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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

    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. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy was underpowered

    Directory of Open Access Journals (Sweden)

    Ortiz A

    2015-11-01

    Full Text Available Alberto Ortiz,1,2 Maria Dolores Sanchez-Niño1,2 1Department of Nephrology, IIS-Fundacion Jimenez Diaz, School of Medicine, Universidad Autónoma de Madrid, 2Department of Nephrology, Instituto Reina Sofia de Investigación Nefrológica, Madrid, Spain We read with interest the report by Goláň et al on the “Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease”.1 Based on the reported results, the authors conclude that no efficacy or safety differences were found when the approved every-other-week (EOW dosage of agalsidase alfa was increased to weekly administration. However, the key question is whether the study, as designed and performed, could have had a different outcome. View original article by Goláň et al.

  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...... after progestin intake. The integrated response, AUC, for TFPI was significantly lower in the HRT groups compared with the reference group. CONCLUSION: The observed changes may increase the early thrombotic risk associated with HRT use. Udgivelsesdato: 2002-Dec...

  5. Subcutaneous Immunoglobulin-G Replacement Therapy with Preparations Currently Available in the United States for Intravenous or Intramuscular Use: Reasons and Regimens

    Directory of Open Access Journals (Sweden)

    Chouksey Akhilesh

    2005-09-01

    Full Text Available Abstract For patients who require replacement therapy for primary immunodeficiency, subcutaneous infusions of immunoglobulin G (IgG may be preferable to intravenous infusions for several reasons. However, at present, there is no preparation marketed for use by this route in North America. In this article, we describe the reasons patients have selected this route of therapy and the range of treatment regimens used. Approximately 20% of our patients have chosen the subcutaneous route, mainly because of adverse effects from intravenous (IV infusions or difficulties with venous access. Unit dose regimens using whole bottles of currently available 16% intramuscular preparations or sucrose-containing lyophilized preparations intended for IV use but reconstituted to 15% IgG for subcutaneous administration were individually tailored to each patient. In most cases, self-infusions or home infusions were administered once or twice a week, most commonly requiring two subcutaneous sites and 2 to 3 hours per infusion. On average, patients took 0.18 mL of IgG per kilogram of body weight per site per hour. There were no systemic adverse effects. In patients for whom comparative data were available, trough serum IgG levels were higher with subcutaneous therapy than with IV therapy.

  6. A systematic review of antibiotic dosing regimens for septic patients receiving continuous renal replacement therapy: do current studies supply sufficient data?

    Science.gov (United States)

    Li, A M M Y; Gomersall, C D; Choi, G; Tian, Q; Joynt, G M; Lipman, J

    2009-11-01

    Drug dosing for septic patients with acute renal failure receiving continuous renal replacement therapy (CRRT) is complicated, and failure to correctly dose may result in either drug toxicity or treatment failure and development of antibiotic resistance. The aim of this study was to establish an ideal dataset that needs to be reported when presenting pharmacokinetic data for these patients and review current literature for completeness of this dataset. An ideal dataset was established of the parameters that should be reported when calculating a drug dosing regimen from first principles. A Medline search was performed of relevant literature producing 64 citations from which completeness of the specified criteria was examined. None of the studies analysed presented the full dataset that we established as necessary. Of concern, basic pharmacokinetic parameters such as volume of distribution (V(d)) and clearance (CL) were specified in only 79% and 81% of studies, respectively. A large proportion of current studies do not report key information necessary to devise a rational dosing regimen for patients with acute renal failure receiving CRRT, and we hope this dataset will be a useful guide when reporting future pharmacokinetic data.

  7. Hormone Replacement Therapy

    Science.gov (United States)

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  8. 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 admini...... treatment, when to follow-up for relapse, which dosage and type of therapy should be recommended or not recommended, and if some patients should not be treated....... 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...

  9. Hybrid Therapy Regimen for Helicobacter Pylori Eradication

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qiang Song; Jian Liu; Li-Ya Zhou

    2016-01-01

    Objective:Helicobacterpylori (H.pylori) eradication remains a challenge with increasing antibiotic resistance.Hybrid therapy has attracted widespread attention because of initial report with good efficacy and safety.However,many issues on hybrid therapy are still unclear such as the eradication efficacy,safety,compliance,influencing factors,correlation with antibiotic resistance,and comparison with other regimens.Therefore,a comprehensive review on the evidence of hybrid therapy for H.pylori infection was conducted.Data Sources:The data used in this review were mainly from PubMed articles published in English up to September 30,2015,searching by the terms of"Helicobacterpylori" or "H.pylori",and "hybrid".Study Selection:Clinical research articles were selected mainly according to their level of relevance to this topic.Results:Totally,1871 patients of 12 studies received hybrid therapy.The eradication rates were 77.6-97.4% in intention-to-treat and 82.6-99.1% in per-protocol analyses.Compliance was 93.3-100.0%,overall adverse effects rate was 14.5-67.5%,and discontinued medication rate due to adverse effects was 0-6.7%.H.pylori culture and sensitivity test were performed only in 13.3% patients.Pooled analysis showed that the eradication rates with dual clarithromycin and metronidazole susceptible,isolated metronidazole or clarithromycin resistance,and dual clarithromycin and metronidazole resistance were 98.5%,97.6%,92.9%,and 80.0%,respectively.Overall,the efficacy,compliance,and safety of hybrid therapy were similar with sequential or concomitant therapy.However,hybrid therapy might be superior to sequential therapy in Asians.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.

  10. Renal replacement therapy in ICU

    Directory of Open Access Journals (Sweden)

    C Deepa

    2012-01-01

    Full Text Available Diagnosing and managing critically ill patients with renal dysfunction is a part of the daily routine of an intensivist. Acute kidney insufficiency substantially contributes to the morbidity and mortality of critically ill patients. Renal replacement therapy (RRT not only does play a significant role in the treatment of patients with renal failure, acute as well as chronic, but also has spread its domains to the treatment of many other disease conditions such as myaesthenia gravis, septic shock and acute on chronic liver failure. This article briefly outlines the role of renal replacement therapy in ICU.

  11. 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.

  12. 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

  13. Renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    Noordzij, Marlies; Kramer, Anneke; Abad Diez, José M

    2014-01-01

    BACKGROUND: This article provides a summary of the 2011 ERA-EDTA Registry Annual Report (available at www.era-edta-reg.org). METHODS: Data on renal replacement therapy (RRT) for end-stage renal disease (ESRD) from national and regional renal registries in 30 countries in Europe and bordering the .......6-47.0], and on dialysis 39.3% (95% CI 39.2-39.4). The unadjusted 5-year patient survival after the first renal transplantation performed between 2002 and 2006 was 86.7% (95% CI 86.2-87.2) for kidneys from deceased donors and 94.3% (95% CI 93.6-95.0) for kidneys from living donors....

  14. 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)....

  15. Drug dosing during continuous renal replacement therapy.

    Science.gov (United States)

    Churchwell, Mariann D; Mueller, Bruce A

    2009-01-01

    Continuous renal replacement therapy (CRRT) has given clinicians an important option in the care of critically ill patients. The slow and continuous dialysate and ultrafiltrate flow rates that are employed with CRRT can yield drug clearances similar to an analogous glomerular filtration rate of the native kidneys. Advantages such as superior volume control, excellent metabolic control, and hemodynamic tolerance by critically ill patients are well documented, but an understanding of drug dosing for CRRT is still a bit of a mystery. Although some pharmaceutical companies have dedicated postmarket research in this direction, many pharmaceutical companies have chosen not to pursue this information as it is not mandated and represents a relatively small part of their market. This lack of valuable information has created many challenges in the care of the critically ill patient as intermittent hemodialysis drug dosing recommendations cannot be extrapolated to CRRT. This drug dosing review will highlight factors that clinicians should consider when determining a pharmacotherapy regimen for a patient receiving CRRT.

  16. 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.

  17. Insulin therapy for diabetes mellitus: treatment regimens and associated costs.

    Science.gov (United States)

    Charbonnel, B; Penfornis, A; Varroud-Vial, M; Kusnik-Joinville, O; Detournay, B

    2012-04-01

    To describe insulin therapy in patients with diabetes, to determine treatment costs and to compare costs among treatment regimens. This observational study was performed by 734 French pharmacists. Adult patients filling an insulin prescription were invited to participate. Participants provided information on their diabetes history and management. Levels of intensification of insulin therapy were determined by the number of injections in type 1 diabetes mellitus (T1DM) patients, and by the different schemes used in type 2 (T2DM) patients, such as basal/intermediate-acting insulin only, and regimens using both basal and rapid-acting insulin. Costs were evaluated according to official medication costs, nurse visits and glucose monitoring kits. A total of 361 patients with T1DM and 1902 with T2DM were enrolled in the survey. Patients with T1DM more frequently took 1-2 injections per day (46.3% of patients) and used single-dose basal insulin together with ≥1 dose of rapid insulin (43.8%). Patients with T2DM used multiple treatment regimens, with 58 different combinations documented. Most took basal/intermediate insulin only (42.5%) or combinations of basal/intermediate and rapid insulins (52.7%). Mean cost of insulin therapy was €27.4/week for T1DM and €45.4/week for T2DM. In T1DM, insulin was the biggest cost component and increased with the number of injections/day. In T2DM, nurse visits were the most important cost contributors irrespective of treatment regimen. Overall, the cost of insulin therapy increased with the complexity of the insulin schemes. Considerable heterogeneity is found in insulin treatment regimens used in everyday diabetes care. Payers should consider the full costs associated with the use of insulin rather than the cost of insulin alone. Treatment algorithms to harmonize insulin therapy should help to improve care, while encouraging patients to self-inject insulin should help to reduce costs. Copyright © 2011 Elsevier Masson SAS. All rights

  18. Renal replacement therapy for acute renal failure.

    Science.gov (United States)

    Macedo, E; Bouchard, J; Mehta, R L

    2009-09-01

    Renal replacement therapy became a common clinical tool to treat patients with severe acute kidney injury (AKI) since the 1960s. During this time dialytic options have expanded considerably; biocompatible membranes, bicarbonate dialysate and dialysis machines with volumetric ultrafiltration control have improved the treatment for acute kidney injury. Along with advances in methods of intermittent hemodialysis, continuous renal replacement therapies have gained widespread acceptance in the treatment of dialysis-requiring AKI. However, many of the fundamental aspects of the renal replacement treatment such as indication, timing of dialytic intervention, and choice of dialysis modality are still controversial and may influence AKI patient's outcomes. This review outlines current concepts in the use of dialysis techniques for AKI and suggests an approach for selecting the optimal method of renal replacement therapy.

  19. [Hormone replacement therapy: curse or blessing?].

    Science.gov (United States)

    Schmidt, M; Fink, D; Lang, U; Kimmig, R

    2006-01-01

    There is a controversial discussion on the risks and benefits of hormonal replacement therapy (HRT), and many women and doctors have revised their opinions of HRT over the last few years. Complementary and alternative therapies can be considered an option to treat menopausal symptoms. The following issue summarizes the actual knowledge of treatment options of menopausal symptoms.

  20. Postmenopausal hormone replacement therapy--clinical implications

    DEFF Research Database (Denmark)

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

    1994-01-01

    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....... Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke...... suggest that every woman showing any signs of hormone deprivation should be treated with hormone replacement therapy. This includes women with subjective or objective vaso-motor symptoms, genito-urinary symptoms, women at risk of osteoporosis (fast bone losers), and women at risk of cardiovascular...

  1. Testosterone replacement therapy and prostate health.

    Science.gov (United States)

    Polackwich, A Scott; Ostrowski, Kevin A; Hedges, Jason C

    2012-12-01

    There is an emerging evolution in the understanding of the relationship between the prostate and testosterone. It has long been generally believed that with testosterone replacement therapy (TRT), increasing serum testosterone levels led to prostatic growth and worsening of voiding dysfunction and associated complications. A new theory, the Saturation Model of Testosterone and its effect on the Prostate has gained attention. This theory suggests that the prostate's response to increasing levels of serum testosterone reaches a limit beyond which there is minimal effect. This model predicts that testosterone replacement therapy occurs above this saturation point, and replacing testosterone to eugonadal levels should not worsen prostate related benign disease. We evaluated the recent published data, with an emphasis on clinical studies done within the last 3 years, for the effects of testosterone supplementation on benign prostatic disease.

  2. 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...

  3. [Acute renal replacement therapy in pediatrics].

    Science.gov (United States)

    Gaillot, T; Ozanne, B; Bétrémieux, P; Tirel, O; Ecoffey, C

    2013-12-01

    In pediatric intensive care unit, the available modalities of acute renal replacement therapy include intermittent hemodialysis, peritoneal dialysis and continuous renal replacement therapies. No prospective studies have evaluated to date the effect of dialysis modality on the outcomes of children. The decision about dialysis modality should therefore be based on local expertise, resources available, and the patient's clinical status. Poor hemodynamic tolerance of intermittent hemodialysis is a common problem in critically ill patients. Moreover, many pediatric intensive care units are not equipped with dedicated water circuit. Peritoneal dialysis, a simple and inexpensive alternative, is the most widely available form of acute renal replacement therapy. However, its efficacy may be limited in critically ill patients. The use of continuous renal replacement therapy permits usually to reach a greater estimated dialysis dose, a better control of fluid balance, and additionally, to provide adequate nutrition. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  4. Enzyme replacement therapy for alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Dali, Christine I.; Fogh, J

    2013-01-01

    Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intrave...... intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment....

  5. Immunoglobulin Replacement Therapy for Primary Immunodeficiency.

    Science.gov (United States)

    Sriaroon, Panida; Ballow, Mark

    2015-11-01

    Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration.

  6. Nicotine replacement therapies: patient safety and persistence

    Directory of Open Access Journals (Sweden)

    Ferguson SG

    2011-06-01

    Full Text Available Stuart G Ferguson1,2, Saul Shiffman3,4, Joseph G Gitchell51School of Pharmacy, 2Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia; 3Pinney Associates, 4University of Pittsburgh, Pittsburgh, PA, USA; 5Pinney Associates, Bethesda, MD, USAAbstract: Nicotine replacement therapy (NRT has become a central part of the treatment of nicotine dependence. However, NRT’s potential efficacy is limited to some extent by patient adherence and persistence. Here we review the relationship between NRT compliance and adherence, and overall treatment outcome. We then examine the factors that likely impact on treatment compliance and persistence, with a special focus on users’ perceptions of treatment safety and efficacy as possible mediators. Potential clinical strategies for improving suboptimal medication use are also discussed.Keywords: nicotine replacement therapy, compliance, safety

  7. Risks of testosterone replacement therapy in men

    Directory of Open Access Journals (Sweden)

    E Charles Osterberg

    2014-01-01

    Full Text Available Testosterone replacement therapy (TRT is a widely used treatment for men with symptomatic hypogonadism. The benefits seen with TRT, such as increased libido and energy level, beneficial effects on bone density, strength and muscle as well as cardioprotective effects, have been well-documented. TRT is contraindicated in men with untreated prostate and breast cancer. Men on TRT should be monitored for side-effects such as polycythemia, peripheral edema, cardiac and hepatic dysfunction.

  8. Mitochondrial Replacement Therapy in Reproductive Medicine

    OpenAIRE

    Wolf, Don P; Mitalipov, Nargiz; Mitalipov, Shoukhrat

    2014-01-01

    Mitochondrial dysfunction is implicated in disease and in age-related infertility. Mitochondrial replacement therapies (MRT) in oocytes or zygotes such as pronuclear (PNT), spindle (ST) or polar body (PBT) transfer could prevent second generation transmission of mitochondrial DNA (mtDNA) defects. PNT, associated with high levels of mtDNA carryover in mice but low levels in human embryos, carries ethical issues secondary to donor embryo destruction. ST, developed in primates, supports normal d...

  9. Drug Dosing During Continuous Renal Replacement Therapies

    OpenAIRE

    Thompson, A. Jill

    2008-01-01

    Continuous renal replacement therapies (CRRT) are used to manage fluid overload and/or renal failure. The continuous nature of the fluid and solute removal has less impact on hemodynamic variables in critically ill patients, making CRRT preferred over intermittent hemodialysis for some patients in the intensive care arena. The impact of CRRT on drug removal is variable depending on the CRRT modality, the ultrafiltrate and dialysate flow rates, the filter, and the patient's residual renal func...

  10. 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

  11. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

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    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.

  12. Alternative hormone replacement regimens: is there a need for further clinical trials?

    Science.gov (United States)

    Welty, Francine K

    2003-12-01

    To review the randomized trials of hormone replacement therapy. Studies have shown that conjugated equine estrogen 0.625 mg a day plus medroxyprogesterone acetate 2.5 mg a day increased the risk of cardiovascular events during the first year of treatment in women both with and without coronary heart disease. Conjugated equine estrogen plus medroxyprogesterone acetate also increased the overall risk of myocardial infarction and stroke in women without coronary heart disease, and myocardial infarction or death in women with coronary heart disease, and also increased the risk of breast cancer, cognitive decline and dementia. Unopposed, oral 17B-estradiol increased the risk of stroke during the first 6 months of treatment in women with a previous stroke. Oral 17B-estradiol with or without cyclic progestin had no effect on the progression of atherosclerosis or reinfarction. Transdermal 17B-estradiol plus cyclic progestin was associated with a non-significant increase in coronary heart disease events in women with coronary heart disease. Compared with placebo, cardiovascular events increased in the ongoing estrogen-only arm of the Women's Health Initiative, indicating that unopposed conjugated equine estrogen is unlikely to be cardioprotective. However, oral 17B-estradiol retarded the progression of subclinical atherosclerosis in younger women without coronary heart disease. Hormone replacement therapy should not be initiated for the primary or secondary prevention of coronary heart disease in women. A trial of 17B-estradiol started at menopause in women without coronary heart disease should be considered.

  13. Mitochondrial replacement therapy in reproductive medicine.

    Science.gov (United States)

    Wolf, Don P; Mitalipov, Nargiz; Mitalipov, Shoukhrat

    2015-02-01

    Mitochondrial dysfunction is implicated in disease and age-related infertility. Mitochondrial replacement therapies (MRT) in oocytes or zygotes, such as pronuclear (PNT), spindle (ST), or polar body (PBT) transfer, could prevent second-generation transmission of mitochondrial DNA (mtDNA) defects. PNT, associated with high levels of mtDNA carryover in mice but low levels in human embryos, carries ethical issues secondary to donor embryo destruction. ST, developed in primates, supports normal development to adults and low mtDNA carryover. PBT in mice, coupled with PN or ST, may increase the yield of reconstructed embryos with low mtDNA carryover. MRT also offers replacement of the deficient cytoplasm in oocytes from older patients, with the expectation of high pregnancy rates following in vitro fertilization.

  14. Testosterone replacement therapy for older men

    Directory of Open Access Journals (Sweden)

    Stephen E Borst

    2008-01-01

    Full Text Available Stephen E Borst, Thomas MulliganGeriatrics Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USAAbstract: Despite intensive research on testosterone therapy for older men, important questions remain unanswered. The evidence clearly indicates that many older men display a partial androgen deficiency. In older men, low circulating testosterone is correlated with low muscle strength, with high adiposity, with insulin resistance and with poor cognitive performance. Testosterone replacement in older men has produced benefits, but not consistently so. The inconsistency may arise from differences in the dose and duration of testosterone treatment, as well as selection of the target population. Generally, studies reporting anabolic responses to testosterone have employed higher doses of testosterone for longer treatment periods and have targeted older men whose baseline circulating bioavailable testosterone levels were low. Most studies of testosterone replacement have reported anabolic that are modest compared to what can be achieved with resistance exercise training. However, several strategies currently under evaluation have the potential to produce greater anabolic effects and to do so in a safe manner. At this time, testosterone therapy can not be recommended for the general population of older men. Older men who are hypogonadal are at greater risk for the catabolic effects associated with a number of acute and chronic medical conditions. Future research is likely to reveal benefits of testosterone therapy for some of these special populations. Testosterone therapy produces a number of adverse effects, including worsening of sleep apnea, gynecomastia, polycythemia and elevation of PSA. Efficacy and adverse effects should be assessed frequently throughout the course of therapy.Keywords: aging, testosterone, hypogonadism, physical function

  15. Testosterone Replacement Therapy and the Cardiovascular System.

    Science.gov (United States)

    Naderi, Sahar

    2016-04-01

    As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

  16. Renal Replacement Therapy in Austere Environments

    Directory of Open Access Journals (Sweden)

    Christina M. Yuan

    2011-01-01

    Full Text Available Myoglobinuric renal failure is the classically described acute renal event occurring in disaster environments—commonly after an earthquake—which most tests the ingenuity and flexibility of local and regional nephrology resources. In recent decades, several nephrology organizations have developed response teams and planning protocols to address disaster events, largely focusing on patients at risk for, or with, acute kidney injury (AKI. In this paper we briefly review the epidemiology and outcomes of patients with dialysis-requiring AKI after such events, while providing greater focus on the management of the end-stage renal disease population after a disaster which incapacitates a pre-existing nephrologic infrastructure (if it existed at all. “Austere” dialysis, as such, is defined as the provision of renal replacement therapy in any setting in which traditional, first-world therapies and resources are limited, incapacitated, or nonexistent.

  17. 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.

  18. Testosterone replacement therapy in obese males.

    Science.gov (United States)

    Drewa, Tomasz; Olszewska-Słonina, Dorota; Chlosta, Piotr

    2011-01-01

    Controversy surrounds testosterone replacement therapy in obese ageing due to no generally accepted lower limits of normal testosterone level and high prevalence of hypogonadal symptoms in the ageing male population and the non-specific nature of these symptoms. Late onset hypogonadism is a clinical and biochemical syndrome associated with advancing age, often coexisting with obesity and metabolic syndrome. High fat and carbohydrates (fructose) consumption is responsible for development of obesity and metabolic syndrome which is one of risk factors for hypogonadism in older men. High fructose intake has been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Obesity and lack of physical activity negatively influence testosterone level. Low testosterone level should be regarded as an effect of obesity, but reverse relationship has not been proved yet. The management of late-onset hypogonadism symptoms has to be treated by a change of a life style and prevented with healthy nutrition and physical activity. The question related to rational indications for testosterone replacement therapy in obese males seems to be still actual.

  19. Renal replacement therapy in Korea, 2012

    Directory of Open Access Journals (Sweden)

    Dong Chan Jin

    2014-03-01

    Full Text Available The Korean Society of Nephrology (KSN launched the official end-stage renal disease (ESRD patient registry in 1985, and an Internet online registry program was opened in 2001 and revised in 2013. The ESRD Registry Committee of KSN has collected data on dialysis therapy in Korea through the online registry program in the KSN Internet website. The status of renal replacement therapy in Korea at the end of 2012 is described in the following. The total number of ESRD patients was 70,211 at the end of 2012, which included 48,531 hemodialysis (HD patients, 7,552 peritoneal dialysis (PD patients, and 14,128 functioning kidney transplant (KT patients. The prevalence of ESRD was 1,353.3 patients per million population (PMP, and the distribution of renal replacement therapy among ESRD patients was as follows: HD, 69.1%; PD, 10.8%; and KT, 20.2%. The number of new ESRD patients in 2012 was 11,742 (HD, 8,811; PD, 923; and KT, 1,738; the incidence rate was 221.1 PMP. The primary causes of ESRD were diabetic nephropathy (50.6%, hypertensive nephrosclerosis (18.5%, and chronic glomerulonephritis (18.1%. The mean urea reduction ratio was 67.9% in male and 74.1% in female HD patients. The mean Kt/V was 1.382 in male and 1.652 in female HD patients. The 5-year survival rates of male and female dialysis patients were 70.6% and 73.5%, respectively.

  20. 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.

  1. β-lactam antibiotic concentrations during continuous renal replacement therapy

    Science.gov (United States)

    2014-01-01

    Introduction The use of standard doses of β-lactam antibiotics during continuous renal replacement therapy (CRRT) may result in inadequate serum concentrations. The aim of this study was to evaluate the adequacy of unadjusted drug regimens (i.e., similar to those used in patients with normal renal function) in patients treated with CRRT and the influence of CRRT intensity on drug clearance. Methods We reviewed data from 50 consecutive adult patients admitted to our Department of Intensive Care in whom routine therapeutic drug monitoring (TDM) of broad-spectrum β-lactam antibiotics (ceftazidime or cefepime, CEF; piperacillin/tazobactam; TZP; meropenem, MEM) was performed using unadjusted β-lactam antibiotics regimens (CEF = 2 g q8h; TZP = 4 g q6h; MEM = 1 g q8h). Serum drug concentrations were measured twice during the elimination phase by high-performance liquid chromatography (HPLC-UV). We considered therapy was adequate when serum drug concentrations were between 4 and 8 times the minimal inhibitory concentration (MIC) of Pseudomonas aeruginosa during optimal periods of time for each drug (≥70% for CEF; ≥ 50% for TZP; ≥ 40% for MEM). Therapy was considered as early (ET) or late (LT) phase if TDM was performed within 48 hours of antibiotic initiation or later on, respectively. Results We collected 73 serum samples from 50 patients (age 58 ± 13 years; Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission 21 (17–25)), 35 during ET and 38 during LT. Drug concentrations were above 4 times the MIC in 63 (90%), but above 8 times the MIC in 39 (53%) samples. The proportions of patients with adequate drug concentrations during ET and LT were quite similar. We found a weak but significant correlation between β-lactam antibiotics clearance and CRRT intensity. Conclusions In septic patients undergoing CRRT, doses of β-lactam antibiotics similar to those given to patients with normal renal function achieved drug

  2. Growth hormone replacement therapy in Costello syndrome.

    Science.gov (United States)

    Triantafyllou, Panagiota; Christoforidis, Athanasios; Vargiami, Euthymia; Zafeiriou, Dimitrios I

    2014-12-01

    Costello syndrome (CS) is considered an overgrowth disorder given the macrosomia that is present at birth .However, shortly after birth the weight drops dramatically and the patients are usually referred for failure to thrive. Subsequently, affected patients develop the distinctive coarse facial appearance and are at risk for cardiac anomalies and solid tumor malignancies. Various endocrine disorders, although not very often, have been reported in patients with CS, including growth hormone deficiency, hypoglycemia, ACTH deficiency, cryptorchidism and hypothyroidism. We report a case of Costello syndrome with hypothyroidism, cryptorchidism and growth hormone deficiency and we evaluate the long-term safety and efficacy of growth hormone replacement therapy. The index patient is a paradigm of successful and safe treatment with growth hormone for almost 7 years. Since patients with CS are at increased risk for cardiac myopathy and tumor development they deserve close monitoring during treatment.

  3. Recombinant Enzyme Replacement Therapy in Hypophosphatasia.

    Science.gov (United States)

    Hofmann, Christine; Jakob, Franz; Seefried, Lothar; Mentrup, Birgit; Graser, Stephanie; Plotkin, Horacio; Girschick, Hermann J; Liese, Johannes

    2015-01-01

    Hypophosphatasia (HPP) is a rare monogenetic and multisystemic disease with involvement of different organs, including bone, muscle, kidney, lung, gastrointestinal tract and the nervous system. The exact metabolic mechanisms of the effects of TNAP deficiency in different tissues are not understood in detail. There is no approved specific treatment for HPP; therefore symptomatic treatment in order to improve the clinical features is of major interest. Enzyme replacement therapy (ERT) is a relatively new type of treatment based on the principle of administering a medical treatment replacing a defective or absent enzyme. Recently ERT with a bone targeted recombinant human TNAP molecule has been reported to be efficient in ten severely affected patients and improved survival of life threatening forms. These results are very promising especially with regard to the skeletal phenotype but it is unclear whether ERT also has beneficial effects for craniosynostosis and in other affected tissues in HPP such as brain and kidney. Long-term data are not yet available and further systematic clinical trials are needed. It is also necessary to establish therapeutic approaches to help patients who are affected by less severe forms of HPP but also suffer from a significant reduction in quality of life. Further basic research on TNAP function and role in different tissues and on its physiological substrates is critical to gain a better insight in the pathogenesis in HPP. This and further experiences in new therapeutic strategies may improve the prognosis and quality of life of patients with all forms of HPP.

  4. Advances in hormone replacement therapy: making the menopause manageable

    Directory of Open Access Journals (Sweden)

    Palacios Santiago

    2008-11-01

    Full Text Available Abstract The importance of the results of some large, randomized controlled trials (RCTs on Hormone Replacement Therapy (HRT has modified the risk/benefit perception of HRT. Recent literature review supports a different management. The differences in age at initiation and the duration of HRT are key points. HRT appears to decrease coronary disease in younger women, near menopause; yet, in older women, HRT increases risk of a coronary event. Although HRT is a recognized method in the prevention and treatment of osteoporosis, it is not licensed for the prevention of osteoporosis as a first-line treatment. The effectiveness of low and ultra-low estrogen doses has been demonstrated for the treatment of vasomotor symptoms, genital atrophy and the prevention of bone loss, with fewer side-effects than the standard dose therapy. Further research, however, is needed to determine the effect both on fractures, as well as on cardiovascular and breast diseases. Newer progestins show effects that are remarkably different from those of other assays. The effectiveness of testosterone at improving both sexual desire and response in surgically and naturally postmenopausal women is shown by the testosterone patch. The intention, dose and regimen of HRT need to be individualized, based on the principle of choosing the lowest appropriate dose in relation to the severity of symptoms and the time and menopause age.

  5. Pharmacokinetics of Procainamide and N-acetylprocainamide during Continuous Renal Replacement Therapy

    OpenAIRE

    Mohamed, Ahmed N.; Abdelhady, Ahmed M.; Spencer, Dustin; Sowinski, Kevin M.; Tisdale, James E; Overholser, Brian R.

    2013-01-01

    Procainamide and its major metabolite, N-acetyl procainamide (NAPA), prolong the QTc interval and can promote potentially fatal ventricular arrhythmias. Excretion of procainamide and NAPA is reduced in patients with chronic kidney disease (CKD) resulting in drug accumulation and toxicity. The elimination of procainamide or NAPA in patients undergoing continuous renal replacement therapy (CRRT) has not been evaluated increasing the risk for subtherapeutic or toxic dosing regimens. This case re...

  6. Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder

    Science.gov (United States)

    ... 1999 Spotlight on Research 2014 February 2014 (historical) Protein Replacement Therapy Shows Promise in Treating Rare Skin Disorder Replacing a protein that is crucial to ensuring that the skin’s ...

  7. Acute Renal Replacement Therapy in Pediatrics

    Directory of Open Access Journals (Sweden)

    Rajit K. Basu

    2011-01-01

    Full Text Available Acute kidney injury (AKI independently increases morbidity and mortality in children admitted to the hospital. Renal replacement therapy (RRT is an essential therapy in the setting of AKI and fluid overload. The decision to initiate RRT is complex and often complicated by concerns related to patient hemodynamic and thermodynamic instability. The choice of which RRT modality to use depends on numerous criteria that are both patient and treatment center specific. Surprisingly, despite decades of use, no randomized, controlled trial study involving RRT in pediatrics has been performed. Because of these factors, clear-cut consensus is lacking regarding key questions surrounding RRT delivery. In this paper, we will summarize existing data concerning RRT use in children. We discuss the major modalities and the data-driven specifics of each, followed by controversies in RRT. As no standard of care is in widespread use for RRT in AKI or in multiorgan disease, we conclude in this paper that prospective studies of RRT are needed to identify best practice guidelines.

  8. [Renal replacement therapy for refractory heart failure].

    Science.gov (United States)

    Schwenger, V; Remppis, A B

    2012-07-01

    After broad cardiological and nephrological evaluation and consideration of optimal conservative options according to national and international guidelines, renal replacement therapy might be helpful in patients with refractory heart failure even if they are not dialysis-dependent. This is even more important as renal failure is a strong predictor for mortality in patients with severe congestive heart failure (CHF) and CHF is one of the fastest growing morbidities in western countries. Although peritoneal dialysis (PD) is frequently used in patients with CHF its role remains unclear. Acute chronic volume overload in refractory CHF is still an unresolved clinical problem. In patients with acute heart and renal failure with need of management in an intensive care unit, extracorporeal ultrafiltration or a dialysis modality should be preferred. In patients with chronic refractory CHF, volume overload and renal failure, peritoneal dialysis should be the therapy of choice. Due to the limited data available, treatment and outcome parameters should be recorded in the registry of the German Society of Nephrology (http://www.herz-niere.de).

  9. Testosterone Replacement Therapy: The Emperor's New Clothes.

    Science.gov (United States)

    Sansone, Andrea; Sansone, Massimiliano; Lenzi, Andrea; Romanelli, Francesco

    2017-02-01

    The mean age of the world population has steadily increased in the last decades, as a result of increased life expectancy and reduced birth rate. Global aging has led to a greater worldwide cost for healthcare: hormonal alterations contribute to the pathogenesis of several conditions and might cause a significant reduction in the perceived sense of well-being. Menopause is archetypal of hormonal alterations occurring during aging: in males, sex hormones do not decrease abruptly, yet testosterone levels decrease steadily and continuously during aging, ultimately resulting in late-onset hypogonadism. Treatment of this condition might mitigate most symptoms; however, testosterone replacement therapy (TRT) should be prescribed only in selected patients and it should not be considered as an antiaging treatment. In recent years, different authors have questioned health risks associated with testosterone treatment; while position statements from many scientific societies seem to be reassuring, the Food and Drug Administration has issued a warning in regard to the possible side effects of this therapy. We aim to review recent controversies and discoveries in regard to TRT.

  10. Drug dosing during continuous renal replacement therapies.

    Science.gov (United States)

    Thompson, A Jill

    2008-04-01

    Continuous renal replacement therapies (CRRT) are used to manage fluid overload and/or renal failure. The continuous nature of the fluid and solute removal has less impact on hemodynamic variables in critically ill patients, making CRRT preferred over intermittent hemodialysis for some patients in the intensive care arena. The impact of CRRT on drug removal is variable depending on the CRRT modality, the ultrafiltrate and dialysate flow rates, the filter, and the patient's residual renal function; all of these may change from patient to patient or even in the same patient depending on the clinical status. However, CRRT modalities are generally more efficient than intermittent hemodialysis at drug removal, in some cases approximating or even exceeding normal renal function, resulting in a significant risk of subtherapeutic dosing if conventional hemodialysis dosing recommendations are followed. This annotated bibliography provides a summary of publications analyzing drug removal during CRRT, including CRRT settings and drug clearance values found in each study. Caution is warranted as findings from one study may not be generalizable to all patients due to the many factors that influence drug removal. Serum drug concentrations should be monitored when available, and patient clinical status is exceedingly important for following expected and unexpected responses to drug therapies. Reviews on general drug dosing calculations in CRRT are available elsewhere.

  11. Partial regimen replacement with aripiprazole reduces serum prolactin in patients with a long history of schizophrenia: A case series.

    Science.gov (United States)

    Naono-Nagatomo, Keiko; Naono, Hisao; Abe, Hiroshi; Takeda, Ryuichiro; Funahashi, Hideki; Uchimura, Daisuke; Ishida, Yasushi

    2017-02-01

    Aripiprazole (ARP) is a popular antipsychotic drug that has demonstrated ameliorative effects on hyperprolactinemia. However, no study to date has studied the utility of ARP in patients with a long history of schizophrenia and antipsychotic treatment. We therefore examined the effect of partial antipsychotic regimen replacement with ARP on hyperprolactinemia induced by chronic antipsychotic use in patients with schizophrenia. Sixteen patients with a schizophrenia diagnosis (F2) based on the International Classification of Diseases (version 10) were recruited. At months 0, 1, 3, and 6 of the study, serum prolactin, body weight, and blood glucose were measured, and QOL and psychotic symptoms were assessed using Global Assessment of Functioning scores and Clinical Global Impressions of Improvement (CGI-I) scores. Nine patients with an average age of 46.7±9.6 years and mean disease duration of 15.9±10.4 years were included in the final analysis. Serum prolactin levels significantly decreased and GAF and CGI-I scores improved significantly over the 6-month period after partial replacement with ARP. Additionally, no changes were observed in body weight or blood glucose over the 6-month period. Partial antipsychotic regimen replacement with ARP improves hyperprolactinemia, and may improve the QOL of patients with a long history of schizophrenia. Japan Medical Association, Center for clinical trials D: JMA-IIA00245. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults : 48-week results from the antiretroviral regimen evaluation study (ARES)

    NARCIS (Netherlands)

    Lowe, SH; Wensing, AMJ; Hassink, EAM; ten Kate, RW; Richter, C; Schreij, G; Koopmans, PP; Juttmann, J.; van der Tweel, I.; Lange, JMA; Borleffs, JCC

    2005-01-01

    Background: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. Method: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

  13. Comparison of two once-daily regimens with a regimen consisting of nelfinavir, didanosine, and stavudine in antiretroviral therapy-naive adults: 48-week results from the Antiretroviral Regimen Evaluation Study (ARES).

    NARCIS (Netherlands)

    Lowe, S.H.; Wensing, B.M.; Hassink, E.A.M.; Kate, R.W. ten; Richter, C.; Schreij, G.; Koopmans, P.P.; Juttmann, J.R.; Tweel, I. van de; Lange, J.M.A.; Borleffs, J.C.

    2005-01-01

    BACKGROUND: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. METHOD: HIV-1-infected, antiretroviral drug-naive adults were randomized to either twice-daily nelfinavir and stavudine and once-daily dida

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

    Science.gov (United States)

    Hormone replacement therapy: Can it cause vaginal bleeding? I'm taking hormone therapy for menopause symptoms, and my monthly menstrual periods have returned. Is this normal? Answers from Shannon K. Laughlin- ...

  15. Delivering enhanced testosterone replacement therapy through nanochannels.

    Science.gov (United States)

    Ferrati, Silvia; Nicolov, Eugenia; Bansal, Shyam; Zabre, Erika; Geninatti, Thomas; Ziemys, Arturas; Hudson, Lee; Ferrari, Mauro; Goodall, Randal; Khera, Mohit; Palapattu, Ganesh; Grattoni, Alessandro

    2015-02-18

    Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In this study, an implantable nanochannel system is investigated as an alternative delivery strategy for the long-term sustained and constant release of testosterone. In vitro release tests are performed using a dissolution set up, with testosterone and testosterone:2-hydroxypropyl-β-cyclodextrin (TES:HPCD) 1:1 and 1:2 molar ratio complexes release from the implantable nanochannel system and quantify by HPLC. 1:2 TES:HPCD complex stably achieve 10-15 times higher testosterone solubility with 25-30 times higher in vitro release. Bioactivity of delivered testosterone is verified by LNCaP/LUC cell luminescence. In vivo evaluation of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels by liquid chromatography mass spectrometry (LC/MS) and multiplex assay is performed in castrated Sprague-Dawley rats over 30 d. Animals are treated with the nanochannel implants or degradable testosterone pellets. The 1:2 TES:HPCD nanochannel implant exhibits sustained and clinically relevant in vivo release kinetics and attains physiologically stable plasma levels of testosterone, LH, and FSH. In conclusion, it is demonstrated that by providing long-term steady release 1:2 TES:HPCD nanochannel implants may represent a major breakthrough for the treatment of male hypogonadism.

  16. 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....

  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 concer

  18. 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

  19. 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....

  20. Renal replacement therapy after cardiac surgery; renal function recovers

    DEFF Research Database (Denmark)

    Steinthorsdottir, Kristin Julia; Kandler, Kristian; Agerlin Windeløv, Nis

    2013-01-01

    To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy.......To assess renal outcome in patients discharged from hospital following cardiac surgery-associated acute kidney injury (CSA-AKI) with need for renal replacement therapy....

  1. Diabetes mellitus and cellular replacement therapy: Expected clinical potential and perspectives

    Institute of Scientific and Technical Information of China (English)

    Alexander; E; Berezin

    2014-01-01

    Diabetes mellitus(DM) is the most prevailing disease with progressive incidence worldwide. Despite contemporary treatment type one DM and type two DM are frequently associated with long-term major microvascular and macrovascular complications. Currently restoration of failing β-cell function, regulation of metabolic processes with stem cell transplantation is discussed as complements to contemporary DM therapy regimens. The present review is considered paradigm of the regenerative care and the possibly effects of cell therapy in DM. Reprogramming stem cells, bone marrowderived mononuclear cells; lineage-specified progenitor cells are considered for regenerative strategy in DM. Finally, perspective component of stem cell replacement in DM is discussed.

  2. Hormone Replacement Therapy After Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mueck AO

    2008-01-01

    Full Text Available So far, patient samples in all studies investigating hormone replacement therapy (HRT after breast cancer have been small.Therefore, HRT should only be used if alternatives such as specifically not contraindicated phytopreparations or selective sero-tonin reuptake inhibitors (SSRIs are not effective. This is primarily due to forensic reasons since clinical data on the risk ofalternatives (based on present evidence are even more sparse. Regarding HRT, four prospective randomized studies and at least15 observational studies after breast cancer are available. Only the HABITS study shows an increased risk of relapse. The authorssuggest that this is probably associated with the relatively high number of patients with HRT treatment after ER-positive cancersas well as due to the preferred use of estrogen/progestin-combined preparations. Based on the results of the randomized pla-cebo-controlled study Women’s Health Initiative (WHI as well as of at least 12 observational studies, the progestin componentseems to be mainly responsible for the probability of increased diagnosis frequency of primary breast cancer. However, no dataare available on the impact of progestin on the use of combined HRT after breast cancer. However, also with estrogen only anincreased risk of relapse must be expected and patients should be informed about it. This has to be concluded due to biologicalplausibility and observational studies although the estrogen-only arm in WHI did not show any increased primary risk. Thus, anyform of HRT should only be performed in exceptional cases, and treatment duration should be as short as possible with thelowest effective dose.

  3. Blood donation and testosterone replacement therapy.

    Science.gov (United States)

    Chin-Yee, Benjamin; Lazo-Langner, Alejandro; Butler-Foster, Terrie; Hsia, Cyrus; Chin-Yee, Ian

    2017-03-01

    Polycythemia is the most common adverse effect of testosterone replacement therapy (TRT) and may predispose patients to adverse vascular events. Current Canadian guidelines recommend regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L). This threshold has been interpreted by some physicians and patients to indicate the need for phlebotomy or blood donation while on TRT. We reviewed all male blood donors in Southwestern Ontario at Canadian Blood Services from December 2013 to March 2016 who self-identified or were found on donor screening to be on TRT. Hemoglobin concentration was measured at the time of donation or clinic visit and with each subsequent appointment in repeat donors. We identified 39 patients on TRT who presented for blood donation over a 2-year period. The mean hemoglobin level at all clinic visits was 173 g/L (range, 134-205 g/L; n = 108). Hemoglobin concentrations of 180 g/L or more (calculated hematocrit, ≥54%) were measured at 25% of appointments. Of the 27 repeat donors, 12 (44%) had persistently elevated hemoglobin levels (≥180 g/L) at subsequent donations. Hemoglobin concentrations were elevated in donors on TRT, and significant numbers had hemoglobin levels above those recommended by current guidelines. These data also suggest that repeat blood donation was insufficient to maintain a hematocrit below 54%. Our findings raise concerns about the persistent risk of vascular events in these donors, particularly when coupled with the misperception by patients and health care providers that donation has reduced or eliminated the risks of TRT-induced polycythemia. © 2017 AABB.

  4. 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...

  5. Incidence of pocket hematoma after electrophysiological device placement:dual antiplatelet therapy versus low-molecular-weight heparin regimen

    Institute of Scientific and Technical Information of China (English)

    Yan CHEN; Xin-Cun YANG; Kang MENG; Yun-Tao LI; Ming-Dong GAO; Ze-Chun ZENG; Jin-Rong ZHANG; Hong-Liang CONG; Yin LIU; Ru ZHAO; Le-Feng WANG

    2014-01-01

    Background Given the increasing number of patients who require dual antiplatelet (DAP) therapy and electrophysiological device (EPD) placement, perioperative antiplatelet management is a current challenge. In this study, we investigated the incidence of pocket hema-toma formation after EPD placement in patients undergoing DAP therapy or an alternative low-molecular-weight heparin (LMWH) regimen. Methods This clinical observational study was performed from July 2010 to July 2012. In total, 171 patients were enrolled in the analysis after meeting the inclusion criteria. These patients were divided into two groups: 86 patients were treated with DAP therapy at the time of device implantation, and the DAP therapy was discontinued for 5 to 7 days and replaced with enoxaparin before device implantation in the other 85 patients. Adenosine phosphate (ADP)-mediated platelet aggregation and arachidonic acid-induced platelet aggregation were tested preoperatively. We compared the incidence of pocket hematoma between the two groups and the association of pocket hematoma develop-ment with ADP-mediated platelet aggregation and arachidonic acid-induced platelet aggregation.Results The incidence of pocket hema-toma in the patients who continued DAP was lower than that in the patients who replaced the dual antiplatelet regimen with LMWH (3.49%vs. 16.47%, respectively;X2 = 6.66,P < 0.01). Among the patients who continued DAP therapies, the rate of ADP-mediated platelet aggre-gation inhibition in patients with pocket hematomas was higher than that in patients without pocket hematomas. None of the patients under-going DAP or enoxaparin therapy developed pocket infection, thromboembolic events, or other serious complications. Multiple logistic re-gression analysis revealed that LMWH therapy was an independent risk factor for the development of pocket hematoma (RR = 0.054, 95%CI = 0.012-0.251). Furthermore, patients undergoing LMWH therapy were 5.1-fold more likely to develop pocket

  6. Implications of human evolution and admixture for mitochondrial replacement therapy

    National Research Council Canada - National Science Library

    Rishishwar, Lavanya; Jordan, I. King

    2017-01-01

    Mitochondrial replacement (MR) therapy is a new assisted reproductive technology that allows women with mitochondrial disorders to give birth to healthy children by combining their nuclei with mitochondria from unaffected egg donors...

  7. Menopausal depression:comparison of hormone replacement therapy and hormone replacement therapy plus fiuoxetine

    Institute of Scientific and Technical Information of China (English)

    刘平; 何方方; 白文佩; 郁琦; 史蔚; 吴宜勇; 贺丹军; 肖计划; 郑晔; 廖秦平

    2004-01-01

    Background To compare the efficacy and safety of hormone replacement therapy (HRT) combined with fluoxetine, with HRT alone, in post-menopausal women suffering from depression.Methods A randomized, open-label, parallel trial was applied. HRT was administered to all patients for 2 cycles, with ]4 days of estrogen therapy and 14 days of estrogen plus progesterone. Patients who were randomly assigned to the HRT plus fluoxetine group were given fluoxetine in combination with HRT. Hamilton Depression Rating Scale (HAMD), Kupperman Menopausal Index (KMI), and Clinical Global Impressions scale were used to measure the efficacy. Results One hundred and twenty-three post-menopausal patients with depression were enrolled in the study. Among them, 120 had at least one post-treatment visit and entered into the statistical analysis. The mean total HAMD scores were significantly lower, and the percentages of HAMD score reductions were higher in the HRT plus fluoxetine Group compared with the HRT Group, after at least 3 weeks of treatment, with an average difference of 5 points at the endpoint. The Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores were significantly different in the 2 groups, in favor of the combination therapy. The mean total KMI was significantly lower in the Combination Group compared with the HRT Group, after at least 6 weeks of treatment, with an average 4. 5-point difference between the groups. No statistically significant differences were found in most of the adverse events reported in the Combination Group compared with the HRT group, with the exception of 3 symptoms, i. e., dry mouth, loss of appetite, and abdominal distention. They were mild to moderate in severity. Two patients in the HRT group, but none in the combination group, dropped out due to adverse events. Conclusion HRT plus fluoxetine therapy was effective in the treatment of menopausal depression with a satisfactory safety profile.

  8. Spontaneous Coronary Artery Dissection following Topical Hormone Replacement Therapy

    OpenAIRE

    2012-01-01

    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...

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

    OpenAIRE

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

    2015-01-01

    Introduction 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. Methods To clarify this issue we conducted a national-level survey at a recent Italian course on nursing practices during continuous renal replacement therapies. Results A total of 119 question...

  10. PECULIARITIES OF REPLACEMENT ENZYME THERAPY IN CHILDREN WITH CYSTIC FIBROSIS: BENEFITS OF HIGH-TECH ENZYMES

    Directory of Open Access Journals (Sweden)

    O.I. Simonova

    2011-01-01

    Full Text Available In the past years we have gained enormous success not only in the field of understanding of pathologic basis and genetics of cystic fibrosis, but we have also developed new therapeutic approach to this disease. Enzyme therapy is one of the main parts of a complex treatment of cystic fibrosis. Correct therapeutic decision upon medication and treatment regimen allows to reach dramatic amelioration o patient’s condition, and significantly decrease the risk of complications of the disease itself and side-effects of the treatment given. This article contains guidelines of enzyme therapy in cystic fibrosis and clinical mistakes analysis that occur while deciding upon therapy. Key words: chronic pancreatic failure, replacement enzyme therapy, kreon, cystic fibrosis, children. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 152–156.

  11. Efavirenz Conceptions and Regimen Management in a Prospective Cohort of Women on Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Sheree Schwartz

    2012-01-01

    Full Text Available Use of the antiretroviral drug efavirenz (EFV is not recommended by the WHO or South African HIV treatment guidelines during the first trimester of pregnancy due to potential fetal teratogenicity; there is little evidence of how clinicians manage EFV-related fertility concerns. Women on antiretroviral therapy (ART were enrolled into a prospective cohort in four public clinics in Johannesburg, South Africa. Fertility intentions, ART regimens, and pregnancy testing were routinely assessed during visits. Women reporting that they were trying to conceive while on EFV were referred for regimen changes. Kaplan-Meier estimators were used to assess incidence across ART regimens. From the 822 women with followup visits between August 2009–March 2011, 170 pregnancies were detected during study followup, including 56 EFV conceptions. Pregnancy incidence rates were comparable across EFV, nevirapine, and lopinavir/ritonavir person-years (95% 100/users (P=0.25; incidence rates on EFV were 18.6 Confidence Interval: 14.2–24.2. Treatment substitution from EFV was made for 57 women, due to pregnancy intentions or actual pregnancy; however, regimen changes were not systematically applied across women. High rates of pregnancy on EFV and inconsistencies in treatment management suggest that clearer guidelines are needed regarding how to manage fertility-related issues in. women on EFV-based regimens.

  12. 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.

  13. Immunoglobulin Replacement Therapy: When You Need It -- and When You Don't

    Science.gov (United States)

    ... Videos Lists Search Patient Resources Immunoglobulin Replacement Therapy Immunoglobulin Replacement Therapy When you need it—and when ... enough germ-fighting antibodies. A treatment known as immunoglobulin replacement (IgG) therapy can be a lifesaver for ...

  14. Continuous Renal Replacement Therapy for Severe Obstetric Sepsis

    Directory of Open Access Journals (Sweden)

    D. L. Shukevich

    2010-01-01

    Full Text Available Objective: to improve the results of treatment for severe obstetric sepsis by pathogenetically founded continuous renal replacement therapies as extracorporeal homeostatic correction. Subjects and methods. Forty-two women with severe abdominal sepsis were divided into 3 groups: 1 14 women with severe extragenital abdominal sepsis who received standard intensive care (a control group; 2 12 women with severe obstetric sepsis who had standard intensive care (a study group; 3 16 with severe obstetric sepsis who had the standard intensive care supplemented with continuous renal replacement therapy (an intervention group. Results. In Group 2, endogenous intoxication and multiple organ dysfunction were controlled later than in Group 1, mortality rates being 41.7 and 7.1%, respectively. Clinical laboratory differences were due to gestosis recorded in 100% of the patients with severe obstetric sepsis. When continuous renal replacement therapy was incorporated into the complex therapy of severe obstetric sepsis, there was a prompter regression of endogenous intoxication and multiple organ dysfunction, mortality was decreased by an average of 35% as compared with that during standard therapy. Conclusion. The inclusion of continuous renal replacement therapy into the complex treatment program for severe obstetric sepsis made it possible to reduce control time _ for endogenous intoxication and multiple organ dysfunction and to decrease mortality by an average of 35% as compared with that during standard intensive care. Key words: obstetric sepsis, abdominal sepsis, gestosis, endogenous intoxication, multiple organ dysfunction, renal replacement therapy.

