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Sample records for replacement therapy trial

  1. 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...

  2. 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.

  3. 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

  4. 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.

  5. Randomized controlled trial of mailed Nicotine Replacement Therapy to Canadian smokers: study protocol

    Directory of Open Access Journals (Sweden)

    Leatherdale Scott T

    2011-09-01

    Full Text Available Abstract Background Considerable public health efforts are ongoing Canada-wide to reduce the prevalence of smoking in the general population. From 1985 to 2005, smoking rates among adults decreased from 35% to 19%, however, since that time, the prevalence has plateaued at around 18-19%. To continue to reduce the number of smokers at the population level, one option has been to translate interventions that have demonstrated clinical efficacy into population level initiatives. Nicotine Replacement Therapy (NRT has a considerable clinical research base demonstrating its efficacy and safety and thus public health initiatives in Canada and other countries are distributing NRT widely through the mail. However, one important question remains unanswered - do smoking cessation programs that involve mailed distribution of free NRT work? To answer this question, a randomized controlled trial is required. Methods/Design A single blinded, panel survey design with random assignment to an experimental and a control condition will be used in this study. A two-stage recruitment process will be employed, in the context of a general population survey with two follow-ups (8 weeks and 6 months. Random digit dialing of Canadian home telephone numbers will identify households with adult smokers (aged 18+ years who are willing to take part in a smoking study that involves three interviews, with saliva collection for 3-HC/cotinine ratio measurement at baseline and saliva cotinine verification at 8-week and 6-month follow-ups (N = 3,000. Eligible subjects interested in free NRT will be determined at baseline (N = 1,000 and subsequently randomized into experimental and control conditions to receive versus not receive nicotine patches. The primary hypothesis is that subjects who receive nicotine patches will display significantly higher quit rates (as assessed by 30 day point prevalence of abstinence from tobacco at 6-month follow-up as compared to subjects who do not

  6. 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, ...

  7. 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...

  8. Protocol for the Smoking, Nicotine and Pregnancy (SNAP trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy

    Directory of Open Access Journals (Sweden)

    Coughtrie Michael WH

    2007-01-01

    Full Text Available Abstract Background Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA-funded smoking, nicotine and pregnancy (SNAP trial will investigate whether or not nicotine replacement therapy (NRT is effective, cost-effective and safe when used for smoking cessation by pregnant women. Methods/Design Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date (defined before randomisation and set within two weeks of this and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups. Discussion This trial is designed to ascertain whether or not standard doses of NRT (as transdermal patches are effective and safe when used for smoking cessation during pregnancy.

  9. Genetic variation in mu-opioid-receptor-interacting proteins and smoking cessation in a nicotine replacement therapy trial.

    Science.gov (United States)

    Ray, Riju; Jepson, Christopher; Wileyto, E Paul; Dahl, John P; Patterson, Freda; Rukstalis, Margaret; Pinto, Angela; Berrettini, Wade; Lerman, Caryn

    2007-11-01

    Extending a previous finding of an association between functional genetic variation in the mu-opioid receptor gene and response to nicotine replacement therapy, we explored the role of genetic variants in two genes encoding mu-opioid-receptor-interacting proteins, namely ARRB2 and HINT1. Participants were 374 smokers treated for nicotine dependence with either transdermal nicotine or nicotine nasal spray for 8 weeks in an open-label randomized trial. In a logistic regression model controlling for OPRM1 genotype, treatment type, and other covariates, we found no significant main effect of ARRB2 genotype on abstinence at either end of treatment or 6-month follow-up. Participants with the HINT1 TT genotype had significantly higher abstinence rates at 6-month follow-up, but this may not be a pharmacogenetic effect, given that the participants were drug free during this time. Haplotype analysis did not reveal any significant associations for either gene. We found an interaction of ARRB2 and OPRM1 genotype on abstinence at 6 months that approached significance; however, interpretation of this finding is limited by the small number of participants with the minor alleles for both genes. Although these data do not provide support for the role of genetic variation in these mu-opioid-receptor-interacting proteins and smoking cessation, further exploration of opioid pathway genes in larger prospective pharmacogenetic trials may be warranted.

  10. 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...

  11. 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

  12. Study protocol for a non-inferiority trial of cytisine versus nicotine replacement therapy in people motivated to stop smoking

    Directory of Open Access Journals (Sweden)

    Walker Natalie

    2011-11-01

    Full Text Available Abstract Background Smokers need effective support to maximise the chances of successful quit attempts. Current smoking cessation medications, such as nicotine replacement therapy (NRT, bupropion, nortriptyline or varenicline, have been shown to be effective in clinical trials but are underused by smokers attempting to quit due to adverse effects, contraindications, low acceptability and/or high cost. Cytisine is a low-cost, plant-based alkaloid that has been sold as a smoking cessation aid in Eastern Europe for 50 years. A systematic review of trial evidence suggests that cytisine has a positive impact on both short- and long-term abstinence rates compared to placebo. However, the quality of the evidence is poor and insufficient for licensing purposes in many Western countries. A large, well-conducted placebo-controlled trial (n = 740 of cytisine for smoking cessation has recently been published and confirms the findings of earlier studies, with 12-month continuous abstinence rates of 8.4% in the cytisine group compared to 2.4% in the placebo group (Relative risk = 3.4, 95% confidence intervals 1.7-7.1. No research has yet been undertaken to determine the effectiveness of cytisine relative to that of NRT. Methods/design A single-blind, randomised controlled, non-inferiority trial has been designed to determine whether cytisine is at least as effective as NRT in assisting smokers to remain abstinent for at least one month. Participants (n = 1,310 will be recruited through the national telephone-based Quitline service in New Zealand and randomised to receive a standard 25-day course of cytisine tablets (Tabex® or usual care (eight weeks of NRT patch and/or gum or lozenge. Participants in both study arms will also receive a behavioural support programme comprising an average of three follow-up telephone calls delivered over an eight-week period by Quitline. The primary outcome is continuous abstinence from smoking at one month, defined as not

  13. A small-scale clinical trial to determine the safety and efficacy of testosterone replacement therapy in hypogonadal men with spinal cord injury.

    Science.gov (United States)

    Bauman, W A; Cirnigliaro, C M; La Fountaine, M F; Jensen, A M; Wecht, J M; Kirshblum, S C; Spungen, A M

    2011-07-01

    Men with spinal cord injury are at an increased risk for secondary medical conditions, including metabolic disorders, accelerated musculoskeletal atrophy, and, for some, hypogonadism, a deficiency, which may further adversely affect metabolism and body composition. A prospective, open label, controlled drug intervention trial was performed to determine whether 12 months of testosterone replacement therapy increases lean tissue mass and resting energy expenditure in hypogonadal males with spinal cord injury. Healthy eugonadal (n = 11) and hypogonadal (n = 11) outpatients with chronic spinal cord injury were enrolled. Hypogonadal subjects received transdermal testosterone (5 or 10 mg) daily for 12 months. Measurements of body composition and resting energy expenditure were obtained at baseline and 12 months. The testosterone replacement therapy group increased lean tissue mass for total body (49.6 ± 7.6 vs. 53.1 ± 6.9 kg; p testosterone replacement therapy, resting energy expenditure (1328 ± 262 vs. 1440 ± 262 kcal/d; p testosterone replacement therapy significantly improved lean tissue mass and energy expenditure in hypogonadal men with spinal cord injury, findings that would be expected to influence the practice of clinical care, if confirmed. Larger, randomized, controlled clinical trials should be performed to confirm and extend our preliminary findings.

  14. Trial Protocol: Using genotype to tailor prescribing of nicotine replacement therapy: a randomised controlled trial assessing impact of communication upon adherence

    Directory of Open Access Journals (Sweden)

    Prevost A Toby

    2010-11-01

    Full Text Available Abstract Background The behavioural impact of pharmacogenomics is untested; informing smokers of genetic test results for responsiveness to smoking cessation medication may increase adherence to this medication. The objective of this trial is to estimate the impact upon adherence to nicotine replacement therapy (NRT of informing smokers that their oral dose of NRT has been tailored to a DNA analysis. Hypotheses to be tested are as follows: IAdherence to NRT is greater among smokers informed that their oral dose of NRT is tailored to an analysis of DNA (genotype, compared to one tailored to nicotine dependence questionnaire score (phenotype. II Amongst smokers who fail to quit at six months, motivation to make another quit attempt is lower when informed that their oral dose of NRT was tailored to genotype rather than phenotype. Methods/Design An open label, parallel groups randomised trial in which 630 adult smokers (smoking 10 or more cigarettes daily using National Health Service (NHS stop smoking services in primary care are randomly allocated to one of two groups: i. NRT oral dose tailored by DNA analysis (OPRM1 gene (genotype, or ii. NRT oral dose tailored by nicotine dependence questionnaire score (phenotype The primary outcome is proportion of prescribed NRT consumed in the first 28 days following an initial quit attempt, with the secondary outcome being motivation to make another quit attempt, amongst smokers not abstinent at six months. Other outcomes include adherence to NRT in the first seven days and biochemically validated smoking abstinence at six months. The primary outcome will be collected on 630 smokers allowing sufficient power to detect a 7.5% difference in mean proportion of NRT consumed using a two-tailed test at the 5% level of significance between groups. The proportion of all NRT consumed in the first four weeks of quitting will be compared between arms using an independent samples t-test and by estimating the 95

  15. Efficacy and safety of testosterone replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials.

    Science.gov (United States)

    Guo, Changcheng; Gu, Wenyu; Liu, Min; Peng, B O; Yao, Xudong; Yang, Bin; Zheng, Junhua

    2016-03-01

    The purpose of the present meta-analysis was to evaluate the efficacy and safety of testosterone replacement therapy in men with hypogonadism. A search was conducted for appropriate randomized controlled trials and the data from 16 trials were pooled. The intended primary outcome of the present study was to determine the efficacy and safety of testosterone replacement therapy. The current data demonstrated that scores for Aging Male Symptoms (AMS) were significantly reduced following testosterone replacement therapy, with a mean decrease in AMS score of 1.52 [95% confidence interval (CI), 0.72 to 2.32; P=0.0002]. Testosterone replacement therapy increased lean body mass [mean difference (MD), 1.22; 95% CI, 0.33 to 2.11; P=0.007], reduced fat mass in a non-significantly manner (MD, -0.85; 95% CI, -1.74 to 0.04; P=0.06) and significantly reduced total cholesterol (MD, -0.16; 95% CI, -0.29 to -0.03; P=0.01). No significant differences were identified in body weight (MD, 0.09; 95% CI, -1.13 to 1.31; P=0.89), body mass index (MD, 0.10; 95% CI, -0.62 to 0.82; P=0.78) or bone mineral density (MD, -0.01; 95% CI, -0.03 to 0.02; P=0.60). Average prostate volume increased (MD, 1.58; 95% CI, 0.6 to 2.56; P=0.002) following testosterone replacement therapy, but the levels of prostate-specific antigen (PSA) (MD, 0.10; 95% CI, -0.03 to 0.22; P=0.14) and the International Prostate Symptom Scores (MD, 0.01; 95% CI, -0.37 to 0.39; P=0.96) did not change. In conclusion, testosterone replacement therapy improves quality of life, increases lean body mass, significantly decreases total cholesterol, and is well-tolerated and safe for men with hypogonadism who are exhibiting PSA levels of <4 ng/ml.

  16. 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.

  17. Testosterone replacement therapy improves health-related quality of life for patients with late-onset hypogonadism: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Nian, Y; Ding, M; Hu, S; He, H; Cheng, S; Yi, L; Li, Y; Wang, Y

    2017-05-01

    Although testosterone replacement therapy can restore serum testosterone concentrations to normal level in late-onset hypogonadism patients, whether it can improve patients' quality of life remains uncertain. Therefore, we perform a meta-analysis of randomized controlled trials on this issue. Five randomized controlled trials total 1,212 patients were included. Fixed-effect model was used to calculate the weighted mean difference of score of Aging Males' Symptom rating scale. Our result reveals that testosterone replacement therapy improves patients' health-related quality of life in terms of the decrease in the AMS total score [WMD = -2.96 (-4.21, -1.71), p < .00001] and the psychological [WMD = -0.89 (-1.41, -0.37), p = .0008], somatic [WMD = -0.89 (-1.41, -0.37), p = .0008] and sexual [WMD = -1.29 (-1.75, -0.83), p < .00001] subscale score. © 2016 Blackwell Verlag GmbH.

  18. The Clinical Phenotype of CNGA3-Related Achromatopsia: Pretreatment Characterization in Preparation of a Gene Replacement Therapy Trial.

    Science.gov (United States)

    Zobor, Ditta; Werner, Annette; Stanzial, Franco; Benedicenti, Francesco; Rudolph, Günther; Kellner, Ulrich; Hamel, Christian; Andréasson, Sten; Zobor, Gergely; Strasser, Torsten; Wissinger, Bernd; Kohl, Susanne; Zrenner, Eberhart

    2017-02-01

    The purpose of this study was to clinically characterize patients with CNGA3-linked achromatopsia (CNGA3-ACHM) in preparation of a gene therapy trial. Thirty-six patients (age 7-56 years) with complete (cACHM) or incomplete (iACHM) CNGA3-ACHM were examined, including detailed psychophysical tests, extended electrophysiology, and assessment of morphology by fundus autofluorescence and spectral-domain optical coherence tomography (SD-OCT). Mean best-corrected visual acuity was 0.78 ± 0.14 logMAR. Color vision tests were consistent with a rod-dominated function in every cACHM patient. Microperimetry indicated an overall lowered retinal sensitivity within 20° of visual field. In electroretinography (ERG), photopic responses were nondetectable in cACHM patients, but residual cone responses were observed in the iACHM patients. Scotopic responses were altered referring to anomalies of photoreceptor and postreceptor signaling, whereas in voltage versus intensity functions, Vmax was significantly below normal values (P < 0.05). In contrast, slope (n) and semisaturation intensity (K) were found to be within normal limits. Spectral-domain OCT examination showed no specific changes in 14.7%, disruption of the ellipsoid zone (EZ) at the fovea in 38.2%, absent EZ in 17.7%, a hyporeflective zone in 20.5%, and outer retinal atrophy in 8.9% of all cases and foveal hypoplasia in 29 patients (85%). No correlation of retinal morphology with visual function or with a specific genotype was found. The severity of morphologic and functional changes lacked a robust association with age. Our extended investigations prove that even among such a genetically homogenous group of patients, no specific correlations regarding function and morphology severity and age can be observed. Therefore, the therapeutic window seems to be wider than previously indicated.

  19. A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe

    Directory of Open Access Journals (Sweden)

    Cornette Luc

    2007-08-01

    Full Text Available Abstract Background Studies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and β cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer β cells are linked to risk of type 2 diabetes later in life. Methods A multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight Trial Registration Current Controlled Trials ISRCTN78428828. EUDRACT Number 2004-002170-34

  20. Intermittent versus continuous renal replacement therapy for acute kidney injury patients admitted to the intensive care unit: results of a randomized clinical trial.

    Science.gov (United States)

    Lins, Robert L; Elseviers, Monique M; Van der Niepen, Patricia; Hoste, Eric; Malbrain, Manu L; Damas, Pierre; Devriendt, Jacques

    2009-02-01

    There is uncertainty on the effect of different dialysis modalities for the treatment of patients with acute kidney injury (AKI), admitted to the intensive care unit (ICU). This controlled clinical trial performed in the framework of the multicentre SHARF 4 study (Stuivenberg Hospital Acute Renal Failure) aimed to investigate the outcome in patients with AKI, stratified according to severity of disease and randomized to different treatment options. This was a multicentre prospective randomized controlled trial with stratification according to severity of disease expressed by the SHARF score. ICU patients were eligible for inclusion when serum creatinine was >2 mg/dL, and RRT was initiated. The selected patients were randomized to intermittent (IRRT) or continuous renal replacement therapy (CRRT). A total of 316 AKI patients were randomly assigned to IRRT (n = 144) or CRRT (n = 172). The mean age was 66 (range 18-96); 59% were male. Intention-to-treat analysis revealed a mortality of 62.5% in IRRT compared to 58.1% in CRRT (P = 0.430). No difference between IRRT and CRRT could be observed in the duration of ICU stay or hospital stay. In survivors, renal recovery at hospital discharge was comparable between both groups. Multivariate analysis, including the SHARF score, APACHE II and SOFA scores for correction of disease severity, showed no difference in mortality between both treatment modalities. This result was confirmed in pre-specified subgroup analysis (elderly, patients with sepsis, heart failure, ventilation) and after exclusion of possible confounders (early mortality, delayed ICU admission). Modality of RRT, either CRRT or IRRT, had no impact on the outcome in ICU patients with AKI. Both modalities need to be considered as complementary in the treatment of AKI (Clinical Trial: SHARF 4, NCT00322933, http://ClinicalTrials.gov).

  1. 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

  2. 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....

  3. 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.

  4. 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.

  5. 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.

  6. Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Cai, Xiang; Tian, Ye; Wu, Tao; Cao, Chen-Xi; Li, Hong; Wang, Kun-Jie

    2014-01-01

    This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy (TRT) on hypogonadal men with type 2 diabetes mellitus (T2DM). A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials (RCTs) were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaboration's Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5-months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels (mean difference (MD): -1.10; 95% confidence interval (CI) (-1.88, -0.31)), fasting serum insulin levels (MD: -2.73; 95% CI (-3.62, -1.84)), HbA1c % (MD: -0.87; 95% CI (-1.32, -0.42)) and triglyceride levels (MD: -0.35; 95% CI (-0.62, -0.07)). The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM.

  7. Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Xiang Cai

    2014-02-01

    Full Text Available This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy (TRT on hypogonadal men with type 2 diabetes mellitus (T2DM. A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials (RCTs were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaboration's Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5-months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels (mean difference (MD: −1.10; 95% confidence interval (CI (−1.88, −0.31, fasting serum insulin levels (MD: −2.73; 95% CI (−3.62, −1.84, HbA1c % (MD: −0.87; 95% CI (−1.32, −0.42 and triglyceride levels (MD: −0.35; 95% CI (−0.62, −0.07. The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM.

