20mg at 23:00h and 10mg at 07:00h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 hr*nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8.5h vs clock time 08:12 hours for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89% and cortisol levels increased linearly with doses between 5 and 30mg. Conclusion A multi-particulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a ‘toothbrush’ regimen provides physiological cortisol exposure. PMID:23980724

  12. Does early use of enzyme replacement therapy alter the natural history of mucopolysaccharidosis I? Experience in three siblings.

    Science.gov (United States)

    Laraway, Sarah; Breen, Catherine; Mercer, Jean; Jones, Simon; Wraith, James E

    2013-07-01

    Enzyme replacement therapy is widely used as treatment for mucopolysaccharidosis I (MPS I), and there is evidence that this produces improvement in certain clinical domains. There does appear to be variation in the response of clinical features to treatment once these are established. In a reported sibling pair, when enzyme replacement therapy was commenced pre-symptomatically in the younger child, the natural history of the condition appeared to be affected. We present data from three siblings treated with enzyme replacement therapy at different ages which supports this finding. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Choice of first-line antiretroviral therapy regimen and treatment outcomes for HIV in a middle income compared to a high income country: a cohort study.

    Science.gov (United States)

    Dragovic, Gordana; Smith, Colette J; Jevtovic, Djordje; Dimitrijevic, Bozana; Kusic, Jovana; Youle, Mike; Johnson, Margaret A

    2016-03-03

    The range of combination antiretroviral therapy (cART) regimens available in many middle-income countries differs from those suggested in international HIV treatment guidelines. We compared first-line cART regimens, timing of initiation and treatment outcomes in a middle income setting (HIV Centre, Belgrade, Serbia - HCB) with a high-income country (Royal Free London Hospital, UK - RFH). All antiretroviral-naïve HIV-positive individuals from HCB and RFH starting cART between 2003 and 2012 were included. 12-month viral load and CD4 count responses were compared, considering the first available measurement 12-24 months post-cART. The percentage that had made an antiretroviral switch for any reason, or for toxicity and the percentage that had died by 36 months (the latest time at which sufficient numbers remained under follow-up) were investigated using standard survival methods. 361/597 (61 %) of individuals initiating cART at HCB had a prior AIDS diagnosis, compared to 337/1763 (19 %) at RFH. Median pre-ART CD4 counts were 177 and 238 cells/mm(3) respectively (p HIV disease, resulting in higher mortality rates than in high income countries, supporting improved testing campaigns for early detection of HIV infection and early introduction of newer cART regimens.

  14. RESULTS OF LONG-TERM THERAPY WITH GROWTH-HORMONE IN 2 DOSE REGIMENS IN TURNER SYNDROME

    NARCIS (Netherlands)

    NIENHUIS, HE; RONGENWESTERLAKEN, C; WIT, JM; OTTEN, BJ; KEIZERSCHRAMA, SMPFD; DRAYER, NM; DELEMARREVANDEWAAL, HA; VULSMA, T; OOSTDIJK, W; WAELKENS, JJJ

    1993-01-01

    Girls with Turner syndrome were divided according to age (group A 6-12 years, and group B 12-19 years) and human growth hormone (GH) dose regimen (A1 and B1, three injections/week; A2 and B2, six injections/week). All groups responded to GH, 24 IU/M2/week, with an increase in height velocity, though

  15. Hair cortisol content in patients with adrenal insufficiency on hydrocortisone replacement therapy.

    Science.gov (United States)

    Gow, Rachel; Koren, Gideon; Rieder, Michael; Van Uum, Stan

    2011-06-01

    Patients with adrenal insufficiency (AI) require life-long replacement therapy with exogenous glucocorticoids. Several studies have shown impaired subjective health status in these patients as well as increased morbidity and mortality risk, which may be caused by glucocorticoid over-replacement. As a measure of long-term cortisol exposure, the usefulness of hair cortisol analysis in patients receiving glucocorticoid replacement therapy was investigated. Hair samples, demographics, medical history and perceived stress scale questionnaires were collected from 93 patients across North America diagnosed with primary or secondary AI. Sixty-two household partners served as a control group. Cortisol was measured in the proximal 2 cm of hair, representing the most recent 2 months of exposure. A modified enzyme immunoassay was used for the measurement of cortisol. The male patients had significantly higher hair cortisol levels than the male controls (P cortisol content correlated significantly with glucocorticoid dose (r = 0·3, P cortisol content correlates with hydrocortisone (HC) dose in patients with AI. Our results suggest that some AI patients may be over-treated and hence may be at risk for the adverse effects of cortisol. Measurement of HC in hair may become a useful monitoring tool for long-term cortisol exposure in patients treated with glucocorticoids. © 2011 Blackwell Publishing Ltd.

  16. Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome.

    Science.gov (United States)

    Nakamura, Tomomi; Tsuburai, Taku; Tokinaga, Aya; Nakajima, Izumi; Kitayama, Reiko; Imai, Yuichi; Nagata, Tomoko; Yoshida, Hiroshi; Hirahara, Fumiki; Sakakibara, Hideya

    2015-01-01

    Estrogen replacement therapy (ERT) is necessary for uterine development and bone mass acquisition in women with Turner syndrome (TS) suffering from ovarian insufficiency. However, adequate ERT regimens have not yet been established. The aim of this study was to evaluate the efficacy of ERT for both uterine development and bone mass acquisition. One hundred TS patients from Yokohama City University Hospital (88 with primary amenorrhea (PA) and 12 patients with spontaneous menstrual cycles (MC)) were enrolled after obtaining consent. Clinical profiles, uterine length (UL) measured by ultrasonic examination, and bone mineral density (BMD) of the lumbar vertebrae (L2-4) assessed by DEXA were evaluated. At the time of the first visit, the ULs of patients in the PA group were significantly shorter than those in the MC group. After receiving ERT, there were no significant differences in UL between patients with PA and MC. Forty-seven patients for whom the ERT initiation age was known were investigated to clarify the influence on BMD. The results showed that the BMD in the late initiation (18 years or older) group at the latest visit (0.770 ± 0.107 g/cm2: n = 16) was significantly lower than that in the early initiation (under 18 years) group (0.858 ± 0.119 g/cm2: n = 21) or the MC group (0.941 ± 0.118 g/cm2: n = 10). No significant differences were seen between the early initiation and MC group. ERT was effective in increasing UL and BMD. However, early initiation of ERT is necessary to increase BMD.

  17. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

    NARCIS (Netherlands)

    van Dussen, Laura; Biegstraaten, Marieke; Dijkgraaf, Marcel Gw; Hollak, Carla Em

    2014-01-01

    Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on

  18. [Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism].

    Science.gov (United States)

    Péter, Ferenc; Muzsnai, Agota

    2013-05-12

    L-thyroxine replacement therapy is the treatment of choice for hypothyroidism. Recently, several studies suggested to complete it with l-triiodothyronine in acquired hypothyroidism. To study the role of combined l-thyroxine and l-triiodothyronine therapy in special cases with congenital hypothyroidism. Data of 16 patients (age: 11.9 ± 6.3 years; mean ± SD) are presented who had high serum free thyroxine values or even above the upper limit of reference range (21.16 ± 2.5 pmol/l) together with nonsuppressed TSH levels (15.7 ± 5.7 mIU/l), and therefore received l-triiodothyronine in completion (0.18 ± 0.09 μg/kg) once a day. The combined replacement therapy resulted in a rapid improvement of the hormone parameters (TSH: 4.2 ± 3.15 mIU/l; free thyroxine: 16.55 ± 2.4 and free triiodothyronine: 7.4 ± 1.8 pmol/l). The efficiency of this combined therapy proved to be more evident (TSH: 4.33 ± 3.2 mIU/l; free thyroxine: 16.85 ± 3.1 and free triiodothyronine: 6.4 ± 0.85 pmol/l) in 10 patients treated for a longer period of time (duration of treatment: 2.9 ± 2.0 years). The dose of thyroxine substitution decreased from 2.6 ± 0.9 to 2.18 ± 0.6 μg/kg/day), the ratio of these hormones was between 5:1 and 19:1 and the quotient of free fractions was normalized (3.8 ± 0.4→2.6 ± 0.3) during the replacement therapy. According to the observation of the authors a serious disturbance of feed-back mechanism may develop in some (>5%) children with congenital hypothyroidism (increased TSH release despite elevated free thyroxine level) after normal function of the feed-back system for years. Hormone parameters of these patients improve, then become normal on combined therapy supporting the rationale for this treatment method.

  19. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    OpenAIRE

    Xue, Peng; Wang, Yan; Yang, Jie; Li, Yukun

    2013-01-01

    Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochr...

  20. [Effect of continuous renal replacement therapy on the plasma concentration of imipenem in severe infection patients with acute renal injury].

    Science.gov (United States)

    Yu, Bin; Liu, Lixia; Xing, Dong; Zhao, Congcong; Hu, Zhenjie

    2015-05-01

    To investigate the extracorporeal clearance rate of imipenem in severe infection patients in the mode of continuous vena-venous hemofiltration (CVVH) during continuous renal replacement therapy (CRRT), in order to approach if the concentration of imipenem in plasma could achieve effective levels of anti-infection, and to explore the effect of time and anticoagulation measure on imipenem clearance during CRRT treatment. A prospective observational study was conducted. All adult severe infection patients complicating acute kidney injury (AKI) in the Department of Critical Care Medicine of the Fourth Hospital of Hebei Medical University from March 2013 to September 2014, who were prescribed imipenem as part of their required medical care, and CRRT for treatment of AKI were enrolled. 0.5 g doses of imipenem was administered intravenously every 6 hours or 8 hours according to random number table, and infused over 0.5 hour. The unfractionated heparin was used for anticoagulation in the patients without contraindications, and no anticoagulation strategy was used in the patients with high risk of bleeding. At 24 hours after first time of administration, postfilter venous blood and ultrafiltrate samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 5, 6, and 8 hours after imipenem administration. The concentration of imipenem in above samples was determined with liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS). A total of 25 patients were enrolled. Thirteen patients received imipenem intravenously every 6 hours, and 12 patients, every 8 hours. The anticoagulation was conducted with heparin in 13 cases, and 12 cases without anticoagulation. The intra-day precision, inter-day precision, matrix effect, and recovery rate in low, medium, and high concentration of plasma and ultrafiltrate, and the stability of samples under different conditions showed a good result, the error of accuracy was controlled in the range of ±15%. With the application of Prismaflex

  1. Fabry disease: the importance of the enzyme replacement therapy (TRE, treating quickly and efficiently

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2014-06-01

    Full Text Available Fabry Disease is a lysosomal disorder due to the absence or deficiency of the Alpha galactosidase A enzyme that causes a pathological accumulation of glycosphingolipids mainly in the endothelial cells, vascular smooth muscle cells and podocytes among others. Enzyme replacement therapy is the only option for a specific treatment at present. Increasing knowledge of the physiopathological mechanisms has changed the management of the disease and above all, when treatment should begin. At present, beginning treatment at an early age seems to be a way of preventing and in some cases reverting some of the signs and symptoms of Fabry disease.

  2. Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review

    Science.gov (United States)

    2014-01-01

    Rhabdomyolysis, a clinical syndrome caused by damage to skeletal muscle and release of its breakdown products into the circulation, can be followed by acute kidney injury (AKI) as a severe complication. The belief that the AKI is triggered by myoglobin as the toxin responsible appears to be oversimplified. Better knowledge of the pathophysiology of rhabdomyolysis and following AKI could widen treatment options, leading to preservation of the kidney: the decision to initiate renal replacement therapy in clinical practice should not be made on the basis of the myoglobin or creatine phosphokinase serum concentrations. PMID:25043142

  3. Description of women's personality traits and psychological vulnerability prior to choosing hormone replacement therapy

    DEFF Research Database (Denmark)

    Loekkegaard, E; Eplov, L F; Køster, A

    2002-01-01

    INTRODUCTION: Data suggest that women using hormone replacement therapy (HRT) represent a special subgroup of the general population regarding, for instance, cardiovascular risk factors and education. OBJECTIVE: To analyse if women who choose HRT are characterised a priori by high neuroticism sco...... confounders. The study suggests that selection bias among women choosing HRT may also include personality traits....... included Eysencks personality questionnaire concerning intro/extroversion and neuroticism. At the age of 45, the re-examination of the women included a test for psychological vulnerability. The participants reported whether or not they used HRT at the age of 40, 45, 51 and 60 years. The analyses comprised...

  4. Effect of renal replacement therapy on retinol-binding protein 4 isoforms

    DEFF Research Database (Denmark)

    Frey, Simone K; Henze, Andrea; Nagl, Britta

    2009-01-01

    Retinol-binding protein 4 (RBP4) levels are elevated in the serum of patients with kidney dysfunction. We recently showed that RBP4 isoforms including apo-RBP4 (RBP4 not bound to retinol) and RBP4 truncated at the C-terminus (RBP4-L, RBP4-LL) are increased in the serum of patients with kidney dis...... diseases but not in serum of patients with various liver diseases. The aim of this study was to investigate the effect of renal replacement therapy on RBP4 isoforms....

  5. Resolution of Hydronephrosis in a Patient With Mucopolysaccharidosis Type II With Enzyme Replacement Therapy.

    Science.gov (United States)

    Nishiyama, Kei; Imai, Takashi; Ohkubo, Kazuhiro; Sanefuji, Masafumi; Takada, Hidetoshi

    2017-03-01

    Mucopolysaccharidosis type II (MPS II) is caused by deficiency of lysosomal enzyme iduronate-2-sulfatase. Insufficient activity of the enzyme results in accumulation of glycosaminoglycans leading to progressive multisystem pathologies. MPS II is less likely to be complicated by kidney and urinary tract problems. We report a boy with MPS II, who developed left hydronephrosis. His hydronephrosis improved after starting enzyme replacement therapy. It was suggested that MPS II was closely associated with the pathogenesis of hydronephrosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients

    International Nuclear Information System (INIS)

    Penoncello, Gregory P.; Ding, George X.

    2016-01-01

    The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, and 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2 cm"3 for head and neck plans and brain plans and a contiguous volume of 5 cm"3 for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens.

  7. Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients.

    Science.gov (United States)

    Penoncello, Gregory P; Ding, George X

    2016-01-01

    The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, and 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2cm(3) for head and neck plans and brain plans and a contiguous volume of 5cm(3) for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens. Copyright © 2016 American Association of Medical Dosimetrists. Published by

  8. Mammographic changes in postmenopausal women : comparative effects between continuous combined hormone and single estrogen replacement therapy

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sug; Choi, Jong Tae; Jung, Kyoon Soon; Jung, Seung Hye [Jeil Women' s Hospital, Seoul (Korea, Republic of)

    1997-06-01

    As the use of hormone replacement therapy for the menopausal women increases, some caution is advised, since there is an increased risk of breast cancer. Accordingly, the importance of regular mammography has been addressed. This cross-setional study analyzed the effects of different hormone therapies on mammographic density. Sixty-seven postemenopausal women who had completed one year of hormone therapy and had undergone follow-up mammography, were divided into two groups : Group I : continuous conjugated equine estrogen, 0.625mg, plus continuous medroxyprogesterone acetate, 2.5mg (n=48), Group II : continuous conjugated equine estrogen 0.625mg (n=19). The mammograms were read by two radiologists. With regard to the radiologists involved, interobserver reliabillity (kappa) was 0.70 and intraobserver reliability (kappa) was 0.51 and 0.67. Before hormone therapy, factors related to decreased mammographic density were age and number of full term pregnancies (p<0.05). After one year of hormone therapy, body fat showed a significant increase (p<0.05), but in spite of this, increased mammographic density induced by hormone therapy remained significantly high (p<0.05). Compared with Group II, Group I showed a significant increase in mammographic density (p<0.05). In Group I, mammographic density increased from P2 to DY pattern in two cases, but there was no such change in Group II. The increase of mammographic density seen in Group II was much more significant statistically than that seen in Group I. The mammograms of women who have undergone continuous combined hormone therapy should therefore be interpreted very cautiously.

  9. Mammographic changes in postmenopausal women : comparative effects between continuous combined hormone and single estrogen replacement therapy

    International Nuclear Information System (INIS)

    Oh, Sug; Choi, Jong Tae; Jung, Kyoon Soon; Jung, Seung Hye

    1997-01-01

    As the use of hormone replacement therapy for the menopausal women increases, some caution is advised, since there is an increased risk of breast cancer. Accordingly, the importance of regular mammography has been addressed. This cross-setional study analyzed the effects of different hormone therapies on mammographic density. Sixty-seven postemenopausal women who had completed one year of hormone therapy and had undergone follow-up mammography, were divided into two groups : Group I : continuous conjugated equine estrogen, 0.625mg, plus continuous medroxyprogesterone acetate, 2.5mg (n=48), Group II : continuous conjugated equine estrogen 0.625mg (n=19). The mammograms were read by two radiologists. With regard to the radiologists involved, interobserver reliabillity (kappa) was 0.70 and intraobserver reliability (kappa) was 0.51 and 0.67. Before hormone therapy, factors related to decreased mammographic density were age and number of full term pregnancies (p<0.05). After one year of hormone therapy, body fat showed a significant increase (p<0.05), but in spite of this, increased mammographic density induced by hormone therapy remained significantly high (p<0.05). Compared with Group II, Group I showed a significant increase in mammographic density (p<0.05). In Group I, mammographic density increased from P2 to DY pattern in two cases, but there was no such change in Group II. The increase of mammographic density seen in Group II was much more significant statistically than that seen in Group I. The mammograms of women who have undergone continuous combined hormone therapy should therefore be interpreted very cautiously

  10. Replacing SUs with incretin-based therapies for type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Knop, Filip K; Holst, Jens Juul; Vilsbøll, Tina

    2008-01-01

    Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by insulin resistance, a steady decline in glucose-induced insulin secretion (most likely caused by a progressive decrease in functional beta-cell mass), and inappropriately regulated glucagon secretion; in combination...... are glucose-dependent, reducing the risk of hypoglycemia. GLP-1 inhibits glucagon secretion and decreases gastrointestinal motility, in turn reducing food intake and body weight. This feature review focuses on the challenges and feasibilities of replacing SU with incretin-based therapy in patients with T2DM....... - glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). More importantly, incretin-based therapies potentiate glucose-stimulated insulin secretion and may restore reduced glucose-induced insulin secretion in T2DM. Furthermore, the insulinotropic effects of GLP-1 and GIP...

  11. Suicidal intoxication with potassium chlorate successfully treated with renal replacement therapy and extracorporeal liver support.

    Science.gov (United States)

    Sein Anand, Jacek; Barwina, Małgorzata; Zajac, Maciej; Kaletha, Krystian

    2012-01-01

    We present a case of a 22-year-old male who, in a suicide attempt, ingested approximately 200 g of potassium chlorate. Upon admission to the hospital, he presented in full respiratory failure with cyanosis. Methylene blue antidote was given but found to be ineffective. The patient was intubated and mechanical ventilation was initiated. Because of renal failure with anuria, intermittent haemodialysis (iHD) followed by continuous venovenous hemodiafiltration (CVVHDF) was performed. His hospital stay was also complicated by hemolysis, disseminated intravascular coagulation, and atrial fibrillation. Transfusions of packed red blood cells, platelets, and fresh frozen plasma were necessary to correct the deficits. He also developed liver failure and required two sessions of molecular adsorbent recirculating system (MARS) therapy. On day 14 of his hospitalization, he regained consciousness, as well as full respiratory and circulatory function. There are no controlled studies addressing management of potassium chlorate poisoning. We suggest that early renal replacement therapy should be strongly considered.

  12. The future of replacement and restorative therapies: from organ transplantation to regenerative medicine.

    Science.gov (United States)

    Daar, A S

    2013-01-01

    As we continue to have severe shortages of organs for transplantation, we need to consider alternatives for the future. The most likely to make a real difference in the long term is regenerative medicine (RM), a field that has emerged from the conjunction of stem cell biology and cell therapies; gene therapy; biomaterials and tissue engineering; and organ transplantation. Transplantation and RM share the same essential goal: to replace or restore organ function. Herein I briefly review some major breakthroughs of RM that are relevant to the future of organ transplantation, with a focus on the needs of people in the developing world. A definition of RM is provided and the ethical, legal, and social issues are briefly highlighted. In conclusion, I provide a projection of what the future may be for RM. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. High cut-off membranes in acute kidney injury and continuous renal replacement therapy.

    Science.gov (United States)

    Ricci, Zaccaria; Romagnoli, Stefano; Ronco, Claudio

    2017-11-24

    Innovation in continuous renal replacement therapies (CRRT) utilized to treat acute kidney injury (AKI) and sepsis, has brought new machines and techniques. Part of these new advances are due to the availability of innovative biomaterials and the construction of membranes with larger pores and wide distribution of pore sizes. This includes the creation of a new generation of high cut-off membranes whose utilization in clinical practice is promising for the wide spectrum of solutes that are removed during extracorporeal therapies.However, the enlargement of pore diameters brings some loss of albumin during treatment and this effect is still under evaluation, since there is a possibility that this is detrimental for the patient. A thorough review of the available clinical literature is reported in this paper with a reappraisal of the potential application of these new technologies.

  14. Percutaneous 17ß-estradiol replacement therapy in hypertensive postmenopausal women

    Directory of Open Access Journals (Sweden)

    M.C. Osório-Wender

    1997-09-01

    Full Text Available The present study evaluated the short-term effects of percutaneous 17ß-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17ß-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administration. Systolic and diastolic blood pressure or heart rate did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued. Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 ± 27.21 to 35.09 ± 20.44 IU/l, P<0.05, and an increase in estradiol levels (15.06 ± 8.76 to 78.7 ± 44.6 pg/ml, P<0.05. There was no effect on LH (18.0 ± 9.5 to 14.05 ± 8.28 IU/l. Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17ß-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women

  15. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Directory of Open Access Journals (Sweden)

    Marco Antonio Botelho

    2014-02-01

    Full Text Available OBJECTIVE: To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10% combined with estriol (0.1% + estradiol (0.25% for relieving postmenopausal symptoms. METHODS: A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. RESULTS: An improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05 after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. CONCLUSION: The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women.

  16. Clinical review: Optimal dose of continuous renal replacement therapy in acute kidney injury.

    Science.gov (United States)

    Prowle, John R; Schneider, Antoine; Bellomo, Rinaldo

    2011-01-01

    Continuous renal replacement therapy (CRRT) is the preferred treatment for acute kidney injury in intensive care units (ICUs) throughout much of the world. Despite the widespread use of CRRT, controversy and center-specific practice variation in the clinical application of CRRT continue. In particular, whereas two single-center studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with acute kidney injury in the ICU, other studies have been inconsistent in their results. Now, however, two large multi-center randomized controlled trials - the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study - have provided level 1 evidence that effluent flow rates above 25 mL/kg per hour do not improve outcomes in patients in the ICU. In this review, we discuss the concept of dose of CRRT, its relationship with clinical outcomes, and what target optimal dose of CRRT should be pursued in light of the high-quality evidence now available.

  17. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    International Nuclear Information System (INIS)

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan; Almeida, Jackson Guedes; Quintans Junior, Lucindo

    2014-01-01

    Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

  18. Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Botelho, Marco Antonio; Queiroz, Dinalva Brito; Barros, Gisele; Guerreiro, Stela; Umbelino, Sonia; Lyra, Arao; Borges, Boniek; Freitas, Allan, E-mail: marcobotelho@pq.cnpq.br [Universidade Potiguar, Natal, RN (Brazil). Lab. de Nanotecnologia; Fechine, Pierre [Universidade Federal do Ceara (GQMAT/UFCE), Fortaleza, CE (Brazil). Dept. de Quimica Analitica. Grupo Avancado de Biomateriais em Quimica; Queiroz, Danilo Caldas de [Instituto Federal de Ciencia e Tecnologia (IFCT), Fortaleza, CE (Brazil). Lab. de Biotecnologia; Ruela, Ronaldo [Instituto de Biotecnologia Aplicada (INBIOS), Fortaleza, CE (Brazil); Almeida, Jackson Guedes [Universidade Federal do Vale de Sao Francisco (UNIVALE), Petrolina, PE (Brazil). Fac. de Ciencias Farmaceuticas; Quintans Junior, Lucindo [Universidade Federal de Sergipe (UFSE), Sao Cristovao, SE (Brazil). Dept. de Fisiologia

    2014-06-01

    Objective:to determine the safety and efficacy of a transdermal nanostructured formulation of progesterone (10%) combined with estriol (0.1%) + estradiol (0.25%) for relieving postmenopausal symptoms. Methods: a total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern. Confocal Raman spectroscopy of hormones in skin layers was performed. Clinical parameters, serum concentrations of estradiol and follicle-stimulating hormone, blood pressure, BI-RADS classification from bilateral mammography, and symptomatic relief were compared between baseline and 60 months post-treatment. Clinicaltrials.gov: NCT02033512. Results: an improvement in climacteric symptoms was reported in 92.5% of women evaluated before and after 60 months of treatment. The serum concentrations of estradiol and follicle-stimulating hormone changed significantly (p<0.05) after treatment; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04 ± 4.9 to 57.12 ± 4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women. No adverse health-related events were attributed to this hormone replacement therapy protocol. Conclusion: the nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause. This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women. (author)

  19. Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

    DEFF Research Database (Denmark)

    Warming, Lise; Ravn, Pernille; Spielman, Danièle

    2004-01-01

    bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy...

  20. Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting

    Directory of Open Access Journals (Sweden)

    Colombo GL

    2013-12-01

    Full Text Available Giorgio L Colombo,1,2 Antonella Castagna,3 Sergio Di Matteo,2 Laura Galli,3 Giacomo Bruno,2 Andrea Poli,3 Stefania Salpietro,3 Alessia Carbone,3 Adriano Lazzarin3,41Department of Drug Sciences, School of Pharmacy, University of Pavia, Italy; 2Studi Analisi Valutazioni Economiche (S.A.V.E., Milan, 3Infectious Diseases Department, San Raffaele Hospital, Milan, 4Vita-Salute San Raffaele University, Milan, ItalyObjective: In the study reported here, single-tablet regimen (STR versus (vs multi-tablet regimen (MTR strategies were evaluated through a cost analysis in a large cohort of patients starting their first highly active antiretroviral therapy (HAART. Adult human immunodeficiency virus (HIV 1-naïve patients, followed at the San Raffaele Hospital, Milan, Italy, starting their first-line regimen from June 2008 to April 2012 were included in the analysis.Methods: The most frequently used first-line HAART regimens (>10% were grouped into two classes: 1 STR of tenofovir disoproxil fumarate (TDF + emtricitabine (FTC + efavirenz (EFV and 2 MTR including TDF + FTC + EFV, TDF + FTC + atazanavir/ritonavir (ATV/r, TDF + FTC + darunavir/ritonavir (DRV/r, and TDF + FTC + lopinavir/ritoavir (LPV/r. Data were analyzed from the point of view of the Lombardy Regional Health Service. HAART, hospitalizations, visits, medical examinations, and other concomitant non-HAART drug costs were evaluated and price variations included. Descriptive statistics were calculated for baseline demographic, clinical, and laboratory characteristics; associations between categorical variables and type of antiretroviral strategy (STR vs MTR were examined using chi-square or Fisher's exact tests. At multivariate analysis, the generalized linear model was used to identify the predictive factors of the overall costs of the first-line HAART regimens.Results: A total of 474 naïve patients (90% male, mean age 42.2 years, mean baseline HIV-RNA 4.50 log10 copies/mL, and cluster of

  1. Potential efficacy of enzyme replacement and substrate reduction therapy in three siblings with Gaucher disease type III

    NARCIS (Netherlands)

    Cox-Brinkman, J.; van Breemen, M. J.; van Maldegem, B. T.; Bour, L.; Donker, W. E.; Hollak, C. E. M.; Wijburg, F. A.; Aerts, J. M. F. G.

    2008-01-01

    We report three siblings with Gaucher disease type III, born between 1992 and 2004. During this period, new developments resulted in different potential therapies, changing clinical practice. The two eldest siblings received enzyme replacement therapy (ERT) from the age of 24 and 5 months

  2. Pancreatic Enzyme Therapy and Coefficient of Fat Absorption in Children and AdolReplacement escents With Cystic Fibrosis

    NARCIS (Netherlands)

    Woestenenk, Janna W; van der Ent, Cornelis K.; Houwen, Roderick H J; van der Ent, CK

    Objectives: Pancreatic enzyme replacement therapy (PERT) is the proven therapy to substantially reduce fat malabsorption in patients with cystic fibrosis (CF). Few details of the daily practice regarding PERT and the resulting coefficient of fat absorption (CFA) are known. We therefore recorded the

  3. Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in classic-infantile patients with Pompe disease

    NARCIS (Netherlands)

    T.A. Kanters (Tim A.); I Hoogenboom-Plug (Iris); M.P.M.H. Rutten-van Mölken (Maureen); W.K. Redekop (Ken); A.T. van der Ploeg (Ans); L. van Hakkaart-van Roijen (Leona)

    2014-01-01

    textabstractBackground: Infantile Pompe disease is a rare metabolic disease. Patients generally do not survive the first year of life. Enzyme replacement therapy (ERT) has proven to have substantial effects on survival in infantile Pompe disease. However, the costs of therapy are very high. In this

  4. Early identification of risk factors for refractory secondary hyperparathyroidism in patients with long-term renal replacement therapy

    NARCIS (Netherlands)

    Jorna, Francisca Hillegonda; Tobe, TJM; Huisman, RM; de Jong, PE; Plukker, JTM; Stegeman, CA

    Background. Secondary hyperparathyroidism can complicate renal replacement therapy (RRT) in patients with end-stage renal disease. Current medical therapies often result in hypercalcaemia and fail to correct hyperparathyroidism, but might be more effective at an early stage of disease. The aim of

  5. Survival of HIV/AIDS patients with antiretroviral therapy in association with first-line regimens from 2007 – 2010 in Haji AdamMalik general hospital Medan

    Science.gov (United States)

    Kembaren, T.; Ginting, Y.; Saragih, R. H.

    2018-03-01

    The mortality related to AIDS have decreased dramatically among HIV infected patients taking HAART. HAART is the combination of at least 3 antiretroviral drugs based on the recommendation of WHO. The recent guideline for 1st line therapy recommended by the Indonesian Ministry of Health was Zidovudine/Lamivudine/Nevirapine (ZDV+3TC+NVP), Zidovudine/Lamivudine/Efavirenz (ZDV+3TC+EFV), Stavudine/Lamivudine/Nevirapine (d4T+3TC+NVP), Stavudine/Lamivudine/Efavirenz (d4T+3TC+EFV). Due to a side effect of Stavudine, Ministry of Health plan to pass out Stavudin from the regimens for 1stline therapy.We wanted to evaluate the survival of HIV/AIDS patients with first-line regimens in HAM general hospital Medan. A cohort retrospective study was conducted to evaluate the survival of HIV/AIDS patients taking a combination of 1st line antiretroviral therapy between January 2007 and December 2010. From 2007-2010, among 609 HIV/AIDS patients with first-line ARV medication, 77.5% were male, and 22.5% were female. The most common risk infection was heterosexual. The majority of the patients were in 25-34 years old group. Most of the patients with CD4 1-50 cell/mm3. 2 years survival rate in HIV/AIDS patients taking ZDV+3TC+NVP, ZDV+3TC+EFV, d4T+3TC+NVP, d4T+3TC+EFV were 61.5%, 61.2%, 57.5% and 59.3% respectively. There were no significant differences of 24 months survival in both regiment with or without d4T, 61.8% vs 63.6%.

  6. Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Brezinski

    Full Text Available OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SELECTION: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept. DATA SYNTHESIS: A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited. CONCLUSION: Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent

  7. Successful switch from enzyme replacement therapy to miglustat in an adult patient with type 1 Gaucher disease: a case report.

    Science.gov (United States)

    Giuffrida, Gaetano; Lombardo, Rita; Di Francesco, Ernesto; Parrinello, Laura; Di Raimondo, Francesco; Fiumara, Agata

    2016-11-08

    Gaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy. We report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient's spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient's quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no

  8. Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy.

    Science.gov (United States)

    Lai, Silvia; Mecarelli, Oriano; Pulitano, Patrizia; Romanello, Roberto; Davi, Leonardo; Zarabla, Alessia; Mariotti, Amalia; Carta, Maria; Tasso, Giorgia; Poli, Luca; Mitterhofer, Anna Paola; Testorio, Massimo; Frassetti, Nicla; Aceto, Paola; Galani, Alessandro; Lai, Carlo

    2016-11-01

    Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy.Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out.The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P = 0.008, P therapy, and Grade 2-3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P = 0.016) and theta band (P = 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive correlation with eGFR, serum nitrogen, CRP, iPTH, and vitamin D.In CKD patients, simple and noninvasive instruments, as EEG, and cognitive-psychological tests, should be performed and careful and constant monitoring of renal risk factors, probably involved in neuropsychological complications (inflammation, disorders of mineral metabolism, electrolyte disorders, etc.), should be carried out. Early identification and adequate therapy of neuropsychological

  9. GH replacement therapy and second neoplasms in adult survivors of childhood cancer: a retrospective study from a single institution.

    Science.gov (United States)

    Brignardello, E; Felicetti, F; Castiglione, A; Fortunati, N; Matarazzo, P; Biasin, E; Sacerdote, C; Ricardi, U; Fagioli, F; Corrias, A; Arvat, E

    2015-02-01

    Growth hormone deficiency (GHD) is the most common endocrine late effect observed in childhood cancer survivors (CCS) previously submitted to cranial irradiation. Radiation therapy can also increase the risk of second neoplasms (SNs). Since in previous studies GH replacement therapy was associated with increased incidence of neoplasia, we explored the association between SNs and GH replacement therapy in a cohort of CCS with GHD. Within the clinical cohort of CCS referred to the Transition Unit for Childhood Cancer Survivors of Turin between November 2001 and December 2012, we considered all patients who developed GHD as a consequence of cancer therapies. GHD was always diagnosed in childhood. To evaluate the quality of data, our cohort was linked to the Childhood Cancer Registry of Piedmont. GHD was diagnosed in 49 out of 310 CCS included in our clinical cohort. At least one SN was diagnosed in 14 patients, meningioma and basal cell carcinoma being the most common SNs. The cumulative incidence of SNs was similar in GH-treated and -untreated patients (8 SNs out of 26 GH-treated and 6 out of 23 GH-untreated patients; p = 0.331). Age, sex and paediatric cancer type had no impact on SNs development. In our CCS, GH replacement therapy does not seem to increase the risk of SNs. Anyway, independently from replacement therapy, in these patients we observed an elevated risk of SNs, possibly related to previous radiation therapy, which suggests the need of a close long-term follow-up.

  10. MANAGEMENT OF ENDOCRINE DISEASE: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults.

    Science.gov (United States)

    de Carvalho, Gisah Amaral; Paz-Filho, Gilberto; Mesa Junior, Cleo; Graf, Hans

    2018-06-01

    Hypothyroidism is one of the most common hormone deficiencies in adults. Most of the cases, particularly those of overt hypothyroidism, are easily diagnosed and managed, with excellent outcomes if treated adequately. However, minor alterations of thyroid function determine nonspecific manifestations. Primary hypothyroidism due to chronic autoimmune thyroiditis is largely the most common cause of thyroid hormone deficiency. Central hypothyroidism is a rare and heterogeneous disorder characterized by decreased thyroid hormone secretion by an otherwise normal thyroid gland, due to lack of TSH. The standard treatment of primary and central hypothyroidism is hormone replacement therapy with levothyroxine sodium (LT4). Treatment guidelines of hypothyroidism recommend monotherapy with LT4 due to its efficacy, long-term experience, favorable side effect profile, ease of administration, good intestinal absorption, long serum half-life and low cost. Despite being easily treatable with a daily dose of LT4, many patients remain hypothyroid due to malabsorption syndromes, autoimmune gastritis, pancreatic and liver disorders, drug interactions, polymorphisms in DIO2 (iodothyronine deiodinase 2), high fiber diet, and more frequently, non-compliance to LT4 therapy. Compliance to levothyroxine treatment in hypothyroidism is compromised by daily and fasting schedule. Many adult patients remain hypothyroid due to all the above mentioned and many attempts to improve levothyroxine therapy compliance and absorption have been made. © 2018 European Society of Endocrinology.