  15. Managing the menopause: British Menopause Society Council consensus statement on hormone replacement therapy.

    Science.gov (United States)

    Pitkin, Joan; Rees, Margaret C P; Gray, Sarah; Lumsden, Mary Ann; Marsden, Jo; Stevenson, John; Williamson, Jennifer

    2005-12-01

    The British Menopause Society Council aims to help health professionals inform and advise women about the menopause. This guidance regarding estrogen-based hormone replacement therapy (HRT), including tibolone, which is classified in the British National Formulary as HRT, responds to the results and analysis of the randomized Women's Health Initiative studies and the observational Million Women Study. Treatment choice should be based on up-to-date information and targeted to individual women's needs. HRT still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.

  16. Effect of a novel bladder preservation therapy, BOAI-CDDP-radiation (OMC-regimen).

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Nomi, Hayahito; Uehara, Hiroshi; Komura, Kazumasa; Minami, Koichiro; Kouno, Junko; Kotake, Yatsugu; Abe, Hirokazu; Takagi, Shizuko; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Kiyama, Satoshi

    2013-07-01

    We have developed a novel form of bladder preservation therapy [OMC (Osaka Medical College)-regimen] involving balloon-occluded-arterial-infusion (BOAI) of an anticancer agent (cisplatin/gemcitabine), used concomitantly with hemodialysis, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects, along with concurrent radiation. We previously reported that the OMC-regimen elicited a complete response (CR) in >90% of patients with organ confined tumors, while LN(+), T4 tumors and a non-UC histological type were statistically significant risk factors for treatment failure and patient survival. In this study, we investigated the effects of the OMC-regimen in patients with organ confined urothelial cancer tumors and the outcomes were compared to those with total cystectomy. Three hundred and one patients were assigned to receive either the OMC-regimen (n=162) or total cystectomy (n=139). Patients in the OMC-regimen group who failed to achieve CR underwent cystectomy, or secondary BOAI with an increased amount of CDDP or gemcitabine (1600 mg). The OMC-regimen yielded 98.1% of clinical response; CR in 93.8% (152/162) of patients; PR in 4.3% (7/162). More than 96% of the CR patients (146/152) were alive with no evidence of recurrence after a mean follow-up of 166 (range 23-960) weeks. No patients suffered grade III toxicity; all patients successfully completed this therapy. The patient survival was significantly better compared to the cystectomy group; the overall 5-, 10- and 15-year survival rates were 87.3, 79.6 and 59.7%, respectively. Moreover, the 5-, 10- and 15-year bladder intact survival rates, the most important issue for bladder preservation therapy, were 85.7, 78.4 and 58.8%, respectively. In conclusion, the OMC-regimen is a useful bladder-preservation strategy, not only in those for whom cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    BACKGROUND: The effect of postmenopausal hormone replacement therapy (HRT) on the risk of subtypes of stroke is as yet unclear. To investigate the effect of oestrogen and combined oestrogen-progestagen therapy on the risk of non-fatal haemorrhagic and thromboembolic stroke, we carried out a case-...

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

    Science.gov (United States)

    Drusano, George L; Neely, Michael; Van Guilder, Michael; Schumitzky, Alan; Brown, David; Fikes, Steven; Peloquin, Charles; Louie, Arnold

    2014-01-01

    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.

  19. 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......L) 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...

  20. Effectiveness of Antiretroviral Therapy in Individuals Who for Economic Reasons Were Switched From a Once-Daily Single-Tablet Regimen to a Triple-Tablet Regimen

    DEFF Research Database (Denmark)

    Engsig, Frederik N; Gerstoft, Jan; Helleberg, Marie

    2014-01-01

    1, 2011 to obtain economic savings. METHODS AND FINDINGS: From the Capital Region of Denmark (covering two-thirds of the Danish HIV patients), we included combination antiretroviral therapy (cART)-naive patients who administered STR-TEE from April 1, 2010 to March 31, 2011 (n = 111) or TTR-TEL from......BACKGROUND: To assess the impact on virological outcomes of a switch from branded single-tablet regimen (STR) including tenofovir, efavirenz, and emtricitabine (STR-TEE) to generic triple-tablet regimen (TTR), including tenofovir, efavirenz, and lamivudine (TTR-TEL), which was implemented on April...

  1. Prospects for retinal gene replacement therapy.

    Science.gov (United States)

    Smith, Alexander J; Bainbridge, James W; Ali, Robin R

    2009-04-01

    Inherited retinal degeneration, which includes conditions such as retinitis pigmentosa and Leber congenital amaurosis (LCA), affects approximately 1/3000 of the population in the Western world. It is characterized by loss of vision and results from mutations in any one of >100 different genes. There are currently no effective treatments, but many of the genes have now been identified and their functions elucidated, providing a major impetus to develop gene-based treatments. Preliminary results from three clinical trials indicate that the treatment of a form of LCA by gene therapy can be safe and effective. Here, we discuss the potential for treating other forms of retinal degeneration by gene therapy, focusing on the gene defects that are likely to be the most amenable to treatment.

  2. Testosterone replacement therapy for older men

    OpenAIRE

    Borst, S E

    2008-01-01

    Stephen E Borst, Thomas MulliganGeriatrics Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USAAbstract: Despite intensive research on testosterone therapy for older men, important questions remain unanswered. The evidence clearly indicates that many older men display a partial androgen deficiency. In older men, low circulating testosterone is correlated with low muscle strength, with high adiposity, with insulin resistance and wit...

  3. Testosterone replacement therapy for older men

    OpenAIRE

    Borst, Stephen E.; Thomas Mulligan

    2007-01-01

    Stephen E Borst, Thomas MulliganGeriatrics Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USAAbstract: Despite intensive research on testosterone therapy for older men, important questions remain unanswered. The evidence clearly indicates that many older men display a partial androgen deficiency. In older men, low circulating testosterone is correlated with low muscle strength, with high adiposity, with insulin resistance and wit...

  4. Testosterone replacement therapy for older men

    OpenAIRE

    Borst, S. E.

    2008-01-01

    Stephen E Borst, Thomas MulliganGeriatrics Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USAAbstract: Despite intensive research on testosterone therapy for older men, important questions remain unanswered. The evidence clearly indicates that many older men display a partial androgen deficiency. In older men, low circulating testosterone is correlated with low muscle strength, with high adiposity, with insulin resistance and wit...

  5. Testosterone replacement therapy for older men

    OpenAIRE

    Stephen E Borst; Thomas Mulligan

    2007-01-01

    Stephen E Borst, Thomas MulliganGeriatrics Research, Education, and Clinical Center, North Florida/South Georgia Veterans Health System, Gainesville, FL, USAAbstract: Despite intensive research on testosterone therapy for older men, important questions remain unanswered. The evidence clearly indicates that many older men display a partial androgen deficiency. In older men, low circulating testosterone is correlated with low muscle strength, with high adiposity, with insulin resistance and wit...

  6. Testosterone Replacement Therapy and Prostate Cancer Incidence

    OpenAIRE

    Eisenberg, Michael Louis

    2015-01-01

    While early studies demonstrated a positive association between testosterone and prostate cancer, evidence on the nature of the relationship has evolved with time and newer data. Studies examining links between baseline testosterone levels as well as testosterone therapy and incident prostate cancer, reveal a more complex relationship. Moreover, investigators have reported their initial experiences with supplementing testosterone in men with a history of both treated and untreated prostate ca...

  7. 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.

  8. [Gene replacement therapy in achromatopsia type 2].

    Science.gov (United States)

    Mühlfriedel, R; Tanimoto, N; Seeliger, M W

    2014-03-01

    Achromatopsia is an autosomal recessive inherited retinal disease caused by a complete loss of cone photoreceptor function. About 80 % of achromatopsia patients show mutations in the alpha or beta subunit (A3 and B3) of the cGMP controlled cation channel CNG (cyclic nucleotide-gated channel) of cone photoreceptors. Homologous to the human disease, CNGA3 deficient mice reveal a loss of cone specific functionality leading to degeneration of affected cone photoreceptors. The Institute for Ophthalmic Research in Tübingen has now succeeded in curing achromatopsia ACHM2 in an animal model. In this article, we explain the recombinant adeno-associated virus-based approach in detail. Furthermore, applied non-invasive diagnostic techniques for quality and success control, ERG, SLO and OCT, are described. The success of the therapy is indicated by a restored cone photoreceptor function as well as the neuronal processing of retinal signals resulting in a specific, cone-mediated behaviour. The outstanding results derived from the animal model are the starting point for the first human translation of a gene therapy for achromatopsia in Germany. Georg Thieme Verlag KG Stuttgart · New York.

  9. Managing the menopause - British Menopause Society Council consensus statement on hormone replacement therapy.

    Science.gov (United States)

    Pitkin, Joan; Rees, Margaret C P; Gray, Sarah; Lumsden, Mary Ann; Stevenson, John; Williamson, Jennifer

    2003-09-01

    The British Menopause Society Council aims to aid health professionals to inform and advise women about the menopause. The oestrogen plus progestogen arm of the Women's Health Initiative was stopped in July 2002. This guidance regarding hormone replacement therapy (HRT) use responds to the results and analysis that have been published since then. Because there are few effective alternatives to HRT for vasomotor and urogenital symptoms, oestrogen-based treatments still have a major role. HRT is also most effective for prevention of osteoporosis. Unopposed oestrogens are contraindicated in women with an intact uterus, and hence a range of oestrogen and progestogen combinations, with differing routes of delivery, now exists under the title of "HRT". Treatment choice should be based on up to date information and targeted to individual women's needs. Hormone replacement still offers the potential for benefit to outweigh harm, providing the appropriate regimen has been instigated in terms of dose, route and combination.

  10. Gene replacement therapy for retinal CNG channelopathies.

    Science.gov (United States)

    Schön, Christian; Biel, Martin; Michalakis, Stylianos

    2013-10-01

    Visual phototransduction relies on the function of cyclic nucleotide-gated channels in the rod and cone photoreceptor outer segment plasma membranes. The role of these ion channels is to translate light-triggered changes in the second messenger cyclic guanosine 3'-5'-monophosphate levels into an electrical signal that is further processed within the retinal network and then sent to higher visual centers. Rod and cone photoreceptors express distinct CNG channels. The rod photoreceptor CNG channel is composed of one CNGB1 and three CNGA1 subunits, whereas the cone channel is formed by one CNGB3 and three CNGA3 subunits. Mutations in any of these channel subunits result in severe and currently untreatable retinal degenerative diseases like retinitis pigmentosa or achromatopsia. In this review, we provide an overview of the human diseases and relevant animal models of CNG channelopathies. Furthermore, we summarize recent results from preclinical gene therapy studies using adeno-associated viral vectors and discuss the efficacy and translational potential of these gene therapeutic approaches.

  11. Antiretroviral therapy in HIV-infected patients: a proposal to assess the economic value of the single-tablet regimen

    Directory of Open Access Journals (Sweden)

    Colombo GL

    2013-02-01

    Full Text Available Giorgio L Colombo,1,2 Sergio Di Matteo,2 Franco Maggiolo31University of Pavia, Department of Drug Sciences, School of Pharmacy, Pavia, Italy, 2Studi Analisi Valutazioni Economiche, Milan, Italy, 3Division of Infectious Diseases, Ospedali Riuniti, Bergamo, ItalyBackground: The aim of this study was to assess the economic value of a reduced number of pills in patients infected with the immunodeficiency virus (HIV and on highly active antiretroviral therapy by a cost-effectiveness model.Methods: An incremental cost-effectiveness analysis of efavirenz, tenofovir, and emtricitabine (TDF-FTC-EFV as a single-tablet regimen versus a multipill regimen, with reference to untreated HIV-infected patients, was carried out from the perspective of the Italian National Health Service. The comparisons were performed with the help of a Markov decision model over a 10-year time horizon. Based on the ADONE (ADherence to ONE pill study, it was then possible to identify the utility score increment in patients switching from a multipill regimen of TDF-FTC + EFV therapy to a single-tablet regimen.Results: The single-tablet regimen (0.755 quality-adjusted life-years [QALYs]/year resulted in better patient quality of life, with a higher number of QALYs than for the TDF-FTC + EFV multipill regimen (0.716 QALYs/year. The single-tablet regimen was the most cost-effective treatment strategy, with an incremental cost-effectiveness ratio of €22,017.00 versus €26,558.00 for the multipill regimen. A 24% decrease in cost of the multipill regimen determined equivalence with the single-tablet regimen in terms of the incremental cost-effectiveness ratio. Univariate sensitivity and probabilistic analysis carried out on the main variables did not highlight significant variations with respect to the base case scenario.Conclusion: The single-tablet regimen resulted in better adherence, and therefore better quality of life as perceived by patients, corresponding to a €4541.00 lower

  12. The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study.

    Science.gov (United States)

    Ruiz, Andres D; Daniels, Kelly R

    2014-01-01

    Prior studies demonstrated improved menopausal symptom relief following treatment with compounded bioidentical hormone replacement therapy; however, clinical effectiveness studies evaluating different routes of bioidentical hormone replacement therapy administration are lacking. The objective of this study was to determine the effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy for the treatment of vasomotor, mood, and other quality-of-life symptoms in post-menopausal women. This was a prospective, observational cohort study of women > or = 18 years of age who received a compounded sublingual or topical bioidentical hormone replacement therapy preparation between January 1, 2003 and October 1, 2010 in a community pharmacy. Data collection included patient demographics, comorbidities, hormone regimens, and therapeutic outcomes. Patients rated their vasomotor, mood, and quality-of-life symptoms as absent, mild, moderate, or severe at baseline, at one to three months follow-up, and three to six months follow-up. Baseline characteristics were compared using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables. Symptom intensity between baseline and follow-up periods were compared using the Wilcoxon signed-rank test. A total of 200 patients met study criteria; 160 received topical bioidentical hormone replacement therapy, and 40 received sublingual bioidentical hormone replacement therapy. Most sublingually-treated patients (70%) received an estrogen combination and 100% received progesterone. Nearly half (43%) of the topically treated patients received an estrogen combination (43%) and 99% received progesterone. The percentage of sublingually treated patients reporting "moderate" or "severe" symptoms was significantly reduced at one to three months follow-up for the following target symptoms: hot flashes (31%, P = 0.04), night sweats (38%, P sublingual bioidentical hormone

  13. Digestive Enzyme Replacement Therapy: Pancreatic Enzymes and Lactase.

    Science.gov (United States)

    Felicilda-Reynaldo, Rhea Faye D; Kenneally, Maria

    2016-01-01

    Maldigestion occurs when digestive enzymes are lacking to help break complex food components into absorbable nutrients within the gastrointestinal tract. Education is needed to help patients manage the intricacies of digestive enzyme replacement therapies and ensure their effectiveness in reducing symptoms of maldigestion.

  14. Trends in Renal Replacement Therapy in Turkey, 1996-2008

    NARCIS (Netherlands)

    G. Suleymanlar; K. Serdengecti; M.R. Altiparmak; K. Jager; N. Seyahi; E. Erek

    2011-01-01

    Background: National renal registry studies providing data for incidence, prevalence, and characteristics of end-stage renal disease and renal replacement therapy (RRT) serve as a basis to determine national strategies for the prevention and treatment of these diseases and identify new areas for spe

  15. Modeling Outcome of Patients on Renal Replacement Therapy

    NARCIS (Netherlands)

    Y.S. Liem (Ylian Serina)

    2008-01-01

    textabstractThe incidence of end-stage renal disease is increasing and therefore, the number of patients requiring renal replacement therapy (RRT), renal dialysis or renal transplantation (RTx), has been rising. The various forms of RRT are associated with differences in survival and quality of life

  16. Pharmacokinetics of Procainamide and N-acetylprocainamide during Continuous Renal Replacement Therapy

    Science.gov (United States)

    Mohamed, Ahmed N.; Abdelhady, Ahmed M.; Spencer, Dustin; Sowinski, Kevin M.; Tisdale, James E.; Overholser, Brian R.

    2013-01-01

    Procainamide and its major metabolite, N-acetyl procainamide (NAPA), prolong the QTc interval and can promote potentially fatal ventricular arrhythmias. Excretion of procainamide and NAPA is reduced in patients with chronic kidney disease (CKD) resulting in drug accumulation and toxicity. The elimination of procainamide or NAPA in patients undergoing continuous renal replacement therapy (CRRT) has not been evaluated increasing the risk for subtherapeutic or toxic dosing regimens. This case report describes a patient undergoing CRRT who was administered procainamide for recurring ventricular tachycardia (VT) over approximately a 36 hour period. The patient required increased vasopressor therapy and developed QTc prolongation during procainamide administration. The VT resided following pacemaker adjustments, procainamide administration, and multiple direct current cardioversion attempts. Procainamide and NAPA concentrations were determined over a 120 hour period as part of routine clinical care and a pharmacokinetic (PK) model was developed using NONMEM. The developed PK model was used to simulate several procainamide dosing regimens to optimize therapy during CRRT. Based on the model-based simulations, a 50% reduction in the procainamide maintenance dose (2 mg/min) in CKD patients on CRRT can achieve therapeutic plasma procainamide and combined procainamide/NAPA concentrations. PMID:23562328

  17. 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

    1992-01-01

    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 ef

  18. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    Science.gov (United States)

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  19. Hormone replacement therapy and the risk of endometrial cancer

    DEFF Research Database (Denmark)

    Sjögren, Lea; Mørch, Lina S; Løkkegaard, Ellen

    2016-01-01

    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......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......, 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...

  20. 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

  1. [Extracorporeal renal replacement therapies in acute renal failure].

    Science.gov (United States)

    Schaefer, R M; Barenbrock, M; Teschner, M; Bahner, U

    2000-05-15

    The most serious forms of acute renal failure (ARF) are nowadays encountered in the intensive care unit (ICU), where up to 25% of new patients are reported to develop ARF. Lethality rates may reach 50 to 90% when the ARF is part of a multiple organ dysfunction syndrome. A multitude of extracorporeal procedures have been introduced into intensive care medicine. Applied with adequate skills and experience, most of these techniques will suffice to replace excretory renal function. However, because of low efficacy arterio-venous procedures (CAVH and CAVHD) have been abandoned for the veno-venous, pump-driven techniques (CVVH and CVVHD). Up to now, there is no consensus whether continuous or intermittent renal replacement therapy is more advantageous. In many cases, oliguric patients with circulatory instability will be treated by CVVH, even though there is no prospective study to show that in terms of outcome continuous treatment is superior to intermittent hemodialysis. It is equally conceivable to treat such patients with daily, prolonged (intermittent) hemodialysis. Apparently, the dose of replacement therapy, be it continuous filtration (36 to 48 l/24 h) or intermittent hemodialysis (daily 3 to 4 h) with a target BUN of less than 50 mg/dl, is more important than the modality of treatment. Moreover, there is good evidence that the use of biocompatible membranes (no complement- or leukocyte activation) is preferable and that with high-volume hemofiltration bicarbonate-containing replacement fluids should be used. However, despite all the technical advances, we firmly believe that the skills and the experience of those physicians and nurses who actually perform renal replacement therapy in the ICU are more important than the modality of treatment applied.

  2. Myelin restoration: progress and prospects for human cell replacement therapies.

    Science.gov (United States)

    Potter, Gregory B; Rowitch, David H; Petryniak, Magdalena A

    2011-06-01

    Oligodendrocytes are the primary source of myelin in the adult central nervous system (CNS), and their dysfunction or loss underlies several diseases of both children and adults. Dysmyelinating and demyelinating diseases are thus attractive targets for cell-based strategies since replacement of a single presumably homogeneous cell type has the potential to restore functional levels of myelin. To understand the obstacles that cell-replacement therapy might face, we review oligodendrocyte biology and emphasize aspects of oligodendrocyte development that will need to be recapitulated by exogenously transplanted cells, including migration from the site of transplantation, axon recognition, terminal differentiation, axon wrapping, and myelin production and maintenance. We summarize studies in which different types of myelin-forming cells have been transplanted into the CNS and highlight the continuing challenges regarding the use of cell-based therapies for human white matter disorders.

  3. Iodinated contrast media and the role of renal replacement therapy.

    Science.gov (United States)

    Weisbord, Steven D; Palevsky, Paul M

    2011-05-01

    Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc.

  4. Controversies in testosterone replacement therapy: testosterone and cardiovascular disease

    OpenAIRE

    Kathleen Hwang; Martin Miner

    2015-01-01

    The role of testosterone in the cardiovascular (CV) health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term ...

  5. Hormone replacement therapy and the prevention of postmenopausal osteoporosis

    OpenAIRE

    Marco Gambacciani; Marco Levancini

    2014-01-01

    Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a ...

  6. Controversies in testosterone replacement therapy: testosterone and cardiovascular disease

    OpenAIRE

    Kathleen Hwang; Martin Miner

    2015-01-01

    The role of testosterone in the cardiovascular (CV) health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term ...

  7. Central nervous system HIV infection in "less-drug regimen" antiretroviral therapy simplification strategies.

    Science.gov (United States)

    Ferretti, Francesca; Gianotti, Nicola; Lazzarin, Adriano; Cinque, Paola

    2014-02-01

    Less-drug regimens (LDR) refer to combinations of either two antiretroviral drugs or ritonavir-boosted protease inhibitor (PI) monotherapy. They may represent a simplification strategy in patients with persistently suppressed human immunodeficiency virus (HIV) viremia, with the main benefits of reducing drug-related toxicities and costs. Systemic virological efficacy of LDR is slightly lower as compared with combined antiretroviral therapy (cART), but patients with failure do not usually develop drug resistance and resuppress HIV replication after reintensification. A major concern of LDR is the lower efficacy in the virus reservoirs, especially in the central nervous system (CNS), where viral compartmentalization and independent evolution of infection may lead to CNS viral escape, often associated with neurologic symptoms. The authors reviewed studies of virological and functional CNS efficacy of LDR, particularly of boosted PI monotherapy regimens, for which more information is available. Symptomatic viral CSF escape was observed mainly in PI/r monotherapy patients with plasma failure and low nadir CD4+ cell counts, and resolved upon reintroduction of triple drug cART, whereas asymptomatic viral failure in CSF was not significantly more frequent in patients on PI/r monotherapy compared with patients on standard cART. In addition, there was no difference in functional outcomes between PI monotherapy and cART patients, irrespective of CSF viral escape. More data are needed on the CNS effect of dual ART regimens and, in general, on long-term efficacy of LDR. Simplification with LDR may be an attractive option in patients with suppressed viral load, if they are well selected and monitored for potential CNS complications.

  8. AARC Clinical Practice Guideline. Surfactant replacement therapy: 2013.

    Science.gov (United States)

    Walsh, Brian K; Daigle, Brandon; DiBlasi, Robert M; Restrepo, Ruben D

    2013-02-01

    We searched the MEDLINE, CINAHL, and Cochrane Library databases for English-language randomized controlled trials, systematic reviews, and articles investigating surfactant replacement therapy published between January 1990 and July 2012. By inspection of titles, references having no relevance to the clinical practice guideline were eliminated. The update of this clinical practice guideline is based on 253 clinical trials and systematic reviews, and 12 articles investigating surfactant replacement therapy. The following recommendations are made following the Grading of Recommendations Assessment, Development, and Evaluation scoring system: 1: Administration of surfactant replacement therapy is strongly recommended in a clinical setting where properly trained personnel and equipment for intubation and resuscitation are readily available. 2: Prophylactic surfactant administration is recommended for neonatal respiratory distress syndrome (RDS) in which surfactant deficiency is suspected. 3: Rescue or therapeutic administration of surfactant after the initiation of mechanical ventilation in infants with clinically confirmed RDS is strongly recommended. 4: A multiple surfactant dose strategy is recommended over a single dose strategy. 5: Natural exogenous surfactant preparations are recommended over laboratory derived synthetic suspensions at this time. 6: We suggest that aerosolized delivery of surfactant not be utilized at this time.

  9. 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

  10. Renal Replacement Therapy [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Zaccaria Ricci

    2016-01-01

    Full Text Available During the last few years, due to medical and surgical evolution, patients with increasingly severe diseases causing multiorgan dysfunction are frequently admitted to intensive care units. Therapeutic options, when organ failure occurs, are frequently nonspecific and mostly directed towards supporting vital function. In these scenarios, the kidneys are almost always involved and, therefore, renal replacement therapies have become a common routine practice in critically ill patients with acute kidney injury. Recent technological improvement has led to the production of safe, versatile and efficient dialysis machines. In addition, emerging evidence may allow better individualization of treatment with tailored prescription depending on the patients’ clinical picture (e.g. sepsis, fluid overload, pediatric. The aim of the present review is to give a general overview of current practice in renal replacement therapies for critically ill patients. The main clinical aspects, including dose prescription, modality of dialysis delivery, anticoagulation strategies and timing will be addressed. In addition, some technical issues on physical principles governing blood purification, filters characteristics, and vascular access, will be covered. Finally, a section on current standard nomenclature of renal replacement therapy is devoted to clarify the “Tower of Babel” of critical care nephrology.

  11. Enzyme replacement therapy for pancreatic insufficiency: present and future

    Directory of Open Access Journals (Sweden)

    Fieker A

    2011-05-01

    Full Text Available Aaron Fieker1, Jessica Philpott1, Martine Armand21Division of Digestive Diseases, University of Oklahoma, OKC, OK, USA; 2INSERM, U476 "Nutrition Humaine et Lipides", Marseille, F-13385 France; Univ Méditerranée Aix-Marseille 2, Faculté de Médecine, IPHM-IFR 125, Marseille, F-13385 FranceAbstract: Pancreatic enzyme replacement therapy is currently the mainstay of treatment for nutrient malabsorption secondary to pancreatic insufficiency. This treatment is safe and has few side effects. Data demonstrate efficacy in reducing steatorrhea and fat malabsorption. Effective therapy has been limited by the ability to replicate the physiologic process of enzyme delivery to the appropriate site, in general the duodenum, at the appropriate time. The challenges include enzyme destruction in the stomach, lack of adequate mixing with the chyme in the duodenum, and failing to deliver and activate at the appropriate time. Treatment is begun when clinically significant malabsorption occurs resulting in steatorrhea and weight loss. Treatment failure is addressed in a sequential fashion. Current research is aimed at studying new enzymes and delivery systems to improve the efficiency of action in the duodenum along with developing better means to monitor therapy.Keywords: exocrine pancreatic insufficiency, chronic pancreatitis, cystic fibrosis, pancreatic enzyme replacement therapy, lipase, lipids

  12. Renal replacement therapy in the intensive care unit

    Directory of Open Access Journals (Sweden)

    Chacko Jose

    2008-01-01

    Full Text Available Acute renal failure is a frequent complication in critically ill patients that carries with it considerable morbidity and mortality. The management of renal failure in patients with multi-organ failure is different from that of renal failure that presents as a single organ failure. Intermittent haemodialysis, done in the conventional manner may not be tolerated by most critically ill patients. Continuous renal replacement therapy is physiologically superior; however, there is lack of strong evidence to prove a clinical benefit. Hybrid therapies that combine the benefits of intermittent haemodialysis and continuous therapies have emerged in the past few years. These are simpler to carry out, provide more flexibility and may be cost effective and need to be studied in a systematic manner.

  13. 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

  14. Alzheimer's disease, apolipoprotein E and hormone replacement therapy.

    Science.gov (United States)

    Depypere, H; Vierin, A; Weyers, S; Sieben, A

    2016-12-01

    Alzheimer's disease is the most frequent cause of dementia in older patients. The prevalence is higher in women than in men. This may be the result of both the higher life expectancy of women and the loss of neuroprotective estrogen after menopause. Earlier age at menopause (spontaneous or surgical) is associated with an enhanced risk of developing Alzheimer's disease. Therefore, it is postulated that estrogen could be protective against it. If so, increasing exposure to estrogen through the use of postmenopausal hormone replacement could also be protective against Alzheimer's disease. The results of the clinical studies that have examined this hypothesis are inconclusive, however. One explanation for this is that estrogen treatment is protective only if it is initiated in the years immediately after menopause. Another possibility is that the neuroprotective effects of estrogen are negated by a particular genotype of apolipoprotein E. This protein plays an important role in cholesterol transport to the neurons. Studies that have examined the link between estrogen replacement therapy, Alzheimer's disease and the E4 allele of ApoE are inconclusive. This article reviews the literature on the influence of hormone replacement therapy on the incidence and progression of Alzheimer's disease.

  15. Testosterone replacement therapy and the risk of prostate cancer.

    Science.gov (United States)

    Warburton, Daniel; Hobaugh, Christopher; Wang, Grace; Lin, Haocheng; Wang, Run

    2015-01-01

    Understanding the role of testosterone replacement therapy (TRT) in the development and progression of prostate cancer is an important concept in treating patients with symptoms of hypogonadism. This article revealed a small number of mostly retrospective, observational studies describing the use of TRT in the general population, in men with prostatic intraepithelial neoplasia (PIN), in men with a history of treated prostate cancer, and in men on active surveillance for prostate cancer. The current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism, and the prostate saturation theory provides a model explaining the basis for these results. The use of TRT in men with a history of prostate cancer is considered experimental, but future results from randomized controlled trials could lead to a change in our current treatment approach.

  16. Testosterone replacement therapy and the risk of prostate cancer

    Directory of Open Access Journals (Sweden)

    Daniel Warburton

    2015-01-01

    Full Text Available Understanding the role of testosterone replacement therapy (TRT in the development and progression of prostate cancer is an important concept in treating patients with symptoms of hypogonadism. This article revealed a small number of mostly retrospective, observational studies describing the use of TRT in the general population, in men with prostatic intraepithelial neoplasia (PIN, in men with a history of treated prostate cancer, and in men on active surveillance for prostate cancer. The current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism, and the prostate saturation theory provides a model explaining the basis for these results. The use of TRT in men with a history of prostate cancer is considered experimental, but future results from randomized controlled trials could lead to a change in our current treatment approach.

  17. [Pharmacokinetics of antibiotics in continuous renal replacement therapies (CRRT)].

    Science.gov (United States)

    Morabito, Santo; Pistolesi, Valentina; Maggiore, Umberto; Fiaccadori, Enrico; Pierucci, Alessandro

    2012-01-01

    In the critically ill patient, acute kidney injury (AKI) is frequently associated with infective complications requiring appropriate antimicrobial treatment. AKI and multiple organ dysfunction syndrome can affect the pharmacokinetic parameters of many drugs. Furthermore, the start of renal replacement therapy (RRT) is an additional variable to be taken into consideration to avoid inappropriate antimicrobial therapy. Continuous renal replacement therapies (CRRT) are widely adopted in the intensive care unit (ICU) and antibiotics that are significantly eliminated by the kidney are likely to be removed during RRT. Generally, drug-dosing adjustments are required if the extracorporeal clearance accounts for more than 25-30% of the total body clearance. The molecular weight cutoffs of the more widely used membranes are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the antibiotics most commonly used in ICU patients. However, CRRTs are still not standardized and the impact of RRT on plasma drug concentrations can be substantially different depending on the CRRT modality (diffusive, convective or both), membrane characteristics and delivered dialysis dose. In any case, drug-dosing adjustments should be based on the knowledge of the pharmacokinetic and pharmacodynamic properties of the different classes of antimicrobials, taking into account that high extracorporeal clearances could lead to drug underexposure in clinical conditions where appropriate antibiotic treatment is essential.

  18. Meropenem in children receiving continuous renal replacement therapy: clinical trial simulations using realistic covariates.

    Science.gov (United States)

    Nehus, Edward J; Mouksassi, Samer; Vinks, Alexander A; Goldstein, Stuart

    2014-12-01

    Meropenem is frequently prescribed in children receiving continuous renal replacement therapy (CRRT). Fluid overload is often present in critically ill children and affects drug disposition. The purpose of this study was to develop a pharmacokinetic model to (1) evaluate target attainment of meropenem dosing regimens against P. aeruginosa in children receiving CRRT and (2) estimate the effect of fluid overload on target attainment. Clinical trial simulations were employed to evaluate target attainment of meropenem in various age groups and degrees of fluid overload in children receiving CRRT. Pharmacokinetic parameters were extracted from published literature, and 287 patients from the prospective pediatric CRRT registry database provided realistic clinical covariates including patient weight, fluid overload, and CRRT prescription characteristics. Target attainment at 40% and 75% time above the minimum inhibitory concentration was evaluated. Clinical trial simulations demonstrated that children greater than 5 years of age achieved acceptable target attainment with a dosing regimen of 20 mg/kg every 12 hours. In children less than 5, however, increased dosing of 20 mg/kg every 8 hours was needed to optimize target attainment. Fluid overload did not affect target attainment. These in silico model predictions will need to be verified in vivo in children receiving meropenem and CRRT. © 2014, The American College of Clinical Pharmacology.

  19. 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

  20. Observational study results in glaucoma patients undergoing a regimen replacement to fixed combination travoprost 0.004%/timolol 0.5% in Germany.

    Science.gov (United States)

    Arend, Kay-Oliver; Raber, Thomas

    2008-08-01

    With the launch of the fixed combination of travoprost 0.004%/timolol 0.5% (trav/tim) in Germany in May 2006, a noninterventional observational study designed as an open-label, multicenter, 6-week trial was initiated in order to evaluate the efficacy and tolerability of this new drug combination in glaucoma patients. Participants were grouped into categories according to previous drug regimens: those on timolol monotherapy; those on prostaglandin analog (PGA) monotherapy; those on concomitant therapy with a PGA and timolol; and those on fixed combinations. Trav/tim was well accepted by the patients, with 87.9% judging the tolerability of the therapy as good, very good, or excellent. Analysis of intraocular pressure (IOP) measurements showed statistically significant IOP decreases in all four categories examined in our study after regimen substitution with fixed-combination trav/tim. Fixed-combination prostaglandin analog/beta-blocker formulations are an attractive therapeutic option due to their strong IOP-lowering efficacy with once-daily dosing. In this study, glaucoma patients who underwent a regimen modification to fixed-combination trav/tim showed further reductions in IOP, irrespective of which selected monoor multiple therapies had been used previously.

  1. Levodopa therapy: consequences of the nonphysiologic replacement of dopamine.

    Science.gov (United States)

    Chase, T N

    1998-05-01

    Normal motor function is dependent on the highly regulated synthesis and release of the transmitter dopamine by neurons projecting from the substantia nigra to the corpus striatum. Parkinson's disease involves the progressive degeneration of these neurons. Its core symptoms are a direct consequence of a striatal insufficiency of intrasynaptic dopamine. Levodopa, the standard of care for the treatment of PD, acts after its conversion to dopamine by restoring striatal dopaminergic transmission. However, there are significant differences between the normally functioning dopamine system and the restoration of function provided by standard levodopa treatment. Increasing clinical and preclinical evidence suggests that the intermittent stimulation of dopamine receptors resulting from current therapeutic regimens contributes to the response complications that ultimately affect most parkinsonian patients. It now appears that chronic nonphysiologic stimulation of dopaminergic receptors on striatal GABAergic neurons activates characteristic signaling pathways, leading to a potentiation of the synaptic efficacy of adjacent glutamatergic receptors of the N-methyl-D-aspartate (NMDA) subtype. As a result, function of these GABAergic efferent neurons changes in ways that favor the appearance of motor complications. Conceivably, use of dopaminomimetic replacement strategies that provide more continuous dopamine receptor stimulation will act to prevent or alleviate these disabling complications. A number of promising approaches to achieving this goal are now under development.

  2. Update on Testosterone Replacement Therapy in Hypogonadal Men.

    Science.gov (United States)

    Leung, Kevin Matthew Yen Bing; Alrabeeah, Khalid; Carrier, Serge

    2015-08-01

    Late-onset male hypogonadism has long been recognized as a treatable medical condition; however, misconceptions about the use of testosterone replacement therapy (TRT) have often led urologists away from its more mainstream use. This paper aims to bring the reader up-to-date on the current understanding of TRT, starting with when and who to treat. Various formulations of TRT, each with its own risks and benefits, are also detailed. Finally, a comprehensive analysis of the current literature's views into the various controversies of TRT including its impact on prostate health, sexual health, cardiovascular health, frailty, and mood is discussed.

  3. [Renal replacement therapy by hemodialysis in Constantine (Algeria)].

    Science.gov (United States)

    Bouhabel, Abdelouahab; Laib, Zoheir; Hannache, Kamel; Aberkane, Abdelhamid

    2014-02-01

    End-stage renal failure is considered a public heath problem that constitutes a heavy cost on communities worldwide. To be able to plan the treatment of this pathology, we must have reliable and updated information through health network which represents the best mean for planning and reflexion locally and nationwide. The aim of our study was to answer to this need through a local registry of renal replacement therapy and nephrology network that we have for the first time an inventory of this pathology in an Algerian town (Constantine), and in this article we present the first results concerning patients under chronic hemodialysis.

  4. 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...

  5. Vascular access for extracorporeal renal replacement therapy in veterinary patients.

    Science.gov (United States)

    Chalhoub, Serge; Langston, Cathy E; Poeppel, Karen

    2011-01-01

    Vascular access is the first and most basic requirement for successful extracorporeal renal replacement therapy (ERRT). Dual-lumen catheters are the most commonly used method of vascular access for ERRT in veterinary patients. An adequately functioning dialysis catheter allows for smooth and efficient patient management, whereas a poorly functioning catheter frustrates the technician, doctor, and patient. These catheters are fairly quick to place but require meticulous care for optimal function. The most common complications are thrombosis and infection. Monitoring catheter performance should be a routine part of dialysis patient care.

  6. A modified regimen of extracorporeal cardiac shock wave therapy for treatment of coronary artery disease

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    Wang Yu

    2012-08-01

    Full Text Available Abstract Background Cardiac shock wave therapy (CSWT improves cardiac function in patients with severe coronary artery disease (CAD. We aimed to evaluate the clinical outcomes of a new CSWT treatment regimen. Methods The 55 patients with severe CAD were randomly divided into 3 treatment groups. The control group (n = 14 received only medical therapy. In group A ( n = 20, CSWT was performed 3 times within 3 months. In group B ( n = 21, patients underwent 3 CSWT sessions/week, and 9 treatment sessions were completed within 1 month. Primary outcome measurement was 6-minute walk test (6MWT. Other measurements were also evaluated. Results The 6MWT, CCS grading of angina, dosage of nitroglycerin, NYHA classification, and SAQ scores were improved in group A and B compared to control group. Conclusions A CSWT protocol with 1 month treatment duration showed similar therapeutic efficacy compared to a protocol of 3 months duration. Clinical trial registry We have registered on ClinicalTrials.gov, the protocol ID is CSWT IN CHINA.

  7. Opioid use among female breast cancer patients using different adjuvant endocrine therapy regimens.

    Science.gov (United States)

    Tan, Xi; Camacho, Tareq Fabian; LeBaron, Virginia T; Blackhall, Leslie J; Balkrishnan, Rajesh

    2017-09-01

    To explore differences in opioid use across different adjuvant endocrine therapy (AET) regimens, factors associated with opioid use, and the impact of opioid use on overall survival in female breast cancer patients treated with AET. This retrospective study analyzed 2006-2012 SEER-Medicare datasets, following patients for at least two years from the index date, defined as the first date they filled an AET prescription. The study included adult women with incident, primary, hormone-receptor-positive, stage I-III breast cancer. They were also first-time AET users, and fee-for-service Medicare enrollees continuously enrolled in Medicare Parts A, B, and D. The main independent variable was the AET regimen. We measured whether patients used opioids after the initiation of AET. After the adjustment of inverse probability treatment weights and unbalanced covariates, the average treatment effect probabilities of opioid use were similar between those who used aromatase inhibitors (AI) only and those used tamoxifen (TAM) only (56.2 vs. 55.3%, respectively). Opioid use probabilities for those who switched from AI to TAM were higher than those for the TAM-only and AI-only groups. Opioid use was also significantly associated with AET non-adherence. Opioid users had a significantly higher risk of death (adjusted hazard ratio [HR] = 1.59, p < 0.001). Switching from AI to TAM was associated with a high likelihood of opioid use. Opioid use was significantly associated with AET non-adherence and higher risk of mortality in female Medicare beneficiaries with breast cancer even after adjusting for adherence.

  8. Persistence to single-tablet regimen versus less-drug regimen in treatment experienced HIV-infected patients on antiretroviral therapy

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    Rocio Jiménez-Galán

    2016-07-01

    Full Text Available Background: Decreased antiretroviral therapy persistence is associated with increased rates of virologic failure, development of antiretroviral resistance, and increased morbidity and mortality. Different therapeutic strategies, such as single-tablet regimens (STR and less-drug regimens (LDR, have been developed in order to simplify antiretroviral therapy (ART and increase persistence. Objectives: The primary objective was to compare antiretroviral persistence among patients receiving STRs and patients receiving LDRs. A secondary objective was to identify factors associated with non-persistence. Methods: This was a retrospective study that included treatment- experienced HIV-infected patients who received ART based on STR or LDR. Baseline patient characteristics collected included demographic information, HIV risk transmission, substance abuse during the therapy, presence of psychiatric disorder and hepatitis B or C virus infection. Kaplan-Meier analysis and Log rank was utilized to compare persistence to STR and LDR. To identify independent predictors of non-persistence we developed a multivariate Cox regression analysis. Results: A total of 244 patients were included, 176 with STR and 68 with LDR. 60 (34.1% patients discontinued in the STR group and 13 (19.1% in the LDR group. The Cox regression model showed that the only variable associated with higher risk of non-persistence was the substance abuse (HR = 2.59; p = 0.005. Adverse events were the main reason for ART discontinuation in the STR group and virologic failure in the LDR group. Conclusions: Persistence to STR and LDR seems to be similar in pretreated HIV-infected patients. Drug abuse was the only factor identified with a higher risk of non-persistence.

  9. Controversies in testosterone replacement therapy: testosterone and cardiovascular disease.

    Science.gov (United States)

    Hwang, Kathleen; Miner, Martin

    2015-01-01

    The role of testosterone in the cardiovascular (CV) health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term prospective studies to determine safety. Literature spanning over the past 30 years has suggested that not only is there a possible increased CV risk in men with low levels of testosterone, but the benefits from testosterone therapy may even lower this risk. We review here the recent studies that have garnered such intense scrutiny. This article is intended as a thorough review of testosterone levels and CV risk, providing the clinician with the facts needed to make informed clinical decisions in managing patients with clinical hypogonadism.

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

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    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. RENAL REPLACEMENT THERAPY IN ACUTE KIDNEY FAILURE - AN OVERVIEW

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    Treesa P. Varghese

    2014-10-01

    Full Text Available Renal failure is the loss of renal function, either acute or chronic, that results in azotemia and syndrome of uremia. Acute renal failure, is also known as acute kidney injury (AKI, is defined as an abrupt (within 48 hours reduction in kidney function. The initial management of acute kidney failure involves treating the underlying cause, stopping nephrotoxic drugs and ensuring that the patient is euvolaemic with an adequate mean arterial blood pressure. However, no specific treatments have been shown to reverse the course AKF so Renal Replacement Therapy (RRT is the cornerstone of further management. RRT therapy can be administrated either intermittently or continuously. Multiple modalities of RRT are currently available. The purpose of this review is to familiarize different modalities of RRT for blood purification.

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    BACKGROUND: The effect of postmenopausal hormone replacement therapy (HRT) on the risk of subtypes of stroke is as yet unclear. To investigate the effect of oestrogen and combined oestrogen-progestagen therapy on the risk of non-fatal haemorrhagic and thromboembolic stroke, we carried out a case......-control study. METHODS: From the Danish National Patient Register we identified all Danish women aged 45-64 years who had a non-fatal, first-ever cerebrovascular attack during 1990-92. Two age-matched controls were randomly selected for each case from the Danish National Person Register. Important correlates...... of hormone use and stroke, on which information was obtained from postal questionnaires, were controlled for by multivariate analyses based on log-linear graphical models. The analyses included data on 1422 cases classified in four subtypes of stroke (160 subarachnoid haemorrhage, 95 intracerebral...

  13. A retrospective study: osteoporosis and hormone replacement therapy

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    H. June Kuczynski

    1989-09-01

    Full Text Available The purpose of this stud y was to determine i f women who undergo hormone replacement therapy postmenopausally, will demonstrate less osteoporosis than women who do not undergo H R T. The osteoporosis subjects were 195 women who volunteered to participate in an NIHsponsored double-blind clinical trial entitled Safely and Efficacy of Fluoride Therapy in Osteoporosis. A convenience sample of 78 controls was obtained by inviting women seeking regular medical attention to join an epidemiological investigation of osteoporosis. The data were analyzed using Chisquare and Student’s t-ratio. The study concludes that future retrospective and prospective analyses appreciate the com plexity of the problem in terms of individual risk for osteoporosis.

  14. Possible removal of topiramate by continuous renal replacement therapy.

    Science.gov (United States)

    Browning, Linda; Parker, Dennis; Liu-DeRyke, Xi; Shah, Aashit; Coplin, William M; Rhoney, Denise H

    2010-01-15

    Topiramate is primarily renally eliminated and requires dosage adjustment based upon renal function. While there is data to suggest drug removal during intermittent hemodialysis (IHD), little is known regarding its clearance and dosing during continuous renal replacement therapy (CRRT). We describe a 59-year-old man with refractory status epilepticus who was started on continuous venovenous hemodiafiltration (CVVHDF) for acute renal failure while receiving topiramate with a series of serum concentrations to assess for removal during CVVHDF. Our data suggest clinically important amounts of topiramate are removed by CRRT, and higher topiramate dosage may be needed for these patients instead of the current recommended 50% of normal dosage. Unfortunately, there is no antiepileptic drug dosing recommendation when used during CRRT due to the paucity of data. This case highlights a need for research evaluating the effect of CRRT on AED elimination in order to optimize therapy for seizure control.

  15. 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

  16. Acute Kidney Injury and Renal Replacement Therapy in Burns

    Directory of Open Access Journals (Sweden)

    Burak Canver

    2011-07-01

    Full Text Available Acute kidney injury (AKI is a common complication in patients with severe burn injury and one of the major causes of death. It has a negative prognostic value and almost always develops in the context of multiple organ dysfunction syndrome (MODS induced by sepsis. Over the last 20 years, according to data avaliable, the mortality rate has been reported to reach about 75%. Several definitions of AKI have been used , but nowadays the RIFLE classification is considered the gold standard, enabling a more objective comparison of populations. There are several ways to treat AKI in burn patients, including peritoneal dialysis (PD, intermittent hemodialysis, and continuous renal replacement therapy (CRRT. CRRT is generally used in patients in whom intermittent hemodialysis has failed to control hypovolemia, as well as in patients who cannot tolerate intermittent hemodialysis. Additionally, PD is not suitable for patients with burns within the abdominal area. For these reasons, most patients with unstable hemodynamic conditions receive CRRT. In burn patients with acute renal failure the dialytic treatment with continuous renal replacement therapies permitted us to achieve a survival and dialytic adequacy; however, mortality rate is high and related to septic shock and MODS. Despite the wide variation of the analysed burn populations and definitions of AKI, this review clearly showed that AKI remains prevalent and is associated with increased mortality in patients with severe burn injury. (Journal of the Turkish Society Intensive Care 2011; 9 Suppl: 46-50

  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. One-week quadruple therapy is an effective salvage regimen for Helicobacter pylori infection in patients after failure of standard triple therapy.

    Science.gov (United States)

    Lin, Chiun-Ku; Hsu, Ping-I; Lai, Kwok-Hung; Lo, Gin-Ho; Tseng, Hui-Hwa; Lo, Ching-Chu; Peng, Nan-Jing; Chen, Hui-Chun; Jou, Huei-Shu; Huang, Wen-Keui; Chen, Jin-Liang; Hsu, Ping-Ning

    2002-01-01

    Standard triple therapy remains an important option for eradicating Helicobacter pylori (Hp) in developing countries because of its relatively low cost. However, salvage therapies after failure of this regimen remain undefined. The authors therefore investigate the efficacy of 1-week quadruple therapy as a second-line treatment of Hp infection after failure of standard triple therapy. Seventy-eight patients who failed Hp eradication using a 2-week bismuth-based triple therapy were enrolled and received a course of 1-week quadruple therapy (lansoprazole, 30 mg twice daily; bismuth subcitrate, 120 mg four times daily; clarithromycin, 500 mg twice daily; and amoxicillin, 1,000 mg twice daily) as a salvage regimen. The Hp status was reassessed 7 weeks after cessation of therapy. Among the 78 patients, Hp eradication was achieved in 65 (83%, 95% confidence interval = 75-91%) by intention-to-treat analysis. Only five (6%) patients had side effects, and all (100%) showed good drug compliance. Multivariate analysis disclosed that coffee drinking was an independent factor for treatment failure (odds ratio = 5.3, 95% confidence interval = 1.2-23.6, p = 0.028). The authors therefore conclude that their 1-week quadruple therapy is an effective salvage regimen for Hp infection after failure of standard triple therapy in the population examined. The benefits of this regimen include the high eradication rate, the short duration of treatment, fewer side effects, and good drug compliance. Coffee consumption possibly is an important factor in failure of the rescue regimen. The mechanisms underlying the association between coffee drinking and eradication failure require further research.

  19. A randomized comparison of triple therapy Helicobacter pylori eradication regimens in children with peptic ulcers.

    Science.gov (United States)

    Shcherbakov, P L; Filin, V A; Volkov, I A; Tatarinov, P A; Belousov, Y B

    2001-01-01

    An open, randomized trial was performed to compare the efficacy of three Helicobacter pylori eradication regimens in children with peptic ulcer disease. A total of 106 children (5 - 15 years) were treated for 1 week with metronidazole, 30 - 40 mg/kg per day depending on age, amoxycillin, 750 mg/day, and one of three anti-secretory agents: proprietary omeprazole, 20 - 40 mg/day depending on age; generic omeprazole, 20 - 40 mg/day; or ranitidine, 150 mg twice daily. The H. pylori eradication rate was significantly higher in patients receiving proprietary omeprazole (88.9%) than in those receiving generic omeprazole (80.0%) or ranitidine (74.3%), and this was associated with a trend towards faster ulcer healing. It is concluded that triple therapy consisting of an anti-secretory agent and two antimicrobials produces effective eradication of H. pylori and ulcer healing in children with peptic ulcer disease, and that proprietary omeprazole is more effective than both ranitidine and the generic formulation used in this study.

  20. 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.