  8. Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

    Science.gov (United States)

    Cai, Xiang; Tian, Ye; Wu, Tao; Cao, Chen-Xi; Li, Hong; Wang, Kun-Jie

    2014-01-01

    This systematic review was aimed at assessing the metabolic effects of testosterone replacement therapy (TRT) on hypogonadal men with type 2 diabetes mellitus (T2DM). A literature search was performed using the Cochrane Library, EMBASE and PubMed. Only randomized controlled trials (RCTs) were included in the meta-analysis. Two reviewers retrieved articles and evaluated the study quality using an appropriate scoring method. Outcomes including glucose metabolism, lipid parameters, body fat and blood pressure were pooled using a random effects model and tested for heterogeneity. We used the Cochrane Collaboration's Review Manager 5.2 software for statistical analysis. Five RCTs including 351 participants with a mean follow-up time of 6.5-months were identified that strictly met our eligibility criteria. A meta-analysis of the extractable data showed that testosterone reduced fasting plasma glucose levels (mean difference (MD): −1.10; 95% confidence interval (CI) (−1.88, −0.31)), fasting serum insulin levels (MD: −2.73; 95% CI (−3.62, −1.84)), HbA1c % (MD: −0.87; 95% CI (−1.32, −0.42)) and triglyceride levels (MD: −0.35; 95% CI (−0.62, −0.07)). The testosterone and control groups demonstrated no significant difference for other outcomes. In conclusion, we found that TRT can improve glycemic control and decrease triglyceride levels of hypogonadal men with T2DM. Considering the limited number of participants and the confounding factors in our systematic review; additional large, well-designed RCTs are needed to address the metabolic effects of TRT and its long-term influence on hypogonadal men with T2DM. PMID:24369149

  9. Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial.

    Science.gov (United States)

    Salmén, Timo; Heikkinen, Anna-Mari; Mahonen, Anitta; Kröger, Heikki; Komulainen, Marja; Pallonen, Heli; Saarikoski, Seppo; Honkanen, Risto; Mäenpää, Pekka H

    2003-02-01

    In women, the influence of androgens on bone health is not clear. It has been suggested that the androgen receptor (AR) genotype is associated with bone mineral density and serum androgen levels in pre- and perimenopausal women, but the association between AR genotype, bone mineral density, and fracture risk has not been studied in postmenopausal women. Therefore, we studied whether AR polymorphism affects bone mineral density, bone mineral density change, or fracture risk in a 5-year randomized hormone replacement therapy (HRT) trial on 331 early postmenopausal women (mean baseline age, 52.7 +/- 2.3 years). The participants consisted of two treatment groups: the HRT group (n = 151) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3, 100-300 IU + 93 mg calcium as lactate/day, and the non-HRT group (n = 180) received 93 mg calcium alone or in combination with vitamin D3, 100-300 IU/day for 5 years. Bone mineral density was measured from lumbar spine and proximal femur (DXA) before and after the 5-year trial. All new symptomatic, radiographically defined fractures were recorded during the follow-up. The length of CAG repeat in exon 1 of AR gene was evaluated after polymerase chain reaction (PCR) amplification. The subjects were divided into three repeat groups according to AR alleles. None of the baseline characteristics were associated with AR gene polymorphism and HRT treatment. The polymorphism did not influence the calculated annual changes of lumbar or femoral neck bone mineral density during the 5-year follow-up in the HRT (p = 0.926 and 0.146, respectively) or non-HRT (p = 0.818 and 0.917, respectively) groups. In all, 28 women sustained 33 fractures during the follow-up. Thus, the numbers of fractures were limited. The AR repeat length variation was not significantly associated with fracture risk in the HRT or non-HRT groups (p = 0.632 and 0.459, respectively; Cox proportional hazards model

  10. 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.

  11. Dialysis complications in acute kidney injury patients treated with prolonged intermittent renal replacement therapy sessions lasting 10 versus 6 hours: results of a randomized clinical trial.

    Science.gov (United States)

    Albino, Bianca Ballarin; Balbi, André Luis; Abrão, Juliana Maria Gera; Ponce, Daniela

    2015-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) has emerged as an alternative to continuous renal replacement therapy in the management of acute kidney injury (AKI) patients. This trial aimed to compare the dialysis complications occurring during different durations of PIRRT sessions in critically ill AKI patients. We included patients older than 18 years with AKI associated with sepsis admitted to the intensive care unit and using noradrenaline doses ranging from 0.3 to 0.7 µg/kg/min. Patients were divided into two groups randomly: in G1, 6-h sessions were performed, and in G2, 10-h sessions were performed. Seventy-five patients were treated with 195 PIRRT sessions for 18 consecutive months. The prevalence of hypotension, filter clotting, hypokalemia, and hypophosphatemia was 82.6, 25.3, 20, and 10.6%, respectively. G1 was composed of 38 patients treated with 100 sessions, whereas G2 consisted of 37 patients treated with 95 sessions. G1 and G2 were similar in male predominance (65.7 vs. 75.6%, P = 0.34), age (63.6 ± 14 vs. 59.9 ± 15.5 years, P = 0.28) and Sequential Organ Failure Assessment score (SOFA; 13.1 ± 2.4 vs. 14.2 ± 3.0, P = 0.2). There was no significant difference between the two groups in hypotension (81.5 vs. 83.7%, P = 0.8), filter clotting (23.6 vs. 27%, P = 0.73), hypokalemia (13.1 vs. 8.1%, P = 0.71), and hypophosphatemia (18.4 vs. 21.6%, P = 0.72). However, the group treated with sessions of 10 h were refractory to clinical measures for hypotension, and dialysis sessions were interrupted more often (9.5 vs. 30.1%, P = 0.03). Metabolic control and fluid balance were similar between G1 and G2 (blood urea nitrogen [BUN]: 81 ± 30 vs. 73 ± 33 mg/dL, P = 1.0; delivered Kt/V: 1.09 ± 0.24 vs. 1.26 ± 0.26, P = 0.09; actual ultrafiltration: 1731 ± 818 vs. 2332 ± 947 mL, P = 0.13) and fluid balance (-731 ± 125 vs. -652 ± 141

  12. 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.

  13. [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.

  14. 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...

  15. Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial.

    Science.gov (United States)

    Baker, Timothy B; Piper, Megan E; Stein, James H; Smith, Stevens S; Bolt, Daniel M; Fraser, David L; Fiore, Michael C

    2016-01-26

    Smoking cessation medications are routinely used in health care; it is vital to identify medications that most effectively treat this leading cause of preventable mortality. To compare the efficacies of varenicline, combination nicotine replacement therapy (C-NRT), and the nicotine patch for 26-week quit rates. Three-group randomized intention-to-treat clinical trial occurring from May 2012 to November 2015 among smokers recruited in the Madison, Wisconsin, and Milwaukee, Wisconsin, communities; 65.5% of smokers offered the study (2687/4102) refused participation prior to randomization. Participants were randomized to one of three 12-week open-label smoking cessation pharmacotherapy groups: (1) nicotine patch only (n = 241); (2) varenicline only (including 1 prequit week; n = 424); and (3) C-NRT (nicotine patch + nicotine lozenge; n = 421). Six counseling sessions were offered. The primary outcome was carbon monoxide-confirmed self-reported 7-day point-prevalence abstinence at 26 weeks. Secondary outcomes were carbon monoxide-confirmed self-reported initial abstinence, prolonged abstinence at 26 weeks, and point-prevalence abstinence at weeks 4, 12, and 52. Among 1086 smokers randomized (52% women; 67% white; mean age, 48 years; mean of 17 cigarettes smoked per day), 917 (84%) provided 12-month follow-up data. Treatments did not differ on any abstinence outcome measure at 26 or 52 weeks, including point-prevalence abstinence at 26 weeks (nicotine patch, 22.8% [55/241]; varenicline, 23.6% [100/424]; and C-NRT, 26.8% [113/421]) or at 52 weeks (nicotine patch, 20.8% [50/241]; varenicline, 19.1% [81/424]; and C-NRT, 20.2% [85/421]). At 26 weeks, the risk differences for abstinence were, for patch vs varenicline, -0.76% (95% CI, -7.4% to 5.9%); for patch vs C-NRT, -4.0% (95% CI, -10.8% to 2.8%); and for varenicline vs C-NRT, -3.3% (95% CI, -9.1% to 2.6%). All medications were well tolerated, but varenicline produced more frequent adverse events than did

  16. 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.

  17. 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...

  18. [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.

  19. 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....

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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...

  5. 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...

  6. Transdermal testosterone replacement therapy in men

    Directory of Open Access Journals (Sweden)

    Ullah MI

    2014-01-01

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

  7. 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.

  8. Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone

    Directory of Open Access Journals (Sweden)

    Lars Rejnmark

    2015-12-01

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

  9. Testosterone replacement therapy in older male subjective memory complainers: double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety.

    Science.gov (United States)

    Asih, Prita R; Wahjoepramono, Eka J; Aniwiyanti, Vilia; Wijaya, Linda K; de Ruyck, Karl; Taddei, Kevin; Fuller, Stephanie J; Sohrabi, Hamid; Dhaliwal, Satvinder S; Verdile, Giuseppe; Carruthers, Malcolm; Martins, Ralph N

    2015-01-01

    Testosterone replacement therapy (TRT) has been investigated in older men as a preventative treatment against Alzheimer's disease and dementia. However, previous studies have been contradictory. We assessed TRT physiological effects in 44 older men (aged 61 ± 7.7 years) with subjective memory complaints using a double blind, randomized, crossover, placebo-controlled study. Participants were randomized into 2 groups, one group received transdermal testosterone (50 mg) daily for 24 weeks, followed by a 4 week wash-out period, then 24 weeks of placebo; the other group received the reverse treatment. Blood evaluation revealed significant increases in total testosterone, free (calculated) testosterone, dihydrotestosterone, and a decrease in luteinizing hormone levels (p<0.001) following TRT. Although there were significant increases in red blood cell counts, hemoglobin and prostate specific antigen levels following TRT, they remained within normal ranges. No significant differences in plasma amyloid beta, estradiol, sex hormone binding globulin, insulin levels, body fat percentage, or body mass index were detected. This is the first carefully controlled study that has investigated the influence of TRT in Indonesian men on blood biomarkers linked to dementia risk. Our study suggests TRT is safe and well-tolerated in this Indonesian cohort, yet longitudinal studies with larger cohorts are needed to assess TRT further, and to establish whether TRT reduces dementia risk.

  10. 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.

  11. Intravenous carbamazepine as short-term replacement therapy for oral carbamazepine in adults with epilepsy: Pooled tolerability results from two open-label trials.

    Science.gov (United States)

    Lee, Deborah; Kalu, Uwa; Halford, Jonathan J; Biton, Victor; Cloyd, James; Klein, Pavel; Bekersky, Ihor; Peng, Guangbin; Dheerendra, Suresh; Tolbert, Dwain

    2015-06-01

    To report tolerability findings and maintenance of seizure control from a pooled analysis of phase I open-label trial OV-1015 (NCT01079351) and phase III study 13181A (NCT01128959). Patients receiving a stable oral dosage of carbamazepine were switched to an intravenous (IV) carbamazepine formulation solubilized in a cyclodextrin matrix (at a 70% dosage conversion) for either a 15- or a 30-min infusion every 6 h for up to 7 days and then switched back. A subset of patients who tolerated 15-min infusions also received 2- to 5-min (rapid) infusions. Assessments included physical and laboratory evaluations, electrocardiography (ECG) studies, as well as adverse event (AE) monitoring for tolerability. Convulsion/seizure AE terms and data from seizure diaries were used as proxies for the assessment of consistency of seizure control between formulations. Of the 203 patients exposed to IV carbamazepine (30 min, n = 43; 15 min, n = 160), 113 received 149 rapid infusions. During infusion, the most commonly reported AEs (≥ 5%) were dizziness (19%), somnolence (6%), headache (6%), and blurred vision (5%). IV carbamazepine was not associated with clinically relevant cardiac AEs. The tolerability profile appeared similar between patients who received oral and IV carbamazepine. IV carbamazepine administered as multiple 30- or 15-min infusions every 6 h, and as a single rapid infusion, was well tolerated as a short-term replacement in adults with epilepsy receiving stable dosages of oral carbamazepine. Infusion site reactions, which were generally mild, were the only unique AEs identified; seizure control was generally unchanged when patients were switching between formulations. © 2015 Lundbeck LLC. Epilepsia published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Trials and Tribulations with VH Replacement

    Directory of Open Access Journals (Sweden)

    Wenzhao eMeng

    2014-01-01

    Full Text Available VH replacement is a type of antibody gene rearrangement in which an upstream heavy chain variable gene segment (VH invades a pre-existing rearrangement (VDJ. In this Hypothesis and Theory article, we begin by reviewing the mechanism of VH replacement, its developmental timing and its potential biological consequences. Then we explore the hypothesis that specific sequence motifs called footprints reflect VH replacement vs. other processes. We provide a compilation of footprint sequences from different regions of the antibody heavy chain, include data from the literature and from a high throughput sequencing experiment to evaluate the significance of footprint sequences. We conclude by discussing the difficulties of attributing footprints to VH replacement.

  3. A retrospective study: osteoporosis and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    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.

  4. 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 ...

  5. [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).

  6. 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.

  7. 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.

  8. Insulin-like growth factor I (IGF-I) replacement therapy increases albumin concentration in liver cirrhosis : Results of a pilot randomized controlled clinical trial

    NARCIS (Netherlands)

    Conchillo, M; de Knegt, RJ; Payeras, M; Quiroga, J; Sangro, B; Herrero, JI; Castilla-Cortazar, [No Value; Frystyk, J; Flyvbjerg, A; Yoshizawa, C; Jansen, PLM; Scharschmidt, B; Prieto, J

    2005-01-01

    Background/Aims: Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesized in the liver whose levels decrease sharply in liver cirrhosis. Methods: We conducted a randomized double-blind placebo-controlled clinical trial to evaluate the effect of subcutaneous administration of IGF-I (20

  9. Insulin-like growth factor I (IGF-I) replacement therapy increases albumin concentration in liver cirrhosis : Results of a pilot randomized controlled clinical trial

    NARCIS (Netherlands)

    Conchillo, M; de Knegt, RJ; Payeras, M; Quiroga, J; Sangro, B; Herrero, JI; Castilla-Cortazar, [No Value; Frystyk, J; Flyvbjerg, A; Yoshizawa, C; Jansen, PLM; Scharschmidt, B; Prieto, J

    2005-01-01

    Background/Aims: Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesized in the liver whose levels decrease sharply in liver cirrhosis. Methods: We conducted a randomized double-blind placebo-controlled clinical trial to evaluate the effect of subcutaneous administration of IGF-I (20

  10. Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement

    NARCIS (Netherlands)

    D. Elstein; A. Dweck; D. Attias; I. Hadas-Halpern; S. Zevin; G. Altarescu; J.F.M.G. Aerts; S. van Weely; A. Zimran

    2007-01-01

    Enzyme replacement therapy (ERT) with imiglucerase reduces hepatosplenomegaly and improves hematologic parameters in Gaucher disease type 1 within 6-24 months. Miglustat reduces organomegaly, improves hematologic parameters, and reverses bone marrow infiltration. This trial evaluates miglustat in pa

  11. 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- ...

  12. 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.

  13. 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.

  14. 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....

  15. Trials and Tribulations with VH Replacement.

    Science.gov (United States)

    Meng, Wenzhao; Jayaraman, Sahana; Zhang, Bochao; Schwartz, Gregory W; Daber, Robert D; Hershberg, Uri; Garfall, Alfred L; Carlson, Christopher S; Luning Prak, Eline T

    2014-01-01

    VH replacement (VHR) is a type of antibody gene rearrangement in which an upstream heavy chain variable gene segment (VH) invades a pre-existing rearrangement (VDJ). In this Hypothesis and Theory article, we begin by reviewing the mechanism of VHR, its developmental timing and its potential biological consequences. Then we explore the hypothesis that specific sequence motifs called footprints reflect VHR versus other processes. We provide a compilation of footprint sequences from different regions of the antibody heavy chain, and include data from the literature and from a high throughput sequencing experiment to evaluate the significance of footprint sequences. We conclude by discussing the difficulties of attributing footprints to VHR.

  16. 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

  17. 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....

  18. 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....

  19. 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...

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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....

  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. 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. 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.

  8. 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.

  9. 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...

  10. 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...

  11. 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.

  12. 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 ...

  13. 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.

  14. 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-...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. [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.

  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. 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.

  7. Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials.

    Science.gov (United States)

    Gagliano-Jucá, Thiago; Içli, Tevhide Betül; Pencina, Karol M; Li, Zhuoying; Tapper, John; Huang, Grace; Travison, Thomas G; Tsitouras, Panayiotis; Harman, S Mitchell; Storer, Thomas W; Bhasin, Shalender; Basaria, Shehzad

    2017-05-01

    Endogenous testosterone levels have been negatively associated with QTc interval in small case series; the effects of testosterone therapy on electrocardiographic parameters have not been evaluated in randomized trials. To evaluate the effects of testosterone replacement on corrected QT interval (QTcF) in two randomized controlled trials. Men with pre- and postrandomization electrocardiograms (ECGs) from the Testosterone and Pain (TAP) and the Testosterone Effects on Atherosclerosis in Aging Men (TEAAM) Trials. Participants were randomized to either placebo or testosterone gel for 14 weeks (TAP) or 36 months (TEAAM). ECGs were performed at baseline and at the end of interventions in both trials; in the TEAAM trial ECGs were also obtained at 12 and 24 months. Difference in change in the QTcF between testosterone and placebo groups was assessed in each trial. Association of changes in testosterone levels with changes in QTcF was analyzed in men assigned to the testosterone group of each trial. Mean total testosterone levels increased in the testosterone group of both trials. In the TAP trial, there was a nonsignificant reduction in mean QTcF in the testosterone group compared with placebo (effect size = -4.72 ms; P = 0.228) and the changes in QTcF were negatively associated to changes in circulating testosterone (P = 0.036). In the TEAAM trial, testosterone attenuated the age-related increase in QTcF seen in the placebo group (effect size= -6.30 ms; P Testosterone replacement attenuated the age-related increase in QTcF duration in men. The clinical implications of these findings require further investigation.

  8. Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study

    DEFF Research Database (Denmark)

    Jensen, L B; Vestergaard, P; Hermann, A P

    2003-01-01

    The aim of this study was to study the influence of hormone replacement therapy (HRT) on weight changes, body composition, and bone mass in early postmenopausal women in a partly randomized comprehensive cohort study design. A total of 2016 women ages 45-58 years from 3 months to 2 years past last...... of the weight gain was a decline in physical fitness. Women opting for HRT had a significantly lower body weight at inclusion than the other participants, but the results in the self-selected part of the study followed the pattern found in the randomized part. The change in fat mass was the strongest predictor...

  9. 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.