  11. Data analytics for continuous renal replacement therapy: historical limitations and recent technology advances.

    Science.gov (United States)

    Clark, William R; Garzotto, Francesco; Neri, Mauro; Lorenzin, Anna; Zaccaria, Marta; Ronco, Claudio

    2016-10-10

    Dialysis is a highly quantitative therapy involving large volumes of both clinical and technical data. While automated data collection has been implemented for chronic dialysis, this has not been done for acute kidney injury patients treated with continuous renal replacement therapy (CRRT). After a brief review of the fundamental aspects of electronic medical records (EMRs), a new tool designed to provide clinicians with individualized CRRT treatment data is analyzed, with emphasis on its quality assurance capabilities. The first platform addressing the problem of data collection and management with current CRRT machines (Sharesource system; Baxter Healthcare) is described. The system provides connectivity for the Prismaflex CRRT machine and enables both EMR connectivity and therapy analytics with 2 basic components: the connect module and the report module. The enormous amount of data in CRRT should be collected and analyzed to enable adequate clinical decisions. Current CRRT technology presents significant limitations with consequent lack of rigorous analysis of technical data and relevant feedback. From a quality assurance perspective, these limitations preclude any systematic assessment of prescription and delivery trends that may be adversely affecting clinical outcomes. A detailed assessment of current practice limitations is provided together with several possible ways to address such limitations by a new technical tool.

  12. Promise and deceit: pharmakos, drug replacement therapy, and the perils of experience.

    Science.gov (United States)

    Meyers, Todd

    2014-06-01

    The problem of lying as a feature of medication compliance has been well documented in anthropological and clinical literatures. Yet the role of the lie-its destabilizing effects on the continuity of drug treatment and therapy, as a technology of drug misuse, or as a way to understand the neuro-chemical processes of treatment (pharmacotherapy "tricking" or lying to the brain)-has been less considered, particularly in the context of opioid replacement therapy. The following paper is set against the backdrop of a three-year study of adolescents receiving a relatively new drug (buprenorphine) for the treatment of opiate dependency inside and outside of highly monitored treatment environments in the United States. Lies give order not only to the experience of addiction but also to the experience of therapy as well. In order to better understand this ordering of experience, the paper puts the widely discussed conceptual duality of the pharmakon (healing and poison) in conversation with a perilously overlooked subject in the critical study of pharmacotherapy, namely the pharmakos or the personification of sacrifice. The paper demonstrates how the patient-subject comes to represent therapeutic promise by allowing for the possibility of (and often performing) deceit.

  13. Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Prasanth N. Surampudi

    2012-01-01

    Full Text Available Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men.

  14. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost.

    Science.gov (United States)

    Taylor, Frederick; Levine, Laurence

    2010-01-01

    The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. Men receiving CC or TGRT with either Androgel 1% or Testim 1% for hypogonadism (defined as testosterone treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8-40 months) vs. 46 months (TGRT, range 6-149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT.

  15. Hypogonadism in the Aging Male Diagnosis, Potential Benefits, and Risks of Testosterone Replacement Therapy

    Science.gov (United States)

    Surampudi, Prasanth N.; Wang, Christina; Swerdloff, Ronald

    2012-01-01

    Hypogonadism in older men is a syndrome characterized by low serum testosterone levels and clinical symptoms often seen in hypogonadal men of younger age. These symptoms include decreased libido, erectile dysfunction, decreased vitality, decreased muscle mass, increased adiposity, depressed mood, osteopenia, and osteoporosis. Hypogonadism is a common disorder in aging men with a significant percentage of men over 60 years of age having serum testosterone levels below the lower limits of young male adults. There are a variety of testosterone formulations available for treatment of hypogonadism. Data from many small studies indicate that testosterone therapy offers several potential benefits to older hypogonadal men. A large multicenter NIH supported double blind, placebo controlled study is ongoing, and this study should greatly enhance the information available on efficacy and side effects of treatment. While safety data is available across many age groups, there are still unresolved concerns associated with testosterone therapy. We have reviewed the diagnostic methods as well as benefits and risks of testosterone replacement therapy for hypogonadism in aging men. PMID:22505891

  16. Pharmaceutical intervention in menopausal patients with hormone replacement therapy in a community pharmacy from Antofagasta

    Directory of Open Access Journals (Sweden)

    Alejandrina Alucema

    2015-02-01

    Full Text Available Context: Hormone replacement therapy (HRT is the most widely used treatment for controlling the effects of menopause. This type of therapy causes some drug-related problems (DRP, which requires monitoring to control the negative effects and ensure patient adherence to therapy. Aims: Perform a pharmacotherapeutic monitoring and educate to menopausal patients in HRT of a community pharmacy from the city of Antofagasta. Methods: A 98-menopausal patients underwent a pharmaceutical intervention to identify the PRM and its resolution. It was applied to them a survey before and after educational activities about this disease and HRT to determine the knowledge on the subject. Results: During the pharmacotherapeutic monitoring was determined that 55% of patients using combined HRT. 62 DRPs were detected, of which 43 were resolved (69%; the most were Patient-Pharmacist (73%. The better resolution DRP were DRP 4(b “frequency of inadequate administration” and DRP 2(a “no medical indication”. At baseline, 90% had an inadequate level of knowledge about the disease and THR, 8% intermediate, and only 2% adequate. After the implementation of the education strategy, the level of knowledge increased, achieving at the end of the study only intermediate (10% and adequate (90% levels. Conclusions: The results confirm the importance of pharmaceutical intervention for the identification and resolution of DRP and the requirement to establish educational strategies to increase the knowledge about menopause and HRT in menopausal patients.

  17. Replacement therapy with levothyroxine modulates platelet activation in recent-onset post-thyroidectomy subclinical hypothyroidism.

    Science.gov (United States)

    Desideri, G; Bocale, R; D'Amore, A; Necozione, S; Boscherini, M; Carnassale, G; Barini, A; Barini, A; Bellantone, R; Lombardi, C P

    2017-10-01

    Subclinical hypothyroidism has been linked to increased risk of atherosclerotic disease. Soluble CD40 ligand (sCD40L), mainly derived from activated platelets, and the lipid peroxidation product 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) are known to play a relevant pathophysiological role in atherogenesis. In this study, we analyzed the relationship between thyroid hormones and circulating levels of sCD40L and 8-iso-PGF 2α in patient with recent-onset post-thyroidectomy subclinical hypothyroidism under replacement therapy. Circulating levels of thyroid hormones, sCD40L, and 8-iso-PGF 2α were assessed in 40 recently thyroidectomized patients (33 females, mean age 52.0 ± 11.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with levothyroxine (LT-4). At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 7.7 ± 3.9 μU/mL, FT3 1.8 ± 0.6 pg/mL, and FT3 8.9 ± 3.0 pg/mL). Circulating levels of sCD40L and 8-iso-PGF 2α were directly correlated with each other (r = 0.360, p = 0.023) and with TSH levels (r = 0.322, p = 0.043 and r = 0.329 p = 0.038, respectively). After 2 months under the replacement therapy with LT-4 circulating levels of TSH (from 7.7 ± 3.9 to 2.7 ± 2.8 μU/mL, p hypothyroidism to develop atherosclerotic disease. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  18. Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study

    DEFF Research Database (Denmark)

    Røge, B T; Barfod, T S; Kirk, O

    2004-01-01

    OBJECTIVES: To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. METHODS: We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA...... copies/mL) among 293 patients randomized to two nucleoside reverse transcriptase inhibitors (NRTIs)+ritonavir+saquinavir (RS-arm) (n=115), two NRTIs+nevirapine+nelfinavir (NN-arm) (n=118), or abacavir+stavudine+didanosine (ASD-arm) (n=60) followed up for a median of 90 weeks. Data on adherence were...... collected from patient files, and genotyping was performed on plasma samples collected at time of failure. RESULTS: Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing...

  19. Pros and Cons of Long-Term use of Nicotine Replacement Therapies: A Qualitative Study

    DEFF Research Database (Denmark)

    Borup, Gitte; Kaae, Susanne; Nørgaard, Lotte Stig

    2016-01-01

    , intrapersonal processes, the social environment of smoking vs. NRTs and finances. None of the ex-smokers feared to relapse to smoking, and few were motivated to quit NRTs. Non-nicotinic factors were found to have an important role in developing an addiction to NRTs. The use of NRTs yields some of the expected......, including perceived pros and cons of using NRTs, the risk of relapse to smoking and their motivation to quit using NRTs. The results identified five major themes that entailed pros and cons of the long-term use of NRTs. These were the non-nicotinic factors of NRTs, health risks of NRTs vs. smoking......In the last decade, harm reduction has been increasingly suggested as a method to reduce the harm caused by smoking in smokers who are unable or unwilling to quit all nicotine products. One of these methods includes long-term substitution of tobacco with nicotine replacement therapies (NRTs...

  20. Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy

    DEFF Research Database (Denmark)

    Stahlberg, Claudia; Pedersen, A T; Andersen, Zorana Jovanovic

    2004-01-01

    of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2......The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were...... retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk...

  1. A population approach to renal replacement therapy epidemiology: lessons from the EVEREST study.

    Science.gov (United States)

    Caskey, Fergus J; Jager, Kitty J

    2014-08-01

    The marked variation that exists in renal replacement therapy (RRT) epidemiology between countries and within countries requires careful systematic examination if the root causes are to be understood. While individual patient-level studies are undoubtedly important, there is a complementary role for more population-level, area-based studies--an aetiological approach. The EVEREST Study adopted such an approach, bringing RRT incidence rates, survival and modality mix together with macroeconomic factors, general population factors and renal service organizational factors for up to 46 countries. This review considers the background to EVEREST, its key results and then the main methodological lessons and their potential application to ongoing work. © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  2. Trends in Renal Replacement Therapy in Bosnia and Herzegovina 2002-2008

    Directory of Open Access Journals (Sweden)

    Halima Resić

    2010-04-01

    Full Text Available Renal Registry (RR of Bosnia and Herzegovina was established in 2002, with aim to follow up the trends of Renal Replacement Therapy in Bosnia and Herzegovina. The prevalence of Renal Replacement Therapy (RRT in Bosnia and Herzegovina is rising steadily. One reason for this is an increasing number of patients starting RRT. The aim is to present the epidemiology and treatment of all aspects of RRT in Bosnia and Herzegovina in period 2002-2008. Centre-related and patient-related questionnaires were sent to all 25 dialysis centres in Bosnia and Herzegovina. The demographic data, prevalence and incidence, type of renal replacement therapy, cause of ESRD, erythropoietin administration, cause of death, and type of vascular access were obtained from the questionnaires. Collected data were analysed using SPSS statistics. The number of patients treated by Renal Replacement Therapy (RRT increased steadily from 1,531 patients in 2002 to the 2,206 at the 2008 (43%. The prevalence has increased from 399 pmp in 2002 to 696 pmp. in 2008. Incidence (new patients in 2002 was 110 pmp and incidence rate in 2008 was 163, and there were 249 new patients (day 1. The mean age for new patients increased from 60 years in 2002 to 63.5 years in 2008 and the population over 75 years rate from 8.79% to 11.3%. Most ESRD patients in Bosnia and Herzegovina are undergoing intermittent hemodialysis (92%, while some patients (8% are treated by peritoneal dialysis and transplantation. The most significant cause of ESRD in 2008 was chronic glomerulonephritis (421 patients, 19.2%, followed by pyelonephritis (414 patients, 18.9%, BEN (14.7% and Diabetes mellitus (12.2%. Hepatitis B and C virus infections had 397 (16.3% patients, out of them 22 had both type of infections and 98 patients had B type infection. Only 10.5% of patients were tested on MRSA and 3 patients were positive on MRSA. There were no HIV-positive patients on RRT. The most common type of vascular access was AV fistula

  3. Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors

    DEFF Research Database (Denmark)

    Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian

    2017-01-01

    OBJECTIVE: Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. METHODS: This nationwide case-control study included all women with an SBT...... diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy...... or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p

  4. Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology.

    Science.gov (United States)

    Isidori, A M; Balercia, G; Calogero, A E; Corona, G; Ferlin, A; Francavilla, S; Santi, D; Maggi, M

    2015-01-01

    We developed clinical practice guidelines to assess the individual risk-benefit profile of androgen replacement therapy in adult male hypogonadism (HG), defined by the presence of specific signs and symptoms and serum testosterone (T) below 12 nmol/L. The task force consisted of eight clinicians experienced in treating HG, selected by the Italian Society of Endocrinology (SIE). The authors received no corporate funding or remuneration. Consensus was guided by a systematic review of controlled trials conducted on men with a mean T treatments for individuals at high risk for complications, such as those with osteoporosis and/or metabolic disorders. We recommend against using TS to improve cardiac outcome and limited mobility. We recommend against using TS in men with prostate cancer, unstable cardiovascular conditions or elevated haematocrit. The task force places a high value on the timely treatment of younger and middle-aged subjects to prevent the long-term consequences of hypoandrogenism.

  5. Review of graft rejection in age-related macular degeneration replacement therapy

    Directory of Open Access Journals (Sweden)

    Xi-Ying Mao

    2016-02-01

    Full Text Available Age-related macular degeneration(AMDis the leading cause of blindness among the elderly worldwide. AMD is classified as either neovascular(wetor non-neovascular(dry. The dysfunction and loss of retinal pigment epithelial(RPEcells is regarded as the main pathological changes of AMD. The recent development of regenerative medicine has witnessed RPE cell-replacement therapy as a new approach to treat AMD, resulting in obvious visual improvement in various studies. However, there are still many problems and challenges that remain unsolved, including graft rejection. This review introduces subretinal immune environment under both normal and AMD condition, putting emphasis on immune response to allogeneic RPE. Lastly, strategies to prevent graft rejection are discussed.

  6. Subgroup analysis of continuous renal replacement therapy in severely burned patients.

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    Jaechul Yoon

    Full Text Available Continuous renal replacement therapy (CRRT is administered to critically ill patients with renal injuries as renal replacement or renal support. We aimed to identify predictors of mortality among burn patients receiving CRRT, and to investigate clinical differences according to acute kidney injury (AKI status. This retrospective observational study evaluated 216 Korean burn patients who received CRRT at a burn intensive care unit. Patients were categorized by AKI status. Data were collected regarding arterial pH, laboratory results, ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio, and urine production. Among surviving patients, CRRT duration and the sequential organ failure assessment score were 6.5 days and 4.7 in the non-AKI group and 23.4 days and 7.4 in the AKI group, respectively (p = 0.003 and p = 0.008. On logistic regression analyses, mortality was significantly associated with a pH of 5.0 mEg/L (p = 0.045, creatinine levels of >2.0 mg/dL (p = 0.011, lactate levels of >2 mmol/L (p2 mmol/L, and a platelet count of 2 mg/dL. In the non-AKI group, poor outcomes were associated with lactate levels of >1.5 mmol/L, a PF ratio of 1.2 mg/dL. Duration of the CRRT application and the requirement for either renal replacement or renal support at the initiation of CRRT application are important considerations depending on its application.

  7. Using continuous renal replacement therapy to manage patients of shock and acute renal failure

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    Soni Sachin

    2009-01-01

    Full Text Available Background: The incidence of acute renal failure (ARF in the hospital setting is increasing. It portends excessive morbidity and mortality and a considerable burden on hospital resources. Extracorporeal therapies show promise in the management of patients with shock and ARF. It is said that the potential of such therapy goes beyond just providing renal support. The aim of our study was to analyze the clinical setting and outcomes of critically ill ARF patients managed with continuous renal replacement therapy (CRRT. Patients and Methods: Ours was a retrospective study of 50 patients treated between January 2004 and November 2005. These 50 patients were in clinical shock and had concomitant ARF. All of these patients underwent CVVHDF (continuous veno-venous hemodiafiltration in the intensive care unit. For the purpose of this study, shock was defined as systolic BP < 100 mm Hg in spite of administration of one or more inotropic agents. SOFA (Sequential Organ Failure Assessment score before initiation of dialysis support was recorded in all cases. CVVHDF was performed using the Diapact ® (Braun CRRT machine. The vascular access used was as follows: femoral in 32, internal jugular in 8, arteriovenous fistula (AVF in 4, and subclavian in 6 patients. We used 0.9% or 0.45% (half-normal saline as a prefilter replacement, with addition of 10% calcium gluconate, magnesium sulphate, sodium bicarbonate, and potassium chloride in separate units, while maintaining careful monitoring of electrolytes. Anticoagulation of the extracorporeal circuit was achieved with systemic heparin in 26 patients; frequent saline flushes were used in the other 24 patients. Results: Of the 50 patients studied, 29 were males and 21 females (1.4:1. The average age was 52.88 years (range: 20-75 years. Causes of ARF included sepsis in 24 (48%, hemodynamically mediated renal failure (HMRF in 18 (36%, and acute over chronic kidney disease in 8 (16% patients. The overall mortality was

  8. Sources of information influencing the state-of-the-science gap in hormone replacement therapy usage.

    Directory of Open Access Journals (Sweden)

    Fiona Chew

    Full Text Available Medical reviews and research comprise a key information source for news media stories on medical therapies and innovations as well as for physicians in updating their practice. The present study examined medical review journal articles, physician surveys and news media coverage of hormone replacement therapy (HT to assess the relationship between the three information sources and whether/if they contributed to a state-of-the-science gap (a condition when the evaluation of a medical condition or therapy ascertained by the highest standards of investigation is incongruent with the science-in-practice such as physician recommendations and patient actions.We content-analyzed 177 randomly sampled HT medical reviews between 2002 and 2014, and HT news valence in three major TV networks, newspapers and magazines/internet sites in 2002-2003, 2008-2009 and 2012-14. The focus in both analyses was whether HT benefits outweighed risks, risks outweighed benefits or both risks and benefits were presented. We also qualitatively content-analyzed all 19 surveys of US physicians' HT recommendations from 2002 to 2009, and 2012 to 2014.Medical reviews yielded a mixed picture about HT (40.1% benefits, 26.0% risks, and 33.9% both benefits and risks. While a majority of physician surveys were pro-HT 10/19, eight showed varied attitudes and one was negative. Newspaper and television coverage reflected a pro and con balance while magazine stories were more positive in the later reporting period.Medical journal review articles, physicians, and media reports all provide varying view points towards hormone therapy use thus leading to limited knowledge about the actual risks and benefits of HT among peri- and menopausal women and a state-of-the-science gap.

  9. Temporal Progression of Retinal Progenitor Cell Identity: Implications in Cell Replacement Therapies

    Directory of Open Access Journals (Sweden)

    Awais Javed

    2017-12-01

    Full Text Available Retinal degenerative diseases, which lead to the death of rod and cone photoreceptor cells, are the leading cause of inherited vision loss worldwide. Induced pluripotent or embryonic stem cells (iPSCs/ESCs have been proposed as a possible source of new photoreceptors to restore vision in these conditions. The proof of concept studies carried out in mouse models of retinal degeneration over the past decade have highlighted several limitations for cell replacement in the retina, such as the low efficiency of cone photoreceptor production from stem cell cultures and the poor integration of grafted cells in the host retina. Current protocols to generate photoreceptors from stem cells are largely based on the use of extracellular factors. Although these factors are essential to induce the retinal progenitor cell (RPC fate from iPSCs/ESCs, developmental studies have shown that RPCs alter fate output as a function of time (i.e., their temporal identity to generate the seven major classes of retinal cell types, rather than spatial position. Surprisingly, current stem cell differentiation protocols largely ignore the intrinsic temporal identity of dividing RPCs, which we argue likely explains the low efficiency of cone production in such cultures. In this article, we briefly review the mechanisms regulating temporal identity in RPCs and discuss how they could be exploited to improve cone photoreceptor production for cell replacement therapies.

  10. Real-world Direct Health Care Costs for Metastatic Colorectal Cancer Patients Treated With Cetuximab or Bevacizumab-containing Regimens in First-line or First-line Through Second-line Therapy.

    Science.gov (United States)

    Johnston, Stephen; Wilson, Kathleen; Varker, Helen; Malangone-Monaco, Elisabetta; Juneau, Paul; Riehle, Ellen; Satram-Hoang, Sacha; Sommer, Nicolas; Ogale, Sarika

    2017-12-01

    The present study examined real-world direct health care costs for metastatic colorectal cancer (mCRC) patients initiating first-line (1L) bevacizumab (BEV)- or cetuximab (CET)-containing regimen in 1L or 1L-through-second-line (1L-2L) therapy. Using a large US insurance claims database, patients with mCRC initiating 1L BEV- or 1L CET-containing regimen from January 1, 2008 to September 30, 2014 were identified. The per-patient per-month (PPPM) all-cause health care costs (2014 US dollars) were measured during 1L therapy and, for patients continuing to a 2L biologic-containing regimen, 1L-2L therapy. Multivariable regression analyses were used to compare PPPM total health care costs between patients initiating a 1L BEV- versus 1L CET-containing regimen. A total of 6095 patients initiating a 1L BEV- and 453 initiating a 1L CET-containing regimen were evaluated for 1L costs; 2218 patients initiating a 1L BEV- and 134 initiating a 1L CET-containing regimen were evaluated for 1L-2L costs. In 1L therapy, 1L CET had adjusted PPPM costs that were $3135 (95% confidence interval [CI], $1174-$5040; P < .001) greater on average than 1L BEV. In 1L-2L therapy, 1L BEV-2L CET had adjusted PPPM costs that were $1402 (95% CI, $1365-$1442; P = .010) greater than those for 1L BEV-2L BEV, and 1L CET-2L BEV had adjusted PPPM costs that were $4279 (95% CI, $4167-$4400; P = .001) greater on average than those for 1L BEV-2L BEV. The adjusted PPPM cost differences for 1L BEV-2L other biologic or 1L CET-2L other biologic agent were numerically greater but statistically insignificant. PPPM total health care costs for 1L and 2L therapy tended to be greater for patients treated with 1L CET-containing regimens than for 1L BEV-containing regimens. Also, continuing treatment with BEV-containing regimens 1L-2L was less costly than switching between BEV and CET. The cost differences between BEV and CET hold important implications for treatment decisions of mCRC patients in real-world clinical

  11. Continuous renal replacement therapy improves renal recovery from acute renal failure.

    Science.gov (United States)

    Jacka, Michael J; Ivancinova, Xenia; Gibney, R T Noel

    2005-03-01

    Acute renal failure (ARF) occurs in up to 10% of critically ill patients, with significant associated morbidity and mortality. The optimal mode of renal replacement therapy (RRT) remains controversial. This retrospective study compared continuous renal replacement therapy (CRRT) and intermittent hemodialysis (IHD) for RRT in terms of intensive care unit (ICU) and hospital mortality, and renal recovery. We reviewed the records of all patients undergoing RRT for the treatment of ARF over a 12-month period. Patients were compared according to mode of RRT, demographics, physiologic characteristics, and outcomes of ICU and hospital mortality and renal recovery using the Chi square, Student's t test, and multiple logistic regression as appropriate. 116 patients with renal insufficiency underwent RRT during the study period. Of these, 93 had ARF. The severity of illness of CRRT patients was similar to that of IHD patients using APACHE II (25.1 vs 23.5, P = 0.37), but they required significantly more intensive nursing (therapeutic intervention scale 47.8 vs 37.6, P = 0.0001). Mortality was associated with lower pH at presentation (P = 0.003) and increasing age (P = 0.03). Renal recovery was significantly more frequent among patients initially treated with CRRT (21/24 vs 5/14, P = 0.0003). Further investigation to define optimal timing, dose, and duration of RRT may be beneficial. Although further study is needed, this study suggests that renal recovery may be better after CRRT than IHD for ARF. Mortality was not affected significantly by RRT mode.

  12. Access to and coverage of renal replacement therapy in minorities and ethnic groups in Venezuela.

    Science.gov (United States)

    Bellorin-Font, Ezequiel; Pernalete, Nidia; Meza, Josefina; Milanes, Carmen Luisa; Carlini, Raul G

    2005-08-01

    Access to and coverage of renal replacement therapy in minorities and ethnic groups in Venezuela. Numerous studies have documented the presence of racial and minority disparities regarding the impact of renal disease and access to renal replacement therapy (RRT). This problem is less well documented in Latin America. Venezuela, like most countries in the region, is subject to severe constraints in the allocation of resources for high-cost chronic diseases, which limits the access of patients with chronic kidney disease to RRT. Although access to health care is universal, there is both a deficit in coverage and disparity in the access to RRT, largely as a result of socioeconomic limitations and budget constrains. With current rising trends of the incidence of end-stage renal disease (ESRD) and costs of medical technology, the long-term goal of complete RRT coverage will become increasingly out of reach. Current evidence suggests that prevention of progression of renal disease is possible at relatively low cost and broad coverage. Based on this evidence, the Ministry of Health has redesigned its policy with respect to renal disease based on 4 elements: 1. Prevention by means of early detection and referral to multidisciplinary health teams, as well as promotion of health habits in the community. 2. Prevention of progression of renal disease by pharmacologic and nonpharmacologic means. 3. An increase in the rate of coverage and reduction of disparities in the access to dialysis. 4. An increase in the rates of renal transplantation through better organ procurement programs and reinforcement of transplant centers. However, the projected increase in the number of patients with ESKD receiving RRT will represent a serious burden to the health care system. Therefore, implementation of these policies will require the involvement of international agencies as well as an adequate partnership between nephrologists and health care planners, so that meeting the increasing demands

  13. Low Impact of Urinary Cortisol in the Assessment of Hydrocortisone Replacement Therapy.

    Science.gov (United States)

    Haas, C S; Rahvar, A-H; Danneberg, S; Lehnert, H; Moenig, H; Harbeck, B

    2016-09-01

    Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 μg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 μg/8 h; range 17.1-120.0, p<0.001); the values correlated with serum cortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Evolution of Technology for Continuous Renal Replacement Therapy: Forty Years of Improvement.

    Science.gov (United States)

    Ronco, Claudio

    2018-01-01

    Continuous arteriovenous hemofiltration (CAVH) was proposed in 1977 as an alternative treatment for acute renal failure in patients in whom peritoneal dialysis or hemodialysis was clinically or technically precluded. In the mid-1980s, this technique was extended to infants and children. CAVH presented important advantages in the areas of hemodynamic stability, control of circulating volume, and nutritional support. However, there were serious shortcomings such as the need for arterial cannulation and limited solute clearance. These problems were solved by the introduction of continuous arteriovenous hemodiafiltration and continuous arteriovenous hemodialysis, where uremic control could be achieved by increasing countercurrent dialysate flow rates to 1.5 or 2 L/h as necessary, or by venovenous techniques utilizing a double-lumen central venous catheter for vascular access. Thus, continuous venovenous hemofiltration replaced CAVH because of its improved performance and safety. From the initial adoptive technology, specific machines have been designed to permit safe and reliable performance of the therapy. These new machines have progressively undergone a series of technological steps that have resulted in the evolution of highly sophisticated equipment utilized today. A significant number of advances have taken place since the time continuous renal replacement therapy was initiated. In particular, there have been successful experiments with high-volume hemofiltration and high-permeability hemofiltration. The additional and combined use of sorbent has also been tested successfully. Progress has been made in the technology as well as the understanding of the pathophysiology of acute kidney injury. Today, new biomaterials and new devices are available and new frontiers are on the horizon. Although improvements have been made, a lot remains to be done. Critical care nephrology is expected to further evolve in the near future, especially in the area of information and

  15. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction

    Science.gov (United States)

    Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L.; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R.; Kohn, Donald B.

    2012-01-01

    Gene therapy (GT) for adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada−/−). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist. PMID:22833548

  16. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

    Science.gov (United States)

    Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

    2012-11-01

    Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

  17. [Application of continuous renal replacement therapy in the treatment of myonephropathic metabolic syndrome caused by acute lower extremity ischemia].

    Science.gov (United States)

    Sun, Jianping; Wang, Tengke; Zhang, Jinglan

    2014-09-16

    To summarize the experiences of using continuous renal replacement therapy in the treatment of myonephropathic metabolic syndrome caused by acute lower limb ischemia. Retrospective study of patients diagnosed acute lower limb ischemia with surgical treatment between January 2008 and December 2013, among which 22 patients with myonephropathic metabolic syndrome received continuous renal replacement therapy. Summarize the change tendency of myoglobin, urine volume and serum creatinine levels during treatment and analysis the condition changes and prognosis of the patients. Among them, 2 patients were amputated and two died after surgery. The major causes of death were acute renal failure, metabolic acidosis, circulation failure and liver failure, etc. Myoglobin was significantly higher at Day 1 after surgery than that was before surgery (P metabolic syndrome, early targeted continuous renal replacement therapy may decrease the serum concentrations of myoglobin and CK, improve urine volume, maintain homeostasis, prevent renal function deterioration and improve the prognosis of patients. And it is highly recommended.

  18. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    Science.gov (United States)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  19. Delay in onset of metabolic alkalosis during regional citrate anti-coagulation in continous renal replacement therapy with calcium-free replacement solution

    Directory of Open Access Journals (Sweden)

    See Kay

    2009-01-01

    Full Text Available Regional citrate anti-coagulation for continuous renal replacement therapy chelates calcium to produce the anti- coagulation effect. We hypothesise that a calcium-free replacement solution will require less citrate and produce fewer metabolic side effects. Fifty patients, in a Medical Intensive Care Unit of a tertiary teaching hospital (25 in each group, received continuous venovenous hemofiltration using either calcium-containing or calcium-free replacement solutions. Both groups had no significant differences in filter life, metabolic alkalosis, hypernatremia, hypocalcemia, and hypercalcemia. However, patients using calcium-containing solution developed metabolic alkalosis earlier, compared to patients using calcium-free solution (mean 24.6 hours,CI 0.8-48.4 vs. 37.2 hours, CI 9.4-65, P = 0.020. When calcium-containing replacement solution was used, more citrate was required (mean 280ml/h, CI 227.2-332.8 vs. 265ml/h, CI 203.4-326.6, P = 0.069, but less calcium was infused (mean 21.2 ml/h, CI 1.2-21.2 vs 51.6ml/h, CI 26.8-76.4, P ≤ 0.0001.

  20. [Echinocandins: searching for differences. The example of their use in patients requiring continuous renal replacement therapy].

    Science.gov (United States)

    de la Llama-Celis, Natalia; Huarte-Lacunza, Rafael; Gómez-Baraza, Cristina; Cañamares-Orbis, Iciar; Sebastián-Aldeanueva, Manuel; Arrieta-Navarro, Raquel

    2012-12-01

    The echinocandins have a growing role in the treatment of fungal infections because of their novel mechanism of action. This is reflected in recently published management guidelines, but available in vitro data, animal studies, and clinical studies do not clearly differentiate the three agents in class. Comparative clinical efficacy among agents within the class, pharmacokinetic profiles in special populations, pharmacoeconomics justifications, and place in therapy have been largely unanswered. They share many common properties but marketing strategies of drug manufacturers are engaged in product differentiation. Although exist similarities in the pharmacokinetic (PK) profiles of the echinocandins, limited data have been published regarding their pharmacokinetics in continuous renal replacement therapy (CRRT) patients. The pharmacokinetics of drug removal in critically ill patients receiving CRRT is very complex, with multiple variables affecting clearance. This review outlines the basic principles that determine whether a dose adjustment is required. Two studies with data on PK parameters of micafungin and anidulafungin in CRRT patients have been published and are compared following that basic principles in the review.

  1. The current status of prophylactic replacement therapy in children and adults with haemophilia.

    Science.gov (United States)

    Ljung, Rolf; Gretenkort Andersson, Nadine

    2015-06-01

    Initiating prophylactic treatment at an early age is considered to be the optimal form of therapy for a child with haemophilia A or B. The pioneering long term experiences of prophylactic treatment from Sweden and The Netherlands demonstrated the benefit of prophylaxis in retrospective and observational studies. Decades later, these benefits were confirmed in a randomized controlled study in USA. We review the current status of prophylactic replacement therapy of haemophilia in children, adolescents, adults and the elderly. Prophylaxis should begin at an early age and there are arguments for continuing it into adulthood. The dose of prophylaxis is dependent on the goal of treatment, economic resources and venous access and should be tailored individually. Starting the first exposures to clotting factor concentrates as prophylactic treatment, instead of on-demand in response to a bleed, may decrease the frequency of inhibitors in patients with haemophilia A. Novel longer-acting products are being introduced that could be helpful for patients with difficult venous access and enable higher trough levels. © 2015 John Wiley & Sons Ltd.

  2. The Challenge of Providing Renal Replacement Therapy in Developing Countries: The Latin American Perspective.

    Science.gov (United States)

    Obrador, Gregorio T; Rubilar, Ximena; Agazzi, Evandro; Estefan, Janette

    2016-03-01

    The costs of health care place developing countries under enormous economic pressure. Latin America is a region characterized by wide ethnic and per capita gross domestic product variations among different countries. Chronic kidney failure prevalence and incidence, as well as provision of renal replacement therapy (RRT), have increased in all Latin American countries over the last 20 years. From an ethical point of view, life-sustaining therapies such as RRT should be available to all patients with chronic kidney disease who might benefit. However, even among Latin American countries with similar per capita incomes and health care expenditures, only some have been able to achieve universal access to RRT. This indicates that it is not just a problem of wealth or distribution of scarce health care resources, but one of social justice. Strategies to increase the availability of RRT and renal palliative-supportive care, as well as implementation of interventions to prevent chronic kidney disease development and progression, are needed in Latin America and other developing countries. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  3. Modification of blood pressure in postmenopausal women: role of hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Cannoletta M

    2014-08-01

    Full Text Available Marianna Cannoletta, Angelo Cagnacci Institute of Obstetrics and Gynecology, Department of Medical and Surgical Sciences of the Mother, Child and Adult, University of Modena and Reggio Emilia, Modena and Reggio Emilia, Emilia-Romagna, Italy Abstract: The rate of hypertension increases after menopause. Whether estrogen and progesterone deficiency associated with menopause play a role in determining a worst blood pressure (BP control is still controversial. Also, studies dealing with the administration of estrogens or hormone therapy (HT have reported conflicting evidence. In general it seems that, despite some negative data on subgroups of later postmenopausal women obtained with oral estrogens, in particular conjugated equine estrogens (CEE, most of the data indicate neutral or beneficial effects of estrogen or HT administration on BP control of both normotensive and hypertensive women. Data obtained with ambulatory BP monitoring and with transdermal estrogens are more convincing and concordant in defining positive effect on BP control of both normotensive and hypertensive postmenopausal women. Overall progestin adjunct does not hamper the effect of estrogens. Among progestins, drospirenone, a spironolactone-derived molecule, appears to be the molecule with the best antihypertensive properties. Keywords: hormone replacement therapy, estrogen, progestin, blood pressure, menopause, hypertension 

  4. Nicotine replacement therapy decision based on fuzzy multi-criteria analysis

    Science.gov (United States)

    Tarmudi, Zamali; Matmali, Norfazillah; Abdullah, Mohd Lazim

    2017-08-01

    It has been observed that Nicotine Replacement Therapy (NRT) is one of the alternatives to control and reduce smoking addiction among smokers. Since the decision to choose the best NRT alternative involves uncertainty, ambiguity factors and diverse input datasets, thus, this paper proposes a fuzzy multi-criteria analysis (FMA) to overcome these issues. It focuses on how the fuzzy approach can unify the diversity of datasets based on NRT's decision-making problem. The analysis done employed the advantage of the cost-benefit criterion to unify the mixture of dataset input. The performance matrix was utilised to derive the performance scores. An empirical example regarding the NRT's decision-making problem was employed to illustrate the proposed approach. Based on the calculations, this analytical approach was found to be highly beneficial in terms of usability. It was also very applicable and efficient in dealing with the mixture of input datasets. Hence, the decision-making process can easily be used by experts and patients who are interested to join the therapy/cessation program.