  1. Enzyme replacement therapy in a mouse model of aspartylglycosaminuria.

    Science.gov (United States)

    Dunder, U; Kaartinen, V; Valtonen, P; Väänänen, E; Kosma, V M; Heisterkamp, N; Groffen, J; Mononen, I

    2000-02-01

    Aspartylglycosaminuria (AGU), the most common lysosomal disorder of glycoprotein degradation, is caused by deficient activity of glycosylasparaginase (AGA). AGA-deficient mice share most of the clinical, biochemical and histopathologic characteristics of human AGU disease. In the current study, recombinant human AGA administered i.v. to adult AGU mice disappeared from the systemic circulation of the animals in two phases predominantly into non-neuronal tissues, which were rapidly cleared from storage compound aspartylglucosamine. Even a single AGA injection reduced the amount of aspartylglucosamine in the liver and spleen of AGU mice by 90% and 80%, respectively. Quantitative biochemical analyses along with histological and immunohistochemical studies demonstrated that the pathophysiologic characteristics of AGU were effectively corrected in non-neuronal tissues of AGU mice during 2 wk of AGA therapy. At the same time, AGA activity increased to 10% of that in normal brain tissue and the accumulation of aspartylglucosamine was reduced by 20% in total brain of the treated animals. Immunohistochemical studies suggested that the corrective enzyme was widely distributed within the brain tissue. These findings suggest that AGU may be correctable by enzyme therapy.-Dunder, U., Kaartinen, V., Valtonen, P., Väänänen, E., Kosma, V.-M., Heisterkamp, N., Groffen, J., Mononen, I. Enzyme replacement therapy in a mouse model of aspartylglycosaminuria.

  2. The appropriateness and persistence of testosterone replacement therapy in Ontario.

    Science.gov (United States)

    Martins, Diana; Yao, Zhan; Tadrous, Mina; Shah, Baiju R; Juurlink, David N; Mamdani, Muhammad M; Gomes, Tara

    2017-02-01

    To examine the concordance between testosterone replacement therapy (TRT) use and established reimbursement criteria, as well as compare the persistence of use among available formulations (injectable, oral, topical gel, transdermal patch) among elderly men in Ontario, Canada. We conducted a retrospective cohort study of men aged 66 years or older in Ontario newly treated with testosterone between 1 January 2009 and 31 December 2012 using linked health administrative data. Continuous use was defined on the basis of prescription refills issued within 180 days of the preceding prescription. We studied men who received at least two consecutive TRT prescriptions. We estimated the prevalence of hypogonadism, human immunodeficiency virus, specialist visits and lab tests for serum testosterone prior to initiation of TRT to investigate concordance with prescribing criteria. We also performed a Kaplan-Meier analysis to test for differences in the median time to discontinuation among formulations. Among the 4797 men who received at least two TRT prescriptions, only 38.7% met the reimbursement criteria for use prior to initiating therapy. The median time to discontinuation differed significantly among formulations and was longest among recipients of oral TRT products (383 days), and lower for recipients of topical gels (319 days), injectable (283 days) and transdermal patches (160 days; Log-rank test p therapy, and many discontinue TRT within a year of initiation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Patients’ willingness to take separate component antiretroviral therapy regimens for HIV in the Netherlands

    Directory of Open Access Journals (Sweden)

    Esther Engelhard

    2014-11-01

    Full Text Available Introduction: The costs of combination antiretroviral therapy (cART consisting of separate, particularly generic, components are generally much lower than of a single tablet regimen (STR including the same active ingredients. Our aim was to evaluate whether patients in care in the Netherlands would be willing to take separate component regimens (SCR instead of an STR and to examine whether willingness was associated with particular patient characteristics. Materials and Methods: Data from the HIV Monitoring Foundation of all adult HIV-1-infected patients in care taking cART>6 months were used to randomly select 1000 patients. As part of a questionnaire developed for a study assessing patient experience, patients were asked whether they were willing to take an SCR instead of an STR. Logistic regression was used to examine associations between age, gender, region of origin, mode of HIV transmission, socioeconomic status, duration of cART and answering “yes” to the question versus “maybe” or “no.” Variables with p<0.1 in the univariate analysis were entered in a multivariate model. Results: Of the 300 patients who completed the questionnaire, 49% answered “yes,” 24% “maybe” and 27% “no” to the question whether they would be willing to use a SCR. Reasons for answering “no” included difficulties swallowing pills, convenience of STR (especially when travelling/at work, and concerns about side effects. Respondents who answered “maybe” often indicated that they preferred STRs, emphasized the importance of taking the pills once daily, and pointed out that efficacy/safety of an SCR should not be less. Having to pay for medication was reported as a reason to consider switching to an SCR. In the multivariate analysis, respondents who were born outside the Netherlands were less likely; and those with cART use ≥15 yrs were more likely to answer “yes” (Table 1. Conclusions: Half of the respondents were willing to take SCRs

  4. Fluconazole dosing predictions in critically-ill patients receiving prolonged intermittent renal replacement therapy: a Monte Carlo simulation approach.

    Science.gov (United States)

    Gharibian, Katherine N; Mueller, Bruce A

    2016-07-01

    Fluconazole is a renally-eliminated antifungal commonly used to treat Candida species infections. In critically-ill patients receiving prolonged intermittent renal replacement therapy (PIRRT), limited pharmacokinetic (PK) data are available to guide fluconazole dosing. We used previously-published fluconazole clearance data and PK data of critically-ill patients with acute kidney injury to develop a PK model with the goal of determining a therapeutic dosing regimen for critically-ill patients receiving PIRRT. Monte Carlo simulations were performed to create a virtual cohort of patients receiving different fluconazole dosing regimens. Plasma drug concentration-time profiles were evaluated on the probability of attaining a mean 24-hour area under the drug concentration-time curve to minimum inhibitory concentration ratio (AUC24h : MIC) of 100 during the initial 48 hours of antifungal therapy. At the susceptibility breakpoint of Candida albicans (2 mg/L), 93 - 96% of simulated subjects receiving PIRRT attained the pharmacodynamic target with a fluconazole 800-mg loading dose plus 400 mg twice daily (q12h or pre and post PIRRT) regimen. Monte Carlo simulations of a PK model of PIRRT provided a basis for the development of an informed fluconazole dosing recommendation when PK data was limited. This finding should be validated in the clinical setting.

  5. 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...

  6. 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...

  7. 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.

  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......, regarding long-term NRT users’ experiences with continuing the use of NRT. Results from a survey study among long-term NRT-users, who had used NRT for 12 months or more, found that out of 92 former smokers 88 % wished to quit using NRT. The primary causes stated for wishing to quit were being tired...

  9. Continuous renal replacement therapy circuit failure after antidote administration.

    Science.gov (United States)

    Jeong, Jinwoo

    2014-12-01

    A 73-year-old man was transferred to the emergency department (ED). He was found unconscious in his house along with an empty 200-mL bottle of Basta(™), a herbicide containing 18% glufosinate. He was comatose with a Glasgow Coma Scale score of 3. As his blood pressure dropped to 60/30 mmHg despite fluids and norepinephrine, 20% intravenous fat emulsion product was injected. He experienced repeated cardiopulmonary arrests during his first 4 h in the ED. When the arrests occurred, standard cardiopulmonary resuscitation was performed, and boluses of fat emulsion were given. He was given a total of 1500 mL of 20% fat emulsion. In an attempt to correct the acidosis, continuous renal replacement therapy (CRRT) was started. Within 5 min of starting CRRT, the transmembrane pressure increased sharply and the machine stopped.

  10. Stroke in women - oral contraception, pregnancy, and hormone replacement therapy.

    Science.gov (United States)

    Rantanen, Kirsi; Tatlisumak, Turgut

    2013-01-01

    Stroke is a devastating disease affecting millions of people worldwide every year. Female stroke victims have higher mortality rates and they do not re-cover as well as men. Women's longevity and different vascular risk factor burden like a larger prevalence of atrial fibrillation play a role. Women also have unique risk factors such as oral contraception, pregnancy, estrogen decrease after the menopause and hormone replacement therapy, which should all be evaluated and taken into consideration in treatment decisions both in the acute phase of stroke and in secondary prevention. In this review, the evidence regarding these hormonal aspects and the risk of stroke in women are evaluated. The relevant guidelines are studied and research gaps identified. Future topics for research are recommended and current treatment possibilities and their risks discussed.

  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. Effect of estrogen and testosterone replacement therapy on cognitive fatigue.

    Science.gov (United States)

    Möller, Marika Christina; Rådestad, Angelique Flöter; von Schoultz, Bo; Bartfai, Aniko

    2013-02-01

    Both estrogen and testosterone insufficiency has been associated with reduced psychological well-being including fatigue. However, hormonal replacement studies on fatigue are rare. Therefore, we wanted to study the effect of testosterone and estrogen replacement therapy on cognitive fatigue and the relation between sex hormone levels and cognitive fatigue in oophorectomized women. Fifty women with surgically induced menopause (mean age: 54.0 ± 2.9 years) were randomly assigned to treatment with estradiol valerate in combination with testosterone undecanoate or placebo for 24 weeks in a double-blind cross-over study. Neuropsychological tests and questionnaires were used to assess cognitive fatigue and psychological well-being. Cognitive fatigue was significantly associated to poor self-rated health and higher body mass index but not to general psychological well-being or sex hormone levels. Treatment with testosterone + estrogen had no significant effect on cognitive fatigue but the results indicated a curvilinear relation for hormonal levels. The estrogen/testosterone ratio was more related to functions rather than high or low hormone levels per se. We found that cognitive fatigue is frequent in oophorectomized women and negatively associated to self-perceived health and positively associated to BMI. A well-balanced ratio between estrogen and testosterone levels may be important for cognitive fatigue.

  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. Low level HIV viremia is more frequent under protease-inhibitor containing firstline therapy than under NNRTI-regimens

    Directory of Open Access Journals (Sweden)

    Frank Wiesmann

    2014-11-01

    Full Text Available Introduction: An association of persistent low level viremia (LLV below 500 copies/mL and a higher risk of therapy failure is still point of controversial discussion. Furthermore, it seems that LLV occurs more frequently in patients with protease-inhibitor regimens than in NNRTI- / or integrase-inhibitor containing therapies. The focus of this work was to assess the prevalence of LLV (50–200 copies/mL and weak viremia (201–500 copies/mL in firstline-treated patients according to their therapy regimen. Methods: A total of 832 and 944 patients from 23 German centres were under firstline therapy in 2012 and 2013, respectively. All patients received their therapy for more than 24 weeks. VL data was related to clinical data retrospectively including ART-composition, subdivided into NNRTIs (Efavirenz, Nevirapine, PIs (Atazanavir, Darunavir, Lopinavir and INIs (Raltegravir. Low viremic patients were classified into two arms of 50–200 copies/mL (group A and 201–500 copies/mL (group B. Results: Success of therapy was defined as <50 copies/mL and was observed in 90.0% and 91.1% (2012/2013, respectively. An additional 2.0% and 2.3% had LLV. The amount of viremic patients with VLs <500 copies/mL differed significantly between NNRTI-based firstline regimens 1.7% and 2.5% and PI-based regimens 4.8% and 5.7% (2012/2013, respectively. LLV was clearly less often observed in EFV-based- (1.6% and 1.1% [group A] / 0.4% and 0.4% [group B] or NVP-based firstline therapies (1.0% and 3.6% [group A] + 0% and 0% [group B] than in ATV-based- (7.5% and 3.8% [group A] + 1.5% and 2.5% [group B], DRV-based- (2.9% and 3.0% [group A] + 2.2% and 0% [group B] or LPV-based firstline therapies (1.6% and 3.3% [group A] + 0.8% and 2.5% [group B] and also in parts for RAL-based regimens (0% and 3.7% [group A] + 0% and 1.9% [group B]. Conclusions: LLV is more often observed under PI-based firstline than under NNRTI-regimens. Only one NNRTI-patient of group B remained on therapy

  15. Controversies in testosterone replacement therapy: testosterone and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Kathleen Hwang

    2015-04-01

    Full Text Available The role of testosterone in the cardiovascular (CV health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term prospective studies to determine safety. Literature spanning over the past 30 years has suggested that not only is there a possible increased CV risk in men with low levels of testosterone, but the benefits from testosterone therapy may even lower this risk. We review here the recent studies that have garnered such intense scrutiny. This article is intended as a thorough review of testosterone levels and CV risk, providing the clinician with the facts needed to make informed clinical decisions in managing patients with clinical hypogonadism.

  16. 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.

  17. Three-Times Daily Ultrafractionated Radiation Therapy, A Novel and Promising Regimen for Glioblastoma Patients

    Energy Technology Data Exchange (ETDEWEB)

    Beauchesne, Patrick [Neuro-Oncology Department, CHU de Nancy, Hospital Central, Nancy 54035 (France)

    2013-09-25

    Glioblastomas are considered to be one of the most radio resistant tumors. Despite new therapies, the prognosis of this disease remains dismal. Also, the mechanisms of radiation resistance in mammalian cells are more complex than once believed. Experimental studies have indicated that some human cell lines are sensitive to low radiation doses of <1 Gy. This phenomenon has been termed low-dose hyper-radio-sensitivity (HRS), and is more apparent in radio resistant cell lines, such as glioblastoma cells. Sensitivity may result from the inability of low dose radiation to efficiently induce repair mechanisms, whereas higher doses cause enough damage to trigger repair responses for radio resistance. In vitro studies have demonstrated this phenomenon using various human malignant glioma cell lines: (1) daily repeated irradiation of cells with low doses compared to irradiation using a single biologically equivalent dose resulted in significantly higher cell killing; (2) experiments conducted on glioma xenografts demonstrated that repeated irradiation with low doses was more effective for inhibiting tumor growth than a single dose. In order to confirm and validate these promising studies on HRS, a few phase II trials were developed. For translating the experimental observations into the clinic, ultra fractionation protocols (with three daily doses) were tested in glioblastoma patients. Tolerance and toxicity were the primary endpoints, with overall survival as a secondary endpoint. These protocols were initiated before concomitant radio chemotherapy became the standard of care. For these trials, patients with an unfavorable clinical prognostic factor of newly unresectable GBM were included. When comparing the results of these trials with international literature using multivariate analysis for both progression free survival and overall survival, ultra fractionated irradiation showed superiority over radiotherapy alone. In addition, it was found to be equivalent to treatment

  18. 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.

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

    Science.gov (United States)

    Behan, Lucy-Ann; Rogers, Bairbre; Hannon, Mark J; O'Kelly, Patrick; Tormey, William; Smith, Diarmuid; Thompson, Christopher J; Agha, Amar

    2011-10-01

    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. 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). 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. 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). 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. © 2011 Blackwell Publishing Ltd.

  20. 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.

  1. 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.

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

    National Research Council Canada - National Science Library

    Tendler, Rabbi Moshe D; Loike, John D

    2015-01-01

    .... 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...

  3. Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Roger, Claire; Wallis, Steven C; Muller, Laurent; Saissi, Gilbert; Lipman, Jeffrey; Lefrant, Jean-Yves; Roberts, Jason A

    2016-08-01

    The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean ± standard deviation parameter estimates were 25.2 ± 17.3 liters for the central volume, 0.89 ± 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 ± 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 ± 2.35 liters/h for hemodiafiltration clearance, and 4.69 ± 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (≥25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (Cmax)/MIC ratio of ≥8 and a minimal concentration of ≤2.5 mg/liter at the end of the dosing interval. The mean clearance of amikacin was 1.8 ± 1.3 liters/h by CVVHDF and 1.3 ± 1 liters/h by CVVH. On the basis of simulations, a strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring (TDM) should be the preferred approach for aminoglycoside treatment in critically ill patients receiving continuous renal replacement therapy (CRRT). (This study is a substudy of a trial registered at ClinicalTrials.gov under number NCT01403220.). Copyright © 2016, American Society

  4. Low-dose hydrocortisone replacement therapy is associated with improved bone remodelling balance in hypopituitary male patients.

    Science.gov (United States)

    Behan, Lucy-Ann; Kelleher, Grainne; Hannon, Mark J; Brady, Jennifer J; Rogers, Bairbre; Tormey, William; Smith, D; Thompson, Christopher J; McKenna, Malachi J; Agha, Amar

    2014-01-01

    Glucocorticoid (GC) therapy is associated with adverse effects on bone metabolism, yet the effects of different GC physiological replacement regimens in hypopituitarism are not well characterised. We aimed to assess the effect of three hydrocortisone (HC) replacement dose regimens on bone turnover. An open cross-over study randomising ten hypopituitary men with severe acth deficiency to three commonly used HC dose regimens: dose A (20 mg mane and 10 mg tarde), dose B (10 mg mane and 10 mg tarde) and dose C (10 mg mane and 5 mg tarde). Following 6 weeks of each regimen, the participants underwent 24-h serum cortisol sampling and measurement of bone turnover markers: bone-specific alkaline phosphatase, procollagen type I N-propeptide (PINP), intact osteocalcin (OC(1-49)), C-terminal cross-linking telopeptide (CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP5b). Bone remodelling balance was estimated as an absolute ratio (PINP:CTX-I) and as an index using standardised scores derived from the matched controls. There were significant increases in the concentrations of the formation markers PINP (P=0.045) and OC(1-49) (P=0.006) and in the PINP:CTX-I ratio (P=0.015), and a more positive bone remodelling balance index (P=0.03) was observed in patients on the lowest dose C than in those on the highest dose A. Mean 24-h cortisol concentrations correlated negatively with CTX-I (r=-0.66 and P=0.04) and TRACP5b (r=-0.74 and P=0.01) in patients on dose B and with OC(1-49) (r=-0.66 and P=0.04) and CTX-I (r=-0.81 and P<0.01) in patients on dose C. In patients receiving the lower-dose regimen, trough cortisol concentrations correlated with increased bone formation and resorption. Low-dose HC replacement (10 mg mane and 5 mg tarde) is associated with increased bone formation and a positive bone remodelling balance. This may have a long-term beneficial effect on bone health.

  5. Hormone replacement therapy diminishes hearing in peri-menopausal mice.

    Science.gov (United States)

    Price, Katharine; Zhu, Xiaoxia; Guimaraes, Patricia F; Vasilyeva, Olga N; Frisina, Robert D

    2009-06-01

    We recently discovered that progestin in hormone replacement therapy (HRT) for post-menopausal women has detrimental effects on the ear and central auditory system [Guimaraes, P., Frisina, S.T., Mapes, F., Tadros, S.F., Frisina, D.R., Frisina, R.D., 2006. Progestin negatively affects hearing in aged women. Proc. Natl. Acad. Sci. - PNAS 103, 14246-14249]. To start determining the generality and neural bases of these human findings, the present study examined the effects of combination HRT (estrogen+progestin) and estrogen alone on hearing in peri-menopausal mice. Specifically, auditory brainstem responses (ABRs-sensitivity of the auditory system) and distortion-product otoacoustic emissions (DPOAEs-cochlear outer hair cell system) were employed. Middle age female CBA mice received either a time-release, subcutaneous implanted pellet of estrogen+progestin, estrogen alone, or placebo. Longitudinal comparisons of ABR threshold data obtained at 4 months of treatment revealed statistically significant declines in auditory sensitivity over time for the combined estrogen+progestin treatment group, with the estrogen only group revealing milder changes at 3, 6 and 32 kHz. DPOAE testing revealed statistically significant differences for the estrogen+progestin treatment group in the high and middle frequency ranges (15-29 and 30-45 kHz) after as early as 2 months of treatment (p<0.01 and p<0.001, respectively). Statistically significant changes were also seen at 4 months of treatment across all frequencies for the combined HRT group. These data suggest that estrogen+progestin HRT therapy of 4 months duration impairs outer hair cell functioning and overall auditory sensitivity. These findings indicate that estrogen+progestin HRT may actually accelerate age-related hearing loss, relative to estrogen monotherapy; findings that are consistent with the clinical hearing loss observed in aging women that have taken combination HRT.

  6. A primer on continuous renal replacement therapy for critically ill patients.

    Science.gov (United States)

    Joy, M S; Matzke, G R; Armstrong, D K; Marx, M A; Zarowitz, B J

    1998-03-01

    To characterize the multiple continuous renal replacement therapy (CRRT) techniques available for the management of critically ill adults, and to review the indications for and complications of use, principles of drug removal during CRRT, drug dosage individualization guidelines, and the influence of CRRT on patient outcomes. MEDLINE (January 1981-December 1996) was searched for appropriate publications by using terms such as hemofiltration, ultrafiltration, hemodialysis, hemodiafiltration, medications, and pharmacokinetics; selected articles were cross-referenced. References selected were those considered to enhance the reader's knowledge of the principles of CRRT, and to provide adequate therapies on drug disposition. CRRTs use filtration/convection and in some cases diffusion to treat hemodynamically unstable patients with fluid overload and/or acute renal failure. Recent data suggest that positive outcomes may also be attained in patients with other medical conditions such as septic shock, multiple organ dysfunction syndrome, and hepatic failure. Age, ventilator support, inotropic support, reduced urine volume, and elevated serum bilirubin concentrations have been associated with poor outcomes. Complications associated with CRRT include bleeding due to excessive anticoagulation and line disconnections, fluid and electrolyte imbalance, and filter and venous clotting. CRRT can complicate the medication regimens of patients for whom it is important to maintain drug plasma concentrations within a narrow therapeutic range. Since the physicochemical characteristics of a drug and procedure-specific factors can alter drug removal, a thorough assessment of all factors needs to be considered before dosage regimens are revised. In addition, an algorithm for drug dosing considerations based on drug and CRRT characteristics, as well as standard pharmacokinetic equations, is proposed. The use of CRRT has expanded to encompass the treatment of disease states other than just

  7. Status of renal replacement therapy and peritoneal dialysis in Mexico.

    Science.gov (United States)

    Cueto-Manzano, Alfonso M; Rojas-Campos, Enrique

    2007-01-01

    Mexico is struggling to gain a place among developed countries; however, there are many socioeconomic and health problems still waiting for resolution. While Mexico has the twelfth largest economy in the world, a large portion of its population is impoverished. Treatment for end-stage renal disease (377 patients per million population) is determined by the individual's access to resources such as private medical care (approximately 3%) and public sources (Social Security System: approximately 40%; Health Secretariat: approximately 57%). With only 6% of the gross national product spent on healthcare and most treatment providers being public health institutions that are often under economic restrictions, it is not surprising that many Mexican patients do not receive renal replacement therapy. Mexico is still the country with the largest utilization of peritoneal dialysis (PD) in the world, with 18% on automated PD, 56% on continuous ambulatory PD (CAPD), and 26% on hemodialysis. Results of PD (patient morbi-mortality, peritonitis rate, and technique survival) in Mexico are comparable to other countries. However, malnutrition and diabetes mellitus are highly prevalent in Mexican patients on CAPD programs, and these conditions are among the most important risk factors for a poor outcome in our setting.

  8. 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.

  9. Plant derived alternatives for hormone replacement therapy (HRT).

    Science.gov (United States)

    Seidlova-Wuttke, Dana; Jarry, Hubertus; Wuttke, Wolfgang

    2013-12-01

    Abstract Hormone replacement therapy (HRT) has undisputable positive effects on climacteric complaints, in the bone and on body weight but also several undesired side effects. Therefore, plant-derived alternatives are currently promoted. Phytoestrogens - primarily the isoflavones genistein, daidzein and coumestrol, stemming from soy (Glycine max) or red clover (Trifolium pratense) - were suggested to have the desired but not the undesired effects of estrogens. Most recently published placebo-controlled studies question the beneficial effects. When taken at the time of puberty however, phytoestrogens appear to protect against mammary cancer later in life. Extracts from the rhizome of Cimicifuga racemosa (black cohosh) have no estrogenic effects. In a narrow dose range they have beneficial effects on climacteric complaints, which are due to several compounds with dopaminergic, noradrenergic, serotoninergic and GABAergic actions that act together in the hypothalamus. Ecdysone is produced by several plants, including spinach (Spinacia oleracea) and was very early on shown to increase muscle mass. Later it became apparent that spinach extracts containing ecdysone decreased body fat load, thereby reducing secretion of proinflammatory cytokines by visceral adipocytes and oxidative stress. This had beneficial effects on body weight and serum lipids not only in obese postmenopausal but also in premenopausal women and in men. For the above-described plant extracts, solid placebo-controlled clinical trials are available. For other plant extracts claiming beneficial effects on climacteric complaints or postmenopausal diseases, no solid data are available.

  10. Hormone replacement therapy and the prevention of postmenopausal osteoporosis.

    Science.gov (United States)

    Gambacciani, Marco; Levancini, Marco

    2014-09-01

    Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT) at different doses rapidly normalizes turnover, preserves bone mineral density (BMD) at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR), is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs) such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC), is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence.

  11. Hormone replacement therapy: real concerns and false alarms.

    Science.gov (United States)

    Bluming, Avrum Z; Tavris, Carol

    2009-01-01

    From 2002 to 2008, reports from the Women's Health Initiative (WHI) claimed that hormone replacement therapy (HRT) significantly increased the risks of breast cancer development, cardiac events, Alzheimer disease, and stroke. These claims alarmed the public and health professionals alike, causing an almost immediate and sharp decline in the numbers of women receiving HRT. However, the actual data in the published WHI articles reveal that the findings reported in press releases and interviews of the principal investigators were often distorted, oversimplified, or wrong. This review highlights the history of research on HRT, including a timeline of studies that have or have not found a link between HRT and breast cancer; discusses how to distinguish important, robust findings from those that are trivial; closely examines the WHI findings on HRT and breast cancer, most of which are weak or statistically insignificant; reviews the current thinking about possible links of HRT with cardiovascular disease and cognitive functioning; and reports research on the benefits of HRT, notably relief of menopausal symptoms, that affect a woman's quality of life. On these complicated matters, physicians and the public must be cautious about accepting "findings by press release" in determining whether to prescribe or take HRT.

  12. EMAS position statement: Testosterone replacement therapy in the aging male‏.

    Science.gov (United States)

    Dimopoulou, Christina; Ceausu, Iuliana; Depypere, Herman; Lambrinoudaki, Irene; Mueck, Alfred; Pérez-López, Faustino R; Rees, Margaret; van der Schouw, Yvonne T; Senturk, Levent M; Simonsini, Tommaso; Stevenson, John C; Stute, Petra; Goulis, Dimitrios G

    2016-02-01

    Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate. The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks. Literature review and consensus of expert opinion. Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function and osteoporosis and should undergo scheduled testing for adverse events regularly. Potential adverse effects of TRT on cardiovascular disease, prostate cancer and sleep apnea are as yet unclear and remain to be investigated in large-scale prospective studies. Management of aging men with LOH should include individual evaluation of co-morbidities and careful risk versus benefit assessment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Hormone replacement therapy and the prevention of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Marco Gambacciani

    2014-09-01

    Full Text Available Fracture prevention is one of the public health priorities worldwide. Estrogen deficiency is the major factor in the pathogenesis of postmenopausal osteoporosis, the most common metabolic bone disease. Different effective treatments for osteoporosis are available. Hormone replacement therapy (HRT at different doses rapidly normalizes turnover, preserves bone mineral density (BMD at all skeletal sites, leading to a significant, reduction in vertebral and non-vertebral fractures. Tibolone, a selective tissue estrogenic activity regulator (STEAR, is effective in the treatment of vasomotor symptoms, vaginal atrophy and prevention/treatment of osteoporosis with a clinical efficacy similar to that of conventional HRT. Selective estrogen receptor modulators (SERMs such as raloxifene and bazedoxifene reduce turnover and maintain or increase vertebral and femoral BMD and reduce the risk of osteoporotic fractures. The combination of bazedoxifene and conjugated estrogens, defined as tissue selective estrogen complex (TSEC, is able to reduce climacteric symptoms, reduce bone turnover and preserve BMD. In conclusion, osteoporosis prevention can actually be considered as a major additional benefit in climacteric women who use HRT for treatment of climacteric symptoms. The use of a standard dose of HRT for osteoporosis prevention is based on biology, epidemiology, animal and preclinical data, observational studies and randomized, clinical trials. The antifracture effect of a lower dose HRT or TSEC is supported by the data on BMD and turnover, with compelling scientific evidence.

  14. Manufacturing heterosexuality: hormone replacement therapy and menopause in urban Oaxaca.

    Science.gov (United States)

    Ramirez, Michelle

    2006-01-01

    For several decades, hormone replacement therapies have been prescribed to women, not only to prevent disease but to improve the sexual functioning of menopausal women. The medical promotion of continued sexual activity in a woman's post-reproductive years is exported to locations outside of North America and Europe, which provides an opportunity to critically examine the cultural roots that have informed expert biomedical representations. This ethnographic study examined menopause and social class in Oaxaca de Juarez, Mexico using interviews, questionnaires, and textual analysis. The research found that biomedicine in conjunction with the pharmaceutical industry promoted culturally constructed gender hierarchies under the guise of optimal menopausal health. However, women's actual experience of gender and sexuality in mid-life diverged significantly from these expert representations. Themes that emerged in interviews and questionnaires included the importance of motherhood in old age, diminished sexual desire as not problematic, and greater sexual freedom at a post-reproductive age. Ultimately, biomedical discourse was not the sole arbiter of appropriate menopausal womanhood and femininity.

  15. OPTIMAL REGIMENS OF THE BASAL-BOLUS INSULIN THERAPY IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    G. A. Galkina

    2015-01-01

    Full Text Available This study was aimed to determine peculiarities in regimens of the pump insulin therapy and to reveal the optimal basal-to-bolus insulin ratio that are necessary for achieving optimal glycemic control in adoles-cents with type 1 diabetes mellitus (T1DM.  82 adolescents at the age of 14–18 with T1DM, using continuous subcutaneous insulin infusion (CSII from 5 months to 7.5 years were monitored with continuous glucose monitoring (CGM system «Guar-dian Real Time» or CGM system, built in MiniMed Paradigm Revel System 722 (Medtronic Minimed, USA. Assessing the quality of glycaemic control was based on the level of glycated haemoglobin (HbA1c. The results of CGM were reviewed and average for 3 days performances: total daily dose of insulin, dose of basal and bolus insulin, basal-to-bolus insulin ratio, carbohydrate content of the meal, expressed in BE, carbohydrate ratio, insulin sensitivity factor were determined. The patients were subdivided into 2 groups: group 1 – adolescents with the optimal/suboptimal glycemic control (n = 55, 2 – adolescents with long-standing poorly controlled T1DM (n = 27. Average total daily dose of basal insulin (U in a day, U per kg in a day in adolescents group 1 was significantly higher, com-pared with patients in group 2 (р = 0.043; р = 0.038 respectively. Patients in group 2 received more car-bohydrates with a meal intake and had higher doses of average total daily bolus insulin. The average ba-sal-to-bolus ratio from group 1 patients was 51/49%, compared with group 2 patients – 45/55% (р = 0.026.  An important condition for achieving optimal glycemic control is a high level of compliance and skills of adolescents. Optimal well-balanced basal-to-bolus insulin ratio in adolescents with T1DM on CSII, which can provide improvements in blood glucose management and reducing the risk of complications of the disease, is 51/49%. 

  16. Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency - a worldwide patient survey

    Directory of Open Access Journals (Sweden)

    Forss M

    2012-06-01

    Full Text Available Abstract Background The aim was to survey current practice in glucocorticoid replacement therapy and self-perceived health outcomes in patients with adrenal insufficiency. Methods Participants were recruited via patient organizations to respond anonymously to a web-based survey developed by clinical experts. Unique entries were set up for each patient organization enabling geographical localization of the entries. Results 1245 participants responded (primary adrenal insufficiency: 84%; secondary adrenal insufficiency: 11%; unsure: 5%. Therapies included hydrocortisone (75%, prednisone/prednisolone (11%, cortisone acetate (6% and dexamethasone (4%. Dosing regimens were once daily (10%, twice daily (42%, thrice daily (32% or other (17%. Compromised subjective health necessitating changes to physical activity or social-, work- or family life was reported by 64% of the participants. 40% of the participants reported absence from work/school in the last 3 months. Irrespective of diagnosis, 76% were concerned about long-term side-effects of therapy, mainly osteoporosis (78%, obesity (64% and cardiovascular morbidity (46%. 38% of the participants had been hospitalized in the last year. Conclusions Glucocorticoid replacement therapy among the respondents consisted primarily of hydrocortisone administered twice or thrice daily. A majority reported impact of their disease or treatment on subjective health requiring alterations in e.g. physical activity or family life. Three quarters reported concerns about long-term side-effects of the treatment. These data demonstrate - from the patients' perspective - a need for improvement in the management of adrenal insufficiency.

  17. 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.

  18. 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.

  19. Discontinuation of hormone replacement therapy after myocardial infarction and short term risk of adverse cardiovascular events

    DEFF Research Database (Denmark)

    Bretler, Ditte-Marie; Hansen, Peter Riis; Sørensen, Rikke;

    2012-01-01

    To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue.......To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue....

  20. Relation between hormone replacement therapy and ischaemic heart disease in women

    DEFF Research Database (Denmark)

    Løkkegaard, E; Pedersen, A T; Heitmann, B L

    2003-01-01

    To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors.......To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors....

  1. Analgesic Nephropathy and Renal Replacement Therapy in Australia: Trends, Comorbidities and Outcomes

    OpenAIRE

    Chang, Sean Haw; Mathew, Timothy Hamish; McDonald, Stephen Peter

    2008-01-01

    Background and objectives: This study examined age-specific incidence and prevalence of renal replacement therapy attributed to analgesic nephropathy from 1971 through 2005 and adjusted comorbidity prevalence and survival of patients who had analgesic nephropathy and were on renal replacement therapy (compared with control subjects without diabetes).

  2. Comparative Effectiveness of Initial Antiretroviral Therapy Regimens: ACTG 5095 and 5142 Clinical Trials Relative to ART-CC Cohort Study

    Science.gov (United States)

    Mugavero, Michael J.; May, Margaret; Ribaudo, Heather J.; Gulick, Roy M.; Riddler, Sharon A.; Haubrich, Richard; Napravnik, Sonia; Abgrall, Sophie; Phillips, Andrew; Harris, Ross; Gill, M. John; de Wolf, Frank; Hogg, Robert; Günthard, Huldrych F.; Chêne, Geneviève; D'Arminio Monforte, Antonella; Guest, Jodie L.; Smith, Colette; Murillas, Javier; Berenguer, Juan; Wyen, Christoph; Domingo, Pere; Kitahata, Mari M.; Sterne, Jonathan A. C.; Saag, Michael S.

    2011-01-01

    Background The generalizability of antiretroviral therapy (ART) clinical trial efficacy findings to routine care settings is not well studied. We compared the relative effectiveness of initial ART regimens estimated in AIDS Clinical Trial Group (ACTG) randomized controlled trials with that among patients receiving ART at Antiretroviral Therapy Cohort Collaboration (ART-CC) study sites. Methods Treatment-naive HIV-infected patients initiating identical ART regimens in ACTG trials (A5095 and A5142) and at 15 ART-CC cohort study sites were included. Virological failure (HIV-1 RNA >200 copies/ml) at 24- and 48-weeks, incident AIDS-defining events and mortality were measured according to study design (ART-CC cohort vs. ACTG trial) and stratified by 3rd drug [Abacavir (ABC), Efavirenz (EFV), and Lopinavir/r (LPV/r)]. We used logistic regression to estimate and compare odds ratios for virological failure between different regimens and study designs, and used Cox models to estimate and compare hazard ratios for AIDS and death. Results Compared with patients receiving ABC, those receiving EFV had roughly half the odds of 24-week virologic failure (>200 copies/mL) in both ACTG 5095 (OR=0.53, 95% CI 0.36–0.79) and ART-CC (0.46, 0.37–0.57). Virologic superiority of EFV (vs. ABC) appeared comparable in ART-CC and ACTG 5095 (ratio of ORs 0.86, 95% CI 0.54–1.35). Odds ratios for 48-week virologic failure, comparing EFV with LPV/r, were also comparable in ACTG 5142 and ART-CC (ratio of ORs 0.87, 0.45–1.69). Conclusions Between ART regimen virologic efficacy of 3rd drugs ABC, EFV, and LPV/r observed in the ACTG 5095 and 5142 trials appear generalizable to the routine care setting of ART-CC clinical cohorts. PMID:21857357

  3. Anti-ischemic effect of chronic oestrogen replacement therapy alone or in combination with medroxyprogesterone acetate in different replacement schemes.

    Science.gov (United States)

    Cerquetani, E; Leonardo, F; Pagnotta, P; Galetta, P; Onorati, D; Fini, M; Rosano, G M

    2001-09-28

    Oestrogen replacement therapy in postmenopausal women has a protective effect upon the cardiovascular system and improves exercise-induced myocardial ischemia. Although in hormone replacement schemes progestins are required to reduce the likelihood of uterine malignancies, little is known on the cardiovascular effect of progestins. The purpose of this study was to evaluate the effect of oestrogen replacement alone and two different estrogen-progestin replacement therapy schemes upon exercise induced myocardial ischemia. The study population included 18 female menopausal patients with coronary artery disease. After a baseline exercise test patients received conjugated equine estrogens (CEE) 0.625 mg alone for 30 days when they underwent a second exercise test and were randomized to receive in a cross-over design medroxyprogesterone acetate (MPA) either in continuous combined therapy (2.5 mg/daily) for 28 days or in cyclical therapy (10 mg o.d. from day 16 to day 28). After CEE alone two patients with a previously positive exercise test showed a negative exercise test. CEE increased time to 1 mm ST compared to baseline (352+/-185 vs 265+/-133 s, Pexercise test was negative after CEE the test remained negative during continuous combined MPA therapy while become positive during cyclical MPA. CEE+continuous combined MPA increased both time to 1 mm ST and exercise time compared to baseline (386+/-165 vs 265+/-133 s, Pexercise time (268+/-164 vs 265+/-133 s, P=NS and 455+/-223 vs 465+/-186 s, P=NS, respectively). Continuous combined therapy with CEE+MPA improves exercise-induced myocardial ischemia in female patients with coronary artery disease while the beneficial effect of CEE is reduced by cyclical therapy.

  4. Testosterone Replacement Therapy and Mortality in Older Men.

    Science.gov (United States)

    Hackett, G I

    2016-02-01

    While US testosterone prescriptions have tripled in the last decade with lower trends in Europe, debate continues over the risks, benefits and appropriate use of testosterone replacement therapy (TRT). Several authors blame advertising and the availability of more convenient formulations, whilst others have pointed out that the routine testing of men with erectile dysfunction (ED) (a significant marker of cardiovascular risk) and those with diabetes would inevitably increase the diagnosis of hypogonadism and lead to an increase in totally appropriate prescribing. They commented that this was merely an appropriate correction of previous under-diagnosis and under-treatment in line with evidence based guidelines. It is unlikely that persuasive advertising or convenient formulations could grow a market over such a sustained period if the treatment was not effective. Urologists and primary care physicians are the most frequent initiators of TRT usually for ED. Benefits are clearly established for sexual function, increase in lean muscle mass and strength, mood and cognitive function, with a possible reduction in frailty and osteoporosis. There remains no evidence that TRT is associated with increased risk of prostate cancer or symptomatic benign prostatic hyperplasia, yet the decision to initiate and continue therapy is often decided by urologists. The cardiovascular issues associated with TRT have been clarified by recent studies showing that therapy associated with clear increases in serum testosterone levels to the normal range is associated with reduced all-cause mortality. Studies reporting to show increased risk have been subject to flawed designs with inadequate baseline diagnosis and follow-up testing. Effectively, they have compared non-treated patients with under-treated or non-compliant subjects involving a range of different therapy regimes. Recent evidence suggests long-acting injections may be associated with decreased cardiovascular risk, but the

  5. PEG-aspargase and DEP regimen combination therapy for refractory Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis

    Directory of Open Access Journals (Sweden)

    Jingshi Wang

    2016-09-01

    Full Text Available Abstract Background Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH is the most frequent subtype of secondary HLH triggered by infections. Previous studies have shown that ~30 % or more of patients with EBV-HLH do not respond to standard therapy. This study investigated the efficacy and safety profile of a modified DEP regimen in combination with PEG-aspargase (L-DEP as a salvage therapy for refractory EBV-HLH. Methods In this study from October 2014 to October 2015, 28 patients with refractory EBV-HLH received a L-DEP regimen at the Beijing Friendship Hospital, Capital Medical University. Treatment efficacy and adverse events were evaluated at 2 and 4 weeks after L-DEP treatment. Results Median EBV-DNA concentrations before and 2 weeks after receiving the L-DEP regimen were 9.6 × 105 (1.5 × 104 − 1 × 109 copies/mL and 2.2 × 105 (3.8 × 102 − 1.2 × 107 copies/mL, respectively; the post-treatment values were significantly lower than that of the pretreatment (P = 0.048. Nine of the 28 study patients achieved complete response (CR and 15 partial response (PR, resulting in an overall response rate of 85.7 % (CR+PR. Four patients who did not achieve response died within 4 weeks of receiving L-DEP. Thirteen of the 24 patients who achieved partial or complete response received subsequent allogenic hematopoietic stem cell transplantation (allo-HSCT. Ten of these 13 patients survived until 1 March 2016. The major adverse effects of the L-DEP regimen were high serum amylase concentrations, abnormal liver function, and coagulation disorders. Conclusions This study suggests that L-DEP is a safe and effective salvage therapy prior to allo-HSCT for refractory EBV-HLH and increases the possibility of such patients receiving allo-HSCT. A prospective multicenter large-scale clinical trial that aims to validate the L-DEP regimen for refractory EBV-HLH is currently underway (Clinical

  6. Cost analysis of the Spanish renal replacement therapy programme.

    Science.gov (United States)

    Villa, Guillermo; Rodríguez-Carmona, Ana; Fernández-Ortiz, Lucía; Cuervo, Jesús; Rebollo, Pablo; Otero, Alfonso; Arrieta, Javier

    2011-11-01

    A cost analysis of the Spanish Renal Replacement Therapy (RRT) programme in the year 2010, for end-stage renal disease (ESRD) patients, was performed from the perspective of the Public Administration. The costs associated with each RRT modality [hemodialysis (HD), peritoneal dialysis (PD) and kidney transplantation (Tx)] were analysed. The Spanish ESRD incidence and prevalence figures in the year 2010 were forecasted in order to enable the calculation of an aggregate cost for each modality. Costs were mainly computed based on a review of the existing literature and of the Official Bulletins of the Spanish Autonomous Communities. Data from Oblikue Consulting eSalud health care costs database and from several Spanish public sources were also employed. In the year 2010, the forecasted incidence figures for HD, PD and Tx were 5409, 822 and 2317 patients, respectively. The forecasted prevalence figures were 22,582, 2420 and 24,761 patients, respectively. The average annual per-patient costs (incidence and prevalence) were €2651 and €37,968 (HD), €1808 and €25,826 (PD) and €38,313 and €6283 (Tx). Indirect costs amounted to €8929 (HD), €7429 (PD) and €5483 (Tx). The economic impact of the Spanish RRT programme on the Public Administration budget was estimated at ~€1829 million (indirect costs included): €1327 (HD), €109 (PD) and €393 (Tx) million. HD accounted for >70% of the aggregate costs of the Spanish RRT programme in 2010. From a costs minimization perspective, it would be preferable if the number of incident and prevalent patients in PD were increased.

  7. Should dehydroepiandrosterone replacement therapy be provided with glucocorticoids?

    Science.gov (United States)

    Robinzon, B; Cutolo, M

    1999-06-01

    Adrenocorticotrophic hormone (ACTH) induces the concomitant secretion of glucocorticoids (GC) and dehydroepiandrosterone (DHEA) from the adrenal cortex. Whereas GC are catabolic, DHEA is anabolic. Long-term GC administration may result in some deleterious side-effects, such as muscular weakness, atrophy and necrosis, diabetes, fattiness, osteopenia, osteoporosis and avascular necrosis and susceptibility to infections. DHEA ameliorates some deleterious effects of GC, such as diabetes, amino acid deamination, fattiness, hypertension and susceptibility to viraemia. By its anabolic effects in muscles, bones and endothelium, DHEA may diminish the severity of GC-induced myopathy, osteopenia, osteoporosis and avascular necrosis. The natural concomitant secretion of DHEA with GC probably enables the latter to protect the body from ill-effects of stress without exerting their deleterious potency. DHEA secretion diminishes during aging and severe or chronic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Anti-inflammatory and immunosuppressive effects of GC and androgens, including DHEA, are now well established. On the other hand, administration of GC inhibits ACTH secretion, involutes the adrenal cortex and results in further DHEA deficiency, particularly harmful in chronic autoimmune diseases (i.e. RA, SLE). Therefore, the deleterious side-effects of chronic administration of GC emerges from both their direct catabolic activity and the suppression of DHEA production. Whereas, in males, most androgens come from the testes, in females, under GC supplementation, DHEA deficiency leads to nullification of the androgen-dependent anabolism, leaving them exposed to the GC-catabolic effects to a larger extent. The viewpoint presented here claims that under chronic GC supplementation, DHEA replacement therapy may reduce damage caused by GC administration.

  8. Principles of antibacterial dosing in continuous renal replacement therapy.

    Science.gov (United States)

    Choi, Gordon; Gomersall, Charles D; Tian, Qi; Joynt, Gavin M; Freebairn, Ross; Lipman, Jeffrey

    2009-07-01

    To outline the concepts involved in optimizing antibacterial dosing in critically ill patients with acute renal failure undergoing continuous renal replacement therapy (CRRT), provide a strategy for optimizing dosing, and summarize the data required to implement the strategy. MEDLINE search from February 1986 to 2008. Optimal dosing of antibacterials is dependent on achieving pharmacokinetic targets associated with maximal killing of bacteria and improved outcomes. The initial dose is dependent on the volume of distribution. Maintenance doses are dependent on clearance. Both should be adjusted according to the pharmacokinetic target associated with optimal bacterial killing, when known. The volume of distribution of some antibacterials is altered by critical illness or acute renal failure or both. Clearance by CRRT is dependent on the dose and mode of CRRT and the sieving or saturation coefficient of the drug. Both sieving and saturation coefficient are related to the plasma protein binding and thus may be altered in renal failure. Appropriate dose calculation requires knowledge of the pharmacokinetic target and the usual minimum inhibitory concentration of the suspected organism in the patient's locality (or if unavailable, the break point for the organism), published pharmacokinetic data (volume of distribution, non-CRRT clearance) on critically ill patients receiving CRRT (which may differ substantially from noncritically ill patients or those without renal failure), the sieving or saturation coefficient of the relevant drug in critically ill patients, the dose and mode of CRRT being used, and the actual dose of CRRT that is delivered. This large number of variables results in considerable inter- and intrapatient heterogeneity in dose requirements. This article provides basic principles and relevant data to guide the clinician in prescribing individualized dosing regimes.

  9. Patient satisfaction with testosterone replacement therapies: the reasons behind the choices.

    Science.gov (United States)

    Kovac, Jason R; Rajanahally, Saneal; Smith, Ryan P; Coward, Robert M; Lamb, Dolores J; Lipshultz, Larry I

    2014-02-01

    Testosterone replacement therapy (TRT) for male hypogonadism is rapidly gaining popularity and acceptance. Options include gels, injections, and implantable subcutaneous pellets. The aim of this study was to determine rates of patient satisfaction and reasons for patient preferences in hypogonadal men on TRT. An anonymous, prospective survey was distributed to men presenting for TRT at an academic urology clinic. The survey was organized into multiple domains including patient satisfaction and treatment motivation. Patient satisfaction responses obtained via anonymous survey. Average patient age was 49 ± 0.7 years (n = 382). Injectable testosterone was chosen by 53%, gel-based regimens by 31%, and pellets by 17%. Overall, 70% of patients were satisfied with their TRT and 14% reported dissatisfaction. Satisfaction rates were similar between gels (68%), injections (73%), and implantable pellets (70%). Doctor recommendation was the sole significant reason for patients preferring gel-based TRT (66% vs. 37% injection users vs. 31% pellet users). Injectable TRT was favored because of lower cost (35% vs. 21% gel users vs. 19% pellet users). Pellets were favored for ease of use (64% vs. 44% injection users vs. 43% gel users) and convenience (58% vs. 26% injection users vs. 19% gel users). Pellets had increased rates of satisfaction within the first 12 months. Improvements in concentration and mood occurred at higher percentages in satisfied patients. Patients are satisfied with TRT. Lower costs are important to patients on injections. Convenience and ease of use are central in choosing pellet therapy. Men on TRT should be questioned about mood and concentration because these factors exhibited the greatest improvements in satisfied patients. © 2013 International Society for Sexual Medicine.

  10. Different regimens of intravenous sedatives or hypnotics for electroconvulsive therapy (ECT) in adult patients with depression.

    Science.gov (United States)

    Lihua, Peng; Su, Min; Ke, Wei; Ziemann-Gimmel, Patrick

    2014-04-11

    Depression is a common mental disorder. It affects millions of people worldwide and is considered by the World Health Organization (WHO) to be one of the leading causes of disability. Electroconvulsive therapy (ECT) is a well-established treatment for severe depression. Intravenous anaesthetic medication is used to minimize subjective unpleasantness and adverse side effects of the induced tonic-clonic seizure. The influence of different anaesthetic medications on the successful reduction of depressive symptoms and adverse effects is unclear. This review evaluated the effects of different regimens of intravenous sedatives and hypnotics on anti-depression efficacy, recovery and seizure duration in depressed adults undergoing ECT. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 12); MEDLINE via Ovid SP (from 1966 to 31 December 2012); and EMBASE via Ovid SP (from 1966 to 31 December 2012). We handsearched related journals and applied no language restrictions. We included randomized controlled trials (RCTs) and cross-over trials evaluating the effects of different intravenous sedatives and hypnotics for ECT. We excluded studies and trials using placebo or inhalational anaesthetics and studies that used no anaesthetic. Two review authors independently assessed trial quality and extracted data. When possible, data were pooled and risk ratios (RRs) and mean differences (MDs), each with 95% confidence intervals (CIs), were computed using the Cochrane Review Manager statistical package (RevMan). We included in the review 18 RCTs (599 participants; published between 1994 and 2012). Most of the included trials were at high risk of bias.We analysed the results of studies comparing six different intravenous anaesthetics.Only a few studies comparing propofol with methohexital (four studies) and with thiopental (three studies) could be pooled.No difference was noted in the reduction of depression scores observed in participants treated with

  11. 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.

  12. Renal Replacement Therapy in Support of Combat Operations

    Science.gov (United States)

    2008-07-01

    was used to create viable sets; pediatric chest tubes were used as PD catheters and dialysate was made using either intravenous saline solution with...important logistic factor in performing RRT is the volume of fluid required for dialysate (for hemodi- alysis and peritoneal dialysis) or replace- ment...treatment may range on the order of 100 to 1000 L per day per patient. Both the dialysate and replacement fluid must be sterile, and no approach for

  13. Menopausal Women's Access Path to Bioidentical Hormone Replacement Therapy: An Exploratory.

    Science.gov (United States)

    Moro, Doris; Young, Wendy; Stein, Richard; Isaac, Winston; Goodman, Deborah

    2010-01-01

    The objective of this exploratory qualitative study was to describe (1) the key factors affecting women's initial decision to explore the use of bioidentical hormone, (2) where women gather their information on bioidentical hormones, (3) the enablers and barriers to obtaining bioidentical hormones, and (4) how to improve the bioidentical hormone replacement therapy access path. The study was conducted in a compounding pharmacy located in a large urban area in southern Ontario, Canada. The participants included four postmenopausal women between the ages of 46 and 72 who self-identified as users of bioidentical hormone replacement therapy and with comprehensive provincial healthcare coverage. Participants were recruited at a compounding pharmacy with the use of tri-fold brochures, tear-sheets, and posters. The women participated in an audio-taped mini focus group. Discussion was guided by six open-ended questions. Verbatim quotes were analyzed using an affinity diagram. Participants identified three key factors related to their initial decision: (1) symptoms unalleviated by synthetic hormone replacement therapy, (2) side effects from synthetic hormone replacement therapy, and (3) personal preference. They obtained information and support from many sources, including: family/friends, publications, and specialists in menopausal health. Once participants had made a decision, they obtained a prescription and accessed bioidentical hormone replacement therapy at a compounding pharmacy. Knowledgeable primary care physicians and compounding pharmacists were seen as enablers. Lack of support/Information and costs were identifies as barriers. Improvements to bioidentical hormone replacement therapy access path were suggested. The results of this study suggest that there may be value in implementing strategies to further encourage family physicians and other specialists in menopausal health to discuss options regarding hormone replacement therapy with patients. For example, the

  14. 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...