  10. 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

  11. 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

  12. Total knee replacement plus physical and medical therapy or treatment with physical and medical therapy alone: a randomised controlled trial in patients with knee osteoarthritis (the MEDIC-study

    Directory of Open Access Journals (Sweden)

    Skou Soren T

    2012-05-01

    Full Text Available Abstract Background There is a lack of high quality evidence concerning the efficacy of total knee arthroplasty (TKA. According to international evidence-based guidelines, treatment of knee osteoarthritis (KOA should include patient education, exercise and weight loss. Insoles and pharmacological treatment can be included as supplementary treatments. If the combination of these non-surgical treatment modalities is ineffective, TKA may be indicated. The purpose of this randomised controlled trial is to examine whether TKA provides further improvement in pain, function and quality of life in addition to optimised non-surgical treatment in patients with KOA defined as definite radiographic OA and up to moderate pain. Methods/Design The study will be conducted in The North Denmark Region. 100 participants with radiographic KOA (K-L grade ≥2 and mean pain during the previous week of ≤ 60 mm (0–100, best to worst scale who are considered eligible for TKA by an orthopaedic surgeon will be included. The treatment will consist of 12 weeks of optimised non-surgical treatment consisting of patient education, exercise, diet, insoles, analgesics and/or NSAIDs. Patients will be randomised to either receiving or not receiving a TKA in addition to the optimised non-surgical treatment. The primary outcome will be the change from baseline to 12 months on the Knee Injury and Osteoarthritis Outcome Score (KOOS4 defined as the average score for the subscale scores for pain, symptoms, activities of daily living, and quality of life. Secondary outcomes include the five individual KOOS subscale scores, EQ-5D, pain on a 100 mm Visual Analogue Scale, self-efficacy, pain pressure thresholds, and isometric knee flexion and knee extension strength. Discussion This is the first randomised controlled trial to investigate the efficacy of TKA as an adjunct treatment to optimised non-surgical treatment in patients with KOA. The results will significantly contribute to

  13. 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

  14. [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.

  15. 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.

  16. 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.

  17. 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 ...

  18. 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 ...

  19. 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)....

  20. 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 ...

  1. 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

  2. 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.

  3. 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

  4. 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...

  5. 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.

  6. 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.

  7. 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 ...

  8. 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.

  9. [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.

  10. 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

  11. 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.

  12. [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.

  13. 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...

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Rajapakse Senaka

    2009-01-01

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

  17. RENAL REPLACEMENT THERAPY IN ACUTE KIDNEY FAILURE - AN OVERVIEW

    Directory of Open Access Journals (Sweden)

    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.

  18. 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...

  19. 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.

  20. 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.

  1. 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

  2. Effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism: a multicenter randomized controlled trial in Japan (EARTH Study

    Directory of Open Access Journals (Sweden)

    Hiroyuki Konaka

    2016-01-01

    Full Text Available Androgen replacement therapy (ART efficacy on late-onset hypogonadism (LOH has been widely investigated in Western countries; however, it remains controversial whether ART can improve health and prolong active lifestyles. We prospectively assessed long-term ART effects on the physical and mental statuses of aging men with LOH in Japan. The primary endpoint was health-related quality of life assessed by questionnaires. Secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body composition, muscular strength, International Prostate Symptom Scores (IPSS, International Index of Erectile Function-5 (IIEF-5 scores, and serum prostate-specific antigen levels. Of the 1637 eligible volunteers, 334 patients > 40 years with LOH were randomly assigned to either the ART (n = 169 or control groups (n = 165. Fifty-two weeks after the initial treatment, ART significantly affected the role physical subdomain of the short form-36 health survey (SF-36 scale (P = 0.0318. ART was also associated with significant decreases in waist circumstance (P = 0.002 and serum triglyceride (TG (P = 0.013 and with significant increases in whole-body and leg muscle mass volumes (P = 0.071 and 0.0108, respectively, serum hemoglobin (P < 0.001, IPSS voiding subscore (P = 0.0418, and the second question on IIEF-5 (P = 0.0049. There was no significant difference between the groups in terms of severe adverse events. In conclusion, in patients with LOH, long-term ART exerted beneficial effects on Role Physical subdomain of the SF-36 scale, serum TG, waist circumstance, muscle mass volume, voiding subscore of IPSS, and the second question of IIEF-5. We hope our study will contribute to the future development of this area.

  3. [Clinical trials with advanced therapy medicinal products].

    Science.gov (United States)

    Schüssler-Lenz, M; Schneider, C K

    2010-01-01

    For advanced therapies, the same basic principles for assessment apply as for any other biotechnological medicinal product. Nevertheless, the extent of data for quality, safety, and efficacy can be highly specific. Until recently, advanced therapies were not uniformly regulated across Europe, e.g., tissue engineered products were regulated either as medicinal products or medical devices. Thus, for some products no data from clinical studies are available, e.g., for autologous chondrocyte products. The draft guideline on Good Clinical Practice for clinical trials with advanced therapies describes specific additional requirements, e.g., ensuring traceability. Most clinical studies with advanced therapies in Germany are still in early phase I or II trials with highly divergent types of products and clinical indications. The Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMEA) has been established to meet the scientific and regulatory challenges with advanced therapies.

  4. 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.

  5. 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.

  6. Comparison of heparin to citrate as a catheter locking solution for non-tunneled central venous hemodialysis catheters in patients requiring renal replacement therapy for acute renal failure (VERROU-REA study): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Bruyère, Rémi; Soudry-Faure, Agnès; Capellier, Gilles; Binquet, Christine; Nadji, Abdelouaid; Torner, Stephane; Blasco, Gilles; Yannaraki, Maria; Barbar, Saber Davide; Quenot, Jean-Pierre

    2014-11-19

    The incidence of acute kidney injury (AKI) is estimated at 10 to 20% in patients admitted to intensive care units (ICU) and often requires renal replacement therapy (RRT). ICU mortality in AKI patients can exceed 50%. Venous catheters are the preferred vascular access method for AKI patients requiring RRT, but carry a risk of catheter thrombosis or infection. Catheter lock solutions are commonly used to prevent such complications. Heparin and citrate locks are both widely used for tunneled, long-term catheters, but few studies have compared citrate versus heparin for patients with short-term, non-tunneled catheters. We aim to compare citrate 4% catheter lock solution versus heparin in terms of event-free survival of the first non-tunneled hemodialysis catheter inserted in ICU patients with AKI requiring RRT. Secondary objectives are the rate of fibrinolysis, incidence of catheter thrombosis and catheter-related infection per 1,000 catheter days, length of stay in ICU and in-hospital and 28-day mortality. The VERROU-REA study is a randomized, prospective, multicenter, double-blind, parallel-group, controlled superiority study carried out in the medical, surgical and nephrological ICUs of two large university hospitals in eastern France. A catheter lock solution composed of trisodium citrate at 4% will be compared to unfractionated heparin at a concentration of 5,000 IU/mL. All consecutive adult patients with AKI requiring extracorporeal RRT, and in whom a first non-tunneled catheter is to be inserted by the jugular or femoral approach, will be eligible. Catheters inserted by the subclavian approach, patients with acute liver failure, thrombopenia or contraindication to systemic anticoagulation will be excluded. Patients will be followed up daily in accordance with standard practices for RRT until death or discharge. Data is scarce regarding the use of non-tunneled catheters in the ICU setting in patients with AKI. This study will provide an evidence base for

  7. 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...

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. 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....

  13. 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.

  14. 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.

  15. 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.

  16. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael

    2011-08-01

    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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....

  10. 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....

  11. 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).

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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....

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Genetic variation (CHRNA5), medication (combination nicotine replacement therapy vs. varenicline), and smoking cessation.

    Science.gov (United States)

    Chen, Li-Shiun; Baker, Timothy B; Jorenby, Douglas; Piper, Megan; Saccone, Nancy; Johnson, Eric; Breslau, Naomi; Hatsukami, Dorothy; Carney, Robert M; Bierut, Laura J

    2015-09-01

    Recent evidence suggests that the efficacy of smoking cessation pharmacotherapy can vary across patients based on their genotypes. This study tests whether the coding variant rs16969968 in the CHRNA5 nicotinic receptor gene predicts the effects of combination nicotine replacement therapy (cNRT) and varenicline on treatment outcomes. In two randomized smoking cessation trials comparing cNRT vs. placebo, and varenicline vs. placebo, we used logistic regression to model associations between CHRNA5 rs16969968 and abstinence at end of treatment. For abstinence at end of treatment, there was an interaction between cNRT and rs16969968 (X(2)=8.15, df=2, omnibus-p=0.017 for the interaction); individuals with the high-risk AA genotype were more likely to benefit from cNRT. In contrast, varenicline increased abstinence, but its effect did not vary with CHRNA5. However, the genetic effects differed between the placebo control groups across two trials (wald=3.94, df=1, p=0.047), this non-replication can alter the interpretation of pharmacogenetic findings. Results from two complementary smoking cessation trials demonstrate inconsistent genetic results in the placebo arms. This evidence highlights the need to compare the most effective pharmacotherapies with the same placebo control to establish pharmacogenetic evidence to aid decisions on medication choice for patients trying to quit smoking. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Citrate versus unfractionated heparin for anticoagulation in continuous renal replacement therapy

    Institute of Scientific and Technical Information of China (English)

    LIAO Yu-jie; ZHANG Ling; ZENG Xiao-xi; FU Ping

    2013-01-01

    Background Unfractionated heparin is the most commonly used anticoagulant in continuous renal replacement therapy (CRRT),but it can increase the risk of bleeding.Citrate is a promising substitute.Our study was to assess the efficacy and safety of citrate versus unfractionated heparin in CRRT.Methods We searched the MEDLINE,the EMBASE,the Cochrane Central Register of Controlled Trials,and the China National Knowledge Infrastructure Database until up to November 2011 for randomized controlled trials comparing citrate with unfractionated heparin in adult patients with acute kidney injury prescribed CRRT.The primary outcome was mortality and the secondary outcomes included circuit survival,control of uremia,risk of bleeding,transfusion rates,acid-base statuses,and disturbance of sodium and calcium homeostasis.Results Four trials met the inclusion criteria.Meta-analysis found no significant difference between two anticoagulants on mortality.Less bleeding and more hypocalcemic episodes were with citrate.Citrate was superior or comparable to unfractionated heparin in circuit life.Conclusions Citrate anticoagulation in CRRT seems to be superior in reducing bleeding risk and with a longer or similar circuit life,although there is more metabolic derangement.Mortality superiority has not been approved.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Replacement gene therapy with a human RPGRIP1 sequence slows photoreceptor degeneration in a murine model of Leber congenital amaurosis.

    Science.gov (United States)

    Pawlyk, Basil S; Bulgakov, Oleg V; Liu, Xiaoqing; Xu, Xiaoyun; Adamian, Michael; Sun, Xun; Khani, Shahrokh C; Berson, Eliot L; Sandberg, Michael A; Li, Tiansen

    2010-08-01

    RPGR-interacting protein-1 (RPGRIP1) is localized in the photoreceptor-connecting cilium, where it anchors the RPGR (retinitis pigmentosa GTPase regulator) protein, and its function is essential for photoreceptor maintenance. Genetic defect in RPGRIP1 is a known cause of Leber congenital amaurosis (LCA), a severe, early-onset form of retinal degeneration. We evaluated the efficacy of replacement gene therapy in a murine model of LCA carrying a targeted disruption of RPGRIP1. The replacement construct, packaged in an adeno-associated virus serotype 8 (AAV8) vector, used a rhodopsin kinase gene promoter to drive RPGRIP1 expression. Both promoter and transgene were of human origin. After subretinal delivery of the replacement gene in the mutant mice, human RPGRIP1 was expressed specifically in photoreceptors, localized correctly in the connecting cilia, and restored the normal localization of RPGR. Electroretinogram and histological examinations showed better preservation of rod and cone photoreceptor function and improved photoreceptor survival in the treated eyes. This study demonstrates the efficacy of human gene replacement therapy and validates a gene therapy design for future clinical trials in patients afflicted with this condition. Our results also have therapeutic implications for other forms of retinal degenerations attributable to a ciliary defect.

  9. Dispersant trial at ANO-2: Qualification for a short-term trial prior to SG replacement

    Energy Technology Data Exchange (ETDEWEB)

    Fruzzetti, K.; Frattini, P. [Electric Power Research Inst., Palo Alto, CA (United States); Robbins, P. [Entergy Operations, Arkansas Nuclear One, Russellville, AR (United States); Miller, A. [Pedro Point Technology, Inc., Pacifica, CA (United States); Varrin, R.; Kreider, M. [Dominion Engineering Inc., McLean, VA (United States)

    2002-07-01

    initiators, polymeric dispersants had not been utilized in the nuclear industry. Only recently has a poly-acrylic acid dispersant, developed by BetzDearborn (PAA), been available off the shelf that meets the criteria for nuclear application. This paper summarizes the qualification program designed to qualify the PAA dispersant for the short-term trial at ANO-2 prior to SG replacement. (authors)

  10. 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. 

  11. Rationale for the tinnitus retraining therapy trial

    Directory of Open Access Journals (Sweden)

    Craig Formby

    2013-01-01

    Full Text Available The Tinnitus Retraining Therapy Trial (TRTT is a National Institutes of Health-sponsored, multi-centered, placebo-controlled, randomized trial evaluating the efficacy of tinnitus retraining therapy (TRT and its component parts, directive counseling and sound therapy, as treatments for subjective debilitating tinnitus in the military. The TRTT will enroll 228 individuals at an allocation ratio of 1:1:1 to: (1 directive counseling and sound therapy using conventional sound generators; (2 directive counseling and placebo sound generators; or (3 standard of care as administered in the military. Study centers include a Study Chair′s Office, a Data Coordinating Center, and six Military Clinical Centers with treatment and data collection standardized across all clinics. The primary outcome is change in Tinnitus Questionnaire (TQ score assessed longitudinally at 3, 6, 12, and 18-month follow-up visits. Secondary outcomes include: Change in TQ sub-scales, Tinnitus Handicap Inventory, Tinnitus Functional Index, and TRT interview visual analog scale; audiometric and psychoacoustic measures; and change in quality of life. The TRTT will evaluate TRT efficacy by comparing TRT (directive counseling and conventional sound generators with standard of care; directive counseling by comparing directive counseling plus placebo sound generators versus standard of care; and sound therapy by comparing conventional versus placebo sound generators. We hypothesize that full TRT will be more efficacious than standard of care, directive counseling and placebo sound generators more efficacious than standard of care, and conventional more efficacious than placebo sound generators in habituating the tinnitus awareness, annoyance, and impact on the study participant′s life.

  12. 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.

  13. Hormone replacement therapy: will it affect seizure control and AED levels?

    Science.gov (United States)

    Harden, Cynthia L

    2008-03-01

    Interest in the years of reproductive changes for women with epilepsy (WWE), specifically perimenopause, menopause and postmenopause has been emerging in the epilepsy community. This article discusses evidence for changes in seizure frequency during perimenopause and postmenopause. Further, a catamenial epilepsy pattern during the reproductive years may be a hallmark for the observed seizure frequency change during these years; that is, an increase at perimenopause but a decrease at menopause. This finding implies that a subset of WWE are particularly susceptible to endogenous reproductive hormonal changes. An adverse effect on seizure frequency with the use of hormone replacement therapy (HRT) during postmenopause for WWE was reported in questionnaires, and was later borne out in a clinical trial. The laboratory counterpart of this human trial, HRT in ovariectomized rodent seizure models, shows that estrogen and progesterone are neuroprotective and do not uniformly increase seizure frequency. Possible reasons for the discrepancy between "the lab and the clinic" are presented. Strategies for managing HRT in symptomatic postmenopausal WWE using estrogenic and progestogenic compounds that may be less likely to promote seizures are discussed.

  14. The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Cui, Y; Zong, H; Yan, H; Zhang, Y

    2014-06-01

    Testosterone replacement therapy (TRT) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism syndrome. Urologists have been concerned about the possibility of TRT causing prostate cancer. The aim of this study was to assess the relationship between TRT and prostate cancer. A literature review was performed to identify all published, randomized controlled trials (RCTs) of testosterone treatment for hypogonadism. The search included the MEDLINE, Embase and the Cochrane Controlled Trials Register databases. Fixed-effect model was chosen for homogeneous studies; otherwise, a random-effect model was used. Inconsistency was quantified by using the I2 statistic, which tests the proportion of heterogeneity across studies. Results of 22 RCTs involving a total of 2351 patients were analyzed. Eleven RCTs were short-term (testosterone administration were >1 indicating increased risk, none of these reached or even approached statistical significance (all P>0.10), which was consistent with the results of subgroup analyses and sensitivity analysis. Besides, sensitivity analysis indicated that short-term TRT was more likely to increase PSA levels than treatment with placebo (P<0.00001). This meta-analysis shows that regardless of the administration method, TRT is the short-term safety and does not promote prostate cancer development or progression but long-term data are warranted with justifiable end points.

  15. Impact of hormone replacement therapy on cardiac metabolic indicators in men with high cardiovascular risk and hypogonadism

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2014-12-01

    Full Text Available The paper evaluates the impact of hormone replacement therapy (HRT with androgens on cardiac metabolic indicators in men with high cardiovascular risk (CVR and androgen deficiency state. An open-label randomized clinical trial enrolled 52 men aged 30–64 years with high CVR and detected androgen-deficiency state. The men were randomized into 2 groups: a control group (CG (n = 26 continued to receive the pre-trial therapy; during the previous therapy, a study group (SG (n = 26 had daily applications of transdermal gel with testosterone (AndroGel in a daily dose of 50 mg of testosterone in 5 g of the gel. The trial lasted 180 days. The changes in the indicators under study were traced 90 days after treatment initiation at an intermediate visit and 180 days after the initiation of treatment – at the end of its treatment.At the end of the trial, HRT in men with androgen deficiency and high CVR led to normalization of testosterone levels in all the SG patients and to improvement in erectile function by 12 %. Androgen therapy caused a statistically significant reduction in blood pressure by 10 %; no changes were virtually observed in the CG. HRT promoted a slight, but significant weight loss (by an average of 2.8 kg and waist circumference (by an average of 1.7 cm. The therapy performed also lowered the concentration of total cholesterol by an average of 11 % and that of triglycerides by 22 %. During the therapy, there was a significant decrease in fasting insulin and glucose levels. Overall, the course therapy with transdermal gel in combination with testosterone resulted in a reduction in the expected total CVR by 30 %. Thus, HRT using testosterone preparations in men with hypogonadism and high CVR led to normalization of testosterone levels and major cardiac metabolic indicators and to improvement in erectile function.

  16. Impact of hormone replacement therapy on cardiac metabolic indicators in men with high cardiovascular risk and hypogonadism

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2014-01-01

    Full Text Available The paper evaluates the impact of hormone replacement therapy (HRT with androgens on cardiac metabolic indicators in men with high cardiovascular risk (CVR and androgen deficiency state. An open-label randomized clinical trial enrolled 52 men aged 30–64 years with high CVR and detected androgen-deficiency state. The men were randomized into 2 groups: a control group (CG (n = 26 continued to receive the pre-trial therapy; during the previous therapy, a study group (SG (n = 26 had daily applications of transdermal gel with testosterone (AndroGel in a daily dose of 50 mg of testosterone in 5 g of the gel. The trial lasted 180 days. The changes in the indicators under study were traced 90 days after treatment initiation at an intermediate visit and 180 days after the initiation of treatment – at the end of its treatment.At the end of the trial, HRT in men with androgen deficiency and high CVR led to normalization of testosterone levels in all the SG patients and to improvement in erectile function by 12 %. Androgen therapy caused a statistically significant reduction in blood pressure by 10 %; no changes were virtually observed in the CG. HRT promoted a slight, but significant weight loss (by an average of 2.8 kg and waist circumference (by an average of 1.7 cm. The therapy performed also lowered the concentration of total cholesterol by an average of 11 % and that of triglycerides by 22 %. During the therapy, there was a significant decrease in fasting insulin and glucose levels. Overall, the course therapy with transdermal gel in combination with testosterone resulted in a reduction in the expected total CVR by 30 %. Thus, HRT using testosterone preparations in men with hypogonadism and high CVR led to normalization of testosterone levels and major cardiac metabolic indicators and to improvement in erectile function.