  5. Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.

    Science.gov (United States)

    Puche, Juan E; Muñoz, Úrsula; García-Magariño, Mariano; Sádaba, María C; Castilla-Cortázar, Inma

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. © 2016 International Union of Biochemistry and Molecular Biology.

  6. Arteriovenous thrombosis in chronic renal failure patients receving renal replacement therapy

    International Nuclear Information System (INIS)

    Shoaib, M.; Naz, A.

    2008-01-01

    To determine the frequency of thrombotic complications and to identify factors associated with arteriovenous thrombosis in patients of chronic renal failure receiving renal replacement therapy. Of the 3000 patients evaluated, 61 End Stage Renal Disease (ESRD) patients on regular dialysis, having recent renal transplant, were selected for the study after informed consent. These patients had arteriovenous thrombosis with temporary central lines thrombosis and vascular access problems. Cases of congenital or acquired thrombotic disorders, e.g. with malignancy, DIC, liver disease, systemic lupus erythematosus or other immunologic diseases, pregnancy or women using oral contraceptives, were excluded. Similarly, patients taking any type of anticoagulant therapy during the preceding one week were not included in the study. Findings were recorded in a structured questionnaire. Laboratory analysis was done after clinical and radiological evaluation. Thrombophilia screening included antithrombin, protein C, protein S deficiencies and lupus anticoagulant. Forty-seven out of 61 patients selected were positive for thrombophilia screening with protein C deficiency in 26.2%, protein S deficiency in 16.3%, antithrombin in 5%, lupus anticoagulant in 13.1% and combined deficiency was observed in 16.3%. Of the 3000 patients, 61 with frequency of 2% were found to be deficient in one or had combined deficiency of these. Thus, the study of ESRD patients presenting with arteriovenous thromboembolism emphasizes the need to reconsider the perception that this clinical entity is rare and requires further studies. (author)

  7. Regional differences in renal replacement therapy in northern Norway 2000–2012

    Science.gov (United States)

    Norum, Jan; Leivestad, Torbjørn; Eriksen, Bjørn Odvar; Skår, Siw; Fagerheim, Anne; Reisæter, Anna Varberg

    2015-01-01

    Objective Distance from residence location to a centre for renal replacement therapy (RRT) may influence patients’ quality of life and prognosis. Northern Norway constitutes 45% of Norway's landmass, but has less than 10% of the population. Methods In this study, we analysed all patients in northern Norway consecutively registered in the Norwegian Renal Registry during 2000–2012. A total of 634 patients (Nordland County 321 patients, Troms County 215 patients and Finnmark County 98 patients) were investigated. Results There were more smokers (31% vs. 22%) and patients with diabetes (32% vs. 22%) in Finnmark, but the difference did not reach statistical significance. Patients undergoing RRT and living in Finnmark County had a significantly worse outcome (P=0.03). The median survivals after initiation of RRT were 3.8 years (Finnmark), 6.4 years (Troms) and 5.4 years (Nordland), respectively. The most common causes of death were cardiovascular disease (53%), infections (16%), withdrawal from therapy (15%) and malignancy (13%). In a Cox analysis, age (P<0.0001), diabetes (P=0.008) and smoking at any time (P<0.004) were individual factors correlated with inferior prognosis. Conclusion Age, smoking and diabetes were prognostic factors. Residents of the northernmost county (Finnmark) experienced an inferior prognosis. Long distance from residence location to hospital may be another factor, but this could not be documented. Preventive strategies should be improved. PMID:25672881

  8. Regional differences in renal replacement therapy in northern Norway 2000-2012.

    Science.gov (United States)

    Norum, Jan; Leivestad, Torbjørn; Eriksen, Bjørn Odvar; Skår, Siw; Fagerheim, Anne; Reisæter, Anna Varberg

    2015-01-01

    Distance from residence location to a centre for renal replacement therapy (RRT) may influence patients' quality of life and prognosis. Northern Norway constitutes 45% of Norway's landmass, but has less than 10% of the population. In this study, we analysed all patients in northern Norway consecutively registered in the Norwegian Renal Registry during 2000-2012. A total of 634 patients (Nordland County 321 patients, Troms County 215 patients and Finnmark County 98 patients) were investigated. There were more smokers (31% vs. 22%) and patients with diabetes (32% vs. 22%) in Finnmark, but the difference did not reach statistical significance. Patients undergoing RRT and living in Finnmark County had a significantly worse outcome (P=0.03). The median survivals after initiation of RRT were 3.8 years (Finnmark), 6.4 years (Troms) and 5.4 years (Nordland), respectively. The most common causes of death were cardiovascular disease (53%), infections (16%), withdrawal from therapy (15%) and malignancy (13%). In a Cox analysis, age (P<0.0001), diabetes (P=0.008) and smoking at any time (P<0.004) were individual factors correlated with inferior prognosis. Age, smoking and diabetes were prognostic factors. Residents of the northernmost county (Finnmark) experienced an inferior prognosis. Long distance from residence location to hospital may be another factor, but this could not be documented. Preventive strategies should be improved.

  9. The use of renal replacement therapy in acute decompensated heart failure.

    Science.gov (United States)

    Udani, Suneel M; Murray, Patrick T

    2009-01-01

    The worsening of renal function in the context of decompensated heart failure is an increasingly common clinical scenario, dubbed the cardiorenal syndrome. Its development is not completely understood; however, it results from the hemodynamic and neurohumoral alterations that occur in the setting of left ventricular pressure and volume overload with poor cardiac output. Diuretics have been the mainstay of treatment; however, they are often unsuccessful in reversing the vicious cycle of volume overload, worsening cardiac function, and azotemia. Renal replacement therapy (RRT) in the form of isolated or continuous ultrafiltration (UF) with or without a component of solute clearance (hemofiltration or hemodialysis) has been increasingly utilized as a therapeutic tool in this setting. Initial clinical trial data on the use of UF have demonstrated promising cardiac outcomes with regard to fluid removal and symptom relief without worsening renal function. The addition of a component of solute clearance may provide additional benefits in these patients with varying degrees of renal impairment. The exact clinical setting in which the various forms of RRT should be applied as initial or early therapy for acute decompensated heart failure (ADHF) remains unknown. More research examining the use of RRT in ADHF is necessary; however, it appears that the patients with the most severe clinical presentations have the best chance of benefiting from the early application of RRT.

  10. A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy.

    Science.gov (United States)

    Ludwig, Natasha G; Radaeli, Rafael F; Silva, Mariana M X; Romero, Camila M; Carrilho, Alexandre J F; Bessa, Danielle; Macedo, Delanie B; Oliveira, Maria L; Latronico, Ana Claudia; Mazzuco, Tânia L

    2016-01-01

    Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

  11. Knowledge and Perceptions about Nicotine, Nicotine Replacement Therapies and Electronic Cigarettes among Healthcare Professionals in Greece

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    Anastasia Moysidou

    2016-05-01

    Full Text Available Introduction. The purpose of this study was to evaluate the knowledge and perceptions of Greek healthcare professionals about nicotine, nicotine replacement therapies and electronic cigarettes. Methods. An online survey was performed, in which physicians and nurses working in private and public healthcare sectors in Athens-Greece were asked to participate through email invitations. A knowledge score was calculated by scoring the correct answers to specific questions with 1 point. Results. A total of 262 healthcare professionals were included to the analysis. Most had daily contact with smokers in their working environment. About half of them considered that nicotine has an extremely or very important contribution to smoking-related disease. More than 30% considered nicotine replacement therapies equally or more addictive than smoking, 76.7% overestimated their smoking cessation efficacy and only 21.0% would recommend them as long-term smoking substitutes. For electronic cigarettes, 45.0% considered them equally or more addictive than smoking and 24.4% equally or more harmful than tobacco cigarettes. Additionally, 35.5% thought they involve combustion while the majority responded that nicotine in electronic cigarettes is synthetically produced. Only 14.5% knew about the pending European regulation, but 33.2% have recommended them to smokers in the past. Still, more than 40% would not recommend electronic cigarettes to smokers unwilling or unable to quit smoking with currently approved medications. Cardiologists and respiratory physicians, who are responsible for smoking cessation therapy in Greece, were even more reluctant to recommend electronic cigarettes to this subpopulation of smokers compared to all other participants. The knowledge score of the whole study sample was 7.7 (SD: 2.4 out of a maximum score of 16. Higher score was associated with specific physician specialties. Conclusions. Greek healthcare professionals appear to overestimate

  12. Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network

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    Alícia Dorneles Dornelles

    2014-01-01

    Full Text Available Mucopolysaccharidosis type I (MPS I is a rare lysosomal disorder caused by deficiency of alph-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34 and at a median time of 2.5 years later (T2; n = 24/34. The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype; B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype. For all variables in which there was no between-group difference at baseline, a delta of ;±20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

  13. Understanding the continuous renal replacement therapy circuit for acute renal failure support: a quality issue in the intensive care unit.

    Science.gov (United States)

    Boyle, Martin; Baldwin, Ian

    2010-01-01

    Delivery of renal replacement therapy is now a core competency of intensive care nursing. The safe and effective delivery of this form of therapy is a quality issue for intensive care, requiring an understanding of the principles underlying therapy and the functioning of machines used. Continuous hemofiltration, first described in 1977, used a system where blood flowed from arterial to venous cannulas through a small-volume, low-resistance, and high-flux filter. Monitoring of these early systems was limited, and without a machine interface, less nursing expertise was required. Current continuous renal replacement therapy machines offer user-friendly interfaces, cassette-style circuits, and comprehensive circuit diagnostics and monitoring. Although these machines conceal complexity behind a user-friendly interface, it remains important that nurses have sufficient knowledge for their use and the ability to compare and contrast circuit setups and functions for optimal and efficient treatment.

  14. Assessment of National Practice for Palliative Radiation Therapy for Bone Metastases Suggests Marked Underutilization of Single-Fraction Regimens in the United States

    Energy Technology Data Exchange (ETDEWEB)

    Rutter, Charles E., E-mail: charles.rutter@yale.edu [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Yale Cancer Center, New Haven, Connecticut (United States); Yu, James B.; Wilson, Lynn D.; Park, Henry S. [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States); Yale Cancer Center, New Haven, Connecticut (United States)

    2015-03-01

    Purpose: To characterize temporal trends in the application of various bone metastasis fractionations within the United States during the past decade, using the National Cancer Data Base; the primary aim was to determine whether clinical practice in the United States has changed over time to reflect the published randomized evidence and the growing movement for value-based treatment decisions. Patients and Methods: The National Cancer Data Base was used to identify patients treated to osseous metastases from breast, prostate, and lung cancer. Utilization of single-fraction versus multiple-fraction radiation therapy was compared according to demographic, disease-related, and health care system details. Results: We included 24,992 patients treated during the period 2005-2011 for bone metastases. Among patients treated to non-spinal/vertebral sites (n=9011), 4.7% received 8 Gy in 1 fraction, whereas 95.3% received multiple-fraction treatment. Over time the proportion of patients receiving a single fraction of 8 Gy increased (from 3.4% in 2005 to 7.5% in 2011). Numerous independent predictors of single-fraction treatment were identified, including older age, farther travel distance for treatment, academic treatment facility, and non-private health insurance (P<.05). Conclusions: Single-fraction palliative radiation therapy regimens are significantly underutilized in current practice in the United States. Further efforts are needed to address this issue, such that evidence-based and cost-conscious care becomes more commonplace.

  15. Comparative study of anticoagulation versus saline flushes in continuous renal replacement therapy

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    Nagarik Amit

    2010-01-01

    Full Text Available Systemic heparinization during continuous renal replacement therapy (CRRT is associated with disadvantage of risk of bleeding. This study analyses the efficacy of frequent saline flushes compared with heparin anticoagulation to maintain filter life. From January 2004 to November 2007, 65 critically ill patients with acute renal failure underwent CRRT. Continuous venovenous hemodialfiltration (CVVHDF was performed using Diapact Braun CRRT machine. 1.7% P.D. fluid was used as dialysate. 0.9% NS with addition of 10% Ca Gluconate, Magnesium Sulphate, Soda bicarbonate and Potassium Chloride added sequentially in separate units were used for replacement, carefully monitoring their levels. Anticoagulation of extracorporeal circuit was achieved with unfractionated heparin (250-500 units alternate hour in 35 patients targeting aPTT of 45-55 seconds. No anticoagulation was used in 30 patients with baseline APTT > 55 seconds and extracorporeal circuit was maintained with saline flushes at 30 min interval. 65 pa-tients including 42 males. Co-morbidities were comparable in both groups. HMARF was signifi-cantly more common in heparin group while Sepsis was comparable in both the groups. CRRT parameters were similar in both groups. Average filter life in heparin group was 26 ± 6.4 hours while it was 24.5 ± 6.36 hours in heparin free group ( P=NS. Patients receiving heparin had 16 bleeding episodes (0.45/patient while only four bleeding episodes occurred in heparin free group (0.13/patient, P< 0.05. Mortality was 71% in heparin group and 67% in heparin free group. Frequent saline flushes is an effective mode of maintainance of extracorporeal circuit in CRRT when aPTT is already on the higher side, with significantly decreased bleeding episodes.

  16. Postoperative radiation therapy after hip replacement in high-risk patients for development of heterotopic bone formation

    International Nuclear Information System (INIS)

    Hashem, R.; Rene, N.; Souhami, L.; Tanzer, M.; Evans, M.

    2011-01-01

    Purpose. - To report the results of postoperative radiation therapy in preventing the development of heterotopic bone formation after hip replacement surgery in high-risk patients. Patients and methods. - Between 1991 and 2007, 44 patients were preventively treated with postoperative RT after total hip replacement. In total, 47 hips were treated. All patients were considered at high risk for developing heterotopic bone formation. Most patients (63.5%) were treated because of a history of severe osteoarthritis or ankylosing spondylitis. All patients were treated with shaped parallel-opposed fields with a single fraction of 7 Gy using 6 or 18 MV photons. Most patients (94%) received radiation therapy within 72 hours postoperative and in only three patients radiation therapy was delivered after 72 hours post-surgery (5-8 days). Results. - Minimum follow-up was 1 year. There were 18 females and 26 males. Median age was 63 years (range: 18-80). Treatments were well tolerated and no acute toxicity was seen post-radiation therapy. Only one of the 47 hips (2%) developed heterotopic bone formation. This patient received postoperative radiation therapy to both hips but only developed heterotopic bone formation in one of them. None of the three patients treated beyond 72 hours failed. To date no late toxicity has been observed. Conclusion. - The use of postoperative radiation therapy was an effective and safe treatment in the prevention of heterotopic bone formation in a high-risk group of patients undergoing total hip replacement. (authors)

  17. Impact of anticoagulation therapy on valve haemodynamic deterioration following transcatheter aortic valve replacement.

    Science.gov (United States)

    Del Trigo, María; Muñoz-García, Antonio J; Latib, Azeem; Auffret, Vincent; Wijeysundera, Harindra C; Nombela-Franco, Luis; Gutierrez, Enrique; Cheema, Asim N; Serra, Vicenç; Amat-Santos, Ignacio J; Kefer, Joelle; Benitez, Luis Miguel; Leclercq, Florence; Mangieri, Antonio; Le Breton, Hervé; Jiménez-Quevedo, Pilar; Garcia Del Blanco, Bruno; Dager, Antonio; Abdul-Jawad Altisent, Omar; Puri, Rishi; Pibarot, Philippe; Rodés-Cabau, Josep

    2018-05-01

    To evaluate the changes in transvalvular gradients and the incidence of valve haemodynamic deterioration (VHD) following transcatheter aortic valve replacement (TAVR), according to use of anticoagulation therapy. This multicentre study included 2466 patients (46% men; mean age 81±7 years) who underwent TAVR with echocardiography performed at 12-month follow-up. Anticoagulation therapy was used in 707 patients (28.7%) following TAVR (AC group). A total of 663 patients received vitamin K antagonists, and 44 patients received direct oral anticoagulants. A propensity score matching analysis was performed to adjust for intergroup (AC vs non-AC post-TAVR) differences. A total of 622 patients per group were included in the propensity-matched analysis. VHD was defined as a ≥10 mm Hg increase in the mean transprosthetic gradient at follow-up (vs hospital discharge). The mean clinical follow-up was 29±18 months. The mean transvalvular gradient significantly increased at follow-up in the non-AC group within the global cohort (P=0.003), whereas it remained stable over time in the AC group (P=0.323). The incidence of VHD was significantly lower in the AC group (0.6%) compared with the non-AC group (3.7%, P<0.001), and these significant differences remained within the propensity-matched populations (0.6% vs 3.9% in the AC and non-AC groups, respectively, P<0.001). The occurrence of VHD did not associate with an increased risk of all-cause death (P=0.468), cardiovascular death (P=0.539) or stroke (P=0.170) at follow-up. The lack of anticoagulation therapy post-TAVR was associated with significant increments in transvalvular gradients and a greater risk of VHD. VHD was subclinical in most cases and did not associate with major adverse clinical events. Future randomised trials are needed to determine if systematic anticoagulation therapy post-TAVR would reduce the incidence of VHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article

  18. Using continuous renal replacement therapy to manage patients of shock and acute renal failure

    Science.gov (United States)

    Soni, Sachin S; Nagarik, Amit P; Adikey, Gopal Kishan; Raman, Anuradha

    2009-01-01

    Background: The incidence of acute renal failure (ARF) in the hospital setting is increasing. It portends excessive morbidity and mortality and a considerable burden on hospital resources. Extracorporeal therapies show promise in the management of patients with shock and ARF. It is said that the potential of such therapy goes beyond just providing renal support. The aim of our study was to analyze the clinical setting and outcomes of critically ill ARF patients managed with continuous renal replacement therapy (CRRT). Patients and Methods: Ours was a retrospective study of 50 patients treated between January 2004 and November 2005. These 50 patients were in clinical shock and had concomitant ARF. All of these patients underwent CVVHDF (continuous veno-venous hemodiafiltration) in the intensive care unit. For the purpose of this study, shock was defined as systolic BP magnesium sulphate, sodium bicarbonate, and potassium chloride in separate units, while maintaining careful monitoring of electrolytes. Anticoagulation of the extracorporeal circuit was achieved with systemic heparin in 26 patients; frequent saline flushes were used in the other 24 patients. Results: Of the 50 patients studied, 29 were males and 21 females (1.4:1). The average age was 52.88 years (range: 20–75 years). Causes of ARF included sepsis in 24 (48%), hemodynamically mediated renal failure (HMRF) in 18 (36%), and acute over chronic kidney disease in 8 (16%) patients. The overall mortality was 74%. The average SOFA score was 14.31. The variables influencing mortality on multivariate analysis were: age [odds ratio (OR):1.65; 95% CI: 1.35 to 1.92; P = 0.04], serum creatinine (OR:1.68; 95% CI: 1.44 to 1.86; P = 0.03), and serum bicarbonate (OR: 0.76; 95% CI: 0.55 to 0.94; P = 0.01). On univariate analysis the SOFA score was found to be a useful predictor of mortality. Conclusions: Despite advances in treating critically ill patients with newer extracorporeal therapies, mortality is dismally high

  19. Testosterone replacement therapy among elderly males: the Testim Registry in the US (TRiUS

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    Bhattacharya RK

    2012-08-01

    Full Text Available Rajib K Bhattacharya,1 Mohit Khera,2 Gary Blick,3 Harvey Kushner,4 Martin M Miner51Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 2Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA; 3Circle Medical LLC, Norwalk, CT, USA; 4Biometrics, Auxilium Pharmaceuticals, Malvern, PA, USA; 5Men's Health Center, Miriam Hospital, Providence, RI, USABackground: Testosterone levels naturally decline with age in men, often resulting in testosterone deficiency (hypogonadism. However, few studies have examined hypogonadal characteristics and treatment in older (≥65 years men.Objective: To compare data at baseline and after 12 months of testosterone replacement therapy (TRT in hypogonadal men ≥65 vs <65 years old. Data for participants 65–74 vs ≥75 years old were also compared.Methods: Data were from TRiUS (Testim Registry in the United States, which enrolled 849 hypogonadal men treated with Testim® 1% (50–100 mg testosterone gel/day for the first time. Anthropometric, laboratory, and clinical measures were taken at baseline and 12 months, including primary outcomes of total testosterone (TT, free testosterone (FT, and prostate-specific antigen (PSA levels. Comparisons of parameters were made using Fisher's exact test or analysis of variance. Nonparametric Spearman's ρ and first-order partial correlation coefficients adjusted for the effect of age were used to examine bivariate correlations among parameters.Results: Of the registry participants at baseline with available age information, 16% (133/845 were ≥65 years old. They were similar to men <65 years old in the duration of hypogonadism prior to enrollment (~1 year, TT and FT levels at baseline, TT and FT levels at 12-month follow-up, and in reported compliance with treatment. Older patients were more likely to receive lower doses of TRT. PSA levels did not statistically differ between groups after 12 months of TRT (2.18 ± 2.18 ng

  20. Quality indicators of continuous renal replacement therapy (CRRT) care in critically ill patients: a systematic review.

    Science.gov (United States)

    Rewa, Oleksa G; Villeneuve, Pierre-Marc; Lachance, Philippe; Eurich, Dean T; Stelfox, Henry T; Gibney, R T Noel; Hartling, Lisa; Featherstone, Robin; Bagshaw, Sean M

    2017-06-01

    Renal replacement therapy is increasingly utilized in the intensive care unit (ICU), of which continuous renal replacement therapy (CRRT) is most common. Despite CRRT being a relatively invasive and resource intensive technology, there remains wide practice variation in its application. This systematic review appraised the evidence for quality indicators (QIs) of CRRT care in critically ill patients. A comprehensive search strategy was developed and performed in five citation databases (Medline, Embase, CINAHL, Cochrane Library, and PubMed) and select grey literature sources. Two reviewers independently screened, selected, and extracted data using standardized forms. Each retrieved citation was appraised for quality using the Newcastle-Ottawa Scale (NOS) and Cochrane risk of bias tool. Data were summarized narratively. Our search yielded 8374 citations, of which 133 fulfilled eligibility. This included 97 cohort studies, 24 randomized controlled trials, 10 case-control studies, and 2 retrospective medical audits. The quality of retrieved studies was generally good. In total, 18 QIs were identified that were mentioned in 238 instances. Identified QIs were classified as related to structure (n = 4, 22.2 %), care processes (n = 9, 50.0 %), and outcomes (n = 5, 27.8 %). The most commonly mentioned QIs focused on filter lifespan (n = 98), small solute clearance (n = 46), bleeding (n = 30), delivered dose (n = 19), and treatment interruption (n = 5). Across studies, the definitions used for QIs evaluating similar constructs varied considerably. When identified, QIs were most commonly described as important (n = 144, 48.3 %), scientifically acceptable (n = 32, 10.7 %), and useable and/or feasible (n = 17, 5.7 %) by their primary study authors. We identified numerous potential QIs of CRRT care, characterized by heterogeneous definitions, varying quality of derivation, and limited evaluation. Further study is needed to prioritize a concise

  1. Association of nicotine metabolism and sex with relapse following varenicline and nicotine replacement therapy.

    Science.gov (United States)

    Glatard, Anaïs; Dobrinas, Maria; Gholamrezaee, Mehdi; Lubomirov, Rubin; Cornuz, Jacques; Csajka, Chantal; Eap, Chin B

    2017-10-01

    Nicotine is metabolized into cotinine and then into trans-3'-hydroxycotinine, mainly by cytochrome P450 2A6. Recent studies reported better effectiveness of varenicline in women and in nicotine normal metabolizers phenotypically determined by nicotine-metabolite ratio. Our objective was to study the influence of nicotine-metabolite ratio, CYP2A6 genotype and sex on the response to nicotine replacement therapy and varenicline. Data were extracted from a longitudinal study which included smokers participating in a smoking cessation program. Response to treatment was defined by the absence of relapse when a set threshold of reduction in cigarettes per day relative to the week before the study was no more reached. The analysis considered total and partial reduction defined by a diminution of 100% and of 90% in cigarettes per day, respectively. The hazard ratio of relapsing was estimated in multivariate Cox regression models including the sex and the nicotine metabolism determined by the phenotype or by CYP2A6 genotyping (rs1801272 and rs28399433). In the normal metabolizers determined by phenotyping and in women, the hazard ratio for relapsing was significantly lower with varenicline for a partial decrease (HR = 0.33, 95% CI [0.12, 0.89] and HR = 0.20, 95% CI [0.04, 0.91], respectively) and nonsignificantly lower for a total cessation (HR = 0.45, 95% CI [0.20, 1.0] and HR = 0.38, 95% CI [0.14, 1.0]). When compared with the normal metabolizers determined by phenotyping, the hazard ratio for a partial decrease was similar in the normal metabolizers determined by genotyping (HR = 0.42, 95% CI [0.18, 0.94]) while it was significantly lower with varenicline for a total cessation (HR = 0.50, 95% CI [0.26, 0.98]). Women and normal nicotine metabolizers may benefit more from varenicline over nicotine replacement therapy. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation.

    Science.gov (United States)

    Andreoli, Maria Claudia Cruz; Souza, Nádia Karina Guimarães de; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Coelho, Maria Paula Vilela; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; Almeida, Marcio Dias de; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; Santos, Oscar Pavão Dos; Santos, Bento Cardoso Dos

    2017-01-01

    Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27-39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (prenal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability

  3. Use of anti-retroviral therapy in tuberculosis patients on second-line anti-TB regimens: a systematic review.

    Directory of Open Access Journals (Sweden)

    Matthew Arentz

    Full Text Available Use of antiretroviral therapy (ART during treatment of drug susceptible tuberculosis (TB improves survival. However, data from HIV infected individuals with drug resistant TB are lacking. Second line TB drugs when combined with ART may increase drug interactions and lead to higher rates of toxicity and greater noncompliance. This systematic review sought to determine the benefit of ART in the setting of second line drug therapy for drug resistant TB.We included individual patient data from studies that evaluated treatment of drug-resistant tuberculosis in HIV-1 infected individuals published between January 1980 and December of 2009. We evaluated the effect of ART on treatment outcomes, time to smear and culture conversion, and adverse events.Ten observational studies, including data from 217 subjects, were analyzed. Patients using ART during TB treatment had increased likelihood of cure (hazard ratio (HR 3.4, 95% CI 1.6-7.4 and decreased likelihood of death (HR 0.4, 95% CI 0.3-0.6 during treatment for drug resistant TB. These associations remained significant in patients with a CD4 less than 200 cells/mm(3 and less than 50 cells/mm(3, and when correcting for drug resistance pattern.We identified only observational studies from which individual patient data could be drawn. Limitations in study design, and heterogeneity in a number of the outcomes of interest had the potential to introduce bias.While there are insufficient data to determine if ART use increases adverse drug interactions when used with second line TB drugs, ART use during treatment of drug resistant TB appears to improve cure rates and decrease risk of death. All individuals with HIV appear to benefit from ART use during treatment for TB.

  4. International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes.

    Science.gov (United States)

    Manickam, Ponnaiah; Mehendale, Sanjay M; Nagaraju, Bathyala; Katoch, Kiran; Jamesh, Abdul; Kutaiyan, Ramalingam; Jianping, Shen; Mugudalabetta, Shivakumar; Jadhav, Vitthal; Rajkumar, Prabu; Padma, Jayasree; Kaliaperumal, Kanagasabai; Pannikar, Vijayakumar; Krishnamurthy, Padabettu; Gupte, Mohan D

    2016-10-01

    Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated. A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable. We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696].

  5. Patients' perceptions of information and education for renal replacement therapy: an independent survey by the European Kidney Patients' Federation on information and support on renal replacement therapy

    NARCIS (Netherlands)

    van Biesen, Wim; van der Veer, Sabine N.; Murphey, Mark; Loblova, Olga; Davies, Simon

    2014-01-01

    Selection of an appropriate renal replacement modality is of utmost importance for patients with end stage renal disease. Previous studies showed provision of information to and free modality choice by patients to be suboptimal. Therefore, the European Kidney Patients' Federation (CEAPIR) explored

  6. An update on renal replacement therapy in Europe: ERA-EDTA Registry data from 1997 to 2006

    NARCIS (Netherlands)

    Kramer, Anneke; Stel, Vianda; Zoccali, Carmine; Heaf, James; Ansell, David; Grönhagen-Riska, Carola; Leivestad, Torbjørn; Simpson, Keith; Pálsson, Runólfur; Postorino, Maurizio; Jager, Kitty

    2009-01-01

    Background. Recent studies have indicated a stabilization in the incidence rates of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in a number of European countries. The aim of this study was to provide an update on the incidence, prevalence and outcomes of RRT in Europe over the

  7. Impact of Renal Replacement Therapy in Childhood on Long-Term Socioprofessional Outcomes: A 30-year Follow-Up Study

    NARCIS (Netherlands)

    Tjaden, Lidwien A.; Maurice-Stam, Heleen; Grootenhuis, Martha A.; Jager, Kitty J.; Groothoff, Jaap W.

    2016-01-01

    To evaluate socioprofessional outcomes after 30 years of renal replacement therapy (RRT) and explore predictors of these outcomes. The cohort comprised all Dutch patients, born before 1979, who started RRT at age <15 years in 1972-1992. Outcomes including family life, educational attainment, and

  8. Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry

    NARCIS (Netherlands)

    Vogelzang, Judith L.; van Stralen, Karlijn J.; Noordzij, Marlies; Diez, Jose Abad; Carrero, Juan J.; Couchoud, Cecile; Dekker, Friedo W.; Finne, Patrik; Fouque, Denis; Heaf, James G.; Hoitsma, Andries; Leivestad, Torbjørn; de Meester, Johan; Metcalfe, Wendy; Palsson, Runolfur; Postorino, Maurizio; Ravani, Pietro; Vanholder, Raymond; Wallner, Manfred; Wanner, Christoph; Groothoff, Jaap W.; Jager, Kitty J.

    2015-01-01

    Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to infections and malignancies in dialysis patients and kidney transplant recipients when compared with

  9. Mortality from infections and malignancies in patients treated with renal replacement therapy: data from the ERA-EDTA registry

    NARCIS (Netherlands)

    Vogelzang, J.L.; Stralen, K.J. van; Noordzij, M.; Diez, J.A.; Carrero, J.J.; Couchoud, C.; Dekker, F.W.; Finne, P.; Fouque, D.; Heaf, J.G.; Hoitsma, A.J.; Leivestad, T.; Meester, J. de; Metcalfe, W.; Palsson, R.; Postorino, M.; Ravani, P.; Vanholder, R.; Wallner, M.; Wanner, C.; Groothoff, J.W.; Jager, K.J.

    2015-01-01

    BACKGROUND: Infections and malignancies are the most common non-cardiovascular causes of death in patients on chronic renal replacement therapy (RRT). Here, we aimed to quantify the mortality risk attributed to infections and malignancies in dialysis patients and kidney transplant recipients when

  10. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury

    DEFF Research Database (Denmark)

    Karvellas, Constantine J; Farhat, Maha R; Sajjad, Imran

    2011-01-01

    Introduction: Our aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI). Methods: Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web ...

  11. Maternal use of nicotine replacement therapy during pregnancy and offspring birthweight: a study within the Danish National Birth Cohort

    DEFF Research Database (Denmark)

    Lassen, Tina H; Madsen, Mia; Skovgaard, Lene T

    2010-01-01

    Smoking is a well-established risk factor for fetal growth restriction and other adverse pregnancy outcomes, and nicotine may be one of the chemical compounds that drive these associations. Nicotine replacement therapy (NRT) is a smoking cessation aid, which can facilitate smoking cessation. It is...

  12. Book review of "The estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins

    Science.gov (United States)

    Sonnenschein, Carlos

    2008-01-01

    "The Estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

  13. Book review of The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins

    Directory of Open Access Journals (Sweden)

    Sonnenschein Carlos

    2008-01-01

    Full Text Available Abstract The Estrogen Elixir: A History of Hormone Replacement Therapy in America by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

  14. Risk of low-energy hip, wrist, and upper arm fractures among current and previous users of hormone replacement therapy

    DEFF Research Database (Denmark)

    Hundrup, Yrsa Andersen; Høidrup, Susanne; Ekholm, Ola

    2004-01-01

    To examine the effect of oestrogen alone and in combination with progestin on the risk of low-energy, hip, wrist, and upper arm fractures. Additionally, to examine to what extent previous use, duration of use as well as recency of discontinuation of hormone replacement therapy (HRT) influences...

  15. Intermittent versus continuous renal replacement therapy in acute methanol poisoning: comparison of clinical effectiveness in mass poisoning outbreaks

    Czech Academy of Sciences Publication Activity Database

    Zakharov, S.; Rulíšek, J.; Nurieva, O.; Kotíková, K.; Navrátil, Tomáš; Komarc, M.; Pelclová, D.; Hovda, K. E.

    2017-01-01

    Roč. 7, č. 1 (2017), č. článku 77. ISSN 2110-5820 Institutional support: RVO:61388955 Keywords : Mass poisoning outbreak * Continuous renal replacement therapy * Intermittent hemodialysis Subject RIV: CG - Electrochemistry OBOR OECD: Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis) Impact factor: 3.656, year: 2016

  16. Changes in arterial stiffness, carotid intima-media thickness, and epicardial fat after L-thyroxine replacement therapy in hypothyroidism.

    Science.gov (United States)

    del Busto-Mesa, Abdel; Cabrera-Rego, Julio Oscar; Carrero-Fernández, Lisván; Hernández-Roca, Cristina Victoria; González-Valdés, Jorge Luis; de la Rosa-Pazos, José Eduardo

    2015-01-01

    To assess the relationship between primary hypothyroidism and subclinical atherosclerosis and its potential changes with L-thyroxine replacement therapy. A prospective cohort study including 101 patients with primary hypothyroidism and 101 euthyroid patients as controls was conducted from July 2011 to December 2013. Clinical, anthropometrical, biochemical, and ultrasonographic parameters were assessed at baseline and after one year of L-thyroxine replacement therapy. At baseline, hypothyroid patients had significantly greater values of blood pressure, total cholesterol, VLDL cholesterol, left ventricular mass, epicardial fat, and carotid intima-media thickness as compared to controls. Total cholesterol, VLDL cholesterol, ventricular diastolic function, epicardial fat, carotid intima-media thickness, carotid local pulse wave velocity, pressure strain elastic modulus, and β arterial stiffness index showed a significant and positive correlation with TSH levels. After one year of replacement therapy, patients with hypothyroidism showed changes in total cholesterol, VLDL cholesterol, TSH, carotid intima-media thickness, and arterial stiffness parameters. Primary hypothyroidism is characterized by an increased cardiovascular risk. In these patients, L-thyroxine replacement therapy for one year is related to decreased dyslipidemia and improvement in markers of subclinical carotid atherosclerosis. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  17. Timing of renal replacement therapy and clinical outcomes in critically ill patients with severe acute kidney injury

    NARCIS (Netherlands)

    Bagshaw, Sean M.; Uchino, Shigehiko; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Oudemans-van Straaten, Heleen M.; Ronco, Claudio; Kellum, John A.; French, Craig; Mulder, John; Pinder, Mary; Roberts, Brigit; Botha, John; Mudholkar, Pradeen; Holt, Andrew; Hunt, Tamara; Honoré, Patrick Maurice; Clerbaux, Gaetan; Schetz, Miet Maria; Wilmer, Alexander; Yu, Luis; Macedo, Ettiene V.; Laranja, Sandra Maria; Rodrigues, Cassio José; Suassuna, José Hermógenes Rocco; Ruzany, Frederico; Campos, Bruno; Leblanc, Martine; Senécal, Lynne; Gibney, R. T. Noel; Johnston, Curtis; Brindley, Peter; Tan, Ian K. S.; Chen, Hui De; Wan, Li; Rokyta, Richard; Krouzecky, Ales; Neumayer, Hans-Helmut; Detlef, Kindgen-Milles; Mueller, Eckhard; Tsiora, Vicky; Sombolos, Kostas; Mustafa, Iqbal; Suranadi, Iwayan; Bar-Lavie, Yaron; Nakhoul, Farid; Ceriani, Roberto; Bortone, Franco; Zamperetti, Nereo; Pappalardo, Federico; Marino, Giovanni; Calabrese, Prospero; Monaco, Francesco; Liverani, Chiara; Clementi, Stefano; Coltrinari, Rosanna; Marini, Benedetto; Fuke, Nobuo; Miyazawa, Masaaki; Katayama, Hiroshi; Kurasako, Toshiaki; Hirasaw, Hiroyuki; Oda, Shigeto; Tanigawa, Koichi; Tanaka, Keiichi; Oudemans-van Straaten, Helena Maria; de Pont, Anne-Cornelie J. M.; Bugge, Jan Frederik; Riddervold, Fridtjov; Nilsen, Paul Age; Julsrud, Joar; Teixeira e Costa, Fernando; Marcelino, Paulo; Serra, Isabel Maria; Yaroustovsky, Mike; Grigoriyanc, Rachik; Lee, Kang Hoe; Loo, Shi; Singh, Kulgit; Barrachina, Ferran; Llorens, Julio; Sanchez-Izquierdo-Riera, Jose Angel; Toral-Vazquez, Darío; Wizelius, Ivar; Hermansson, Dan; Gaspert, Tomislav; Maggiorini, Marco; Davenport, Andrew; Lombardi, Raúl; Llopart, Teresita; Venkataraman, Ramesh; Kellum, John; Murray, Patrick; Trevino, Sharon; Benjamin, Ernest; Hufanda, Jerry; Paganini, Emil; Warnock, David; Guirguis, Nabil

    2009-01-01

    The aim of this study is to evaluate the relationship between timing of renal replacement therapy (RRT) in severe acute kidney injury and clinical outcomes. This was a prospective multicenter observational study conducted at 54 intensive care units (ICUs) in 23 countries enrolling 1238 patients.