  15. 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...

  16. Eradication of Helicobacter pylori in Children by Triple Therapy Regimens of Amoxicillin, Omeprazole, and Clarithromycin or Azithromycin

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Esmaeili-Dooki

    2015-12-01

    Full Text Available Background and Objectives: The present study aimed to evaluate the effect of classical and azithromycin-containing triple therapy eradication regimen against H. Pylori in children, and to determine the level of patients’ tolerance. Patients and Methods: This single clinical trial was performed in 2014 on 2 to 15 years old children. All children, in whom H. Pylori infection was confirmed through multiple biopsies of the stomach and required treatment, were enrolled in the study. H. Pylori-positive patients were treated alternately with two different drug regimens; Group OCA received clarithromycin 7.5 mg/kg/day every 12 hours for 10 days, amoxicillin 50 mg/kg/day every 12 hours for 10 days, and omeprazole 1 mg/kg/day every 12 hours for two weeks, and Group OAA received azithromycin 10 mg/kg/day once a day (before meal for 6 days along with amoxicillin and omeprazole. Four to six weeks after completion of treatment, patients’ stool was tested for H. Pylori through the monoclonal method using the Helicobacter antigen quick kit. Results: There were no significant differences between the two groups regarding gender and age of patients. Based on ITT analysis, the therapeutic response in the OAA and OCA groups were 56.2% and 62.5%, respectively (P = 0.40. Drug adverse effects were 15.6% in the OCA and 3.1% in the OAA group (P = 0.19. Conclusions: The therapeutic response was seen in more than half of the patients treated with triple therapy of H. Pylori eradication regimen including azithromycin or clarithromycin, and there was no significant difference between the two treatment groups.

  17. Persistence to single-tablet regimen versus less-drug regimen in treatment experienced HIV-infected patients on antiretroviral therapy.

    Science.gov (United States)

    Jiménez-Galán, Rocio; Cantudo Cuenca, Maria-Rosa; Robustillo-Cortés, María Aguas; Borrego Izquierdo, Y; Almeida-Gonzalez, Carmen Victoria; Morillo-Verdugo, Ramón

    2016-06-01

    Objetivos: Analizar y comparar la persistencia entre las estrategias basadas en Single-Tablet Regimen (STR) y Less Drug Regimen (LDR) en pacientes VIH+. El objetivo secundario del estudio fue determinar factores predictores de persistencia. Material y métodos: Estudio observacional retrospectivo que incluyo los siguientes criterios: pacientes VIH+ con tratamiento antirretroviral (TAR) con un regimen basado en STR o LDR. Se recogieron variables demograficas, factores de riesgo de adquisicion, consumo de drogas, presencia de algun trastorno psiquiatrico y coinfeccion por el virus de la hepatitis B o C. Para comparar la persistencia entre ambas estrategias se realizo un analisis de supervivencia de Kaplan-Meir y se aplico el metodo de log-rank. Se realizo un analisis de regresion de Cox para identificar los factores predictores de persistencia. Resultados: Se incluyeron 244 pacientes, 176 con STR y 68 con LDR. El 34,1% (n = 60) de los pacientes que recibieron un regimen STR abandonaron y en el LDR el 19,1% (n = 13). Los efectos adversos fueron la principal causa de abandono del tratamiento en los pacientes que recibieron STR y el fallo virologico en el regimen LDR. La persistencia de las estrategias STR y LDR fue similar, no encontrandose diferencias estadisticamente significativas entre ambas. El consumo de drogas fue el unico factor predictivo asociado con una menor persistencia (HR = 2,59; p = 0,005). Conclusiones: La persistencia entre los regimenes STR y LDR fue similar, no detectandose diferencias significativas entre ambos. El consumo de drogas fue el unico factor independiente asociado con una menor persistencia del tratamiento antirretroviral.

  18. Hybrid Therapy as First-Line Regimen for Helicobacter pylori Eradication in Populations with High Antibiotic Resistance Rates.

    Science.gov (United States)

    Song, Zhiqiang; Zhou, Liya; Zhang, Jianzhong; He, Lihua; Bai, Peng; Xue, Yan

    2016-10-01

    Hybrid therapy has recently attracted widespread attention. However, many issues require further exploration. For example, research in regions with high antibiotic resistance rates is limited, and the correlation between eradication efficacy and antibiotic resistance remains unclear. The aim of this study was to determine the efficacy, compliance, safety, and risk factors of hybrid therapy as first-line regimen in a region with high antibiotic resistance rates. This prospective study was conducted in a tertiary hospital between January 2014 and June 2015. A total of 196 patients with dyspepsia but without prior eradication therapy received hybrid regimen (esomeprazole 20 mg and amoxicillin 1000 mg twice daily for 14 days with the addition of clarithromycin 500 mg and tinidazole 500 mg twice daily for the final 7 days). All patients underwent Helicobacter pylori culture, antibiotic susceptibility testing and cytochrome P450 isoenzyme 2C19 polymorphism testing. Hybrid therapy achieved eradication rates of 77.0% (95% confidence interval (CI), 70.9-83.7%) in intention-to-treat (ITT), 83.9% (78.9-88.9%) in modified ITT and 86.0% (80.2-91.3%) in per-protocol analyses in a setting with high antibiotic resistance rates (amoxicillin 2.0%, clarithromycin 44.9%, metronidazole 67.3% and dual clarithromycin and metronidazole 33.3%). Adverse reactions occurred in 31.9% patients and 2.7% discontinued medications due to adverse reactions. Good compliance was achieved by 92.0%. Multivariate analyses identified clarithromycin resistance (odds ratio, 3.494; 95% CI, 1.237-9.869), metronidazole resistance (3.012; 1.013-12.054) and poor compliance (5.840; 1.126-30.296) as independent predictors of treatment failure. The eradication rate with dual clarithromycin and metronidazole resistance (70.2%) was markedly decreased compared to isolated clarithromycin resistance (87.5%), isolated metronidazole resistance (88.6%), or dual susceptibility (96.4%) (p = .014). Despite good compliance and

  19. 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 <50 copies/mL at week 48. ART regime 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.

  20. RENAL REPLACEMENT THERAPY FOR END-STAGE RENAL DISEASE PATIENTS IN RUSSIAN FEDERATION, 1998–2011 (Report of the Russian Registry of Renal Replacement Therapy

    Directory of Open Access Journals (Sweden)

    N. A. Tomilina

    2015-01-01

    Full Text Available The report of the Russian Renal Replacement Therapy Registry covers the period from the year 1998 to 2011 and represents data on the national, regional, and individual patient levels. We summarize information about epidemiology of treated end-stage renal disease in Russia, and describe in details incidence and prevalence for all modalities of renal replacement therapy. The article contains broad spectrum of data on quality of treatment indicators, waiting list, pharmacological treatment, mortality, and survival patterns in patients on hemodialysis, peritoneal dialysis and with functioning renal graft. 

  1. Primary hypothyroidism in the community: Lower daily dosages of levothyroxine replacement therapy for Asian patients.

    Science.gov (United States)

    Tan, Ngiap Chuan; Chew, Rong Quan; Koh, Yi Ling Eileen; Subramanian, Reena Chandini; Sankari, Usha; Meyappan, Meykkumar; Cho, Li Wei

    2017-02-01

    The goal of treatment in patients with primary hypothyroidism is to attain euthyroidism guided by the stipulated thyroid-stimulating hormone (TSH) levels range so as to minimize any potential long-term adverse effects. However, various factors may result in their Levothyroxine (T4) under and over-replacement.Our study aimed to evaluate the mean daily dose of L-T4 replacement for Asian patients with primary hypothyroidism. The secondary aims were to determine the proportion of those who were either over or under-replaced, and the factors associated with their thyroid function status and replacement adherence.Data collected using questionnaire survey from targeted patients managed in a typical public primary care center in Singapore: socio-demographic characteristics, clinical parameters, laboratory investigations, mean daily L-T4-replacement doses, and replacement regimens. The thyroid status of patients was classified based on thyroid function investigations.Complete data of 229 patients were analyzed. A total of 59.8% of patients had TSH within the normal range, 27.5% and 12.7% were under and over-replaced, respectively. About 60% of Asian patients with primary hypothyroidism achieved normal TSH status requiring average of 1.1 μg of daily L-T4/kgBW (kg body weight). Subjects who were over-replaced had a higher daily L-T4 dose/kgBW when compared to the euthyroid and the under replaced groups. Those with L-T4 over-replacement were largely due to excessive dosage. Patients who were younger, from lower socioeconomic strata, and higher BMI were more likely to be over or under-replaced.Majority of Asian patients with hypothyroidism required replacement of 1.1 μg of daily L-T4/kgBW. Their thyroid status was influenced by demographic and dosing factors.

  2. Drug dosing during intermittent hemodialysis and continuous renal replacement therapy : special considerations in pediatric patients.

    Science.gov (United States)

    Veltri, Michael A; Neu, Alicia M; Fivush, Barbara A; Parekh, Rulan S; Furth, Susan L

    2004-01-01

    Chronic renal failure is, fortunately, an unusual occurrence in children; however, many children with various underlying illnesses develop acute renal failure, and transiently require renal replacement therapy - peritoneal dialysis, intermittent hemodialysis (IHD), or continuous renal replacement therapy (CRRT). As children with acute and chronic renal failure often have multiple comorbid conditions requiring drug therapy, generalists, intensivists, nephrologists, and pharmacists need to be aware of the issues surrounding the management of drug therapy in pediatric patients undergoing renal replacement therapy. This article summarizes the pharmacokinetics and dosing of many drugs commonly prescribed for pediatric patients, and focuses on the management of drug therapy in pediatric patients undergoing IHD and CRRT in the intensive care unit setting. Peritoneal dialysis is not considered in this review. Finally, a summary table with recommended initial dosages for drugs commonly encountered in pediatric patients requiring IHD or CRRT is presented.

  3. Development of nanoparticle-bound arylsulfatase B for enzyme replacement therapy of mucopolysaccharidosis VI

    National Research Council Canada - National Science Library

    Mühlstein, A; Gelperina, S; Kreuter, J

    2013-01-01

    .... Even though an enzyme replacement therapy (ERT) of recombinant arylsulfatase B (ASB) is available for MPS VI, the administration cannot positively affect the neurologic manifestations such as spinal cord compression...

  4. 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.

    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.

  5. 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.

  6. 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.

    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. T

  7. Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy.

    Science.gov (United States)

    Ulldemolins, Marta; Vaquer, Sergi; Llauradó-Serra, Mireia; Pontes, Caridad; Calvo, Gonzalo; Soy, Dolors; Martín-Loeches, Ignacio

    2014-06-23

    Although early and appropriate antibiotic therapy remains the most important intervention for successful treatment of septic shock, data guiding optimization of beta-lactam prescription in critically ill patients prescribed with continuous renal replacement therapy (CRRT) are still limited. Being small hydrophilic molecules, beta-lactams are likely to be cleared by CRRT to a significant extent. As a result, additional variability may be introduced to the per se variable antibiotic concentrations in critically ill patients. This article aims to describe the current clinical scenario for beta-lactam dosing in critically ill patients with septic shock and CRRT, to highlight the sources of variability among the different studies that reduce extrapolation to clinical practice, and to identify the opportunities for future research and improvement in this field. Three frequently prescribed beta-lactams (meropenem, piperacillin and ceftriaxone) were chosen for review. Our findings showed that present dosing recommendations are based on studies with drawbacks limiting their applicability in the clinical setting. In general, current antibiotic dosing regimens for CRRT follow a one-size-fits-all fashion despite emerging clinical data suggesting that drug clearance is partially dependent on CRRT modality and intensity. Moreover, some studies pool data from heterogeneous populations with CRRT that may exhibit different pharmacokinetics (for example, admission diagnoses different to septic shock, such as trauma), which also limit their extrapolation to critically ill patients with septic shock. Finally, there is still no consensus regarding the %T>MIC (percentage of dosing interval when concentration of the antibiotic is above the minimum inhibitory concentration of the pathogen) value that should be chosen as the pharmacodynamic target for antibiotic therapy in patients with septic shock and CRRT. For empirically optimized dosing, during the first day a loading dose is required

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

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, Henrik Enghusen; 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....

  9. Safety and efficacy of testosterone replacement therapy in adolescents with Klinefelter syndrome.

    Science.gov (United States)

    Mehta, Akanksha; Clearman, Theresa; Paduch, Darius A

    2014-05-01

    We investigated the safety and tolerability of testosterone replacement therapy in adolescents with Klinefelter syndrome. We reviewed the medical records of all consecutive adolescents with Klinefelter syndrome evaluated between 2007 and 2012. Patients receiving testosterone replacement and aromatase inhibitor therapy were identified. Data on demographics, physical characteristics, medical history and serum hormone concentrations were collected for each patient. We evaluated longitudinal changes in serum testosterone, luteinizing hormone and follicle-stimulating hormone as well as changes in body mass index after the initiation of testosterone replacement therapy. We identified 151 adolescents with Klinefelter syndrome. Mean age at presentation was 11.6 years. Testosterone replacement therapy and aromatase inhibitors were initiated in 110 and 75 patients, respectively, at an average age of 13 to 14 years. Topical testosterone replacement therapy was used in 95% of patients with good clinical efficacy and compliance based on serial serum testosterone values. After the initiation of testosterone replacement therapy average serum testosterone improved from 240 to 650 ng/ml. Serum luteinizing hormone and follicle-stimulating hormone increased with the progression of puberty from 2.6 to 16.6 and 7 to 42 mIU/ml, respectively. No adverse outcomes related to testosterone replacement therapy were reported. Hormone supplementation with testosterone and aromatase inhibitors in adolescents with Klinefelter syndrome appears to be safe and effective for maintaining serum testosterone within the normal range. Compliance with topical formulations is high. Topical testosterone replacement therapy is not associated with the suppression of endogenous serum luteinizing hormone or follicle-stimulating hormone. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Effect of two intensive insulin therapy regimens on perioperative glycemic control in bone fracture patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    DENG Wei; HUO Li-li; LAN Ling; L(U) Yan-wei; WANG Man-yi

    2013-01-01

    Background Currently,there are no uniform standards and methods for perioperative glycemic control in bone fracture patients with Type 2 diabetes mellitus (T2DM).We retrospectively analyzed the efficacy and safety of two intensive insulin therapy regimens administered to bone fracture patients with T2DM in the perioperative period,to explore the best method of achieving perioperative glycemic control.Methods A number of 159 bone fracture patients with T2DM were divided into two groups.One group (n=81) received multiple subcutaneous insulin injections (MSⅡ group) and the other (n=78) received continuous subcutaneous insulin infusion (CSⅡ group).Blood glucose (BG) levels,time to achieve glycemic target,insulin dosage,and the incidence of hypoglycemia and complications were compared between groups.Results Both regimens reduced BG to desired levels before surgery.The time to reach glycemic target in CSⅡ group (2.5 days) was significantly shorter than that in the MSII group (7.3 days; P<0.001).Mean insulin dosage in the CSⅡ group (0.66 IU·kg-1·d-1) was significantly lower than that in the MSⅡ group (0.74 IU·kg1·d-1; P=0.005),as were the incidences of hypoglycemia (15.4% vs 32.1%) and infection (6.4% vs.23.5%).Multiple regression analysis showed that the time to reach glycemia target was associated with the insulin therapy regimen and dosage.The insulin dosage on reaching glycemia target was positively associated with body mass index (BMI),diabetes mellitus course,glycated hemoglobin A1c (HbA1c),and β-hydroxybutyric acid,and was negatively associated with age.Conclusion The efficacy and safety of CSⅡ was superior to that achieved with MSⅡ,suggesting that CSⅡ should be considered as initial therapy to control perioperative BG in bone fracture patients with T2DM.

  11. Pharmacokinetics of meropenem during intermittent and continuous intravenous application in patients treated by continuous renal replacement therapy.

    Science.gov (United States)

    Langgartner, Julia; Vasold, Antje; Glück, Thomas; Reng, Michel; Kees, Frieder

    2008-06-01

    The clinical effect of beta-lactam antibiotics depends on the time of drug concentration above the minimal inhibitory concentration (MIC) for a susceptible bacterium. Continuous infusion (CI) of beta-lactams such as meropenem may therefore be a more rational approach than intermittent bolus injections (IB). The aim of this study was to test whether CI of meropenem achieves effective drug concentrations comparable to IB in patients treated by continuous renal replacement therapy (CRRT). Prospective, randomised cross-over study. Twelve-bed medical intensive care unit (ICU). Six ICU patients were randomised to receive either meropenem 1 g IB every 12 h or a 0.5 g i.v. loading dose followed by 2 g i.v. CI over 24 h. After 2 days, regimens were crossed over. Meropenem pharmacokinetics were determined on days 2 and 4. Peak serum concentration [median (25% and 75% quartiles)] after short infusion of 1 g meropenem were 62.8 (51.4; 85.0) mg/l, trough levels at 12 h were 8.1 (4.5; 18.7) mg/l, and serum half-life was 5.3 (5.1; 7.0) h. Steady-state concentrations during CI were 18.6 (13.3; 24.5) mg/l. The AUCs during either treatment were comparable and determined as 233 (202; 254) mg/l*h (IB) and 227 (182; 283) mg/l*h (CI), respectively. Four hours after IB, drug concentrations dropped below CI steady-state concentrations. Appropriate antibacterial concentrations of meropenem in patients with CRRT are easily achievable with CI. CI may be an effective alternative dosing regimen to IB. A prospective comparison of the clinical efficacy of the two dosage regimens is warranted.

  12. Cell replacement therapy for central nervous system diseases

    Institute of Scientific and Technical Information of China (English)

    Danju Tso; Randall D. McKinnon

    2015-01-01

    The brain and spinal cord can not replace neurons or supporting glia that are lost through trau-matic injury or disease. In pre-clinical studies, however, neural stem and progenitor cell transplants can promote functional recovery. Thus the central nervous system is repair competent but lacks endogenous stem cell resources. To make transplants clinically feasible, this ifeld needs a source of histocompatible, ethically acceptable and non-tumorgenic cells. One strategy to generate pa-tient-speciifc replacement cells is to reprogram autologous cells such as ifbroblasts into pluripotent stem cells which can then be differentiated into the required cell grafts. However, the utility of pluripotent cell derived grafts is limited since they can retain founder cells with intrinsic neoplastic potential. A recent extension of this technology directly reprograms ifbroblasts into the ifnal graft-able cells without an induced pluripotent stem cell intermediate, avoiding the pluripotent caveat. For both types of reprogramming the conversion efficiency is very low resulting in the need to amplify the cells in culture which can lead to chromosomal instability and neoplasia. Thus to make reprogramming biology clinically feasible, we must improve the efifciency. The ultimate source of replacement cells may reside in directly reprogramming accessible cells within the brain.

  13. 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

    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......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...

  14. 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

    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......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...

  15. 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

  16. Testosterone replacement therapy following the diagnosis of prostate cancer: outcomes and utilization trends.

    Science.gov (United States)

    Kaplan, Alan L; Trinh, Quoc-Dien; Sun, Maxine; Carter, Stacey C; Nguyen, Paul L; Shih, Ya-Chen Tina; Marks, Leonard S; Hu, Jim C

    2014-04-01

    Late-onset hypogonadism may impair quality of life and contribute to metabolic and cardiovascular comorbidity in aging men. Testosterone replacement therapy is effective in treating hypogonadism. However, for the millions of men with a history of prostate cancer, exogenous testosterone has long been considered contraindicated, even though little data in such men are available. Clarification of this safety issue could allow treatment to be considered for a sizeable segment of the aging male population. The aim of this study is to examine population-based utilization and impact of testosterone replacement therapy in men with prostate cancer. Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1992 to 2007. Of those, 1181 (0.79%) men received exogenous testosterone following their cancer diagnosis. We used propensity scoring analysis to examine the effect of testosterone replacement on the use of salvage hormone therapy and overall and prostate cancer-specific mortality. We assessed overall mortality, cancer-specific mortality, and the use of salvage hormone therapy. Following prostate cancer diagnosis, testosterone replacement was directly related to income and educational status and inversely related to age (all P testosterone (all P testosterone replacement therapy was not associated with overall or cancer-specific mortality or with the use of salvage hormone therapy. In this population-based observational study of testosterone replacement therapy in men with a history of prostate cancer, treatment was not associated with increased overall or cancer-specific mortality. These findings suggest testosterone replacement therapy may be considered in men with a history of prostate cancer, but confirmatory prospective studies are needed. © 2014 International Society for Sexual Medicine.

  17. Daily Enema Regimen Is Superior to Traditional Therapies for Nonneurogenic Pediatric Overactive Bladder

    Directory of Open Access Journals (Sweden)

    Steve J. Hodges MD

    2016-03-01

    Full Text Available Our objective was to evaluate the efficacy of daily enemas for the treatment of overactive bladder (OAB in children. This study was a prospective, controlled trial of 60 children with nonneurogenic OAB. The control patients (40 were treated with standard therapies, including timed voiding, constipation treatment with osmotic laxatives, anticholinergics, and biofeedback physical therapy, whereas the treatment patients (20 received only daily enemas and osmotic laxatives. On assessment of improvement of OAB symptoms, only 30% of the traditionally treated patients’ parents reported resolution of symptoms at 3 months, whereas 85% of enema patients did. At the onset of the study, the average pediatric voiding dysfunction score of all patients was 14, whereas on follow-up, the average scores for traditionally treated patients and enema-treated patients were 12 and 4, respectively. This study demonstrated that daily enema therapy is superior to traditional methods for the treatment of OAB.

  18. Short-time, high-dosage penicillin infusion therapy of syphilis: an alternative to recommended regimens?

    DEFF Research Database (Denmark)

    Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming;

    2003-01-01

    The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

  19. Cost-Utility Analysis of Mycophenolate Mofetil versus Azathioprine Based Regimens for Maintenance Therapy of Proliferative Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Robert Nee

    2015-01-01

    Full Text Available Background/Aims. We aimed to examine the cost-effectiveness of mycophenolate mofetil (MMF and azathioprine (AZA as maintenance therapy for patients with Class III and Class IV lupus nephritis (LN, from a United States (US perspective. Methods. Using a Markov model, we conducted a cost-utility analysis from a societal perspective over a lifetime horizon. The modeled population comprised patients with proliferative LN who received maintenance therapy with MMF (2 gm/day versus AZA (150 mg/day for 3 years. Risk estimates of clinical events were based on a Cochrane meta-analysis while costs and utilities were retrieved from other published sources. Outcome measures included costs, quality-adjusted life-years (QALY, incremental cost-effectiveness ratios (ICER, and net monetary benefit. Results. The base-case model showed that, compared with AZA strategy, the ICER for MMF was $2,630,592/QALY at 3 years. Over the patients’ lifetime, however, the ICER of MMF compared to AZA was $6,454/QALY. Overall, the ICER results from various sensitivity and subgroup analyses did not alter the conclusions of the model simulation. Conclusions. In the short term, an AZA-based regimen confers greater value than MMF for the maintenance therapy of proliferative LN. From a lifelong perspective, however, MMF is cost-effective compared to AZA.

  20. Continuous Renal Replacement Therapy and Extracorporeal Membrane Oxygenation in Cardias Surgery

    Directory of Open Access Journals (Sweden)

    S. V. Kolesnikov

    2014-01-01

    Full Text Available Objective: to analyze the combined use of extracorporeal membrane oxygenation (ECMO and continuous renal replacement therapy with switching into the ECMO circuit in cardiac surgical patients over 18 years of age and to reveal predictors of a fatal outcome in this combination of auxiliary organ support techniques. Materials and methods. The retrospective cohort study postoperatively used a combination of ECMO and continuous renal replacement therapy in 27 cardiac surgical patients aged over 18 years with severe cardiopulmonary insufficiency concurrent with acute kidney lesion. In all cases, the continuous renal replacement therapy circuit was switched into the line after an ECMO pump. The end points of the study were the duration of dialysis-dependent acute renal failure, the frequency of complications, and hospital mortality. Results. In all cases with a favorable outcome, the duration of continuous renal replacement therapy was 3 days longer than that of ECMO. There were no cases of recovery if the duration of continuous renal replacement therapy was shorter than that of ECMO and the duration of the latter was more than 10 days. The duration of sympathomimetic support (>3.5 days was shown to be an independent and significant predictor of death (AUC 0.99; CI 99.9%, 0.96—1.0 in the patients receiving continuous renal replacement therapy and ECMO. It was established that the number of inotrophic drugs (>2 and the highest lactate level (>1.99 mmol/l could be used to predict hospital mortality in patients with acute kidney injury and severe cardiopulmonary insufficiency (AUC 0.85 and 0.86; sensitivity/specificity 0.83/0.67 and 0.86/0.67, respectively.Conclusion. The concurrent use of ECMO and continuous renal replacement therapy in severe cardiac surgical patients with potentially reversible cardiopulmonary insufficiency and acute kidney injury is a sound and complementary combination of auxiliary organ support techniques.  

  1. Interstitial cystitis/bladder pain syndrome and glycosaminoglycans replacement therapy

    Science.gov (United States)

    2015-01-01

    Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disease characterized by discomfort or recurrent abdominal and pelvic pains in the absence of urinary tract infections. Its symptomatology includes discomfort, increased bladder pressure, sensitivity and intense pain in the bladder and pelvic areas, increased voiding frequency and urgency, or a combination of these symptoms. For these reasons, this pathology has a very negative impact on quality of life. The etiology of IC/BPS is still not well understood and different hypotheses have been formulated, including autoimmune processes, allergic reactions, chronic bacterial infections, exposure to toxins or dietary elements, and psychosomatic factors. The finding of an effective and specific therapy for IC/BPS remains a challenge for the scientific community because of the lack of a consensus regarding the causes and the inherent difficulties in the diagnosis. The last recent hypothesis is that IC/BPS could be pathophysiologically related to a disruption of the bladder mucosa surface layer with consequent loss of glycosaminoglycans (GAGs). This class of mucopolysaccharides has hydrorepellent properties and their alteration expose the urothelium to many urinary toxic agents. It has been hypothesized that when these substances penetrate the bladder wall a chain is triggered in the submucosa. In order to improve the integrity and function of the bladder lining, GAG layer replenishment therapy is widely accepted as therapy for patients with IC/BPS who have poor or inadequate response to conventional therapy. Currently, Chondroitin sulfate (CS), heparin, hyaluronic acid (HA), and pentosan polysulphate (PPS), and combinations of two GAGs (CS and HA) are the available substances with different effectiveness rates in patients with IC/BPS. There are four different commercially available products for GAG replenishment including CS, heparin, HA and PPS. Each product has different concentrations and

  2. Current status of myelin replacement therapies in multiple sclerosis.

    Science.gov (United States)

    Huang, Jeffrey K; Franklin, Robin J M

    2012-01-01

    Multiple sclerosis is an autoimmune disease of the human central nervous system characterized by immune-mediated myelin and axonal damage, and chronic axonal loss attributable to the absence of myelin sheaths. There are two aspects to the treatment of MS-first, the prevention of damage by suppressing the maladaptive immune system, and second, the long-term preservation of axons by the promotion of remyelination, a regenerative process in which new axons are restored to demyelinated axons. Medicine has made significant progress in the first of these in recent years-there is an increasing number of ever more effective disease-modifying immunomodulatory interventions. However, there are currently no widely used regenerative therapies in MS. Conceptually, there are two approaches to remyelination therapy-transplantation of myelinogenic cells and promotion of endogenous remyelination mediated by myelinogenic cells present within the diseased tissue. In this chapter, in addition to describing why remyelination therapies are important, we review both these approaches, outlining their current status and future developments.

  3. 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.

  4. Clinical evaluation of four one-week triple therapy regimens in eradicating Helicobacter pyloriinfection

    Institute of Scientific and Technical Information of China (English)

    Chuan-Yong Guo; Yun-Bin Wu; Heng-Lu Liu; Jian-Ye Wu; Min-Zhang Zhong

    2004-01-01

    AIM: TO evaluate clinical efficacy of four one-week triple therapies in eradicating Helicobacter pylori infection.METHODS: In this clinical trial, 132 patients with duodenal ulcer and chronic gastritis were randomly divided into four 20 mg+ amoxicillin 1 000 mg + clarithromycin 250 mg), OFC (omeprazole 20 mg + furazolidone 100 mg + clarithromycin 250 mg), OFA (omeprazole 20 mg + furazolidone 100 mg + amoxicillin 1000 mg) and OMC (omeprazole 20 mg +metronidazole 200 mg + cladthromycin 250 mg), respectively.Each drug was taken twice daily for one week. The 13C urea breath test was carried out 4-8 weeks after treatment to determine the success of H pylori eradication.RESULTS: A total of 127 patients completed the treatment.The eradication rate for H pylori infection was 90.3%,90.9%, 70.9% and 65.6%, respectively in OAC, OFC OMC and OFA groups.CONCLUSION: A high eradication rate can be achieved with one-week OAC or OFC triple therapy. Thus, oneweek triple therapies with OAC and OFC are recommended for Chinese patients with duodenal ulcers and chronic gastritis.

  5. Renal replacement therapies after abdominal aortic aneurysm repair--a review.

    Science.gov (United States)

    Hudorović, Narcis; Lovricević, Ivo; Brkić, Petar; Ahel, Zaky; Vicić-Hudorović, Visnja

    2011-09-01

    The objective of this review is to assess the incidence of postoperative acute renal failure that necessitates the application of hemofiltration and to determine the factors that influence the outcome in patients undergoing surgical repair of abdominal aortic aneurysm. In addition, the review aims to assess the outcomes of postoperative early hemofiltration as compared to late intensive hemofiltration. Different forms of renal replacement therapies for use in abdominal aortic aneurysm surgery patients are discussed. Electronic literature searches were performed using Pubmed, Medline, Embase, Sumsearch, Cinahil, The Cochrane Central Register of Controlled Trials and Excerpta Medica. The search identified 419 potentially eligible studies, of which 119 were excluded based on the title and abstract. Of the remaining 300 studies, full articles were collected and re-evaluated. Forty-five articles satisfied our inclusion criteria, of which only 12 were of the IA Level of evidence. The search results indicated that the underlying disease, its severity and stage, the etiology of acute renal failure, clinical and hemodynamic status of the patient, the resources available, and different costs of therapy might all influence the choice of the renal replacement therapy strategy. However, clear guidelines on renal replacement therapy duration are still lacking. Moreover, it is not known whether in acute renal failure patients undergoing abdominal aortic aneurysm surgery, renal replacement therapy modalities can eliminate significant amounts of clinically relevant inflammatory mediators. This review gives current information available in the literature on the possible mechanisms underlying acute renal failure and recent developments in continuous renal replacement treatment modalities.

  6. Effects of hormone replacement therapy on depressive and anxiety symptoms after oophorectomy

    Directory of Open Access Journals (Sweden)

    Danijela D. Ðoković

    2015-02-01

    Full Text Available Aim To assess the effect of hormone replacement therapy on postoperative depression and anxiety symptoms. Methods In observational prospective study 80 women divided into two groups were evaluated: women who received estrogen and androgen replacement therapy after hysterectomy with bilateral oophorectomy before onset of menopause (35-45 years old and a control group that consisted of perimenipausal women (45-55 years old. Hormone replacement therapy began one week after surgery. The severity of depression and anxiety was evaluated through the use of Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale. Subjects from the study group were interviewed right after the surgical treatment, one, two and three months later. Subjects from the control group were interviewed only once. Results The women who underwent surgery had a statistically significantly higher score in Hamilton Depression Scale (p<0.001 and Hamilton Anxiety Scale (p=0.002 compared to the control perimenopausal women. There was a significant reduction of depressive and anxiety symptoms during hormone replacement therapy. Statistically significant difference in depressive score was found immediately after one month of hormone replacement therapy (first week/one month later: p=0.0057. Statistically significant difference in anxiety score appeared three months after the introduction of hormone therapy (first week/one month later: p=0.309; first week/two months later: p=0.046; first week/three months later: p<0.001. Level of serum luteinizing hormone was in correlation with depressive and anxiety score. Conclusion Estrogen-androgen replacement therapy may reduce the risk of psychiatric disorders developing in women with bilateral oophorectomy (indication for hysterectomy with oophorectomy was leiomyomata uteri.

  7. Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Jamshid Vafaeimanesh

    2014-01-01

    Full Text Available To compare a triple-therapy regimen based on change of antibiotic (azithromycin and clarithromycin for the eradication of Helicobacter pylori in hemodialysis (HD patients, we studied in a prospective, randomized, double-blinded clinical trial 39 patients who had dyspepsia and showed two positive results from the diagnostic tests of H. pylori infection including anti-H. pylori serology and stool antigen (HpSAg and urease breath test (UBT. The patients were divided into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg, amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and compliance with triple therapy were reviewed at one visit per week. Both groups were prescribed their medications for 14 days. Of the 39 patients, only 37 patients completed the treatment schedule (20 men and 19 women, with the mean being 59 years. Two patients died due to myocardial infarction before the start of treatment and were out of the study. The eradication rate of H. pylori, evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P-value = 1.0. The results of our study showed no significant difference of azitromycin versus claritromycin in the eradication of H. pylori infection in HD patients.

  8. Expression comparison of azithromycin and clarithromycin in triple-therapy regimens for eradication of Helicobacter pylori in hemodialysis patients.

    Science.gov (United States)

    Vafaeimanesh, Jamshid; Jalalzadeh, Mojgan; Nazarian, Morteza

    2014-01-01

    To compare a triple-therapy regimen based on change of antibiotic (azithromycin and clarithromycin) for the eradication of Helicobacter pylori in hemodialysis (HD) patients, we studied in a prospective, randomized, double-blinded clinical trial 39 patients who had dyspepsia and showed two positive results from the diagnostic tests of H. pylori infection including anti-H. pylori serology and stool antigen (HpSAg) and urease breath test (UBT). The patients were divided into two groups: Group-A received omeprazol 20 mg, amoxycilin 500 mg and clarithromycin 500 mg twice a day and Group-B received omeprazol 20 mg, amoxicillin 500 mg and azithromycin 250 mg twice a day. The adverse events and compliance with triple therapy were reviewed at one visit per week. Both groups were prescribed their medications for 14 days. Of the 39 patients, only 37 patients completed the treatment schedule (20 men and 19 women, with the mean being 59 years). Two patients died due to myocardial infarction before the start of treatment and were out of the study. The eradication rate of H. pylori, evaluated by negative results of UBT, was 82.4% in Group-A and 80% in Group-B (P-value = 1.0). The results of our study showed no significant difference of azitromycin versus claritromycin in the eradication of H. pylori infection in HD patients.

  9. Adherence to Antiretroviral Therapy (ART) in Yaoundé-Cameroon: Association with Opportunistic Infections, Depression, ART Regimen and Side Effects.

    Science.gov (United States)

    Fonsah, Julius Y; Njamnshi, Alfred K; Kouanfack, Charles; Qiu, Fang; Njamnshi, Dora M; Tagny, Claude T; Nchindap, Emilienne; Kenmogne, Léopoldine; Mbanya, Dora; Heaton, Robert; Kanmogne, Georgette D

    2017-01-01

    Following global efforts to increase antiretroviral therapy (ART) access in Sub-Saharan Africa, ART coverage among HIV-infected Cameroonians increased from 0% in 2003 to 22% in 2014. However, the success of current HIV treatment programs depends not only on access to ART, but also on retention in care and good treatment adherence. This is necessary to achieve viral suppression, prevent virologic failure, and reduce viral transmission and HIV/AIDS-related deaths. Previous studies in Cameroon showed poor adherence, treatment interruption, and loss to follow-up among HIV+ subjects on ART, but the factors that influence ART adherence are not well known. In the current cross-sectional study, patient/self-reported questionnaires and pharmacy medication refill data were used to quantify ART adherence and determine the factors associated with increased risk of non-adherence among HIV-infected Cameroonians. We demonstrated that drug side-effects, low CD4 cell counts and higher viral loads are associated with increased risk of non-adherence, and compared to females, males were more likely to forego ART because of side effects (pART regimen, age, gender, and education showed that subjects with opportunistic infections had 3.1-times higher odds of having been non-adherent (p40 years) were less likely to be non-adherent (pART during antibiotic treatment (r = 0.53, p = 0.04), and was associated with lower CD4 cell counts (p = 0.04) and longer non-adherent periods (p = 0.04). Change in ART regimen was significantly associated with increased likelihood of non-adherence and increased duration of the non-adherence period. Addressing these underlying risk factors could improve ART adherence, retention in care and treatment outcomes for HIV/AIDS patients in Cameroon.

  10. Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C–Coinfected Persons

    Science.gov (United States)

    Brunet, Laurence; Moodie, Erica E. M.; Young, Jim; Cox, Joseph; Hull, Mark; Cooper, Curtis; Walmsley, Sharon; Martel-Laferrière, Valérie; Rachlis, Anita; Klein, Marina B.

    2016-01-01

    Background. Liver diseases progress faster in human immunodeficiency virus (HIV)–hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV–coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). Methods. Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction–positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. Results. A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, −3%, 19%) or NNRTI users (3% per 5 years, 95% CI, −7%, 12%). Conclusions. Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV–coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used. PMID:26400998

  11. Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C-Coinfected Persons.

    Science.gov (United States)

    Brunet, Laurence; Moodie, Erica E M; Young, Jim; Cox, Joseph; Hull, Mark; Cooper, Curtis; Walmsley, Sharon; Martel-Laferrière, Valérie; Rachlis, Anita; Klein, Marina B; Cohen, Jeff; Conway, Brian; Cooper, Curtis; Côté, Pierre; Cox, Joseph; Gill, John; Haider, Shariq; Sadr, Aida; Johnston, Lynn; Hull, Mark; Montaner, Julio; Moodie, Erica; Pick, Neora; Rachlis, Anita; Rouleau, Danielle; Sandre, Roger; Tyndall, Joseph Mark; Vachon, Marie-Louise; Sanche, Steve; Skinner, Stewart; Wong, David

    2016-01-15

    Liver diseases progress faster in human immunodeficiency virus (HIV)-hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV-coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction-positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, -3%, 19%) or NNRTI users (3% per 5 years, 95% CI, -7%, 12%). Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV-coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. The nanochannel delivery system for constant testosterone replacement therapy.

    Science.gov (United States)

    Ferrati, Silvia; Nicolov, Eugenia; Zabre, Erika; Geninatti, Thomas; Shirkey, Beverly A; Hudson, Lee; Hosali, Sharath; Crawley, Michael; Khera, Mohit; Palapattu, Ganesh; Grattoni, Alessandro

    2015-06-01

    The goal of testosterone replacement is to provide long-term physiological supplementation at sufficient levels to mitigate the symptoms of hypogonadism. The objective of this work is to determine if the implantable nanochannel delivery system (nDS) can present an alternative delivery strategy for the long-term sustained and constant release of testosterone. A formulation of common testosterone esters (F1) was developed to enable nanochannel delivery of the low water soluble hormone. In vivo evaluation of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels by liquid chromatography/mass spectrometry and a multiplex assay, respectively, in castrated Sprague-Dawley rats implanted with nDS-F1 implants or polymeric pellets was performed over a 6-month period. The percent of testosterone concentrations observed that fell within the normal range of testosterone levels for each animal was calculated and used to compare the study groups. Sustain release of testosterone in vivo for over 6 months. The subcutaneous release of F1 from nDS implants exhibited sustained in vivo release kinetics and attained stable clinically relevant plasma testosterone levels. Plasma LH and FSH levels were significantly diminished in nDS-F1 implant-treated animals, confirming biological activity of the released testosterone. In conclusion, we demonstrate that nDS-F1 implants represents a novel approach for the treatment of male hypogonadism. Further studies will be performed in view of translating the technology to clinical use. © 2015 International Society for Sexual Medicine.

  13. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy.

    Science.gov (United States)

    Hsieh, Tung-Chin; Pastuszak, Alexander W; Hwang, Kathleen; Lipshultz, Larry I

    2013-02-01

    Testosterone replacement therapy results in decreased serum gonadotropins and intratesticular testosterone, and impairs spermatogenesis, leading to azoospermia in 40% of patients. However, intratesticular testosterone can be maintained during testosterone replacement therapy with co-administration of low dose human chorionic gonadotropin, which may support continued spermatogenesis in patients on testosterone replacement therapy. We retrospectively reviewed the records of hypogonadal men treated with testosterone replacement therapy and concomitant low dose human chorionic gonadotropin. Testosterone replacement consisted of daily topical gel or weekly intramuscular injection with intramuscular human chorionic gonadotropin (500 IU) every other day. Serum and free testosterone, estradiol, semen parameters and pregnancy rates were evaluated before and during therapy. A total of 26 men with a mean age of 35.9 years were included in the study. Mean followup was 6.2 months. Of the men 19 were treated with injectable testosterone and 7 were treated with transdermal gel. Mean serum hormone levels before vs during treatment were testosterone 207.2 vs 1,055.5 ng/dl (p testosterone 8.1 vs 20.4 pg/ml (p = 0.02) and estradiol 2.2 vs 3.7 pg/ml (p = 0.11). Pretreatment semen parameters were volume 2.9 ml, density 35.2 million per ml, motility 49.0% and forward progression 2.3. No differences in semen parameters were observed during greater than 1 year of followup. No impact on semen parameters was observed as a function of testosterone formulation. No patient became azoospermic during concomitant testosterone replacement and human chorionic gonadotropin therapy. Nine of 26 men contributed to pregnancy with the partner during followup. Low dose human chorionic gonadotropin appears to maintain semen parameters in hypogonadal men on testosterone replacement therapy. Concurrent testosterone replacement and human chorionic gonadotropin use may preserve fertility in hypogonadal males

  14. New Product Marketing Blurs the Line Between Nicotine Replacement Therapy and Smokeless Tobacco Products.

    Science.gov (United States)

    Kostygina, Ganna; England, Lucinda; Ling, Pamela

    2016-07-01

    Tobacco companies have begun to acquire pharmaceutical subsidiaries and recently started to market nicotine replacement therapies, such as Zonnic nicotine gum, in convenience stores. Conversely, tobacco companies are producing tobacco products such as tobacco chewing gum and lozenges that resemble pharmaceutical nicotine replacement products, including a nicotine pouch product that resembles snus pouches. This convergence of nicotine and tobacco product marketing has implications for regulation and tobacco cessation.

  15. Breast density changes associated with postmenopausal hormone replacement therapy

    DEFF Research Database (Denmark)

    Nielsen, Mads; Pettersen, Paola; Alexandersen, P

    2010-01-01

    Objective: The aim of this study was to assess the impact of oral hormone therapy (HT) on breast density in postmenopausal women and to compare the use of computer-based automated approaches for the assessment of breast density with reference to traditional methods. Methods: Low-dose oral estrogen...... (1 mg) continuously combined with drospirenone (2 mg) was administered to postmenopausal women for up to 2 years (26 treatment cycles, 28 d/cycle) in a randomized, placebo-controlled trial. This post hoc analysis assessed the changes in breast density measured from digitized images by two radiologist.......01) but not in the placebo group. Conclusions: HT for 2 years in postmenopausal women significantly increased radiologist-assessed breast density compared with placebo, in addition to significant changes in estrogen levels, markers of bone metabolism, and bone mineral density. Computer-automated techniques may be comparable...

  16. 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 explore the influence of age, gender, comorbidity and prescribed medication. METHODS: By individual-level linkage between nationwide administrative registries, the risk of fracture was compared between the group of patients receiving chronic dialysis treatment and patients receiving their first renal...... transplanted group: 1.82 (95% CI: 1.62-2.06)]. Prescribed diuretics, lipid-modifying agents and proton pump inhibitors also modulated the fracture risk. CONCLUSIONS: Patients on dialysis or living with a transplanted kidney have a significantly higher risk of fracture than the Danish background population...

  17. 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.

  18. Population pharmacokinetics of daptomycin in adult patients undergoing continuous renal replacement therapy.

    Science.gov (United States)

    Xu, Xiaoying; Khadzhynov, Dmytro; Peters, Harm; Chaves, Ricardo L; Hamed, Kamal; Levi, Micha; Corti, Natascia

    2017-03-01

    The objective of this population pharmacokinetic (PK) analysis was to provide guidance for the dosing interval of daptomycin in patients undergoing continuous renal replacement therapy (CRRT). A previously published population PK model for daptomycin was updated with data from patients undergoing continuous veno-venous haemodialysis (CVVHD; n = 9) and continuous veno-venous haemodiafiltration (CVVHDF; n = 8). Model-based simulations were performed to compare the 24 h AUC, Cmax and Cmin of daptomycin following various dosing regimens (4, 6, 8, 10, and 12 mg kg(-1) every [Q] 24 h and Q48 h), with the safety and efficacy exposure references for Staphylococcus aureus bacteraemia/right-sided infective endocarditis. The previously developed daptomycin structural population PK model could reasonably describe data from the patients on CRRT. The clearance in patients undergoing CVVHDF and CVVHD was estimated at 0.53 and 0.94 l h(-1) , respectively, as compared with 0.75 l h(-1) in patients with creatinine clearance (CrCl) ≥ 30 ml min(-1) . Daptomycin Q24 h dosing in patients undergoing CRRT resulted in optimal exposure for efficacy, with AUC comparable to that in patients with CrCl ≥ 30 ml min(-1) . In contrast, Q48 h dosing was associated with considerably lower AUC24-48h in all patients for doses up to 12 mg kg(-1) and is therefore inappropriate. Q24 h dosing of daptomycin up to 12 mg kg(-1) provides comparable drug exposure in patients on CVVHD and in those with CrCl ≥ 30 ml min(-1) . Daily daptomycin use up to 8 mg kg(-1) doses are appropriate for patients on CVVHDF, but higher doses may increase the risk of toxicity. © 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  19. The Impact of Renal Failure and Renal Replacement Therapy on Outcome During Extracorporeal Membrane Oxygenation Therapy.

    Science.gov (United States)

    Antonucci, Elio; Lamanna, Irene; Fagnoul, David; Vincent, Jean-Louis; De Backer, Daniel; Silvio Taccone, Fabio

    2016-08-01

    Acute kidney injury (AKI) is common in patients treated with veno-arterial (VA-) or veno-venous (VV-) extracorporeal membrane oxygenation (ECMO). In this setting, the use of continuous renal replacement therapy (CRRT) can help to optimize fluid status but may also negatively impact on patients' outcome. In contrast, the relationship between AKI, CRRT, and survival in critically ill adult patients receiving ECMO is not well defined. The institutional ECMO database (n = 162) from November 2008 to December 2013, excluding patients with ICU survival ECMO and 56 with VV-ECMO). Of these, 95 developed AKI, 63 (47%) of whom required CRRT; thus three groups of patients were identified: (a) no AKI; (b) AKI without CRRT (AKINOCRRT ); and (c) CRRT with AKI (AKICRRT ). AKINOCCRT patients were more likely to have preexisting heart disease, to be more severely ill, and to be treated with VA-ECMO than those without AKI. AKICRRT patients were also more likely to be treated with VA-ECMO, had more organ dysfunction at the time of ECMO insertion, and needed more transfusions and inotropic agents than patients without AKI. ICU mortality was 53% (72/135) and was similar in the three groups, even when different AKI stages or VA/VV-ECMO were analyzed separately. In this study, the use of CRRT was not associated with an increased mortality in an adult population of patients treated with ECMO, even after adjustment for confounders.

  20. Surfactant replacement therapy for preterm and term neonates with respiratory distress.

    Science.gov (United States)

    Polin, Richard A; Carlo, Waldemar A

    2014-01-01

    Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in preterm infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This statement summarizes the evidence regarding indications, administration, formulations, and outcomes for surfactant-replacement therapy. The clinical strategy of intubation, surfactant administration, and extubation to continuous positive airway pressure and the effect of continuous positive airway pressure on outcomes and surfactant use in preterm infants are also reviewed.

  1. [A new regimen for TS-1 therapy designed to minimize adverse reactions by introducing a one-week interval after each two-week dosing session].

    Science.gov (United States)

    Kimura, Yutaka; Kikkawa, Nobuteru; Iijima, Shohei; Kato, Takeshi; Naoi, Yasuto; Hayashi, Taro; Tanigawa, Takahiko; Yamamoto, Hitoshi; Kurokawa, Eiji

    2002-08-01

    It has been reported that the response rate to TS-1 of advanced recurrent gastric cancer was the highest rate (46.5%) of effectiveness among anti-cancer agents, but the incidence of adverse reactions to this drug has been found to be as high as 83.2%, with grade 3 or severer reactions occurring in 20.3% of patients. Taking into consideration the post-marketing survey finding that adverse reactions to the drug first appear 2-3 weeks after the start of oral TS-1 therapy, we attempted a new dosing regimen for this drug, wherein each session of therapy lasted for 2 weeks, with a one-week interval between two consecutive sessions (herein-after called "the 2-week regimen"). This regimen was employed based on the expectation that the adverse reactions to the drug would be minimized and that the consecutive dosing period could be prolonged, while keeping the anti-cancer potency at a level similar to that expected with the 4-week dosing regimen with a 2-week interval between sessions (the 4-week regimen). The subjects were 38 patients with advanced or recurrent stomach cancer who were treated with TS-1 at our center between September 1999 and November 2001. Twenty-four patients treated using the 4-week method until January 2001 were taken as a historical control, and compared with 14 patients treated using the 2-week method from February 2001 and afterwards. The incidence of adverse reactions was 71% in the 2-week regimen group against 92% in the 4-week regimen group. The incidence of grade 3 or severe adverse reactions was 8% in the 2-week group and 21% in the 4-week group. Thus, the incidence of adverse reactions was lower in the 2-week group. The percentage of patients who complied with the dosing instructions completely during a 6-month period, as evaluated by the Kaplan-Meier method, was 86% in the 2-week group and 58% in the 4-week group. The response rate, as calculated in patients whose lesions could be evaluated, was 25% in the 2-week group and 19% in the 4-week

  2. Weekly TP regimen versus tri-weekly TP regimen therapy in concurrent chemoradiotherapy for esophageal cancer%食管癌同期放化疗TP方案周疗与三周疗法对照研究

    Institute of Scientific and Technical Information of China (English)

    刘锐; 蒙渡

    2013-01-01

    Objective To contrast short-term efficacy and toxicity in concurrent chemoradiotherapy for advanced esophageal cancer with weekly TP regimen and Tri-weekly TP regimen therapy.Methods 56 patients with advanced esophageal cancer were randomly assigned into either the first group accepted weekly TP regimen (28cases) or the second group accepted tri-weekly TP regimen therapy (28cases) and the data were analyzed using software SPSS 17.Both groups accepted Intensity modulated radiation therapy (IMRT) ; the total dose of IMRT was 59.4 Gy.The Former group was treated with paclitaxel 40mg/m2 and cisplatin 25mg/m2 once per week,and the treatment lasted for 6 weeks.The latter group was treated with paclitaxel 135 mg/m2,d1,and cisplatin 25mg/m2,d2.3.4,the treatment was recycled every 21days and last for 2 cycles.Results For short-term efficacy,remission rate (CR+PR) of the first group and the second group were 89.3% and 96%,there was no significant statistic difference (P>0.05).For toxicity,gastrointestinal reactions,leucopenia and neurotoxicity of the second group were apparently higher than the first group; the P value was 0.01,0.03,0 for gastrointestinal reactions leucopenia and neurotoxicity,there was significant statistic difference.Conclusion There is no significant difference in short-term efficacy between weekly TP regimen and triweekly TP regimen therapy in concurrent chemoradiotherapy for advanced esophageal? cancer,weekly TP regimen has a significantly lower toxicity.The long-term efficacy remains to be seen.%目的 探讨中晚期食管癌同步放化疗TP方案周疗与3周疗法的近期疗效及毒副反应.方法 56例中晚期食管癌患者,进行前瞻性数字法随机分成周方案组和3周方案组各28例.两组均采用三维适形调强放疗,总剂量59.4Gy.周方案组:紫杉醇40mg/m2,顺铂25mg/m2,1次/周,连用6周;3周方案组:紫杉醇135mg/m2,第1天,顺铂25mg/m2,第2~4天.21天为1个周期,共2周期.治疗结

  3. Adrenal insufficiency and adrenal replacement therapy. Current status in Spain.

    Science.gov (United States)

    Aulinas, Anna; Casanueva, Felipe; Goñi, Fernando; Monereo, Susana; Moreno, Basilio; Picó, Antonio; Puig-Domingo, Manel; Salvador, Javier; Tinahones, Francisco J; Webb, Susan M

    2013-03-01

    Adrenal insufficiency (AI) is a rare endocrine disease, associated to increased mortality if left untreated. It can be due to a primary failure of the adrenal glands (primary AI) or malfunctioning of the hypothalamic-pituitary-adrenal axis (HPA) (secondary AI). The lack of data on incidence/prevalence of adrenal insufficiency in Spain complicates any evaluation of the magnitude of the problem in our country. Initial symptoms are non-specific, so often there is a delay in diagnosis. Current therapy with available glucocorticoids is associated with decreased quality of life in patients with treated AI, as well as with increased mortality and morbidity, probably related to both over-treatment and lack of hydrocortisone, associated with non-physiological peaks and troughs of the drug over the 24 hours. The availability of a new drug with a modified dual release (immediate and retarded), that requires one only daily dose, improves and simplifies the treatment, increases compliance as well as quality of life, morbidity and possibly mortality. This revision deals with the knowledge on the situation both globally and in Spain, prior to the availability of this new drug.