  17. 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

    (HR 1·11, 95% CI 1·03-1·20) and cardiovascular events (HR 1·26, 95% CI 1·09-1·46) compared with controls. By contrast, those in the highest tertile of testosterone exposure had decreased risk of mortality (HR 0·67, 95% CI 0·62-0·73) and cardiovascular events (HR 0·84, 95% CI 0·72-0·98), with a significant trend across tertiles (ptestosterone replacement therapy was associated with reduced risks of mortality, cardiovascular events, and prostate cancer. However, testosterone replacement therapy increased the risk of mortality and cardiovascular events with short durations of therapy. In view of the limitations of observational data and the potential for selection bias, these results warrant confirmation in a randomised trial. Physicians' Services Incorporated Foundation and Ajmera Family Chair in Urologic Oncology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. 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...

  19. 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.

  20. 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.

  1. 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

  2. The Effect of Testosterone Replacement Therapy on Prostate-Specific Antigen (PSA) Levels in Men Being Treated for Hypogonadism

    Science.gov (United States)

    Kang, De-Ying; Li, Hong-Jun

    2015-01-01

    Abstract Testosterone replacement therapy is used for the treatment of age-related male hypogonadism, and prostate-specific antigen (PSA) is a primary screening tool for prostate cancer. The systematic review and meta-analysis aimed to determine the effect of testosterone replacement therapy on PSA levels. Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until February 28, 2014, and inclusion criteria were as follows: randomized controlled trial; intervention group received testosterone/androgen replacement therapy; control group did not receive treatment; and no history of prostate cancer. The primary outcome was change of PSA level between before and after treatment. Secondary outcomes were elevated PSA level after treatment, and the number of patients who developed prostate cancer. After initially identifying 511 articles, 15 studies with a total of 739 patients that received testosterone replacement and 385 controls were included. The duration of treatment ranged from 3 to 12 months. Patients treated with testosterone tended to have higher PSA levels, and thus a greater change than those that received control treatments (difference in means of PSA levels = 0.154, 95% confidence interval [CI] 0.069 to 0.238, P testosterone intramuscularly (IM) than controls (difference in means of PSA levels = 0.271, 95% CI 0.117–0.425, P = 0.001). Elevated PSA levels after treatment were similar between patients that received treatment and controls (odds ratio [OR] = 1.02, 95% CI 0.48–2.20, P = 0.953). Only 3 studies provided data with respect to the development of prostate cancer, and rates were similar between those that received treatment and controls. Testosterone replacement therapy does not increase PSA levels in men being treated for hypogonadism, except when it is given IM and even the increase with IM administration is minimal. PMID:25621688

  3. 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.

  4. 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....

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.  

  10. 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...

  11. 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

  12. 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.

  13. 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.

  14. 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

  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. Loyalties in clinical research on drugs: the case of hormone replacement therapy.

    Science.gov (United States)

    Palmlund, Ingar

    2006-07-01

    In this study, physicians' loyalties toward patients and pharmaceutical companies in clinical drug research are explored, using Bourdieu's conceptual tools. The utilization of estrogen supplements in so-called hormone replacement therapy (HRT) for healthy menopausal and postmenopausal women is used as a case. For over 60 years a multitude of reports in medical journals have praised the benefits of HRT, even though some studies indicated hazards. Clinical studies and promotional campaigns resulted in prescriptions of HRT for millions of women. A large randomized controlled clinical trial known as the Women's Health Initiative (WHI) in 2002 demonstrated that many of the claims of benefits of HRT had been misguiding; the risks of cancer and heart disease had been proven higher than most purported benefits. I draw on Bourdieu's theories to emphasize that a more distinct demarcation line between those who dispose their economic capital in the interests of producing and promoting products for profit, and those who exchange their cultural capital for economic benefits, is needed to ensure trust in physicians' loyalty to patients is not eroded.

  17. Andropause or male menopause? Rationale for testosterone replacement therapy in older men with low testosterone levels.

    Science.gov (United States)

    Cunningham, Glenn R

    2013-01-01

    To provide rationale for testosterone replacement therapy (TRT) in older men with low testosterone levels and symptoms consistent with testosterone deficiency. The relevant literature was reviewed using PubMed. Cross-sectional and longitudinal population-based studies indicate that total and free testosterone levels fall with aging, and they may be accompanied by symptoms consistent with androgen deficiency. Testosterone treatment of younger men with very low testosterone levels and hypothalamic, pituitary, or testicular disease is associated with improvements in symptoms, body composition, bone density, and hematocrit/hemoglobin. Studies evaluating testosterone treatment of older men with low testosterone levels are limited, but they suggest some increase in fat free mass, some decrease in fat mass, and some increase in bone density of the lumbar spine and femoral neck. The Testosterone Trial should provide definitive information regarding the potential benefits of TRT in men ≥65 years of age. If efficacy is confirmed, we will still need more information regarding the risks of TRT in older men.

  18. Lipid Replacement Therapy Drink Containing a Glycophospholipid Formulation Rapidly and Significantly Reduces Fatigue While Improving Energy and Mental Clarity

    Directory of Open Access Journals (Sweden)

    Robert Settineri

    2011-08-01

    Full Text Available Background: Fatigue is the most common complaint of patients seeking general medical care and is often treated with stimulants. It is also important in various physical activities of relatively healthy men and women, such as sports performance. Recent clinical trials using patients with chronic fatigue have shown the benefit of Lipid Replacement Therapy in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Methods: Lipid Replacement Therapy was administered for the first time as an all-natural functional food drink (60 ml containing polyunsaturated glycophospholipids but devoid of stimulants or herbs to reduce fatigue. This preliminary study used the Piper Fatigue Survey instrument as well as a supplemental questionnaire to assess the effects of the glycophospholipid drink on fatigue and the acceptability of the test drink in adult men and women. A volunteer group of 29 subjects of mean age 56.2±4.5 years with various fatigue levels were randomly recruited in a clinical health fair setting to participate in an afternoon open label trial on the effects of the test drink. Results: Using the Piper Fatigue instrument overall fatigue among participants was reduced within the 3-hour seminar by a mean of 39.6% (p<0.0001. All of the subcategories of fatigue showed significant reductions. Some subjects responded within 15 minutes, and the majority responded within one hour with increased energy and activity and perceived improvements in cognitive function, mental clarity and focus. The test drink was determined to be quite acceptable in terms of taste and appearance. There were no adverse events from the energy drink during the study.Functional Foods in Health and Disease 2011; 8:245-254Conclusions: The Lipid Replacement Therapy functional food drink appeared to be a safe, acceptable and potentially useful new method to reduce fatigue, sustain energy and improve perceptions of mental function.

  19. Taliglucerase alfa: an enzyme replacement therapy using plant cell expression technology.

    Science.gov (United States)

    Grabowski, Gregory A; Golembo, Myriam; Shaaltiel, Yoseph

    2014-05-01

    Gaucher disease (GD) is a rare, genetic lysosomal storage disorder caused by functional defects of acid β-glucosidase that results in multiple organ dysfunction. Glycosylation of recombinant acid human β-glucosidase and exposure of terminal mannose residues are critical to the success of enzyme replacement therapy (ERT) for the treatment of visceral and hematologic manifestations in GD. Three commercially available ERT products for treatment of GD type 1 (GD1) include imiglucerase, velaglucerase alfa, and taliglucerase alfa. Imiglucerase and velaglucerase alfa are produced in different mammalian cell systems and require production glycosylation modifications to expose terminal α-mannose residues, which are needed for mannose receptor-mediated uptake by target macrophages. Such modifications add to production costs. Taliglucerase alfa is a plant cell-expressed acid β-glucosidase approved in the United States and other countries for ERT in adults with GD1. A plant-based expression system, using carrot root cell cultures, was developed for production of taliglucerase alfa and does not require additional processing for postproduction glycosidic modifications. Clinical trials have demonstrated that taliglucerase alfa is efficacious, with a well-established safety profile in adult, ERT-naïve patients with symptomatic GD1, and for such patients previously treated with imiglucerase. These included significant improvements in organomegaly and hematologic parameters as early as 6months, and maintenance of achieved therapeutic values in previously treated patients. Ongoing clinical trials will further characterize the long-term efficacy and safety of taliglucerase alfa in more diverse patient populations, and may help to guide clinical decisions for achieving optimal outcomes for patients with GD1.

  20. 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.

  1. Risks and benefits of hormone replacement therapy in older men Riscos e benefícios da terapia de reposição hormonal em homens idosos

    Directory of Open Access Journals (Sweden)

    Fábio Firmbach Pasqualotto

    2004-02-01

    Full Text Available The use of testosterone in older men, known as male hormonal replacement therapy or androgen replacement therapy, has become of increasing interest to both the medical and lay communities over the past decade. Even though the knowledge of the potential benefits and risks of male Androgen Replacement Therapy has increased dramatically, there is still much that needs to be determined. Although there are a number of potential benefits of male Androgen Replacement Therapy and data concerning clinical effects of such replacement have accumulated, as yet there have not been any large multicenter randomized controlled trials of this therapy. It is the purpose of this article to review what is currently known about the possible risks and benefits of male Androgen Replacement Therapy by discussing the clinical trials to date.O uso da testosterona em homens idosos, conhecido como Terapia de Reposição Hormonal no homem ou Terapia de Reposição com Androgênios, têm aumentado o interesse para as comunidades médica e leiga na última década. Muito embora o conhecimento a respeito dos potenciais benefícios e riscos da Terapia de Reposição Hormonal nos homens tem aumentado dramaticamente, ainda existe muito que precisa ser determinado. Embora existam vários benefícios potenciais da Terapia de Reposição com Androgênios e dados clínicos relacionados com o uso de tal terapia, não existem ainda nenhum estudo controlado, randomizado e multicêntrico avaliando o uso de tal terapia. O objetivo deste artigo é revisar os aspectos atuais sobre os possíveis riscos e benefícios da Terapia de Reposição com Androgênios discutindo os estudos clínicos publicados sobre o assunto.

  2. Initiation time of renal replacement therapy on patients with acute kidney injury: A systematic review and meta-analysis of 8179 participants.

    Science.gov (United States)

    Wang, Caixia; Lv, Lin-Sheng; Huang, Hui; Guan, Jianqiang; Ye, Zengchun; Li, Shaomin; Wang, Yanni; Lou, Tanqi; Liu, Xun

    2017-01-01

    The early initiation of renal replacement therapy has been recommended for patients with acute renal failure by some studies, but its effects on mortality and renal recovery are unknown. We conducted an updated meta-analysis to provide quantitative evaluations of the association between the early initiation of renal replacement therapy and mortality for patients with acute kidney injury. After applying inclusion/exclusion criteria, 51 studies, including 10 randomized controlled trials, with a total of 8179 patients were analyzed. Analysis of the included trials showed that patients receiving early renal replacement therapy had a 25% reduction in all-cause mortality compared to those receiving late renal replacement therapy (risk ratio [RR] 0.75, 95% CI [0.69, 0.82]). We also noted a 30% increase in renal recovery (RR 1.30, 95% CI [1.07, 1.56]), a reduction in hospitalization of 5.84 days (mean difference [MD], 95% CI [-10.27, -1.41]) and a reduction in the duration of mechanical ventilation of 2.33 days (MD, 95% CI [-3.40, -1.26]) in patients assigned to early renal replacement therapy. The early initiation of renal replacement therapy was associated with a decreased risk of all-cause mortality compared with the late initiation of RRT in patients with acute kidney injury. These findings should be interpreted with caution given the heterogeneity between studies. Further studies are needed to identify the causes of mortality and to assess whether mortality differs by dialysis dose.

  3. 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.

  4. 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.

  5. 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

  6. Bacteriophage Therapy: Advances in Formulation Strategies and Human Clinical Trials.

    Science.gov (United States)

    Vandenheuvel, Dieter; Lavigne, Rob; Brüssow, Harald

    2015-11-01

    Recently, a number of phage therapy phase I and II safety trials have been concluded, showing no notable safety concerns associated with the use of phage. Though hurdles for efficient treatment remain, these trials hold promise for future phase III clinical trials. Interestingly, most phage formulations used in these clinical trials are straightforward phage suspensions, and not much research has focused on the processing of phage cocktails in specific pharmaceutical dosage forms. Additional research on formulation strategies and the stability of phage-based drugs will be of key importance, especially with phage therapy advancing toward phase III clinical trials.

  7. 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.

  8. 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.

  9. 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...

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

    Science.gov (United States)

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

    2016-12-01

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

  11. Assigned versus Perceived Placebo Effects in Nicotine Replacement Therapy for Smoking Reduction in Swiss Smokers

    Science.gov (United States)

    Dar, Reuven; Stronguin, Florencia; Etter, Jean-Francois

    2005-01-01

    In this report, the authors explore the relationships of perceived treatment to outcome in a large, placebo-controlled trial of nicotine replacement treatment for smoking reduction. In the original study (J. F. Etter, E. Laszlo, J. P. Zellweger, C. Perrot, & T. V. Perneger, 2002), which was conducted in French-speaking Switzerland, smokers were…

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Zygmunt Zdrojewicz

    2017-03-01

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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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....

  2. 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...

  3. 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.

  4. Transcatheter Aortic Valve Replacement in Lower Surgical Risk Patients: Review of Major Trials and Future Perspectives.

    Science.gov (United States)

    Saji, Mike; Lim, D Scott

    2016-10-01

    Following the first successful transcatheter aortic valve replacement (TAVR) in 2002, TAVR has globally evolved to become a standard procedure in high-risk patients. Surgical aortic valve replacement in non-high-risk patients remains the gold standard for treatment of severe aortic stenosis. However, a paradigm shift appears to be occurring in the direction of treating lower-risk patients, and several studies have suggested its impact on clinical outcomes. In this review, we highlight the current status of TAVR in intermediate-risk patients and review major trials including Placement of AoRTic TraNscathetER (PARTNER) 2A randomized intermediate-risk trial using SAPIEN XT (Edwards Lifesciences Corp, Irvine, CA) recently presented with excellent outcomes and the lowest major complications rate at the American College of Cardiology's 65th Annual Scientific Session in Chicago. Clinical trials in low-risk patients using SAPIEN 3 and CoreValve Evolut R have just been launched, and they are going to be important milestones in the TAVR field.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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...

  10. 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

  11. 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...

  12. 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...

  13. 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...

  14. 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

  15. 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

  16. 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

  17. 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

  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. 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

  20. 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,

  1. 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

  2. [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.

  3. [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.

  4. 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...

  5. 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....

  6. 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

  7. Dispersant trial at ANO-2: Results from a short-term trial prior to SG replacement

    Energy Technology Data Exchange (ETDEWEB)

    Fruzzetti, K.; Frattini, P. [Electric Power Research Inst., Palo Alto, CA (United States); Robbins, P. [Entergy Operations, Arkansas Nuclear One, Russellville, AR (United States); Miller, A. [Pedro Point Technology, Inc., Pacifica, CA (United States); Varrin, R.; Kreider, M. [Dominion Engineering Inc., McLean, VA (United States)

    2002-07-01

    Corrosion products in the secondary side of pressurized water reactor (PWR) steam generators (SGs) primarily deposit on the SG tubes. These deposits can inhibit heat transfer, lead to thermal-hydraulic instabilities through blockage of tube supports, and create occluded regions where corrosive species can concentrate along tubes and in tube-to-tube support plate crevices. The performance of the SGs is compromised not only by formation of an insulating scale, but by the removal of tubes from service due to corrosion. A potential strategy for minimizing deposition of corrosion products on SG internal surfaces is to use an online dispersant to help prevent the corrosion products from adhering to the steam generator surfaces. By inhibiting the deposition of the corrosion products, the dispersant can facilitate more effective removal from the SGs via blowdown. This type of strategy has been employed at fossil boilers for many decades. However, due to the use of inorganic (sulfur and other impurities) polymerization initiators, polymeric dispersants had not been utilized in the nuclear industry. Only recently has a poly-acrylic acid dispersant, developed by BetzDearborn (PAA), been available that meets the criteria for nuclear application. This paper summarizes the results of the short-term PAA dispersant trial in Winter/Spring 2000, lasting approximately 3 months, performed at Arkansas nuclear one unit 2 (ANO-2)-including the chronology of the trial, the increase in blowdown iron removal efficiency with use of the dispersant, and observed effects on SG performance. (authors)

  8. Core journals that publish clinical trials of physical therapy interventions.

    Science.gov (United States)

    Costa, Leonardo Oliveira Pena; Moseley, Anne M; Sherrington, Catherine; Maher, Christopher G; Herbert, Robert D; Elkins, Mark R

    2010-11-01

    The objective of this study was to identify core journals in physical therapy by identifying those that publish the most randomized controlled trials of physical therapy interventions, provide the highest-quality reports of randomized controlled trials, and have the highest journal impact factors. This study was an audit of a bibliographic database. All trials indexed in the Physiotherapy Evidence Database (PEDro) were analyzed. Journals that had published at least 80 trials were selected. The journals were ranked in 4 ways: number of trials published; mean total PEDro score of the trials published in the journal, regardless of publication year; mean total PEDro score of the trials published in the journal from 2000 to 2009; and 2008 journal impact factor. The top 5 core journals in physical therapy, ranked by the total number of trials published, were Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation, Spine, British Medical Journal (BMJ), and Chest. When the mean total PEDro score was used as the ranking criterion, the top 5 journals were Journal of Physiotherapy, Journal of the American Medical Association (JAMA), Stroke, Spine, and Clinical Rehabilitation. When the mean total PEDro score of the trials published from 2000 to 2009 was used as the ranking criterion, the top 5 journals were Journal of Physiotherapy, JAMA, Lancet, BMJ, and Pain. The most highly ranked physical therapy-specific journals were Physical Therapy (ranked eighth on the basis of the number of trials published) and Journal of Physiotherapy (ranked first on the basis of the quality of trials). Finally, when the 2008 impact factor was used for ranking, the top 5 journals were JAMA, Lancet, BMJ, American Journal of Respiratory and Critical Care Medicine, and Thorax. There were no significant relationships among the rankings on the basis of trial quality, number of trials, or journal impact factor. Physical therapists who are trying to keep up-to-date by reading the best

  9. 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

  10. Gene therapy clinical trials worldwide to 2012 - an update.

    Science.gov (United States)

    Ginn, Samantha L; Alexander, Ian E; Edelstein, Michael L; Abedi, Mohammad R; Wixon, Jo

    2013-02-01

    To date, over 1800 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical trials from official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our June 2012 update, we have entries on 1843 trials undertaken in 31 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our searchable database are available on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in clinical trials of gene therapy approaches around the world and discuss the prospects for the future.