  18. Determinants of durability of first-line antiretroviral therapy regimen and time from first-line failure to second-line antiretroviral therapy initiation

    DEFF Research Database (Denmark)

    Desmonde, Sophie; Eboua, François T; Malateste, Karen

    2015-01-01

    BACKGROUND: We described reasons for switching to second-line antiretroviral treatment (ART) and time to switch in HIV-infected children failing first-line ART in West Africa. METHODS: We included all children aged 15 years or less, starting ART (at least three drugs) in the paediatric Ie...... post-ART initiation, 188 (7%) had switched to second-line. The most frequent reasons were drug stock outs (20%), toxicity (18%), treatment failure (16%) and poor adherence (8%). Over the 24-month follow-up period, 322 (12%) children failed first-line ART after a median time of 7 months...... rare and switches after an immunological failure were insufficient. These gaps reveal that it is crucial to advocate for both sustainable access to first-line and alternative regimens to provide adequate roll-out of paediatric ART programmes....

  19. Timing of renal replacement therapy after cardiac surgery: a retrospective multicenter Spanish cohort study.

    Science.gov (United States)

    García-Fernández, Nuria; Pérez-Valdivieso, José Ramón; Bes-Rastrollo, Maira; Vives, Marc; Lavilla, Javier; Herreros, Jesús; Monedero, Pablo

    2011-01-01

    The optimal time to initiate renal replacement therapy (RRT) in cardiac surgery-associated acute kidney injury (CSA-AKI) is unknown. Evidence suggests that the early use of RRT in critically ill patients is associated with improved outcomes. We studied the effects of time to initiation of RRT on outcome in patients with CSA-AKI. This was a retrospective observational multicenter study (24 Spanish hospitals). We analyzed data on 203 patients who required RRT after cardiac surgery in 2007. The cohort was divided into 2 groups based on the time at which RRT was initiated: in the early RRT group, therapy was initiated within the first 3 days after cardiac surgery; in the late group, RRT was begun after the 3rd day. Multivariate nonconditional logistic and linear regression models were used to adjust for potential confounders. In-hospital mortality was significantly higher in the late RRT group compared with early RRT patients (80.4 vs. 53.2%; p < 0.001; adjusted odds ratio of 4.1, 95% CI: 1.6-10.0). Also, patients in the late RRT group had longer adjusted hospital stays by 11.6 days (95% CI: 1.4-21.9) and higher adjusted percentage increases in creatinine at discharge compared with baseline by 67.7% (95% CI: 28.5-106.4). Patients who undergo early initiation of RRT after CSA-AKI have improved survival rates and renal function at discharge and decreased lengths of hospital stay. Copyright © 2011 S. Karger AG, Basel.

  20. Comparison of circuit patency and exchange rates between 2 different continuous renal replacement therapy machines.

    Science.gov (United States)

    Razavi, Seyed Amirhossein; Still, Mary D; White, Sharon J; Buchman, Timothy G; Connor, Michael J

    2014-04-01

    Continuous renal replacement therapy (CRRT) is an important tool in the care of critically ill patients. However, the impact of a specific CRRT machine type on the successful delivery of CRRT is unclear. The purpose of this study was to evaluate the effectiveness of CRRT delivery with an intensive care unit (ICU) bedside nurse delivery model for CRRT while comparing circuit patency and circuit exchange rates in 2 Food and Drug Administration-approved CRRT devices. This article presents the data comparing circuit exchange rates for 2 different CRRT machines. A group of ICU nurses were selected to undergo expanded training in CRRT operation and empowered to deliver all aspects of CRRT. The ICU nurses then provided all aspects of CRRT on 2 Food and Drug Administration-approved CRRT devices for 6 months. Each device was used exclusively in the designated ICU for a 2-week run-in period followed by 3-month data collection period. The primary end point for the study was the differences in average number of filter exchanges per day during each CRRT event. A total of 45 unique patients who underwent 64 separate CRRT treatment periods were included. Four CRRT events were excluded (see text for details). Twenty-eight CRRT events occurred in the NxStage System One arm (NxStage Medical, Lawrence, Mass) and 32 events in the Gambro Prismaflex arm (Gambro Renal Products, Boulder, Colo). Average (SD) filter exchanges per day was 0.443 (0.60) for the NxStage System One machine and 0.553 (0.65) for Gambro Prismaflex machine (P = .09). There was no demonstrable difference in circuit patency as defined by the rate of filter exchanges per day of CRRT therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Fabry disease under enzyme replacement therapy-new insights in efficacy of different dosages.

    Science.gov (United States)

    Krämer, Johannes; Lenders, Malte; Canaan-Kühl, Sima; Nordbeck, Peter; Üçeyler, Nurcan; Blaschke, Daniela; Duning, Thomas; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Gottschling, Timo; Störk, Stefan; Wanner, Christoph; Sommer, Claudia; Brand, Eva; Weidemann, Frank

    2017-11-23

    Fabry patients on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in estimated glomerular filtration rate (eGFR) and an increase of the Mainz Severity Score Index. In this prospective observational study, we assessed end-organ damage and clinical symptoms in 112 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, who were (i) non-randomly assigned to continue this treatment regime (regular-dose group, n = 37); (ii) received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n = 38); or (iii) were re-switched to agalsidase-beta after receiving agalsidase-alfa for at least 12 months (re-switch group, n = 37) with a median follow-up of 53 (38-57) months. eGFR of patients in the regular-dose group remained stable. Patients in the switch group showed an annual eGFR loss of - 4.6  ±  9.1 mL/min/1.73 m2 (P risk 0.42; 95% confidence interval 0.19-0.93; P = 0.02). Lyso-Gb3 remained stable in the switch (P = 0.97) and the regular-dose (P = 0.48) groups, but decreased in the re-switch group after change of the therapy regimen (P < 0.05). After switch to agalsidase-alfa, Fabry patients experienced a continuous decline in eGFR, while this decline was attenuated in patients who were re-switched to agalsidase-beta. Decreasing lyso-Gb3 levels may indicate a better treatment response in the latter group. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  2. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use

    Directory of Open Access Journals (Sweden)

    J Abram McBride

    2016-01-01

    Full Text Available The use of testosterone replacement therapy (TRT for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.

  3. Pancreatic enzyme replacement therapy in cystic fibrosis: dose, variability and coefficient of fat absorption.

    Science.gov (United States)

    Calvo-Lerma, Joaquim; Martínez-Barona, Sandra; Masip, Etna; Fornés, Victoria; Ribes-Koninckx, Carmen

    2017-10-01

    Pancreatic enzyme replacement therapy (PERT) remains a backbone in the nutritional treatment of cystic fibrosis. Currently, there is a lack of an evidence-based tool that allows dose adjustment. To date, no studies have found an association between PERT dose and fat absorption. Therefore, the aim of the study was to assess the influence of both the PERT dose and the variability in this dose on the coefficient of fat absorption (CFA). This is a retrospective longitudinal study of 16 pediatric patients (192 food records) with three consecutive visits to the hospital over a twelve-month period. Dietary fat intake and PERT were assessed via a four-day food record and fat content in stools was determined by means of a three-day stool sample collection. A beta regression model was built to explain the association between the CFA and the interaction between the PERT dose (lipase units [LU]/g dietary fat) and the variability in the PERT dose (standard deviation [SD]). The coefficient of fat absorption increased with the PERT dose when the variability in the dose was low. In contrast, even at the highest PERT dose values, the CFA decreased when the variability was high. The confidence interval suggested an association, although the analysis was not statistically significant. The variability in the PERT dose adjustment should be taken into consideration when performing studies on PERT efficiency. A clinical goal should be the maintenance of a constant PERT dose rather than trying to obtain an optimal value.

  4. We Offer Renal Replacement Therapy to Patients Who Are Not Benefitted by It.

    Science.gov (United States)

    Holley, Jean L

    2016-07-01

    Nephrologists offer renal replacement therapy (RRT) to patients who are unlikely to benefit in part because of our discomfort discussing goals of care in the setting of an uncertain prognosis for a given individual. Permanent neurological impairment, terminal illness (life expectancy <6 months), medical conditions precluding the safe delivery of dialysis, elderly patients with poor prognosis, and those who begin "early" RRT are categories of patients for whom dialysis may not be beneficial. Successful use of time-limited trials of dialysis may reduce the number of patients who are started on RRT without significant benefit. However, clear achievable milestones and goals need to be incorporated into plans for time-limited trials to ensure that continuing RRT beyond the trial period is appropriate. The lack of information on outcomes and symptom management using a "palliative approach" to dialysis suggests this should not be a clinical option until additional study is done and efficacy data available. Clinical practice guidelines are available to assist nephrologists in the appropriate withholding of RRT. © 2016 Wiley Periodicals, Inc.

  5. INFLUENCES OF HORMONE REPLACEMENT THERAPY ON OLFACTORY AND COGNITIVE FUNCTION IN THE MENOPAUSE

    Science.gov (United States)

    Doty, Richard L.; Tourbier, Isabelle; Ng, Victoria; Neff, Jessica; Armstrong, Deborah; Battistini, Michelle; Sammel, Mary D.; Gettes, David; Evans, Dwight L.; Mirza, Natasha; Moberg, Paul J.; Connolly, Tim; Sondheimer, Steven J.

    2015-01-01

    Olfactory dysfunction can be an early sign of Alzheimer’s disease (AD). Since hormone replacement therapy (HRT) may protect against developing AD in postmenopausal women, the question arises as to whether it also protects against olfactory dysfunction in such women. Three olfactory and 12 neurocognitive tests were administered to 432 healthy postmenopausal women with varied HRT histories. Serum levels of reproductive hormones were obtained for all subjects; APOE-ε4 haplotype was determined for 77. National Adult Reading Test and Odor Memory/Discrimination Test (OMT) scores were positively influenced by HRT. Odor identification and OMT test scores were lower for women who scored poorly on a delayed recall test, a surrogate for mild cognitive impairment. WAIS-R NI Spatial Span Backwards Test scores were higher in women receiving estrogen plus progestin HRT and directly correlated with serum testosterone levels, the latter implying a positive effect of testosterone on spatial memory. APOE-ε4 was associated with poorer odor threshold test scores. These data suggest that HRT positively influences a limited number of olfactory and cognitive measures in the menopause. PMID:25850354

  6. The effects of progesterone selection on psychological symptoms in hormone replacement therapy.

    Science.gov (United States)

    Caglayan, Emel Kiyak; Kara, Mustafa; Etiz, Sema; Kumru, Pinar; Aka, Nurettin; Kose, Gultekin

    2014-01-01

    The aim of this study is to evaluate the effects of hormone replacement therapy using dienogest and medroxyprogesterone acetate on psychological symptoms in perimenopausal and postmenopausal women. A total of 73 patients who sought treatment at the menopause units of the authors' gynecology and obstetrics clinics between of November 2003 and October 2004 complaining of vasomotor symptoms were included in the study prospectively. The cases were divided into two groups: Group I (37 patients) was given 2 mg estradiol valerate and 2 mg dienogest, and Group II (36 patients) was given 2 mg estradiol valerate and 10 mg medroxyprogesterone acetate. The groups' results in months 0 and 6 were compared through the evaluation of vasomotor and psychological symptom levels. No significant difference was found between the groups when the initial levels of vasomotor and psychological symptom subtypes were compared (p = 0.16). It was observed that all the psychological symptoms decreased in the 6th month in the group using dienogest in comparison with the initial situation, and that psychological symptoms increased in the group using medroxyprogesterone acetate in the evaluation performed in the 6th month compared with the initial levels. It was also found out that there was a statistically significant difference between the two groups when compared in terms of these symptoms (p psychological situation and sleep, it was observed that the use of medroxyprogesterone acetate (MPA) worsens the general psychological situation.

  7. CRRTnet: a prospective, multi-national, observational study of continuous renal replacement therapy practices.

    Science.gov (United States)

    Heung, Michael; Bagshaw, Sean M; House, Andrew A; Juncos, Luis A; Piazza, Robin; Goldstein, Stuart L

    2017-07-06

    Continuous renal replacement therapy (CRRT) is the recommended modality of dialysis for critically ill patients with hemodynamic instability. Yet there remains significant variability in how CRRT is prescribed and delivered, and limited evidence-basis to guide practice. This is a prospective, multi-center observational study of patients undergoing CRRT. Initial enrollment phase will occur at 4 academic medical centers in North America over 5 years, with a target enrollment of 2000 patients. All adult patients (18-89 years of age) receiving CRRT will be eligible for inclusion; patients who undergo CRRT for less than 24 h will be excluded from analysis. Data collection will include patient characteristics at baseline and at time of CRRT initiation; details of CRRT prescription and delivery, including machine-generated treatment data; and patient outcomes. The goal of this study is to establish a large comprehensive registry of critically ill adults receiving CRRT. Specific aims include describing variations in CRRT prescription and delivery across quality domains; validating quality measures for CRRT care by correlating processes and outcomes; and establishing a large registry for use in quality improvement and benchmarking efforts. For initial analyses, some particular areas of interest are anticoagulation protocols; approach to fluid overload; CRRT-related workload; and patient safety. Registered on ClinicalTrials.gov 1/10/2014: NCT02034448.

  8. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial.

    Science.gov (United States)

    Bartels, Rosalie H; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A; Mponda, John S; Muller Kobold, Anneke C; Bandsma, Robert H; Boele van Hensbroek, Michael; Voskuijl, Wieger P

    2017-11-01

    To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central Hospital in Malawi. All children received standard care; the intervention group also received PERT for 28 days. Children treated with PERT for 28 days did not gain more weight than controls (13.7 ± 9.0% in controls vs 15.3 ± 11.3% in PERT; P = .56). Exocrine pancreatic insufficiency was present in 83.1% of patients on admission and fecal elastase-1 levels increased during hospitalization mostly seen in children with nonedematous severe acute malnutrition (P Children who died had low fecal fatty acid split ratios at admission. Exocrine pancreatic insufficiency was not improved by PERT, but children receiving PERT were more likely to be discharged with every passing day (P = .02) compared with controls. PERT does not improve weight gain in severely malnourished children but does increase the rate of hospital discharge. Mortality was lower in patients on PERT, a finding that needs to be investigated in a larger cohort with stratification for edematous and nonedematous malnutrition. Mortality in severe acute malnutrition is associated with markers of poor digestive function. ISRCTN.com: 57423639. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Replacement therapy for bleeding episodes in factor VII deficiency. A prospective evaluation.

    Science.gov (United States)

    Mariani, Guglielmo; Napolitano, Mariasanta; Dolce, Alberto; Pérez Garrido, Rosario; Batorova, Angelika; Karimi, Mehran; Platokouki, Helen; Auerswald, Günter; Bertrand, Anne-Marie; Di Minno, Giovanni; Schved, Jean F; Bjerre, Jens; Ingerslev, Jorgen; Sørensen, Benny; Ruiz-Saez, Arlette

    2013-02-01

    Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one post-rFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal.

  10. The cost and effectiveness of surfactant replacement therapy at Johannesburg Hospital, November 1991-December 1992.

    Science.gov (United States)

    Davies, V A; Ballot, D E; Rothberg, A D

    1995-07-01

    To assess the impact of surfactant replacement therapy (SRT) on the outcome of hyaline membrane disease (HMD) and to assess the cost implications of a policy of selective administration of artificial surfactant. The short-term outcome of 103 newborns ventilated for HMD (61 selected for SRT according to initial and/or ongoing oxygen requirements) was compared with that of a historical control group of 173 infants ventilated for HMD before the introduction of SRT. Mortality and morbidity of HMD including death, bronchopulmonary dysplasia, pneumothorax, pulmonary haemorrhage, patent ductus arteriosus and intraventricular haemorrhage. There were significant demographic differences between the treatment and control groups (black patients 74% v. 28%, P cost of treating a patient ventilated for HMD. The selective use of SRT had the effect of converting severe disease into moderate disease rather than achieving maximal benefit in all cases of HMD through routine use of the product. A policy of restricting use may result in cost savings where resources are limited.

  11. Impact of testosterone replacement therapy on thromboembolism, heart disease and obstructive sleep apnoea in men.

    Science.gov (United States)

    Cole, Alexander P; Hanske, Julian; Jiang, Wei; Kwon, Nicollette K; Lipsitz, Stuart R; Kathrins, Martin; Learn, Peter A; Sun, Maxine; Haider, Adil H; Basaria, Shehzad; Trinh, Quoc-Dien

    2018-05-01

    To assess the association of testosterone replacement therapy (TRT) with thromboembolism, cardiovascular disease (stroke, coronary artery disease and heart failure) and obstructive sleep apnoea (OSA). A cohort of 3 422 male US military service members, retirees and their dependents, aged 40-64 years, was identified, who were prescribed TRT between 2006 and 2010 for low testosterone levels. The men in this cohort were matched on a 1:1 basis for age and comorbidities to men without a prescription for TRT. Event-free survival and rates of thromboembolism, cardiovascular events and OSA were compared between men using TRT and the control group, with a median follow-up of 17 months. There was no difference in event-free survival with regard to thromboembolism (P = 0.239). Relative to controls, men using TRT had improved cardiovascular event-free survival (P = 0.004), mainly as a result of lower incidence of coronary artery disease (P = 0.008). The risk of OSA was higher in TRT users (2-year risk 16.5% [95% confidence interval 15.1-18.1] in the TRT group vs 12.7% [11.4-14.1] in the control group. This study adds to growing evidence that the cardiovascular risk associated with TRT may be lower than once feared. The elevated risk of OSA in men using TRT is noteworthy. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

  12. Simulating continuous renal replacement therapy: usefulness of a new simulator device.

    Science.gov (United States)

    Mencía, Santiago; López, Manuel; López-Herce, Jesús; Ferrero, Luis; Rodríguez-Núñez, Antonio

    2014-03-01

    Simulation allows the training of life-support procedures without patient risk. We analyzed the performance and usefulness of a new device that makes feasible the external control of continuous renal replacement therapy (CRRT) machines in order to realistically generate clinical conditions and problems in simulated patients. A simple mechanical device was designed according to training needs and then hand made. This device permits the control of all monitorable pressures and therefore allows simulation of a range of clinical situations and eventual complications that might occur in real patients. We tested its performance in vitro and then during 16 high-fidelity patient-simulation scenarios included in the program of pediatric CRRT courses. Student and teacher satisfaction was assessed through an anonymous survey. Quick, accurate, real-time monitor of pressure changes, concordant with the usual clinical problems to be simulated (catheter complications, filter coagulation, inadequate CRRT device settings), were easily achieved with the new device. Instructors rated the device as user friendly and well adapted to the reality being simulated. During scenarios, students were not aware of the simulator and considered that simulated clinical conditions were realistic. Our device may be very useful for training healthcare professionals in CRRT management, thus avoiding risk to patients.

  13. In vivo genome editing of the albumin locus as a platform for protein replacement therapy

    Science.gov (United States)

    Sharma, Rajiv; Anguela, Xavier M.; Doyon, Yannick; Wechsler, Thomas; DeKelver, Russell C.; Sproul, Scott; Paschon, David E.; Miller, Jeffrey C.; Davidson, Robert J.; Shivak, David; Zhou, Shangzhen; Rieders, Julianne; Gregory, Philip D.; Holmes, Michael C.; Rebar, Edward J.

    2015-01-01

    Site-specific genome editing provides a promising approach for achieving long-term, stable therapeutic gene expression. Genome editing has been successfully applied in a variety of preclinical models, generally focused on targeting the diseased locus itself; however, limited targeting efficiency or insufficient expression from the endogenous promoter may impede the translation of these approaches, particularly if the desired editing event does not confer a selective growth advantage. Here we report a general strategy for liver-directed protein replacement therapies that addresses these issues: zinc finger nuclease (ZFN) –mediated site-specific integration of therapeutic transgenes within the albumin gene. By using adeno-associated viral (AAV) vector delivery in vivo, we achieved long-term expression of human factors VIII and IX (hFVIII and hFIX) in mouse models of hemophilia A and B at therapeutic levels. By using the same targeting reagents in wild-type mice, lysosomal enzymes were expressed that are deficient in Fabry and Gaucher diseases and in Hurler and Hunter syndromes. The establishment of a universal nuclease-based platform for secreted protein production would represent a critical advance in the development of safe, permanent, and functional cures for diverse genetic and nongenetic diseases. PMID:26297739

  14. The ocular benefits of estrogen replacement therapy: a population-based study in postmenopausal Korean women.

    Directory of Open Access Journals (Sweden)

    Kyung-Sun Na

    Full Text Available PURPOSE: To elucidate the prevalence of cataract, glaucoma, pterygia, and diabetic retinopathy among Korean postmenopausal women with or without estrogen replacement therapy (ERT. METHODS: A cross-sectional, nationally representative sample from the 4th Korea National Health and Nutrition Examination Survey (KNHANES IV (2007-2009 was used. Participants were interviewed for the determination of socioeconomic and gynecologic factors. Each woman also underwent an ophthalmologic examination and provided a blood sample for risk factor assessment. RESULTS: Of 3968 postmenopausal women enrolled, 3390 had never received estrogen, and 578 were undergoing estrogen treatment. After adjusting for age, diabetes, hypertension, high cholesterol levels, and high low-density lipoprotein levels, the prevalence of anterior polar cataract, retinal nerve fiber layer (RNFL defect, and flesh pterygium was higher in the non-ERT group (OR, 3.24; 95% CI, 1.12-9.35, OR 1.70; 95% CI, 1.04-2.78, OR 3.725; 95% CI, 1.21-11.45, respectively. Further, the prevalence of atrophic pterygium was lower in the non-ERT group compared to that in the ERT group (OR, 0.21, 95% CI, 0.07-0.63. CONCLUSIONS: These data suggest that ERT has a protective effect against the development of anterior polar cataract, flesh pterygium, and RNFL defect.

  15. Empirical relationships among oliguria, creatinine, mortality, and renal replacement therapy in the critically ill.

    Science.gov (United States)

    Mandelbaum, Tal; Lee, Joon; Scott, Daniel J; Mark, Roger G; Malhotra, Atul; Howell, Michael D; Talmor, Daniel

    2013-03-01

    The observation periods and thresholds of serum creatinine and urine output defined in the Acute Kidney Injury Network (AKIN) criteria were not empirically derived. By continuously varying creatinine/urine output thresholds as well as the observation period, we sought to investigate the empirical relationships among creatinine, oliguria, in-hospital mortality, and receipt of renal replacement therapy (RRT). Using a high-resolution database (Multiparameter Intelligent Monitoring in Intensive Care II), we extracted data from 17,227 critically ill patients with an in-hospital mortality rate of 10.9 %. The 14,526 patients had urine output measurements. Various combinations of creatinine/urine output thresholds and observation periods were investigated by building multivariate logistic regression models for in-hospital mortality and RRT predictions. For creatinine, both absolute and percentage increases were analyzed. To visualize the dependence of adjusted mortality and RRT rate on creatinine, the urine output, and the observation period, we generated contour plots. Mortality risk was high when absolute creatinine increase was high regardless of the observation period, when percentage creatinine increase was high and the observation period was long, and when oliguria was sustained for a long period of time. Similar contour patterns emerged for RRT. The variability in predictive accuracy was small across different combinations of thresholds and observation periods. The contour plots presented in this article complement the AKIN definition. A multi-center study should confirm the universal validity of the results presented in this article.

  16. Update on Renal Replacement Therapy: Implantable Artificial Devices and Bioengineered Organs.

    Science.gov (United States)

    Attanasio, Chiara; Latancia, Marcela T; Otterbein, Leo E; Netti, Paolo A

    2016-08-01

    Recent advances in the fields of artificial organs and regenerative medicine are now joining forces in the areas of organ transplantation and bioengineering to solve continued challenges for patients with end-stage renal disease. The waiting lists for those needing a transplant continue to exceed demand. Dialysis, while effective, brings different challenges, including quality of life and susceptibility to infection. Unfortunately, the majority of research outputs are far from delivering satisfactory solutions. Current efforts are focused on providing a self-standing device able to recapitulate kidney function. In this review, we focus on two remarkable innovations that may offer significant clinical impact in the field of renal replacement therapy: the implantable artificial renal assist device (RAD) and the transplantable bioengineered kidney. The artificial RAD strategy utilizes micromachining techniques to fabricate a biohybrid system able to mimic renal morphology and function. The current trend in kidney bioengineering exploits the structure of the native organ to produce a kidney that is ready to be transplanted. Although these two systems stem from different technological approaches, they are both designed to be implantable, long lasting, and free standing to allow patients with kidney failure to be autonomous. However, for both of them, there are relevant issues that must be addressed before translation into clinical use and these are discussed in this review.

  17. Gender-specific and gonadectomy-specific effects upon swim analgesia: role of steroid replacement therapy.

    Science.gov (United States)

    Romero, M T; Cooper, M L; Komisaruk, B R; Bodnar, R J

    1988-01-01

    Both gender-specific and gonadectomy-specific effects have been observed for the analgesic responses following continuous and intermittent cold-water swims (CCWS and ICWS respectively): female rats display significantly less analgesia than males, and gonadectomized rats display significantly less analgesia than sham-operated controls. The present study evaluated the effects of steroid replacement therapy with testosterone propionate (TP: 2 mg/kg, SC) upon CCWS and ICWS analgesia on the tail-flick and jump tests and hypothermia in sham-operated or gonadectomized male and female rats. Thirty days following surgery, rats received either no treatment, a sesame oil vehicle or TP for 14 days prior to, and then during testing. Relative to the no treatment condition, repeated vehicle injections in sham-operated rats eliminated the gender-specific, but did not affect the gonadectomy-specific effects upon CCWS and ICWS analgesia. TP reversed the deficits in CCWS and ICWS analgesia observed in both castrated and ovariectomized rats on both pain tests. TP only potentiated CCWS analgesia in sham-operated males on the tail-flick test. TP potentiated CCWS and ICWS hypothermia in gonadectomized rats and in male sham-operated rats. These data indicate that gonadal steroids play a major modulatory role in the etiology of swim analgesia, and that the observed gender effects are sensitive to possible adaptational variables.

  18. Cardiovascular risk assessment with oxidised LDL measurement in postmenopausal women receiving intranasal estrogen replacement therapy.

    Science.gov (United States)

    Kurdoglu, Mertihan; Yildirim, Mulazim; Kurdoglu, Zehra; Erdem, Ahmet; Erdem, Mehmet; Bilgihan, Ayse; Goktas, Bulent

    2011-08-01

    To investigate the effect of intranasal estrogen replacement therapy administered to postmenopausal women alone or in combination with progesterone on markers of cardiovascular risk. The study was conducted with 44 voluntary postmenopausal women. In group I (n = 15), the patients were treated with only intranasal estradiol (300 μg/day estradiol hemihydrate). In group II (n = 11), the patients received cyclic progesterone (200 mg/day micronized progesterone) for 12 days in each cycle in addition to continuous intranasal estradiol. Group III (n = 18) was the controls. Serum lipid profiles, oxidised low-density lipoprotein (LDL) and other markers of cardiovascular risk were assessed at baseline and at the 3rd month of the treatment. Lipid profile, LDL apolipoprotein B, lipoprotein a, homocysteine, oxidised LDL values and oxidised LDL/LDL cholesterol ratio were not observed to change after 3 months compared to baseline values within each group (p > 0.016). In comparison to changes between the groups after the treatment, only oxidised LDL levels and oxidised LDL/LDL cholesterol ratios of group II were increased compared to control group (p < 0.05). Intranasal estradiol alone did not appear to have an effect on markers of cardiovascular risk in healthy postmenopausal women. However, the addition of cyclic oral micronized progesterone to intranasal estradiol influenced the markers of cardiovascular risk negatively in comparison to non-users in healthy postmenopausal women.

  19. [Long-term outcomes of children treated with continuous renal replacement therapy].

    Science.gov (United States)

    Almarza, S; Bialobrzeska, K; Casellas, M M; Santiago, M J; López-Herce, J; Toledo, B; Carrillo, Á

    2015-12-01

    The objective of this study is to analyze long-term outcomes and kidney function in children requiring continuous renal replacement therapy (CRRT) after an acute kidney injury episode. A retrospective observational study was performed using a prospective database of 128 patients who required CRRT admitted to the pediatric intensive care unit between years 2006 and 2012. The subsequent outcomes were assessed in those surviving at hospital discharge. Of the 128 children who required RRT in the pediatric intensive care unit, 71 survived at hospital discharge (54.4%), of whom 66 (92.9%) were followed up. Three patients had chronic renal failure prior to admission to the NICU. Of the 63 remaining patients, 6 had prolonged or relapses of renal function disturbances, but only one patient with atypical Hemolytic Uremic Syndrome developed end-stage renal failure. The rest had normal kidney function at the last check-up. Most of surviving children that required CRRT have a positive outcome later on, presenting low mortality rates and recovery of kidney function in the medium term. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  20. A systematic review of possible serious adverse health effects of nicotine replacement therapy.

    Science.gov (United States)

    Lee, Peter N; Fariss, Marc W

    2017-04-01

    We conducted a systematic literature review to identify and critically evaluate studies of serious adverse health effects (SAHEs) in humans using nicotine replacement therapy (NRT) products. Serious adverse health effects refer to adverse events, leading to substantial disruption of the ability to conduct normal life functions. Strength of evidence evaluations and conclusions were also determined for the identified SAHEs. We evaluated 34 epidemiological studies and clinical trials, relating NRT use to cancer, reproduction/development, CVD, stroke and/or other SAHEs in patients, and four meta-analyses on effects in healthy populations. The overall evidence suffers from many limitations, the most significant being the short-term exposure (≤12 weeks) and follow-up to NRT product use in most of the studies, the common failure to account for changes in smoking behaviour following NRT use, and the sparse information on SAHEs by type of NRT product used. The only SAHE from NRT exposure we identified was an increase in respiratory congenital abnormalities reported in one study. Limited evidence indicated a lack of effect between NRT exposure and SAHEs for CVD and various reproduction/developmental endpoints. For cancer, stroke and other SAHEs, the evidence was inadequate to demonstrate any association with NRT use. Our conclusions agree with recent statements from authoritative bodies.

  1. Enzyme replacement therapy prevents dental defects in a model of hypophosphatasia.

    Science.gov (United States)

    McKee, M D; Nakano, Y; Masica, D L; Gray, J J; Lemire, I; Heft, R; Whyte, M P; Crine, P; Millán, J L

    2011-04-01

    Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2(-/-)) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B(6)-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2(-/-) mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD(10)). sALP-FcD(10) prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin--a marker of acellular cementum--was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2(-/-) mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life--where the majority of tooth root development occurs, including acellular cementum formation--could prevent the accelerated tooth loss seen in individuals with HPP.

  2. Hormone Replacement Therapy and Risk of Breast Cancer in Korean Women: A Quantitative Systematic Review

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    Jong-Myon Bae

    2015-09-01

    Full Text Available Objectives: The epidemiological characteristics of breast cancer incidence by age group in Korean women are unique. This systematic review aimed to investigate the association between hormone replacement therapy (HRT and breast cancer risk in Korean women. Methods: We searched electronic databases such as KoreaMed, KMbase, KISS, and RISS4U as well as PubMed for publications on Korean breast cancer patients. We also conducted manual searching based on references and citations in potential papers. All of the analytically epidemiologic studies that obtained individual data on HRT exposure and breast cancer occurrence in Korean women were selected. We restricted the inclusion of case-control studies to those that included age-matched controls. Estimates of summary odds ratio (SOR with 95% confidence intervals (CIs were calculated using random effect models. Results: One cohort and five case-control studies were finally selected. Based on the heterogeneity that existed among the six studies (I-squared=70.2%, a random effect model was applied. The summary effect size of HRT history from the six articles indicated no statistical significance in breast cancer risk (SOR, 0.983; 95% CI, 0.620 to 1.556. Conclusions: These facts support no significant effect of HRT history in the risk of breast cancer in Korean women. It is necessary to conduct a pooled analysis.

  3. Prevalence of hormone replacement therapy in a sample of middle-aged women

    DEFF Research Database (Denmark)

    Pedersen, S H; Jeune, B

    1988-01-01

    A survey based on a postal questionnaire sent to a random sample of Danish women aged 40-59 yr living on the island of Fünen (n = 401, response rate = 79%) revealed that the overall prevalence of the use of hormone replacement therapy (HRT) was 16%, the highest rate being in the 50-54 age group (21......%). Among post-menopausal women the rate was 21% and it was highest of all (37%) in those who had undergone an artificial menopause. The median age at the start of treatment was 44.3 yr among the artificial menopause and 48.9 yr among the natural menopause subjects. About half of the women were treated...... with natural oestrogen alone and over a third with cyclic natural oestrogen in combination with progestogens. Almost one-third of the women had consulted their doctor about climacteric complaints and two-thirds of these were current or past users of HRT. The women had ambiguous feelings towards HRT...

  4. Are women who are taking Hormone Replacement Therapy doing so with informed consent?

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, E.M

    2003-11-01

    Just over half the population in Britain today are women, and each is likely to spend over one-third of her life in the post menopausal state. The number of post-war 'Baby Boomers' is having a profound effect on interest in the menopause and increasing awareness of Hormone Replacement Therapy (HRT). Patients are no longer prepared to passively accept the advice of their doctor, and should make an informed decision over its use, after having been given up-to-date information. Some of the claimed benefits of taking HRT are not fully proven and the risks and disadvantages must be considered, notably the increased risk of breast cancer and the effect on the sensitivity and specificity of the mammographic image. The long-term benefits are still uncertain. Available information needs to be comprehensible, credible, and up to date. Whether to initiate the taking of HRT is one of the most important decisions a woman entering mid-life will make, so she needs to be given information she can understand in order to make an informed decision. HRT and informed consent are topics relevant to mammography, which was the rationale in writing this paper as part of a Post Graduate Certificate in Mammographic Studies.