  4. Efficacy of continuous renal replacement therapy on patients with severe pulmonary infection

    Institute of Scientific and Technical Information of China (English)

    Ji-Feng Wang; Wen-Qiang Li; Peng Xu; Xiao-Yun Liu; Wen-Li Ji

    2016-01-01

    Objective:To analyze the efficacy of continuous renal replacement therapy on patients with severe pulmonary infection. Method:A total of 50 patients with severe pulmonary infection in our hospital from May 2014 to May 2015 were selected and were given continuous renal replacement therapy. Clinical symptoms, acute physiology and chronic health evaluation(APACHE)Ⅱ, blood routine and blood gas indexes, renal function (urea, creatinine, uric acid) and electrolyte (blood potassium, blood sodium) changes and success rate of treatment were observed and analyzed before and after treatment. Results:After continuous renal replacement therapy, dyspnea was significantly relieved for 47 cases of patients. Temperature was decreased accordingly. After treatment, electrolyte, APACHEⅡand renal function of patients were significantly improved (P<0.01);blood routine and blood gas indexes were signiicantly improved (P<0.01). Successful cases:36;death cases:14. Conclusions:continuous renal replacement therapy had better efficacy and could effectively improve the electrolyte, APACHEⅡand renal function for patients with severe pulmonary infection, which is an effective kind of adjuvant therapy.

  5. 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.

  6. The treatment of hemophilia A: from protein replacement to AAV-mediated gene therapy.

    Science.gov (United States)

    Youjin, Shen; Jun, Yin

    2009-03-01

    Factor VIII (FVIII) is an essential component in blood coagulation, a deficiency of which causes the serious bleeding disorder hemophilia A. Recently, with the development of purification level and recombinant techniques, protein replacement treatment to hemophiliacs is relatively safe and can prolong their life expectancy. However, because of the possibility of unknown contaminants in plasma-derived FVIII and recombinant FVIII, and high cost for hemophiliacs to use these products, gene therapy for hemophilia A is an attractive alternative to protein replacement therapy. Thus far, the adeno-associated virus (AAV) is a promising vector for gene therapy. Further improvement of the virus for clinical application depends on better understanding of the molecular structure and fate of the vector genome. It is likely that hemophilia will be the first genetic disease to be cured by somatic cell gene therapy.

  7. Ductal carcinoma In-Situ in turner syndrome patient undergoing hormone replacement therapy: A case report

    Directory of Open Access Journals (Sweden)

    Rashmi Bawa

    2016-03-01

    Full Text Available Turner’s syndrome is a rare congenital disease which affects about 1 in every 2500-3000 live-born females. This happens due to chromosomal abnormalities in a phenotypic female, causing increased gonadotropin concentrations and low concentrations of estrogens from infancy. As a result, hormone replacement therapy is started in most adolescent Turner syndrome patients to initiate and sustain sexual maturation. Accordingly, most Turner’s syndrome patients undergo several decades of estrogen replacement therapy, from puberty to post-menopausal age. The highly publicized findings of the Women’s Health Initiative have called into question the appropriateness of hormone replacement therapy in adolescents with Turner’s syndrome. Those concerns were mostly theoretical extrapolations, as few prospective studies of cancer occurrence in women with Turner syndrome have been reported. Consequently, several recent publications have challenged those extrapolations, based on the assertion that the levels of hormone replacement in Turner syndrome patients are well below the physiologic levels observed in normal menstruating women, as well as the fact that these women are significantly younger than those studied by the Women’s Health Initiative. In discord to those reports, we present a case of ductal carcinoma in-situ in a 40-year-old Turner patient, who had undergone over two decades of combined hormone replacement therapy. The patient underwent an elective excisional biopsy for a palpable mass, with histopathology revealing a complex fibroadenoma with a nidus of ductal carcinoma in-situ. The lesion was noted to be estrogen receptor positive and progesterone receptor negative, with heavy staining for HER-2/Neu receptor. The patient was treated with tamoxifen. While a rare case, it is imperative for the astute clinician to keep in mind the consequences of long-term hormone replacement therapy in Turner’s syndrome patients in order to avoid missed

  8. 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.

  9. Measuring biomarkers of acute kidney injury during renal replacement therapy: wisdom or folly?

    Science.gov (United States)

    Ostermann, Marlies; Forni, Lui G

    2014-06-19

    Early data are now appearing relating to the measurement of biomarkers of acute kidney injury during renal replacement therapy. These data go some way in describing the clearance of these molecules during renal support. Understanding the potential clearance, or otherwise, of these proteins may lead to directing our therapies in the future particularly with regard to cessation of renal support. We describe a recent study which has provided data that may aid in addressing this issue.

  10. Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

    Science.gov (United States)

    Case, Laura E; Koeberl, Dwight D; Young, Sarah P; Bali, Deeksha; DeArmey, Stephanie M; Mackey, Joanne; Kishnani, Priya S

    2008-12-01

    Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those with advanced disease. We report a case of a 63-year-old patient with significant morbidity who made notable motor and pulmonary function gains after two years on therapy. Thus, improvements in those with advanced disease may be possible after long-term treatment.

  11. 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(...... features describing the local elongatedness or stripiness, especially trained to see the effect of HRT (Hormone Replacement Therapy ) thereby providing a non-subjective and reproducible measure and compare it to the BIRADS and percentage density measure....

  12. Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy

    OpenAIRE

    Ulldemolins, Marta; Vaquer, Sergi; Llauradó-Serra, Mireia; Pontes, Caridad; Calvo, Gonzalo; Soy, Dolors; Martín-Loeches, Ignacio

    2014-01-01

    Although early and appropriate antibiotic therapy remains the most important intervention for successful treatment of septic shock, data guiding optimization of beta-lactam prescription in critically ill patients prescribed with continuous renal replacement therapy (CRRT) are still limited. Being small hydrophilic molecules, beta-lactams are likely to be cleared by CRRT to a significant extent. As a result, additional variability may be introduced to the per se variable antibiotic concentrati...

  13. Renal histology before and after effective enzyme replacement therapy in a patient with classical Fabry's disease.

    Science.gov (United States)

    Hirashio, S; Taguchi, T; Naito, T; Maki, K; Ogata, S; Taniyama, K; Taniguchi, Y; Yorioka, N

    2009-05-01

    A 38-year-old man underwent renal biopsy because of proteinuria. It revealed swelling and vacuolation of glomerular epithelial cells, as well as myelin-like structures characteristic of Fabry's disease. Detection of decreased plasma activity of alpha-galactosidase A confirmed the diagnosis. Enzyme replacement therapy was provided with recombinant agalsidase-beta, resulting in improvement of his symptoms. When renal biopsy was repeated, specific staining for globotriaosylceramide showed that renal deposits were decreased by enzyme therapy.

  14. 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

  15. 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

    DEFF Research Database (Denmark)

    Schallig, Henk D. F. H.; Tinto, Halidou; Sawa, Patrick

    2017-01-01

    Background 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...... whether prolonged ACT-based regimens using currently available formulations can eliminate potentially resistant parasites. The protocol investigates whether a sequential course of two licensed ACT in 1080 children aged 6–120 months exhibits superior efficacy against acute P. falciparum malaria and non...... gametocytaemia, occurrence of treatment-related adverse events in the double-ACT versus single-ACT arms, carriage of molecular markers of drug resistance, drug kinetics and patient adherence to treatment. Discussion This protocol addresses efficacy and safety of sequential ACT regimens in P. falciparum malaria...

  16. Effect of Hormone Replacement Therapy on Serum Complement (C3,C4) and Immunoglobulin (IgG, IgM) Levels in Post-menopausal Women

    Institute of Scientific and Technical Information of China (English)

    Yi LIU; Liqun LV

    2008-01-01

    Serum C3, C4, IgG and IgM levels were evaluated in healthy post-menopausal women receiving short-term hormone replacement therapy (HRT) regimens and in untreated women. Serum C3, C4, IgM and IgG levels were assessed in 54 women receiving HRT therapy (CEE 0.625 mg+MPA 2.5 mg/day), and in 54 control women not receiving HRT. The results showed that the mean serum C3 and C4 levels were significantly higher in women receiving HRT than those untreated women (P<0.01). There was significant difference in lgG and IgM levels between two groups. It was con-cluded that HRT might be involved in the development of cardiovascular diseases through inflamma- tory mechanisms, as suggested by increased serum levels of C3 and C4.

  17. 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, double-blin

  18. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy

    NARCIS (Netherlands)

    Royakkers, A.A.N.M.; Korevaar, J.C.; van Suijlen, J.D.E.; Hofstra, L.S.; Kuiper, M.A.; Spronk, P.E.; Schultz, M.J.; Bouman, C.S.C.

    2011-01-01

    To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Multicenter prospective observational cohort stu

  19. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy.

    NARCIS (Netherlands)

    Royakkers, A.A.N.M.; Korevaar, J.C.; Suijlen, J.D.E. van; Hofstra, L.S.; Kuiper, M.A.; Spronk, P.E.; Schultz, M.J.; Bouman, C.S.C.

    2011-01-01

    Purpose : To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Methods: Multicenter prospective obser

  20. 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

  1. Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe

    DEFF Research Database (Denmark)

    Spithoven, Edwin M; Kramer, Anneke; Meijer, Esther

    2014-01-01

    BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common renal disease requiring renal replacement therapy (RRT). Still, there are few epidemiological data on the prevalence of, and survival on RRT for ADPKD. METHODS: This study used data from the ERA-EDTA Registry...

  2. Demographics of blood pressure and hypertension in children on renal replacement therapy in Europe

    NARCIS (Netherlands)

    A.M. Kramer; K.J. van Stralen; K.J. Jager; F. Schaefer; E. Verrina; T. Seeman; M.A. Lewis; M. Boehm; G.D. Simonetti; G. Novljan; J.W. Groothoff

    2011-01-01

    Hypertension is a well-known complication in children on renal replacement therapy and an important risk factor for cardiovascular disease in later life. In order to define the prevalence of and risk factors for hypertension among children, we enrolled 3337 pediatric patients from 15 countries in th

  3. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women

    DEFF Research Database (Denmark)

    Mosekilde, Leif; Beck-Nielsen, H.; Sørensen, O.H.

    2000-01-01

    OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual...... and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention....

  4. Use of postmenopausal hormone replacement therapy and risk of non-Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Nørgaard, M; Poulsen, A H; Pedersen, L;

    2006-01-01

    Use of postmenopausal hormone replacement therapy (HRT) has been hypothesised to be associated with a reduced risk of non-Hodgkin's lymphoma (NHL), but the epidemiologic evidence is conflicting. To examine the risk of NHL in HRT users aged 40 and older, we conducted a cohort study in the County...

  5. The validity of self-reported use of hormone replacement therapy among Danish nurses

    DEFF Research Database (Denmark)

    Løkkegaard, Ellen Christine Leth; Johnsen, Søren Påske; Heitmann, Berit Lillienthal

    2004-01-01

    Recent findings from randomized clinical trials on the effects of hormone replacement therapy (HRT) among postmenopausal women contradict findings from observational studies indicating a protective effect on the development of cardiovascular disease. Most observational studies on HRT are based...... on self-reported data, although data on the validity of HRT in postmenopausal women are sparse....

  6. Outcomes of male patients with Alport syndrome undergoing renal replacement therapy

    DEFF Research Database (Denmark)

    Temme, Johanna; Kramer, Anneke; Jager, Kitty J;

    2012-01-01

    Patients with the hereditary disease Alport syndrome commonly require renal replacement therapy (RRT) in the second or third decade of life. This study compared age at onset of RRT, renal allograft, and patient survival in men with Alport syndrome receiving various forms of RRT (peritoneal dialys...

  7. Insights about serum sodium behavior after 24 hours of continuous renal replacement therapy

    Science.gov (United States)

    Romano, Thiago Gomes; Martins, Cassia Pimenta Barufi; Mendes, Pedro Vitale; Besen, Bruno Adler Maccagnan Pinheiro; Zampieri, Fernando Godinho; Park, Marcelo

    2016-01-01

    Objective The aim of this study was to investigate the clinical and laboratorial factors associated with serum sodium variation during continuous renal replacement therapy and to assess whether the perfect admixture formula could predict 24-hour sodium variation. Methods Thirty-six continuous renal replacement therapy sessions of 33 patients, in which the affluent prescription was unchanged during the first 24 hours, were retrieved from a prospective collected database and then analyzed. A mixed linear model was performed to investigate the factors associated with large serum sodium variations (≥ 8mEq/L), and a Bland-Altman plot was generated to assess the agreement between the predicted and observed variations. Results In continuous renal replacement therapy 24-hour sessions, SAPS 3 (p = 0.022) and baseline hypernatremia (p = 0.023) were statistically significant predictors of serum sodium variations ≥ 8mEq/L in univariate analysis, but only hypernatremia demonstrated an independent association (β = 0.429, p < 0.001). The perfect admixture formula for sodium prediction at 24 hours demonstrated poor agreement with the observed values. Conclusions Hypernatremia at the time of continuous renal replacement therapy initiation is an important factor associated with clinically significant serum sodium variation. The use of 4% citrate or acid citrate dextrose - formula A 2.2% as anticoagulants was not associated with higher serum sodium variations. A mathematical prediction for the serum sodium concentration after 24 hours was not feasible. PMID:27410407

  8. Incidence of renal replacement therapy for diabetic nephropathy in the Netherlands: Dutch diabetes estimates (DUDE)-3

    NARCIS (Netherlands)

    Dijk, P.R. van; Kramer, A.; Logtenberg, S.J.; Hoitsma, A.J.; Kleefstra, N.; Jager, K.J.; Bilo, H.J.G.

    2015-01-01

    OBJECTIVES: Describe the incidence, prevalence and survival of patients needing renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetes mellitus (DM)-related glomerulosclerosis or nephropathy (diabetic nephropathy, DN) in the Netherlands. DESIGN: Using the national registr

  9. Incidence of renal replacement therapy for diabetic nephropathy in the Netherlands : Dutch diabetes estimates (DUDE)-3

    NARCIS (Netherlands)

    van Dijk, Peter R.; Kramer, Anneke; Logtenberg, Susan J. J.; Hoitsma, Andries J.; Kleefstra, Nanne; Jager, Kitty J.; Bilo, Henk J. G.

    2015-01-01

    Objectives: Describe the incidence, prevalence and survival of patients needing renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetes mellitus (DM)-related glomerulosclerosis or nephropathy (diabetic nephropathy, DN) in the Netherlands. Design: Using the national registr

  10. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy.

    NARCIS (Netherlands)

    Royakkers, A.A.N.M.; Korevaar, J.C.; Suijlen, J.D.E. van; Hofstra, L.S.; Kuiper, M.A.; Spronk, P.E.; Schultz, M.J.; Bouman, C.S.C.

    2011-01-01

    Purpose : To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Methods: Multicenter prospective obser

  11. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy

    NARCIS (Netherlands)

    Royakkers, A.A.N.M.; Korevaar, J.C.; van Suijlen, J.D.E.; Hofstra, L.S.; Kuiper, M.A.; Spronk, P.E.; Schultz, M.J.; Bouman, C.S.C.

    2011-01-01

    To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Multicenter prospective observational cohort stu

  12. The Miracle Drug : Hormone Replacement Therapy and Labor Market Behavior of Middle-Aged Women

    NARCIS (Netherlands)

    Meltem Daysal, N.; Orsini, C.

    2012-01-01

    Abstract: In an aging society, determining which factors contribute to the employment of older individuals is increasingly important. This paper sheds light on the impact of medical innovation in the form of Hormone Replacement Therapy (HRT) on employment of middle-aged women. HRT are drugs taken by

  13. 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,

  14. 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

  15. [Continuous veno-venous renal replacement therapies in critically ill neonates and children].

    Science.gov (United States)

    López-Herce Cid, J; Carrillo Alvarez, A; Panadero Carlavilla, E; Sánchez Sánchez, C; Moral Torrero, R; Bustinza Arriourtúa, A

    1998-07-01

    The objective of this study was to analyze the efficacy of continuous veno-venous renal replacement therapies in neonates and children. We analyzed 10 episodes of acute renal failure in 9 patients, between 7 days and 2 years of age and weighing between 2.9 and 13 kg, treated with continuous veno-venous renal replacement therapies (hemofiltration or hemodiafiltration) by using a BSM-32-IC (Hospal) monitor and two types of hemofilters, Miniflow of 0.04 m2 (Hospal) and FH22 of 0.2 m2 (Gambro). We used a blood flow between 15 and 40 ml/min and obtained an ultrafiltration rate of 190 +/- 61 ml/hour. The mean life of the hemofilters was 16 +/- 14 hours, with the duration of the technique between 5 and 58 hours. In three episodes the technique was ended because of normalization of renal function. All patients tolerated continuous renal replacement therapies without important secondary effects (one patient had moderate ischemia of the leg because of erroneous arterial catheterization, 3 patients had electrolyte alterations. 1 patient had hypothermia and 5 patients needed platelet transfusions). Seven patients died because of shock and multiple organ failure which was not related to the technique. Continuous veno-venous renal replacement therapies are useful in the treatment of critically ill children. Veno-venous techniques can be used in term neonate and infants.

  16. [The impact of continuous renal replacement therapy training on nursing competence].

    Science.gov (United States)

    Voltzenlogel, Sabine

    2015-06-01

    Specific training adapted to the needs of caregivers in intensive care enables professional competence and quality of care to be developed in continuous renal replacement therapy. In addition, it contributes to reducing the stress felt by caregivers and the costs of this technique. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. Regional and social inequalities in chronic renal replacement therapy in Denmark

    DEFF Research Database (Denmark)

    Hommel, Kristine; Rasmussen, Soren; Kamper, Anne-Lise

    2010-01-01

    Background. The incidence of chronic renal replacement therapy (RRT) varies markedly between Danish nephrology centres. The aim of the present study was to establish if there is regional and social variation in the incidence of chronic RRT in Denmark when analysed according to patient residence...

  18. 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....

  19. Incidence of renal replacement therapy for diabetic nephropathy in the Netherlands: Dutch diabetes estimates (DUDE)-3

    NARCIS (Netherlands)

    Dijk, P.R. van; Kramer, A.; Logtenberg, S.J.; Hoitsma, A.J.; Kleefstra, N.; Jager, K.J.; Bilo, H.J.G.

    2015-01-01

    OBJECTIVES: Describe the incidence, prevalence and survival of patients needing renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetes mellitus (DM)-related glomerulosclerosis or nephropathy (diabetic nephropathy, DN) in the Netherlands. DESIGN: Using the national

  20. 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...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides...

  1. Human protein C: new preparations. Effective replacement therapy for some clotting disorders.

    Science.gov (United States)

    2003-02-01

    (1) Depending on its severity, congenital protein C deficiency can cause a variety of problems, such as increasing the frequency of venous thrombosis in high risk situations; recurrent venous thrombosis; skin necrosis at the start of treatment with a vitamin K antagonist; and severe thrombotic events in neonates. For many years the only available replacement treatment consisted of fresh frozen plasma which, among other adverse effects, carries a risk of hypervolemia. (2) Two human protein C concentrates prepared from donated blood have been given marketing authorisation in Europe for intravenous replacement therapy (Ceprotin from Baxter, and Protexel from LFB). (3) Their clinical files contain only retrospective case series (22 children with severe deficiency treated with Ceprotin; and 10 patients of various ages and with different degrees of severity treated with Protexel). The two preparations have not been compared with each other. (4) In patients with severe protein C deficiency, including neonates, replacement therapy with human protein C is effective, especially for treating cutaneous thrombosis and preventing thrombosis in high risk situations. (5) In patients with moderate deficiency, a short-course of human protein C prophylaxis reduces the frequency of thrombosis in high risk situations. (6) In long-term prophylaxis, human protein C replacement therapy, added to ongoing (but inadequately effective) vitamin K antagonist therapy, seems to reduce the risk of recurrent venous thrombosis even though it has some constraints. (7) The adverse effects of the two preparations are poorly documented. Allergic reactions and bleeding have been reported. Human protein C is a blood product, and therefore carries a risk of infection. (8) Ceprotin offers a small advantage, being available in two dose strengths: for a given dose the volume injected is halved. (9) In practice, Ceprotin and Protexel are the reference drugs for replacement therapy of constitutional protein C

  2. The Relationship Between Testosterone-Replacement Therapy and Lower Urinary Tract Symptoms: A Systematic Review.

    Science.gov (United States)

    Kathrins, Martin; Doersch, Karen; Nimeh, Tony; Canto, Arturo; Niederberger, Craig; Seftel, Allen

    2016-02-01

    To systematically review prospective trials evaluating the clinical effects of testosterone-replacement therapy on lower urinary tract symptoms and prostate volume. We performed a literature review through PubMed, Embase, and Cochrane Library from 1994 to 2015 for prospective trials of hypogonadal men with benign prostatic hyperplasia or lower urinary tract symptoms treated with testosterone-replacement therapy. We evaluated the abstracts for outcomes related to International Prostate Symptom Score, prostate volume, and urodynamic parameters. An original cohort of 3079 abstracts was reviewed. Thirty-five trials were selected for inclusion. The majority of trials reviewed found no significant prostate growth due to testosterone-replacement therapy. Studies of men with baseline mild lower urinary tract symptoms demonstrated either no change or an improvement in symptoms after treatment. There was a lack of relevant urodynamic studies. Trials of men with the metabolic syndrome demonstrated uniform improvement in lower urinary tract symptoms. Forty-six percent of all the trials identified included exclusion criteria for baseline severe-range lower urinary tract symptoms or other signs of obstructive lower urinary tract symptoms. The current literature demonstrates scant support for a causative relationship between testosterone-replacement therapy, de novo or worsening lower urinary tract symptoms, and prostate volume. Furthermore, our review found an absence of high quality evidence that would support guideline recommendations that testosterone-replacement therapy is relatively contraindicated in men with severe-range lower urinary tract symptoms. Future clinical trials with more inclusive voiding criteria are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease.

    Science.gov (United States)

    Oder, Daniel; Nordbeck, Peter; Wanner, Christoph

    2016-01-01

    Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies. Early ERT treatment at young age, a personalized approach, and adjunctive therapies for specific disease manifestations appear to impact on prognosis and are currently favored with the expectance of more effective intravenous and oral treatments in the short future.

  4. Adherence to Antiretroviral Therapy (ART) in Yaoundé-Cameroon: Association with Opportunistic Infections, Depression, ART Regimen and Side Effects

    Science.gov (United States)

    Fonsah, Julius Y.; Njamnshi, Alfred K.; Kouanfack, Charles; Qiu, Fang; Njamnshi, Dora M.; Tagny, Claude T.; Nchindap, Emilienne; Kenmogne, Léopoldine; Mbanya, Dora; Heaton, Robert; Kanmogne, Georgette D.

    2017-01-01

    Following global efforts to increase antiretroviral therapy (ART) access in Sub-Saharan Africa, ART coverage among HIV-infected Cameroonians increased from 0% in 2003 to 22% in 2014. However, the success of current HIV treatment programs depends not only on access to ART, but also on retention in care and good treatment adherence. This is necessary to achieve viral suppression, prevent virologic failure, and reduce viral transmission and HIV/AIDS-related deaths. Previous studies in Cameroon showed poor adherence, treatment interruption, and loss to follow-up among HIV+ subjects on ART, but the factors that influence ART adherence are not well known. In the current cross-sectional study, patient/self-reported questionnaires and pharmacy medication refill data were used to quantify ART adherence and determine the factors associated with increased risk of non-adherence among HIV-infected Cameroonians. We demonstrated that drug side-effects, low CD4 cell counts and higher viral loads are associated with increased risk of non-adherence, and compared to females, males were more likely to forego ART because of side effects (p40 years) were less likely to be non-adherent (p<0.01) and had shorter non-adherent periods (p<0.0001). The presence of depression symptoms correlated with non-adherence to ART during antibiotic treatment (r = 0.53, p = 0.04), and was associated with lower CD4 cell counts (p = 0.04) and longer non-adherent periods (p = 0.04). Change in ART regimen was significantly associated with increased likelihood of non-adherence and increased duration of the non-adherence period. Addressing these underlying risk factors could improve ART adherence, retention in care and treatment outcomes for HIV/AIDS patients in Cameroon. PMID:28141867

  5. 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....

  6. Utility of the novel bladder preservation therapy, BOAI-CDDP-radiation (OMC-regimen), for elderly patients with invasive bladder cancer.

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Ibuki, Naokazu; Ubai, Takanobu; Kotake, Yatsugu; Takahara, Kiyoshi; Kiyama, Satoshi; Nomi, Hayahito; Uehara, Hiroshi; Komura, Kazumasa; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Katsuoka, Yoji

    2011-01-01

    In this study, we investigated the novel bladder preservation therapy, the balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, concomitantly with hemodialysis, along with concurrent irradiation [the 'Osaka Medical College (OMC)-regimen'] in patients >70 years of age with muscle-invasive bladder cancer. Eighty-three such patients were assigned to receive either the OMC-regimen (n=56) or cystectomy (n=27). The OMC-regimen patients who failed to achieve complete response (CR) underwent cystectomy, or secondary BOAI with gemcitabine (1600 mg). The OMC-regimen, which delivers an extremely high concentration of anti-cancer agent to the tumor site without systemic adverse effects, yielded CR in >90% (39/43) of patients with locally invasive tumors [70% (39/56) of all patients including those with T4 and N+ disease]. None of the CR patients showed recurrence after a mean follow-up of 162 (range, 35-683) weeks, and 2 patients died of unrelated causes. The 5- and 12-year overall survival rates were 92.7 and 69.5% (vs. 59.6 and 20.9% for cystectomy; POMC-regimen group was significantly greater than that in the cystectomy group (median, 77; range, 70-98; vs. 74; 70-79; pOMC-regimen is a useful bladder preservation strategy for elderly patients with locally invasive bladder cancer, not only for those for whom cystectomy has been indicated, but also for patients whose condition is not amenable to curative treatment and for whom palliation would otherwise seem the only option.

  7. Estrogen replacement therapy among postmenopausal women and its effects on signs and symptoms of temporomandibular disorders.

    Science.gov (United States)

    Nekora-Azak, Aysen; Evlioglu, Gulumser; Ceyhan, Arzu; Keskin, Haluk; Berkman, Sinan; Issever, Halim

    2008-07-01

    The prevalence of temporomandibular disorders (TMD) is about two to five times higher in females than in males. Data for the higher prevalence of TMD in women and prevalence rates peak during the reproductive years and decrease after menopause. This indicated that female sex hormones may play a role in the etiology or maintenance of TMD. The aim of this study was to investigate the relationship between postmenopausal hormone use and TMD in Turkish postmenopausal women. One hundred-eighty (180), postmenopausal women, aged 42-72 years, were examined both clinically and by questionnaire with regard to the signs and symptoms of temporomandibular disorders, general health status and use of postmenopausal hormone replacement therapy in the preceding year. Ninety-one (91) postmenopausal women (50.6%) were on hormone replacement therapy (HRT). The remaining 89 (49.4%) postmenopausal women were not on hormone replacement therapy. There was no significant difference found in the signs and symptoms of TMD between postmenopausal women using hormone therapy and those not using postmenopausal hormones. There was no association between the use of postmenopausal hormones and the signs and symptoms of TMD in this study.

  8. Hepatic adenomatosis associated with hormone replacement therapy and hemosiderosis: A case report

    Institute of Scientific and Technical Information of China (English)

    Satoshi Hagiwara; Hiroyuki Kuwano; Masatomo Mori; Hitoshi Takagi; Daisuke Kanda; Naondo Sohara; Satoru Kakizaki; Kenji Katakai; Teruo Yoshinaga; Tsugio Higuchi; Kenichi Nomoto

    2006-01-01

    We have reported a case of hepatic adenomatosis associated with hormone replacement therapy (estrogen and progesterone) and hemosiderosis caused by excessive blood transfusion for the treatment of chronic myeloid leukemia. A 34-year-old woman was found to have several hepatic tumors on a routine medical examination. The general condition was good.Laboratory studies showed iron overload. Abdominal computed tomography and selective hepatic angiography showed several hypervascular tumors in the right lobe of the liver (up to 20 mm in diameter). Since hepatocellular carcinoma could not be ruled out, subsegmental hepatectomy was performed. Histopathological examination of the surgical specimen showed hepatic adenomatosis with hemosiderosis. Both hormone replacement therapy and iron overload could be the cause of hepatic adenomatosis.

  9. Use and discontinuation of hormone replacement therapy in women with myocardial infarction: a nationwide study

    DEFF Research Database (Denmark)

    Bretler, Ditte-Marie; Hansen, P. R.; Abildstrom, S. Z.

    2011-01-01

    center dot General use of hormone replacement therapy (HRT) dropped drastically after 2002 when pivotal randomized trials showed increased risk of coronary artery disease and other complications with HRT. center dot HRT is not recommended for primary or secondary prevention of coronary heart...... disease and guidelines recommend discontinuation of HRT after myocardial infarction (MI). center dot It is unknown whether women actually discontinue HRT after MI. WHAT THIS STUDY ADDS center dot Women who use HRT when they experience their MI generally continue using HRT. center dot We found a remarkably...... low increase in discontinuation after 2002, in contrast to the general drop in use of HRT. AIM To characterize the pattern of use and discontinuation of postmenopausal hormone replacement therapy (HRT) in women with myocardial infarction (MI) before and after 2002, where the general use of HRT dropped...

  10. Pharmacokinetics and antimicrobial dosing adjustment in critically ill patients during continuous renal replacement therapy.

    Science.gov (United States)

    Kuang, D; Verbine, A; Ronco, C

    2007-05-01

    Appropriate antimicrobial therapy poses one of the greatest challenges during the management of a septic patient in the intensive care unit (ICU). Acute renal failure (ARF) is a common complication of sepsis and often occurs as a component of multiple organ dysfunction syndrome. Continuous renal replacement therapy (CRRT) is increasingly used as an effective extracorporeal blood purification therapy in this critically ill patient population. Available data demonstrate that sepsis, ARF and different modalities of CRRT may have profound effects on the pharmacokinetics and pharmacodynamics of various antimicrobial agents used in the ICU. Guidelines for antimicrobial prescription which will fit the individual patient undergoing a particular method of treatment are still unavailable. Understanding the principles of drug removal by CRRT and pharmacokinetics of various agents can help to modify the drug dosage and dosing intervals for individualized therapy. Meanwhile, monitoring the drug serum concentration is still mandatory whenever clinically feasible.

  11. 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.

  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. Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review

    OpenAIRE

    Villa, Gianluca; Di Maggio, Paola; De Gaudio, A Raffaele; Novelli, Andrea; Antoniotti, Riccardo; Fiaccadori, Enrico; Adembri, Chiara

    2016-01-01

    Background 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. Method Citations published on PubMed up to January 2016 were systematica...

  14. Antimicrobial Doses in Continuous Renal Replacement Therapy: A Comparison of Dosing Strategies

    OpenAIRE

    Anna P. Kempke; Leino, Abbie S.; Farzad Daneshvar; John Andrew Lee; Mueller, Bruce A.

    2016-01-01

    Purpose. Drug dose recommendations are not well defined in patients undergoing continuous renal replacement therapy (CRRT) due to limited published data. Several guidelines and pharmacokinetic equations have been proposed as tools for CRRT drug dosing. Dose recommendations derived from these methods have yet to be compared or prospectively evaluated. Methods. A literature search of PubMed, Micromedex, and Embase was conducted for 40 drugs commonly used in the ICU to gather pharmacokinetic dat...

  15. Population pharmacokinetics of daptomycin in adult patients undergoing continuous renal replacement therapy

    OpenAIRE

    Xu, Xiaoying; Khadzhynov, Dmytro; Peters, Harm; Chaves, Ricardo L.; Hamed, Kamal; Levi, Micha; Corti, Natascia

    2016-01-01

    Aim The objective of this population pharmacokinetic (PK) analysis was to provide guidance for the dosing interval of daptomycin in patients undergoing continuous renal replacement therapy (CRRT). Methods A previously published population PK model for daptomycin was updated with data from patients undergoing continuous veno?venous haemodialysis (CVVHD; n?=?9) and continuous veno?venous haemodiafiltration (CVVHDF; n?=?8). Model?based simulations were performed to compare the 24?h AUC, C max an...

  16. Enzyme replacement therapy in type 1 Gaucher disease and a review of the literature

    Directory of Open Access Journals (Sweden)

    Gökhan Kabaçam

    2010-09-01

    Full Text Available Gaucher disease (GD is the most common lysosomal storage disorder. Deficiency of the lysosomal enzyme glucocerebrosidase results in the intracellular accumulation of undegraded substrates in the spleen, liver and bone marrow. Enzyme replacement therapy (ERT is a standard approach for type 1 GD. Here, we present an adult patient with hematological disorders due to type 1 GD, who markedly improved with ERT.

  17. ACD-A solution as anticoagulant during continuous renal replacement therapy in high risk bleeding patients

    Institute of Scientific and Technical Information of China (English)

    杨松涛

    2014-01-01

    Objective To assess the efficacy and safety of ACDA solution as anticoagulant during continuous renal replacement therapy(CRRT)in high risk of bleeding patients.Methods Forty high risk bleeding patients on continuous veno-venous hemofiltration(CVVH)were randomly divided into two groups:ACD-A group(22 patients,61 cases)and heparin-free group(18 patients,47cases).Serum creatinine,function of the coagulation

  18. The Miracle Drug : Hormone Replacement Therapy and Labor Market Behavior of Middle-Aged Women

    OpenAIRE

    Meltem Daysal, N.; Orsini, C.

    2012-01-01

    Abstract: In an aging society, determining which factors contribute to the employment of older individuals is increasingly important. This paper sheds light on the impact of medical innovation in the form of Hormone Replacement Therapy (HRT) on employment of middle-aged women. HRT are drugs taken by middle-aged women to soften symptoms related to menopause. Before 2002, HRT products were among the most popular prescription drugs in America. We use the timing of the release of information of t...

  19. femoral neck fracture during physical therapy following surface replacement arthroplasty: a preventable complication? A case report

    Directory of Open Access Journals (Sweden)

    Dayton Michael R

    2010-02-01

    Full Text Available Abstract This case report describes two cases of peri-prosthetic fracture during physical therapy in patients who underwent a hip resurfacing, or surface replacement arthroplasty. The fractures occurred with forceful passive combined flexion and external rotation. Functional results were ultimately obtained in both cases, requiring conversion to total hip arthroplasty. Recognizing patient risk factors and cautioning therapists about the possibility of fracture may have prevented these complications.

  20. Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial

    DEFF Research Database (Denmark)

    Yeni, P; Cooper, DA; Aboulker, J-P

    2006-01-01

    BACKGROUND: Antiretroviral therapy has greatly reduced HIV mortality and morbidity. However, the best sequence of regimens and implications of initial regimen for long-term therapeutic success are not well defined. METHODS: In INITIO, a large international randomised trial, we compared antiretrov...

  1. 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.

  2. Comparison of Ciprofloxacin-Based Triple Therapy with Conventional Triple Regimen for Helicobacter pylori Eradication in Children.

    Science.gov (United States)

    Farahmand, Fatemeh; Mohammadi, Tayebeh; Najafi, Mehri; Fallahi, Gholamhosein; Khodadad, Ahmad; Motamed, Farzaneh; Mahdi Marashi, Sayed; Shoaran, Maryam; Nabavizadeh Rafsanjani, Raheleh

    2016-06-01

    Helicobacter pylori infection is a prevalent disease among Iranian children. The purpose of this study was to compare the effect of ciprofloxacin and furazolidone on eradicating helicobacter pylori in Iranian children in combination with amoxicillin and omeprazole. In this cohort study, helicobacter pylori infection was confirmed by gastroscopy, rapid urease test or pathologic assessments. A total of 66 children were randomly enrolled; based on the random number table, and were divided into two groups; first, a combination regimen consisting of ciprofloxacin, amoxicillin, and omeprazole; second, a three-medication regimen consisting of amoxicillin, furazolidone, and omeprazole. The effect of both medical regimens on the successful eradication of helicobacter pylori infection was assessed and compared. Chi-square test was used for evaluating the association between quantitative variables. All comparisons were made at the significance of Phelicobacter pylori infection was reported 87.9% (29/33) in the first group (CAO) and 60.6% (20.33) in the second group (FAO) (P=0.011). It appears that a major advantage of our proposed regimen over others is a lack of wide use of fluoroquinolones for treating children's diseases. Given FDA's recommendation about the possibility of prescribing ciprofloxacin for infected patients with multidrug resistance, we can use the regimen proposed in this study in patients with resistance to standard treatments.

  3. Associations of race and ethnicity with anemia management among patients initiating renal replacement therapy.

    Science.gov (United States)

    Weisbord, Steven D; Fried, Linda F; Mor, Maria K; Resnick, Abby L; Kimmel, Paul L; Palevsky, Paul M; Fine, Michael J

    2007-11-01

    Many patients initiate renal replacement therapy with suboptimal anemia management. The factors contributing to this remain largely unknown. The aim of this study was to assess the associations of race and ethnicity with anemia care prior to the initiation of renal replacement therapy. Using data from the medical evidence form filed for patients who initiated renal replacement therapy between 1995-2003, we assessed racial and ethnic differences in pre-end-stage renal disease hematocrit levels, the use of erythropoiesis stimulation agents (ESAs), the proportion of patients with hematocrit levels > or = 33% and the proportion of patients with hematocrit levels or = 33% (OR = 0.78, 95% CI: 0.77-0.79) or to receive ESA if the hematocrit was or = 33% (OR = 0.91, 95% CI: 0.89-0.93) or to receive ESA if the hematocrit was < 33% (OR = 0.85, 95% CI: 0.83-0.87) than non-Hispanic whites. These disparities persisted over the eight-year study period. African-American race and Hispanic ethnicity are associated with suboptimal pre-end-stage renal disease anemia management. Efforts to improve anemia care should incorporate targeted interventions to decrease these disparities.

  4. [Hormone replacement therapy among Norwegian women. Self-reported use and sales of estrogen preparations].

    Science.gov (United States)

    Søgaard, A J; Fønnebø, V; Magnus, J H; Tollan, A

    1998-02-10

    In order to analyse the use of hormone replacement therapy (HRT) and the predicting factors for its use, two random samples of Norwegian women (30-79 years) were interviewed by the Central Bureau of Statistics in 1994 (n = 565) and in 1996 (n = 470). The extent of use of HRT was compared with statistics for sales of oestrogen in Norway and the Nordic countries. In the age group 45-69 years the use of hormone replacement therapy increased from 16.3% in 1994 to 19.1% in 1996. The proportion of users did not increase with a higher level of education. In addition to information received, and after adjusting for other variables, attitudes towards oestrogen and knowledge about it were the most important contributing factors for using HRT. Sales figures show that the use of systemic oestrogen in Norway has increased more than 280% since 1990. None of the Nordic countries have had a corresponding increase, but the Norwegian figures are still low compared to most other Nordic countries. In 1996 14.5% of Norwegian women (50-79 years) used oestrogen for urogenital disorders. Norwegian women need to be better informed and more knowledgeable to enable them to make conscious choice regarding use of hormone replacement therapy.

  5. 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.

  6. Epidemiologic trends in chronic renal replacement therapy over forty years: A Swiss dialysis experience

    Directory of Open Access Journals (Sweden)

    Lehmann Petra

    2012-07-01

    Full Text Available Abstract Background Long term longitudinal data are scarce on epidemiological characteristics and patient outcomes in patients on maintenance dialysis, especially in Switzerland. We examined changes in epidemiology of patients undergoing renal replacement therapy by either hemodialysis or peritoneal dialysis over four decades. Methods Single center retrospective study including all patients which initiated dialysis treatment for ESRD between 1970 and 2008. Analyses were performed for subgroups according to dialysis vintage, based on stratification into quartiles of date of first treatment. A multivariate model predicting death and survival time, using time-dependent Cox regression, was developed. Results 964 patients were investigated. Incident mean age progressively increased from 48 ± 14 to 64 ± 15 years from 1st to 4th quartile (p  Discussion We document an increase of a predominantly elderly incident and prevalent dialysis population, with progressively shortened survival after initiation of renal replacement over four decades, and, nevertheless, a prolonged lifespan. Analysis of the data is limited by lack of information on comorbidity in the study population. Conclusions Survival in patients on renal replacement therapy seems to be affected not only by medical and technical advances in dialysis therapy, but may mostly reflect progressively lower mortality of individuals with cardiovascular and metabolic complications, as well as a policy of accepting older and polymorbid patients for dialysis in more recent times. This is relevant to make demographic predictions in face of the ESRD epidemic nephrologists and policy makers are facing in industrialized countries.

  7. 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.

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

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    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

  9. Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with LPV/r+3TC for initial ART in HIV infected adults

    Directory of Open Access Journals (Sweden)

    Josép M Gatell

    2014-11-01

    Full Text Available Introduction: The National AIDS Plan and the Spanish AIDS study group (GESIDA panel of experts propose “preferred regimens” of antiretroviral treatment (ART as initial therapy in HIV-infected patients for 2013 [1]. All these regimens are triple therapy regimens. The Gardel Study assessed the efficacy and safety of a dual therapy (DT combination of lopinavir/ritonavir (LPV/r 400/100 mg BID+ lamivudine (3TC 150 mg BID [2]. The objective of this study is to evaluate the costs and efficiency of initiating treatment with the GESIDA “preferred regimens” and DT. Materials and Methods: Economic assessment of costs and efficiency (cost/efficacy through decision tree analysis models. Efficacy was defined as the probability of having viral load <50 copies/mL at week 48, 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 tests during the first 48 weeks. The payer perspective (Spanish National Health System was applied considering only differential direct costs: ART (official prizes, management of adverse effects, resistance tests, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was conducted, building three scenarios for each regime: base, most favourable and most unfavourable cases. Results: In the base case scenario, the cost of initiating treatment ranges from 5138 euros for DT, to 12,059 euros for tenofovir DF/emtricitabine (TDF/FTC+raltegravir (RAL. The efficacy ranges between 0.66 for abacavir (ABC/3TC+LPV/r and ABC/3TC+atazanavir (ATV/r, and 0.88 for DT. Efficiency, in terms of cost/efficacy, varies between 5817 and 13,930 euros per responder at 48 weeks, for DT and TDF/FTC+RAL respectively. DT is the most efficient regimen in the most favourable (5503 euros per responder and most unfavourable (6169 euros per responder

  10. [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.

  11. 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 testosterone 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 testosterone 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.

  12. Functional tooth regenerative therapy: tooth tissue regeneration and whole-tooth replacement.

    Science.gov (United States)

    Oshima, Masamitsu; Tsuji, Takashi

    2014-07-01

    Oral and general health is compromised by irreversible dental problems, including dental caries, periodontal disease and tooth injury. Regenerative therapy for tooth tissue repair and whole-tooth replacement is currently considered a novel therapeutic concept with the potential for the full recovery of tooth function. Several types of stem cells and cell-activating cytokines have been identified in oral tissues. These cells are thought to be candidate cell sources for tooth tissue regenerative therapies because they have the ability to differentiate into tooth tissues in vitro and in vivo. Whole-tooth replacement therapy is regarded as an important model for the development of an organ regenerative concept. A novel three-dimensional cell-manipulation method, designated the organ germ method, has been developed to recapitulate organogenesis. This method involves compartmentalisation of epithelial and mesenchymal cells at a high cell density to mimic multicellular assembly conditions and epithelial-mesenchymal interactions. A bioengineered tooth germ can generate a structurally correct tooth in vitro and erupt successfully with the correct tooth structure when transplanted into the oral cavity. We have ectopically generated a bioengineered tooth unit composed of a mature tooth, periodontal ligament and alveolar bone, and that tooth unit was successfully engrafted into an adult jawbone through bone integration. Such bioengineered teeth were able to perform normal physiological tooth functions, such as developing a masticatory potential in response to mechanical stress and a perceptive potential for noxious stimuli. In this review, we describe recent findings and technologies underpinning tooth regenerative therapy.

  13. 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

  14. Cost-effectiveness of tipranavir versus comparator protease inhibitor regimens in HIV infected patients previously exposed to antiretroviral therapy in the Netherlands

    Directory of Open Access Journals (Sweden)

    Kappelhoff Bregt S

    2007-11-01

    Full Text Available Abstract Background This study compares the costs and effects of a regimen with ritonavir-boosted tipranavir (TPV/r to a physician-selected genotypically-defined standard-of-care comparator protease inhibitor regimen boosted with ritonavir (CPI/r in HIV infected patients that were previously exposed to antiretroviral therapy in the Netherlands. Methods We compared the projected lifetime costs and effects of two theoretical groups of 1000 patients, one receiving a standard of care regimen with TPV/r as a component and the other receiving a standard of care regimen with CPI/r. A 3-stage Markov model was formulated to represent three different consecutive HAART regimens. The model uses 12 health states based on viral load and CD4+ count to simulate disease progression. The transition probabilities for the Markov model were derived from a United States cohort of treatment experienced HIV patients. Furthermore, the study design was based on 48-week data from the RESIST-2 clinical trial and local Dutch costing data. Cost and health effects were discounted at 4% and 1.5% respectively according to the Dutch guideline. The analysis was conducted from the Dutch healthcare perspective using 2006 unit cost prices. Results Our model projects an accumulated discounted cost to the Dutch healthcare system per patient receiving the TPV/r regimen of €167,200 compared to €145,400 for the CPI/r regimen. This results in an incremental cost of €21,800 per patient. The accumulated discounted effect is 7.43 life years or 6.31 quality adjusted life years (QALYs per patient receiving TPV/r, compared to 6.91 life years or 5.80 QALYs per patient receiving CPI/r. This translates into an incremental effect of TPV/r over CPI/r of 0.52 life years gained (LYG or 0.51 QALYs gained. The corresponding incremental cost effectiveness ratios (iCERs are €41,600 per LYG and €42,500 per QALY. Conclusion We estimated the iCER for TPV/r compared to CPI/r at approximately €40

  15. 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.

  16. 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

  17. Neutrophil and Monocyte Function in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy with Regimens Containing Protease Inhibitors with and without Interferon

    Science.gov (United States)

    González, Patricia; Cañete, Nuria; Mariño, Zoe; Lens, Sabela; Bonacci, Martín; Bartres, Concepció; Sánchez-Tapias, José-María; Carrión, José A.; Forns, Xavier; Juan, Manel; Pérez-del-Pulgar, Sofía

    2016-01-01

    Real-life data showed an increased incidence of bacterial infections in patients with advanced liver disease receiving a protease inhibitor (PI)-containing antiviral regimen against hepatitis C (HCV). However, the causes of this event are unknown. We hypothesized that PIs might impair innate immune responses through the inhibition of proteases participating in the anti-bacterial functions of neutrophils and monocytes. The aims of the study were to assess phagocytic and oxidative burst capacity in neutrophils and monocytes obtained from patients receiving a PI containing-antiviral regimen, and to determine cytokine secretion after neutrophil stimulation with flagellin. Forty patients with chronic HCV (80% with cirrhosis) were enrolled in the study, 28 received triple therapy (Group A) with pegylated-interferon and ribavirin for 4 weeks followed by the addition of a PI (telaprevir, boceprevir or simeprevir), and 12 patients received an interferon-free regimen (Group B) with simeprevir and sofosbuvir. Phagocytosis and oxidative burst capacity were analyzed by flow cytometry at baseline, week 4, and week 8 of therapy. In neutrophils from Group A patients, oxidative burst rate and oxidative enzymatic activity per cell significantly decreased throughout the study period (p = 0.014 and p = 0.010, respectively). Pairwise comparisons showed a decrease between baseline and week 4 and 8 of therapy. No differences were observed after the introduction of the PI. The oxidative enzymatic activity per cell in monocytes significantly decrease during the study period (p = 0.042) due to a decrease from baseline to week 8 of therapy (p = 0.037) in patients from Group A. None of these findings were observed in Group B patients. Cytokine secretion did not significantly change during the study in both groups. In conclusion, our data suggest that the use interferon (rather than the PI) has a deleterious effect on neutrophil and monocyte phagocytic and oxidative burst capacity in this

  18. A simplified combination antiretroviral therapy regimen enhances adherence, treatment satisfaction and quality of life : results of a randomized clinical trial

    NARCIS (Netherlands)

    Langebeek, N.; Sprenger, H. G.; Gisolf, E. H.; Reiss, P.; Sprangers, M. A. G.; Legrand, J. C.; Richter, C.; Nieuwkerk, P. T.