  11. Pre-quitting nicotine replacement therapy: Findings from a pilot study

    Directory of Open Access Journals (Sweden)

    Wallace-Bell Mark

    2006-08-01

    Full Text Available Abstract Background Using nicotine replacement therapy (NRT while still smoking in the lead up to quitting could enhance success at quitting, one of the most cost-effective means of improving health, but little is known about its acceptability and tolerability. Aim To test the acceptability and tolerability of using NRT while smoking for two weeks before quitting, to inform a randomised controlled trial of pre-quitting NRT versus usual NRT-based quitting practice. Methods Prospective pragmatic uncontrolled clinic-based pilot study in which 14 adult smokers recruited from a smoking cessation clinic were prescribed nicotine patches or gum with follow up for two weeks. Data were collected on participants' concerns about smoking while using NRT, importance of quitting, urges to smoke, smoking behaviour, previous NRT use and the length of the pre-quitting period. Urine tests were collected weekly for cotinine, and participants recorded smoking activity and noted experiences and changes in their health in diaries. Results Only 21% of 14 participants expressed concerns about using NRT while smoking. All of the nine followed up used it as recommended, 56% of these reporting no unpleasant symptoms. Median urine cotinine levels declined over the two weeks. Urges to smoke averaged 1.8 on a 4-point scale. All participants decreased the number of cigarettes per day. Diary records showed wide variation in smoking and NRT use, with an increased sense of control and determination to quit. Conclusion Smokers using pre-quitting NRT over two weeks appeared to titrate nicotine levels and symptoms of toxicity were uncommon and of low intensity.

  12. 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.

  13. 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....

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Comparison of manual therapy and exercise therapy in osteoarthritis of the hip: a randomized clinical trial.

    NARCIS (Netherlands)

    Hoeksma, H.L.; Dekker, J.; Ronday, H.K.; Heering, A.; Lubbe, N. van der; Vel, C.; Breedveld, F.C.; Ende, C.H.M. van den

    2004-01-01

    OBJECTIVE: To determine the effectiveness of a manual therapy program compared with an exercise therapy program in patients with osteoarthritis (OA) of the hip. METHODS: A single-blind, randomized clinical trial of 109 hip OA patients was carried out in the outpatient clinic for physical therapy of

  20. Comparison of manual therapy and exercise therapy in osteoarthritis of the hip: a randomized clinical trial.

    NARCIS (Netherlands)

    Hoeksma, H.L.; Dekker, J.; Ronday, H.K.; Heering, A.; Lubbe, N. van der; Vel, C.; Breedveld, F.C.; Ende, C.H.M. van den

    2004-01-01

    OBJECTIVE: To determine the effectiveness of a manual therapy program compared with an exercise therapy program in patients with osteoarthritis (OA) of the hip. METHODS: A single-blind, randomized clinical trial of 109 hip OA patients was carried out in the outpatient clinic for physical therapy of

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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.

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. [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.

  11. 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.

  12. 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.

  13. Risk of discontinuation of Advanced Therapy Medicinal Products clinical trials.

    Science.gov (United States)

    Hanna, Eve; Rémuzat, Cecile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation. We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation. Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven. No failure risk rate per development phase is available for ATMPs. The discontinuation rate may prove helpful when assessing the

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

    Directory of Open Access Journals (Sweden)

    Szeinbach SL

    2012-08-01

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

  15. [Multicenter trial for sudden hearing loss therapy - planning and concept].

    Science.gov (United States)

    Plontke, S K; Girndt, M; Meisner, C; Probst, R; Oerlecke, I; Richter, M; Steighardt, J; Dreier, G; Weber, A; Baumann, I; Plößl, S; Löhler, J; Laszig, R; Werner, J A; Rahne, T

    2016-04-01

    Systemic steroids are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids for primary therapy of ISSHL, without evidence from randomized controlled trials (RCTs). The rationale for the treatment of ISSHL using high dose steroids is only based on retrospective cohort studies.This article describes the planning and initiation of a multicenter, national, randomized, controlled clinical trial entitled Efficacy and safety of high dose glucocorticosteroid treatment for idiopathic sudden sensorineural hearing loss - a three-armed, randomized, triple-blind, multicenter trial (HODOKORT). This clinical trial aims to compare standard dose with two types of high-dose steroids for primary systemic therapy with respect to their efficacy in improving hearing, and thus communication ability, in patients with idiopathic sudden sensorineural hearing loss.This study is funded by the "Clinical Trials with High Patient Relevance" research program in the health research framework of the German Federal Ministry of Education and Research. It is one of two studies by the German Study Center of Clinical Trials of the German Society of Otorhinolaryngology, Head and Neck Surgery (DSZ-HNO). Planning and initiation was done in cooperation with the DSZ-HNO, the Coordination Center of Clinical Trials of the Martin-Luther-University Halle-Wittenberg, and the Study Center of the University Hospital Freiburg.

  16. Imaging and Data Acquisition in Clinical Trials for Radiation Therapy.

    Science.gov (United States)

    FitzGerald, Thomas J; Bishop-Jodoin, Maryann; Followill, David S; Galvin, James; Knopp, Michael V; Michalski, Jeff M; Rosen, Mark A; Bradley, Jeffrey D; Shankar, Lalitha K; Laurie, Fran; Cicchetti, M Giulia; Moni, Janaki; Coleman, C Norman; Deye, James A; Capala, Jacek; Vikram, Bhadrasain

    2016-02-01

    Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials.

  17. 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.

  18. 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.

  19. Total knee replacement plus physical and medical therapy or treatment with physical and medical therapy alone

    DEFF Research Database (Denmark)

    Skou, Soren T; Roos, Ewa M.; Laursen, Mogens B

    2012-01-01

    ABSTRACT: BACKGROUND: There is a lack of high quality evidence concerning the efficacy of total knee arthroplasty (TKA). According to international evidence-based guidelines, treatment of knee osteoarthritis (KOA) should include patient education, exercise and weight loss. Insoles......: This is the first randomised controlled trial to investigate the efficacy of TKA as an adjunct treatment to optimised non-surgical treatment in patients with KOA. The results will significantly contribute to evidence-based recommendations for the treatment of patients with KOA. Trial Registration: clinicaltrials...

  20. New trial designs and potential therapies for pulmonary artery hypertension.

    Science.gov (United States)

    Gomberg-Maitland, Mardi; Bull, Todd M; Saggar, Rajeev; Barst, Robyn J; Elgazayerly, Amany; Fleming, Thomas R; Grimminger, Friedrich; Rainisio, Maurizio; Stewart, Duncan J; Stockbridge, Norman; Ventura, Carlo; Ghofrani, Ardeschir H; Rubin, Lewis J

    2013-12-24

    A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH.

  1. Telerehabilitation Versus Traditional Care Following Total Hip Replacement: A Randomized Controlled Trial Protocol

    Science.gov (United States)

    Bourke, Michael; Crossley, Kay; Russell, Trevor

    2017-01-01

    Background Total hip replacement (THR) is the gold standard treatment for severe hip osteoarthritis. Effectiveness of physical rehabilitation for THR patients following discharge from hospital is supported by evidence; however, barriers such as geographical location and transport can limit access to appropriate health care. One solution to this issue is using an alternative model of care using telerehabilitation technology to deliver rehabilitation programs directly into patients’ homes. A telerehabilitation model may also have potential health care cost savings for health care providers. Objective This study aims to determine if a telerehabilitation model of care delivered remotely is as effective as face-to-face rehabilitation in the THR population and cost effective for health care providers and patients. Methods A total of 70 people undergoing THR will be recruited to participate in a randomized, single-blind, controlled noninferiority clinical trial. The trial will compare a technology-based THR rehabilitation program to in-person care. On discharge from hospital, participants randomized to the in-person group will receive usual care, defined as a paper home exercise program (HEP) targeting strengthening exercises for quadriceps, hip abductors, extensors, and flexors; they will be advised to perform their HEP 3 times per day. At 2, 4, and 6 weeks postoperatively, they will receive a 30-minute in-person physiotherapy session with a focus on gait retraining and reviewing and progressing their HEP. The telerehabilitation protocol will involve a program similar in content to the in-person rehabilitation program, except delivery will be directly into the homes of the participants via telerehabilitation technology on an iPad. Outcomes will be evaluated preoperatively, day of discharge from in-patient physiotherapy, 6 weeks and 6 months postoperatively. The primary outcome will be the quality of life subscale of the hip disability and osteoarthritis outcome score

  2. 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.

  3. 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.

  4. 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.

  5. Functional exercise after total hip replacement (FEATHER a randomised control trial

    Directory of Open Access Journals (Sweden)

    Monaghan Brenda

    2012-11-01

    Full Text Available Abstract Background Prolonged physical impairments in range of movement, postural stability and walking speed are commonly reported following total hip replacement (THR. It is unclear from the current body of evidence what kind of exercises should be performed to maximize patient function and quality of life. Methods/design This will be a single blind multi centre randomized control trial with two arms. Seventy subjects post primary total hip arthroplasty will be randomized into either an experimental group (n=35, or to a control group (n=35. The experimental group will attend a functional exercise class twice weekly for a six week period from week 12 to week 18 post surgery. The functional exercise group will follow a circuit based functional exercise class supervised by a chartered Physiotherapist. The control group will receive usual care. The principal investigator (BM will perform blinded outcome assessments on all patients using validated measures for pain, stiffness, and function using the Western Ontario and Mc Master Universities Osteoarthritis index (WOMAC. This is the primary outcome measurement tool. Secondary outcome measurements include Quality of life (SF-36, 6 min walk test, Visual Analogue Scale, and the Berg Balance score. The WOMAC score will be collated on day five post surgery and repeated at week twelve and week eighteen. All other measurements will be taken at week 12 and repeated at week eighteen. In addition a blinded radiologist will measure gluteus medius cross sectional area using real time ultrasound for all subjects at week 12 and at week 18 to determine if the functional exercise programme has any effect on muscle size. Discussion This randomised controlled trial will add to the body of evidence on the relationship between muscle size, functional ability, balance, quality of life and time post surgery in patients following total hip arthroplasty. The CONSORT guidelines will be followed to throughout. Ethical

  6. 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.

  7. Adverse Event Recording and Reporting in Clinical Trials Comparing Lumbar Disk Replacement with Lumbar Fusion: A Systematic Review

    OpenAIRE

    HIRATZKA, JAYME; Rastegar, Farbod; Contag, Alec G.; Norvell, Daniel C.; Anderson, Paul A.; Hart, Robert A

    2015-01-01

    Study Design Systematic review. Objectives (1) To compare the quality of adverse event (AE) methodology and reporting among randomized trials comparing lumbar fusion with lumbar total disk replacement (TDR) using established AE reporting systems; (2) to compare the AEs and reoperations of lumbar spinal fusion with those from lumbar TDR; (3) to make recommendations on how to report AEs in randomized controlled trials (RCTs) so that surgeons and patients have more-detailed and comprehensive inf...

  8. Patient values and preferences on transcatheter or surgical aortic valve replacement therapy for aortic stenosis: a systematic review

    Science.gov (United States)

    Lytvyn, Lyubov; Guyatt, Gordon H; Manja, Veena; Siemieniuk, Reed A; Zhang, Yuan; Agoritsas, Thomas; Vandvik, Per O

    2016-01-01

    Objective To investigate patients' values and preferences regarding aortic valve replacement therapy for aortic stenosis. Setting Studies published after transcatheter aortic valve insertion (TAVI) became available (2002). Participants Adults with aortic stenosis who are considering or have had valve replacement, either TAVI or via surgery (surgical aortic valve replacement, SAVR). Outcome measures We sought quantitative measurements, or qualitative descriptions, of values and preferences. When reported, we examined correlations between preferences and objective (eg, ejection fraction) or subjective (eg, health-related quality of life) measures of health. Results We reviewed 1348 unique citations, of which 2 studies proved eligible. One study of patients with severe aortic stenosis used a standard gamble study to ascertain that the median hypothetical mortality risk patients were willing to tolerate to achieve full health was 25% (IQR 25–50%). However, there was considerable variability; for mortality risk levels defined by current guidelines, 130 participants (30%) were willing to accept low-to-intermediate risk (≤8%), 224 (51%) high risk (>8–50%) and 85 (19%) a risk that guidelines would consider prohibitive (>50%). Study authors did not, however, assess participants' understanding of the exercise, resulting in a potential risk of bias. A second qualitative study of 15 patients identified the following factors that influence patients to undergo assessment for TAVI: symptom burden; expectations; information support; logistical barriers; facilitators; obligations and responsibilities. The study was limited by serious risk of bias due to authors' conflict of interest (5/9 authors industry-funded). Conclusions Current evidence on patient values and preferences of adults with aortic stenosis is very limited, and no studies have enrolled patients deciding between TAVI and SAVR. On the basis of the data available, there is evidence of variability in individual

  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. 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.

  11. 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

  12. 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

  13. 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

  14. Acute migraine therapy: recent evidence from randomized comparative trials

    DEFF Research Database (Denmark)

    Mett, A.; Tfelt-Hansen, P.

    2008-01-01

    (1) A wide array of data regarding acute migraine treatment are available, but few trials strictly adhere to International Headache Society guidelines for patient inclusion criteria. (2) Triptans appear to have similar efficacy profiles, but among newer triptans, almotriptan offers improved...... tolerability over sumatriptan. (3) Combination indomethacin/caffeine/prochlorperazine most likely has similar therapeutic efficacy to triptan therapy, with further research needed to complete understanding of any potential differences between these treatments. (4) Multi-targeted combination therapy...

  15. The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels in men being treated for hypogonadism: a systematic review and meta-analysis.

    Science.gov (United States)

    Kang, De-Ying; Li, Hong-Jun

    2015-01-01

    Testosterone replacement therapy is used for the treatment of age-related male hypogonadism, and prostate-specific antigen (PSA) is a primary screening tool for prostate cancer. The systematic review and meta-analysis aimed to determine the effect of testosterone replacement therapy on PSA levels.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until February 28, 2014, and inclusion criteria were as follows: randomized controlled trial; intervention group received testosterone/androgen replacement therapy; control group did not receive treatment; and no history of prostate cancer. The primary outcome was change of PSA level between before and after treatment. Secondary outcomes were elevated PSA level after treatment, and the number of patients who developed prostate cancer.After initially identifying 511 articles, 15 studies with a total of 739 patients that received testosterone replacement and 385 controls were included. The duration of treatment ranged from 3 to 12 months. Patients treated with testosterone tended to have higher PSA levels, and thus a greater change than those that received control treatments (difference in means of PSA levels = 0.154, 95% confidence interval [CI] 0.069 to 0.238, P testosterone intramuscularly (IM) than controls (difference in means of PSA levels = 0.271, 95% CI 0.117-0.425, P = 0.001). Elevated PSA levels after treatment were similar between patients that received treatment and controls (odds ratio [OR] = 1.02, 95% CI 0.48-2.20, P = 0.953). Only 3 studies provided data with respect to the development of prostate cancer, and rates were similar between those that received treatment and controls.Testosterone replacement therapy does not increase PSA levels in men being treated for hypogonadism, except when it is given IM and even the increase with IM administration is minimal.

  16. Amino Acid requirements in critically ill patients with acute kidney injury treated with continuous renal replacement therapy.

    Science.gov (United States)

    Btaiche, Imad F; Mohammad, Rima A; Alaniz, Cesar; Mueller, Bruce A

    2008-05-01

    Acute kidney injury in critically ill patients is often a complication of an underlying condition such as organ failure, sepsis, or drug therapy. In these patients, stress-induced hypercatabolism results in loss of body cell mass. Unless nutrition support is provided, malnutrition and negative nitrogen balance may ensue. Because of metabolic, fluid, and electrolyte abnormalities, optimization of nutrition to patients with acute kidney injury presents a challenge to the clinician. In patients treated with conventional intermittent hemodialysis, achieving adequate amino acid intake can be limited by azotemia and fluid restriction. With the use of continuous renal replacement therapy (CRRT), however, better control of azotemia and liberalization of fluid intake allow amino acid intake to be maximized to support the patient's metabolic needs. High amino acid doses up to 2.5 g/kg/day in patients treated with CRRT improved nitrogen balance. However, to our knowledge, no studies have correlated increased amino acid intake with improved outcomes in critically ill patients with acute kidney injury. Data from large, prospective, randomized, controlled trials are needed to optimize the dosing of amino acids in critically ill patients with acute kidney injury who are treated with CRRT and to study the safety of high doses and their effects on patient morbidity and survival.

  17. Appropriate patient selection or health care rationing? Lessons from surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves I trial.

    Science.gov (United States)

    Szeto, Wilson Y; Svensson, Lars G; Rajeswaran, Jeevanantham; Ehrlinger, John; Suri, Rakesh M; Smith, Craig R; Mack, Michael; Miller, D Craig; McCarthy, Patrick M; Bavaria, Joseph E; Cohn, Lawrence H; Corso, Paul J; Guyton, Robert A; Thourani, Vinod H; Lytle, Bruce W; Williams, Mathew R; Webb, John G; Kapadia, Samir; Tuzcu, E Murat; Cohen, David J; Schaff, Hartzell V; Leon, Martin B; Blackstone, Eugene H

    2015-09-01

    The study objectives were to (1) compare the safety of high-risk surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves (PARTNER) I trial with Society of Thoracic Surgeons national benchmarks; (2) reference intermediate-term survival to that of the US population; and (3) identify subsets of patients for whom aortic valve replacement may be futile, with no survival benefit compared with therapy without aortic valve replacement. From May 2007 to October 2009, 699 patients with high surgical risk, aged 84 ± 6.3 years, were randomized in PARTNER-IA; 313 patients underwent surgical aortic valve replacement. Median follow-up was 2.8 years. Survival for therapy without aortic valve replacement used 181 PARTNER-IB patients. Operative mortality was 10.5% (expected 9.3%), stroke 2.6% (expected 3.5%), renal failure 5.8% (expected 12%), sternal wound infection 0.64% (expected 0.33%), and prolonged length of stay 26% (expected 18%). However, calibration of observed events in this relatively small sample was poor. Survival at 1, 2, 3, and 4 years was 75%, 68%, 57%, and 44%, respectively, lower than 90%, 81%, 73%, and 65%, respectively, in the US population, but higher than 53%, 32%, 21%, and 14%, respectively, in patients without aortic valve replacement. Risk factors for death included smaller body mass index, lower albumin, history of cancer, and prosthesis-patient mismatch. Within this high-risk aortic valve replacement group, only the 8% of patients with the poorest risk profiles had estimated 1-year survival less than that of similar patients treated without aortic valve replacement. PARTNER selection criteria for surgical aortic valve replacement, with a few caveats, may be more appropriate, realistic indications for surgery than those of the past, reflecting contemporary surgical management of severe aortic stenosis in high-risk patients at experienced sites. Copyright © 2015 The American Association for Thoracic Surgery. Published by

  18. 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....