  5. Guidelines to start enzyme replacement therapy in classic Fabry Disease patients in Latin America

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    Juan Manuel Politei

    2017-01-01

    Full Text Available Introduction: Fabry disease is a rare inherited X-linked disorder resulting from the absence or deficient activity of the α-galactosidase A enzyme. Objetive: To provide the first guideline on the best time to start enzyme replacement therapy to treat classic Fabry disease, based on the knowledge and experience of experts from ten Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Chile, Ecuador, Mexico, Peru, Uruguay and Venezuela. Methods: The project coordinator designed a survey based on the criteria for starting the treatment which are established in different international guidelines published to date. This document was later sent to all the participants for its evaluation. Results: Fifty experts responded to the survey, whose criteria was divided into 5 sections according to specialty, and they arrived at a consensus. Discussion: The criteria for an early treatment were defined given the growing evidence of a better response and prognosis associated with it. Conclusion: We believe that the importance of this guideline relies on the participation of experts from ten Latin American countries. However, as it deals with a systemic disease whose physiopathological mechanisms and complications are still being described, some manifestations have not been included in the criteria, making it necessary to revise this guideline in order to report any changes that may arise in the future.

  6. Association between hormone replacement therapy and dementia: is it time to forget?

    Science.gov (United States)

    Almeida, Osvaldo P; Flicker, Leon

    2005-06-01

    The results of in vitro and animal studies provide a strong rationale for the use of hormone replacement therapy (HRT) to prevent dementia and Alzheimer's disease (AD). In humans, the results of 16 observational studies are consistent with the hypothesis that estrogen use reduces the risk of AD by 10 to 60%. However, women who are prescribed HRT are less likely to have hypertension, diabetes and history of stroke than nonusers. As all of these factors have been associated with increased risk of dementia (including AD), this "prescription bias" may have a significant impact on the results of observational studies. Randomized trials are designed with the aim of avoiding many of the potential biases and confounding (measured or unmeasured) of observational studies. The results of the Women's Health Initiative Memory Study (WHIMS) indicate that HRT (estrogen plus progestin or estrogen alone) increases the risk of dementia (hazard ratio, HR = 1.8, 95% CI = 1.2-2.6). Taking into account the results of the WHIMS and the adverse health events associated with the use of estrogen plus progestin or estrogen alone, we conclude that HRT cannot be recommended as a safe and effective strategy to prevent dementia.

  7. Effect of regional citrate anticoagulation on critical patients with continuous renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Li-Li You

    2016-12-01

    Full Text Available Objective: To investigate the efficacy and safety of regional citrate anticoagulation (RCA in continuous renal replacement therapy (CRRT for critical patients. Methods: A total of 83 critical patients need CRRT in the intensive care units of our hospital from July 2012 to June 2016 were recruited in the study, and the patients were divided into two groups randomly, the patients in observation group received the RCA treatment, and the patients in control group received traditional low molecular heparin anticoagulation. The difference of safety indicators, biochemical indicators, extracorporeal circulation blood coagulation condition and complications in patients were determined between two groups. Results: Compared with control group, the patients in observation group had an elevated level of iCa2+, the level of chloride ion reduced, the use time of filter increased, the bleeding cases reduced, the concentrations of urea nitrogen, creatinine TNF-α , IL-1β, IL-8 and NO were all significantly downregulated, the data have a significant difference (P < 0.05. Conclusions: RCA is a safe and effective method for CRRT in patients with a high risk of bleeding.

  8. Differences and inequalities in relation to access to renal replacement therapy in the BRICS countries.

    Science.gov (United States)

    Ferraz, Fábio Humberto Ribeiro Paes; Rodrigues, Cibele Isaac Saad; Gatto, Giuseppe Cesare; Sá, Natan Monsores de

    2017-07-01

    End-stage renal disease (ESRD) is an important public health problem, especially in developing countries due to the high level of economic resources needed to maintain patients in the different programs that make up renal replacement therapy (RRT). To analyze the differences and inequalities involved in access to RRT in the BRICS countries (Brazil, Russian Federation, India, China and South Africa). This is an applied, descriptive, cross-sectional, quantitative and qualitative study, with documentary analysis and a literature review. The sources of data were from national censuses and scientific publications regarding access to RRT in the BRICS countries. There is unequal access to RRT in all the BRICS countries, as well as the absence of information regarding dialysis and transplants (India), the absence of effective legislation to inhibit the trafficking of organs (India and South Africa) and the use of deceased prisoners as donors for renal transplants (China). The construction of mechanisms to promote the sharing of benefits and solidarity in the field of international cooperation in the area of renal health involves the recognition of bioethical issues related to access to RRT in the BRICS countries.

  9. Developmental hippocampal neuroplasticity in a model of nicotine replacement therapy during pregnancy and breastfeeding.

    Directory of Open Access Journals (Sweden)

    Ian Mahar

    Full Text Available The influence of developmental nicotine exposure on the brain represents an important health topic in light of the popularity of nicotine replacement therapy (NRT as a smoking cessation method during pregnancy.In this study, we used a model of NRT during pregnancy and breastfeeding to explore the consequences of chronic developmental nicotine exposure on cerebral neuroplasticity in the offspring. We focused on two dynamic lifelong phenomena in the dentate gyrus (DG of the hippocampus that are highly sensitive to the environment: granule cell neurogenesis and long-term potentiation (LTP.Pregnant rats were implanted with osmotic mini-pumps delivering either nicotine or saline solutions. Plasma nicotine and metabolite levels were measured in dams and offspring. Corticosterone levels, DG neurogenesis (cell proliferation, survival and differentiation and glutamatergic electrophysiological activity were measured in pups.Juvenile (P15 and adolescent (P41 offspring exposed to nicotine throughout prenatal and postnatal development displayed no significant alteration in DG neurogenesis compared to control offspring. However, NRT-like nicotine exposure significantly increased LTP in the DG of juvenile offspring as measured in vitro from hippocampal slices, suggesting that the mechanisms underlying nicotine-induced LTP enhancement previously described in adult rats are already functional in pups.These results indicate that synaptic plasticity is disrupted in offspring breastfed by dams passively exposed to nicotine in an NRT-like fashion.

  10. Automated electronic monitoring of circuit pressures during continuous renal replacement therapy: a technical report.

    Science.gov (United States)

    Zhang, Ling; Baldwin, Ian; Zhu, Guijun; Tanaka, Aiko; Bellomo, Rinaldo

    2015-03-01

    Automated electronic monitoring and analysis of circuit pressures during continuous renal replacement therapy (CRRT) has the potential to predict failure and allow intervention to optimise function. Current CRRT machines can measure and store pressure readings for downloading into databases and for analysis. We developed a procedure to obtain such data at intervals of 1 minute and analyse them using the Prismaflex CRRT machine, and we present an example of such analysis. We obtained data on pressures obtained at intervals of 1 minute in a patient with acute kidney injury and sepsis treated with continuous haemofiltration at 2 L/hour of ultrafiltration and a blood flow of 200 mL/minute. Data analysis identified progressive increases in transmembrane pressure (TMP) and prefilter pressure (PFP) from time 0 until 33 hours or clotting. TMP increased from 104 mmHg to 313 mmHg and PFP increased from from 131 mmHg to 185 mmHg. Effluent pressure showed a progressive increase in the negative pressure applied to achieve ultrafiltration from 0 mmHg to -168 mmHg. The inflection point for such changes was also identified. Blood pathway pressures for access and return remained unchanged throughout. Automated electronic monitoring of circuit pressure during CRRT is possible and provides useful information on the evolution of circuit clotting.

  11. The cost of successful antiviral therapy in hepatitis C patients: a comparison of IFN-free versus IFN-based regimens at an individual patient level in Australia

    Directory of Open Access Journals (Sweden)

    Lee AS

    2017-10-01

    Full Text Available Allister Sebastian Lee,1 Mieke L van Driel,2 Darrell HG Crawford3,4 1Faculty of Medicine, 2Primary Care Clinical Unit, Faculty of Medicine, 3School of Clinical Medicine, Faculty of Medicine, University of Queensland, 4Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Brisbane, Australia Background: Chronic hepatitis C remains a major global health burden with serious long-term consequences if left untreated. Recently the treatment standard of care has shifted to new interferon (IFN-free drug regimens, which have been shown to be safe and effective. The aim of our study was to assess and compare medical resource utilization and costs of successfully treating patients with IFN-based and IFN-free therapies in Australia. Methods: We performed a retrospective chart review of 30 HCV-infected patients successfully treated with IFN-based therapy between 2013 and 2015. We also generated a model for a virtual group of 100 genotype 1 (GT1 and 100 genotype 3 (GT3 patients treated with IFN-free therapy derived from national guidelines and clinical trial data. Results: In comparison to virtual patients receiving IFN-free therapy, our IFN-treated patients on average had distinctively more liver clinic visits and blood tests. However, mean total cost per patient was $19,164 and $85,300 (AUD more for GT1 and GT3 patients receiving IFN-free therapy, respectively. This difference was largely accounted for by higher antiviral drug costs. Of our 30 patients treated with IFN, total mean cost per patient during the study period was $33,595. Conclusion: Resource utilization is lower with IFN-free treatment, which reflects the reduced need for patient monitoring and improved side-effect profile of these new drugs. However, total costs are still largely dominated by antiviral drug costs, representing a huge burden on national budgets. Our insight into resource utilization and costs associated with both types of treatment can serve as a reference for

  12. Use of Renal Replacement Therapy May Influence Graft Outcomes following Liver Transplantation for Acute Liver Failure: A Propensity-Score Matched Population-Based Retrospective Cohort Study.

    Science.gov (United States)

    Knight, Stephen R; Oniscu, Gabriel C; Devey, Luke; Simpson, Kenneth J; Wigmore, Stephen J; Harrison, Ewen M

    2016-01-01

    Acute kidney injury is associated with a poor prognosis in acute liver failure but little is known of outcomes in patients undergoing transplantation for acute liver failure who require renal replacement therapy. A retrospective analysis of the United Kingdom Transplant Registry was performed (1 January 2001-31 December 2011) with patient and graft survival determined using Kaplan-Meier methods. Cox proportional hazards models were used together with propensity-score based full matching on renal replacement therapy use. Three-year patient and graft survival for patients receiving renal replacement therapy were 77.7% and 72.6% compared with 85.1% and 79.4% for those not requiring renal replacement therapy (Prenal replacement therapy was a predictor of both patient death (hazard ratio (HR) 1.59, 95% CI 1.01-2.50, P = 0.044) but not graft loss (HR 1.39, 95% CI 0.92-2.10, P = 0.114). In groups fully matched on baseline covariates, those not receiving renal replacement therapy with a serum creatinine greater than 175 μmol/L had a significantly worse risk of graft failure than those receiving renal replacement therapy. In patients being transplanted for acute liver failure, use of renal replacement therapy is a strong predictor of patient death and graft loss. Those not receiving renal replacement therapy with an elevated serum creatinine may be at greater risk of early graft failure than those receiving renal replacement therapy. A low threshold for instituting renal replacement therapy may therefore be beneficial.

  13. Total Skin Electron Beam Therapy in the Treatment of Mycosis Fungoides: A Review of Conventional and Low-Dose Regimens.

    Science.gov (United States)

    Chowdhary, Mudit; Chhabra, Arpit M; Kharod, Shivam; Marwaha, Gaurav

    2016-12-01

    Mycosis fungoides (MF) is the most prevalent subtype of cutaneous T-cell lymphoma, which is characterized by the proliferation of CD4 + T cells. While often an indolent disease, most patients eventually develop progression from isolated patches to tumors and finally nodal or visceral involvement. Treatment choice is largely based on disease burden, though prognostic factors such as disease stage, patient age, and extracutaneous involvement must be taken into consideration. Radiotherapy represents one of the most effective therapeutic modalities in the treatment of MF. Lymphocytes are exquisitely radiosensitive, and excellent responses are observed even with low doses of radiation. Total skin electron beam therapy (TSEBT) is a special technique that allows for the homogenous irradiation of the entire skin. There are well-documented radiation dose-response relationships for achieving a complete response. As such, TSEBT doses ≥ 30 Gy comprise the current standard of care. Although highly effective, most patients experience recurrent disease even after conventional-dose (≥ 30 Gy) TSEBT. In addition, toxicity is cumulatively dose dependent, and there is reluctance to administer multiple courses of conventional-dose TSEBT. Consequently, there has been renewed interest in determining the utility of TSEBT at lower total (≤ 30 Gy) doses. Advantages of low-total-dose (with standard dose per fraction) TSEBT include a shortened treatment course, the potential to minimize the risk of adverse events, and the opportunity to allow for retreatment in cases of disease recurrence. This comprehensive review compares the impact of different TSEBT dosing schemes on clinical outcomes of MF. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review.

    Science.gov (United States)

    Villa, Gianluca; Di Maggio, Paola; De Gaudio, A Raffaele; Novelli, Andrea; Antoniotti, Riccardo; Fiaccadori, Enrico; Adembri, Chiara

    2016-11-19

    Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT. Citations published on PubMed up to January 2016 were systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients with AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the CRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported. Among 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53 treatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off membranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst the studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2-2.3 L/h for CVVH, 0.9-2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported. The optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with an MIC of 4 mg/L in one study only. Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with AKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in these patients. Strategies to improve the effectiveness of

  15. Is testosterone replacement therapy in males with hypogonadism cost-effective? An analysis in Sweden.

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    Arver, Stefan; Luong, Ba; Fraschke, Anina; Ghatnekar, Ola; Stanisic, Sanja; Gultyev, Dmitry; Müller, Elvira

    2014-01-01

    Testosterone replacement therapy (TRT) has been recommended for the treatment of primary and secondary hypogonadism. However, long-term implications of TRT have not been investigated extensively. The aim of this analysis was to evaluate health outcomes and costs associated with life-long TRT in patients suffering from Klinefelter syndrome and late-onset hypogonadism (LOH). A Markov model was developed to assess cost-effectiveness of testosterone undecanoate (TU) depot injection treatment compared with no treatment. Health outcomes and associated costs were modeled in monthly cycles per patient individually along a lifetime horizon. Modeled health outcomes included development of type 2 diabetes, depression, cardiovascular and cerebrovascular complications, and fractures. Analysis was performed for the Swedish health-care setting from health-care payer's and societal perspective. One-way sensitivity analyses evaluated the robustness of results. The main outcome measures were quality-adjusted life-years (QALYs) and total cost in TU depot injection treatment and no treatment cohorts. In addition, outcomes were also expressed as incremental cost per QALY gained for TU depot injection therapy compared with no treatment (incremental cost-effectiveness ratio [ICER]). TU depot injection compared to no-treatment yielded a gain of 1.67 QALYs at an incremental cost of 28,176 EUR (37,192 USD) in the Klinefelter population. The ICER was 16,884 EUR (22,287 USD) per QALY gained. Outcomes in LOH population estimated benefits of TRT at 19,719 EUR (26,029 USD) per QALY gained. Results showed to be considerably robust when tested in sensitivity analyses. Variation of relative risk to develop type 2 diabetes had the highest impact on long-term outcomes in both patient groups. This analysis suggests that lifelong TU depot injection therapy of patients with hypogonadism is a cost-effective treatment in Sweden. Hence, it can support clinicians in decision making when considering

  16. Modified Sequential Therapy Regimen versus Conventional Triple Therapy for Helicobacter pylori Eradication in Duodenal Ulcer Patients in China: A Multicenter Clinical Comparative Study

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    Ying-Qun Zhou

    2012-01-01

    Full Text Available Objective. Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. To observe the effect of eradicating Helicobacter pylori (H. pylori and the treatment of duodenal ulcer by 2 kinds of modified sequential therapy through comparing with that of 10-day standard triple therapy. Methods. A total of 210 patients who were confirmed in duodenal ulcer active or heal period by gastroscopy and H. pylori positive confirmed by rapid urease test, serum anti-H. pylori antibody (ELASE, or histological examination enrolled in the study. All the patients were randomly divided into three groups: group A (70 cases and group B (70 cases were provided 10-day modified sequential therapy; group C (70 cases was provided 10-day standard triple therapy. Patients of group A received 20 mg of Esomeprazole, 500 mg of Clarithromycin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group B received 20 mg of Esomeprazole, 1000 mg of Amoxicillin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group C received 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for standard 10-day therapy. All drugs were given twice daily. H. pylori eradication rate was checked four to eight weeks after taking the medicine by using a 13C urea breath test. In the first, second, third, seventh, twenty-first, thirty-fifth days respectively, the symptoms of patients such as epigastric gnawing, burning pain, and acidity were evaluated simultaneously. Results. Overall, 210 patients accomplished all therapy schemes, 9 case patients were excluded. The examination result indicated that the H. pylori eradication rate of each group was as follows: group A 92.5% (62/67, group B 86.8% (59/68, and group C 78.8% (52/66. The H. pylori

  17. The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

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    Jing Lu

    2015-01-01

    Full Text Available The International Staging System (ISS is the most important prognostic system for multiple myeloma (MM. It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p<0.001, and the median progression-free survival (PFS was 30/29.5/25 months (p=0.072, respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system.

  18. Should high risk patients with Hodgkin's disease be singled out for heavier therapeutic regimens while low risk patients are spared such therapies?

    Science.gov (United States)

    Reece, D

    1995-01-01

    In order to optimize the use of intensive therapy and autologous transplantation in patients with progressive Hodgkin's disease, we have examined the outcome of our initial 100 patients entered into autograft studies between 1985 and 1992. At a median follow-up of 3.6 (range 1.6-8.2) years, the actuarial progression free survival (PFS) was 46% (95% confidence intervals 33%-57%). The most significant determinant of PFS was the disease status at the time of protocol entry. Patients entered into transplant studies at the time of first untested relapse had a PFS of 61% compared with 38% in those who had failed induction chemotherapy, 25% in patients treated in > or = second untested relapse and 0% in those in a chemoresistant relapse. The reasons for failure differed, however, in that a high non-relapse mortality was seen in the > or = second untested relapse and resistant relapse groups while a high probability of relapse was observed in the induction failures and resistant relapse group. The most obvious group to target with more intensive therapeutic regimens consists of patients who have failed induction chemotherapy.

  19. Randomised Controlled Trial (RCT) of cannabinoid replacement therapy (Nabiximols) for the management of treatment-resistant cannabis dependent patients: a study protocol.

    Science.gov (United States)

    Bhardwaj, Anjali K; Allsop, David J; Copeland, Jan; McGregor, Iain S; Dunlop, Adrian; Shanahan, Marian; Bruno, Raimondo; Phung, Nghi; Montebello, Mark; Sadler, Craig; Gugusheff, Jessica; Jackson, Melissa; Luksza, Jennifer; Lintzeris, Nicholas

    2018-05-18

    The cannabis extract nabiximols (Sativex®) effectively supresses withdrawal symptoms and cravings in treatment resistant cannabis dependent individuals, who have high relapse rates following conventional withdrawal treatments. This study examines the efficacy, safety and cost-effectiveness of longer-term nabiximols treatment for outpatient cannabis dependent patients who have not responded to previous conventional treatment approaches. A phase III multi-site outpatient, randomised, double-blinded, placebo controlled parallel design, comparing a 12-week course of nabiximols to placebo, with follow up at 24 weeks after enrolment. Four specialist drug and alcohol outpatient clinics in New South Wales, Australia. One hundred forty-two treatment seeking cannabis dependent adults, with no significant medical, psychiatric or other substance use disorders. Nabiximols is an oromucosal spray prescribed on a flexible dose regimen to a maximum daily dose of 32 sprays; 8 sprays (total 21.6 mg tetrahydrocannabinol (THC) and 20 mg cannabidiol (CBD)) four times a day, or matching placebo, dispensed weekly. All participants will receive six-sessions of individual cognitive behavioural therapy (CBT) and weekly clinical reviews. Primary endpoints are use of non-prescribed cannabis (self-reported cannabis use days, urine toxicology), safety measures (adverse events and abuse liability), and cost effectiveness (incremental cost effectiveness in achieving additional Quality Adjusted Life Years). Secondary outcomes include, improvement in physical and mental health parameters, substance use other than cannabis, cognitive functioning and patient satisfaction measures. This is the first outpatient community-based randomised controlled study of nabiximols as an agonist replacement medication for treating cannabis dependence, targeting individuals who have not previously responded to conventional treatment approaches. The study and treatment design is modelled upon an earlier study with

  20. Renal replacement therapy in Latin American end-stage renal disease.

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    Rosa-Diez, Guillermo; Gonzalez-Bedat, Maria; Pecoits-Filho, Roberto; Marinovich, Sergio; Fernandez, Sdenka; Lugon, Jocemir; Poblete-Badal, Hugo; Elgueta-Miranda, Susana; Gomez, Rafael; Cerdas-Calderon, Manuel; Almaguer-Lopez, Miguel; Freire, Nelly; Leiva-Merino, Ricardo; Rodriguez, Gaspar; Luna-Guerra, Jorge; Bochicchio, Tomasso; Garcia-Garcia, Guillermo; Cano, Nuria; Iron, Norman; Cuero, Cesar; Cuevas, Dario; Tapia, Carlos; Cangiano, Jose; Rodriguez, Sandra; Gonzalez, Haydee; Duro-Garcia, Valter

    2014-08-01

    The Latin American Dialysis and Renal Transplant Registry (RLADTR) was founded in 1991; it collects data from 20 countries which are members of Sociedad Latinoamericana de Nefrología e Hipertension. This paper presents the results corresponding to the year 2010. This study is an annual survey requesting data on incident and prevalent patients undergoing renal replacement treatment (RRT) in all modalities: hemodialysis (HD), peritoneal dialysis (PD) and living with a functioning graft (LFG), etc. Prevalence and incidence were compared with previous years. The type of renal replacement therapy was analyzed, with special emphasis on PD and transplant (Tx). These variables were correlated with the gross national income (GNI) and the life expectancy at birth. Twenty countries participed in the surveys, covering 99% of the Latin American. The prevalence of end stage renal disease (ESRD) under RRT in Latin America (LA) increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (HD 413 pmp, PD 135 pmp and LFG 111 pmp). HD proportionally increased more than PD, and Tx HD continues to be the treatment of choice in the region (75%). The kidney Tx rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of Tx's in 2010 was 10 397, with 58% deceased donors. The total RRT prevalence correlated positively with GNI ( r 2 0.86; P chronic kidney disease (CKD) and its associated risk factors. PD is still an underutilized strategy for RRT in the region. Even though renal Tx is feasible, its growth rate is still not as fast as it should be in order to compensate for the increased prevalence of patients on waiting lists. Diagnostic and prevention programs for hypertension and diabetes, appropriate policies promoting the expansion of PD and organ procurement as well as transplantation as cost-effective forms of RRT are needed in the region. Regional cooperation among Latin American countries, allowing the more developed to

  1. A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

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    Micheli Valeria

    2011-06-01

    Full Text Available Abstract Background HIV-1 genotypic susceptibility scores (GSSs were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb and other covariates by means of Cox regression and random survival forests (RSF. Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70, while RSF showed a better performance (c-index≈0.73, p Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.

  2. Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism.

    Science.gov (United States)

    Doğan, Berçem Ayçiçek; Karakılıç, Ersen; Tuna, Mazhar Müslüm; Arduç, Ayşe; Berker, Dilek; Güler, Serdar

    2015-03-01

    Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder. Forty-three male patients aged 30 (range: 24-39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26-39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness. The carotid intima-media thickness (P hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = -0·556, P = hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months. © 2014 John Wiley & Sons Ltd.

  3. Urea kinetics during sustained low-efficiency dialysis in critically ill patients requiring renal replacement therapy.

    Science.gov (United States)

    Marshall, Mark R; Golper, Thomas A; Shaver, Mary J; Alam, Muhammad G; Chatoth, Dinesh K

    2002-03-01

    Continuous renal replacement therapies have practical and theoretical advantages compared with conventional intermittent hemodialysis in hemodynamically unstable or severely catabolic patients with acute renal failure (ARF). Sustained low-efficiency dialysis (SLED) is a hybrid modality introduced July 1998 at the University of Arkansas for Medical Sciences that involves the application of a conventional hemodialysis machine with reduced dialysate and blood flow rates for 12-hour nocturnal treatments. Nine critically ill patients with ARF were studied during a single SLED treatment to determine delivered dialysis dose and the most appropriate model for the description of urea kinetics during treatment. Five patients were men, mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 28.9 and mean weight was 92.5 kg. Kt/V was determined by the reference method of direct dialysate quantification (DDQ) combined with an equilibrated postdialysis plasma water urea nitrogen (PUN) concentration and four other methods that were either blood or dialysate based, single or double pool, or model independent (whole-body kinetic method). Solute removal indices (SRIs) were determined from net urea removal and urea distribution volume supplied from DDQ (reference method) and by mass balance using variables supplied from blood-based formal variable-volume single-pool (VVSP) urea kinetic modeling. Equivalent renal urea clearances (EKRs) were calculated from urea generation rates and time-averaged concentrations for PUN based on weekly mass balance with kinetic variables supplied by either DDQ (reference method) or formal blood-based VVSP modeling. Mean Kt/V determined by the reference method was 1.40 and not significantly different when determined by formal VVSP modeling, DDQ using an immediate postdialysis PUN, or the whole-body kinetic method. Correction of single-pool Kt/V by a Daugirdas rate equation did not yield plausible results. Mean SRI and EKR by the

  4. Cardiovascular risks in smokers treated with nicotine replacement therapy: a historical cohort study

    Directory of Open Access Journals (Sweden)

    Dollerup J

    2017-04-01

    Full Text Available Jens Dollerup,1 Jørgen Vestbo,2 Tarita Murray-Thomas,3 Alan Kaplan,4 Richard J Martin,5 Emilio Pizzichini,6 Marcia M M Pizzichini,6 Anne Burden,7 Jessica Martin,7 David B Price7,8 1Dollerup Medical Consultancy, Kongens Lyngby, Denmark; 2Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, UK; 3Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency, London, UK; 4Family Physician Airways Group of Canada, Richmond Hill, ON, Canada; 5National Jewish Health, Denver, CO, USA; 6Federal University of Santa Catarina, Santa Catarina, Brazil; 7Observational and Pragmatic Research Institute Pte Ltd, Singapore; 8Centre for Academic Primary Care, University of Aberdeen, Aberdeen, UK Background: Previous research suggests exposure to nicotine replacement therapy (NRT may be associated with an increased risk of cardiovascular disease (CVD.Methods: Using data from the United Kingdom’s Clinical Practice Research Datalink, this study aimed to evaluate CVD events and survival among individuals who attempted smoking cessation with the support of NRT compared with those aided by smoking cessation advice only. We studied CVD outcomes over 4 and 52 weeks in 50,214 smokers attempting to quit – 33,476 supported by smoking cessation advice and 16,738 with the support of NRT prescribed by their primary care physician. Patients were matched (2 smoking cessation advice patients:1 NRT patient on demographic and clinical characteristics during a baseline year preceding their quit attempt. Cox proportional hazard regression, conditional negative binomial regression model, and conditional logistic regression were used to analyze data.Results: Mean (standard deviation population age was 47 (11.2 years; 51% were females. Time to first diagnosis of ischemic heart disease (IHD among NRT and smoking cessation advice patients was similar within the first 4 weeks, but

  5. Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease.

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    Yi, Haiqing; Sun, Tao; Armstrong, Dustin; Borneman, Scott; Yang, Chunyu; Austin, Stephanie; Kishnani, Priya S; Sun, Baodong

    2017-05-01

    Pompe disease is characterized by accumulation of both lysosomal and cytoplasmic glycogen primarily in skeletal and cardiac muscles. Mannose-6-phosphate receptor-mediated enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) targets the enzyme to lysosomes and thus is unable to digest cytoplasmic glycogen. Studies have shown that anti-DNA antibody 3E10 penetrates living cells and delivers "cargo" proteins to the cytosol or nucleus via equilibrative nucleoside transporter ENT2. We speculate that 3E10-mediated ERT with GAA will target both lysosomal and cytoplasmic glycogen in Pompe disease. A fusion protein (FabGAA) containing a humanized Fab fragment derived from the murine 3E10 antibody and the 110 kDa human GAA precursor was constructed and produced in CHO cells. Immunostaining with an anti-Fab antibody revealed that the Fab signals did not co-localize with the lysosomal marker LAMP2 in cultured L6 myoblasts or Pompe patient fibroblasts after incubation with FabGAA. Western blot with an anti-GAA antibody showed presence of the 150 kDa full-length FabGAA in the cell lysates, in addition to the 95- and 76 kDa processed forms of GAA that were also seen in the rhGAA-treated cells. Blocking of mannose-6-phosphate receptor with mannose-6-phosphate markedly reduced the 95- and the 76 kDa forms but not the 150 kDa form. In GAA-KO mice, FabGAA achieved similar treatment efficacy as rhGAA at an equal molar dose in reducing tissue glycogen contents. Our data suggest that FabGAA retains the ability of rhGAA to treat lysosomal glycogen accumulation and has the beneficial potential over rhGAA to reduce cytoplasmic glycogen storage in Pompe disease. FabGAA can be delivered to both the cytoplasm and lysosomes in cultured cells. FabGAA equally reduced lysosomal glycogen accumulation as rhGAA in GAA-KO mice. FabGAA has the beneficial potential over rhGAA to clear cytoplasmic glycogen. This study suggests a novel antibody-enzyme fusion protein therapy

  6. Faster Blood Flow Rate Does Not Improve Circuit Life in Continuous Renal Replacement Therapy: A Randomized Controlled Trial.

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    Fealy, Nigel; Aitken, Leanne; du Toit, Eugene; Lo, Serigne; Baldwin, Ian

    2017-10-01

    To determine whether blood flow rate influences circuit life in continuous renal replacement therapy. Prospective randomized controlled trial. Single center tertiary level ICU. Critically ill adults requiring continuous renal replacement therapy. Patients were randomized to receive one of two blood flow rates: 150 or 250 mL/min. The primary outcome was circuit life measured in hours. Circuit and patient data were collected until each circuit clotted or was ceased electively for nonclotting reasons. Data for clotted circuits are presented as median (interquartile range) and compared using the Mann-Whitney U test. Survival probability for clotted circuits was compared using log-rank test. Circuit clotting data were analyzed for repeated events using hazards ratio. One hundred patients were randomized with 96 completing the study (150 mL/min, n = 49; 250 mL/min, n = 47) using 462 circuits (245 run at 150 mL/min and 217 run at 250 mL/min). Median circuit life for first circuit (clotted) was similar for both groups (150 mL/min: 9.1 hr [5.5-26 hr] vs 10 hr [4.2-17 hr]; p = 0.37). Continuous renal replacement therapy using blood flow rate set at 250 mL/min was not more likely to cause clotting compared with 150 mL/min (hazards ratio, 1.00 [0.60-1.69]; p = 0.68). Gender, body mass index, weight, vascular access type, length, site, and mode of continuous renal replacement therapy or international normalized ratio had no effect on clotting risk. Continuous renal replacement therapy without anticoagulation was more likely to cause clotting compared with use of heparin strategies (hazards ratio, 1.62; p = 0.003). Longer activated partial thromboplastin time (hazards ratio, 0.98; p = 0.002) and decreased platelet count (hazards ratio, 1.19; p = 0.03) were associated with a reduced likelihood of circuit clotting. There was no difference in circuit life whether using blood flow rates of 250 or 150 mL/min during continuous renal replacement therapy.

  7. A better cure rate with 800 mg than with 400 mg clarithromycin regimens in one-week triple therapy for Helicobacter pylori infection in cigarette-smoking peptic ulcer patients.

    Science.gov (United States)

    Ishioka, Hidehiko; Mizuno, Motowo; Take, Susumu; Ishiki, Kuniharu; Nagahara, Yasuhiro; Yoshida, Tomowo; Okada, Hiroyuki; Yokota, Kenji; Oguma, Keiji

    2007-01-01

    In Helicobacter pylori eradication therapy, using a proton pump inhibitor plus amoxicillin and clarithromycin (PPI/AC regimen), the impact of the clarithromycin dose and smoking on efficacy is conflicting. Here, we compared the efficacy of 400 and 800 mg of clarithromycin in the regimen in relation to smoking in patients with peptic ulcer disease. We studied 601 H. pylori-positive patients with peptic ulcer disease who had received amoxicillin 750 mg and clarithromycin 200 or 400 mg together with lansoprazole 30 mg b.i.d. 305 patients were treated with a regimen containing 400 mg of clarithromycin (C400 group), and 296 patients with a regimen containing 800 mg (C800 group). Overall cure rates between the two groups were not significantly different, but the cure rate in the C800 group was significantly better than that in the C400 group among patients infected with clarithromycin-sensitive strains (p = 0.03). This difference could be attributed to differences among smokers versus non-smokers: the cure rate among smokers in the C800 group (91.0%) was better than that in the C400 group (80.0%, p = 0.003). 800 mg of clarithromycin is recommended in the PPI/AC regimen for patients who smoke and are infected with clarithromycin-sensitive H. pylori. 2007 S. Karger AG, Basel

  8. Androgen replacement therapy in late-onset hypogonadism: current concepts and controversies - a mini-review.

    Science.gov (United States)

    Mäkinen, Juuso I; Huhtaniemi, Ilpo

    2011-01-01

    Normal testicular function is essential for the maintenance of male physical strength and behaviour irrespective of age. A new term of late-onset hypogonadism (LOH) has been coined for the condition of decreased testosterone (T) and hypogonadal symptoms in ageing men. The most important testicular hormone, T, is responsible for the gender-specific androgenic-anabolic effects in men. Testicular T production remains stable until around the age of 40 years after which it declines by 1-2% annually. Despite this age-related decline, serum T levels in most older men remain within the reference range of younger men. The decreasing androgen levels are paralleled by well-defined objective biological and nonspecific subjective signs and symptoms of ageing. Because these symptoms are similar to those observed in young men with documented hypogonadism, androgen replacement therapy (ART) has been considered a logical way to treat them. A thorough review of the existing literature was performed to evaluate the current concepts and controversies related to ageing men and ART. Although it is intuitively logical that the symptoms of LOH are due to the ageing-related deficiency of T, and that they can be reversed by ART, the evidence for this is still variable and often weak. In particular, evidence-based information about long-term benefits and risks of ART in ageing men is largely missing. Despite widespread use, evidence-based proof for the objective benefits and side effects of ART of elderly men is still scanty, and such treatments should be considered experimental. Copyright © 2010 S. Karger AG, Basel.

  9. Pancreatic enzyme replacement therapy in cystic fibrosis: dose, variability and coefficient of fat absorption

    Directory of Open Access Journals (Sweden)

    Joaquim Calvo-Lerma

    Full Text Available Objectives: Pancreatic enzyme replacement therapy (PERT remains a backbone in the nutritional treatment of cystic fibrosis. Currently, there is a lack of an evidence-based tool that allows dose adjustment. To date, no studies have found an association between PERT dose and fat absorption. Therefore, the aim of the study was to assess the influence of both the PERT dose and the variability in this dose on the coefficient of fat absorption (CFA. Methods: This is a retrospective longitudinal study of 16 pediatric patients (192 food records with three consecutive visits to the hospital over a twelve-month period. Dietary fat intake and PERT were assessed via a four-day food record and fat content in stools was determined by means of a three-day stool sample collection. A beta regression model was built to explain the association between the CFA and the interaction between the PERT dose (lipase units [LU]/g dietary fat and the variability in the PERT dose (standard deviation [SD]. Results: The coefficient of fat absorption increased with the PERT dose when the variability in the dose was low. In contrast, even at the highest PERT dose values, the CFA decreased when the variability was high. The confidence interval suggested an association, although the analysis was not statistically significant. Conclusion: The variability in the PERT dose adjustment should be taken into consideration when performing studies on PERT efficiency. A clinical goal should be the maintenance of a constant PERT dose rather than trying to obtain an optimal value.