    2014-01-01

    Objectives The aim of the study was to investigate the effect of a simplified regimen, in terms of reducing pill burden, dietary requirements and possible adverse effects, on patients' adherence, treatment satisfaction and quality of life (QoL). Methods Antiretroviral-naive patients who achieved a v

  19. Impacto da terapia hormonal sobre o peso corpóreo Impact of hormone replacement therapy on body weight

    Directory of Open Access Journals (Sweden)

    Joana Palmira Martins Almeida

    2011-10-01

    Full Text Available OBJETIVO: avaliar o efeito da terapêutica hormonal (TH no peso de mulheres na peri-menopausa, assim como o efeito de diferentes regimes terapêuticos no referido parâmetro. MÉTODOS: estudo retrospectivo de 139 mulheres, com menopausa há menos de 2 anos, acompanhadas na consulta de climatério do nosso departamento. Obtiveram-se dois grupos: mulheres a quem se iniciou TH (n=89 e outro, grupo controle, sem terapia hormonal (n=50. Em cada grupo, foi avaliada a modificação ponderal no intervalo de 1 ano após a primeira consulta. Nas submetidas a TH, avaliou-se esse mesmo parâmetro em função de diferentes regimes terapêuticos preconizados: estrogênio isolado vs estroprogestagênio e dose standard vs baixa dosagem. A análise estatística foi realizada com recurso ao programa SPSS®, adotando-se como nível de significância valores pPURPOSE: to evaluate the effect of hormone replacement therapy (HT on the weight on perimenopausal women as well as the effect of different treatment regimens on this parameter. METHODS: a retrospective study of 139 women with menopause for less than 2 years, who were monitored with periodical visits in our department. We compared two groups: women who started HT (n=89 with women who had no hormonal treatment (n=50 and in the two groups, we evaluated the changes in body weight over a 1-year period. In the first group, we assessed the same parameter as a function of different treatment regimens: estrogen alone versus estrogen combined with progestin and standard dose versus low dose. The SPSS® program was used for statistical analysis, with the level of significance set at p<0.05. RESULTS: the groups were similar with respect to demographic and baseline characteristics; weight gain was higher in the untreated group (434 vs 76 g, but the difference observed was not significant (p = 0.406; among HT users, those taking estrogen alone had an increased weight gain compared to women taking estrogen with progestin

  20. Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy.

    Science.gov (United States)

    Oshima, Masamitsu; Mizuno, Mitsumasa; Imamura, Aya; Ogawa, Miho; Yasukawa, Masato; Yamazaki, Hiromichi; Morita, Ritsuko; Ikeda, Etsuko; Nakao, Kazuhisa; Takano-Yamamoto, Teruko; Kasugai, Shohei; Saito, Masahiro; Tsuji, Takashi

    2011-01-01

    Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy.

  1. 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.

  2. Effects of leptin replacement therapy on pancreatic β-cell function in patients with lipodystrophy.

    Science.gov (United States)

    Muniyappa, Ranganath; Brown, Rebecca J; Mari, Andrea; Joseph, Jalaja; Warren, Mary A; Cochran, Elaine K; Skarulis, Monica C; Gorden, Phillip

    2014-04-01

    OBJECTIVE Leptin administration is known to directly modulate pancreatic β-cell function in leptin-deficient rodent models. However, human studies examining the effects of leptin administration on β-cell function are lacking. In this study, we examined the effects (16-20 weeks) of leptin replacement on β-cell function in patients with lipodystrophy. RESEARCH DESIGN AND METHODS In a prospective, open-label, currently ongoing study, we studied the effects of leptin replacement on β-cell function in 13 patients with congenital or acquired lipodystrophy. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution from plasma glucose and C-peptide levels measured during oral glucose tolerance tests (OGTTs) performed at baseline and after 16-20 weeks of leptin replacement. β-Cell glucose sensitivity and rate sensitivity were assessed by mathematical modeling of OGTT. RESULTS There was a significant decrease in triglycerides, free fatty acids, and glycosylated hemoglobin levels (A1C) after leptin therapy. Patients with lipodystrophy have high fasting and glucose-stimulated ISR. However, leptin therapy had no significant effect on fasting ISR, total insulin secretion during OGTT, β-cell glucose sensitivity, rate sensitivity, or insulin clearance. CONCLUSIONS In contrast to the suppressive effects of leptin on β-cell function in rodents, 16-20-week treatment with leptin in lipodystrophy patients did not significantly affect insulin secretion or β-cell function in leptin-deficient individuals with lipodystrophy.

  3. Effect of testosterone replacement therapy on bone mineral density in patients with Klinefelter syndrome.

    Science.gov (United States)

    Jo, Dae Gi; Lee, Hyo Serk; Joo, Young Min; Seo, Ju Tae

    2013-11-01

    Klinefelter syndrome (KS) is related to testicular insufficiency, which causes low testosterone levels in serum. Generally, sex hormone levels and bone mineral density (BMD) are lower in patients with KS than normal. We investigated the effects of testosterone replacement on serum testosterone levels and BMD in KS patients. From December 2005 to March 2008, 18 KS patients with a 47, XXY karyotype were treated with initial intramuscular injections of long-acting testosterone undecanoate (Nebido®, 1000 mg/4 mL) at baseline and second injections after six weeks. An additional four injections were administered at intervals of 12 weeks after the second injection. BMD was measured at the lumbar spine (L2-4), the left femoral neck and Ward's triangle, using dual energy X-ray absorptiometry. Medical histories, physical examinations and prostate specific antigen, hematology and serum chemistry were conducted for each patient. In addition, total testosterone and sex hormone-binding globulin levels were measured. Following testosterone replacement, mean serum total testosterone increased significantly from baseline (0.90 vs. 4.51 ng/mL, ptestosterone rose to normal levels after replacement in all patients. The mean BMD of the lumbar spine increased significantly (0.91 vs. 0.97 g/cm², ptestosterone replacement therapy may be effective in treating BMD deficiency in men with testosterone deficiency, especially those with Klinefelter syndrome.

  4. 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.

  5. Pharmacokinetics of Continuous Infusion Meropenem With Concurrent Extracorporeal Life Support and Continuous Renal Replacement Therapy: A Case Report.

    Science.gov (United States)

    Cies, Jeffrey J; Moore, Wayne S; Conley, Susan B; Dickerman, Mindy J; Small, Christine; Carella, Dominick; Shea, Paul; Parker, Jason; Chopra, Arun

    2016-01-01

    Pharmacokinetic parameters can be significantly altered for both extracorporeal life support (ECLS) and continuous renal replacement therapy (CRRT). This case report describes the pharmacokinetics of continuous-infusion meropenem in a patient on ECLS with concurrent CRRT. A 2.8-kg, 10-day-old, full-term neonate born via spontaneous vaginal delivery presented with hypothermia, lethargy, and a ~500-g weight loss from birth. She progressed to respiratory failure on hospital day 2 (HD 2) and developed sepsis, disseminated intravascular coagulation, and liver failure as a result of disseminated adenoviral infection. By HD 6, acute kidney injury was evident, with progressive fluid overload >1500 mL (+) for the admission. On HD 6 venoarterial ECLS was instituted for lung protection and fluid removal. On HD 7 she was initiated on CRRT. On HD 12, a blood culture returned positive and subsequently grew Pseudomonas aeruginosa with a minimum inhibitory concentration (MIC) for meropenem of 0.25 mg/L. She was started on vancomycin, meropenem, and amikacin. A meropenem bolus of 40 mg/kg was given, followed by a continuous infusion of 10 mg/kg/hr (240 mg/kg/day). On HD 15 (ECLS day 9) a meropenem serum concentration of 21 mcg/mL was obtained, corresponding to a clearance of 7.9 mL/kg/min. Repeat cultures from HDs 13 to 15 (ECLS days 7-9) were sterile. This meropenem regimen was successful in providing a target attainment of 100% for serum concentrations above the MIC for ≥40% of the dosing interval and was associated with a sterilization of blood in this complex patient on concurrent ECLS and CRRT circuits.

  6. Glial-restricted precursors as potential candidates for ALS cell-replacement therapy.

    Science.gov (United States)

    Kruminis-Kaszkiel, Ewa; Wojtkiewicz, Joanna; Maksymowicz, Wojciech

    2014-01-01

    Amyotrophic lateral sclerosis is a multifactorial progressive neurodegenerative disorder leading to severe disability and death within 3-5 years after diagnosis. The main mechanisms underlying the disease progression are poorly known but according to the current knowledge, neuroinflammation is a key player in motor neurons damage. Astrocytes constitute an important cell population involved in neuroinflammatory reaction. Many studies confirmed their striking connection with motor neuron pathology and therefore they might be a target for the treatment of ALS. Cell-based therapy appears to be a promising strategy. Since direct replacement or restoring of motor neurons using various stem cells is challenging, enrichment of healthy donor-derived astrocytes appears to be a more realistic and beneficial approach. The effects of astrocytes have been examined using transplantation of glial-restricted precursors (GRPs) that represent one of the earliest precursors within the oligodendrocytic and astrocytic cell lineage. In this review, we focused on evidence-based data on astrocyte replacement transplantation therapy using GRPs in animal models of motor neuron diseases. The efficacy of GRPs engrafting is very encouraging. Furthermore, the lesson learned from application of lineage-restricted precursors in spinal cord injury (SCI) indicates that differentiation of GRPs into astrocytes before transplantation might be more advantageous in the context of axon regeneration. To sum up, the studies of glial-restricted precursors have made a step forward to ALS research and might bring breakthroughs to the field of ALS therapy in the future.

  7. Endocrine studies in postmenopausal women during oral replacement therapy with unconjugated oestrogens.

    Science.gov (United States)

    Vasquez, J M; Samaras, C A; Nezhat, C

    1982-01-01

    Two groups of postmenopausal women were seen at monthly intervals during a three-month trial of continuous therapy with oral unconjugated oestrogens. Ten women in the first group were administered daily Hormonin No. 1 containing oestriol (E3) 0.135 mg, oestradiol (E2) 0.3 mg and oestrone (E1) 0.7 mg. Eight women in the second group received Hormonin No. 2 containing E3 0.27 mg, E2 0.6 mg and E1 1.4 mg. E1, E2, E3 and dehydroepiandrosterone (DHA) as well as follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay. Maturation index of vaginal smears and clinical effects were also evaluated. Oral replacement therapy with these unconjugated oestrogens produced a significant elevation of E1 (p less than 0.05) and E2 (p less than 0.05) to values corresponding well with the premenopausal range measured in our laboratory. Postmenopausal levels of FSH and LH showed only a moderate but significant decrease (p less than 0.05). There was consistent relief of vasomotor symptoms. One case of endometrial focal adenomatous hyperplasia uncovered during the period of treatment was transformed to functional secretory endometrium after an appropriate course with progestogens. Oral administration of unconjugated oestrogens and periodic withdrawal bleeding induced with a progestational agent seems to be an effective method of replacement therapy in postmenopausal women.

  8. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy

    NARCIS (Netherlands)

    J.B. Madalinska; M. van Beurden; E.M.A. Bleiker; H.B. Valdimarsdottir; J. Hollenstein; L.F. Massuger; K.N. Gaarenstroom; M.J.E. Mourits; R.H.M. Verheijen; E.B.L. van Dorst; H. van der Putten; K. van der Velden; H. Boonstra; N.K. Aaronson

    2006-01-01

    Purpose Preventive health strategies for women at increased hereditary risk of ovarian cancer include gynecologic screening (GS) and/or prophylactic oophorectomy (PBSO). Hormone replacement therapy (HRT) is often prescribed to compensate for postsurgical endocrine deficiencies. This study examined t

  9. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy.

    NARCIS (Netherlands)

    Madalinska, J.B.; Beurden, M. van; Bleiker, E.M.A.; Valdimarsdottir, H.B.; Hollenstein, J.; Massuger, L.F.A.G.; Gaarenstroom, K.N.; Mourits, M.J.E.; Verheijen, R.H.; Dorst, E.B.L. van; Putten, H. van der; Velden, K. van der; Boonstra, H.; Aaronson, N.K.

    2006-01-01

    PURPOSE: Preventive health strategies for women at increased hereditary risk of ovarian cancer include gynecologic screening (GS) and/or prophylactic oophorectomy (PBSO). Hormone replacement therapy (HRT) is often prescribed to compensate for postsurgical endocrine deficiencies. This study examined

  10. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy.

    NARCIS (Netherlands)

    Madalinska, J.B.; Beurden, M. van; Bleiker, E.M.A.; Valdimarsdottir, H.B.; Hollenstein, J.; Massuger, L.F.A.G.; Gaarenstroom, K.N.; Mourits, M.J.E.; Verheijen, R.H.; Dorst, E.B.L. van; Putten, H. van der; Velden, K. van der; Boonstra, H.; Aaronson, N.K.

    2006-01-01

    PURPOSE: Preventive health strategies for women at increased hereditary risk of ovarian cancer include gynecologic screening (GS) and/or prophylactic oophorectomy (PBSO). Hormone replacement therapy (HRT) is often prescribed to compensate for postsurgical endocrine deficiencies. This study examined

  11. A Retrospective Study of Capecitabine/Temozolomide (CAPTEM Regimen in the Treatment of Metastatic Pancreatic Neuroendocrine Tumors (pNETs after Failing Previous Therapy

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2013-09-01

    Full Text Available Context Pancreatic neuroendocrine tumors (pNETs are notoriously resistant to currently available chemotherapy agents.Preclinical data has suggested synergy between temozolomide and capecitabine. Objective To report a retrospective data on the efficacy and safety of capecitabine and temozolomide (CAPTEM regimen in patients with metastatic pancreaticneuroendocrine tumors (pNETs who have failed prior therapies. Methods We reviewed the medical records of 7 patientswith metastatic pNETs who had had progressive cancer prior to treatment despite therapy, including long-acting releaseoctreotide (60 mg/month, chemotherapy and hepatic chemoembolization. Capecitabine was administered at a flat dose of1,000 mg orally twice daily on days 1-14 and temozolomide 200 mg/m2 was given in two divided doses daily on days 10-14of a 28-day cycle. Tumor assessments were repeated every two cycles and serum tumor markers were measured every cycle. Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors (RECIST parameters, and toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 3.0. Results Among 7 patients treated, three patients achieved a partial response, and two patients had stable disease. Totalresponse rate was 43%, and clinical benefit (responders and stable disease was 71%. Median duration of response was 8months (range: 4-12 months. Grade 3 and 4 toxicities included grade 3 thrombocytopenia in one patient and grade 3 fatigue in one patient. The most common toxicities were grade 1 and 2 neutropenia, grade 1 fatigue, grade 1 and 2 hand-foot syndrome. Conclusions Our retrospective study showed that modified CAPTEM regimen was well-tolerated and produced comparable response to historical data in neuroendocrine tumors, including pNETs. Our study is unique as it only included patients with pNETs. Further prospective studies are warranted to evaluate the combination of

  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 Hvarregaard;

    2012-01-01

    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.......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....

  13. Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women.

    Science.gov (United States)

    Kabat, Geoffrey C; Miller, Anthony B; Rohan, Thomas E

    2008-02-01

    Evidence from epidemiologic studies suggests a possible role of exogenous and endogenous hormones in colorectal carcinogenesis in women. However, with respect to exogenous hormones, in contrast to hormone replacement therapy, few cohort studies have examined oral contraceptive use in relation to colorectal cancer risk. We used data from a large cohort study of Canadian women enrolled in a randomized controlled trial of breast cancer screening to assess the association of oral contraceptive use, hormone replacement therapy and reproductive factors with risk of colorectal cancer, overall and by subsite within the colorectum. Cancer incidence and mortality were ascertained by linkage to national databases. Among 89,835 women aged 40-59 at enrollment and followed for an average of 16.4 years, we identified 1,142 incident colorectal cancer cases. Proportional hazards models were used to estimate the associations between the exposures of interest and risk of colorectal cancer. Ever use of oral contraceptives at baseline was associated with a modest reduction in the risk of colorectal cancer (hazard ratio 0.83, 95% confidence interval 0.73-0.94), with similar effects for different subsites within the colorectum. No trend was seen in the hazard ratios with increasing duration of oral contraceptive use. No associations were seen with use of hormone replacement therapy (ever use or duration of use) or reproductive factors. Our results are suggestive of an inverse association between oral contraceptive use and colorectal carcinogenesis. However, given the lack of a dose-response relationship and the potential for confounding, studies with more complete assessment of exogenous hormone use throughout the life course are needed to clarify this association. (c) 2007 Wiley-Liss, Inc.

  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

    .08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. CONCLUSIONS: In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable...

  15. 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

  16. Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C–Coinfected Persons

    OpenAIRE

    Brunet, Laurence; Moodie, Erica E. M.; Young, Jim; Cox, Joseph; Hull, Mark; Cooper, Curtis; Walmsley, Sharon; Martel-Laferrière, Valérie; Rachlis, Anita; Marina B Klein

    2015-01-01

    Background.  Liver diseases progress faster in human immunodeficiency virus (HIV)–hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV–coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamiv...

  17. 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)

    Roge, BT; Barfod, TS; 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...... adherent patients on randomized treatment failed in the RS-arm, none in the NN-arm, and six in the ASD-arm. CONCLUSIONS: Primary virological failure was caused mainly by treatment interruption. No primary protease inhibitor (PI) mutations were found in patients failing on boosted saquinavir, whereas...

  18. Quality control system to support comparability assessment for the Renal Bio-Replacement therapy system.

    Science.gov (United States)

    Pitkin, Z

    2005-01-01

    Cell therapies offer great promise for treating serious and life-threatening diseases, as cells provide the dynamic, interactive therapy that responds to the patient's condition. The spectrum of cell therapies is very broad, but each requires characterization during product development. During the development of a cell therapy, changes are made to improve product quality, purity, yield, and consistency, as well as to meet other production requirements. Multiple factors have to be considered when changes are made. A well thought-out design of comparability protocols has to reflect the international consensus set forth by the International Conference on Harmonization (ICH) and Food and Drug Administration (FDA). Comparability studies, due to their importance for the entire product development, constitute an additional challenge for the Quality System, which supports manufacturing. A comparability study was conducted to support the transfer of a cell-based technology, the Renal Bio-Replacement (RBR) system, from an academic laboratory to a contract manufacturing facility. The quality control programme supporting the RBR, and issues encountered in the comparability of the RBR therapy system, are discussed in this article.

  19. Hormone replacement therapy and risk of breast cancer: the role of progestins

    DEFF Research Database (Denmark)

    Stahlberg, Claudia Irene; Pederson, Anette Tønnes; Lynge, Elsebeth;

    2003-01-01

    Epidemiological studies have shown an increased risk of breast cancer associated with the use of hormone replacement therapy (HRT). This notion is mostly based on studies from the USA. During the last decades unopposed estrogen treatment has been used to a lesser extent, whereas the combined...... estrogen-progestin treatment regime is now prescribed worldwide. In the USA the predominant compounds are conjugated estrogens and medroxyprogesterone-acetate, whereas oestradiol combined with testosterone-like progestins is commonly used in Europe. These differences are largely the result of traditions...

  20. Long-term hormone replacement therapy preserves bone mineral density in Turner syndrome

    DEFF Research Database (Denmark)

    Cleemann, Line; Hjerrild, Britta E; Lauridsen, Anna L;

    2009-01-01

    at baseline and follow-up (5.9+/-0.7 years). SETTING: Tertiary hospital. PARTICIPANTS: Fifty-four women with TS (43.0+/-9.95 years). Interventions Hormone replacement therapy (HRT) and calcium and vitamin D supplementation. Main outcome measures BMD (g/cm(2)) measured at lumbar spine, hip, and the non.......010+/-0.144, PTestosterone, IGF1, and maximal oxygen uptake was significantly reduced in TS. CONCLUSION: Longitudinal changes in BMD in TS were slight. BMD can be maintained at most sites in well...

  1. Androgen deficiency in older men: indications, advantages, and pitfalls of testosterone replacement therapy.

    Science.gov (United States)

    McGill, John J; Shoskes, Daniel A; Sabanegh, Edmund S

    2012-11-01

    The decline in testosterone with age has been associated with specific physical changes that affect quality of life and life expectancy, although a cause-and-effect relationship is yet to be established. While female menopause is rapid and well described, "male menopause" or androgen decline in older men is gradual and marked by nonspecific symptoms. This makes diagnosis of true testosterone deficiency and prediction of response to testosterone replacement therapy (TRT) challenging. This article reviews androgen decline in men, focusing on those over age 40, and covers symptoms, indications, contraindications,diagnosis, treatments, and the risks and benefits of treatment [corrected].

  2. Testosterone Replacement Therapy and BPH/LUTS. What is the Evidence?

    Science.gov (United States)

    Baas, Wesley; Köhler, Tobias S

    2016-06-01

    Contrary to the previous dogma that prostatic growth is directly proportional to testosterone levels, emerging research has suggested a lack of testosterone may be a risk factor for lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Within this review article, we have demonstrated the current understanding of the physiology of hypogonadism and its interplay with prostatic and lower urinary tract physiology. The current evidence suggests that not only does testosterone replacement therapy (TRT) not worsen LUTS, but that hypogonadism itself is an important risk factor for LUTS/BPH.

  3. Effects of hormone replacement therapy on endothelial function in menopausal women

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To observe the effects of hormone replacement therapy (HRT) on endothelial function in menopausal women. Methods A total of 30 menopausal women were treated with 2.5 mg of Tibolone (Livial) daily. At the same time,30 women with natural menopause without any treatment served as the control group. Endothelium-dependent (EDD),endothelium-independent (NID) vasodilatation function,and estradiol (E2) were examined by the non-invasive high-resolution ultrasonography before the treatment and at 12th,24th,...

  4. Evaluation of the hemodynamic impact of continuous renal replacement therapy in healthy dogs.

    Science.gov (United States)

    Shimokawa Miyama, Takako; Itamoto, Kazuhito; Yoshioka, Chihiro; Minami, Koji; Okawa, Takumi; Fujisaki, Yuka; Hiraoka, Hiroko; Mizuno, Takuya; Okuda, Masaru

    2010-04-01

    We performed continuous renal replacement therapy (CRRT) on clinically healthy dogs to evaluate the effects of CRRT on hemodynamics. Heart rate, arterial blood pressure, and central venous pressure of the dogs (n=6) were recorded during the procedure, which was performed under general anesthesia. Throughout the CRRT, heart rate and arterial blood pressure were stable. Central venous pressure increased after CRRT termination but returned to the basal level within 30 min. In this study, hemodynamic alterations, including hypotension, hypertension, and arrhythmias, were not observed during CRRT. These observations suggest that the CRRT protocol used in the present study can be safely applied to clinical cases with acute renal failure.

  5. Renal Replacement Therapy in Congestive Heart Failure Requiring Left Ventricular Assist Device Augmentation

    OpenAIRE

    Thomas, Bernadette A.; Logar, Christine M.; Anderson, Arthur E.

    2012-01-01

    “Cardiorenal syndrome” is a term used to describe a dys-regulation of the heart affecting the kidneys, or vice versa, in an acute or chronic manner (1,2). Renal impairment can range from reversible ischemic damage to renal failure requiring short- or long-term renal replacement therapy (2). Patients who require mechanical circulatory support, such as a left ventricular assist device (LVAD), as definitive treatment for congestive heart failure or as a bridge to cardiac transplantation pose a u...

  6. Breast cancer after hormone replacement therapy--does prognosis differ in perimenopausal and postmenopausal women?

    Science.gov (United States)

    Baumgärtner, A K; Häusler, A; Seifert-Klauss, V; Schuster, T; Schwarz-Boeger, U; Kiechle, M

    2011-10-01

    Hormone replacement therapy (HRT) has been associated with higher incidence of breast cancer in postmenopausal women, but it is unclear if breast cancers developing after HRT use have different prognosis. 1053 women with hormone receptor positive non-metastasized breast cancer were analyzed in a retrospective trial, stratifying by HRT use before diagnosis. Postmenopausal HRT users had significantly more early tumor stages (pprognosis in perimenopausal women only (TTP: HR=1.16; OS: HR=1.31). In this retrospective analysis postmenopausal HRT users seemed to have a better breast cancer prognosis. For perimenopausal HRT users however, a trend towards worse prognosis was found.

  7. Understanding renal replacement therapy and dosing of drugs in pediatric patients with kidney disease.

    Science.gov (United States)

    Zuppa, Athena F

    2012-01-01

    Multifaceted factors need to be considered when prescribing renal replacement therapy (RRT) and dosing of drugs in pediatric patients with kidney disease. RRTs in pediatrics such as intermittent hemodialysis, continuous venovenous hemofiltration, continuous venovenous hemodialysis, and continuous venovenous hemodiafiltration affect solute and drug clearance. Drug properties such as molecular weight, molecular charge, volume of distribution, and protein binding affect drug clearance. RRT prescription parameters such as blood flow rate, ultrafiltration rate, membrane size, and pore size can also influence drug clearance. Furthermore, the pediatric patient presents additional concerns because of developmental factors in children that affect both pharmacokinetics of drugs.

  8. A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery

    Science.gov (United States)

    Pannu, Neesh; Graham, Michelle; Klarenbach, Scott; Meyer, Steven; Kieser, Teresa; Hemmelgarn, Brenda; Ye, Feng; James, Matthew

    2016-01-01

    Background: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy. Methods: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer–Lemeshow goodness-of-fit test and Net Reclassification Improvement index. Results: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00–4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15–2.40), diabetes mellitus (1.61, 1.12–2.31), baseline estimated glomerular filtration rate (0.96, 0.95–0.97), increasing hemoglobin concentration (0.85, 0.77–0.93), proteinuria (1.65, 1.07–2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64–2.43), other cardiac procedure (v. CABG only, 3.11, 2.12–4.58) and emergent status for surgery booking (4.63, 2.61–8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79–0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score). Interpretation: We have developed

  9. 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...... to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. METHODS: A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations...

  10. [Transdermal estradiol--the possibility for replacement therapy in the postmenopause].

    Science.gov (United States)

    Rachev, E

    1994-01-01

    The author presents his experience in the treatment of 21 early postmenopausal women (mean age of 49.2 yrs) with transdermal delivery of 17 beta-oestradiol (Estraderm TTS, Ciba). During the treatment Kuppermann index falls from 28.5 to 10.9. Karyopyknotic index increases from 6.8 to 23.4 and maturation index moves from 39:52:9 to 0:71:29. Genital bleeding occurs in 52% of the patients. The author concludes that the treatment with transdermal delivery of oestradiol could be used more widely for replacement therapy in the postmenopause.

  11. [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

  12. Insomnia related to postmenopausal syndrome and hormone replacement therapy: sleep laboratory studies on baseline differences between patients and controls and double-blind, placebo-controlled investigations on the effects of a novel estrogen-progestogen combination (Climodien, Lafamme) versus estrogen alone.

    Science.gov (United States)

    Saletu-Zyhlarz, Gerda; Anderer, Peter; Gruber, Georg; Mandl, Magdalena; Gruber, Doris; Metka, Markus; Huber, Johannes; Oettel, Michael; Gräser, Thomas; Abu-Bakr, Manal Hassan; Grätzhofer, Elisabeth; Saletu, Bernd

    2003-09-01

    Differences in sleep and awakening quality between 51 insomniac postmenopausal syndrome patients and normal controls were evaluated. In a subsequent double-blind, placebo-controlled, comparative, randomized, three-arm trial (Climodien 2/3 = estradiol valerate 2 mg + the progestogen dienogest 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P), the effects of 2 months of hormone replacement therapy were investigated, followed by a 2-month open-label phase in which all patients received Climodien 2/2 (EV 2 mg + dienogest 2 mg = regimen A*). Polysomnography at baseline demonstrated significantly deteriorated sleep initiation and maintenance, increased S1 and decreased S2 in patients. Subjective sleep and awakening quality, well-being, morning drive, wakefulness, memory and reaction time performance were deteriorated too. Treatment with both regimen A and regimen EV induced a moderate, although nonsignificant, improvement in the primary efficacy variable wakefulness during the total sleep period compared with baseline, while under placebo no changes occurred. Secondary efficacy variables concerning sleep initiation and maintenance, and sleep architecture showed similar findings. The apnea and apnea-hypopnea indices improved significantly under regimen A, compared with both baseline and placebo. Subjective sleep and awakening quality improved significantly after regimen A and EV compared with baseline, with the drug-induced changes being superior to those induced by placebo. In the open-label phase, subjective sleep quality improved further, significantly in the former regimen A group. Awakening quality, somatic complaints and morning thymopsyche did not yield any significant findings. Concerning morning noopsychic performance, memory improved significantly after regimen A compared with baseline, fine motor activity after regimen EV. Reaction time performance increased with all three compounds. In conclusion, Climodien significantly improved

  13. 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.

  14. Hospital costs and clinical characteristics of continuous renal replacement therapy patients: a continuous ethical dilemma.

    Science.gov (United States)

    Coustasse, Alberto

    2008-01-01

    This study describes the clinical characteristics and examines hospital costs involved in the care of 117 patients undergoing Continuous Renal Replacement Therapy (CRRT) between January 1999 and August 2002. The majority (70.9%) of the patients undergoing CRRT expired in the hospital. Statistically significant differences were found with respect to the length of stay for discharge status and gender; and with respect to costs for surgery versus no surgery and gender. Significant differences were also found between discharge status and gender, age, and cardiovascular surgery. The results of this study raise economic and ethical questions related to the cost/benefit of CRRT and the futility of the treatment. Hospitals should ensure that they have utilization protocols in place for CRRT, promote cooperation between intensive care unit (ICU) physicians and nephrologists, and create multi-disciplinary CRRT teams in an effort to maximize the effectiveness of therapy and minimize costs.

  15. Considerations for Medication Management and Anticoagulation During Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Thompson, Ashley; Li, Fanny; Gross, A Kendall

    2017-01-01

    Providing safe and high-quality care to critically ill patients receiving continuous renal replacement therapy (CRRT) includes adequate drug dosing and evaluation of patients' response to medications during therapy. Pharmacokinetic drug studies in acute kidney injury and CRRT are limited, considering the number of medications used in critical care. Therefore, it is important to understand the basic principles of drug clearance during CRRT by evaluating drug properties, CRRT modalities, and how they affect medication clearance. Few published studies have addressed drug disposition and clinical response during CRRT. Additionally, clotting in the CRRT circuit is a concern, so a few options for anticoagulation strategies are presented. This article reviews (1) the CRRT system and drug property factors that affect medication management, (2) the evidence available to guide drug dosing, and (3) anticoagulation strategies for critically ill patients receiving CRRT. ©2017 American Association of Critical-Care Nurses.

  16. 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

    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...... cell transplantation will require optimizing the best cell type and site for engraftment, overcoming limitations to cell migration and tissue integration, and occasionally needing to control immunologic reactivity, as well as a number of other challenges. Collaboration among scientists, clinicians...

  17. Cyclosporin promotes neurorestoration and cell replacement therapy in pre-clinical models of Parkinson's disease.

    Science.gov (United States)

    Tamburrino, Anna; Churchill, Madeline J; Wan, Oi W; Colino-Sanguino, Yolanda; Ippolito, Rossana; Bergstrand, Sofie; Wolf, Daniel A; Herz, Niculin J; Sconce, Michelle D; Björklund, Anders; Meshul, Charles K; Decressac, Mickael

    2015-12-14

    The early clinical trials using fetal ventral mesencephalic (VM) allografts in Parkinson's disease (PD) patients have shown efficacy (albeit not in all cases) and have paved the way for further development of cell replacement therapy strategies in PD. The preclinical work that led to these clinical trials used allografts of fetal VM tissue placed into 6-OHDA lesioned rats, while the patients received similar allografts under cover of immunosuppression in an α-synuclein disease state. Thus developing models that more faithfully replicate the clinical scenario would be a useful tool for the translation of such cell-based therapies to the clinic. Here, we show that while providing functional recovery, transplantation of fetal dopamine neurons into the AAV-α-synuclein rat model of PD resulted in smaller-sized grafts as compared to similar grafts placed into the 6-OHDA-lesioned striatum. Additionally, we found that cyclosporin treatment was able to promote the survival of the transplanted cells in this allografted state and surprisingly also provided therapeutic benefit in sham-operated animals. We demonstrated that delayed cyclosporin treatment afforded neurorestoration in three complementary models of PD including the Thy1-α-synuclein transgenic mouse, a novel AAV-α-synuclein mouse model, and the MPTP mouse model. We then explored the mechanisms for this benefit of cyclosporin and found it was mediated by both cell-autonomous mechanisms and non-cell autonomous mechanisms. This study provides compelling evidence in favor for the use of immunosuppression in all grafted PD patients receiving cell replacement therapy, regardless of the immunological mismatch between donor and host cells, and also suggests that cyclosporine treatment itself may act as a disease-modifying therapy in all PD patients.

  18. 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

    2016-01-01

    Abstract 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 2D3) (P 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, and cognitive disorders, might enable a better quality of life and a major compliance with a probable reduction in the healthcare costs. PMID

  19. The novel bladder preservation therapy BOAI-CDDP-radiation (OMC-regimen): a new treatment option for invasive bladder cancer patients with lymph node metastasis.

    Science.gov (United States)

    Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Nomi, Hayahito; Hirano, Hajime; Ibuki, Naokazu; Uehara, Hiroshi; Komura, Kazumasa; Minami, Koichiro; Uchimoto, Taizo; Saito, Kenkichi; Takai, Tomoaki; Tanda, Naoki; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Kiyama, Satoshi

    2014-06-01

    We have developed a novel bladder preservation therapy for patients with muscle-invasive bladder cancer and lymph node metastasis: balloon-occluded arterial infusion (BOAI) of cisplatin/gemcitabine, with concomitant hemodialysis and irradiation [the so-called 'OMC (Osaka Medical College) regimen']. The OMC regimen delivers an extremely high concentration of anticancer agent to the site of the tumor, as well as the pelvic area, without causing any adverse systemic effects. In this study, we investigated the efficiency of the OMC regimen in 34 patients who underwent BOAI with cisplatin (100, 200 or 300 mg) along with 60 Gy of irradiation; patients who failed to achieve CR underwent secondary BOAI with gemcitabine (1,600 mg). The overall clinical response was 73.5% (CR: 35.3%; PR: 17.6%; SD: 20.6%). The 5-year overall and progression-free survival rates were 54.4% and 52.5%, respectively. For treatment failure, N2 stage was selected as a significant risk factor by simple and multiple logistic regression analyses. Cox proportional hazards analyses showed that N2 stage, T4 stage and the presence of hydronephrosis were significant risk factors for overall survival. Indeed, 55.6% of patients with N1 stage achieved a complete response (CR) (vs. 12.5% for N2 patients, p=0.0151), and 90% (9/10) of the CR patients survived without recurrence with an intact bladder after a mean follow-up of 85 (range 7-193) weeks. The 3-year progrssion-free survival rate with an intact bladder was 65.8% (vs. 37.5% for N2, p=0.034), and the 5-year overall survival rate was 71.8% (vs. 30.6% for N2, p=0.004). No patients suffered severe toxicities of Grade II or more; the oldest patient, aged 85 years, successfully completed this therapy. In conclusion, the OMC regimen can be regarded as a new option for patients with macroscopic lymph node involvement, especially those at stage N1. Therapy will improve the feasibility of radical cure even without the need for cystectomy in patients for whom

  20. Stem cells for cell replacement therapy: a therapeutic strategy for HD?

    Science.gov (United States)

    Rosser, Anne; Svendsen, Clive N

    2014-09-15

    Much interest has been expressed over the last couple of decades in the potential application of stem cells to medicine, both for research and diagnostic tools and as a source of donor cells for therapeutic purposes. Potential therapeutic applications include replacement of cells in many body organs where the capacity for intrinsic repair is limited, including the pancreas, heart, and brain. A key challenge is to generate the relevant donor cell types, and this is particularly challenging in the brain where the number of different neuronal subtypes is so great. Although dopamine neuron replacement in Parkinson's disease has been the focus of most clinical studies, great interest has been shown in this approach for other disorders, including Huntington's disease. Replacing complete neural circuits in the adult brain is clearly challenging, and there are many other complexities with regard to both donor cells and host. This article presents the pros and cons of taking a cell therapy approach in Huntington's disease. It considers the implantation both of cells that are already of the same neural subtype as those lost in the disease process (ie, primary fetal cells derived from the developing striatum) and those derived from stem cells, which require "directing" toward that phenotype.

  1. Phase II trial of temozolomide plus concurrent whole-brain radiation followed by TNV regimen as adjuvant therapy for patients with newly diagnosed primary CNS lymphoma

    Directory of Open Access Journals (Sweden)

    Yong Wang

    2013-01-01

    Full Text Available Background: Primary central nervous system lymphoma (PCNSL is an aggressive extranodal non-Hodgkin′s lymphoma limited to the CNS. Treatment of PCNSL with high-dose methotrexate (HD-MTX-based chemotherapy and whole-brain radiotherapy (WBRT is associated with high rates of relapse and severe treatment-related neurotoxicity. Aim: To report our experience of treating newly diagnosed PCNSL with temozolomide, nedaplatin, and vincristine (TNV, as the replacement of HD-MTX, in combination with concurrent chemoradiotherapy. Materials and Methods: Newly diagnosed PCNSL patients were given concurrent temozolomide (75 mg/m 2 , orally daily during WBRT. Then, the TNV regimen was given after four weeks. The TNV regimen consisted of temozolomide (200 mg/m 2 orally: Days 1-5, nedaplatin (80 mg/m 2 intravenous: Day 1, and vincristine (1.4 mg/m 2 intravenous: Day 1. Each cycle was of a duration of four weeks and a maximum of six cycles were applied. The primary end point was response to treatment obtained by magnetic resonance imaging (MRI. Secondary end points were progression-free survival (PFS and fewer toxic effects. Results: The study subjects included 14 patients (median age: 53.5, median Karnofsky Performance Scale (KPS: 75. The median number of TNV cycles given was five. Response to treatment: Complete response in 12 (85.7% patients, partial response in 2 (14.3% patients, and none with progressive disease. The objective response rate was 100%, and median PFS was 21.4 months. Toxicity was relatively mild, which mainly included nausea in six and fatigue in five, grade 3-4 hematotoxicity in one, and abnormal liver functions in five patients. No neurotoxicity has been observed till date. Conclusion: The efficacy outcomes in this study are comparable to other reported HD-MTX-based regimens plus WBRT, with an added favorable toxicity profile. Prospective, randomized controlled trials are warranted to confirm such results.

  2. Efficacy of Drospirenone-Containing Hormone Replacement Therapy to Reduce Vasomotor Symptoms of Menopause

    Directory of Open Access Journals (Sweden)

    Dana A. Brown

    2013-10-01

    Full Text Available Hormone replacement therapy has been proven efficacious for controlling vasomotor symptoms such as hot flushes associated with menopause. Drospirenone is a progestin with antiandrogenic and antimineralocorticoid activity that may be used in combination with estrogen to control hot flushes and offers the potential benefit of minimizing breast tenderness, blood pressure elevations and weight gain. Six clinical trials were reviewed. Of these, four trials explicitly listed hot flushes as a primary outcome. Efficacy with regards to hot flushes was found to range from modest to large (i.e., 37.5% to 94.6%, and four of the studies utilized diary cards to assess hot flushes. Results from these studies must be interpreted cautiously as quite a few limitations existed such as small population sizes involving specific ethnic groups, lack of p values with regards to baseline characteristics lending question to homogeneity, and inclusion of mostly healthy participants. Additionally, while the studies were long enough to see an effect, the long term effects of drospirenone-containing hormone replacement therapy (HRT is unknown. The available data supports the use of drospirenone-containing HRT for the treatment of hot flushes associated with menopause.

  3. Pharmacists' perceptions of participation in a community pharmacy-based nicotine replacement therapy distribution program.

    Science.gov (United States)

    Hoch, Matthew A; Hudmon, Karen Suchanek; Lee, Linh; Cupp, Rebecca; Aragon, Linda; Tyree, Rachel A; Corelli, Robin L

    2012-08-01

    The community pharmacy has been proposed as an ideal location for providing smoking cessation therapy to large numbers of patients. Studies of public health initiatives providing free nicotine replacement products through telephone quitlines have found increased call volumes and cessation rates. The purpose of this study was to evaluate a program where nicotine replacement therapy starter packs were provided to patients through community pharmacies at no cost. An online survey was developed to assess community pharmacists' participation in the program, perceptions of the initiative as a whole, and perceptions of smoking cessation counseling activities. Eighty-three pharmacists working at participating pharmacies completed the survey (65% response rate). Ninety-nine percent of pharmacists provided smoking cessation counseling during the study period; the median (IQR) number of patients counseled over the initial 3.5-months of the NRT distribution program was 50 (24-100), and the median number of minutes per counseling session was five (3-7). Most (89%) agreed smoking cessation counseling was accommodated into the pharmacy work-flow. A majority (85%) agreed the community pharmacy is an ideal location for distributing free NRT products and that the program should be replicated in other pharmacies (78%). Participating pharmacists viewed the program positively and perceived it to be effective in helping patients quit smoking. In conclusion, the community pharmacy is a viable location for implementation of community-based public health initiatives related to smoking cessation.

  4. 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.

  5. Enzyme replacement therapy in late-onset Pompe's disease: a three-year follow-up.

    Science.gov (United States)

    Winkel, Léon P F; Van den Hout, Johanna M P; Kamphoven, Joep H J; Disseldorp, Janus A M; Remmerswaal, Maaike; Arts, Willem F M; Loonen, M Christa B; Vulto, Arnold G; Van Doorn, Pieter A; De Jong, Gerard; Hop, Wim; Smit, G Peter A; Shapira, Stuart K; Boer, Marijke A; van Diggelen, Otto P; Reuser, Arnold J J; Van der Ploeg, Ans T

    2004-04-01

    Pompe's disease is an autosomal recessive myopathy. The characteristic lysosomal storage of glycogen is caused by acid alpha-glucosidase deficiency. Patients with late-onset Pompe's disease present with progressive muscle weakness also affecting pulmonary function. In search of a treatment, we investigated the feasibility of enzyme replacement therapy with recombinant human alpha-glucosidase from rabbit milk. Three patients (aged 11, 16, and 32 years) were enrolled in the study. They were all wheelchair-bound and two of them were ventilator dependent with a history of deteriorating pulmonary function. After 3 years of treatment with weekly infusions of alpha-glucosidase, the patients had stabilized pulmonary function and reported less fatigue. The youngest and least affected patient showed an impressive improvement of skeletal muscle strength and function. After 72 weeks of treatment, he could walk without support and finally abandoned his wheelchair. Our findings demonstrate that recombinant human alpha-glucosidase from rabbit milk has a therapeutic effect in late-onset Pompe's disease. There is good reason to continue the development of enzyme replacement therapy for Pompe's disease and to explore further the production of human therapeutic proteins in the milk of mammals.

  6. 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)

  7. Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency disease

    Directory of Open Access Journals (Sweden)

    Suzanne Skoda-Smith

    2009-12-01

    Full Text Available Suzanne Skoda-Smith, Troy R Torgerson, Hans D OchsSeattle Children’s Research Institute and Department of Pediatrics, University of Washington, Seattle, WashingtonAbstract: Antibody deficiency is the most frequently encountered primary immunodeficiency disease (PIDD and patients who lack the ability to make functional immunoglobulin require life-long replacement therapy to prevent serious bacterial infections. Human serum immunoglobulin manufactured from pools of donated plasma can be administered intramuscularly, intravenously or subcutaneously. With the advent of well-tolerated preparations of intravenous immunoglobulin (IVIg in the 1980s, the suboptimal painful intramuscular route of administration is no longer used. However, some patients continued to experience unacceptable adverse reactions to the intravenous preparations, and for others, vascular access remained problematic. Subcutaneously administered immunoglobulin (SCIg provided an alternative delivery method to patients experiencing difficulties with IVIg. By 2006, immunoglobulin preparations designed exclusively for subcutaneous administration became available. They are therapeutically equivalent to intravenous preparations and offer patients the additional flexibility for the self-administration of their product at home. SCIg as replacement therapy for patients with primary antibody deficiencies is a safe and efficacious method to prevent serious bacterial infections, while maximizing patient satisfaction and improving quality of life.Keywords: subcutaneous immunoglobulin, primary immunodeficiency disease, antibody deficiency, X-linked agammaglobulinemia, common variable immune deficiency

  8. [Peritoneal dialysis for acute renal failure: Rediscovery of an old modality of renal replacement therapy].

    Science.gov (United States)

    Issad, Belkacem; Rostoker, Guy; Bagnis, Corinne; Deray, Gilbert

    2016-07-01

    Acute renal failure (ARF) in adults in the intensive care unit (ICU) often evolves in a context of multiple organ failure, which explains the high mortality rate and increase treatment needs. Among, two modalities of renal replacement therapy, peritoneal dialysis (PD) was the first modality used for the treatment of ARF in the 1950s. Today, while PD is generalized for chronic renal failure treatment, its use in the ICU is limited, particularly, due to the advent of new hemodialysis techniques and the development of continuous replacement therapy. Recently, a renewed interest in the use of PD in patients with ARF has manifested in several emerging countries (Brazil, Vietnam). A systematic review in 2013 showed a similar mortality in ARF patients having PD (58%) and those treated by hemodialysis or hemodiafiltration/hemofiltration (56.1%). In the International society of peritoneal dialysis (ISPD)'s guideline (2013), PD may be used in adult ARF as the other blood extracorporeal epuration technics (recommendation with grade 1B). PD is the preferred method in cardiorenal syndromes, in frailty patients with hemodynamic instability and those lacking vascular access; finally PD is also an option in elderly and patients with bleeding tendency. In industrial countries, high volume automated PD with a flexible catheter (usually Tenckhoff) is advocated. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  9. [Pharmacokinetic principles and drug-dosing adjustments during continuous renal replacement therapies (CRRT)].

    Science.gov (United States)

    Morabito, S; Guzzo, I; Vitaliano, E; Muzi, L; Solazzo, A; Pistolesi, V; Pierucci, A

    2006-01-01

    In the critically ill, acute renal failure (ARF) and "Multiple Organ Dysfunction Syndrome" (MODS) can be associated with significant modifications of many pharmacokinetic parameters, such as protein binding, volume of distribution and total body clearance. The start of renal replacement therapy (RRT) represents an additional variable to take in consideration for drug-dosing adjustments. Drugs significantly eliminated by the kidney are likely to be removed during RRT and a supplemental dose or further dosing adjustments are required if extracorporeal clearance is more than 25-30% of total body clearance. The impact of RRT on plasma drug concentrations can be substantially different in relation to the type of treatment (diffusive, convective or both), membrane characteristics (low-flux or high-flux), filter surface area and prescribed dialysis dose. The molecular weight cut-offs of high-flux membrane are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the drugs most commonly used in the critically ill undergoing continuous renal replacement therapy (CRRT). However, diffusive clearance could be significantly lower than convective clearance for drugs in the middle molecular weight range. In any case, the extracorporeal clearances report-ed with the use of high-volume CRRT (>50-60 L/2 h) are often surprisingly elevated and can lead to drug underdosing in clinical conditions where adequate antibiotic treatment is essential.

  10. Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP.

    Science.gov (United States)

    Pawlyk, Basil S; Smith, Alexander J; Buch, Prateek K; Adamian, Michael; Hong, Dong-Hyun; Sandberg, Michael A; Ali, Robin R; Li, Tiansen

    2005-09-01

    Retinitis pigmentosa GTPase regulator (RPGR) is a photoreceptor protein anchored in the connecting cilia by an RPGR-interacting protein (RPGRIP). Loss of RPGRIP causes Leber congenital amaurosis (LCA), a severe form of photoreceptor degeneration. The current study was an investigation of whether somatic gene replacement could rescue degenerating photoreceptors in a murine model of LCA due to a defect in RPGRIP. An RPGRIP expression cassette, driven by a mouse opsin promoter, was packaged into recombinant adeno-associated virus (AAV). The AAV vector was delivered into the right eyes of RPGRIP(-/-) mice by a single subretinal injection into the superior hemisphere. The left eyes received a saline injection as a control. Full-field electroretinograms (ERGs) were recorded from both eyes at 2, 3, 4, and 5 months after injection. After the final follow-up, retinas were analyzed by immunostaining or by light and electron microscopy. Delivery of the AAV vector led to RPGRIP expression and restoration of normal RPGR localization at the connecting cilia. Photoreceptor preservation was evident by a thicker cell layer and well-developed outer segments in the treated eyes. Rescue was more pronounced in the superior hemisphere coincident with the site of delivery. Functional preservation was demonstrated by ERG. AAV-mediated RPGRIP gene replacement preserves photoreceptor structure and function in a mouse model of LCA, despite ongoing cell loss at the time of intervention. These results indicate that gene replacement therapy may be effective in patients with LCA due to a defect in RPGRIP and suggest that further preclinical development of gene therapy for this disorder is warranted.

  11. Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Pedersen, Court; Law, Matthew;

    2002-01-01

    OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA) star......OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (Euro......SIDA) starting their first HAART regimen. METHODS: Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified...... to ITT/s=f, 22-70% of the patients starting a HAART regimen in a RCT experienced a virological response at week 48. Only two RCTs had complete follow-up data (n=424): between 29 and 62% achieved a virological response at week 48 in the six treatment arms evaluated in the studies according to ITT...

  12. Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Pedersen, Court; Law, Matthew

    2002-01-01

    OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA) star......OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (Euro......SIDA) starting their first HAART regimen. METHODS: Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified...... to ITT/s=f, 22-70% of the patients starting a HAART regimen in a RCT experienced a virological response at week 48. Only two RCTs had complete follow-up data (n=424): between 29 and 62% achieved a virological response at week 48 in the six treatment arms evaluated in the studies according to ITT...

  13. 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

    Energy Technology Data Exchange (ETDEWEB)

    Penoncello, Gregory P.; Ding, George X., E-mail: george.ding@vanderbilt.edu

    2016-04-01

    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{sup 3} for head and neck plans and brain plans and a contiguous volume of 5 cm{sup 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.

  14. 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

  15. 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

    2015-01-01

    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

  16. 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

  17. 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

    markdownabstract__Abstract__ Background: 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

  18. Prostate volume and growth during testosterone replacement therapy is related to visceral obesity in Klinefelter syndrome.

    Science.gov (United States)

    Selice, R; Caretta, N; Di Mambro, A; Torino, M; Palego, P; Ferlin, A; Foresta, C

    2013-12-01

    Klinefelter syndrome (KS) is a chromosomal alteration characterized by increased risk of metabolic syndrome, mainly caused by visceral obesity. In the last years, obesity has been studied as a potential risk factor for prostate disease and recently a link has been demonstrated between visceral adiposity with prostate volume. The aim of this study was to analyze the relationship between obesity and prostate volume and growth during testosterone therapy in KS subjects. We evaluated reproductive hormones, metabolic parameters, anthropometric measures, PSA, and prostate volume in 121 naïve non-mosaic KS patients and 60 age-matched healthy male controls. Fifty-six KS hypogonadic subjects were treated with testosterone-gel 2% and reevaluated after 18 months of treatment. Prostate volume in KS was positively related to waist circumference (WC). The KS group with WC ≥94 cm had significantly higher prostate volume, BMI, insulin plasma levels, homeostasis model assessment index, total cholesterol, triglycerides, and glycemia with respect to the KS group with WC testosterone replacement therapy, only hypogonadic KS men with WC ≥94 cm had a statistically significant increase in prostate volume. Furthermore, in untreated KS subjects, prostate volume showed a statistically significant increase after 18 months of follow-up only in subjects with WC ≥94 cm. This study showed that visceral obesity, insulin resistance, and lipid and glucose metabolism alterations are associated with prostate volume and growth during testosterone replacement therapy in KS, independently from androgen or estrogen levels. These latter findings might provide the basis for a better management and follow-up of KS subjects.