  19. 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.

  20. Gene therapy clinical trials worldwide 1989-2004-an overview.

    Science.gov (United States)

    Edelstein, Michael L; Abedi, Mohammad R; Wixon, Jo; Edelstein, Richard M

    2004-06-01

    In 1989, Rosenberg et al. performed the first human gene therapy trial when they used a retrovirus to introduce the gene coding for resistance to neomycin into human tumor-infiltrating lymphocytes before infusing them into five patients with advanced melanoma. This study demonstrated the feasibility of using retroviral gene transduction in humans and set the stage for further studies. Since then, over 900 clinical trials have been completed, are ongoing or have been approved worldwide. These trials have been designed to establish feasibility and safety, to demonstrate the reality of expression of therapeutic protein(s) in vivo by the genes transferred and, in some cases, to show therapeutic benefit. There is no single source of information that presents an overview of all the clinical trials undertaken worldwide. In 1997 we set up a database to bring all the information on clinical trials together as comprehensively and as globally as possible. The data were compiled and are regularly updated from official agency sources, the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. As of January 31, 2004, we have identified 918 trials in 24 countries. The USA accounts for two-thirds of these trials. Cancer is by far the most common disease indication, followed by inherited monogenic diseases, and cardiovascular diseases. Viral vectors have been the most frequently used vehicles for transferring genes into human cells, with retroviruses and adenoviruses representing the vast majority. Plasmid (naked) DNA and other non-viral vectors have been used in one-quarter of the trials. Over 100 distinct genes have been transferred. This article aims to provide a descriptive overview of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. Details of the data presented, including an interactive, searchable database that currently holds information on 918

  1. 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...

  2. 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...

  3. 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].

  4. 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.

  5. 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,...

  6. 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.

  7. 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...

  8. 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.

  9. 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

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

    DEFF Research Database (Denmark)

    Biegstraaten, Marieke; Arngrímsson, Reynir; Barbey, Frederic;

    2015-01-01

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

  11. 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.

  12. [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.

  13. Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A Randomized Controlled Trial

    Science.gov (United States)

    Campbell, Melissa; Decker, Kathleen P.; Kruk, Kerry; Deaver, Sarah P.

    2016-01-01

    This randomized controlled trial was designed to determine if art therapy in conjunction with Cognitive Processing Therapy (CPT) was more effective for reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone. Veterans (N = 11) were randomized to receive either individual CPT, or individual CPT in conjunction with individual…

  14. Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A Randomized Controlled Trial

    Science.gov (United States)

    Campbell, Melissa; Decker, Kathleen P.; Kruk, Kerry; Deaver, Sarah P.

    2016-01-01

    This randomized controlled trial was designed to determine if art therapy in conjunction with Cognitive Processing Therapy (CPT) was more effective for reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone. Veterans (N = 11) were randomized to receive either individual CPT, or individual CPT in conjunction with individual…

  15. 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

  16. Therapy of nephrolithiasis: where is the evidence from clinical trials?

    Science.gov (United States)

    Pachaly, Maria Aparecida; Baena, Cristina Pellegrino; Carvalho, Mauricio de

    2016-03-01

    The prevalence of kidney stone disease is increasing worldwide with significant health and economic burden. Newer research is finding that stones are associated with several serious morbidities. Yet, few randomized clinical trials or high quality observational studies have assessed whether clinical interventions decrease the recurrence of kidney stones. Therefore, in this review we analyze the available evidence on medical expulsive therapy for ureteral stones; describe the evidence about non-pharmacological stone therapy including dietary modifications and citrus juice-based therapy; and discuss the efficacy of thiazide diuretics for the treatment of hypercalciuria in recurrent nephrolithiasis.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. Oral nutrition or water loading before hip replacement surgery; a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Ljunggren Stefan

    2012-07-01

    Full Text Available Abstract Background Surgery induces insulin resistance that might be alleviated by a nutritional drink given preoperatively. The authors hypothesized that some of the beneficial effects of the drink could be attributed to the volume component (approximately 1 L rather than to the nutrients. Methods Sixty patients scheduled for elective total hip replacement under spinal anesthesia were recruited to a clinical trial, and randomly allocated to preoperative fasting, to oral ingestion of tap water, or to oral ingestion of a carbohydrate drink. An intravenous glucose tolerance test calculated glucose clearance and insulin sensitivity on the day before surgery, in the postoperative ward, and on the day after surgery. Other parameters were stress (cortisol in plasma and urine, muscle catabolism (urinary 3-methylhistidine, and wellbeing. Results Fifty-seven patients completed the study. In the postoperative ward, the glucose clearance and the insulin response had decreased from the previous day by 23% and 36%, respectively. Insulin sensitivity did not decrease until the next morning (−48% and was due to an increased insulin response (+51%. Cortisol excretion was highest on the day of surgery, while 3-methylhistidine increased 1 day later. Follow-up on the third postoperative day showed an average of 1.5 complications per patient. Wellbeing was better 2 weeks after than before the surgery. None of the measured parameters differed significantly between the study groups. Conclusions Preoperative ingestion of tap water or a nutritional drink had no statistically significant effect on glucose clearance, insulin sensitivity, postoperative complications, or wellbeing in patients undergoing elective hip surgery. Trial registration Registration number: NCT 01211184 (http://www.clinicaltrials.gov

  2. 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

  3. "To whom do the results of this trial apply?" External validity of a randomized controlled trial involving 130 patients scheduled for primary total hip replacement

    DEFF Research Database (Denmark)

    Petersen, Mette K; Andersen, Karen Vestergaard; Andersen, Niels T

    2007-01-01

    , but they should at least allow patients and clinicians to judge to whom trial results can reasonably be applied. We assessed the external validity of an RCT investigating the efficacy of a fast-track program after total hip replacement. METHODS: 130 patients were identified as potential participants.18 patients...

  4. 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...

  5. 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...

  6. Lipid Replacement Therapy: a Functional Food Approach with New Formulations for Reducing Cellular Oxidative Damage, Cancer-Associated Fatigue and the Adverse Effects of Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2011-04-01

    Full Text Available Backgroud:Cancer-associated fatigue and the chronic adverse effects of cancer therapy can be reduced by Lipid Replacement Therapy (LRT using membrane phospholipid mixtures given as food supplements.Methods:This is a review of the published literature on LRT and its uses.Results: LRT significantly reduced fatigue in cancer patients as well as patients suffering from chronic fatiguing illnesses and other medical conditions. It also reduced the adverse effects of chemotherapy, resulting in improvements in incidence of fatigue, nausea, diarrhea, impaired taste, constipation, insomnia and other quality of life indicators. In other diseases, such as chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses, LRT reduced fatigue by 35.5-43.1% in different clinical trials and increased mitochondrial function.Conclusions: LRT formulations appear to be useful as non-toxic dietary supplements for direct use or placed in functional foods to reduce fatigue and restore mitochondrial and other cellular membrane functions. Formulations of LRT phospholipids are suitable for addition to variousfood products for the treatment of a variety of chronic illnesses as well as their application inanti-aging and other health supplements and products.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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)

  12. 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

  13. [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.

  14. [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.

  15. 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.

  16. First-line therapy in ovarian cancer trials.

    Science.gov (United States)

    Thigpen, Tate; duBois, Andreas; McAlpine, Jessica; DiSaia, Philip; Fujiwara, Keiichi; Hoskins, William; Kristensen, Gunnar; Mannel, Robert; Markman, Maurie; Pfisterer, Jacobus; Quinn, Michael; Reed, Nick; Swart, Ann Marie; Berek, Jonathan; Colombo, Nicoletta; Freyer, Gilles; Gallardo, Dolores; Plante, Marie; Poveda, Andres; Rubinstein, Lawrence; Bacon, Monica; Kitchener, Henry; Stuart, Gavin C E

    2011-05-01

    At the 4th Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG) held in Vancouver, Canada, in June 2010, representatives of 23 cooperative research groups studying gynecologic cancers gathered to establish international consensus on issues critical to the conduct of large randomized trials. The process focused on 13 predetermined questions. Group A, 1 of the 3 discussion groups, addressed the first 5 questions, examining first-line therapies in newly diagnosed ovarian cancer patients. A1: What are the appropriate end points for different trials (maintenance, upfront chemotherapy trials including molecular drugs)? A2: Are there any subgroups defined by tumor biology who need specific treatment options/trials? A3: Is the 2004 GCIG-recommended standard comparator arm still valid? A4: What is the role of modifying dose, schedule, and delivery of chemotherapy? A5: What role does surgery play today?

  17. Comparison of Piascledine (Avocado and Soybean Oil) and Hormone Replacement Therapy in Menopausal-Induced Hot Flashing

    Science.gov (United States)

    Panahi, Yunes; Beiraghdar, Fatemeh; Kashani, Nafise; Baharie Javan, Nika; dadjo, yahya

    2011-01-01

    Different symptoms in Climacteric period, includes hot flash. Hormone replacement therapy (HRT) is common therapy for relief of menopausal symptoms but has possible contraindications and side effects. Recently Piascledine (combination of Avocado oil with Soybean oil) showed effects in reducing hot flash severity. Present study designed to compare the effects of HRT with Piascledine in treatment of hot flash. The cases of this study were sixty-six women at the age range of 40 to 70 years and complaints of menopause-induced hot flashing, whose last menstruation dated at least 6 months prior to the beginning of the study. The patients in this open label clinical trial, randomized to receive Piascledine capsule 1 mg or HRT (0.625 mg oral daily Conjugated Estrogen tablets, plus 2.5 mg continuous oral daily Medroxyprogesterone Acetate tablets) for 2 month. Hot flash property and severity was assessed via a daily check list and Visual analog scale. Climacteric symptom was measured before and after intervention using Greene Climacteric Scale (GCS) and Blatt-kupperman Menopausal Index (BKMI). Thirty-three eligible patients were allocated in each group. From the Piascledine group, one patient and from the HRT group, 16 patients weren›t willing to attend the study; therefore, 32 and 17 woman received treatment in Piascledine and HRT groups. 4 patients were withdrawn for vaginal bleeding and one for breast tenderness from HTR group. Hot flash severity in both groups decreased during the time similarly. With regard to GCS (p = 0.571) and BMKI (p = 0.891), the outcome was similar among the two groups. Due to low HRT compliance and its possible risks in long period of time and considering the same activity of soybean supplement and HRT in relieving the hot flash as menopausal symptoms in women, it seems that soybean supplements can be an alternative therapy to hormone. PMID:24250433

  18. 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

  19. 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

  20. 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

  1. 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

  2. A prospective, randomised trial of transapical transcatheter aortic valve implantation vs. surgical aortic valve replacement in operable elderly patients with aortic stenosis

    DEFF Research Database (Denmark)

    Nielsen, Hans Henrik Møller; Klaaborg, Kaj E; Nissen, Henrik

    2012-01-01

    In a prospective randomised trial we aimed to compare transapical transcatheter aortic valve implantation (a-TAVI) with surgical aortic valve replacement (SAVR) in operable elderly patients.......In a prospective randomised trial we aimed to compare transapical transcatheter aortic valve implantation (a-TAVI) with surgical aortic valve replacement (SAVR) in operable elderly patients....

  3. 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.

  4. 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

  5. Baseline characteristics in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

    DEFF Research Database (Denmark)

    Pfeffer, Marc A; Burdmann, Emmanuel A; Chen, Chao-Yin

    2009-01-01

    BACKGROUND: Anemia augments the already high rates of fatal and major nonfatal cardiovascular and renal events in individuals with type 2 diabetes. In 2004, we initiated the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). This report presents the baseline characteristics......: the composite end point of death or cardiovascular morbidity (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia). The composite end point of death or need for long-term renal replacement therapy also is a primary end point. CONCLUSIONS: With several......-fold more patient-years and a placebo arm, TREAT will provide a robust estimate of the safety and efficacy of darbepoetin alfa and generate prospective data regarding the risks of major cardiovascular and renal events in a contemporarily managed cohort of patients with type 2 diabetes, CKD, and anemia....

  6. Acupressure therapy for morning sickness. A controlled clinical trial.

    Science.gov (United States)

    Hyde, E

    1989-01-01

    A prospective, controlled clinical trial examined the efficacy of acupressure therapy for morning sickness, using a two group, random assignment, crossover design. Subjects in Group 1 (N = 8) used acupressure wristbands for five days, followed by five days without therapy. Subjects in Group 2 (N = 8) had no therapy for five days, followed by five days use of wristbands. The Multiple Affect Adjective Checklist and Sickness Impact Profile were used, and extent of nausea was assessed at baseline, day five, and day ten. Use of acupressure wristbands relieved morning sickness for 12 of 16 subjects (chi 2 = 5.31 with Yates' correction factor, df = 1, p less than .025). Acupressure therapy resulted in statistically significant (p less than .05) reductions in anxiety, depression, behavioral dysfunction, and nausea. Limitations of the study and suggestions for future research are presented.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease

    Science.gov (United States)

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11–12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11–12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11–12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease. PMID:27081853

  17. Declining incidence of breast cancer after decreased use of hormone-replacement therapy: magnitude and time lags in different countries.

    Science.gov (United States)

    Zbuk, Kevin; Anand, Sonia S

    2012-01-01

    Throughout the latter half of the 20th century, hormone-replacement therapy (HRT) use steadily increased in the Western world. In 2002, the early termination of the Women's Health Initiative trial due to an excess of adverse events attributable to HRT, led to a precipitous decline in its use. Breast cancer incidence began to decline soon thereafter in the USA and several other countries. However, the magnitude of the decline in breast cancer incidence, and its timing with respect to HRT cessation, shows considerable variability between nations. The impact of HRT cessation appears most significant and immediate in countries with the largest absolute decline in HRT use. In countries in which peak prevalence of HRT use was high, several studies have convincingly excluded decreasing rates of mammographic screening as an explanation for the decline in breast cancer incidence. Conversely, in some countries, no decline in breast cancer incidence is apparent that can be readily attributed to declining trends in HRT use. In such cases, declines in breast cancer incidence may be related instead to saturation or decreased utilisation of mammographic screening programmes. In other cases, it is difficult to disentangle the respective influence of trends in HRT use, and the influence of changes relating to mammographic screening. However, irrespective of time lags and varying magnitudes of effect, the data convincingly support a direct association between decreasing HRT use and declining breast cancer incidence.

  18. Clinical Strategies to Enhance the Efficacy of Nicotine Replacement Therapy for Smoking Cessation: A Review of the Literature

    Science.gov (United States)

    Carpenter, Matthew J.; Jardin, Bianca F.; Burris, Jessica L.; Mathew, Amanda R.; Schnoll, Robert A.; Rigotti, Nancy A.; Cummings, K. Michael

    2013-01-01

    A number of smoking cessation pharmacotherapies have led to increases in quitting and thus to significant benefits to public health. Among existing medications, nicotine replacement therapy (NRT) has been available the longest, has the largest literature base in support, and is the only option for over-the-counter access. While the short term efficacy of NRT is well documented in clinical trials, long term abstinence rates associated with using NRT are modest, as most smokers will relapse. This literature review examines emerging clinical strategies to improve NRT efficacy. After an initial overview of NRT and its FDA-approved indications for use, we review randomized trials in which clinical delivery of NRT was manipulated and tested, in an attempt to enhance efficacy, through a) duration of use (pre-quit and extended use), b) amount of use (high dose and combination NRT), c) tailoring to specific smoker groups (genotype and phenotype), or d) use of NRT for novel purposes (relapse prevention, temporary abstinence, cessation induction). Outcomes vary within and across topic area, and we highlight areas that offer stronger promise. Combination NRT likely represents the most promising strategy moving forward; other clinical strategies offer conflicting evidence but deserve further testing (pre-quit NRT or tailored treatment), or offer potential utility but are in need of further, direct tests. Some areas, though based on a limited set of studies, do not offer great promise (high dose and extended treatment NRT). We conclude with a brief discussion of emergent NRT products (e.g., oral nicotine spray, among others), which may ultimately offer greater efficacy than current formulations. In order to further lower the prevalence of smoking, novel strategies designed to optimize NRT efficacy are needed. PMID:23572407

  19. 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.

  20. [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.

  1. 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.

  2. 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.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    OBJECTIVE: Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. METHODS: This nationwide case-control study included all women with an SBT...... diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy...... 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...

  4. 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.

  5. 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...

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. 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.

  11. 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...

  12. 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.

  13. 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...

  14. [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.

  15. 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.

  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. 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.

  19. 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

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

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    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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  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. [New trial designs and potential therapies for pulmonary artery hypertension].

    Science.gov (United States)

    Gomberg-Maitland, Mardi; Bull, Todd M; Saggar, Rajeev; Barst, Robyn J; Elgazayerly, Amany; Fleming, Thomas R; Grimminger, Friedrich; Rainisio, Maurizio; Stewart, Duncan J; Stockbridge, Norman; Ventura, Carlo; Ghofrani, Ardeschir H; Rubin, Lewis J

    2014-10-01

    A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial I concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH. (J Am Coil Cardiol 2013;62:D82-91) ©2013 by the American College of Cardiology Foundation.

  11. Safety of hormonal replacement therapy and oral contraceptives in systemic lupus erythematosus: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Adriana Rojas-Villarraga

    Full Text Available There is conflicting data regarding exogenous sex hormones [oral contraceptives (OC and hormonal replacement therapy (HRT] exposure and different outcomes on Systemic Lupus Erythematosus (SLE. The aim of this work is to determine, through a systematic review and meta-analysis the risks associated with estrogen use for women with SLE as well as the association of estrogen with developing SLE.MEDLINE, EMBASE, SciElo, BIREME and the Cochrane library (1982 to July 2012, were databases from which were selected and reviewed (PRISMA guidelines randomized controlled trials, cross-sectional, case-control and prospective or retrospective nonrandomized, comparative studies without language restrictions. Those were evaluated by two investigators who extracted information on study characteristics, outcomes of interest, risk of bias and summarized strength of evidence. A total of 6,879 articles were identified; 20 full-text articles were included. Thirty-two meta-analyses were developed. A significant association between HRT exposure (Random model and an increased risk of developing SLE was found (Rate Ratio: 1.96; 95%-CI: 1.51-2.56; P-value<0.001. One of eleven meta-analyses evaluating the risk for SLE associated with OC exposure had a marginally significant result. There were no associations between HRT or OC exposure and specific outcomes of SLE. It was not always possible to Meta-analyze all the available data. There was a wide heterogeneity of SLE outcome measurements and estrogen therapy administration.An association between HRT exposure and SLE causality was observed. No association was found when analyzing the risk for SLE among OC users, however since women with high disease activity/Thromboses or antiphospholipid-antibodies were excluded from most of the studies, caution should be exercised in interpreting the present results. To identify risk factors that predispose healthy individuals to the development of SLE who are planning to start HRT or OC

  12. 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.