  10. Effect of nicotine replacement therapy on cardiovascular outcomes after acute coronary syndromes.

    Science.gov (United States)

    Woolf, Kevin J; Zabad, Mohammed Nour; Post, Jennifer M; McNitt, Scott; Williams, Geoffrey C; Bisognano, John D

    2012-10-01

    The optimal approach to encourage smoking cessation after acute coronary syndrome (ACS) remains unclear. The safety of nicotine replacement therapy (NRT) after ACS is not well established. The aim of the present study was to determine the relationship between NRT use and adverse cardiovascular outcomes after ACS. Using a pre-existing database, 663 smokers with ACS were identified. The patients were separated into the NRT (n = 184) or control (n = 479) groups according to whether NRT was prescribed on hospital discharge. Multivariate logistic regression analysis was used to account for the baseline differences between the 2 groups. Of the 663 patients, 202 had adverse events in the first year after ACS. No significant differences were seen with NRT use for the 1-year combined end point of death, myocardial infarction), repeat revascularization, or rehospitalization for angina, congestive heart failure or arrhythmia (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.61 to 1.30, p = 0.54). There were no differences in the individual 1-year end points of death (odds ratio 0.80, 95% confidence interval 0.33 to 1.91, p = 0.61), myocardial infarction (odds ratio 0.90, 95% confidence interval 0.40 to 2.06, p = 0.80), repeat revascularization (odds ratio 0.77, 95% confidence interval 0.44 to 1.36, p = 0.37), or rehospitalization for angina, congestive heart failure, or arrhythmia (odds ratio 1.01, 95% confidence interval 0.66 to 1.53, p = 0.97). In conclusion, NRT use was not associated with an increased risk of adverse cardiovascular events in the first year after ACS. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Doubling in the use of thyroid hormone replacement therapy in Denmark: association to iodization of salt?

    International Nuclear Information System (INIS)

    Cerqueira, Charlotte; Knudsen, Nils; Ovesen, Lars; Laurberg, Peter; Perrild, Hans; Rasmussen, Lone Banke; Jørgensen, Torben

    2011-01-01

    Iodization of salt is an effective strategy to prevent iodine deficiency disorders. Recent studies, however, indicate that increasing the iodine intake in a population may give rise to an increased incidence of hypothyroidism, but the association has not been fully clarified. In Denmark, iodization of salt was initiated in 1998 because of mild-to-moderate iodine deficiency. The aim of this study was to evaluate the effect of the raised iodine intake on the nationwide incident use of thyroid hormone replacement therapy (levothyroxine) to treat hypothyroidism. Data on all use of levothyroxine was extracted from the Register of Medicinal Product Statistics during the period 1995–2009 and linked to other nationwide registers by use of the Danish identification number. Persons with previous thyroid surgery were excluded. In the studied period 71,565 incident users were identified. The incidence rate increased 75% in the moderately iodine deficient region (72.2 incident users/100,000 person-years in 1997 to 126.6 in 2008) and 87% in the mildly deficient region (86.9–162.9). When stratified by sex and age-group (00–39, 40–64, 65+) the largest relative increase was seen among women in the youngest age-group, where more than a doubling was seen. The mechanisms behind the increase may be a result of iodine-induced hypothyroidism, although a higher diagnostic activity with regard to thyroid dysfunction and intensified treatment of subclinical hypothyroidism may also play a role. Our findings stress the need for caution when initiating iodine fortification programs to keep the intake within the optimal range, and the need for continuous monitoring.

  12. Enzyme replacement therapy for Fabry disease: some answers but more questions

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    Majid Alfadhel

    2011-02-01

    Full Text Available Majid Alfadhel1, Sandra Sirrs21Division of Biochemical Diseases, Department of Paediatrics, BC Children’s and Women’s Hospital, University of British Columbia, Vancouver, BC, Canada; 2Adult Metabolic Diseases Clinic, Division of Endocrinology, Department of Medicine, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, BC, CanadaAbstract: Fabry disease (FD is a multisystem, X-linked disorder of glycosphingolipid metabolism caused by enzyme deficiency of α-galactosidase A. Affected patients have symptoms including acroparesthesias, angiokeratomas, and hypohidrosis. More serious manifestations include debilitating pain and gastrointestinal symptoms, proteinuria and gradual deterioration of renal function leading to end-stage renal disease, hypertrophic cardiomyopathy, and stroke. Heterozygous females may have symptoms as severe as males with the classic phenotype. Before 2001, treatment of patients with FD was supportive. The successful development of enzyme replacement therapy (ERT has been a great advancement in the treatment of patients with FD and can stabilize renal function and cardiac size, as well as improve pain and quality of life of patients with FD. In this review, we have provided a critical appraisal of the literature on the effects of ERT for FD. This analysis shows that data available on the treatment of FD are often derived from studies which are not controlled, rely on surrogate markers, and are of insufficient power to detect differences on hard clinical endpoints. Further studies of higher quality are needed to answer the questions that remain concerning the efficacy of ERT for FD.Keywords: Fabry disease, agalsidase α, agalsidase β, Replagal, Fabrazyme, critical appraisal, evidence-based medicine

  13. Management of hypercalcaemic crisis in adults: Current role of renal replacement therapy.

    Science.gov (United States)

    Bentata, Yassamine; El Maghraoui, H; Benabdelhak, M; Haddiya, I

    2018-06-01

    Neoplasms and hematologic diseases are the predominant etiologies of hypercalcemic crisis in adults and the immediate treatment is mainly medical and symptomatic. The use of renal replacement therapy (RRT) is often necessary to correct the hypercalcemia, uremia and electrolyte disturbances related to Acute Kidney Injury (AKI). The aim of this work was to determine the etiologies and the place of RRT in treating patients with hypercalcaemic crisis. We conducted a retrospective study for 36months at the Nephrology Unit, University Hospital, Oujda, eastern of Morocco. We included all adult patients diagnosed with hypercalcemic crisis that was defined as corrected total serum calcium of >3.5mmol/l. 12 patients were collected. All patients were female and 5 patients were elderly (≥65years). Three patients had a serum calcium value of >4mmol/l and the highest calcium value was 5.8mmol/l. Electrocardiographic abnormalities were observed in 8 cases. AKI was observed in 8 cases. Three patients had chronic kidney disease on hemodialysis. Neoplasm was noted in 9 cases. All patients received venous rehydration, glucocorticoids and biphosphonates. The use of RRT with low calcium dialysate was performed in 11 cases. Three patients died during the first 24h of hospitalization. RRT must play its full role as first line treatment of hypercalcemia crisis. Improvements in hemodialysis techniques and the use of low calcium or calcium-free dialysates currently allows this therapeutic measure to be prescribed safely, and the benefit-risk balance is positive for the great benefit provided by dialysis. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Hormone replacement therapy is associated with gastro-oesophageal reflux disease: a retrospective cohort study

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    Close Helen

    2012-05-01

    Full Text Available Abstract Background Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT. Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. Methods 51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs were calculated for GORD and proton-pump inhibitor (PPI use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. Results In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89. Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74. Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22. Conclusions This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.

  15. Protein metabolism in Turner syndrome and the impact of hormone replacement therapy.

    Science.gov (United States)

    Gravholt, Claus Højbjerg; Riis, Anne Lene; Møller, Niels; Christiansen, Jens Sandahl

    2007-09-01

    Studies have documented an altered body composition in Turner syndrome (TS). Body fat is increased and muscle mass is decreased. Ovarian failure necessitates substitution with female hormone replacement therapy (HRT), and HRT induces favourable changes in body composition. It is unknown how HRT affects protein metabolism. To test whether alterations in body composition before and after HRT in TS are a result of altered protein metabolism. We performed a randomized crossover study with active treatment (HRT in TS and oral contraceptives in controls) or no treatment. We studied eight women (age 29.7 +/- 5.6 (mean +/- SD) years) with TS, verified by karyotype, and eight age-matched controls (age 27.3 +/- 4.9 years). All subjects underwent a 3-h study in the postabsorptive state. Protein dynamics of the whole body and of the forearm muscles were measured by an amino acid tracer dilution technique using [(15)N]phenylalanine and [(2)H(4)]tyrosine. Substrate metabolism was examined by indirect calorimetry. Energy expenditure was comparable among TS and controls, and did not change during active treatment. Whole-body phenylalanine and tyrosine fluxes were similar in the untreated situations, and did not change during active treatment. Amino acid degradation and protein synthesis were similar in all situations. Muscle protein breakdown was similar among groups, and was not affected by treatment. Muscle protein synthesis rate and forearm blood flow did not differ among groups or due to treatment. Protein metabolism in TS is comparable to controls, and is not affected by HRT.

  16. Prevalence of patients receiving renal replacement therapy in El Salvador in 2014.

    Science.gov (United States)

    García-Trabanino, Ramón; Trujillo, Zulma; Colorado, Ana Verónica; Magaña Mercado, Salvador; Henríquez, Carlos Atilio

    El Salvador has the highest renal failure mortality rate in the Americas. Five healthcare providers offer renal replacement therapy (RRT) in the country. The national RRT prevalence has never been reported. To determine the RRT prevalence in El Salvador and some basic characteristics. The association of nephrology coordinated a nationwide cross-sectional survey during the third quarter of 2014. 31 renal centres participated in the survey, covering 99.5% of patients. National RRT prevalence: 595 per million population (pmp), N=3807, average age 50.4 years, 67.5% male. By modality: peritoneal dialysis (PD) 289 pmp, haemodialysis (HD) 233 pmp, with functioning kidney transplantation 74 pmp (living donor only). Social security covers 25% of the population but treats 49.7% of RRT patients. Generally, higher prevalence was observed in municipalities with renal centres or located on the coast or lowlands. Ninety-five percent of HD patients receive fewer than 3 weekly sessions. Of PD patients, 59% do not belong to a continuous outpatient or automated programme, and 25% still use rigid catheter. Aetiology of chronic kidney disease: unavailable/undetermined 50%, hypertension 21.1%, diabetes 18.9%, glomerulonephritis 6.7%, obstructive causes 1.2%, tubulointerstitial 0.9%, polycystic 0.4% and other 0.7%. Despite the increase in RRT services, the prevalence is lower than the Latin American average (660 pmp). Three quarters of HD and PD patients are under-dialysed. Obsolete RRT techniques are still used. The presence of Mesoamerican nephropathy influences the demographic characteristics (many young patients, two-thirds male, high prevalence in lowlands and coastlands). Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  17. Correlates of use of electronic cigarettes versus nicotine replacement therapy for help with smoking cessation.

    Science.gov (United States)

    Pokhrel, Pallav; Little, Melissa A; Fagan, Pebbles; Kawamoto, Crissy T; Herzog, Thaddeus A

    2014-12-01

    Electronic- or e-cigarettes are nicotine-delivery devices commonly used by smokers to quit or reduce smoking. At present, not much is known about the characteristics of smokers who specifically try e-cigarettes to quit smoking compared to the nicotine replacement therapy (NRT) products approved by the U.S. Food and Drug Administration (FDA). Determining the characteristics of smokers who are likely to choose e-cigarettes as cessation aids would help develop strategies to impart valid information about e-cigarettes to such smokers as facts regarding the safety and utility of e-cigarettes emerge. This study is based on 834 daily smokers [mean age=45.8 (standard deviation=13)] from Hawaii. Demographic, smoking- and cessation-related variables were examined as correlates of ever use of e-cigarette only or any FDA-approved NRT product only or both as cessation aids. Results indicated that younger smokers, non-White smokers, and smokers reporting higher income, lower nicotine dependence, shorter smoking history, and higher lifetime quit attempts were more likely to have tried e-cigarettes but not NRT products for help with smoking cessation. Smokers who are attracted to use e-cigarettes but not FDA-approved NRT products may differ from smokers who are likely to have used NRT products but not e-cigarettes in terms of demographic (e.g., age, ethnicity) and smoking- or cessation-related characteristics (e.g., nicotine dependence, quit attempts). Given the lack of knowledge regarding the health effects of e-cigarettes and their efficacy as cessation aids, future research needs to continue characterizing smokers who are likely to use e-cigarettes for smoking cessation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease.

    Science.gov (United States)

    Smans, Lisanne; Lentjes, Eef; Hermus, Ad; Zelissen, Pierre

    2013-01-01

    Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects. The aim of this study was to investigate the use of salivary cortisol day curves (SCDC) in the individual adjustment of GRT in order to approach normal cortisol levels as closely as possible, reduce over- and underreplacement and study the short-term effects on quality of life (QoL). Twenty patients with Addison's disease were included in this prospective study. A SCDC was obtained and compared to normal controls; general and disease specific QoL-questionnaires were completed. Based on SCDC assessment of over- and undertreatment (calculated as duration (h) × magnitude (nmol/L) at different time points, glucocorticoid dose and regime were adjusted. After 4 weeks SCDC and QoL assessment were repeated and the effect of adjusting GRT was analysed. At baseline, underreplacement was present in 3 and overreplacement in 18 patients; total calculated overreplacement was 32.8 h.nmol/L. Overreplacement decreased significantly to 13.3 h. nmol/L (p =0.005) after adjustment of GRT. Overreplacement was found particularly in the afternoon and evening. After reducing overreplacement in the evening, complaints about sleep disturbances significantly decreased. Individual adjustment of GRT based on SCDC to approach normal cortisol concentrations during the day can reduce overreplacement, especially in the evening. This can lead to a reduction of sleep disturbances and fatigue in patients with Addison's disease. A SCDC is a simple and patient-friendly tool for adjusting GRT and can be useful in the follow-up of patients with Addison's disease.

  19. Effects of androgen replacement therapy on cornea and tear function in men with idiopathic hypogonadotropic hypogonadism.

    Science.gov (United States)

    Gokce, Gokcen; Hurmeric, Volkan; Mumcuoglu, Tarkan; Ozge, Gokhan; Basaran, Yalcin; Unal, Hilmi Umut; Bolu, Erol; Mutlu, Fatih Mehmet

    2015-05-01

    Idiopathic hypogonadotropic hypogonadism (IHH) is an endocrine disorder defined with the presence of typical clinical signs and symptoms plus laboratory confirmation of serum testosterone (T) levels lower than 300 ng/dl. Androgen replacement therapy (ART) is the first-step treatment of male IHH. To date, no clinical trial, which investigates the changes on corneal structure and tear function, of systemic ART in men have been published. The objective of this study was to investigate the effects of ART on cornea and tear function in patients with IHH. This prospective, interventional study was conducted at the Gulhane Military Medical Academy, Ankara, Turkey, a tertiary referral military hospital. Thirty-four eyes of 17 men with IHH patients were evaluated with Schirmer I test, ultrasound pachymeter, applanation tonometer and confocal microscopy. A Testosterone compound (Sustanon® 250 mg) was administered by intramuscular injection in the course of a 3-week period to induce puberty, and human chorionic gonadotropin (Pregnyl® 5000 IU) was administered twice weekly for 3 months to induce fertility. The patients were re-evaluated at the third month of the treatment. Main Outcome Measures were Schirmer score, central corneal thickness (CCT), intraocular pressure (IOP), endothelial cell density, coefficient of variation and cell shape. Schirmer scores showed similar results after the treatment compared to pre-treatment levels (p = 0.14). There was no statistically significant difference in CCT and IOP compared to baseline data (p = 0.96, p = 0.73, respectively), and no significant differences were found in corneal endothelial cell density, percentage of cell size variability or hexagonality (p = 0.83, p = 0.58, p = 0.64, respectively). This is the first study that investigates the effects of ART on corneal structure and tear function in men. ART seems to have no short-term effects on corneal structure and tear function. Further publications of larger, long-term and

  20. Effects of Estrogen Replacement Therapy to the Renal Function in Postmenopausal Women

    Directory of Open Access Journals (Sweden)

    Setenay Arzu Yılmaz

    2011-12-01

    Full Text Available Objective: To asses the effect of estrogen replacement therapy to the renal functions in postmenopausal women following the surgery. Design: This is prospestive randomised cross-sectional descriptive study. Setting: Gazi University School Of Medicine Obstetrics and Gynecology Department between October 2000 through July 2001 Patients: Fifty-eight patients who had been undergone total abdominal hysterectomy and bilateral salpingo-oopherectomy due to benign gynecologic disorders were enrolled in this present study. Interventions: Breast and pelvic examination had been before operation. Cervical smear, blood glucose, lipid profile, liver and renal functional tests, complete blood count and urine analysis revelaed. Mammography and pelvic ultrasonography applied to all patients. Main outcome measures: Body mass index (BMI has been measured with patient’s weight (kg and heights by the formula ‘weight(kg /height (m2. Obese patients defined as boy mass index over 30. The patients who can use ERT randomised as two groups. Group I received transdermal estrogen (Climara TTS or oral conjugated estrogen (Premarin 0,625 mg, group II did not. Microalbuminuria, creatinine clearance in 24 hour urine specimen were compared preoperatively and postoperative 1st and 6 th months respectively. Results: At the end of six month of observation in the group who were in surgical menopause and given ERT, statistically significant decline in microalbuminuria was observed. However, in the group who were in surgically menopause and did not receive ERT, level of microalbuminuria did not change significantly. In the group who were oopherectomised following naturel menopause, microalbuminuria level changed clinically after ERT but was not stastistically significant. Whereas in the group who were not given ERT, decline in the level of microalbuminuria was seen and this finding is stastistically significant (p<0,05. Conclusion: We concluded that ERT is protective on

  1. Comparative Effectiveness of Replacement Therapy with L-thyroxine in Women with Postoperative and Autoimmune Hypothyroidism

    Directory of Open Access Journals (Sweden)

    M Sch Madiyarova

    2014-03-01

    Full Text Available Objective. To compare the lipid profile, psychoemotional features, cognitive function, quality of life in women receiving adequate replacement therapy with levothyroxine for postoperative hypothyroidism and autoimmune (Hashimoto's hypothyroidism.Methods. 121 women (18-45 y.o. with primary hypothyroidism receiving levothyroxine for more than one year participated in the study. 66 women with autoimmune hypothyroidism, 55 - with hypothyroidism after subtotal thyroidectomy for Graves' disease. The scores for the Short-Form 36, Hospital Anxiety and Depression Scale, symptoms of hypothyroidism, Inventory of memory and attention, TSH, free T3, free T4 and lipid profiles were analyzed. Results. There were no significant differences between groups in the age, BMI, TSH, fT3, fT4 levels. The total cholesterol was higher in patients with postoperative hypothyroidism in comparison to autoimmune hypothyroidism ( р = 0,041. The levels of social functioning and mental health that reflect mental component of health were lower in patients with autoimmune hypothyroidism than with postoperative hypothyroidism ( p = 0,038, p = 0,019, respectively. The anxiety was higher in the same group ( p = 0,004. There was no difference in memory and attention levels. The anxiety level was higher in autoimmune hypothyroidism and “low-normal” TSH (0,4 - 2 µU/L than in postoperative hypothyroidism and the same TSH ( p = 0,016. Also in the group with postoperative hypothyroidism and “low-normal” TSH the cholesterol and prevalence of hypercholesterolemia were higher than in autoimmune hypothyroidism ( p = 0,017; р = 0,013. Conclusion. In young women with compensated autoimmune hypothyroidism the mental component of health is lower and the anxiety - higher than in postoperative hypothyroidism. Even in stable compensation of postoperative hypothyroidism the cholesterol level is higher comparing to the patients with autoimmune thyroiditis. And even in “low-normal” TSH

  2. [Utilization of hormone replacement therapy in Spain: Trends in the period 2000-2014].

    Science.gov (United States)

    Baladé Martínez, Laura; Montero Corominas, Dolores; Macías Saint-Gerons, Diego

    2016-10-07

    The objective of the study was to describe the trends of utilization, supply and prevalence of hormone replacement therapy (HRT) in Spain during the period 2000-2014. Annual prevalence of HRT use including the 95% CI was calculated for women aged≥40 using individual data from the national population-based database BIFAP. Annual and total-period consumptions were expressed in defined daily doses (DDD) per 1,000 inhabitants per day and were obtained from the databases of medications dispensed in community pharmacies and charged through official prescriptions to the Spanish National Health System. In the year 2000, overall HRT consumption was 33.12 DDDs/1000 inhabitans/day: 19.81 for oestrogen only, 6.88 for tibolone and 6.44 for combined oestrogen and progestagen. In 2014 overall HRT consumption was 5.32 DDDs/1000 inhabitans/day: 1.08 for oestrogen only, 1.61 for tibolone and 2.62 for combinations of oestrogen and progestagen. The marketed presentations of HRT decreased by 46.9%. Prevalence of HRT use in women aged≥40 in BIFAP was 7.19% (95% CI 6.97-7.40) in 2001 and 0.21% (95% CI 0.20-0.22) in 2014. Women aged 40-45 registered the highest prevalence of use in 2014: 0.71% (95% CI 0.66-0.76). A sharp decline in the consumption and prevalence of HRT has been observed in Spain since the publication of the Women's Health Initiative and Million Women Study and the regulatory measures taken restricting conditions of use, showing a similar trend to that of other western countries. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  3. Exercise therapy may postpone total hip replacement surgery in patients with hip osteoarthritis

    DEFF Research Database (Denmark)

    Svege, Ida; Nordsletten, Lars; Fernandes, Linda

    2015-01-01

    Exercise treatment is recommended for all patients with hip osteoarthritis (OA), but its effect on the long-term need for total hip replacement (THR) is unknown.......Exercise treatment is recommended for all patients with hip osteoarthritis (OA), but its effect on the long-term need for total hip replacement (THR) is unknown....

  4. Perceived efficacy of e-cigarettes versus nicotine replacement therapy among successful e-cigarette users: a qualitative approach

    OpenAIRE

    Barbeau, Amanda M; Burda, Jennifer; Siegel, Michael

    2013-01-01

    Background Nicotine is widely recognized as an addictive psychoactive drug. Since most smokers are bio-behaviorally addicted, quitting can be very difficult and is often accompanied by withdrawal symptoms. Research indicates that nicotine replacement therapy (NRT) can double quit rates. However, the success rate for quitting remains low. E-cigarettes (electronic cigarettes) are battery-powered nicotine delivery devices used to inhale doses of vaporized nicotine from a handheld device similar ...

  5. Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links

    OpenAIRE

    Pardini,Dolores Perovano; Sabino,Anibal Tagliaferri; Meneses,Ana Maria; Kasamatsu,Teresa; Vieira,José Gilberto Henriques

    2000-01-01

    CONTEXT: The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. OBJECTIVE: To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN: Cohort correlational study. SETTING: Academic...

  6. Effects of early changes in organ dysfunctions on the outcomes of critically ill patients in need of renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Elizabeth Maccariello

    2008-01-01

    Full Text Available INTRODUCTION: Acute kidney injury usually develops in critically ill patients in the context of multiple organ dysfunctions. OBJECTIVE: To evaluate the effect of changes in associated organ dysfunctions over the first three days of renal replacement therapy on the outcomes of patients with acute kidney injury. METHODS: Over a 19-month period, we evaluated 260 patients admitted to the intensive care units of three tertiary-care hospitals who required renal replacement therapy for > 48 h. Organ dysfunctions were evaluated by SOFA score (excluding renal points on the first (D1 and third (D3 days of renal replacement therapy. Absolute (A-SOFA and relative (D-SOFA changes in SOFA scores were also calculated. RESULTS: Hospital mortality rate was 75%. Organ dysfunctions worsened (A-SOFA>0 in 53%, remained unchanged (A-SOFA=0 in 17% and improved (A-SOFA<0 in 30% of patients; and mortality was lower in the last group (80% vs. 84% vs. 61%, p=0.003. SOFA on D1 (p<0.001, SOFA on D3 (p<0.001, A-SOFA (p=0.019 and D-SOFA (p=0.016 were higher in non-survivors. However, neither A-SOFA nor D-SOFA discriminated survivors from non-survivors on an individual basis. Adjusting for other covariates (including SOFA on D1, A-SOFA and D-SOFA were associated with increased mortality, and patients in whom SOFA scores worsened or remained unchanged had poorer outcomes. CONCLUSIONS: In addition to baseline values, early changes in SOFA score after the start of renal replacement therapy were associated with hospital mortality. However, no prognostic score should be used as the only parameter to predict individual outcomes.

  7. Effects of long-term estrogen replacement therapy on bone turnover in periarticular tibial osteophytes in surgically postmenopausal cynomolgus monkeys

    OpenAIRE

    Olson, Erik J.; Lindgren, Bruce R.; Carlson, Cathy S.

    2007-01-01

    The aims of the present study were to assess the effects of long-term estrogen replacement therapy (ERT) on size and indices of bone turnover in periarticular osteophytes in ovariectomized cynomolgus monkeys and to compare dynamic indices of bone turnover in osteophyte bone with those of subchondral bone (SCB) and epiphyseal/metaphyseal cancellous (EMC) bone. One hundred sixty-five adult female cynomolgus macaques were bilaterally ovariectomized and randomly divided into three age- and weight...

  8. Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

    International Nuclear Information System (INIS)

    Yulish, B.S.; Stern, R.C.; Polmar, S.H.

    1980-01-01

    A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions

  9. Renal replacement therapy in Latin American end-stage renal disease

    Science.gov (United States)

    Rosa-Diez, Guillermo; Gonzalez-Bedat, Maria; Pecoits-Filho, Roberto; Marinovich, Sergio; Fernandez, Sdenka; Lugon, Jocemir; Poblete-Badal, Hugo; Elgueta-Miranda, Susana; Gomez, Rafael; Cerdas-Calderon, Manuel; Almaguer-Lopez, Miguel; Freire, Nelly; Leiva-Merino, Ricardo; Rodriguez, Gaspar; Luna-Guerra, Jorge; Bochicchio, Tomasso; Garcia-Garcia, Guillermo; Cano, Nuria; Iron, Norman; Cuero, Cesar; Cuevas, Dario; Tapia, Carlos; Cangiano, Jose; Rodriguez, Sandra; Gonzalez, Haydee; Duro-Garcia, Valter

    2014-01-01

    The Latin American Dialysis and Renal Transplant Registry (RLADTR) was founded in 1991; it collects data from 20 countries which are members of Sociedad Latinoamericana de Nefrología e Hipertension. This paper presents the results corresponding to the year 2010. This study is an annual survey requesting data on incident and prevalent patients undergoing renal replacement treatment (RRT) in all modalities: hemodialysis (HD), peritoneal dialysis (PD) and living with a functioning graft (LFG), etc. Prevalence and incidence were compared with previous years. The type of renal replacement therapy was analyzed, with special emphasis on PD and transplant (Tx). These variables were correlated with the gross national income (GNI) and the life expectancy at birth. Twenty countries participed in the surveys, covering 99% of the Latin American. The prevalence of end stage renal disease (ESRD) under RRT in Latin America (LA) increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (HD 413 pmp, PD 135 pmp and LFG 111 pmp). HD proportionally increased more than PD, and Tx HD continues to be the treatment of choice in the region (75%). The kidney Tx rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of Tx's in 2010 was 10 397, with 58% deceased donors. The total RRT prevalence correlated positively with GNI (r2 0.86; P < 0.05) and life expectancy at birth (r2 0.58; P < 0.05). The HD prevalence and the kidney Tx rate correlated significantly with the same indexes, whereas the PD rate showed no correlation with these variables. A tendency to rate stabilization/little growth was reported in the most regional countries. As in previous reports, the global incidence rate correlated significantly only with GNI (r2 0.63; P < 0.05). Diabetes remained the leading cause of ESRD. The most frequent causes of death were cardiovascular (45%) and infections (22%). Neoplasms accounted for 10% of the causes of death. The

  10. A distinct urinary biomarker pattern characteristic of female Fabry patients that mirrors response to enzyme replacement therapy.

    Directory of Open Access Journals (Sweden)

    Andreas D Kistler

    Full Text Available Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naïve female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2% sensitivity and 97.8% specificity when tested in an independent validation cohort consisting of 17 treatment-naïve Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy.

  11. Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Peng Xue

    2013-01-01

    Full Text Available Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

  12. In-vivo luminescence model for the study of tumor regression and regrowth following combination regimens with differentiation-promoting agents and photodynamic therapy

    Science.gov (United States)

    Rollakanti, K.; Anand, S.; Maytin, E. V.

    2013-03-01

    Photodynamic therapy with aminolevulinic acid can be modified by pretreatment regimens with drugs such as 5- Fluorouracil (5-FU) or Vitamin D (calcitriol) that enhance accumulation of protoporphyrin IX (PpIX) within tumor tissue which presumably will enhance the therapeutic response to light. However, histological approaches for monitoring therapeutic responses are poorly suited for studying long term survival because large numbers of mice need to be sacrificed. To address this limitation, a non-invasive model to monitor tumor regression and regrowth has been established. Breast cancer cells, stably transfected with firefly luciferase (MDA-Luc cell line), are implanted orthotopically in nude mice (0.25 - 1 x 106 cells/site), and monitored 0-60 min after s.c. injection of luciferin, with Xenogen in-vivo imaging system. Luminescence is detectable at day 1 post-implantation. Tumors are suitable for experimentation on day 6, when daily injections of pretreatment agents (5-FU, 300 mg/kg; calcitriol, 1 μg/kg) begin. On day 9, ALA (75 mg/kg i.p.) is given for 4 hr, followed by illumination (633 nm, 100 J/cm2). Tumor luminescence post- PDT is monitored daily and compared with caliper measurements. Pretreatments (5-FU, calcitriol) by themselves do not inhibit luciferase expression, and all tumors grow at a similar rate during the pretreatment period. Results from in vivo survival experiments can be correlated to survival responses of MDA-Luc cells grown in monolayer cultures +/- PDT and +/- pretreatments, and additional mechanistic information (e.g. Ki67 and E-cadherin expression) obtained. In summary, this noninvasive model will permit testing of the therapeutic survival advantages of various pretreatments during cPDT.

  13. Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies.

    Science.gov (United States)

    Pizot, Cécile; Boniol, Mathieu; Mullie, Patrick; Koechlin, Alice; Boniol, Magali; Boyle, Peter; Autier, Philippe

    2016-01-01

    Lower risk of breast cancer has been reported among physically active women, but the risk in women using hormone replacement therapy (HRT) appears to be higher. We quantified the association between physical activity and breast cancer, and we examined the influence that HRT use and other risk factors had on this association. After a systematic literature search, prospective studies were meta-analysed using random-effect models applied on highest versus lowest level of physical activity. Dose-response analyses were conducted with studies reporting physical activity either in hours per week or in hours of metabolic equivalent per week (MET-h/week). The literature search identified 38 independent prospective studies published between 1987 and 2014 that included 116,304 breast cancer cases. Compared to the lowest level of physical activity, the highest level was associated with a summary relative risk (SRR) of 0.88 (95% confidence interval [CI] 0.85, 0.90) for all breast cancer, 0.89 (95% CI 0.83, 0.95) for ER+/PR+ breast cancer and 0.80 (95% CI 0.69, 0.92) for ER-/PR- breast cancer. Risk reductions were not influenced by the type of physical activity (occupational or non-occupational), adiposity, and menopausal status. Risk reductions increased with increasing amounts of physical activity without threshold effect. In six studies, the SRR was 0.78 (95% CI 0.70, 0.87) in women who never used HRT and 0.97 (95% CI 0.88, 1.07) in women who ever used HRT, without heterogeneity in results. Findings indicate that a physically inactive women engaging in at least 150 min per week of vigorous physical activity would reduce their lifetime risk of breast cancer by 9%, a reduction that might be two times greater in women who never used HRT. Increasing physical activity is associated with meaningful reductions in the risk of breast cancer, but in women who ever used HRT, the preventative effect of physical activity seems to be cancelled out. Copyright © 2015 Elsevier Ltd. All

  14. [The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism].

    Science.gov (United States)

    Ding, Zhiwei; Li, Tiancheng; Liu, Yuhe; Xiao, Shuifang

    2015-12-01

    To investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model. Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 µg/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay. The rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 µg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (P0.05). Calcium and phosphorus return to normal level by administration of rPTH(1-84) in the dose of 80 µg/kg or 160 µg/kg, with increase in BMD. Calcitriol can return the level of calcium to normal and

  15. Electrodiagnostic studies in presumptive primary hypothyroidism and polyneuropathy in dogs with reevaluation during hormone replacement therapy.

    Science.gov (United States)

    Giza, Elżbieta Gabriela; Płonek, Marta; Nicpoń, Józef Marian; Wrzosek, Marcin Adam

    2016-05-21

    Peripheral neuropathy is the most common neurological manifestation of canine hypothyroidism. Data concerning electrodiagnostic studies in hypothyroid associated polyneuropathy in dogs are very limited and usually lack a reevaluation after hormone replacement therapy. The objective of this study was to perform a detailed, retrospective analysis of electromyographic (EMG), motor nerve conduction velocity (MNCV), F-wave and brainstem auditory evoked response (BAER) findings in 24 dogs with presumptive primary hypothyroidism and polyneuropathy with a comparison of the results before and after initiation of levothyroxine treatment with the assessment of the clinical outcome. The results obtained from hypothyroid dogs showed a significant reduction in MNCV at a proximal-distal and middle-distal stimulation, decreased amplitudes of compound muscle action potentials (CMAP), an increased CMAP duration and a prolonged distal latency prior to treatment. Fifty percent of the dogs had an increased F-wave latency. A normal BAER recording was found in 78 % of the hypothyroid patients without vestibular impairment. Bilaterally increased peak V latencies and increased interpeak I-V latencies were found in the remaining individuals. Dogs with concurrent vestibular impairment had ipsilaterally increased peak latencies with normal interpeak latencies and decreased amplitudes of wave I and II. A comparison of the findings before and after 2 months of treatment revealed a decrease in the pathological activity on EMG, an improvement of proximal, middle and distal CMAP amplitudes and an increase in the proximal-distal conduction velocity in all dogs. F-wave latency improved in 38 % of dogs. The BAER reexamination revealed a persistent prolongation of peak I, II, III and V latencies and decreased wave I amplitude on the affected side in all dogs manifesting vestibular signs. Conversely, in dogs without vestibular signs, the peak V and interpeak I-V latencies decreased to normal values

  16. General Practitioners' views on the provision of nicotine replacement therapy and bupropion

    Directory of Open Access Journals (Sweden)

    West Robert

    2001-10-01

    Full Text Available Abstract Background Nicotine replacement therapies (NRT and a new drug, bupropion, are licensed in several countries as aids to smoking cessation. General practitioners (GPs play a crucial role in recommending or prescribing these medications. In the UK there has been discussion about whether the medications should be reimbursable by the National Health Service (NHS. This study assessed English GPs' attitudes towards reimbursement of NRT and bupropion. Methods Postal survey of a randomly selected national sample of GPs; 376 GPs completed the questionnaire after one reminder; effective response rate: 53%. There was no difference between the responses of GPs who responded to the initial request and those who responded only after a reminder suggesting minimal bias due to non-response. Results Attitudes of GPs were remarkably divided on most issues relating to the medications. Forty-three percent thought that bupropion should not be on NHS prescription while 42% thought that it should be (15% did not know; Fifty percent thought that NRT should not be on NHS prescription while 42% thought it should be (8% did not know. Requiring that smokers attend behavioural support programmes to be eligible to receive the medications on NHS prescription made no appreciable difference to the GPs' views. GPs were similarly divided on whether having the medications reimbursable would add unacceptably to their workload or offer a welcome opportunity to discuss smoking with their patients. A principal components analysis of responses to the individual questions on NRT and bupropion revealed that GPs' attitudes could be understood in terms of a single 'pro-con' dimension accounting for 53% of the total variance which made no distinction between the two medications. Conclusions GPs in England appear to be divided in their attitudes to medications to aid smoking cessation and appear not to discriminate in their views between different types of medication or different

  17. Human neural stem cell replacement therapy for amyotrophic lateral sclerosis by spinal transplantation.

    Directory of Open Access Journals (Sweden)

    Michael P Hefferan

    clinically-adequate treatment, cell-replacement/gene therapy strategies will likely require both spinal and supraspinal targets.