  19. Partial Restoration of CFTR Function in cftr-Null Mice following Targeted Cell Replacement Therapy.

    Science.gov (United States)

    Duchesneau, Pascal; Besla, Rickvinder; Derouet, Mathieu F; Guo, Li; Karoubi, Golnaz; Silberberg, Amanda; Wong, Amy P; Waddell, Thomas K

    2017-03-01

    Cystic fibrosis (CF) is a fatal recessive genetic disorder caused by a mutation in the gene encoding CF transmembrane conductance regulator (CFTR) protein. Alteration in CFTR leads to thick airway mucus and bacterial infection. Cell therapy has been proposed for CFTR restoration, but efficacy has been limited by low engraftment levels. In our previous studies, we have shown that using a pre-conditioning regimen in combination with optimization of cell number and time of delivery, we could obtain greater bone marrow cell (BMC) retention in the lung. Here, we found that optimized delivery of wild-type (WT) BMC contributed to apical CFTR expression in airway epithelium and restoration of select ceramide species and fatty acids in CFTR(-/-) mice. Importantly, WT BMC delivery delayed Pseudomonas aeruginosa lung infection and increased survival of CFTR(-/-) recipients. Only WT BMCs had a beneficial effect beyond 6 months, suggesting a dual mechanism of BMC benefit: a non-specific effect early after cell delivery, possibly due to the recruitment of macrophages and neutrophils, and a late beneficial effect dependent on long-term CFTR expression. Taken together, our results suggest that BMC can improve overall lung function and may have potential therapeutic benefit for the treatment of CF.

  20. 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

  1. Use of testosterone replacement therapy in the United States and its effect on subsequent prostate cancer outcomes.

    Science.gov (United States)

    Kaplan, Alan L; Hu, Jim C

    2013-08-01

    To assess utilization trends and determine the effect of testosterone replacement therapy on outcomes in men who subsequently developed prostate cancer. We used linked Surveillance, Epidemiology, and End Results-Medicare data to identify 149,354 men diagnosed with prostate cancer from 1992 to 2007. Of those, 2,237 men (1.5%) underwent testosterone replacement therapy before their prostate cancer diagnosis. Propensity scoring methods were used to assess cancer-specific outcomes of testosterone replacement vs no replacement therapy. Testosterone replacement was associated with older age at cancer diagnosis, nonwhite race, and higher comorbidity (P testosterone vs testosterone before the prostate cancer diagnosis was associated with higher grade (34% vs 30%, P therapy after initial treatment. Through our observational study design, we show that testosterone use was low throughout the study period. Testosterone use was not associated with aggressive prostate cancer and did not affect overall or disease-specific mortality. Although our findings support growing evidence that testosterone replacement is safe with respect to prostate cancer, confirmatory prospective studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. [RIGHT VENTRICULAR DIASTOLIC FUNCTION AND PERIPHERAL HEMODYNAMICS IN PATIENTS WITH CHRONIC COR PULMONALE RECEIVING VARIOUS THERAPY REGIMENS].

    Science.gov (United States)

    2010-01-01

    Right ventricular diastolic function, pulmonary hemodynamics, and peripheral endothelial vasoregulatory function were studied in patients with chronic cor pulmonale during complex treatment over time. The study confirmed the vasodilatory effect of ozone therapy and amlodipine during standard therapy, which appeared as lower blood pressure and better right ventricular diastolic function.

  7. A randomized controlled comparison of three quadruple therapy regimens in a population with low Helicobacter pylori eradication rates

    NARCIS (Netherlands)

    Sotudehmanesh, Rasool; Malekzadeh, Reza; Fazel, Ali; Massarrat, Sadegh; Ziad-Alizadeh, Behrooz; Eshraghian, Mohammed Reza

    2001-01-01

    Background and Aim: We sought to compare the efficacy and tolerability of an omeprazole/clarithromycin/bismuth/tetracycline-based quadruple therapy to that of a ranitidine/metronidazole/bismuth/tetracycline-based quadruple therapy of 2 or 3 weeks duration in a population with a high prevalence of me

  8. Continuous Renal Replacement Therapy: Reviewing Current Best Practice to Provide High-Quality Extracorporeal Therapy to Critically Ill Patients.

    Science.gov (United States)

    Connor, Michael J; Karakala, Nithin

    2017-07-01

    Continuous renal replacement therapy (CRRT) use continues to expand globally. Despite improving technology, CRRT remains a complex intervention. Delivery of high-quality CRRT requires close collaboration of a multidisciplinary team including members of the critical care medicine, nephrology, nursing, pharmacy, and nutrition support teams. While significant gaps in medical evidence regarding CRRT persist, the growing evidence base supports evolving best practice and consensus to define high-quality CRRT. Unfortunately, there is wide variability in CRRT operating characteristics and limited uptake of these best practices. This article will briefly review the current best practice on important aspects of CRRT delivery including CRRT dose, anticoagulation, dialysis vascular access, fluid management, and drug dosing in CRRT. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  9. 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

  10. Pulmonary thrombosis associated with antidiuretic hormone replacement therapy due to secondary diabetes insipidus after traumatic brain injury: A case report

    Science.gov (United States)

    Naito, Kiyohito; Watari, Taiji; Yasunari, Eisuke; Yamano, Miki; Mogami, Atsuhiko; Obayashi, Osamu; Kaneko, Kazuo

    2012-01-01

    INTRODUCTION Diabetes insipidus is a well-recognized complication of traumatic brain injury. The majority of patients with post-traumatic diabetes insipidus will require antidiuretic hormone (ADH) replacement therapy and tend to show dehydration. On the other hand, some negative effects of ADH on blood coagulation, such as increased platelet cohesion and the promotion of von Willebrand factor release, have also been reported. However, the incidence of thrombosis during antidiuretic hormone replacement therapy is disputed. PRESENTATION OF CASE A case of pulmonary thrombosis associated with ADH replacement therapy due to secondary diabetes insipidus after traumatic brain injury is presented here. DISCUSSION In our case, there were three factors that may have contributed to the observed thrombosis (dehydration, bed rest for a long period and ADH replacement therapy). CONCLUSION We believe that controlling urinary output and monitoring urinary and serum osmotic pressure are necessary for the management for diabetes insipidus patients after traumatic brain injury. In particular, we must carefully monitor the management of such patients during antidiuretic hormone replacement therapy. PMID:23131855

  11. Pulmonary thrombosis associated with antidiuretic hormone replacement therapy due to secondary diabetes insipidus after traumatic brain injury: A case report.

    Science.gov (United States)

    Naito, Kiyohito; Watari, Taiji; Yasunari, Eisuke; Yamano, Miki; Mogami, Atsuhiko; Obayashi, Osamu; Kaneko, Kazuo

    2013-01-01

    Diabetes insipidus is a well-recognized complication of traumatic brain injury. The majority of patients with post-traumatic diabetes insipidus will require antidiuretic hormone (ADH) replacement therapy and tend to show dehydration. On the other hand, some negative effects of ADH on blood coagulation, such as increased platelet cohesion and the promotion of von Willebrand factor release, have also been reported. However, the incidence of thrombosis during antidiuretic hormone replacement therapy is disputed. A case of pulmonary thrombosis associated with ADH replacement therapy due to secondary diabetes insipidus after traumatic brain injury is presented here. In our case, there were three factors that may have contributed to the observed thrombosis (dehydration, bed rest for a long period and ADH replacement therapy). We believe that controlling urinary output and monitoring urinary and serum osmotic pressure are necessary for the management for diabetes insipidus patients after traumatic brain injury. In particular, we must carefully monitor the management of such patients during antidiuretic hormone replacement therapy. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  12. Structured self-monitoring of blood glucose regimens improve glycemic control in poorly controlled Chinese patients on insulin therapy: Results from COMPASS.

    Science.gov (United States)

    Ji, Linong; Su, Qing; Feng, Bo; Shan, Zhongyan; Hu, Renming; Xing, Xiaoping; Xue, Yaoming; Yang, Tao; Hua, Yanyin

    2017-05-01

    The use of self-monitoring of blood glucose (SMBG) among patients with insulin-treated, type 2 diabetes (T2DM) in China is suboptimal. Herein we evaluated the effectiveness of structured SMBG for improving glycemic control and increasing the frequency of SMBG. Insulin-treated (>3 months) T2DM patients aged ≥18 years with HbA1c >8.0 % (64 mmol/mol) were recruited to the study. They received SMBG materials and were advised on a structured SMBG regimen for their insulin therapy. Patients were trained to self-adjust insulin dosage according to SMBG readings and were seen by physicians at Months 3 and 6. Endpoints included changes in HbA1c, SMBG frequency, and hypoglycemia frequency. The study enrolled 820 patients, with mean (± SD) age 55.1 ± 9.8 years, body mass index 24.9 ± 3.6 kg/m(2) , HbA1c 9.7 ± 1.6 % (83 mmol/mol), and diabetes duration 9.8 ± 7.1 years, with median insulin therapy of 30.3 (3.0-274.1) months, from 19 Chinese clinics. By Month 3, 99.9 % of patients performed daily SMBG. At Months 3 and 6, HbA1c had decreased from baseline (-1.81 % and -1.73 %, respective; P insulin therapy. A structured SMBG regimen, with training on interpretation of and responses to SMBG readings, increased SMBG frequency and improved HbA1c and the management of insulin-treated T2DM. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  13. Effectiveness and tolerance of single tablet versus once daily multiple tablet regimens as first-line antiretroviral therapy - Results from a large french multicenter cohort study

    Science.gov (United States)

    Cotte, Laurent; Ferry, Tristan; Pugliese, Pascal; Valantin, Marc-Antoine; Allavena, Clotilde; Cabié, André; Poizot-Martin, Isabelle; Rey, David; Duvivier, Claudine; Cheret, Antoine; Dellamonica, Pierre; Pradat, Pierre; Parienti, Jean-Jacques

    2017-01-01

    Objectives Pill burden during antiretroviral treatment (ART) is associated with worse adherence and impaired virological suppression. We compared the effectiveness, tolerance, and persistence on treatment of single tablet regimens (STRs) with non-STR once-daily regimens in patients receiving first-line ART. Methods Retrospective analysis of naïve HIV-1 infected patients prospectively enrolled in the French Dat’AIDS cohort and initiating first-line ART with STRs or once-daily non-STRs from 2004 to 2013. The primary outcome was time to treatment discontinuation defined by any change in the treatment regimen. STR and non-STR groups were compared controlling for baseline risk factors by inverse probability weighted treatment Cox analysis (IPWT) and propensity-score matching (PSM). Results Overall, 3212 patients (STR 499, non-STR 2713) were included. Median time to treatment discontinuation was shorter in non-STR patients than in STR patients, both in the IPWT (HR = 0.61, pPSM cohort (HR = 0.55, pPSM cohort (HR = 0.91, p = 0.33). A lower rate of virological failure was observed with STRs than with non-STRs in both cohorts (HR = 0.23; p = 0.002 and HR = 0.22, p = 0.003, respectively). A lower rate of treatment modification for adverse event was observed with non-STRs in the IPWT cohort (HR = 1.46, pPSM cohort (HR = 1.22, p = 0.11). Conclusion First-line therapy with STRs was associated with a longer time to treatment discontinuation than with non-STRs. However, when ART modification for simplification was not considered as a failure, STRs and non-STRs were similar. PMID:28152047

  14. Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy.

    Science.gov (United States)

    Smetana, Keaton S; Cook, Aaron M; Bastin, Melissa L Thompson; Oyler, Douglas R

    2016-12-01

    The aim of this review was to evaluate current literature for dosing recommendations for the use of antiepileptic medications in patients receiving renal replacement therapy (RRT). With the assistance of an experienced medical librarian specialized in pharmacy and toxicology, we searched MEDLINE, EMBASE, CINAHL, Web of Science, WorldCat, and Scopus through May 2016. Four hundred three articles were screened for inclusion, of which 130 were identified as potentially relevant. Micromedex® DRUGDEX as well as package inserts were used to obtain known pharmacokinetic properties and dosage adjustment recommendations in RRT if known. Data regarding antiepileptic drug use in RRT are limited and mostly consist of case reports limiting our proposed dosing recommendations. Known pharmacokinetic parameters should guide dosing, and recommendations are provided where possible. Additional studies are necessary before specific dosing recommendations can be made for most antiepileptic drugs in critically ill patients receiving RRT, specifically with newer agents. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. [Testosterone replacement therapy and prostate cancer: the downfall of a paradigm?].

    Science.gov (United States)

    Castillo, Octavio A; López-Fontana, Gastón; Vidal-Mora, Ivar; López Laur, José Daniel

    2015-04-06

    For six decades, it has been a part of the conventional medical wisdom that higher levels of testosterone increase the risk of prostate cancer. This belief is mostly derived from the well-documented regression of prostate cancer after surgical or pharmacological castration. However, there is an absence of scientific data supporting the concept that higher testosterone levels are associated with an increased risk of prostate cancer. Moreover, men with hypogonadism have substantial rates of prostate cancer in prostatic biopsies, suggesting that low testosterone has no protective effect against the development of prostate cancer. Moreover, prostate cancer rate is higher in elderly patients when hormonal levels are low. These results argue against an increased risk of prostate cancer with testosterone replacement therapy.

  16. Subcutaneous pellet testosterone replacement therapy: the "first steps" in treating men with spinal cord injuries.

    Science.gov (United States)

    Gray, Kendra M; Derosa, Angela

    2013-12-01

    The authors describe the case of a 36-year-old man who presented with hormone level concerns 6 months after a rock climbing accident that resulted in paraplegia. Hypogonadism was diagnosed, and the patient received subcutaneous pellet testosterone replacement therapy. Within 6 months, the patient had substantial improvement in muscle function and was able to take several steps with the assistance of crutches or a walker. This case highlights the potential improvement in quality of life and overall prognosis resulting from the subcutaneous pellet form of testosterone when used as part of the overall treatment plan in such patients. Considering the overwhelming preponderance of hypogonadism in men with spinal cord injuries, the standard of care for such patients should include screening, laboratory hormone evaluation, and prompt treatment for testosterone deficiency.

  17. Expression and purification of a human, soluble Arylsulfatase A for Metachromatic Leukodystrophy enzyme replacement therapy.

    Science.gov (United States)

    Martino, Sabata; Consiglio, Antonella; Cavalieri, Cristina; Tiribuzi, Roberto; Costanzi, Egidia; Severini, Giovanni Maria; Emiliani, Carla; Bordignon, Claudio; Orlacchio, Aldo

    2005-05-25

    The production of active Arylsulfatase A is a key step in the development of enzyme replacement therapy for Metachromatic Leukodystrophy. To obtain large amounts of purified Arylsulfatase A for therapeutic use, we combined a retroviral expression system with a versatile and rapid purification protocol that can easily and reliably be adapted to high-throughput applications. The purification method consists of an initial ion-exchange DEAE-cellulose chromatography step followed by immuno-affinity purification using a polyclonal antibody against a 29-mer peptide of the Arylsulfatase A sequence. Immuno-adsorbed protein was eluted with a combination of acidic pH and an optimal concentration of the 29-mer peptide. This protocol reproducibly yielded approximately 100 microg of >99% pure human Arylsulfatase A, corresponding to 152 mU of enzyme activity, per liter of culture medium with properties similar to those of human non-recombinant protein.

  18. 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...... birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0...

  19. 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.

  20. Hormone Replacement Therapy: An Increased Risk of Recurrence and Mortality for Breast Cancer Patients?

    Science.gov (United States)

    Lupo, Molly; Dains, Joyce E.; Madsen, Lydia T.

    2015-01-01

    Historically, randomized controlled trials (RCTs) have shown an increased risk of recurrence and mortality among women who have used primarily oral HRT after breast cancer. However, many of these studies have had design flaws that may impact the findings. Numerous investigators have concluded that additional RCTs should be performed, but because of ethical issues and logistic challenges, large-scale RCTs are unlikely. Thus, the authors conducted an integrative review investigating recurrence and mortality data among breast cancer survivors who have used hormone replacement therapy (HRT). They recommend a stepwise algorithm for treating vaginal symptoms in breast cancer survivors: (1) start with nonhormonal treatments; (2) progress to a detailed discussion among patients and health-care professionals about the current known risks and benefits of vaginal estrogen; and (3) conclude with mutual decision-making between health-care providers and patients regarding the use of vaginal estrogen treatment. PMID:26705493

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

    DEFF Research Database (Denmark)

    Fosbøl, Emil L; Kamper, Anne-Lise; Køber, Lars;

    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...... and Transplantation, including etiological diagnosis. The use of NSAID before the start of RRT was studied by linkage to the National Prescription Register and comorbidity by linkage to the National Patient Registry. RESULTS: A total of 6663 patients were included in the study, and 2407 patients (36.1%) were...

  2. Delivery and performance of surfactant replacement therapies to treat pulmonary disorders.

    Science.gov (United States)

    El-Gendy, Nashwa; Kaviratna, Anubhav; Berkland, Cory; Dhar, Prajnaparamita

    2013-08-01

    Lung surfactant is crucial for optimal pulmonary function throughout life. An absence or deficiency of surfactant can affect the surfactant pool leading to respiratory distress. Even if the coupling between surfactant dysfunction and the underlying disease is not always well understood, using exogenous surfactants as replacement is usually a standard therapeutic option in respiratory distress. Exogenous surfactants have been extensively studied in animal models and clinical trials. The present article provides an update on the evolution of surfactant therapy, types of surfactant treatment, and development of newer-generation surfactants. The differences in the performance between various surfactants are highlighted and advanced research that has been conducted so far in developing the optimal delivery of surfactant is discussed.

  3. Adjacent central venous catheters can result in immediate aspiration of infused drugs during renal replacement therapy.

    Science.gov (United States)

    Kam, K Y R; Mari, J M; Wigmore, T J

    2012-02-01

    Dual-lumen haemodiafiltration catheters enable continuous renal replacement therapy in the critically ill and are often co-located with central venous catheters used to infuse drugs. The extent to which infusions are immediately aspirated by an adjacent haemodiafiltration catheter remains unknown. A bench model was constructed to evaluate this effect. A central venous catheter and a haemodiafiltration catheter were inserted into a simulated central vein and flow generated using centrifugal pumps within the simulated vein and haemodiafiltration circuit. Ink was used as a visual tracer and creatinine solution as a quantifiable tracer. Tracers were completely aspirated by the haemodiafiltration catheter unless the infusion was at least 1 cm downstream to the arterial port. No tracer was aspirated from catheters infusing at least 2 cm downstream. Orientation of side ports did not affect tracer elimination. Co-location of central venous and haemodiafiltration catheters may lead to complete aspiration of infusions into the haemodiafilter with resultant drug under-dosing.

  4. Predictive value of NGAL for use of renal replacement therapy in patients with severe sepsis

    DEFF Research Database (Denmark)

    Hjortrup, P B; Haase, N; Treschow, F;

    2015-01-01

    BACKGROUND: The predictive value of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) for use of renal replacement therapy (RRT) and acute kidney injury (AKI) is not established in patients with severe sepsis. METHODS: This was a prospective observational study in three general...... intensive care units (ICUs) in adult ICU patients with severe sepsis needing fluid resuscitation and a sub-study of the 6S trial. Plasma and urine were sampled at baseline and NGAL was measured using particle-enhanced turbidimetric immunoassay (The NGAL Test). Outcome measures were use of RRT in ICU......ROCs. CONCLUSION: In ICU patients with severe sepsis, plasma and urine NGAL had low predictive power for use of RRT, AKI and 90-day mortality. These results were supported by sensitivity and exploratory analyses....

  5. European consensus for starting and stopping enzyme replacement therapy in adult patients with Pompe disease

    DEFF Research Database (Denmark)

    van der Ploeg, Ans T.; Kruijshaar, Michelle E.; Toscano, A.

    2017-01-01

    synthesis is presented. RESULTS: Consensus was reached on how the diagnosis of Pompe disease should be confirmed, when treatment should be started, reasons for stopping treatment and the use of ERT during pregnancy. This was based on expert opinion and supported by the literature. One clinical trial and 43......BACKGROUND AND PURPOSE: Pompe disease is a rare inheritable muscle disorder for which enzyme replacement therapy (ERT) has been available since 2006. Uniform criteria for starting and stopping ERT in adult patients were developed and reported here. METHODS: Three consensus meetings were organized...... through the European Pompe Consortium, a network of experts from 11 European countries in the field of Pompe disease. A systematic review of the literature was undertaken to determine the effectiveness of ERT in adult patients on a range of clinical outcome measures and quality of life. A narrative...

  6. Exploratory survey study of long-term users of nicotine replacement therapy in Danish consumers

    DEFF Research Database (Denmark)

    Borup, Gitte; Christrup, Lona Louring; Lyngby Mikkelsen, Kim

    Background Long-term use of nicotine replacement therapy (NRT) has been approved in several countries for smokers who are unable or unwilling to quit smoking. However, information on basic characteristics, degree of nicotine dependence, health status and contentment with long-term use of NRT...... is scarce. The aim of this study was to collect information on the characteristics of long-term NRT users, having used NRT for at least 12 months, reasons for, and contentment with, their continued use of NRT including reasons for wishing to quit or sustain use and an estimation of their degree of nicotine...... to estimate nicotine dependence. Linear regression was used to test association between time to first NRT and daily dosage of NRT. Results A total of 92 respondents were included in the data analysis. A majority of 88% wished to quit NRT for the following reasons: costs of NRT, being tired of feeling addicted...

  7. Exploratory survey study of long-term users of nicotine replacement therapy in Danish consumers

    DEFF Research Database (Denmark)

    Borup, Gitte; Lyngby Mikkelsen, Kim; Tønnesen, Philip

    2015-01-01

    Background: Long-term use of nicotine replacement therapy (NRT) has been approved in several countries for smokers who are unable or unwilling to quit smoking. However, information on basic characteristics, degree of nicotine dependence, health status and contentment with long-term use of NRT...... is scarce. The aim of this study was to collect information on the characteristics of long-term NRT users, having used NRT for at least 12 months, reasons for, and contentment with, their continued use of NRT including reasons for wishing to quit or sustain use and an estimation of their degree of nicotine...... to estimate nicotine dependence. Linear regression was used to test association between time to first NRT and daily dosage of NRT. Results: A total of 92 respondents were included in the data analysis. A majority of 88% wished to quit NRT for the following reasons: costs of NRT, being tired of feeling...

  8. 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

    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......, 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......, 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...

  9. Changing pattern of thyroid and adrenal function in postmenopausal women after hormone replacement therapy

    Institute of Scientific and Technical Information of China (English)

    Lu Shu-lan; Yu Shan-shan; Cao Zuan-sun

    2005-01-01

    Objective:To investigate the changing pattern of thyroid and adrenal function in postmenopausal women; and the relationship between hormone replacement therapy (HRT) and thyroid and adrenal function. Methods:The levels of tT3, tT4, fT3, fT4, TSH and cortisol were measured in 60 postmenopausal women (30 cases in HRT group; 30 cases in control group) before and 12 months after HRT.Results:The serum levels of tT3, tT4, fT3, fT4, TSH and cortisol had no significant difference before and 12 months after HRT in postmenopausal women. The values of them were all in normal ranges.Conclusion:Changing pattern of thyroid and adrenal function was not as significant as that of gonads in postmenopausal women and the impact of HRT on it was not so significantly evident.

  10. 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

    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...... 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...

  11. Enhancing team-based active learning through hands-on experience with nicotine replacement therapy.

    Science.gov (United States)

    Franks, Andrea S

    2013-08-12

    To enhance tobacco cessation active-learning in an ambulatory care elective course by adding hands-on experience with nicotine replacement therapy to a team-based learning (TBL) session. A hands-on experience that included students chewing a piece of nicotine gum was added to a TBL class session. Student pairs used a skills checklist to evaluate and give peer feedback on appropriate counseling and gum use. Students' scores on a tobacco cessation examination were higher than those of students enrolled in the previous course in which TBL alone had been used. Based on pre- and post-experience survey responses, students' perceptions regarding their abilities to provide tobacco cessation counseling improved. Subjective student comments regarding the experience were positive. Participating in a TBL session that incorporated hands-on experience with nicotine gum in an ambulatory care elective course increased students' confidence in their ability to provide tobacco cessation counseling and provided a unique perspective on the product's characteristics.

  12. 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 score...... 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...... "never users" of HRT and "future users", defined as women who started HRT subsequent to baseline registration during the observation period. The groups were compared by multivariate statistical methods to adjust for confounding factors. RESULTS: Women with high neuroticism score at the age of 40 were...

  13. [Hormone replacement therapy--growth hormone, melatonin, DHEA and sex hormones].

    Science.gov (United States)

    Fukai, Shiho; Akishita, Masahiro

    2009-07-01

    The ability to maintain active and independent living as long as possible is crucial for the healthy longevity. Hormones responsible for some of the manifestations associated with aging are growth hormone, insulin-like growth factor-1 (IGF-1), melatonin, dehydroepiandrosterone (DHEA), sex hormones and thyroid hormones. These hormonal changes are associated with changes in body composition, visceral obesity, muscle weakness, osteoporosis, urinary incontinence, loss of cognitive functioning, reduction in well being, depression, as well as sexual dysfunction. With the prolongation of life expectancy, both men and women today live the latter third life with endocrine deficiencies. Hormone replacement therapy may alleviate the debilitating conditions of secondary partial endocrine deficiencies by preventing or delaying some aspects of aging.

  14. Phytoestrogens as alternative hormone replacement therapy in menopause: What is real, what is unknown.

    Science.gov (United States)

    Moreira, Ana C; Silva, Ana M; Santos, Maria S; Sardão, Vilma A

    2014-09-01

    Menopause is characterized by an altered hormonal status and by a decrease in life quality due to the appearance of uncomfortable symptoms. Nowadays, with increasing life span, women spend one-third of their lifetime under menopause. Understanding menopause-associated pathophysiology and developing new strategies to improve the treatment of menopausal-associated symptoms is an important topic in the clinic. This review describes physiological and hormone alterations observed during menopause and therapeutic strategies used during this period. We critically address the benefits and doubts associated with estrogen/progesterone-based hormone replacement therapy (HRT) and discuss the use of phytoestrogens (PEs) as a possible alternative. These relevant plant-derived compounds have structural similarities to estradiol, interacting with cell proteins and organelles, presenting several advantages and disadvantages versus traditional HRT in the context of menopause. However, a better assessment of PEs safety/efficacy would warrant a possible widespread clinical use.

  15. Hormone replacement therapy and age-related brain shrinkage: regional effects.

    Science.gov (United States)

    Raz, Naftali; Rodrigue, Karen M; Kennedy, Kristen M; Acker, James D

    2004-11-15

    Neuroprotective properties of estrogen have been established in animal models, but clinical trials of hormone replacement therapy (HRT) produced contradictory results. We examined the impact of HRT on age-related regional changes in human brain volume. Six brain regions were measured twice, five years apart, in 12 healthy women who took HRT and in matched controls who did not. The controls showed a typical pattern of differential brain shrinkage in the association cortices and the hippocampus with no change in the primary visual cortex. In contrast, women who took HRT showed comparable shrinkage of the hippocampus but no significant shrinkage of the neocortex. Future large scale studies may benefit from applying regional rather than global measures in assessment of brain integrity.

  16. Mortality from infections and malignancies in patients treated with renal replacement therapy

    DEFF Research Database (Denmark)

    Vogelzang, Judith L; van Stralen, Karlijn J; Noordzij, Marlies

    2015-01-01

    disease were associated with an increased risk of infection-related mortality. The sex difference was most pronounced for dialysis patients aged 0-39 years, with women having a 32% (adjusted HR 1.32 95% CI 1.09-1.60) higher risk of infection-related mortality than men. Mortality from malignancies was 2...... compared with the general population by age group and sex. METHODS: We followed 168 156 patients included in the ERA-EDTA registry who started RRT in 1993-2007 until 1 January 2012. Age- and cause-specific mortality rates per 1000 person-years (py) and mortality rate ratios (MRRs) compared......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...

  17. Replacing SUs with incretin-based therapies for type 2 diabetes mellitus: challenges and feasibility

    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...... with increased beta-cell apoptosis, suggesting that SU may actually accelerate the progressive decrease in beta-cell mass, thereby promoting the need for insulin replacement. In contrast, the newly developed incretin-based therapies for T2DM employ the beta-cell-preserving properties of incretin hormones......, these effects result in hyperglycemia. In 1958, sulfonylurea (SU) was introduced to the market as one of the first oral treatments for T2DM. Since then, the ability of SU to stimulate the release of insulin from pancreatic beta-cells by the closure of ATP-sensitive K+-channels has been employed as one...

  18. 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

  19. Knockdown and replacement therapy mediated by artificial mirtrons in spinocerebellar ataxia 7.

    Science.gov (United States)

    Curtis, Helen J; Seow, Yiqi; Wood, Matthew J A; Varela, Miguel A

    2017-07-27

    We evaluate a knockdown-replacement strategy mediated by mirtrons as an alternative to allele-specific silencing using spinocerebellar ataxia 7 (SCA7) as a model. Mirtrons are introns that form pre-microRNA hairpins after splicing, producing RNAi effectors not processed by Drosha. Mirtron mimics may therefore avoid saturation of the canonical processing pathway. This method combines gene silencing mediated by an artificial mirtron with delivery of a functional copy of the gene such that both elements of the therapy are always expressed concurrently, minimizing the potential for undesirable effects and preserving wild-type function. This mutation- and single nucleotide polymorphism-independent method could be crucial in dominant diseases that feature both gain- and loss-of-function pathologies or have a heterogeneous genetic background. Here we develop mirtrons against ataxin 7 with silencing efficacy comparable to shRNAs, and introduce silent mutations into an ataxin 7 transgene such that it is resistant to their effect. We successfully express the transgene and one mirtron together from a single construct. Hence, we show that this method can be used to silence the endogenous allele of ataxin 7 and replace it with an exogenous copy of the gene, highlighting the efficacy and transferability across patient genotypes of this approach. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Directory of Open Access Journals (Sweden)

    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

  1. Initial catch-up growth in children with hypothyroidism on thyroxine replacement therapy

    Directory of Open Access Journals (Sweden)

    Rajitha D

    2015-07-01

    Full Text Available Background: There is a paucity of observational data from India on initial catch up growth in hypothyroid children started on thyroxine replacement therapy. Methods: We retrospectively studied 44 children and adolescents (32 girls with a diagnosis of primary hypothyroidism i.e., (thyrotropin > 15 µIU/mL and thyroxine < 55ng/mL. All were started on treatment with oral thyroxine. The dose was adjusted to maintain thyrotropin between 0.5-5 µIU/mL. Height was measured at baseline and at each follow-up visit and height standard deviation scores (HtSDS were calculated. We studied the therapeutic benefit of thyroxine replacement therapy on growth in the initial couple of years of treatment. Results: Dose of thyroxine required to restore euthyroidism was 4.1±2.5 µg/kg body weight. The dose fell from 9.7±2.4 µg/kg body weight in infants to 3.0±1.5 µg/kg body weight in adolescence (p<0.001. Likewise, the dose per unit body surface area also fell consistently from 207 ± 70.3 µg/m2 in infants to only 89.3±17.9 µg/m2 in adolescents (p<0.001. The initial HtSDS was 2.0±1.5 and this improved by 0.4 to final value of 1.6±1.3 (p < 0.001 after an average follow up of 14.1±2.5 months. The mean catch-up growth velocity, weighted for the duration of follow-up was 7.7 cm/year. Conclusions: The HtSDS deficit because of hypothyroidism is partially regained in the first few years after treatment.

  2. Dialysis patients refusing kidney transplantation: data from the Slovenian Renal Replacement Therapy Registry.

    Science.gov (United States)

    Buturović-Ponikvar, Jadranka; Gubenšek, Jakob; Arnol, Miha; Bren, Andrej; Kandus, Aljoša; Ponikvar, Rafael

    2011-06-01

    Kidney transplantation is considered the best renal replacement therapy (RRT) for patients with end-stage renal disease; nevertheless, some dialysis patients refuse to be transplanted. The aim of our registry-based, cross-sectional study was to compare kidney transplant candidates to dialysis patients refusing transplantation. Data were collected from the Slovenian Renal Replacement Therapy Registry database, as of 31 December 2008. Demographic and some RRT data were compared between the groups. There were 1448 dialysis patients, of whom 1343 were treated by hemodialysis and 105 by peritoneal dialysis (PD); 132 (9%) were on the waiting list for transplantation, 208 (14%) were preparing for enrollment (altogether 340 [23%] dialysis patients were kidney transplant candidates); 200 (13.7%) patients were reported to refuse transplantation, all ≤ 65 years of age; 345 (24%) were not enrolled due to medical contraindications, 482 (33%) due to age, and 82 (6%) due to other or unknown reasons. No significant difference was found in age, gender, or presence of diabetes between kidney transplant candidates vs. patients refusing transplantation (mean age 50.5 ± 13.9 vs. 51.3 ± 9.6 years, males 61% vs. 63%, diabetics 18% vs. 17%). The proportion of patients ≤ 65 years old who were refusing transplantation was 28% (187/661) for hemodialysis and 17% (13/79) for PD patients (P = 0.03). There is a considerable group of dialysis patients in Slovenia refusing kidney transplantation. Compared to the kidney transplant candidates, they are similar in age, gender and prevalence of diabetes. Patients treated by peritoneal dialysis refuse kidney transplantation less often than hemodialysis patients.

  3. 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, pcortisol 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.

  4. Ultrafiltration rate is an important determinant of microcirculatory alterations during chronic renal replacement therapy.

    Science.gov (United States)

    Veenstra, Gerke; Pranskunas, Andrius; Skarupskiene, Inga; Pilvinis, Vidas; Hemmelder, Marc H; Ince, Can; Boerma, E Christiaan

    2017-02-20

    Hemodialysis (HD) with ultrafiltration (UF) in chronic renal replacement therapy is associated with hemodynamic instability, morbidity and mortality. Sublingual Sidestream Dark Field (SDF) imaging during HD revealed reductions in microcirculatory blood flow (MFI). This study aims to determine underlying mechanisms. The study was performed in the Medical Centre Leeuwarden and the Lithuanian University of Health Sciences. Patients underwent 4-h HD session with linear UF. Nine patients were subject to combinations of HD and UF: 4 h of HD followed by 1 h isolated UF and 4 h HD with blood-volume-monitoring based UF. Primary endpoint: difference in MFI before and after intervention. During all sessions monitoring included blood pressure, heartrate and SDF-imaging. NCT01396980. Baseline characteristics were not different between the two centres as within the HD/UF modalities. MFI was not different before and after HD with UF. Total UF did not differ between modalities. Median MFI decreased significantly during isolated UF [2.8 (2.5-2.9) to 2.5 (2.2-2.8), p = 0.03]. Baseline MFI of each UF session was correlated with MFI after the intervention (r s = 0.52, p = 0.006). During HD with UF or isolated HD we observed no changes in MFI. This indicates that non-flow mediated mechanisms are of unimportance. During isolated UF we observed a reduction in MFI in conjunction with a negative intravascular fluid balance. The correlation between MFI before and after intervention suggests that volume status at baseline is a factor in microvascular alterations. In conclusion we observed a significant decrease of sublingual MFI, related to UF rate during chronic renal replacement therapy.

  5. Hormone Replacement Therapy and Physical Function in Healthy Older Men. Time to Talk Hormones?

    Science.gov (United States)

    Giannoulis, Manthos G.; Martin, Finbarr C.; Nair, K. Sreekumaran; Umpleby, A. Margot

    2012-01-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established

  6. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones?

    Science.gov (United States)

    Giannoulis, Manthos G; Martin, Finbarr C; Nair, K Sreekumaran; Umpleby, A Margot; Sonksen, Peter

    2012-06-01

    Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established.

  7. Quality of pharmacokinetic studies in critically ill patients receiving continuous renal replacement therapy.

    Science.gov (United States)

    Vaara, S; Pettila, V; Kaukonen, K-M

    2012-02-01

    Continuous renal replacement therapy (CRRT) is the preferred renal replacement therapy modality in the critically ill. We aimed to reveal the literature on the pharmacokinetic studies in critically ill patients receiving CRRT with special reference to quality assessment of these studies and the CRRT dose. We conducted a systematic review by searching the MEDLINE, EMBASE, and the Cochrane databases to December 2009 and bibliographies of relevant review articles. We included original studies reporting from critically ill adult subjects receiving CRRT because of acute kidney injury with a special emphasis on drug pharmacokinetics. We used the minimum reporting criteria for CRRT studies by Acute Dialysis Quality Initiative (ADQI) and, second, the Downs and Black checklist to assess the quality of the studies. We calculated the CRRT dose per study. We included pharmacokinetic parameters, residual renal function, and recommendations on drug dosing. Of 182 publications, 95 were considered relevant and 49 met the inclusion criteria. The median [interquartile range (IQR)] number of reported criteria by ADQI was 7.0 (5.0-8.0) of 12. The median (IQR) Downs and Black quality score was 15 (14-16) of 32. None of the publications reported CRRT dose directly. The median (IQR) weighted CRRT dose was 23.7 (18.8-27.9) ml/kg/h. More attention should be paid both to standardizing the CRRT dose and reporting of the CRRT parameters in pharmacokinetic studies. The general quality of the studies during CRRT in the critically ill was only moderate and would be greatly improved by reports in concordant with the ADQI recommendations. © 2011 The Authors Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.

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

    Science.gov (United States)

    Chew, Fiona; Wu, Xianwei

    2017-01-01

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

    Science.gov (United States)

    Wu, Xianwei

    2017-01-01

    Objective 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). Methods 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. Results 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. Conclusion 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. PMID:28158240

  10. 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

    OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1.......0 and -2.5 SD of the premenopausal mean value] were enrolled in a 2-year prospective, randomized study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All received a daily supplement of 500 mg calcium and 400 IU...... 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...

  11. Application of a pattern of incremental haemodialysis, based on residual renal function, when starting renal replacement therapy.

    Science.gov (United States)

    Merino, José L; Domínguez, Patricia; Bueno, Blanca; Amézquita, Yésika; Espejo, Beatriz; Paraíso, Vicente

    The interest in the preservation of residual kidney function on starting renal replacement therapy (RRT) is very common in techniques such as peritoneal dialysis but less so in haemodialysis (HD). In our centre the pattern of incremental dialysis (2 HD/week) has been an option for a group of patients. Here we share our experience with this regimen from March 2008. We included incident patients with residual diuresis >1,000ml/24h, clinical stability, absence of oedema, absence of hyperkalaemia >6.5 mEq/l and phosphoremia >6mg/dl, with acceptable comprehension of dietetic care. Exclusion criteria were: Clinical instability, no dietary or medical compliance and the afore mentioned laboratory abnormalities. A total of 24patients were included in incremental technique. The mean age at start of RRT was 60 (15 years. The average time on incremental technique was 19 (18 months (range: 7-80), with a mean time on dialysis of 31 (23 months (range: 12-86). The reasons for transfer to thrice-weekly HD were: in 6patients due to laboratory tests, in 2patients for heart failure events, one for poor compliance and 3for receiving a kidney graft. The residual diuresis decreased in the first year from 2,106 (606ml/day to 1,545 (558 (P=.17) with the urea clearance and calculated residual renal function, basal 5.7 (1.5vs. 3.8 (1.9ml/min per year (P=.01) and basal 8.9 (2.4vs. 6.9 (4.3 per year (P=.28), respectively. Incremental HD treatment, with twice-weekly HD, may be an alternative in selected patients. This approach can largely preserve residual renal function at least for the first year. Although this pattern probably is not applicable to all patients starting RRT, it can and should be an initial alternative to consider. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome.

    Science.gov (United States)

    Hendriksz, Christian J; Parini, Rossella; AlSayed, Moeenaldeen D; Raiman, Julian; Giugliani, Roberto; Solano Villarreal, Martha L; Mitchell, John J; Burton, Barbara K; Guelbert, Norberto; Stewart, Fiona; Hughes, Derralynn A; Berger, Kenneth I; Slasor, Peter; Matousek, Robert; Jurecki, Elaina; Shaywitz, Adam J; Harmatz, Paul R

    2016-09-01

    Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and

  13. 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.

  14. Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy.

    Science.gov (United States)

    Chan, Sharon; Debono, Miguel

    2010-06-01

    Cortisol has one of the most distinct and fascinating circadian rhythms in human physiology. This is regulated by the central clock located in the suprachiasmatic nucleus of the hypothalamus. It has been suggested that cortisol acts as a secondary messenger between central and peripheral clocks, hence its importance in the synchronization of body circadian rhythms. Conventional immediate-release hydrocortisone, either at twice- or thrice-daily doses, is not capable of replicating physiological cortisol circadian rhythm and patients with adrenal insufficiency or congenital adrenal hyperplasia still suffer from a poor quality of life and increased mortality. Novel treatments for replacement therapy are therefore essential. Proof-of-concept studies using hydrocortisone infusions suggest that the circadian delivery of hydrocortisone may improve biochemical control and life quality in patients lacking cortisol with an impaired cortisol rhythm. Recently oral formulations of modified-release hydrocortisone are being developed and it has been shown that it is possible to replicate cortisol circadian rhythm and also achieve better control of morning androgen levels. These new drug therapies are promising and potentially offer a more effective treatment with less adverse effects. Definite improvements clearly need to be established in future clinical trials.

  15. 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.

  16. 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 

  17. 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.

  18. Testosterone replacement therapy among HIV-infected men in the CFAR Network of Integrated Clinical Systems.

    Science.gov (United States)

    Bhatia, Ramona; Murphy, Adam B; Raper, James L; Chamie, Gabriel; Kitahata, Mari M; Drozd, Daniel R; Mayer, Kenneth; Napravnik, Sonia; Moore, Richard; Achenbach, Chad

    2015-01-02

    The objectives of this study were to determine the rate of testosterone replacement therapy (TRT) initiation, TRT predictors and associated monitoring in HIV-infected men. A multisite cohort study. We examined TRT initiation rates and monitoring among adult HIV-infected men in routine care at seven sites in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) from 1996 to 2011. We determined TRT predictors using Cox regression modelling. Of 14 454 men meeting inclusion criteria, TRT was initiated in 1482 (10%) with an initiation rate of 19.7/1000 person-years [95% confidence interval (95% CI) 18.7-20.7]. In the multivariable model, TRT was significantly associated with age at least 35 years, white race, diagnosis of AIDS wasting, hepatitis C coinfection, protease inhibitor based antiretroviral therapy and nadir CD4 cell count of 200 cells/μl or less. Overall, 1886 out of 14 454 (13%) had testosterone deficiency. Among those initiating TRT, 992 out of 1482 (67%) had a pre-TRT serum total testosterone measured, and deficiency [testosterone was measured within 6 months of TRT initiation in 377 out of 1482 (25%) men. TRT was common in HIV-infected men, though evidence for pre-TRT testosterone deficiency was lacking in 76%. Endocrine guidelines for post-TRT monitoring were uncommonly followed. Given cardiovascular and other risks associated with TRT, efforts should focus on understanding factors driving these TRT practices in HIV-infected men.

  19. Current practice in continuous renal replacement therapy: An epidemiological multicenter study.

    Science.gov (United States)

    Tomasa Irriguible, T M; Sabater Riera, J; Poch López de Briñas, E; Fort Ros, J; Lloret Cora, M J; Roca Antònio, J; Navas Pérez, A; Ortiz Ballujera, P; Servià Goixart, L; González de Molina Ortiz, F J; Rovira Anglès, C; Rodríguez López, M; Roglan Piqueras, A

    2017-05-01

    The aim of the study is to ascertain the most relevant aspects of the current management of renal replacement therapy (RRT) in critically ill patients, and to analyze renal function recovery and mortality in patients undergoing RRT. A non-interventional three-month observational study was made in 2012, with a follow-up period of 90 days, in 21 centers in Catalonia (Spain). Demographic information, severity scores and clinical data were obtained, as well as RRT parameters. patients aged ≥ 16 years admitted to Intensive Care Units (ICUs) and subjected to RRT. A total of 261 critically ill patients were recruited, of which 35% had renal dysfunction prior to admission. The main reason for starting RRT was oliguria; the most widely used RRT modality was hemodiafiltration; and the median prescribed dose at baseline was 35mL/kg/h. The median time of RRT onset from ICU admission was one day. The mortality rate at 30 and 90 days was 46% and 54%, respectively, and was associated to greater severity scores and a later onset of RRT. At discharge, 85% of the survivors had recovered renal function. Current practice in RRT in Catalonia abides with the current clinical practice guidelines. Mortality related to RRT is associated to later onset of such therapy. The renal function recovery rate at hospital discharge was 85% among the patients subjected to RRT. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  20. Continuous renal replacement therapy. Keeping pace with changes in technology and technique.

    Science.gov (United States)

    Baldwin, Ian

    2002-01-01

    The rapidly changing nature of new technologies and techniques in acute health care means it can be difficult keeping pace. Most facilities, large or small, are usually in continuous evaluation of a new technology. Published reviews and professional group guidelines can assist the process of change for continuous renal replacement therapy (CRRT) technologies and techniques. The current techniques and technologies are a mixed application of old and new technologies providing a combination of convective and diffusive solute clearance methods. There are a variety of anticoagulation approaches. New, purpose-built CRRT machines offer many advantages over old technology but their costs can be prohibitive and users do not always meet them with rapid behavioral change. Reading journal publications and texts, scientific meetings, education and training, Internet web site review/participation, quality improvement activities and an accurate local data base are the keys to keeping pace with changes and identifying whether a benefit can be anticipated and demonstrated. Possible changes for the future of techniques and technologies may be in the areas of modified approaches to continuous therapy with tailored approaches for specific patient care settings. Improved membrane characteristics for wider indications and the bio-artificial kidney are emerging along with blood pump and circuit design improvements, with new machine/operator interfaces.

  1. The levonorgestrel-releasing intrauterine system for endometrial protection during estrogen replacement therapy: a clinical review.

    Science.gov (United States)

    Depypere, H; Inki, P

    2015-01-01

    Estrogen replacement therapy (ERT) is a well-established method of managing climacteric symptoms in women approaching the menopause, but it is associated with a significant risk of endometrial hyperplasia if unopposed by concomitant progestogen administration. The levonorgestrel-releasing intrauterine system (LNG-IUS) offers a highly effective method of minimizing this risk and has additional benefits beyond endometrial protection. The LNG-IUS provides excellent contraception, which may still be necessary in perimenopausal women, and is suitable for women with underlying conditions that may preclude their use of estrogen-containing contraceptive methods. It can effectively manage bleeding problems through the transition from perimenopause into menopause, with many women developing amenorrhea. The LNG-IUS is well tolerated with a favorable safety profile, which generally mirrors that of women of reproductive age using it for contraception only. Moreover, the LNG-IUS plus ERT combination does not appear to be associated with clinically relevant effects on plasma lipids or other markers of cardiovascular risk. Women using the LNG-IUS plus ERT also experience improvements in quality of life, and adherence and continuation rates are high. This review will summarize the clinical evidence for the use of the LNG-IUS plus ERT in peri- and postmenopausal women and present the key attributes of this combined therapy.

  2. Antiepileptic Drug Removal by Continuous Renal Replacement Therapy: A Review of the Literature.

    Science.gov (United States)

    Mahmoud, Sherif Hanafy

    2017-01-01

    Continuous renal replacement therapy (CRRT) is used for managing acute kidney injury in critically ill patients. Removal of antiepileptic drugs (AEDs) by CRRT could be significant and may complicate patients' intensive care unit stay. The objective of the current review was to summarize the available evidence for AED removal by CRRT. An electronic literature search of PubMed (1946 to May 2016), Medline (1946 to May 2016), and Embase (1974 to May 2016) databases for studies discussing AED removal by CRRT was conducted. A total of 31 case reports discussing 32 patients were found. AEDs reported were levetiracetam (n = 3), valproic acid (n = 9), carbamazepine (n = 10), phenytoin (n = 3), phenobarbital (n = 4), lacosamide (n = 1), gabapentin (n = 1), and topiramate (n = 1). Two-thirds of the reports were about using CRRT in drug overdose and one-third was about AED removal by CRRT during therapy. Based on the current limited evidence and pharmacokinetic characteristics of AEDs, renally eliminated AEDs and/or AEDs with limited protein binding such as levetiracetam are more likely to be removed by CRRT than AEDs that are mainly metabolized and extensively protein bound such as carbamazepine. In conclusion, there is not enough evidence to provide robust dosing recommendations for AEDs in patients undergoing CRRT. Further studies are needed.

  3. [Drugs dosing in intensive care unit during continuous renal replacement therapy].

    Science.gov (United States)

    Bourquin, Vincent; Ponte, Belén; Saudan, Patrick; Martin, Pierre-Yves

    2009-11-01

    Drug dosing in the intensive care unit can be challenging. Acute kidney injury (AKI) is a common complication of sepsis and a part of multiple organ dysfunction syndrome. Continuous renal replacement therapy (CRRT) is increasingly used as dialysis therapy in this critically ill population. Available data demonstrate that sepsis, AKI and different modalities of CRRT can profoundly change drugs pharmacokinetic. The severity of these changes depends on molecules characteristics (volume of distribution, plasma protein binding, molecular weight, plasma half-life, plasma clearance), patient itself (volemia, residual renal function, tissue perfusion, hepatic dysfunction) and modality of CRRT (diffusion, convection, adsorption). There are no available recommendations to adapt drug dosing in a given critically ill patient with a given modality of CRRT. It is necessary to fully understand the different methods of CRRT and drug pharmacokinetic to prescribe the appropriate dose and to avoid under or potentially toxic overdosing. Monitoring the plasma level of drug - when available - can establish a relation between the blood concentration and its effect; thus, facilitating drug dosing.

  4. The role of hormone replacement therapy in the intensive care management of deceased organ donors: a primer for nurses.

    Science.gov (United States)

    Smetana, Keaton S; Kimmons, Lauren A; Jones, G Morgan

    2015-01-01

    Donation after brain death remains the primary contributor to the supply of organs available for transplantation in the United States. After brain death, both a surge of catecholamines and a dysregulation of the neurohormonal axis may result in hypotension, decreased organ perfusion, and reduced viability of organs to be transplanted. Hormone replacement therapy is widely used to maintain organ perfusion and has been shown to increase the number of organs procured. This article reviews the literature and mechanisms supporting the use of hormone replacement therapy in brain-dead organ donors and provides clinicians with information regarding the administration, monitoring, and preparation of thyroid hormone, arginine vasopressin, and corticosteroids.

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

    Directory of Open Access Journals (Sweden)

    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

  6. Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson's disease.