  13. 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.

  14. 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 

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. [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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. The effect of 5α-reductase inhibitors on prostate growth in men receiving testosterone replacement therapy: a systematic review and meta-analysis.

    Science.gov (United States)

    Cui, Yuanshan; Zong, Huantao; Yang, Chenchen; Yan, Huilei; Zhang, Yong

    2013-08-01

    Androgen replacement therapy is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism (LOH) syndrome. Urologists have been concerned with the use of androgen supplements due to the possibility of enhancing prostate growth. We performed a systematic review and meta-analysis to assess the effect of 5α-reductase inhibitors on prostate growth in men receiving testosterone replacement therapy. A literature review was performed to identify all published randomized placebo-controlled trials (RCT) that used exogenous testosterone combined with 5α-reductase inhibitor therapy for the treatment of hypogonadism. The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated, and a systematic review and meta-analysis were conducted. Five publications involving a total of 250 patients were used in the analysis, including 4 RCTs that were short-term (≤6 mo) comparisons of testosterone plus a 5α-reductase inhibitor with testosterone plus placebo and 3 RCTs that were long-term (18-36 mo) comparisons of testosterone plus a 5α-reductase inhibitor with testosterone plus placebo. In our meta-analysis, we found that testosterone plus a 5α-reductase inhibitor may slow the progression of prostate growth. For the comparison of short-term testosterone plus 5α-reductase inhibitor treatment with testosterone plus placebo therapy, the prostate-specific antigen (PSA) level (the standardized mean difference (SMD) = -0.24, 95 % confidence interval (CI) = -0.45 to 0.04, p = 0.02)) and the prostate volume (SMD = -1.66, 95 % CI = -4.54 to 1.22, p = 0.26) indicated that, compared with testosterone plus placebo therapy, the testosterone plus 5α-reductase inhibitor may decrease the PSA level. For the comparison of long-term testosterone plus 5α-reductase inhibitor with testosterone plus placebo, the PSA level (SMD = -0.53, 95 % CI = -0.84 to 0

  8. Cell Therapy for Stroke: Review of Previous Clinical Trials and Introduction of Our New Trials

    Science.gov (United States)

    SHICHINOHE, Hideo; HOUKIN, Kiyohiro

    2016-01-01

    Stroke is still a leading cause of death and disability, and despite intensive research, few treatment options exist. A recent breakthrough in cell therapy is expected to reverse the neurological sequelae of stroke. Although some pioneer studies on the use of cell therapy for the treatment of stroke have been reported, certain problems still remain unsolved. We investigated the use of autologous bone marrow stromal cell (BMSC) transplantation for the treatment of stroke, to develop it as the next-generation cell therapy. In this study, we introduce the preparation of a new clinical trial, the Research on Advanced Intervention using Novel Bone marrow stem cell (RAINBOW) study. The trial will start in 2016, and we hope that it will not only be helpful for treating patients but also for clarifying the therapeutic mechanisms. Moreover, we review stem cell therapeutics as an emerging paradigm in stroke (STEPS) and the guidelines for the development of cell therapy for stroke in the United States as well as introduce the development of new guidelines in Japan. These guidelines are expected to encourage the development of cell therapy for stroke management. PMID:27302193

  9. 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.

  10. 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.

  11. Randomized Trial of Telephone-Delivered Acceptance and Commitment Therapy Versus Cognitive Behavioral Therapy for Smoking Cessation: A Pilot Study

    Science.gov (United States)

    Bush, Terry; Zbikowski, Susan M.; Mercer, Laina D.; Heffner, Jaimee L.

    2014-01-01

    Objective: We conducted a pilot randomized trial of telephone-delivered acceptance and commitment therapy (ACT) versus cognitive behavioral therapy (CBT) for smoking cessation. Method: Participants were 121 uninsured South Carolina State Quitline callers who were adult smokers (at least 10 cigarettes/day) and who wanted to quit within the next 30 days. Participants were randomized to 5 sessions of either ACT or CBT telephone counseling and were offered 2 weeks of nicotine replacement therapy (NRT). Results: ACT participants completed more calls than CBT participants (M = 3.25 in ACT vs. 2.23 in CBT; p = .001). Regarding satisfaction, 100% of ACT participants reported their treatment was useful for quitting smoking (vs. 87% for CBT; p = .03), and 97% of ACT participants would recommend their treatment to a friend (vs. 83% for CBT; p = .06). On the primary outcome of intent-to-treat 30-day point prevalence abstinence at 6 months postrandomization, the quit rates were 31% in ACT versus 22% in CBT (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 0.7–3.4). Among participants depressed at baseline (n = 47), the quit rates were 33% in ACT versus 13% in CBT (OR = 1.2, 95% CI = 1.0–1.6). Consistent with ACT’s theory, among participants scoring low on acceptance of cravings at baseline (n = 57), the quit rates were 37% in ACT versus 10% in CBT (OR = 5.3, 95% CI = 1.3–22.0). Conclusions: ACT is feasible to deliver by phone, is highly acceptable to quitline callers, and shows highly promising quit rates compared with standard CBT quitline counseling. As results were limited by the pilot design (e.g., small sample), a full-scale efficacy trial is now needed. PMID:24935757

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. Clinical trial registration in physical therapy journals: a cross-sectional study.

    Science.gov (United States)

    Babu, Abraham Samuel; Veluswamy, Sundar Kumar; Rao, Pratiksha Tilak; Maiya, Arun G

    2014-01-01

    Clinical trial registration has become an important part of editorial policies of various biomedical journals, including a few physical therapy journals. However, the extent to which editorial boards enforce the need for trial registration varies across journals. The purpose of this study was to identify editorial policies and reporting of trial registration details in MEDLINE-indexed English-language physical therapy journals. This study was carried out using a cross-sectional design. Editorial policies on trial registration of MEDLINE-indexed member journals of the International Society of Physiotherapy Journal Editors (ISPJE) (Journal of Geriatric Physical Therapy, Journal of Hand Therapy, Journal of Neurologic Physical Therapy, Journal of Orthopaedic and Sports Physical Therapy, Journal of Physiotherapy [formerly Australian Journal of Physiotherapy], Journal of Science and Medicine in Sport, Manual Therapy, Physical Therapy, Physical Therapy in Sport, Physiotherapy, Physiotherapy Research International, Physiotherapy Theory and Practice, and Revista Brasileira de Fisioterapia) were reviewed in April 2013. Full texts of reports of clinical trials published in these journals between January 1, 2008, and December 31, 2012, were independently assessed for information on trial registration. Among the 13 journals, 8 recommended trial registration, and 6 emphasized prospective trial registration. As of April 2013, 4,618 articles were published between January 2008 and December 2012, of which 9% (417) were clinical trials and 29% (121/417) of these reported trial registration details. A positive trend in reporting of trial registration was observed from 2008 to 2012. The study was limited to MEDLINE-indexed ISPJE member journals. Editorial policies on trial registration of physical therapy journals and a rising trend toward reporting of trial registration details indicate a positive momentum toward trial registration. Physical therapy journal editors need to show

  18. 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.

  19. 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

  20. 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...

  1. 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 ...

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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...

  7. 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...

  8. 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

  9. 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...

  10. 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

  11. [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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Bone mineral density in young women with primary ovarian insufficiency: results of a three-year randomized controlled trial of physiological transdermal estradiol and testosterone replacement.

    Science.gov (United States)

    Popat, Vaishali B; Calis, Karim A; Kalantaridou, Sophia N; Vanderhoof, Vien H; Koziol, Deloris; Troendle, James F; Reynolds, James C; Nelson, Lawrence M

    2014-09-01

    Women with primary ovarian insufficiency have significantly lower serum estradiol and T levels compared with regularly menstruating women. They also have significantly reduced bone mineral density (BMD). The objective of the study was to evaluate the efficacy of hormone replacement in maintaining BMD in these young women. This was a randomized, double-blind, single-center, placebo-controlled clinical trial at the National Institutes of Health clinical center (Bethesda, Maryland). Young women with primary ovarian insufficiency participated in the study. We compared the effect of estradiol and progestin replacement (n = 72) vs estradiol, progestin, and T replacement (n = 73) on BMD. We also compared findings with a contemporaneous control group of normal women (n = 70). All patients received transdermal estradiol (100 μg/d) plus oral medroxyprogesterone acetate 10 mg/d (12 d/mo) for a 3-month run-in period before being randomized in a double-blinded fashion to the addition of transdermal T (150 μg/d) or placebo. Change in BMD at the femoral neck was measured by dual-energy x-ray absorptiometry. At screening, patients had significantly lower femoral neck BMD compared with control women (0.77 vs 0.81 g/cm(2), P = .001) and did not differ in body mass index, age at menarche, or education level. Normal control women lost femoral neck BMD over the study period, whereas patients on estradiol and progestin therapy gained BMD; and at the end of the study period, femoral neck BMD of patients on estradiol and progestin therapy did not differ from that of control women (0.80 g/cm(2) in both groups, P = .9). The addition of T showed no further benefit (percentage change in BMD 3.9 vs 2.4, respectively, P = .9). Nonetheless, using a repeated-measures model, the T group achieved a mean BMD in the femoral neck 0.015 g/cm(2) higher than the placebo group at 3 years (95% confidence interval -0.005 to 0.034, P = .13). Similar findings were observed in the lumbar spine BMD as well

  1. Seal, replacement or monitoring amalgam restorations with occlusal marginal defects? Results of a 10-year clinical trial.

    Science.gov (United States)

    Moncada, G; Fernández, E; Mena, K; Martin, J; Vildósola, P; De Oliveira Junior, O B; Estay, J; Mjör, I A; Gordan, V V

    2015-11-01

    The aim of this prospective and blind clinical trial was to assess the effectiveness of sealing localized marginal defects of amalgam restoration that were initially scheduled to be replaced. A cohort of twenty six patients with 60 amalgam restorations (n=44Class I and n=16Class II), that presented marginal defects deviating from ideal (Bravo) according to USPHS criteria, were assigned to either sealing or replacement groups: A: sealing n=20, Replacement n=20, and no treatment (n=20). Two blind examiners evaluated the restorations at baseline (K=0.74) and after ten years (K=0.84) according with USPHS criteria, in four parameters: marginal adaptation (MA), secondary caries (SC), marginal staining (MS) and teeth sensitivity (TS). Multiple comparison of restorations degradation/upgrade was analyzed by Friedman test and the comparisons within groups were performed by Wilcoxon test. After 10 years, 44 restorations were assessed (73.3%), Group A: n=14 and Group B: n=16; and Group C: n=14 sealing and replacement amalgam restorations presented similar level of quality in MA (p=0.76), SC (p=0.25) and TS (p=0.52), while in MS (p=0.007) presented better performance in replacement group after 10-years. Most of the occlusal amalgam restorations with marginal gaps showed similar long term outcomes than the restorations were sealed, replaced, or not treated over a 10-year period. Most of the restorations of the three groups were clinically acceptable, under the studied parameters. All restorations had the tendency to present downgrade/deterioration over time.

  2. 75 FR 54351 - Cell and Gene Therapy Clinical Trials in Pediatric Populations; Public Workshop

    Science.gov (United States)

    2010-09-07

    ... HUMAN SERVICES Food and Drug Administration Cell and Gene Therapy Clinical Trials in Pediatric... public workshop entitled ``Cell and Gene Therapy Clinical Trials in Pediatric Populations.'' The purpose... therapy clinical researchers, and other stakeholders regarding best practices related to cell and...

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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...

  12. 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

  13. 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.

  14. Effects of hormone replacement therapy on platelet activation in postmenopausal women

    Institute of Scientific and Technical Information of China (English)

    古健; 杨冬梓; 王良岸; 尹松梅; 邝健全

    2003-01-01

    Objective To assess the effects of hormone replacement therapy (HRT) on platelet activation in postmenopausal women compared with premenopausal women. Methods The expressions of CD41 and CD62P in fifteen postmenopausal women before and after HRT were detected using flow cytometry (FCM), with fifteen premenopausal women with a mean age of 47 years as controls.Results The expressions of CD41 and CD62P in postmenopausal women were higher than those in the control group. CD62P(%), CD62P(I) and CD41 were reduced from 36.40±5.9, 37.75±5.8, and 470.11±74.0 to 27.97±5.6, 26.64±4.9, and 303.23±72.8 after six months of HRT (P<0.05). Conclusions Platelet activation in postmenopausal women was higher than in premenopausal women and was reduced significantly after six months of HRT. HRT may have a favorable effect on reduction of platelet activity.

  15. Update on Renal Replacement Therapy: Implantable Artificial Devices and Bioengineered Organs.

    Science.gov (United States)

    Attanasio, Chiara; Latancia, Marcela T; Otterbein, Leo E; Netti, Paolo A

    2016-08-01

    Recent advances in the fields of artificial organs and regenerative medicine are now joining forces in the areas of organ transplantation and bioengineering to solve continued challenges for patients with end-stage renal disease. The waiting lists for those needing a transplant continue to exceed demand. Dialysis, while effective, brings different challenges, including quality of life and susceptibility to infection. Unfortunately, the majority of research outputs are far from delivering satisfactory solutions. Current efforts are focused on providing a self-standing device able to recapitulate kidney function. In this review, we focus on two remarkable innovations that may offer significant clinical impact in the field of renal replacement therapy: the implantable artificial renal assist device (RAD) and the transplantable bioengineered kidney. The artificial RAD strategy utilizes micromachining techniques to fabricate a biohybrid system able to mimic renal morphology and function. The current trend in kidney bioengineering exploits the structure of the native organ to produce a kidney that is ready to be transplanted. Although these two systems stem from different technological approaches, they are both designed to be implantable, long lasting, and free standing to allow patients with kidney failure to be autonomous. However, for both of them, there are relevant issues that must be addressed before translation into clinical use and these are discussed in this review.

  16. Pancreatic enzyme replacement therapy in cystic fibrosis: dose, variability and coefficient of fat absorption.

    Science.gov (United States)

    Calvo-Lerma, Joaquim; Martínez-Barona, Sandra; Masip, Etna; Fornés, Victoria; Ribes-Koninckx, Carmen

    2017-07-27

    Pancreatic enzyme replacement therapy (PERT) remains a backbone in the nutritional treatment of cystic fibrosis. Currently, there is a lack of an evidence-based tool that allows dose adjustment. To date, no studies have found an association between PERT dose and fat absorption. Therefore, the aim of the study was to assess the influence of both the PERT dose and the variability in this dose on the coefficient of fat absorption (CFA). This is a retrospective longitudinal study of 16 pediatric patients (192 food records) with three consecutive visits to the hospital over a twelve-month period. Dietary fat intake and PERT were assessed via a four-day food record and fat content in stools was determined by means of a three-day stool sample collection. A beta regression model was built to explain the association between the CFA and the interaction between the PERT dose (lipase units [LU]/g dietary fat) and the variability in the PERT dose (standard deviation [SD]). The coefficient of fat absorption increased with the PERT dose when the variability in the dose was low. In contrast, even at the highest PERT dose values, the CFA decreased when the variability was high. The confidence interval suggested an association, although the analysis was not statistically significant. The variability in the PERT dose adjustment should be taken into consideration when performing studies on PERT efficiency. A clinical goal should be the maintenance of a constant PERT dose rather than trying to obtain an optimal value.

  17. Systemic delivery of factor IX messenger RNA for protein replacement therapy

    Science.gov (United States)

    Ramaswamy, Suvasini; Tonnu, Nina; Tachikawa, Kiyoshi; Limphong, Pattraranee; Vega, Jerel B.; Karmali, Priya P.; Chivukula, Pad; Verma, Inder M.

    2017-01-01

    Safe and efficient delivery of messenger RNAs for protein replacement therapies offers great promise but remains challenging. In this report, we demonstrate systemic, in vivo, nonviral mRNA delivery through lipid nanoparticles (LNPs) to treat a Factor IX (FIX)-deficient mouse model of hemophilia B. Delivery of human FIX (hFIX) mRNA encapsulated in our LUNAR LNPs results in a rapid pulse of FIX protein (within 4–6 h) that remains stable for up to 4–6 d and is therapeutically effective, like the recombinant human factor IX protein (rhFIX) that is the current standard of care. Extensive cytokine and liver enzyme profiling showed that repeated administration of the mRNA–LUNAR complex does not cause any adverse innate or adaptive immune responses in immune-competent, hemophilic mice. The levels of hFIX protein that were produced also remained consistent during repeated administrations. These results suggest that delivery of long mRNAs is a viable therapeutic alternative for many clotting disorders and for other hepatic diseases where recombinant proteins may be unaffordable or unsuitable. PMID:28202722

  18. Effect of regional citrate anticoagulation on critical patients with continuous renal replacement therapy

    Institute of Scientific and Technical Information of China (English)

    Li-Li You

    2016-01-01

    Objective:To investigate the efficacy and safety of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) for critical patients.Methods:A total of 83 critical patients need CRRT in the intensive care units of our hospital from July 2012 to June 2016 were recruited in the study, and the patients were divided into two groups randomly, the patients in observation group received the RCA treatment, and the patients in control group received traditional low molecular heparin anticoagulation. The difference of safety indicators, biochemical indicators, extracorporeal circulation blood coagulation condition and complications in patients were determined between two groups.Results: Compared with control group, the patients in observation group had an elevated level of iCa2+, the level of chloride ion reduced, the use time of filter increased, the bleeding cases reduced, the concentrations of urea nitrogen, creatinine TNF-α, IL-1β, IL-8 and NO were all significantly downregulated, the data have a significant difference (P < 0.05).Conclusions:RCA is a safe and effective method for CRRT in patients with a high risk of bleeding.

  19. AN ULTRASTRUTURAL STUDY OF HUMAN LUMINAL ENDOMETRIAL CELLS FOLLOWING DIFFERENT DOSES OF OESTROGEN REPLACEMENT THERAPY

    Directory of Open Access Journals (Sweden)

    SARANI SH.A

    2001-01-01

    Full Text Available Introduction: The effects of different doses of oestrogen on the endometrium of women with premature ovarian failure have been examined in this study. Materials and Methods: Four groups of women of reproductive age were studied; 1 normal fertile controls 2. patients given a standard, variable hormone replacement therapy (HRT 3. a group given a fixed daily dose of 1 mg of oestrogen and 4. a group given a fixed daily dose of 4 mg of oestrogen. Endrometrial diposises were taken at a bout 5-6 days after ovulation and tissue was prepared for light and electron microscopy. Morphometry was used to evaluate quantitatively various features of endometrial luminal epithelial cells. The volume fraction (Vv of nucleus to cell in the standard group was significantly larger than the 4 mg group. Results: The Vv of euchromatin to nucleus was larger in the controls and 4 mg group than the 1 mg subjects. The Vv of mitochondria to cell was largest in the control group. The ratio of desmosomes to surface membrane was increased (P<0.05 in the 1 mg subjects. Conclusion: These results suggest that, while standard HRT is generally a good mimic of controls, the 1 mg fixed dose delayed some membrane features and the fixed 4 mg group showed advancement in some organelle growth.