  18. The Concordance between Patients' Renal Replacement Therapy Choice and Definitive Modality: Is It a Utopia?

    Science.gov (United States)

    Prieto-Velasco, Mario; Quiros, Pedro; Remon, Cesar

    2015-01-01

    It is desirable for patients to play active roles in the choice of renal replacement therapy (RRT). Patient decision aid tools (PDAs) have been developed to allow the patients to choose the option best suited to their individual needs. An observational, prospective registry was conducted in 26 Spanish hospitals between September 2010 and May 2012. The results of the patients' choice and the definitive RRT modality were registered through the progressive implementation of an Education Process (EP) with PDAs designed to help Chronic Kidney Disease (CKD) patients choose RRT. Patients included in this study: 1044. Of these, 569 patients used PDAs and had made a definitive choice by the end of registration. A total of 88.4% of patients chose dialysis [43% hemodialysis (HD) and 45% peritoneal dialysis (PD)] 3.2% preemptive living-donor transplant (TX), and 8.4% conservative treatment (CT). A total of 399 patients began RRT during this period. The distribution was 93.4% dialysis (53.6% HD; 40% PD), 1.3% preemptive TX and 5.3% CT. The patients who followed the EP changed their mind significantly less often [kappa value of 0.91 (95% CI, 0.86-0.95)] than those who did not follow it, despite starting unplanned treatment [kappa value of 0.85 (95% CI, 0.75-0.95]. A higher agreement between the final choice and a definitive treatment was achieved by the EP and planned patients [kappa value of 0.93 (95% CI, 0.89-0.98)]. Those who did not go through the EP had a much lower index of choosing PD and changed their decision more frequently when starting definitive treatment [kappa value of 0.73 (95% CI, 0.55-0.91)]. Free choice, assisted by PDAs, leads to a 50/50 distribution of PD and HD choice and an increase in TX choice. The use of PDAs, even with an unplanned start, achieved a high level of concordance between the chosen and definitive modality.

  19. Physiologic Growth Hormone-Replacement Therapy and Craniopharyngioma Recurrence in Pediatric Patients: A Meta-Analysis.

    Science.gov (United States)

    Alotaibi, Nawaf M; Noormohamed, Nadia; Cote, David J; Alharthi, Salman; Doucette, Joanne; Zaidi, Hasan A; Mekary, Rania A; Smith, Timothy R

    2018-01-01

    A systematic review and meta-analysis were conducted to examine the effect of growth hormone-replacement therapy (GHRT) on the recurrence of craniopharyngioma in children. PubMed, Embase, and Cochrane databases were searched through April 2017 for studies that evaluated the effect of GHRT on the recurrence of pediatric craniopharyngioma. Pooled effect estimates were calculated with fixed- and random-effects models. Ten studies (n = 3487 patients) met all inclusion criteria, including 2 retrospective cohorts and 8 case series. Overall, 3436 pediatric patients were treated with GHRT after surgery and 51 were not. Using the fixed effect model, we found that the overall craniopharyngioma recurrence rate was lower among children who were treated by GHRT (10.9%; 95% confidence interval 9.80%-12.1%; I 2  = 89.1%; P for heterogeneity <0.01; n = 10 groups) compared with those who were not (35.2%; 95% confidence interval 23.1%-49.6%; I 2  = 61.7%; P for heterogeneity = 0.11; n = 3); the P value comparing the 2 groups was <0.01. Among patients who were treated with GHRT, subgroup analysis revealed that there was a greater prevalence of craniopharyngioma recurrence among studies conducted outside the United States (P < 0.01), single-center studies (P < 0.01), lower impact factor studies (P = 0.03), or studies with a lower quality rating (P = 0.01). Using the random-effects model, we found that the results were not materially different except for when stratifying by GHRT, impact factor, or study quality; this led to nonsignificant differences. Both Begg's rank correlation test (P = 0.7) and Egger's linear regression test (P = 0.06) indicated no publication bias. This meta-analysis demonstrated a lower recurrence rate of craniopharyngioma among children treated with GHRT than those who were not. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Respiratory muscle training with enzyme replacement therapy improves muscle strength in late - onset Pompe disease.

    Science.gov (United States)

    Jevnikar, Mitja; Kodric, Metka; Cantarutti, Fabiana; Cifaldi, Rossella; Longo, Cinzia; Della Porta, Rossana; Bembi, Bruno; Confalonieri, Marco

    2015-12-01

    Pompe disease is an autosomal recessive metabolic disorder caused by the deficiency of the lysosomal enzyme acid α-glucosidase. This deficiency leads to glycogen accumulation in the lysosomes of muscle tissue causing progressive muscular weakness particularly of the respiratory system. Enzyme replacement therapy (ERT) has demonstrated efficacy in slowing down disease progression in infants. Despite the large number of studies describing the effects of physical training in juvenile and adult late onset Pompe disease (LOPD). There are very few reports that analyze the benefits of respiratory muscle rehabilitation or training. The effectiveness of respiratory muscle training was investigated using a specific appliance with adjustable resistance (Threshold). The primary endpoint was effect on respiratory muscular strength by measurements of MIP and MEP. Eight late-onset Pompe patients (aged 13 to 58 years; 4 female, 4 male) with respiratory muscle deficiency on functional respiratory tests were studied. All patients received ERT at the dosage of 20 mg/kg/every 2 weeks and underwent training with Threshold at specified pressures for 24 months. A significant increase in MIP was observed during the follow-up of 24 month: 39.6 cm H 2 O (+ 25.0%) at month 3; 39.5 cm H 2 O (+ 24.9%) at month 6; 39.1 cm H 2 O (+ 23.7%) at month 9; 37.3 cm H 2 O (+ 18.2%) at month 12; and 37.3 cm H 2 O (+ 17.8%) at month 24. Median MEP values also showed a significant increase during the first 9 months: 29.8 cm H 2 O, (+ 14.3%) at month 3; 31.0 cm H 2 O (+ 18.6) at month 6; and 29.5 cm H 2 O (+ 12.9) at month 9. MEP was then shown to be decreased at months 12 and 24; median MEP was 27.2 cm H 2 O (+ 4.3%) at 12 months and 26.6 cm H 2 O (+ 1.9%) at 24 months. The FVC remain stable throughout the study. An increase in respiratory muscular strength was demonstrated with Threshold training when used in combination with ERT.

  1. Predicting intention to use nicotine replacement therapy in people attending residential treatment for substance dependency.

    Science.gov (United States)

    Kelly, Peter J; Townsend, Camilla J; Osborne, Briony A; Baker, Amanda L; Deane, Frank P; Keane, Carol; Ingram, Isabella; Lunn, Joanne

    2018-02-28

    Nicotine Replacement Therapy (NRT) is recommended as a frontline smoking cessation tool for people attending mental health and substance dependence treatment services. Previous research suggests that NRT is underutilized in these settings. To improve the use of NRT amongst people attending residential treatment for substance use disorders (SUDs) it is important that the factors influencing smokers' decisions to use NRT are understood. The study aimed to examine: (1) smoking cessation strategies used by participants in previous quit attempts, (2) participants' attitudes towards NRT (i.e. safety concerns and perceived efficacy), and (3) the predictors of participants' intention to use NRT to support future quit attempts. Participants completed a cross-sectional survey that examined their smoking behaviours, previous experiences using smoking cessation strategies, attitudes and beliefs regarding NRT, and intention to use NRT as part of future quit attempts (N = 218). All participants were attending residential treatment for substance use disorders provided by We Help Ourselves (WHOS), a large provider of specialist alcohol and other drug treatment in Australia. The majority of respondents (98%) reported that they had smoked regularly in their lifetime, and 89% were current smokers. Forty-five percent of the current smokers reported that they had previously used NRT to support a quit attempt, with 54% reporting that they intended to use NRT to support a future quit attempt. Intentions to use NRT were not related to the participants' mental health status or the participants' perceptions regarding the safety or potential drawbacks associated with using NRT. However, participants were more likely to report that they would use NRT to support future quit attempts if they were female, had previously used NRT and perceived NRT to be effective. Improving the use of evidence based smoking cessation strategies within substance use treatment continues to be a priority. To enhance

  2. Abnormal imaging findings of the breast related to hormone replacement therapy: analysis of surgically excised cases

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Woo Kyung; Cha, Joo Hee; Cho, Kyung Soo; Choi, Een Wan; Lee, Yu Jin; Im, Jung Gi [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Kim, Hyung Seok [Wooridul Spine Hospital, Seoul (Korea, Republic of); Chung, Sun Yang [Bundang CHA General Hospital, Sungnam (Korea, Republic of); Cho, Nariya [Gil Medical Center, Incheon (Korea, Republic of)

    2004-02-01

    To correlate the mammographic and ultrasonographic findings with the pathologic results in women undergoing hormone replacement therapy (HRT), and to determine the characteristic clinical, mammographic or histologic findings of breast cancer in these patients. Twenty-five breast lesions in 25 patients aged 44-65 (mean, 55.5) years undergoing HRT were surgically removed due to abnormal mammographic findings or the presence of palpable masses. Mammograms in all patients and ultrasonograms in 23 were retrospectively analyzed in terms of the shape and margin of the mass, and microcalcifications, and the imaging findings were correlated with the pathologic results. As a control group, 45 cancer patients not undergoing HRT were selected. Using the student t test, detection methods, tumor size, mammographic findings, and the proportion of intraductal cancers were compared between to two groups. Surgical excision revealed ten benign lesions (four fibroadenomas and six cases of fibrocystic change) and 15 cancers (three intraductal and twelve invasive ductal cancers). Abnormal findings at mammography were a mass in 16 cases, clustered microcalcifications in seven, and a mass with microcalcifications in two. Mammography showed that all four circumscribed masses were benign. Five of seven ill-defined masses (71%) and all six spiculated masses were malignant. Three of seven cases (43%) with microcalcifications, and both with a mass and microcalcification, were malignant. In two cases in which ultrasonography revealed cystic lesions, histologic examination showed that fibrocystic change had occurred. Compared to non-HRT-related cancers, HRT-related cancers were more often detected by mammography (60% vs 16%; p<0.001), smaller (17 mm vs 24 mm, p<0.01), showed microcalcification only (20% vs 13%; p<0.05), and were intraductal (20% vs 7%; p<0.01). In patients with HRT, mammographic findings of an ill-defined or spiculated mass, or one with microcalcifications, were associated with

  3. Abnormal imaging findings of the breast related to hormone replacement therapy: analysis of surgically excised cases

    International Nuclear Information System (INIS)

    Moon, Woo Kyung; Cha, Joo Hee; Cho, Kyung Soo; Choi, Een Wan; Lee, Yu Jin; Im, Jung Gi; Kim, Hyung Seok; Chung, Sun Yang; Cho, Nariya

    2004-01-01

    To correlate the mammographic and ultrasonographic findings with the pathologic results in women undergoing hormone replacement therapy (HRT), and to determine the characteristic clinical, mammographic or histologic findings of breast cancer in these patients. Twenty-five breast lesions in 25 patients aged 44-65 (mean, 55.5) years undergoing HRT were surgically removed due to abnormal mammographic findings or the presence of palpable masses. Mammograms in all patients and ultrasonograms in 23 were retrospectively analyzed in terms of the shape and margin of the mass, and microcalcifications, and the imaging findings were correlated with the pathologic results. As a control group, 45 cancer patients not undergoing HRT were selected. Using the student t test, detection methods, tumor size, mammographic findings, and the proportion of intraductal cancers were compared between to two groups. Surgical excision revealed ten benign lesions (four fibroadenomas and six cases of fibrocystic change) and 15 cancers (three intraductal and twelve invasive ductal cancers). Abnormal findings at mammography were a mass in 16 cases, clustered microcalcifications in seven, and a mass with microcalcifications in two. Mammography showed that all four circumscribed masses were benign. Five of seven ill-defined masses (71%) and all six spiculated masses were malignant. Three of seven cases (43%) with microcalcifications, and both with a mass and microcalcification, were malignant. In two cases in which ultrasonography revealed cystic lesions, histologic examination showed that fibrocystic change had occurred. Compared to non-HRT-related cancers, HRT-related cancers were more often detected by mammography (60% vs 16%; p<0.001), smaller (17 mm vs 24 mm, p<0.01), showed microcalcification only (20% vs 13%; p<0.05), and were intraductal (20% vs 7%; p<0.01). In patients with HRT, mammographic findings of an ill-defined or spiculated mass, or one with microcalcifications, were associated with

  4. Reductions in red blood cell 2,3-diphosphoglycerate concentration during continuous renal replacment therapy.

    Science.gov (United States)

    Sharma, Shilpa; Brugnara, Carlo; Betensky, Rebecca A; Waikar, Sushrut S

    2015-01-07

    Hypophosphatemia is a frequent complication during continuous renal replacement therapy (CRRT), a dialytic technique used to treat AKI in critically ill patients. This study sought to confirm that phosphate depletion during CRRT may decrease red blood cell (RBC) concentration of 2,3-diphosphoglycerate (2,3-DPG), a crucial allosteric effector of hemoglobin's (Hgb's) affinity for oxygen, thereby leading to impaired oxygen delivery to peripheral tissues. Phosphate mass balance studies were performed in 20 patients with severe AKI through collection of CRRT effluent. RBC concentrations of 2,3-DPG, venous blood gas pH, and oxygen partial pressure required for 50% hemoglobin saturation (P50) were measured at CRRT initiation and days 2, 4, and 7. Similar measurements were obtained on days 0 and 2 in a reference group of 10 postsurgical patients, most of whom did not have AKI. Associations of 2,3-DPG with laboratory parameters and clinical outcomes were examined using mixed-effects and Cox regression models. Mean 2,3-DPG levels decreased from a mean (±SD) of 13.4±3.4 µmol/g Hgb to 11.0±3.1 µmol/g Hgb after 2 days of CRRT (Plevels decreased from 29.7±4.4 mmHg to 26.7±4.0 mmHg (Plevels after 2 days of CRRT were not significantly lower than those in the reference group on day 2. Among patients receiving CRRT, 2,3-DPG decreased by 0.53 µmol/g Hgb per 1 g phosphate removed (95% confidence interval 0.38 to 0.68 µmol/g Hgb; P<0.001). Greater reductions in 2,3-DPG were associated with higher risk for death (hazard ratio, 1.43; 95% confidence interval, 1.09 to 1.88; P=0.01). CRRT-induced phosphate depletion is associated with measurable reductions in RBC 2,3-DPG concentration and a shift in the O2:Hgb affinity curve even in the absence of overt hypophosphatemia. 2,3-DPG reductions may be associated with higher risk for in-hospital death and represent a potentially avoidable complication of CRRT. Copyright © 2015 by the American Society of Nephrology.

  5. Renal function predicts long-term outcome on enzyme replacement therapy in patients with Fabry disease.

    Science.gov (United States)

    Lenders, Malte; Schmitz, Boris; Stypmann, Jörg; Duning, Thomas; Brand, Stefan-Martin; Kurschat, Christine; Brand, Eva

    2017-12-01

    Renal and cardiac involvement is responsible for substantial morbidity and mortality in Fabry disease (FD). We analysed the incidence of FD-related renal, cardiac and neurologic end points in patients with FD on long-term enzyme replacement therapy (ERT). A retrospective analysis of prospectively collected data from two German FD centres was performed. The impact of renal and cardiac function at ERT-naïve baseline on end point development despite ERT was analysed. Fifty-four patients (28 females) receiving ERT (mean 81 ± 21 months) were investigated. Forty per cent of patients were diagnosed with clinical end points before ERT initiation and 50% of patients on ERT developed new clinical end points. In patients initially diagnosed with an end point before ERT initiation, the risk for an additional end point on ERT was increased {hazard ratio [HR] 3.83 [95% confidence interval (CI) 1.61-9.08]; P = 0.0023}. A decreased glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 in ERT-naïve patients at baseline was associated with an increased risk for cardiovascular end points [HR 3.59 (95% CI 1.15-11.18); P = 0.0273] as well as for combined renal, cardiac and neurologic end points on ERT [HR 4.77 (95% CI 1.93-11.81); P = 0.0007]. In patients with normal kidney function, left ventricular hypertrophy at baseline predicted a decreased end point-free survival [HR 6.90 (95% CI 2.04-23.27); P = 0.0018]. The risk to develop an end point was independent of sex. In addition to age, even moderately impaired renal function determines FD progression on ERT. In patients with FD, renal and cardiac protection is warranted to prevent patients from deleterious manifestations of the disease. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  6. Myxedema coma and cardiac ischemia in relation to thyroid hormone replacement therapy in a 38-year-old Japanese woman.

    Science.gov (United States)

    Taguchi, Takafumi; Iwasaki, Yasumasa; Asaba, Koichi; Takao, Toshihiro; Hashimoto, Kozo

    2007-12-01

    Although thyroid hormone deficiency, either clinical or subclinical, is an established risk factor for cardiovascular disease, coronary ischemia in a premenopausal woman in her 30s is relatively rare. A 38-year-old woman was referred to our hospital with severe breathlessness and depressed consciousness. Physical examination found facial, abdominal, and pretibial edema; coarse hair, hoarse voice, and dry skin; engorged jugular veins; a distant heart sound; and reduced bilateral entry of air into the chest. Laboratory examinations revealed severe hypothyroidism, hyperlipidemia, and elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125). A computed tomography scan showed massive pleural and pericardial effusions. After 3 months of levothyroxine replacement therapy (initial dose: 12.5 microg/d; maintenance dose: 125 microg/d), all abnormal laboratory values associated with hypothyroidism returned to within normal ranges, with the exception of a transient and paradoxical rise in serum thyroid-stimulating hormone levels. However, 3 weeks after the initiation of therapy, the patient reported intermittent chest pains during the course of therapy, and a coronary artery angiogram revealed diffuse stenosis of all 3 branches. The patient underwent coronary artery bypass grafting, with subsequent improvement in coronary perfusion. Careful cardiovascular evaluation is recommended before the start of thyroid hormone replacement therapy. In addition, care should be taken in the interpretation of serum biomarkers of malignancy (eg, CEA, CA125) in patients with myxedema, as values may be elevated in a hypothyroid state. Long-standing hypothyroidism may be associated with severe coronary atherosclerosis, even in a relatively young, premenopausal woman. The potential adverse cardiovascular effects of thyroid hormone must be considered during replacement therapy, even in relatively young patients.

  7. Patients' perceptions of information and education for renal replacement therapy: an independent survey by the European Kidney Patients' Federation on information and support on renal replacement therapy.

    Directory of Open Access Journals (Sweden)

    Wim Van Biesen

    Full Text Available Selection of an appropriate renal replacement modality is of utmost importance for patients with end stage renal disease. Previous studies showed provision of information to and free modality choice by patients to be suboptimal. Therefore, the European Kidney Patients' Federation (CEAPIR explored European patients' perceptions regarding information, education and involvement on the modality selection process.CEAPIR developed a survey, which was disseminated by the national kidney patient organisations in Europe.In total, 3867 patients from 36 countries completed the survey. Respondents were either on in-centre haemodialysis (53% or had a functioning graft (38% at the time of survey. The majority (78% evaluated the general information about kidney disease and treatment as helpful, but 39% did not recall being told about alternative treatment options than their current one. Respondents were more often satisfied with information provided on in-centre haemodialysis (90% and transplantation (87% than with information provided on peritoneal dialysis (79% or home haemodialysis (61%, and were more satisfied with information from health care professionals vs other sources such as social media. Most (75% felt they had been involved in treatment selection, 29% perceived they had no free choice. Involvement in modality selection was associated with enhanced satisfaction with treatment (OR 3.13; 95% CI 2.72-3.60. Many respondents (64% could not remember receiving education on how to manage their kidney disease in daily life. Perceptions on information seem to differ between countries.Kidney patients reported to be overall satisfied with the information they received on their disease and treatment, although information seemed mostly to have been focused on one modality. Patients involved in modality selection were more satisfied with their treatment. However, in the perception of the patients, the freedom to choose an alternative modality showed room for

  8. Comparison of survival analysis and palliative care involvement in patients aged over 70 years choosing conservative management or renal replacement therapy in advanced chronic kidney disease.

    Science.gov (United States)

    Hussain, Jamilla A; Mooney, Andrew; Russon, Lynne

    2013-10-01

    There are limited data on the outcomes of elderly patients with chronic kidney disease undergoing renal replacement therapy or conservative management. We aimed to compare survival, hospital admissions and palliative care access of patients aged over 70 years with chronic kidney disease stage 5 according to whether they chose renal replacement therapy or conservative management. Retrospective observational study. Patients aged over 70 years attending pre-dialysis clinic. In total, 172 patients chose conservative management and 269 chose renal replacement therapy. The renal replacement therapy group survived for longer when survival was taken from the time estimated glomerular filtration rate management, in patients older than 80 years or with a World Health Organization performance score of 3 or more. There was also a significant reduction in the effect of renal replacement therapy on survival in patients with high Charlson's Comorbidity Index scores. The relative risk of an acute hospital admission (renal replacement therapy vs conservative management) was 1.6 (p management patients died in hospital, compared to 69% undergoing renal replacement therapy (Renal Registry data). Seventy-six percent of the conservative management group accessed community palliative care services compared to 0% of renal replacement therapy patients. For patients aged over 80 years, with a poor performance status or high co-morbidity scores, the survival advantage of renal replacement therapy over conservative management was lost at all levels of disease severity. Those accessing a conservative management pathway had greater access to palliative care services and were less likely to be admitted to or die in hospital.

  9. Induced Pluripotent Stem Cell Therapies for Degenerative Disease of the Outer Retina: Disease Modeling and Cell Replacement.

    Science.gov (United States)

    Di Foggia, Valentina; Makwana, Priyanka; Ali, Robin R; Sowden, Jane C

    2016-06-01

    Stem cell therapies are being explored as potential treatments for retinal disease. How to replace neurons in a degenerated retina presents a continued challenge for the regenerative medicine field that, if achieved, could restore sight. The major issues are: (i) the source and availability of donor cells for transplantation; (ii) the differentiation of stem cells into the required retinal cells; and (iii) the delivery, integration, functionality, and survival of new cells in the host neural network. This review considers the use of induced pluripotent stem cells (iPSC), currently under intense investigation, as a platform for cell transplantation therapy. Moreover, patient-specific iPSC are being developed for autologous cell transplantation and as a tool for modeling specific retinal diseases, testing gene therapies, and drug screening.

  10. COMPARING THE ENZYME REPLACEMENT THERAPY COST IN POST PANCREATECTOMY PATIENTS DUE TO PANCREATIC TUMOR AND CHRONIC PANCREATITIS.

    Science.gov (United States)

    Fragoso, Anna Victoria; Pedroso, Martha Regina; Herman, Paulo; Montagnini, André Luis

    2016-01-01

    Among late postoperative complications of pancreatectomy are the exocrine and endocrine pancreatic insufficiencies. The presence of exocrine pancreatic insufficiency imposes, as standard treatment, pancreatic enzyme replacement. Patients with chronic pancreatitis, with intractable pain or any complications with surgical treatment, are likely to present exocrine pancreatic insufficiency or have this condition worsened requiring adequate dose of pancreatic enzymes. The aim of this study is to compare the required dose of pancreatic enzyme and the enzyme replacement cost in post pancreatectomy patients with and without chronic pancreatitis. Observational cross-sectional study. In the first half of 2015 patients treated at the clinic of the Department of Gastrointestinal Surgery at Hospital das Clínicas, Universidade de São Paulo, Brazil, who underwent pancreatectomy for at least 6 months and in use of enzyme replacement therapy were included in this series. The study was approved by the Research Ethics Committee. The patients were divided into two groups according to the presence or absence of chronic pancreatitis prior to pancreatic surgery. For this study, Ptreatment was R$ 2150.5 ± 729.39; R$ 2118.18 ± 731.02 in patients without pancreatitis and R$ 2217.74 ± 736.30 in patients with pancreatitis. There was no statistically significant difference in the cost of treatment of enzyme replacement post pancreatectomy in patients with or without chronic pancreatitis prior to surgical indication.

  11. Fatal Candida septic shock during systemic chemotherapy in lung cancer patient receiving corticosteroid replacement therapy for hypopituitarism. A case report

    International Nuclear Information System (INIS)

    Morichika, Daisuke; Sato-Hisamoto, Akiko; Hotta, Katsuyuki

    2014-01-01

    Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage 3A. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (1) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (2) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome. (author)

  12. IGF-I replacement therapy in children with congenital IGF-I deficiency (Laron syndrome) maintains heart dimension and function.

    Science.gov (United States)

    Scheinowitz, Mickey; Feinberg, Micha S; Laron, Zvi

    2009-06-01

    Untreated patients with congenital growth hormone deficiency (GHD) and IGF-I deficiency are characterized not only by dwarfism but also by acromicria and organomicria, such as the heart. We assessed cardiac dimensions and function in very young patients with Laron syndrome (LS) undergoing IGF-I replacement therapy. Two to seven echocardiographic measurements were performed during IGF-I replacement therapy on male (n=4) and female (n=4) LS -patients, mean+/-SD age of 7.1+/-3.6 years (range 1.6-11.6 years), weight 16.1+/-9.7 kg, and height 89.9+/-18.5 cm. As aged- and gender-matched controls served 44 healthy children, age: 8.7+/-5.5 years, weight: 36.1+/-22.4 kg, and height: 129.7+/-33.1cm. Data of LS patients were normalized to body surface area and compared to the control group as well as nomograms of normal echocardiographic parameters for this age group. Left ventricular diastolic and systolic dimensions (LVDD/ LVSD, mm) and LV mass (gr) were significantly smaller in boys and girls with IGF-I treated LS compared with controls while the shortening fraction (%) and intraventricular septum thickness (mm) were similar. When compared with standard values for this age group, all treated LS patients were within 1 standard deviation of the mean. IGF-I therapy of young patients with Laron syndrome maintain LV dimensions and function within the normal range of aged-matched controls.

  13. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease

    DEFF Research Database (Denmark)

    Hughes, Derralynn A.; Nicholls, Kathleen; Shankar, Suma P.

    2017-01-01

    Background Fabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement t...

  14. Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe

    DEFF Research Database (Denmark)

    Chesnaye, Nicholas C; Schaefer, Franz; Bonthuis, Marjolein

    2017-01-01

    HR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. FINDINGS: Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate......BACKGROUND: We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. METHODS: In this registry analysis, we extracted...... patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (a...

  15. Hormone Replacement Therapy and Colorectal Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

    Science.gov (United States)

    Symer, Matthew M; Wong, Natalie Z; Abelson, Jonathan S; Milsom, Jeffrey W; Yeo, Heather L

    2018-06-01

    Hormone replacement therapy has been shown to reduce colorectal cancer incidence, but its effect on colorectal cancer mortality is controversial. The objective of this study was to determine the effect of hormone replacement therapy on survival from colorectal cancer. We performed a secondary analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter randomized trial run from 1993 to 2001, with follow-up data recently becoming mature. Participants were women aged 55 to 74 years, without recent colonoscopy. Data from the trial were analyzed to evaluate colorectal cancer incidence, disease-specific mortality, and all-cause mortality based on subjects' use of hormone replacement therapy at the time of randomization: never, current, or former users. A total of 75,587 women with 912 (1.21%) incident colorectal cancers and 239 associated deaths were analyzed, with median follow-up of 11.9 years. Overall, 88.6% were non-Hispanic white, and colorectal cancer incidence in current users compared to never-users was lower (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69-0.94; P = .005), as was death from colorectal cancer (HR, 0.63; 95% CI, 0.47-0.85; P = .002) and all-cause mortality (HR, 0.76; 95% CI, 0.72-0.80; P colorectal cancer incidence and improved colorectal cancer-specific survival, as well as all-cause mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Sexual dysfunctions in men affected by autoimmune Addison's disease before and after short-term gluco- and mineralocorticoid replacement therapy.

    Science.gov (United States)

    Granata, Antonio; Tirabassi, Giacomo; Pugni, Valeria; Arnaldi, Giorgio; Boscaro, Marco; Carani, Cesare; Balercia, Giancarlo

    2013-08-01

    There is evidence suggesting that autoimmune Addison's disease (AD) could be associated with sexual dysfunctions probably caused by gluco- and mineralocorticoid deficiency; however, no study has yet treated this subject in males. To evaluate male sexuality and psychological correlates in autoimmune AD before and after gluco- and mineralocorticoid replacement therapy. Twelve subjects with a first diagnosis of autoimmune AD were studied before (baseline) and 2 months after (recovery phase) initiating hormone replacement therapy. Erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), overall satisfaction (OS), depression, and anxiety were studied using a number of questionnaires (International Index of Erectile Function, Beck Depression Inventory, and Spielberger State-Trait Anxiety Inventory); clinical, biochemical, and hormone data were included in the analysis. At baseline, low values were found for EF, OF, SD, IS, and OS and high values for depression and anxiety; all of these parameters improved significantly in the recovery phase compared with baseline. EF variation between the two phases correlated significantly and positively with the variation of serum cortisol, urinary free cortisol, systolic blood pressure, and diastolic blood pressure and inversely with that of upright plasma renin activity. Multiple linear regression analysis using EF variation as dependent variable confirmed the relationship of the latter with variation of serum cortisol, urinary free cortisol, and upright plasma renin activity but not with variation of systolic and diastolic blood pressure. Our study showed that onset of autoimmune AD in males is associated with a number of sexual dysfunctions, all reversible after initiating replacement hormone therapy; cortisol and aldosterone deficiency seems to play an important role in the genesis of erectile dysfunction although the mechanism of their activity is not clear. © 2012 International Society

  17. Lipid Replacement Therapy Drink Containing a Glycophospholipid Formulation Rapidly and Significantly Reduces Fatigue While Improving Energy and Mental Clarity

    Directory of Open Access Journals (Sweden)

    Robert Settineri

    2011-08-01

    Full Text Available Background: Fatigue is the most common complaint of patients seeking general medical care and is often treated with stimulants. It is also important in various physical activities of relatively healthy men and women, such as sports performance. Recent clinical trials using patients with chronic fatigue have shown the benefit of Lipid Replacement Therapy in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Methods: Lipid Replacement Therapy was administered for the first time as an all-natural functional food drink (60 ml containing polyunsaturated glycophospholipids but devoid of stimulants or herbs to reduce fatigue. This preliminary study used the Piper Fatigue Survey instrument as well as a supplemental questionnaire to assess the effects of the glycophospholipid drink on fatigue and the acceptability of the test drink in adult men and women. A volunteer group of 29 subjects of mean age 56.2±4.5 years with various fatigue levels were randomly recruited in a clinical health fair setting to participate in an afternoon open label trial on the effects of the test drink. Results: Using the Piper Fatigue instrument overall fatigue among participants was reduced within the 3-hour seminar by a mean of 39.6% (p<0.0001. All of the subcategories of fatigue showed significant reductions. Some subjects responded within 15 minutes, and the majority responded within one hour with increased energy and activity and perceived improvements in cognitive function, mental clarity and focus. The test drink was determined to be quite acceptable in terms of taste and appearance. There were no adverse events from the energy drink during the study.Functional Foods in Health and Disease 2011; 8:245-254Conclusions: The Lipid Replacement Therapy functional food drink appeared to be a safe, acceptable and potentially useful new method to reduce fatigue, sustain energy and improve perceptions of mental function.

  18. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...

  19. Optimal timing of renal replacement therapy initiation in acute kidney injury: the elephant felt by the blindmen?

    Science.gov (United States)

    Shiao, Chih-Chung; Huang, Tao-Min; Spapen, Herbert D; Honore, Patrick M; Wu, Vin-Cent

    2017-06-20

    Renal replacement therapy (RRT) is a key component in the management of severe acute kidney injury (AKI) in critically ill patients. Many cohort studies, meta-analyses, and two recent large randomized prospective trials which evaluated the relationship between the timing of RRT initiation and patient outcome remain inconclusive due to substantial differences in study design, patient population, AKI definition, and RRT indication. A cause-specific diagnosis of AKI based on current staging criteria plus a sensitive biomarker (panel) that allows creating a homogeneous study population is definitely needed to assess the impact of early versus late initiation of RRT on patient outcome.

  20. Benign Phyllodes Tumor Mimicking a Malignancy in a Turner Syndrome Woman with Hormone Replacement Therapy: A Case Report

    International Nuclear Information System (INIS)

    Lee, Woong Jae; Chong, Se Min; Pang, Jae Choon; Seo, Jae Seung; Byun, Jun Soo; Seok, Ju Won; Shin, Hee Jung; Gong, Gyung Yub

    2010-01-01

    Phyllodes tumor of the breast is a relatively rare fibroepithelial tumor. Turner syndrome is a condition that affects approximately 50 per 100,000 females and includes total or partial absence of one X chromosome in all or part of the cells, reduced final height, absence of female sex hormone, and infertility. In this case report, we describe the first case of a benign phyllodes tumor mimicking a malignancy at breast US in a 26-year-old woman with Turner syndrome who had been undergoing hormone replacement therapy

  1. Benign Phyllodes Tumor Mimicking a Malignancy in a Turner Syndrome Woman with Hormone Replacement Therapy: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Woong Jae; Chong, Se Min; Pang, Jae Choon; Seo, Jae Seung; Byun, Jun Soo; Seok, Ju Won [Chung-Ang University Medical Center, Chung-Ang University College of Medicine, Seoul (Korea, Republic of); Shin, Hee Jung; Gong, Gyung Yub [Asan Medical Center, University of Ulsan College of Mdeicine, Seoul (Korea, Republic of)

    2010-12-15

    Phyllodes tumor of the breast is a relatively rare fibroepithelial tumor. Turner syndrome is a condition that affects approximately 50 per 100,000 females and includes total or partial absence of one X chromosome in all or part of the cells, reduced final height, absence of female sex hormone, and infertility. In this case report, we describe the first case of a benign phyllodes tumor mimicking a malignancy at breast US in a 26-year-old woman with Turner syndrome who had been undergoing hormone replacement therapy

  2. Renal Replacement Therapy in End-Stage Sickle Cell Nephropathy: Presentation of Two Cases and Literature Review

    International Nuclear Information System (INIS)

    Al-Mueilo, Samir H.

    2005-01-01

    Chronic renal failure develops in 4-18% of patients with sickle cell anemia. Hemodialysis and kidney transplant are viable options in the management of end-stage renal disease in patients with sickle cell diseases (SCD). Information on kidney disease among Saudi patients with SCD is non-existing. In this report, the clinical course of two adult males with end-stage sickle cell nephropathy from Eastern Saudi Arabia is described. Literature on renal replacement therapy in sickle cell anemia (SCA) is discussed. (author)

  3. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease

    Directory of Open Access Journals (Sweden)

    Goláň L

    2015-07-01

    Full Text Available Lubor Goláň,1 Ozlem Goker-Alpan,2 Myrl Holida,3 Ikka Kantola,4 Mariusz Klopotowski,5 Johanna Kuusisto,6 Aleš Linhart,1 Jacek Musial,7 Kathleen Nicholls,8 Derlis Gonzalez-Rodriguez,9 Reena Sharma,10 Bojan Vujkovac,11 Peter Chang,12 Anna Wijatyk12 1First Faculty of Medicine, Department of Cardiovascular Medicine, Charles University, Prague, Czech Republic; 2Lysosomal Research and Treatment Unit, Fairfax, VA, USA; 3Stead Family Department of Pediatrics, Division of Medical Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 4Division of Medicine, Turku University Hospital, Turku, Finland; 5Institute of Cardiology, Warsaw, Poland; 6Department of Medicine, Center for Medicine and Clinical Research, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; 7Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland; 8Department of Nephrology, Royal Melbourne Hospital and the University of Melbourne, VIC, Australia; 9Instituto Privado de Hematologia E Investigacion Clinica (IPHIC, Asuncion, Paraguay; 10Salford Royal NHS Foundation Trust, Salford, UK; 11General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia; 12Shire, Lexington, MA, USA Purpose: Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW. Exploratory analyses were performed for 0.4 mg/kg weekly.Patients and methods: This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643 in treatment-naïve adults (≥18 years with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New York Heart Association classification, renal (Modification of Diet in Renal Disease, estimated glomerular filtration rate, and biomarker (plasma globotriaosylceramide assessments. Safety endpoints were adverse events and anti–agalsidase alfa antibodies.Results: Twenty patients were randomized to 0.2 mg/kg EOW (mean age, 50.3 years; 70% male, 19 to 0.2 mg/kg weekly (51.8 years; 53% male, and 5 to 0.4 mg/kg weekly (49.4 years; 40% male. The mean change in left ventricular mass indexed to height by Week 53 in the 0.2-mg/kg EOW and weekly groups was 3.2 g/m2.7 and 0.5 g/m2.7, with no significant difference between groups. No clinically meaningful changes by Week 53 were found within or between the 0.2-mg/kg groups for peak oxygen consumption, 6-minute walk test, or Minnesota Living with Heart Failure Questionnaire. Two patients in each group improved by ≥1 New York Heart Association classi­fication. No significant differences were found between 0.2 mg/kg EOW and weekly for mean change in estimated glomerular filtration rate (-1.21 mL/min/1.73 m2 vs -3.32 mL/min/1.73 m2 or plasma globotriaosylceramide (-1.05 nmol/mL vs -2.13 nmol/mL, respectively. Infusion-related adverse events were experienced by 25% and 21% in the 0.2-mg/kg EOW and weekly groups. Tachycardia, fatigue, and hypotension were experienced by two or more patients overall. Anti–agalsidase alfa antibodies were detected in 11.4% of patients and neutralizing antibodies in 6.8%. Infusion-related reactions did not appear to be correlated with antibody status.Conclusion: No efficacy or safety differences were found when the approved EOW dosage of agalsidase alfa was increased to weekly administration. Exploratory analyses for 0.4 mg/kg weekly showed similar results. Keywords: adverse events, exercise tolerance, left ventricular hypertrophy, lysosomal storage disorder, quality of life, renal function

  4. Impaired health-related quality of life in Addison's disease--impact of replacement therapy, comorbidities and socio-economic factors.