    Science.gov (United States)

    Chen, L W; Kuang, F; Wei, L C; Ding, Y X; Yung, K K L; Chan, Y S

    2011-06-01

    Parkinson's disease (PD), a common degenerative disease in humans, is known to result from loss of dopamine neurons in the substantia nigra and is characterized by severe motor symptoms of tremor, rigidity, bradykinsia and postural instability. Although levodopa administration, surgical neural lesion, and deep brain stimulation have been shown to be effective in improving parkinsonian symptoms, cell replacement therapy such as transplantation of dopamine neurons or neural stem cells has shed new light on an alternative treatment strategy for PD. While the difficulty in securing donor dopamine neurons and the immuno-rejection of neural transplants largely hinder application of neural transplants in clinical treatment, induced pluripotent stem cells (iPS cells) derived from somatic cells may represent a powerful tool for studying the pathogenesis of PD and provide a source for replacement therapies in this neurodegenerative disease. Yamanaka et al. [2006, 2007] first succeeded in generating iPS cells by reprogramming fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc in both mouse and human. Animal studies have further shown that iPS cells from fibroblasts could be induced into dopamine neurons and transplantation of these cells within the central nervous system improved motor symptoms in the 6-OHDA model of PD. More interestingly, neural stem cells or fibroblasts from patients can be efficiently reprogrammed and subsequently differentiated into dopamine neurons. Derivation of patient-specific iPS cells and subsequent differentiation into dopamine neurons would provide a disease-specific in vitro model for disease pathology, drug screening and personalized stem cell therapy for PD. This review summarizes current methods and modifications in producing iPS cells from somatic cells as well as safety concerns of reprogramming procedures. Novel reprogramming strategies that deter abnormal permanent genetic and epigenetic alterations are essential for

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

    Science.gov (United States)

    Dornelles, Alícia Dorneles; de Camargo Pinto, Louise Lapagesse; de Paula, Ana Carolina; Steiner, Carlos Eduardo; Lourenço, Charles Marques; Kim, Chong Ae; Horovitz, Dafne Dain Gandelman; Ribeiro, Erlane Marques; Valadares, Eugênia Ribeiro; Goulart, Isabela; Neves de Souza, Isabel C; da Costa Neri, João Ivanildo; Santana-da-Silva, Luiz Carlos; Silva, Luiz Roberto; Ribeiro, Márcia; de Oliveira Sobrinho, Ruy Pires; Giugliani, Roberto; Schwartz, Ida Vanessa Doederlein

    2014-03-01

    Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-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.

  8. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy.

    Science.gov (United States)

    Pastuszak, Alexander W; Pearlman, Amy M; Lai, Win Shun; Godoy, Guilherme; Sathyamoorthy, Kumaran; Liu, Joceline S; Miles, Brian J; Lipshultz, Larry I; Khera, Mohit

    2013-08-01

    Testosterone replacement therapy in men with prostate cancer is controversial, with concern that testosterone can stimulate cancer growth. We evaluated the safety and efficacy of testosterone in hypogonadal men with prostate cancer treated with radical prostatectomy. We performed a review of 103 hypogonadal men with prostate cancer treated with testosterone after prostatectomy (treatment group) and 49 nonhypogonadal men with cancer treated with prostatectomy (reference group). There were 77 men with low/intermediate (nonhigh) risk cancer and 26 with high risk cancer included in the analysis. All men were treated with transdermal testosterone, and serum hormone, hemoglobin, hematocrit and prostate specific antigen were evaluated for more than 36 months. Median (IQR) patient age in the treatment group was 61.0 years (55.0-67.0), and initial laboratory results included testosterone 261.0 ng/dl (213.0-302.0), prostate specific antigen 0.004 ng/ml (0.002-0.007), hemoglobin 14.7 gm/dl (13.3-15.5) and hematocrit 45.2% (40.4-46.1). Median followup was 27.5 months, at which time a significant increase in testosterone was observed in the treatment group. A significant increase in prostate specific antigen was observed in the high risk and nonhigh risk treatment groups with no increase in the reference group. Overall 4 and 8 cases of cancer recurrence were observed in treatment and reference groups, respectively. Thus, testosterone therapy is effective and, while followed by an increase in prostate specific antigen, does not appear to increase cancer recurrence rates, even in men with high risk prostate cancer. However, given the retrospective nature of this and prior studies, testosterone therapy in men with history of prostate cancer should be performed with a vigorous surveillance protocol. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. 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.

  10. An antiretroviral regimen containing 6 months of stavudine followed by long-term zidovudine for first-fine HIV therapy is optimal in resource-limited settings: a prospective, multicenter study in China

    Institute of Scientific and Technical Information of China (English)

    Li Taisheng; Guo Fuping; Li Yijia; Zhang Chengda; Han Yang; Lye Wei; He Yun

    2014-01-01

    Background An zidovudine (AZT)-substitution regimen containing 24-week stavudine (d4T) followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resourcelimited settings.However,evidence is scarce.This study aims to assess the efficacy and safety of AZT-substitution regimen,aiming to find a regimen with better efficacy,less adverse events,and more affordability in resource-limited settings.Methods This prospective,multicenter study enrolled 499 (190 on d4T regimen,172 on AZT regimen,and 137 on AZT-substitution regimen) HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011.Lamivudine (3TC) and either nevirapine (NVP) or efavirenz (EFV) were the other two drugs in the antiretroviral regimens.Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4,12,24,36,48,60,72,84,and 96.Results In terms of hematological adverse effects,AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group.In comparison with AZT-substitution group,AZT group was associated with higher risk of developing anemia (adjusted hazard ratio (aHR)for anemia ≥ grade Ⅱ,8.44,95% CI 1.81-39.46) and neutropenia (aHR for neutropenia ≥ grade Ⅱ,1.86,95% CI 1.19-2.93).The prevalence of lipodystrophy in d4T group was 19.5%,while that in AZT-substitution group was zero.As to antiretroviral efficacy,these three groups showed no differences.Conclusion AZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.

  11. Therapeutic efficiency of continuous renal replacement therapy--experience of a single Romanian center.

    Science.gov (United States)

    Voiculescu, M; Ionescu, Camelia; Ismail, G; Roşu, Mihaela; Szigeti, A; Iliescu, Olguţa

    2004-01-01

    We have studied 24 patients with acute renal failure (ARF) or acutization of chronic renal failure (CRF) caused by a variety of different disorders. A rapid decline in renal excretory function, fluid, electrolyte, and divalent ion disturbances determined us to initiate continuous renal replacement: continuous venovenous hemofiltration (CVVHF)--28 procedures in 15 patients and continuous venovenous hemodiafiltration (CVVHDF)--11 procedures in 11 patients. Mean duration of CVVHF was 21.6+/-6.9 h, with a mean blood flow rate of 116.9+/-16.4 ml/min and an ultrafiltration rate of 6.4+/-4.6 ml/min. Serum creatinine level decreased from 12.6 to 8.3 mg% and the concentration of urea from 237 to 166 mg%. Mean duration of hemodiafiltration was 24+/-8.5 h, with mean blood flow rate of 134+/-15.2 ml/min, mean dialysate flow of 35+/-7 ml/min and mean ultrafiltration rate of 5.6+/-2.1 ml/min. Serum creatinine level decreased from 11.6 to 6.36 mg% and the concentration of urea from 236 to 137 mg%. Survival rate was 79.2% (19/24 patients). Complete recover of renal function was achieved in 5 patients, partial recover in 5 patients and 9 patients were included in chronic dialysis. In 8/24 (30%) patients we encountered complications, such as hypotension in 2 cases, bleeding disorders in 5 cases or diselectrolithemias in 2 cases. As a consequence, continuous renal replacement therapy is efficient, having an acceptable rate of adverse effects in patients with ARF or acutization of CRF.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Ovarian carcinoma: improved survival following abdominopelvic irradiation in patients with a completed pelvic operation. [Complications of the various therapy regimens

    Energy Technology Data Exchange (ETDEWEB)

    Dembo, A.J.; Bush, R.S.; Beale, F.A.; Bean, H.A.; Pringle, J.F.; Sturgeon, J.; Reid, J.G.

    1979-08-01

    A prospective, stratified, randomized study of 190 postoperative ovarian carcinoma patients with Stages IB, II, and III (asymptomatic) presentations is reported. The median time of follow-up was 52 months. Patients in whom bilateral salpingo-oophorectomy and hysterectomy (BSOH) could not be completed because of extensive pelvic tumor had a poor prognosis which did not differ for any of the therapies tested. When BSOH was completed, pelvic plus abdominopelvic irradiation (P + AB) with no diaphragmatic shielding significantly improved patient survival rate and long-term control of occult upper abdominal disease in approximately 25% more patients than pelvic irradiation alone or followed by adjuvant daily chlorambucil therapy. The effectiveness of P + AB in BSOH-completed patients was independent of stage or tumor grade and was most clearly appreciated in patients with all gross tumor removed. Chlorambucil added to pelvic irradiation delayed the time to treatment failure without reducing the number of treatment failures.

  14. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study.

    Science.gov (United States)

    Wallis, Christopher J D; Lo, Kirk; Lee, Yuna; Krakowsky, Yonah; Garbens, Alaina; Satkunasivam, Raj; Herschorn, Sender; Kodama, Ronald T; Cheung, Patrick; Narod, Steven A; Nam, Robert K

    2016-06-01

    Conflicting evidence exists for the association between testosterone replacement therapy and mortality and cardiovascular events. The US Food and Drug Administration recently cautioned that testosterone replacement therapy might increase risk of heart attack and stroke, based on evidence from studies with short treatment duration and follow-up. No previous study has assessed the effect of duration of testosterone treatment on these outcomes. We aimed to assess the association between long-term use of testosterone replacement therapy and mortality, cardiovascular events, and prostate cancer diagnoses, using a time-varying exposure analysis. We did a population-based matched cohort study of men aged 66 years or older newly treated with testosterone replacement therapy and controls matched for age, region of residence, comorbidity, diabetes status, and index year from 2007-12 in Ontario, Canada, using data from the Ontario Drug Benefit database, the Canadian Institute for Health Information (CIHI) Discharge Abstract Database, the CIHI National Ambulatory Care Reporting System, the Ontario Health Insurance Plan database, the Ontario Myocardial Infarction Database, the Ontario Diabetes Database, the Ontario Cancer Registry, and the Registered Persons database. We assessed the association between cumulative testosterone replacement therapy exposure and mortality, cardiovascular events, and prostate cancer using marginal models with a time-varying testosterone exposure. We included 10 311 men treated with testosterone replacement therapy and 28 029 controls between Jan 1, 2007, and June 30, 2012. Over a median follow-up of 5·3 years (IQR 3·6-7·5) in the testosterone replacement therapy group and 5·1 years (3·4-7·4) in the control group, patients treated with testosterone replacement therapy had lower mortality than did controls (hazard ratio [HR] 0·88, 95% CI 0·84-0·93). Patients in the lowest tertile of testosterone exposure had increased risk of mortality

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

    Directory of Open Access Journals (Sweden)

    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

  16. Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism.

    Science.gov (United States)

    Pan, Tianrong; Zhong, Mingkui; Zhong, Xing; Zhang, Yanqing; Zhu, Defa

    2013-04-01

    Hypothyroidism has a variety of adverse effects on cognitive function. The treatment of levothyroxine alone cannot restore cognitive defects of hypothyroid patients. Antioxidant vitamin E supplementation could be useful in disturbances which are associated with oxidative stress and could effectively slow the progression of Alzheimer disease. Thus, the purpose of this study was to evaluate oxidative stress status of the serum and hippocampus in hypothyroidism and to examine the effects of levothyroxine replacement therapy with vitamin E supplementation on cognitive deficit. Sprague-Dawley rats were randomly divided into five groups: control group, PTU group, PTU + Vit E group, PTU + L-T4 group, and PTU + L-T4 + Vit E group. Serum and hippocampus malondialdehyde (MDA) levels were determined using the thiobarbituric-acid reactive substances method. Serum and hippocampus superoxide dismutase (SOD) levels were determined by measuring its ability to inhibit the photoreduction of nitroblue tetrazolium. Learning and memory was assessed by Morris water maze test. In the present study, we found that the rats of PTU + Vit E group spent less time to find the platform on days 2, 3, 4, and 5 than the PTU group. Moreover, the rats of PTU + L-T4 + Vit E group spent less time to find the platform on days 4 and 5 than the PTU + L-T4 group. The time spent in the target quadrants was measured in the probe test and no difference was observed in all groups. Oxidative damage has been observed in the serum and hippocampus of hypothyroidism rat. SOD levels of serum and hippocampus tissue were significantly increased and MDA levels were significantly decreased in the PTU + Vit E and PTU + L-T4 + Vit E groups than the PTU and PTU + L-T4 groups. Therefore, these findings indicate that levothyroxine replacement therapy with vitamin E supplementation may ameliorate cognitive deficit in PTU-induced hypothyroidism through the decrease of oxidative stress status.

  17. Effects of continuous and intermittent renal replacement therapies among adult patients with acute kidney injury.

    Science.gov (United States)

    Schoenfelder, Tonio; Chen, Xiaoyu; Bleß, Hans-Holger

    2017-01-01

    Background: Dialysis-dependent acute kidney injury (AKI) can be treated using continuous (CRRT) or intermittent renal replacement therapies (IRRT). Although some studies suggest that CRRT may have advantages over IRRT, study findings are inconsistent. This study assessed differences between CRRT and IRRT regarding important clinical outcomes (such as mortality and renal recovery) and cost-effectiveness. Additionally, ethical aspects that are linked to renal replacement therapies in the intensive care setting are considered. Methods: Systematic searches in MEDLINE, EMBASE, and Cochrane Library including RCTs, observational studies, and cost-effectiveness studies were performed. Results were pooled using a random effects-model. Results: Forty-nine studies were included. Findings show a higher rate of renal recovery among survivors who initially received CRRT as compared with IRRT. This advantage applies to the analysis of all studies with different observation periods (Relative Risk (RR) 1.10; 95% Confidence Interval (CI) [1.05, 1.16]) and to a selection of studies with observation periods of 90 days (RR 1.07; 95% CI [1.04, 1.09]). Regarding observation periods beyond there are no differences when only two identified studies were analyzed. Patients initially receiving CRRT have higher mortality as compared to IRRT (RR 1.17; 95% CI [1.06, 1.28]). This difference is attributable to observational studies and may have been caused by allocation bias since seriously ill patients more often initially receive CRRT instead of IRRT. CRRT do not significantly differ from IRRT with respect to change of mean arterial pressure, hypotensive episodes, hemodynamic instability, and length of stay. Data on cost-effectiveness is inconsistent. Recent analyzes indicate that initial CRRT is cost-effective compared to initial IRRT due to a reduction of the rate of long-term dialysis dependence. As regards a short time horizon, this cost benefit has not been shown. Conclusion: Findings of

  18. Effects of continuous and intermittent renal replacement therapies among adult patients with acute kidney injury

    Directory of Open Access Journals (Sweden)

    Schoenfelder, Tonio

    2017-03-01

    Full Text Available Background: Dialysis-dependent acute kidney injury (AKI can be treated using continuous (CRRT or intermittent renal replacement therapies (IRRT. Although some studies suggest that CRRT may have advantages over IRRT, study findings are inconsistent. This study assessed differences between CRRT and IRRT regarding important clinical outcomes (such as mortality and renal recovery and cost-effectiveness. Additionally, ethical aspects that are linked to renal replacement therapies in the intensive care setting are considered.Methods: Systematic searches in MEDLINE, EMBASE, and Cochrane Library including RCTs, observational studies, and cost-effectiveness studies were performed. Results were pooled using a random effects-model.Results: Forty-nine studies were included. Findings show a higher rate of renal recovery among survivors who initially received CRRT as compared with IRRT. This advantage applies to the analysis of all studies with different observation periods (Relative Risk (RR 1.10; 95% Confidence Interval (CI [1.05, 1.16] and to a selection of studies with observation periods of 90 days (RR 1.07; 95% CI [1.04, 1.09]. Regarding observation periods beyond there are no differences when only two identified studies were analyzed. Patients initially receiving CRRT have higher mortality as compared to IRRT (RR 1.17; 95% CI [1.06, 1.28]. This difference is attributable to observational studies and may have been caused by allocation bias since seriously ill patients more often initially receive CRRT instead of IRRT. CRRT do not significantly differ from IRRT with respect to change of mean arterial pressure, hypotensive episodes, hemodynamic instability, and length of stay. Data on cost-effectiveness is inconsistent. Recent analyzes indicate that initial CRRT is cost-effective compared to initial IRRT due to a reduction of the rate of long-term dialysis dependence. As regards a short time horizon, this cost benefit has not been shown

  19. Renal replacement therapy practices for patients with acute kidney injury in China.

    Science.gov (United States)

    Clark, William R; Ding, Xiaoqiang; Qiu, Haibo; Ni, Zhaohui; Chang, Ping; Fu, Ping; Xu, Jiarui; Wang, MinMin; Yang, Li; Wang, Jing; Ronco, Claudio

    2017-01-01

    Recent data indicate AKI is very common among hospitalized Chinese patients and continuous renal replacement therapy (CRRT) is increasingly offered for treatment. However, only anecdotal information regarding CRRT's use in relation to other modalities and the specific manner in which it is prescribed exists currently. This report summarizes the results of a comprehensive physician survey designed to characterize contemporary dialytic management of AKI patients in China, especially with respect to the utilization of CRRT. The survey queried both nephrologists and critical care physicians across a wide spectrum of hospitals about factors influencing initial RRT modality selection, especially patient clinical characteristics and willingness to receive RRT, treatment location, and institutional capabilities. For patients initially treated with CRRT, data related to indication, timing of treatment initiation, dose, anticoagulation technique, and duration of therapy were also collected. Among AKI patients considered RRT candidates, the survey indicated 15.1% (95% CI, 12.3%-17.9%) did not actually receive dialysis at Chinese hospitals. The finding was largely attributed to prohibitively high therapy costs in the view of patients or their families. The survey confirmed the dichotomy in RRT delivery in China, occurring both in the nephrology department (with nephrologists responsible) and the intensive care unit (with critical care physicians responsible). For all patients who were offered and received RRT, the survey participants reported 63.9% (56.4%-71.3%) were treated initially with CRRT and 24.8% (19.2%-30.3%) with intermittent hemodialysis (HD) (Phr while approximately 20% of prescriptions fell above this range. Daily prescribed therapy duration demonstrated a marked divergence from values reported in the literature and standard clinical practice. Overall, the most common average prescribed value (50% of respondents) fell in the 10-20 hr range, with only 18% in the 20

  20. Meta-analysis of first-line therapies with maintenance regimens for advanced non-small-cell lung cancer (NSCLC) in molecularly and clinically selected populations.

    Science.gov (United States)

    Tan, Pui San; Bilger, Marcel; de Lima Lopes, Gilberto; Acharyya, Sanchalika; Haaland, Benjamin

    2017-08-01

    Evidence has suggested survival benefits of maintenance for advanced NSCLC patients not progressing after first-line chemotherapy. Additionally, particular first-line targeted therapies have shown survival improvements in selected populations. Optimal first-line and maintenance therapies remain unclear. Here, currently available evidence was synthesized to elucidate optimal first-line and maintenance therapy within patient groups. Literature was searched for randomized trials evaluating first-line and maintenance regimens in advanced NSCLC patients. Bayesian network meta-analysis was performed within molecularly and clinically selected groups. The primary outcome was combined clinically meaningful OS and PFS benefits. A total of 87 records on 56 trials evaluating first-line treatments with maintenance were included. Results showed combined clinically meaningful OS and PFS benefits with particular first-line with maintenance treatments, (1) first-line intercalated chemotherapy+erlotinib, maintenance erlotinib in patients with EGFR mutations, (2) first-line afatinib, maintenance afatinib in patients with EGFR deletion 19, (3) first-line chemotherapy + bevacizumab, maintenance bevacizumab in EGFR wild-type patients, (4) chemotherapy+conatumumab, maintenance conatumumab in patients with squamous histology, (5) chemotherapy+cetuximab, maintenance cetuximab or chemotherapy + necitumumab, maintenance necitumumab in EGFR FISH-positive patients with squamous histology, and (6) first-line chemotherapy+bevacizumab, maintenance bevacizumab or first-line sequential chemotherapy+gefitinib, maintenance gefitinib in patients clinically enriched for EGFR mutations with nonsquamous histology. No treatment showed combined clinically meaningful OS and PFS benefits in patients with EGFR L858R or nonsquamous histology. Particular first-line with maintenance treatments show meaningful OS and PFS benefits in patients selected by EGFR mutation or histology. Further research is needed

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

    Science.gov (United States)

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

    2014-07-24

    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 long-term complications and associated conditions, the course of Gaucher disease was modelled.

  2. Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy

    NARCIS (Netherlands)

    A.A.N.M. Royakkers; J.C. Korevaar; J.D.E. van Suijlen; L.S. Hofstra; M.A. Kuiper; P.E. Spronk; M.J. Schultz; C.S.C. Bouman

    2011-01-01

    To evaluate whether cystatin C in serum (sCyC) and urine (uCyC) can predict early acute kidney injury (AKI) in a mixed heterogeneous intensive care unit (ICU), and also whether these biomarkers can predict the need for renal replacement therapy (RRT). Multicenter prospective observational cohort stu

  3. The effect of timing of the first kidney transplantation on survival in children initiating renal replacement therapy

    DEFF Research Database (Denmark)

    Kramer, Anneke; Stel, Vianda S; Geskus, Ronald B;

    2012-01-01

    Controversy exists concerning the timing of the first kidney transplantation for children who need to start renal replacement therapy (RRT). Our aim was to estimate the effect of timing of the first transplantation on patient survival in children, for the first time also taking into account...

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

    DEFF Research Database (Denmark)

    Kramer, Anneke; Stel, Vianda; Zoccali, Carmine;

    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 ...

  5. Long-term Clinical Outcome of Antibody Replacement Therapy in Humoral Immunodeficient Adults With Respiratory Tract Infections

    NARCIS (Netherlands)

    van Kessel, Diana A; Hoffman, Thijs W; van Velzen-Blad, Heleen; Zanen, Pieter|info:eu-repo/dai/nl/173876412; Grutters, Jan|info:eu-repo/dai/nl/258116129; Rijkers, Ger T

    In severe humoral immunodeficiency the indication for antibody replacement therapy (ART) is clear, and supported by several large studies. However, for milder forms of humoral immunodeficiency, the indication for ART is less clear. This is a retrospective cohort study of 87 adults with recurrent

  6. Impact of enzyme replacement therapy on survival in adults with Pompe disease: Results from a prospective international observational study

    NARCIS (Netherlands)

    D. Güngör (Deniz); M.E. Kruijshaar (Michelle); I. Plug (Iris); R.B. D'Agostino (Ralph); M.L.C. Hagemans (Marloes); P.A. van Doorn (Pieter); A.J.J. Reuser (Arnold); A.T. van der Ploeg (Ans)

    2013-01-01

    textabstractBackground: Pompe disease is a rare metabolic myopathy for which disease-specific enzyme replacement therapy (ERT) has been available since 2006. ERT has shown efficacy concerning muscle strength and pulmonary function in adult patients. However, no data on the effect of ERT on the survi

  7. 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.

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

    NARCIS (Netherlands)

    A. Kramer; V. Stel; C. Zoccali; J. Heaf; D. Ansell; C. Grönhagen-Riska; T. Leivestad; K. Simpson; R. Pálsson; M. Postorino; K. Jager

    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

  9. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury

    DEFF Research Database (Denmark)

    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...

  10. Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study

    DEFF Research Database (Denmark)

    Mosekilde, Leif; Beck-Nielsen, H; Sørensen, O H

    2000-01-01

    OBJECTIVES: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. METHODS: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45-58 years, from three to 24 months past last menstrual ...

  11. 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 th...

  12. The growth hormone (GH)-insulin-like growth factor axis during testosterone replacement therapy in GH-treated hypopituitary males

    DEFF Research Database (Denmark)

    Fisker, Sidse; Nørrelund, Helene; Juul, A

    2001-01-01

    -independent effect on IGF-I and related parameters. Eight adult hypopituitary men (39.9 +/- 5.7 years) receiving growth hormone (GH) and testosterone replacement therapy (250 mg testosterone enantate every fourth week) participated in this prospective study. Frequent blood samples were drawn over a 5 week period...

  13. Enzyme-replacement Therapy in Classic Infantile Pompe Disease: Long-term outcome, dosing and the role of antibodies

    NARCIS (Netherlands)

    C.M. Van Gelder (Carin)

    2013-01-01

    textabstract__Abstract__ The introduction of enzyme-replacement therapy (ERT) in 2006 has dramatically increased the interest in Pompe disease. In the three decades following the discovery of acid a-glucosidase deficiency as cause of the disease by H.G. Hers in 1963 only very few research

  14. [The transrectal ultrasonography of prostate in men with congenital hypogonadism treated by long term testosterone replacement therapy].

    Science.gov (United States)

    Heráček, Jiří; El Balouly, Karim; Sobotka, Vladimír; Šnajderová, Marta; Kalvachová, Božena; Urban, Michael

    2012-01-01

    The aim of the study was to evaluate prostate transrectal ultrasonography findings in men with congenital hypogonadism treated by long term testosterone replacement therapy. We have gradually included 31 men with congenital hypogonadism in period of 2001-2011. The average follow-up was 7.3 years (2 months - 10.8 years). We have used Sustanon® 250 i.m. every 3 weeks or Nebido® i.m. every 3 months for continual testosterone replacement therapy. We performed to all patients the transrectal ultrasonography of prostate and seminal vesicles by biplanar rectal probe every 6 months. During the transrectal ultrasonography we observed in 22 (71.0 %) patients changes in prostatic tissue. In case of 12 patients were diagnosed asymptomatic prostatic cysts, in 9 patients prostatolithiasis and in 5 patients changes in echogenity of prostatic tissue. In 2 patients was found simultaneous occurrence of prostatic cyst and prostolithiasis, in further 2 patients simultaneous occurrence of hyperechogenic prostatic lesion and prostatolithiasis. The above described findings were diagnosed in 5 patients in the treatment lasting from 3 to 5 years, for the other 17 men with hormone replacement therapy longer than 5 years. The study presents long term results of complex treatment in patients with disorders of sexual development, onset and progress of puberty. The long term treatment of these patients in interdisciplinary cooperation of endocrinologist and andrologist may significantly contribute to clarify an impact of testosterone replacement therapy on prostate development.

  15. Pharmacokinetics of cefotaxime in critically ill patients with acute kidney injury treated with continuous renal replacement therapy : a pilot study

    NARCIS (Netherlands)

    Koedijk, Joost B; Valk-Swinkels, Corinne G H; Rijpstra, Tom A; Touw, Daan J; Mulder, Paul G H; van der Voort, Peter H J; Van't Veer, Nils E; van der Meer, Nardo J M

    2016-01-01

    INTRODUCTION: The objective of this study is to describe the pharmacokinetics of cefotaxime (CTX) in critically ill patients with acute kidney injury (AKI) when treated with continuous renal replacement therapy (CRRT) in the Intensive Care Unit (ICU). MATERIALS AND METHODS: This single-center prospe

  16. Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Daniel A Shoskes

    2015-12-01

    Full Text Available Introduction: The relationship between Testosterone Replacement Therapy (TRT and prostate cancer remains controversial. Most TRT studies show no change in prostate specific antigen (PSA but some men do have PSA rise or develop an abnormal digital rectal exam (aDRE. Our objective was to examine the biopsy results of men with symptomatic hypogonadism before or during therapy. Materials and Methods: Data was extracted from our medical record on men with hypogonadism who had a prostate biopsy within the past 4 years done by 3 Urologists with guideline driven practice patterns. Results: 96 men were identified. Mean age at biopsy was 63 (range 40–85 and median PSA was 3.78ng/dL (0.5–662. Of the 61 men not on TRT, median PSA was 4.34 (0.5 to 662 and mean total testosterone 254 (191–341. There were 29 (47.5% prostate cancers found (6 Gleason score 6, 13 Gleason score 7, 10 Gleason score 8 or 9. Of the 35 men on TRT, median PSA was 3.27 (0.5 to 13.7. The %PSA increase ranged from 2 to 251% (mean 93.5%. Mean total testosterone was 383 (146–792. Of the 14 men treated < 2 years, none had cancer. Of the 21 men treated 2 or more years 5 had cancer (2 Gleason score 6, 3 Gleason score 7. Conclusions: Men with hypogonadism and a clinical indication for biopsy often have prostate cancer, many high grade. No men with an initial PSA rise on TRT had cancer. Men on long term TRT should be monitored with PSA and DRE per guidelines.

  17. Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review.

    Science.gov (United States)

    Le Houezec, J

    2003-09-01

    Smoking is a complex behaviour involving both pharmacological and psychological components. Nicotine is the main alkaloid found in tobacco, and is responsible for its addictive potential. Nicotine-positive effects on mood and cognition are strong reinforcements for smokers that contribute to their addiction, and cigarette smoking is particularly addictive because inhaled nicotine is absorbed through the pulmonary venous rather than the systemic venous system, and thus reaches the brain in 10-20 seconds. As the likelihood that a substance will be abused depends on the time between administration and central reinforcement, tobacco smoking can easily become addictive. Nicotine replacement therapy (NRT) is available in different forms (gum, transdermal patch, nasal spray, inhaler, sublingual tablet and lozenge), and has been shown to relieve withdrawal symptoms and to double abstinence rates compared to placebo. Most NRT forms deliver nicotine more slowly than smoking, and the increase in nicotine blood levels is more gradual. Compared to tobacco smoking or even tobacco chewing, few positive (reinforcing) effects are obtained from NRT use. Nasal spray provides faster withdrawal relief than other NRT, but compared to smoking absorption is slower and nicotine blood levels obtained are lower than with smoking. These differences in pharmacokinetic profiles compared with smoking may explain that some smokers still have difficulties quitting smoking even when using NRT (apart from psychological and/or social factors). Combination therapy (e.g., patch+gum, patch+inhaler), higher dosage, temporary abstinence or smoking reduction (using NRT to reduce smoke intake) may be needed to help more smokers to quit.

  18. Testosterone replacement therapy in men with prostate cancer: a time-varying analysis.

    Science.gov (United States)

    Kaplan, Alan L; Lenis, Andrew T; Shah, Adit; Rajfer, Jacob; Hu, Jim C

    2015-02-01

    The use of testosterone replacement therapy (TRT) in men with prostate cancer is controversial given concerns of androgen-related cancer progression. Although emerging evidence suggests that TRT may be safe in this setting, no study has investigated dose-related effects. We used time-varying analysis to determine whether increasing TRT exposure is associated with worse outcomes. Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1991 to 2007. Subjects treated with TRT were stratified by duration of treatment. Weighted propensity score methods were used to adjust for differences between groups. A Cox proportional hazards model was constructed to assess the effect of injectable TRT exposure on outcomes. Overall mortality (OM), prostate cancer-specific mortality (PCSM), and use of salvage androgen deprivation therapy (ADT). Men treated with TRT, regardless of duration, did not experience higher OM or PCSM (all hazard ratio [HR] <1.0, all P ≤ 0.002). We found no difference in use of salvage ADT in the ≤ 30-day and 31-60 day groups compared with no-TRT (HR 1.23 and 1.05, P=0.06 and 0.81, respectively), whereas it was lower for men on long-term TRT (HR 0.70, P=0.04). TRT following prostate cancer diagnosis and treatment does not increase mortality or the use of salvage ADT. Using time-varying analysis, we demonstrate that longer duration of TRT is not associated with adverse mortality or greater need for ADT. © 2014 International Society for Sexual Medicine.

  19. Outcomes of Prostate Biopsy in Men with Hypogonadism Prior or During Testosterone Replacement Therapy.

    Science.gov (United States)

    Shoskes, Daniel A; Barazani, Yagil; Fareed, Khaled; Sabanegh, Edmund

    2015-01-01

    The relationship between Testosterone Replacement Therapy (TRT) and prostate cancer remains controversial. Most TRT studies show no change in prostate specific antigen (PSA) but some men do have PSA rise or develop an abnormal digital rectal exam (aDRE). Our objective was to examine the biopsy results of men with symptomatic hypogonadism before or during therapy. Data was extracted from our medical record on men with hypogonadism who had a prostate biopsy within the past 4 years done by 3 Urologists with guideline driven practice patterns. 96 men were identified. Mean age at biopsy was 63 (range 40-85) and median PSA was 3.78ng/dL (0.5-662). Of the 61 men not on TRT, median PSA was 4.34 (0.5 to 662) and mean total testosterone 254 (191-341). There were 29 (47.5%) prostate cancers found (6 Gleason score 6, 13 Gleason score 7, 10 Gleason score 8 or 9). Of the 35 men on TRT, median PSA was 3.27 (0.5 to 13.7). The %PSA increase ranged from 2 to 251% (mean 93.5%). Mean total testosterone was 383 (146-792). Of the 14 men treated < 2 years, none had cancer. Of the 21 men treated 2 or more years 5 had cancer (2 Gleason score 6, 3 Gleason score 7). Men with hypogonadism and a clinical indication for biopsy often have prostate cancer, many high grade. No men with an initial PSA rise on TRT had cancer. Men on long term TRT should be monitored with PSA and DRE per guidelines.

  20. Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients

    Directory of Open Access Journals (Sweden)

    Rossella Parini

    2015-06-01

    Full Text Available Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs and multi-organ impairment. The central nervous system (CNS is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood–brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11 started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m2 decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood–brain barrier, might in the future improve the MPS II outcome.

  1. Continuous infusion of vancomycin in septic patients receiving continuous renal replacement therapy.

    Science.gov (United States)

    Covajes, Cecilia; Scolletta, Sabino; Penaccini, Laura; Ocampos-Martinez, Eva; Abdelhadii, Ali; Beumier, Marjorie; Jacobs, Frédérique; de Backer, Daniel; Vincent, Jean-Louis; Taccone, Fabio Silvio

    2013-03-01

    Vancomycin is frequently administered as a continuous infusion to treat severe infections caused by Gram-positive bacteria. Previous studies have suggested a loading dose of 15 mg/kg followed by continuous infusion of 30 mg/kg in patients with normal renal function; however, there are no dosing recommendations in patients with renal failure undergoing continuous renal replacement therapy (CRRT). Data from all adult septic patients admitted to a Department of Intensive Care over a 3-year period in whom vancomycin was given as a continuous infusion were reviewed. Patients were included if they received vancomycin for ≥48h during CRRT. Vancomycin levels were obtained daily. During the study period, 85 patients (56 male; mean age 65±15 years; weight 85±24kg) met the inclusion criteria. Median (interquartile range) APACHE II and SOFA scores were 24 (20-29) and 11 (7-14), respectively, and the overall mortality rate was 59%. Mean vancomycin doses were 16.4±6.4 (loading dose), 23.5±8.1 (Day 1), 23.2±7.4 (Day 2) and 23.3±11.0 (Day 3) mg/kg, resulting in blood concentrations of 24.7±9.0 (Day 1), 26.0±8.1 (Day 2) and 27.7±9.3 (Day 3) μg/mL. On Day 1, 43 patients (51%) had adequate drug concentrations (20-30 μg/mL), 17 (20%) had levels >30 μg/mL and 25 (29%) had levels drug concentrations received a daily dose of 16-35 mg/kg. The intensity of CRRT directly influenced vancomycin concentrations on Day 1 of therapy. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. Therapeutic Drug Monitoring in Neonatal HSV Infection on Continuous Renal Replacement Therapy.

    Science.gov (United States)

    Funaki, Takanori; Miyata, Ippei; Shoji, Kensuke; Enomoto, Yuki; Sakamoto, Seisuke; Kasahara, Mureo; Miyairi, Isao

    2015-07-01

    Optimal acyclovir dosing under continuous renal replacement therapy (CRRT) in neonates is unknown. We monitored serum acyclovir levels and herpes simplex virus 1 (HSV-1) DNA levels in a neonate with disseminated HSV-1 infection and renal failure undergoing CRRT. A full-term, 5-day-old female presented with a 2-day history of lethargy and fever. She developed fulminant hepatitis and was diagnosed with HSV-1 infection by real-time polymerase chain reaction. Acyclovir was initiated at 60 mg/kg/day, which was lowered to 20 mg/kg/day because of development of renal failure. She was placed on continuous hemodialysis. Acyclovir dosing was adjusted according to serum acyclovir levels, and HSV-1 viral load was sequentially monitored. Semiquantification of serum HSV-1 levels was performed by real-time polymerase chain reaction. Acyclovir levels were measured by using liquid chromatography-tandem mass spectrometry. Acyclovir was administered at 20 mg/kg intravenously over 1 hour; peak concentration was 18.9 μg/mL. The half-life of acyclovir was estimated to be 2 to 3 h. Viral load remained high during dosing every 24 hours, with a decline of 0.17 log copies/24 hours. Acyclovir dosing was changed to 20 mg/kg/dose every 8 hours, with an average viral load decline of 0.44 log copies/24 hours. Despite the guideline recommendation of 24-hour redosing, acyclovir was dialyzed at a rate that resulted in suboptimal treatment. Individual therapeutic drug monitoring for acyclovir and dosing adjustment may be required to optimize therapy for patients undergoing CRRT. Copyright © 2015 by the American Academy of Pediatrics.

  3. Outcomes of Second Combination Antiretroviral Therapy Regimens Among HIV-Infected Persons in Clinical Care: A Multicenter Cohort Study

    OpenAIRE

    2013-01-01

    Data on the effectiveness of second-line combination antiretroviral therapy (cART) are limited. We evaluated virologic outcomes of second cART in a multicenter cohort collaboration. The study population initiated first and second modern cART between 1996 and 2010. The second cART required a switch in at least the anchor agent of first cART. We evaluated time to virologic failure of second cART and factors associated with greater risk of failure using multivariable Cox proportional hazards mod...

  4. Coenzyme Q10 in combination with triple therapy regimens ameliorates oxidative stress and lipid peroxidation in chronic gastritis associated with H. pylori infection.

    Science.gov (United States)

    Rahmani, Asghar; Abangah, Ghobad; Moradkhani, Atefeh; Hafezi Ahmadi, Mohammad Reza; Asadollahi, Khairollah

    2015-08-01

    Chronic gastritis associated with H. pylori infection causes oxidative stress in the stomach. This study aimed to evaluate the therapeutic effects of coenzyme q10 among gastric patients infected by H. pylori. By a clinical trial, chronic gastric patients infected by H. pylori were randomly divided into 2 groups: intervention and placebo. The placebo group received a standard triple therapy regimen, and the intervention group received the triple regimen + coenzyme Q10 (CoQ10). Mean inflammation score; serum levels of 3 serum markers were then compared. A total of 100 participants of whom 67% were female were evaluated. The mean age of participants was 59.4 ± 11.4 years. The mean inflammation score was considerably decreased at the end of the study, in the intervention group. The mean levels of total antioxidant capacity (TAC) and glutathione peroxidase (GPx) at the end of the study were reduced among the triple therapy group (P gastritis.

  5. 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.

  6. Effect of Testosterone Replacement Therapy on Cognitive Performance and Depression in Men with Testosterone Deficiency Syndrome

    Science.gov (United States)

    Jung, Hyun Jin

    2016-01-01

    Purpose We aimed to evaluate the effect of testosterone replacement therapy (TRT) on cognitive function and depression in men with testosterone deficiency syndrome. Materials and Methods We carried out a prospective, placebo-controlled trial involving 106 men with total testosterone levels testosterone undecanoate) or a placebo (advice to modify lifestyle), the study population was divided into a TRT group (n=54) and a control group (n=52). Results The age among patients in the TRT and control groups was 56.7±12.6 years and 57.8±11.4 years, respectively (p> 0.05). At baseline, no significant differences between the TRT and control groups were noted regarding serum testosterone or prostate-specific antigen levels, or regarding the scores for aging symptoms (Aging Males' Symptoms scale), erectile function (5-item International Index of Erectile Function questionnaire), cognitive function (Korean Mini-Mental State Examination), and depression (Beck Depression Inventory). At 8 months after intervention total serum testosterone levels and erectile function scores had significantly increased (ptestosterone deficiency syndrome if low testosterone levels are associated with depression or cognitive impairment. PMID:28053949

  7. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients

    Directory of Open Access Journals (Sweden)

    Ravaioli Laura

    2011-02-01

    Full Text Available Abstract Background In male patients suffering from chronic pain, opioid administration induces severe hypogonadism, leading to impaired physical and psychological conditions such as fatigue, anaemia and depression. Hormone replacement therapy is rarely considered for these hypogonadic patients, notwithstanding the various pharmacological solutions available. Methods To treat hypogonadism and to evaluate the consequent endocrine, physical and psychological changes in male chronic pain patients treated with morphine (epidural route, we tested the administration of testosterone via a gel formulation for one year. Hormonal (total testosterone, estradiol, free testosterone, DHT, cortisol, pain (VAS and other pain questionnaires, andrological (Ageing Males' Symptoms Scale - AMS and psychological (POMS, CES-D and SF-36 parameters were evaluated at baseline (T0 and after 3, 6 and 12 months (T3, T6, T12 respectively. Results The daily administration of testosterone increased total and free testosterone and DHT at T3, and the levels remained high until T12. Pain rating indexes (QUID progressively improved from T3 to T12 while the other pain parameters (VAS, Area% remained unchanged. The AMS sexual dimension and SF-36 Mental Index displayed a significant improvement over time. Conclusions In conclusion, our results suggest that a constant, long-term supply of testosterone can induce a general improvement of the male chronic pain patient's quality of life, an important clinical aspect of pain management.

  8. Phytoandrogenic properties of Eurycoma longifolia as natural alternative to testosterone replacement therapy.

    Science.gov (United States)

    George, A; Henkel, R

    2014-09-01

    The testosterone deficiency syndrome (TDS) is characterised by numerous symptoms, including low libido, increased fat mass, fatigue, erectile dysfunction or osteoporosis, and up to 80% of men will experience some kind of ageing males' symptoms. This is caused by the age-depending decline in serum testosterone levels with concentrations being about 40-50% lower in men older than 60 years compared with young men. This significant decline in testosterone levels is further closely linked with medical conditions such as obesity, metabolic syndrome, diabetes or hypertension. The conventional way of treating TDS is the testosterone replacement therapy (TRT), for which preparations are on the market. Apart from the beneficial effects of TRT, significant adverse side effects have been described, and prostate cancer (PCa) as absolute contraindication is debated. Eurycoma longifolia (Tongkat Ali; TA) is natural alternative to TRT and has been shown to restore serum testosterone levels, thus significantly improving sexual health. This includes significant positive effects on bone health and physical condition of patients. In addition, a significant antihyperglycaemic effect and cytotoxicity against PCas cells has been shown. Thus far, at therapeutic concentrations, no significant side effects of the treatment were obvious. Therefore, TA might be a safe alternative to TRT.

  9. Preliminary Diffusive Clearance of Silicon Nanopore Membranes in a Parallel Plate Configuration for Renal Replacement Therapy

    Science.gov (United States)

    Kim, Steven; Heller, James; Iqbal, Zohora; Kant, Rishi; Kim, Eun Jung; Durack, Jeremy; Saeed, Maythem; Do, Loi; Hetts, Steven; Wilson, Mark; Brakeman, Paul; Fissell, William H.; Roy, Shuvo

    2015-01-01

    Silicon nanopore membranes (SNM) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here we present an initial evaluation of the SNM’s mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200ml/min) and pressures (1,448mmHg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4-hours in an extra-corporeal porcine model. The pressure drop across the flow cell was 4.6mmHg at 200ml/min. Mechanical testing showed that SNM could withstand up to 775.7mmHg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extra-corporeal studies showed blood was successfully driven via the arterial-venous pressure differential without thrombus formation. Bare silicon showed increased cell adhesion with a 4.1 fold increase and 1.8 fold increase over polyethylene-glycol (PEG)-coated surfaces for tissue plasminogen factor (t-PA) and platelet adhesion (CD-41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy. PMID:26692401

  10. Development of nanoparticle-bound arylsulfatase B for enzyme replacement therapy of mucopolysaccharidosis VI.

    Science.gov (United States)

    Mühlstein, A; Gelperina, S; Kreuter, J

    2013-07-01

    Lysosomal storage disorders like mucopolysaccharidosis (MPS) VI are rare diseases with a lack of well-suited treatments. Even though an enzyme replacement therapy (ERT) of recombinant arylsulfatase B (ASB) is available for MPS VI, the administration cannot positively affect the neurologic manifestations such as spinal cord compression. Since nanoparticles (NP) have shown to be effective drug carriers, the feasibility of arylsulfatase B adsorption onto poly(butyl cyanoacrylate) (PBCA) nanoparticles was investigated in this study. In order to advance the ERT of ASB, the adsorption of the latter on the surface of PBCA NP as well as in vitro release in serum was investigated. With alteration of parameters like temperature, incubation time, pH, and enzyme amount, the adsorption process revealed to be stable with a maximum capacity of 67 microg/mg NP at a pH of 6.3. In vitro release experiments demonstrated that the adsorption is stable for at least 60 minutes in human blood serum, indicating that the ASB-loaded PBCA nanoparticles represent a promising candidate for ERT of MPS VI.

  11. Nicotine replacement therapy, tobacco products, and electronic cigarettes in pharmacies in St. Louis, Missouri.

    Science.gov (United States)

    Barnoya, Joaquin; Jin, Linda; Hudmon, Karen Suchanek; Schootman, Mario

    2015-01-01

    To compare availability of nicotine replacement therapy (NRT), tobacco products, and electronic cigarettes (e-cigarettes) in pharmacies in St. Louis, MO. Cross-sectional study, on-site store audits of 322 pharmacies. St. Louis, MO. 242 eligible community pharmacies located in the study area. Pharmacies were visited by trained research assistants who conducted a 5- to 10-minute store audit using a paper-based data collection tool. Availability, accessibility, and pricing of NRT as a function of neighborhood poverty rate and proportion of black residents as well as availability of tobacco products and e-cigarettes. NRT availability decreased as neighborhood poverty rate increased (P = 0.02). Availability without pharmacy personnel assistance also decreased with increasing poverty rate (r = -0.19; 95% CI = -0.06, -0.31) and higher percentage of black residents (r = -0.18; 95% CI = -0.06, -0.31). Prices were lower in neighborhoods with higher poverty rates (P = 0.02) and a higher percentage of black residents (P = 0.03). E-cigarettes were available in 43% of pharmacies, and their availability and price did not differ by poverty rate or percentage of black residents. Low access to NRT might perpetuate smoking disparities in disadvantaged and racially diverse neighborhoods. Study data support policies to ensure equal NRT access to reduce disparities.

  12. Hormone Replacement Therapy and Risk of Breast Cancer in Korean Women: A Quantitative Systematic Review

    Science.gov (United States)

    Bae, Jong-Myon; Kim, Eun Hee

    2015-01-01

    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. PMID:26429288

  13. A case of sodium chlorite toxicity managed with concurrent renal replacement therapy and red cell exchange.

    Science.gov (United States)

    Romanovsky, Adam; Djogovic, Dennis; Chin, Dat

    2013-03-01

    Sodium chlorite is a powerful oxidizing agent with multiple commercial applications. We report the presentation and management of a single case of human toxicity of sodium chlorite. A 65-year-old man presented to hospital after accidentally ingesting a small amount of a sodium chlorite solution. His principal manifestations were mild methemoglobinemia, severe oxidative hemolysis, disseminated intravascular coagulation, and anuric acute kidney injury. He was managed with intermittent hemodialysis, followed by continuous venovenous hemofiltration for management of acute kidney injury and in an effort to remove free plasma chlorite. Concurrently, he underwent two red cell exchanges, as well as a plasma exchange, to reduce the burden of red cells affected by chlorite. These interventions resulted in the cessation of hemolysis with stabilization of serum hemoglobin and platelets. The patient survived and subsequently recovered normal renal function. This is only the second case of sodium chlorite intoxication reported in the medical literature and the first to report the use of renal replacement therapy in combination with red cell exchange in its management.

  14. Effects of hormone replacement therapy on endothelial function in menopausal women

    Institute of Scientific and Technical Information of China (English)

    Jin-rn Yang; Fen Li

    2009-01-01

    Objective To observe the effects of hormone replacement therapy (HRT) on endothelial function in menopausal women. Methods A total of 30 menopausal women were treated with 2.5 mg of Tibolone (Livial) daily. At the same time, 30 women with natural menopause without any treatment served as the control group. Endothelium-dependent (EDD), endothelium-independent (NID) vasodilatation function, and estradiol (E2) were examined by the non-invasive high-resolution ultrasonography before the treatment and at 12th, 24th, 36th and 48th week of treatment, respectively. Results After hormone treatment, E2 increased significantly and EDD was improved significantly (P<0.05), and E2 was positively related with EDD (r=0.8092, P<0.001). No change of EDD was observed in the control group whereas a significant increase was observed in the treatment group. Conclusion Endothelium-dependent vasodilatation dysfunction is prominent in menopausal women. Tibolone can help improve the condition.

  15. Hormone replacement therapy and menopause%绝经期激素替代疗法

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    SUMMARY Hormone replacement therapy (HRT) was initiated almost half a century ago to treat menopausal symptoms. Initially, its use remained limited even among symptomatic women and the move toward postmenopausal hormone use for disease prevention came later. Improved treatment schedules and delivery systems expanded the use of HRT worldwide. However, large trials of postmenopausal hormones with disease outcomes were even later in coming and today HRT has become a specialized, multidisciplinary area of research. As the population continues to grow older, there has been an increased focus on the effects of ageing. HRT may affect length and quality of life through disease prevention. It may have possible beneficial effects on cognition, on the incidence of hip fracture, myocardial infarction and stroke, and adverse effects on the incidence of breast cancer, endometrial cancer, and venous thromboembolism.Today's attitudes about the hormonal treatments for the menopausal transition have moved from expansive optimism to contracting disappointment amidst safety concerns and equivocal results and faces greater skepticism and scrutiny. The health and well being of large numbers of women are at stake, and researchers, clinicians and the general public are watching and weighing the options.

  16. 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...

  17. Hereditary Angioedema due to C1 Inhibitor Deficiency: C1-INH Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Mauro Cancian

    2014-04-01

    Full Text Available Hereditary angioedema (HAE is a rare condition affecting about 1 in 50.000 individuals and caused by a mutation in the gene encoding the C1-esterase inhibitor (C1-INH, which is involved in the control of complement, clotting, fibrinolytic and kinin pathways. HAE is characterized by plasma outflow from blood vessels, leading to fluid collecting (edema in the deep tissue layers of the face, larynx, abdomen, and extremities. Three different types of HAE have been identified: in type I the mutation leads to the lack of production of C1-INH, in type II the mutation leads to the production of dysfunctional C1-INH, while type III is extremely rare and still not fully understood. Therapeutic approaches for HAE include on-demand treatments to stop angioedema attacks and prophylactic treatment to prevent attacks both by pre-procedural (short-term and routine (long-term prophylaxis. Aim of the present review is to present an overview of C1-INH replacement therapy with the plasma-derived concentrate of C1-INH Berinert® (CSL Behring GmbH in the treatment of type I and II HAE.http://dx.doi.org/10.7175/rhc.v5i2.913

  18. Comparison of Hospitalization and Survival Between Patients Treated With Renal Replacement Therapy

    Directory of Open Access Journals (Sweden)

    Murat MERAL

    2011-01-01

    Full Text Available AIM: Renal replacement therapy (RRT prolongs survival in patients with end-stage-renal-disease (ESRD. We compared patient survival, number and duration of hospitalization in patients treated with RRT in this study. MATERIAL and METHODS: Two hundred and eighty seven patients (87 hemodialysis (HD, 97 peritoneal dialysis (PD, 103 renal transplant (RT patients were enrolled in this study. Patients' data were collected retrospectively from hospital records. RESULTS: HD patients were older and had more comorbid diseases compared to PD and RT patients. Mortality rates were not different between the modalitites. The number and duration of hospitalization episodes were significantly lower in the PD group than that of the other two groups. Survival rates of HD patients were 84%, 55% and 30% for the 1st, 5th and 10th years, respectively while these rates were 93%, 81% and 59% for PD and 95%, 81% and 77% for RT patients. CONCLUSION: PD and RT patients were younger than HD patients and had less comorbid diseases. As a result, the number and duration of hospitalization episodes were significantly lower in the PD group when compared to the others. Survival rates in the RT group were better than that of the HD and PD groups.

  19. Effects of hormone replacement therapy on platelet activation in postmenopausal women

    Institute of Scientific a