    Science.gov (United States)

    Kluger, Nicolas; Matikainen, Niina; Sintonen, Harri; Ranki, Annamari; Roine, Risto P; Schalin-Jäntti, Camilla

    2014-10-01

    Patients with Addison's disease (AD) on conventional replacement therapy have impaired health-related quality of life (HRQoL). It is possible that lower hydrocortisone (HC) doses recommended by current guidelines could restore HRQoL. We compared HRQoL in AD patients treated according to current HC recommendations to that of the age- and gender-standardized general population. We assessed HRQoL in a cross-sectional setting with the 15D instrument in a Finnish AD cohort (n = 107) and compared the results with those of a large sample of general population (n = 5671). We examined possible predictors of HRQoL in AD. Within the patient group, HRQoL was also assessed by SF-36. Mean HC dose was 22 mg/d, corresponding to 12 ± 4 mg/m2. HRQoL was impaired in AD compared with the general population (15D score; 0·853 vs 0·918, P < 0·001). Within single 15D dimensions, discomfort and symptoms, vitality and sexual activity were most affected. Stepwise regression analysis demonstrated that Patient's Association membership (P = 0·02), female gender (P < 0·01), presence of other autoimmune or inflammatory comorbidity (P < 0·02), lower education (P < 0·02) and longer disease duration (P < 0·05) independently predicted impaired HRQoL, whereas replacement regimens, autoimmune-related comorbidities, total number of comorbidities or level of healthcare follow-up did not. In AD, HRQoL was impaired also as assessed by SF-36. HRQoL is significantly impaired in AD compared with the general population despite use of recommended HC doses. Patient's Association membership was the most significant predictor of impaired HRQoL. This finding should be explored in more detail in the future. © 2014 John Wiley & Sons Ltd.

  5. Prepubertal ultra-low-dose estrogen therapy is associated with healthier lipid profile than conventional estrogen replacement for pubertal induction in adolescent girls with Turner syndrome: preliminary results.

    Science.gov (United States)

    Ruszala, Anna; Wojcik, Malgorzata; Zygmunt-Gorska, Agata; Janus, Dominika; Wojtys, Joanna; Starzyk, Jerzy B

    2017-08-01

    The metabolic effects of prepubertal low-dose estrogen replacement (LE) therapy in Turner syndrome (TS) have not been fully investigated to date. The present study aimed to compare glucose and lipids metabolism in adolescents with TS on LE and conventional estrogen replacement (CE). In 14 TS (mean age 13.8), LE (17β-estradiol, 62.5 μg daily) was introduced before age 12 (mean age 10.5), and followed by a pubertal induction regimen after age 12, and in 14 CE was started after age 12 (mean 14, SD 1.96). Before, and 3 years after starting 17β-estradiol growth velocity, bone age, BMI, and selected parameters of glucose and lipids metabolism were assessed. There were no significant differences between LE and CE in the mean levels of any parameter before introduction of 17β-estradiol [total cholesterol (TC): 4.1 vs 4.3 mmol/L, LDL cholesterol (LDLc): 2.2 vs 2.4 mmol/L, HDL cholesterol (HDLc): 1.6 vs 1.4 mmol/L, triglycerides: 0.9 vs 1.0 mmol/L, fasting glucose: 4.2 vs 4.4 mmol/L, post-load glucose: 4.8 vs 5.5 mmol/L; fasting insulin: 6.8 vs 8.0 post-load insulin: 21.3 vs 67.0 μIU/mL, HOMA-IR 1.3 vs 1.6]. After three years of treatment, TC and LDLc levels were significantly lower in LE group (3.8 vs 4.4 mmol/L, p = 0.004; 1.9 vs 2.4 mmol/L, p = 0.03). The other parameters did not differ significantly. There was no negative impact on growth course and bone age advancement nor on BMI in LE group. Prepubertal LE is associated with healthier lipid profile than CE in girls with TS.

  6. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century.

    Science.gov (United States)

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-09-07

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.

  7. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century

    Science.gov (United States)

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-01-01

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy. PMID:25206255

  8. Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen.

    LENUS (Irish Health Repository)

    Cassidy, Eugene M

    2012-10-01

    The aim of the study was to compare symptom-triggered and standard benzodiazepine regimens for the treatment of alcohol withdrawal syndrome in an emergency department clinical decision unit. The authors found that the symptom-triggered approach reduced cumulative benzodiazepine dose and length of stay.

  9. Comparison of therapy augmentation and deviation rates from the recommended once-daily dosing regimen between LDX and commonly prescribed long-acting stimulants for the treatment of ADHD in youth and adults.

    Science.gov (United States)

    Setyawan, Juliana; Hodgkins, Paul; Guérin, Annie; Gauthier, Geneviève; Cloutier, Martin; Wu, Eric; Erder, M Haim

    2013-10-01

    To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants. ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models. Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically

  10. Tobacco Industry Research on Nicotine Replacement Therapy: "If Anyone Is Going to Take Away Our Business It Should Be Us".

    Science.gov (United States)

    Apollonio, Dorie; Glantz, Stanton A

    2017-10-01

    Nicotine replacement therapy (NRT) is recommended for tobacco cessation on the basis of pharmaceutical industry research showing its effectiveness when combined with counseling. The tobacco industry opposed NRT when it first appeared in the 1980s but by 2016 was marketing its own NRT products. We used internal tobacco industry documents dated 1960 through 2010 to identify the industry's perceptions of NRT. As early as the 1950s, tobacco companies developed nonsmoked nicotine replacements for cigarettes, but they stopped out of concern that marketing such products would trigger Food and Drug Administration regulation of cigarettes. In the 1990s, after pharmaceutical companies began selling prescription NRT, tobacco companies found that many smokers used NRT to supplement smoking rather than to quit. In 2009, once the Food and Drug Administration began regulating tobacco, tobacco companies restarted their plans to capture the nicotine market. Although the tobacco industry initially viewed NRT as a threat, it found that smokers often combined NRT with smoking rather than using it as a replacement and began marketing their own NRT products.

  11. Sleeve gastrectomy leads to easy management of hormone replacement therapy and good weight loss in patients treated for craniopharyngioma.

    Science.gov (United States)

    Trotta, Manuela; Da Broi, Joël; Salerno, Angelo; Testa, Rosa M; Marinari, Giuseppe M

    2017-03-01

    The aim of this study is to investigate the effects of sleeve gastrectomy on hormone replacement therapy and on hypothalamic obesity in patients affected by craniopharyngioma with post-surgical pan-hypopituitarism. A retrospective review of three patients, treated for hypothalamic obesity with laparoscopic sleeve gastrectomy, who have previously undergone surgery for craniopharyngioma in their childhood, was done. Patients' mean age and BMI were 22.3 years (range 21-24) and 49.2 kg/m 2 (range 41.6-58.1), respectively. The mean time of delay between neurosurgery and bariatric surgery was 12.3 years (range 6-16). There were no major complications or deaths. At 24 months follow-up, the mean BMI was 35.3 kg/m 2 (range 31.2-40.6). No hydrocortisone and sex steroids dose changes were observed, while levothyroxine was decreased in two patients. Growth hormone replacement therapy was increased in two patients, whereas it was started in one patient. Desmopressin was significantly decreased in all of them. Patients with surgically induced pan-hypopituitarism after craniopharyngioma who become obese, can expect good results from sleeve gastrectomy: this procedure does not have significant negative effects on hormone substitution and leads to a good stabilization of body weight in a mid-term follow-up.

  12. Serum estrogen and SHBG levels and breast cancer incidence among users and never users of hormone replacement therapy

    DEFF Research Database (Denmark)

    Würtz, Anne Mette Lund; Tjønneland, Anne; Christensen, Jane

    2012-01-01

    OBJECTIVE: Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT. METHODS: A nested case-control study was conducted within the ...... and baseline HRT users. More studies are needed to support the findings for HRT users and to further investigate estrogen levels in relation to estrogen receptor-specific breast cancer and other histological and molecular subtypes.......OBJECTIVE: Levels of endogenous estrogen and SHBG are associated with risk of breast cancer among women who have never used hormone replacement therapy (HRT). We investigated these associations in both never and baseline users of HRT. METHODS: A nested case-control study was conducted within...... logistic regression yielded incidence rate ratios and 95 % confidence intervals for exposures analyzed continuously and categorically in models adjusted for potential confounders. RESULTS: Modest direct associations were identified between estrogen levels and breast cancer incidence among both never...

  13. Effect of hormone replacement therapy on the bone mass and urinary excretion of pyridinium cross-links.

    Science.gov (United States)

    Pardini, D P; Sabino, A T; Meneses, A M; Kasamatsu, T; Vieira, J G

    2000-01-06

    The menopause accelerates bone loss and is associated with an increased bone turnover. Bone formation may be evaluated by several biochemical markers. However, the establishment of an accurate marker for bone resorption has been more difficult to achieve. To study the effect of hormone replacement therapy (HRT) on bone mass and on the markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. Cohort correlational study. Academic referral center. 53 post-menopausal women, aged 48-58 years. Urinary pyr and d-pyr were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion measured before treatment and after 1, 2, 4 and 12 months. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DEXA) before treatment and after 12 months of HRT. The BMD after HRT was about 4.7% (P < 0.0004); 2% (P < 0.002); and 3% (P < 0. 01) higher than the basal values in lumbar spine, neck and trochanter respectively. There were no significant correlations between pyridinium cross-links and age, weight, menopause duration and BMD. The decrease in pyr and d-pyr was progressive after HRT, reaching 28.9% (P < 0.0002), and 42% (P < 0.0002) respectively after 1 year. Urinary pyridinoline and deoxypyridinoline excretion decreases early in hormone replacement therapy, reflecting a decrease in the bone resorption rate, and no correlation was observed with the bone mass evaluated by densitometry.

  14. EVALUATING THE EFFECTIVENESS OF PROPHYLACTIC REPLACEMENT THERAPY IN CHILDREN WITH HEMOPHILIC ARTHROPATHY IN DYNAMICS ON MAGNETIC RESONANCE IMAGING

    Directory of Open Access Journals (Sweden)

    I. S. Remzantseva

    2015-01-01

    Full Text Available Modifications in treatment guidelines of hemophilic arthropathy changed the role of diagnostic X-ray imaging methods. Diagnostic methods are used both for determination of the degree of joint destruction and long-term evaluation of the joint conditions and therapy adequacy and effectiveness. Aim. Magnetic resonance imaging (MRI dynamics for joint condition assessment in children with hemophilic arthropathy receiving prophylactic factor replacement therapy concentrated rolling VIII. Materials and methods. We studied 13 boys aged 5 to 14 years (mean age 8.9 years with hemophilia type A severe form of the disease (factor VIII deficiency <1% at the baseline. The average age of appearance of hemarthrosis is 2.1 years (from 1.8 to 2.9 years. The frequency of bleeding into the joints of patients older than 1 year was 2-3 times per year. Magnetic resonance imaging (ToshibaExcelArtVantage, 1,5 T was performed in 13 patients, 35 joints were examined, 57 studies were executed. Control study of joints was conducted in 1, 2 or 3 years depending on the frequency of hemarthrosis during the year and the severity of joint damage primarily identified. Results. The results included both the improvement along with the stabilization of intra-state structures and the negative dynamic shifts. MRI showed that the reduction of bleeding in the joints on the background of hemostatic replacement therapy led to subsiding inflammation in the joints and significant decrease in the amount of intra-articular effusion (n = 11; p = 0.03, decrease in the number of joints with symptoms of bone marrow edema (n = 8, the absence of observations with negative changes in the form of increasing the thickness of the synovial membrane. Negative dynamics of joint condition presented as increasing of the depth and length of erosive process (n = 5; 22.7%, degenerative changes in ligaments and menisci (n = 2; 9% under the condition of regular administration of clotting factors was associated

  15. COMPARING THE ENZYME REPLACEMENT THERAPY COST IN POST PANCREATECTOMY PATIENTS DUE TO PANCREATIC TUMOR AND CHRONIC PANCREATITIS

    Directory of Open Access Journals (Sweden)

    Anna Victoria FRAGOSO

    Full Text Available ABSTRACT Background - Among late postoperative complications of pancreatectomy are the exocrine and endocrine pancreatic insufficiencies. The presence of exocrine pancreatic insufficiency imposes, as standard treatment, pancreatic enzyme replacement. Patients with chronic pancreatitis, with intractable pain or any complications with surgical treatment, are likely to present exocrine pancreatic insufficiency or have this condition worsened requiring adequate dose of pancreatic enzymes. Objective - The aim of this study is to compare the required dose of pancreatic enzyme and the enzyme replacement cost in post pancreatectomy patients with and without chronic pancreatitis. Methods - Observational cross-sectional study. In the first half of 2015 patients treated at the clinic of the Department of Gastrointestinal Surgery at Hospital das Clínicas, Universidade de São Paulo, Brazil, who underwent pancreatectomy for at least 6 months and in use of enzyme replacement therapy were included in this series. The study was approved by the Research Ethics Committee. The patients were divided into two groups according to the presence or absence of chronic pancreatitis prior to pancreatic surgery. For this study, P<0.05 was considered statistically significant. Results - The annual cost of the treatment was R$ 2150.5 ± 729.39; R$ 2118.18 ± 731.02 in patients without pancreatitis and R$ 2217.74 ± 736.30 in patients with pancreatitis. Conclusion - There was no statistically significant difference in the cost of treatment of enzyme replacement post pancreatectomy in patients with or without chronic pancreatitis prior to surgical indication.

  16. Cell-replacement and gene-therapy strategies for Parkinson's and Alzheimer's disease

    NARCIS (Netherlands)

    Korecka, Joanna A; Verhaagen, J.; Hol, Elly M

    Parkinson's disease and Alzheimer's disease are the most common neurodegenerative diseases in the elderly population. Given that age is the most important risk factor in these diseases, the number of patients is expected to rise dramatically in the coming years. Therefore, an effective therapy for

  17. Primary hypothyroidism mimicking a pituitary macroadenoma: regression after thyroid hormone replacement therapy

    International Nuclear Information System (INIS)

    Eom, Ki Seong; Kim, Jong Moon; Kim, Tae Young; See-Sung, Choi; Kim, Jong Duck

    2009-01-01

    We report a 9-year-old girl with pituitary hyperplasia due to primary hypothyroidism. She presented with growth arrest, abnormal thyroid function studies, and a pituitary mass on MRI. With thyroxine therapy, the pituitary mass regressed and her symptoms resolved. Primary hypothyroidism should be considered in the differential diagnosis of solid mass lesions of the pituitary gland. (orig.)

  18. An automatic framework for assessing breast cancer risk due to various hormone replacement therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal; Brandt, Sami; Nielsen, Mads

    It is well known that menopausal hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998), J.M. Boone(...

  19. An Automatic Framework for Assessing Breast Cancer Risk Due to Various Hormone Replacement Therapies (HRT)

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Brandt, Sami; Nielsen, Mads

    Background: It is well known that Menopausal Hormone therapy increases mammographic density. Increase in breast density may relate to breast cancer risk. Several computer assisted automatic methods for assessing mammographic density have been suggested by J.W. Byng (1996), N. Karssemeijer (1998),...

  20. Effect of hormone replacement therapy on bone quality in early postmenopausal women

    DEFF Research Database (Denmark)

    Paschalis, E P; Boskey, A L; Kassem, M

    2003-01-01

    HRT is an effective prophylaxis against postmenopausal bone loss. Infrared imaging of paired iliac crest biopsies obtained at baseline and after 2 years of HRT therapy demonstrate an effect on the mineral crystallinity and collagen cross-links that may affect bone quality. Several studies have de...

  1. Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk

    DEFF Research Database (Denmark)

    Rudolph, Anja; Hein, Rebecca; Lindström, Sara

    2013-01-01

    Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case...

  2. Primary hypothyroidism mimicking a pituitary macroadenoma: regression after thyroid hormone replacement therapy

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Ki Seong; Kim, Jong Moon; Kim, Tae Young [Wonkwang University School of Medicine, Department of Neurosurgery, Iksan (Korea); See-Sung, Choi [Wonkwang University School of Medicine, Department of Radiology, Iksan (Korea); Kim, Jong Duck [Wonkwang University School of Medicine, Department of Pediatrics, Iksan (Korea)

    2009-02-15

    We report a 9-year-old girl with pituitary hyperplasia due to primary hypothyroidism. She presented with growth arrest, abnormal thyroid function studies, and a pituitary mass on MRI. With thyroxine therapy, the pituitary mass regressed and her symptoms resolved. Primary hypothyroidism should be considered in the differential diagnosis of solid mass lesions of the pituitary gland. (orig.)

  3. Randomized phase II trial evaluating two paclitaxel and cisplatin-containing chemoradiation regimens as adjuvant therapy in resected gastric cancer (RTOG-0114).

    Science.gov (United States)

    Schwartz, Gary K; Winter, Kathryn; Minsky, Bruce D; Crane, Christopher; Thomson, P John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

    2009-04-20

    The investigational arm of INT0116, a fluorouracil (FU) and leucovorin-containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin-containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials.

  4. Proteome-wide analysis of neural stem cell differentiation to facilitate transition to cell replacement therapies

    Czech Academy of Sciences Publication Activity Database

    Žižková, Martina; Suchá, Rita; Tylečková, Jiřina; Jarkovská, Karla; Mairychová, Kateřina; Kotrčová, Eva; Marsala, M.; Gadher, S. J.; Kovářová, Hana

    2015-01-01

    Roč. 12, č. 1 (2015), s. 83-95 ISSN 1478-9450 R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR(CZ) TA01011466 Institutional support: RVO:67985904 Keywords : cell therapy * immunomodulation * neural stem cell differentiation * neural subpopulation * neurodegenerative disease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.465, year: 2015

  5. Psychosocial issues and quality of life in patients on renal replacement therapy

    International Nuclear Information System (INIS)

    Panagopoulou, Alkioni; Hardalias, Andreas; Fourtounas, Costas; Berati, Stavroula

    2009-01-01

    The aim of the present study was to investigate psychosocial variables related to objective and subjective indicators of quality of life in a single center cohort study of patients undergoing in-center hemodialysis (Hd), Continuous Ambulatory Peritoneal Dialysis (CAPD) and renal transplant recipients (RTx). We studied 40 HD patients, 36 CAPD, and 48 RTx patients by a special questionnaire examining demographics, functional status, employment status, and impact of therapy on psychosocial issues such as anxiety and depression. The RTx patients disclosed a better functional and employment status than the CAPD and the HD patients. They were also more compliant and satisfied with their therapy and their relationship with the medical and nursing personnel. The CAPD patients were also more satisfied, more compliant, better motivated, and less anxious and depressed compared with the HD patients who scored low in every aspect studied. Successful renal transplantation is a superior modality of therapy than HD or CAPD regarding psychosocial and quality of life issues. However these results can partially be explained by some selection bias, as RTx patients are usually younger and CAPD patients are selected for this modality after examining functional and social status. (author)

  6. No Effect of Acupuncture as Adjunctive Therapy for Patients with Total Knee Replacement

    DEFF Research Database (Denmark)

    Petersen, Tom; Hautopp, Holger; Duus, Benn

    2018-01-01

    Objective: Acupuncture is a low risk option in pain management following total knee replacement as an alternative to opioid analgesics. Therefore, the benefit of acupuncture as adjunct to an exercise program was investigated. Furthermore, the modifying effect of previous benefit from acupuncture...... was explored. Design: Three weeks postoperatively, eligible patients were randomized to acupuncture and exercises or exercises alone. Setting: An outpatient rehabilitation centre in the municipality of Copenhagen, Denmark. Subjects: A total of 172 patients were included. Methods: Main outcome was proportion...... of the course of treatment were assessed. Results: No additional benefit of acupuncture was found on any of the main outcomes. Between-group differences were non-significant in proportions of patients with a clinically important reduction of night pain (Relative Risk: 0.98; 95% Confidence Interval (CI): 0...

  7. Modulatory Effects of Antibody Replacement Therapy to Innate and Adaptive Immune Cells

    Directory of Open Access Journals (Sweden)

    Isabella Quinti

    2017-06-01

    Full Text Available Intravenous immunoglobulin administered at replacement dosages modulates innate and adaptive immune cells in primary antibody deficiencies (PAD in a different manner to what observed when high dosages are used or when their effect is analyzed by in vitro experimental conditions. The effects seem to be beneficial on innate cells in that dendritic cells maturate, pro-inflammatory monocytes decrease, and neutrophil function is preserved. The effects are less clear on adaptive immune cells. IVIg induced a transient increase of Treg and a long-term increase of CD4 cells. More complex and less understood is the interplay of IVIg with defective B cells of PAD patients. The paucity of data underlies the need of more studies on patients with PAD before drawing conclusions on the in vivo mechanisms of action of IVIg based on in vitro investigations.

  8. Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement.

    Science.gov (United States)

    Napoli, Eleonora; Lippert, Trenton; Borlongan, Cesar V

    2018-02-27

    Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.

  9. Lipoproteína a, aterosclerosis y terapia hormonal de reemplazo Lipoprotein a, atherosclerosis and replacement hormone therapy

    Directory of Open Access Journals (Sweden)

    Miguel Lugones Botell

    2005-08-01

    Full Text Available Se realizó una revisión sobre la lipoproteína plasmática, Lp(a, cuyo papel fisiológico es poco conocido. Se ha descrito una asociación entre las concentraciones aumentadas de Lp(a y el proceso aterosclerótico. Además, su exceso podría inducir una disminución de la actividad fibrinolítica y, por tanto, favorecer la trombosis. También analizamos la terapia hormonal de reemplazo. En relación con los efectos positivos, mejora los síntomas climatéricos y previene la osteoporosis, aunque entre los efectos adversos en las mujeres que la siguen, se ha descrito un ligero aumento del riesgo del tromboembolismo venoso, y más recientemente, en estudios realizados en EE.UU. en los años 2002 y 2004, en el ya conocido estudio (Women´s Health Initiative Study, se reportó mayor incidencia de eventos cardiovasculares para la terapia combinada con estrógenos conjugados equinos y medroxiprogesterona, y de stroke para la terapia estrogénica. Estos estudios pusieron en su lugar los efectos de esta terapia, que no es totalmente inocua. Se precisan estudios más amplios para definir el papel de la terapia hormonal de reemplazo y otras medidas terapéuticas sobre el sistema hemostático, el metabolismo lipídico y la enfermedad cardiovascular.A review of plasmatic lipoprotein, Lp(a, whose physiological role is little known, was made. An association between the augmented concentrations of Lp(a and the atherosclerotic proccess has been described. Besides, its excess may lead to a reduction of the fibrinolytic activity and, therefore, favor thrombosis. The replacement hormone therapy was also analyzed. In relation to its positive effects, it improves the climacteric symptoms and prevents osteoporosis. Among its adverse effects, it has been observed a mild increase of the risk for venous thromboembolism and, more recently, in the aleady known Women's Health Initiative Study, it was reported a higher incidence of cardiovascular events for the combined

  10. Androgen deprivation therapy impact on quality of life and cardiovascular health, monitoring therapeutic replacement.

    Science.gov (United States)

    Trost, Landon W; Serefoglu, Ege; Gokce, Ahmet; Linder, Brian J; Sartor, Alton O; Hellstrom, Wayne J G

    2013-02-01

    Androgen deprivation therapy (ADT) is commonly utilized in the management of both localized and advanced adenocarcinoma of the prostate. The use of ADT is associated with several adverse events, physical changes, and development of medical comorbidities/mortality. The current article reviews known adverse events associated with ADT as well as treatment options, where available. Current recommendations and guidelines are cited for ongoing monitoring of patients receiving ADT. A PubMed search of topics relating to ADT and adverse outcomes was performed, with select articles highlighted and reviewed based on level of evidence and overall contribution. Reported outcomes of studies detailing adverse effects of ADT were reviewed and discussed. Where available, randomized trials and meta-analyses were reported. ADT may result in several adverse events including decreased libido, erectile dysfunction, vasomotor symptoms, cognitive, psychological and quality of life impairments, weight gain, sarcopenia, increased adiposity, gynecomastia, reduced penile/testicular size, hair changes, periodontal disease, osteoporosis, increased fracture risk, diabetes and insulin resistance, hyperlipidemia, and anemia. The definitive impact of ADT on lipid profiles, cardiovascular morbidity/mortality, and all-cause mortality is currently unknown with available data. Treatment options to reduce ADT-related adverse events include changing to an intermittent treatment schedule, biophysical therapy, counseling, and pharmacotherapy. Patients treated with ADT are at increased risk of several adverse events and should be routinely monitored for the development of potentially significant morbidity/mortality. Where appropriate, physicians should reduce known risk factors and counsel patients as to known risks and benefits of therapy. © 2013 International Society for Sexual Medicine.

  11. Continuation rate of hormone replacement therapy in Hong Kong public health sector.

    Science.gov (United States)

    Leung, K Y; Ling, M; Tang, G W K

    2004-12-10

    To assess the 1-year continuation rate of HRT prescribed in Hong Kong public health sector and to identify factors affecting this continuation rate. All women who received at least one dispensed prescription of estrogens between January 1998 and December 2000 from 36 specialist outpatient clinics of the Hospital Authority were selected, and observed for at least 2 years and at most 3 years. The duration of use and variables including age, types of hormones, routes of delivery, dose of estrogen, and prescribing specialty were retrieved from the central prescription database of the Hospital Authority. Of 12,711 incident users of HRT, more than half were aged 50-59. Most (78.5%) of the users took conjugated equine estrogens (CEE) 0.625 mg or related products. Only a small proportion (3.0%) of women used CEE 0.3 mg. Initial estrogen prescriptions were written by gynaecologists in 86.7%. The overall 1-year continuation rate was 68.3%. The highest and lowest continuation rates were observed in women aged 40-49 and the two extreme age groups (35-39 and 70-79), respectively. Better continuation rate was observed in women taking estrogen-only therapy such as CEE or estradiol (overall 76.3%) than in women using continuous combined therapy (58.6%), sequential combined therapy (64.8%), or transdermal estrogen (60.6%). In the age group 60-69, the use of CEE 0.3 mg was associated with better continuation rate than CEE 0.625 mg. Better continuation rate at 1 year was associated with age younger than 60, oral route of HRT and hysterectomy.

  12. Associations between preoperative physical therapy and post-acute care utilization patterns and cost in total joint replacement.

    Science.gov (United States)

    Snow, Richard; Granata, Jaymes; Ruhil, Anirudh V S; Vogel, Karen; McShane, Michael; Wasielewski, Ray

    2014-10-01

    Health-care costs following acute hospital care have been identified as a major contributor to regional variation in Medicare spending. This study investigated the associations of preoperative physical therapy and post-acute care resource use and its effect on the total cost of care during primary hip or knee arthroplasty. Historical claims data were analyzed using the Centers for Medicare & Medicaid Services Limited Data Set files for Diagnosis Related Group 470. Analysis included descriptive statistics of patient demographic characteristics, comorbidities, procedures, and post-acute care utilization patterns, which included skilled nursing facility, home health agency, or inpatient rehabilitation facility, during the ninety-day period after a surgical hospitalization. To evaluate the associations, we used bivariate and multivariate techniques focused on post-acute care use and total episode-of-care costs. The Limited Data Set provided 4733 index hip or knee replacement cases for analysis within the thirty-nine-county Medicare hospital referral cluster. Post-acute care utilization was a significant variable in the total cost of care for the ninety-day episode. Overall, 77.0% of patients used post-acute care services after surgery. Post-acute care utilization decreased if preoperative physical therapy was used, with only 54.2% of the preoperative physical therapy cohort using post-acute care services. However, 79.7% of the non-preoperative physical therapy cohort used post-acute care services. After adjusting for demographic characteristics and comorbidities, the use of preoperative physical therapy was associated with a significant 29% reduction in post-acute care use, including an $871 reduction of episode payment driven largely by a reduction in payments for skilled nursing facility ($1093), home health agency ($527), and inpatient rehabilitation ($172). The use of preoperative physical therapy was associated with a 29% decrease in the use of any post-acute care

  13. Myogenic Precursors from iPS Cells for Skeletal Muscle Cell Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Isart Roca

    2015-01-01

    Full Text Available The use of adult myogenic stem cells as a cell therapy for skeletal muscle regeneration has been attempted for decades, with only moderate success. Myogenic progenitors (MP made from induced pluripotent stem cells (iPSCs are promising candidates for stem cell therapy to regenerate skeletal muscle since they allow allogenic transplantation, can be produced in large quantities, and, as compared to adult myoblasts, present more embryonic-like features and more proliferative capacity in vitro, which indicates a potential for more self-renewal and regenerative capacity in vivo. Different approaches have been described to make myogenic progenitors either by gene overexpression or by directed differentiation through culture conditions, and several myopathies have already been modeled using iPSC-MP. However, even though results in animal models have shown improvement from previous work with isolated adult myoblasts, major challenges regarding host response have to be addressed and clinically relevant transplantation protocols are lacking. Despite these challenges we are closer than we think to bringing iPSC-MP towards clinical use for treating human muscle disease and sporting injuries.

  14. Salivary cortisol and explicit memory in postmenopausal women using hormone replacement therapy.

    Science.gov (United States)

    Hampson, Elizabeth; Duff-Canning, Sarah J

    2016-02-01

    Circulating cortisol levels are known to influence explicit memory in humans and other primates. The present study investigated salivary cortisol and its association with explicit memory performance in 99 postmenopausal women (64 treated with conjugated equine estrogens or estradiol, and 35 matched controls not using any form of hormone therapy). Controls were compared with treated women taking estrogens alone (n=39), or taking estrogens in combination with a progestin (n=25). Mean time on hormone therapy was approximately 5 years, with initiation of treatment in close proximity to the onset of menopause. Explicit memory was assessed with the California Verbal Learning Test (CVLT). Saliva was collected before (basal or resting sample) and after (post-test sample) completing a set of cognitive tasks. Cortisol was measured using a high-sensitivity radioimmunoassay. Treated women were found to have higher resting cortisol concentrations than controls matched for time of day. Basal cortisol was a modest predictor of learning and memory on the CVLT. Higher cortisol was associated with better recall and fewer memory errors, which is consistent with experimental studies examining explicit memory under small increases in circulating cortisol load. Potential cumulative effects on the central nervous system of sustained exposure to mildly increased cortisol in conjunction with the long-term use of oral estrogens are discussed in the context of aging and dementia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.

    Science.gov (United States)

    Liu, Qian; Sun, Jessica D; Wang, Jingli; Ahluwalia, Dharmendra; Baker, Amanda F; Cranmer, Lee D; Ferraro, Damien; Wang, Yan; Duan, Jian-Xin; Ammons, W Steve; Curd, John G; Matteucci, Mark D; Hart, Charles P

    2012-06-01

    Subregional hypoxia is a common feature of tumors and is recognized as a limiting factor for the success of radiotherapy and chemotherapy. TH-302, a hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors, delivers a cytotoxic warhead to the tumor, while maintaining relatively low systemic toxicity. The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models. Seven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH-302 in eleven human xenograft models, including non-small cell lung cancer (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic cancer. The antitumor activity of docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when combined with TH-302 in nine out of eleven models tested. Administration of TH-302 2-8 h prior to the other chemotherapeutics yielded superior efficacy versus other sequences tested. Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations. In a dosing optimization study, TH-302 administered daily at 50 mg/kg intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal response with minimal toxicity. TH-302 enhances the activity of a wide range of conventional anti-neoplastic agents in a broad panel of in vivo xenograft models. These data highlight in vivo effects of schedule and order of drug administration in regimen efficacy and toxicity and have relevance to the design of human regimens incorporating TH-302.

  16. Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)

    Science.gov (United States)

    Schwartz, Gary K.; Winter, Kathryn; Minsky, Bruce D.; Crane, Christopher; Thomson, P. John; Anne, Pramila; Gross, Howard; Willett, Christopher; Kelsen, David

    2009-01-01

    Purpose The investigational arm of INT0116, a fluorouracil (FU) and leucovorin–containing chemoradiotherapy regimen, is a standard treatment for patients with resected gastric cancer with a 2-year disease-free survival rate (DFS) of 52%. Toxicity is also significant. More beneficial and safer regimens are needed. Patients and Methods We performed a randomized phase II study among 39 cancer centers to evaluate two paclitaxel and cisplatin–containing regimens, one with FU (PCF) and the other without (PC) in patients with resected gastric cancer. Patients received two cycles of postoperative chemotherapy followed by 45 Gy of radiation with either concurrent FU and paclitaxel or paclitaxel and cisplatin. The primary objective was to show an improvement in 2-year DFS to 67% as compared with INT 0116. Results From May 2001 to February 2004 (study closure), 78 patients entered this study, and 73 were evaluable. At the planned interim analysis of 22 patients on PCF, grade 3 or higher GI toxicity was 59%. This was significantly worse than INT0116, and this arm was closed. Accrual continued on PC. The median DFS was 14.6 months for PCF and has not been reached for PC. For PC the 2-year DFS is 52% (95% CI, 36% to 68%). Conclusion Though PC appears to be safe and the median DFS favorable, the DFS failed to exceed the lower bound of 52.9% for the targeted 67% DFS at 2 years and can not be recommended as the adjuvant arm for future randomized trials. PMID:19273696

  17. Will Transcatheter Aortic Valve Replacement (TAVR be the Primary Therapy for Aortic Stenosis?

    Directory of Open Access Journals (Sweden)

    Jose F. Condado, MD, MS

    2016-05-01

    Full Text Available Transcatheter aortic valve replacement (TAVR is increasingly used for the treatment of high or very high surgical risk patients with severe aortic stenosis (AS or failing surgical bioprosthesis (valve-in-valve, VIV-TAVR. In TAVR, the collapsed transcatheter heart valve (THV is introduced using the delivery system inserted from the femoral artery (preferred or other alternative accesses (transapical, transaortic, transcarotid, subclavian/transinnominate or transcaval. The delivery system is then advanced until coaxially aligned with the aortic annulus, where the THV is deployed. This procedure can be associated with complications such as access site injury (vascular complication, paravalvar leak, cerebrovascular events and conduction disturbances. However, the rapid acceptance and successes observed with TAVR have been made possible through careful patient selection, preprocedural planning (i.e. MDCT annular sizing, THV technology (i.e. new generation valves, and procedural techniques (i.e. minimalist TF-TAVR and alternative percutaneous access options, as well as a decrease in complications as TAVR experience grows. Though the results or ongoing clinical trials evaluating TAVR in intermediate surgical risk patients are pending, it is likely that TAVR will soon be approved for lower risk patients as well.

  18. Inherent Immunogenicity or Lack Thereof of Pluripotent Stem Cells: Implications for Cell Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Arvind Chhabra

    2017-08-01

    Full Text Available Donor-specific induced pluripotent stem cells (iPSCs offer opportunities for personalized cell