  20. Composite HPMC and sodium alginate based buccal formulations for nicotine replacement therapy.

    Science.gov (United States)

    Okeke, Obinna C; Boateng, Joshua S

    2016-10-01

    Smoking cessation is of current topical interest due to the significant negative health and economic impact in many countries. This study aimed to develop buccal films and wafers comprising HPMC and sodium alginate (SA) for potential use in nicotine replacement therapy via the buccal mucosa, as a cheap but effective alternative to currently used nicotine patch and chewing gum. The formulations were characterised using texture analyser (tensile and hardness, mucoadhesion), scanning electron microscopy, X-ray diffractometry, attenuated total reflection-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC) and swelling capacity. Drug loaded films and wafers were characterised for content uniformity (HPLC) whilst the drug loaded wafers only were further characterised for in vitro drug dissolution. SA modified and improved the functional properties of HPMC at optimum ratio of HPMC: SA of 1.25: 0.75. Generally, both films and wafers (blank and drug loaded) were amorphous in nature which impacted on swelling and mucoadhesive performance. HPMC-SA composite wafers showed a porous internal morphology with higher mucoadhesion, swelling index and drug loading capacity compared to the HPMC-SA composite films which were non-porous. The study demonstrates the potential use of composite HPMC-SA wafers in the buccal delivery nicotine. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Analysis of the Influence of Hormone Replacement Therapy on Osteocalcin Gene Expression in Postmenopausal Women.

    Science.gov (United States)

    Rahnama, Mansur; Jastrzębska-Jamrogiewicz, Izabela; Jamrogiewicz, Rafał; Trybek, Grzegorz

    2015-01-01

    Osteocalcin (OC) contributes to the process of bone mineralization. Present study was designed to investigate the changes in OC gene expression of postmenopausal women treated with hormone replacement therapy (HRT). Study was also designed to evaluate OC gene expression in cells which are not part of connective tissue. Research was carried out on 30 postmenopausal women not treated and 30 treated with HRT. Examination of OC gene expression was conducted on peripheral blood lymphocytes (PBL) and buccal epithelial lining (BEL). Densitometry was conducted on femur and mandible. Tests revealed OC gene expression in BEL and PBL. BMD was higher in groups treated with HRT. Assessment of correlation between the OC gene expression in BEL and BMD of mandible revealed significant positive relation. OC gene expression can be stated BEL and PBL. Analysis of correlation between OC gene expression in oral cavity and mandible BMD showed significant correlation between local OC expression and local bone metabolism. The relation between OC gene expression and bone metabolism is complex and further research is needed to clear all of the uncertainties.

  2. Morphological changes in muscle tissue of patients with infantile Pompe's disease receiving enzyme replacement therapy.

    Science.gov (United States)

    Winkel, Léon P F; Kamphoven, Joep H J; van den Hout, Hannerieke J M P; Severijnen, Lies A; van Doorn, Pieter A; Reuser, Arnold J J; van der Ploeg, Ans T

    2003-06-01

    Pompe's disease (glycogen storage disease type II) is an autosomal recessive myopathy caused by lysosomal alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) is currently under development for this disease. We evaluated the morphological changes in muscle tissue of four children with infantile Pompe's disease who received recombinant human alpha-glucosidase from rabbit milk for 72 weeks. The patients were 2.5-8 months of age at entry. Prior to treatment, all patients showed lysosomal glycogen storage in skeletal and smooth muscle cells, vascular endothelium, Schwann cells, and perineurium. The first response to treatment was noticed in vascular endothelium and in peripheral nerves after 12 weeks of treatment at an enzyme dose of 15-20 mg/kg. Increasing the dose to 40 mg/kg led, after 72 weeks of treatment, to a reduction of glycogen storage and substantial improvement of muscle architecture in the least affected patient. Not all patients responded equally well, possibly due to differences in degree of glycogen storage and concomitant muscle pathology at the start of treatment. We conclude that intravenous administration of recombinant human alpha-glucosidase from rabbit milk can improve muscle morphology in classic infantile Pompe's disease when treatment is started before irreversible damage has occurred.

  3. First experience with enzyme replacement therapy during pregnancy and lactation in Pompe disease.

    Science.gov (United States)

    de Vries, Juna M; Brugma, Jan-Dietert C; Ozkan, Lale; Steegers, Eric A P; Reuser, Arnold J J; van Doorn, Pieter A; van der Ploeg, Ans T

    2011-12-01

    Enzyme replacement therapy (ERT) with alglucosidase alfa was registered as a treatment for Pompe disease in 2006. It is as yet unknown whether ERT can be safely applied during pregnancy and lactation. A primiparous 40-year-old woman diagnosed with Pompe disease continued receiving ERT during pregnancy and lactation. Before pregnancy, she had moderate limb-girdle weakness and used nocturnal ventilation. During pregnancy, her clinical condition remained fairly stable until the 25th gestational week. Thereafter she experienced more problems with mobility and respiration. Fetal growth was normal as monitored by regular ultrasound investigations. A healthy boy was born at a gestational age of 37 weeks and 5 days by elective Cesarean section. There were no maternal complications and the child developed normally. One year after delivery the mother's physical condition was similar as prior to her pregnancy. Pharmacokinetic studies following enzyme infusion showed that alglucosidase alfa was secreted into the breast milk. Activity levels in the milk (245 nmol/ml.h) peaked at 2.5h after the end of the infusion; which was 2h later than in the plasma (80 μmol/ml.h). Twenty-four hours after start of the infusion, the enzyme activity in the breast milk was back to the pre-infusion level. In this case report, the continuation of treatment with alglucosidase alfa during pregnancy and lactation has been safe for the mother and the child.

  4. The ocular benefits of estrogen replacement therapy: a population-based study in postmenopausal Korean women.

    Directory of Open Access Journals (Sweden)

    Kyung-Sun Na

    Full Text Available PURPOSE: To elucidate the prevalence of cataract, glaucoma, pterygia, and diabetic retinopathy among Korean postmenopausal women with or without estrogen replacement therapy (ERT. METHODS: A cross-sectional, nationally representative sample from the 4th Korea National Health and Nutrition Examination Survey (KNHANES IV (2007-2009 was used. Participants were interviewed for the determination of socioeconomic and gynecologic factors. Each woman also underwent an ophthalmologic examination and provided a blood sample for risk factor assessment. RESULTS: Of 3968 postmenopausal women enrolled, 3390 had never received estrogen, and 578 were undergoing estrogen treatment. After adjusting for age, diabetes, hypertension, high cholesterol levels, and high low-density lipoprotein levels, the prevalence of anterior polar cataract, retinal nerve fiber layer (RNFL defect, and flesh pterygium was higher in the non-ERT group (OR, 3.24; 95% CI, 1.12-9.35, OR 1.70; 95% CI, 1.04-2.78, OR 3.725; 95% CI, 1.21-11.45, respectively. Further, the prevalence of atrophic pterygium was lower in the non-ERT group compared to that in the ERT group (OR, 0.21, 95% CI, 0.07-0.63. CONCLUSIONS: These data suggest that ERT has a protective effect against the development of anterior polar cataract, flesh pterygium, and RNFL defect.

  5. Deleterious effects of interruption followed by reintroduction of enzyme replacement therapy on a lysosomal storage disorder.

    Science.gov (United States)

    Schneider, Ana Paula; Matte, Ursula; Pasqualim, Gabriela; Tavares, Angela Maria Vicente; Mayer, Fabiana Quoos; Martinelli, Barbara; Ribas, Graziela; Vargas, Carmen Regla; Giugliani, Roberto; Baldo, Guilherme

    2016-10-01

    Temporary interruption of enzyme replacement therapy (ERT) in patients with different lysosomal storage disorders may happen for different reasons (adverse reactions, issues with reimbursement, logistic difficulties, and so forth), and the impact of the interruption is still uncertain. In the present work, we studied the effects of the interruption of intravenous ERT (Laronidase, Genzyme) followed by its reintroduction in mice with the prototypical lysosomal storage disorder mucopolysaccharidosis type I, comparing to mice receiving continuous treatment, untreated mucopolysaccharidosis type I mice, and normal mice. In the animals which treatment was temporarily interrupted, we observed clear benefits of treatment in several organs (liver, lung, heart, kidney, and testis) after reintroduction, but a worsening in the thickness of the aortic wall was detected. Furthermore, these mice had just partial improvements in behavioral tests, suggesting some deterioration in the brain function. Despite worsening is some disease aspects, urinary glycosaminoglycans levels did not increase during interruption, which indicates that this biomarker commonly used to monitor treatment in patients should not be used alone to assess treatment efficacy. The deterioration observed was not caused by the development of serum antienzyme antibodies. All together our results suggest that temporary ERT interruption leads to deterioration of function in some organs and should be avoided whenever possible.

  6. Is the oral contraceptive or hormone replacement therapy a risk factor for cholelithiasis

    Science.gov (United States)

    Wang, Siqi; Wang, Yuqiong; Xu, Jinming; Chen, Yuxin

    2017-01-01

    Abstract Background: Association between exogenous estrogen intake and cholelithiasis risk has been reported in several epidemiological studies, including oral contraceptive (OC) and hormone replacement therapy (HRT), while the results were controversial. This study aimed to perform a comprehensive meta-analysis of this issue. Methods: PUBMED, EMBASE, and Cochrane library database were searched up to October 2016. Two reviewers independently extracted data from eligible studies, relative risks (RRs), and/or odds ratios (ORs) with 95% confidence intervals (95% CIs) for the highest versus lowest categories of intake were adopted. Either a fixed- or a random-effects model was adopted to estimate overall RRs or ORs. Besides, subgroup and publication bias analyses were applied to explain the heterogeneity. An original study was also conducted to verify our conclusion. Results: A total of 19 studies with approximately 556,620 participants were included in this meta-analysis. The pooled RR of cholelithiasis for the highest versus the lowest categories was 1.59 (95% CI: 1.44–1.75), indicating that exogenous estrogen was positive associated with the intake of exogenous estrogen. However, the pooled RR of OC intake and cholelithiasis risk was 1.19 (95% CI: 0.97–1.45), and the RR for HRT was 1.79 (95% CI: 1.61–2.00). Conclusion: The HRT was positively associated with the cholelithiasis risk, and the OC will not increase the risk of cholelithiasis. PMID:28383429

  7. Long circulating enzyme replacement therapy rescues bone pathology in mucopolysaccharidosis VII murine model.

    Science.gov (United States)

    Rowan, Daniel J; Tomatsu, Shunji; Grubb, Jeffrey H; Haupt, Bisong; Montaño, Adriana M; Oikawa, Hirotaka; Sosa, Angela C; Chen, Anping; Sly, William S

    2012-09-01

    Mucopolysaccharidosis (MPS) type VII is a lysosomal storage disease caused by deficiency of the lysosomal enzyme β-glucuronidase (GUS), leading to accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy (ERT) effectively clears GAG storage in the viscera. Recent studies showed that a chemically modified form of GUS (PerT-GUS), which escaped clearance by mannose 6-phosphate and mannose receptors and showed prolonged circulation, reduced CNS storage more effectively than native GUS. Clearance of storage in bone has been limited due to the avascularity of the growth plate. To evaluate the effectiveness of long-circulating PerT-GUS in reducing the skeletal pathology, we treated MPS VII mice for 12 weeks beginning at 5 weeks of age with PerT-GUS or native GUS and used micro-CT, radiographs, and quantitative histopathological analysis for assessment of bones. Micro-CT findings showed PerT-GUS treated mice had a significantly lower BMD. Histopathological analysis also showed reduced storage material and a more organized growth plate in PerT-GUS treated mice compared with native GUS treated mice. Long term treatment with PerT-GUS from birth up to 57 weeks also significantly improved bone lesions demonstrated by micro-CT, radiographs and quantitative histopathological assay. In conclusion, long-circulating PerT-GUS provides a significant impact to rescue of bone lesions and CNS involvement.

  8. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use.

    Science.gov (United States)

    McBride, J Abram; Coward, Robert M

    2016-01-01

    The use of testosterone replacement therapy (TRT) for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS) within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG) axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.

  9. Recovery of spermatogenesis following testosterone replacement therapy or anabolic-androgenic steroid use

    Directory of Open Access Journals (Sweden)

    J Abram McBride

    2016-01-01

    Full Text Available The use of testosterone replacement therapy (TRT for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.

  10. Disappearance of cerebral cortical atrophy following replacement therapy with vitamin B12 in an infant

    Directory of Open Access Journals (Sweden)

    Ebru Yilmaz Keskin

    2016-03-01

    Full Text Available Vitamin B12 (cobalamin deficiency during infancy is seen most commonly in exclusively breast-fed infants born to mothers with inadequate vitamin B12 stores. In addition to megaoblastic anemia, physical, social and neuromotor retardation may be seen in affected patients. In severe cases, thrombocytopenia and neutropenia may accompany anemia mimicking leukemia or aplastic anemia. Patients may rarely develop cerebral cortical atrophy evident on neuroimaging. In this article, a 12-month-old female infant with psychomotor developmental retardation who was referred to our hospital with the initial diagnosis of leukemia due to the finding of pancytopenia is presented. Further investigations revealed severe nutritional vitamin B12 deficiency in this case. Cranial magnetic resonance imaging (MRI showed cerebral cortical atrophy. Replacement therapy with vitamin B12 resulted in marked improvement of psychomotor status, and cranial MRI performed 7 months following the diagnosis and treatment initiation revealed resolution of cortical atrophy. [Cukurova Med J 2016; 41(1.000: 152-160

  11. 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

    2016-01-01

    Silicon nanopore membranes (SNMs) 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 (200 ml/min) and pressures (1,448 mm Hg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25 ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4 hours in an extracorporeal porcine model. The pressure drop across the flow cell was 4.6 mm Hg at 200 ml/min. Mechanical testing showed that SNM could withstand up to 775.7 mm Hg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extracorporeal 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 (CD41), respectively. These initial results warrant further design and development of a fully scaled SNM-based parallel plate dialyzer for renal replacement therapy.

  12. Continuous infusion of enzyme replacement therapy is inferior to weekly infusions in MPS I dogs.

    Science.gov (United States)

    Passage, M B; Krieger, A W; Peinovich, M C; Lester, T; Le, S Q; Dickson, P I; Kakkis, E D

    2009-12-01

    Intravenous enzyme replacement therapy with recombinant human α-L-iduronidase (rhIDU) is used weekly to treat mucopolysaccharidosis (MPS) I. We tested continuous administration of rhIDU at two dosing levels (0.58 mg/kg per week and 2 mg/kg per week) in MPS I dogs, and compared the efficacy of continuous infusion with the clinically used 0.58 mg/kg weekly three-hour infusion. Peak plasma concentrations of rhIDU were much higher in weekly-treated dogs (mean 256 units/ml) than steady-state concentrations in dogs treated with continuous infusion (mean 1.97 units/ml at 0.58 mg/kg per week; 8.44 units/ml at 2 mg/kg per week). Dogs receiving continuous IV rhIDU, even at a higher (2 mg/kg per week) dose, had consistently lower iduronidase levels in tissues than dogs receiving a weekly (0.58 mg/kg per week) dose. GAG storage was also less improved by continuous intravenous infusion. Adverse events were similar in all dosing groups. We found that continuous administration of 2 mg/kg per week rhIDU to MPS I dogs was insufficient to achieve GAG storage reduction comparable to 0.58 mg/kg weekly dosing.

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

    Science.gov (United States)

    Bhattacharya, Rajib K; Khera, Mohit; Blick, Gary; Kushner, Harvey; Miner, Martin M

    2012-01-01

    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. To compare data at baseline and after 12 months of testosterone replacement therapy (TRT) in hypogonadal men ≥65 vs 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. Of the registry participants at baseline with available age information, 16% (133/845) were ≥65 years old. They were similar to men 75-year-old subcohort were not significantly different from subcohorts aged 65-74 years and testosterone level regardless of age, and did not significantly increase PSA levels in older men.

  14. [Long-term outcomes of children treated with continuous renal replacement therapy].

    Science.gov (United States)

    Almarza, S; Bialobrzeska, K; Casellas, M M; Santiago, M J; López-Herce, J; Toledo, B; Carrillo, Á

    2015-12-01

    The objective of this study is to analyze long-term outcomes and kidney function in children requiring continuous renal replacement therapy (CRRT) after an acute kidney injury episode. A retrospective observational study was performed using a prospective database of 128 patients who required CRRT admitted to the pediatric intensive care unit between years 2006 and 2012. The subsequent outcomes were assessed in those surviving at hospital discharge. Of the 128 children who required RRT in the pediatric intensive care unit, 71 survived at hospital discharge (54.4%), of whom 66 (92.9%) were followed up. Three patients had chronic renal failure prior to admission to the NICU. Of the 63 remaining patients, 6 had prolonged or relapses of renal function disturbances, but only one patient with atypical Hemolytic Uremic Syndrome developed end-stage renal failure. The rest had normal kidney function at the last check-up. Most of surviving children that required CRRT have a positive outcome later on, presenting low mortality rates and recovery of kidney function in the medium term. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  15. Bench-to-bedside review: Citrate for continuous renal replacement therapy, from science to practice.

    Science.gov (United States)

    Oudemans-van Straaten, Heleen M; Ostermann, Marlies

    2012-12-07

    To prevent clotting in the extracorporeal circuit during continuous renal replacement therapy (CRRT) anticoagulation is required. Heparin is still the most commonly used anticoagulant. However, heparins increase the risk of bleeding, especially in critically ill patients. Evidence has accumulated that regional anticoagulation of the CRRT circuit with citrate is feasible and safe. Compared to heparin, citrate anticoagulation reduces the risk of bleeding and requirement for blood products, not only in patients with coagulopathy, but also in those without. Metabolic complications are largely prevented by the use of a strict protocol, comprehensive training and integrated citrate software. Recent studies indicate that citrate can even be used in patients with significant liver disease provided that monitoring is intensified and the dose is carefully adjusted. Since the citric acid cycle is oxygen dependent, patients at greatest risk of accumulation seem to be those with persistent lactic acidosis due to poor tissue perfusion. The use of citrate may also be associated with less inflammation due to hypocalcemia-induced suppression of intracellular signaling at the membrane and avoidance of heparin, which may have proinflammatory properties. Whether these beneficial effects increase patient survival needs to be confirmed. However, other benefits are the reason that citrate should become the first choice anticoagulant for CRRT provided that its safe use can be guaranteed.

  16. [Neuropathic Gaucher disease treated with long enzyme replacement therapy. Two clinical cases].

    Science.gov (United States)

    Correa, Cecilia

    2013-01-01

    Gaucher disease (GD) is the most common of all inherited lipid storage diseases. It is an autosomal recessive disorder portraying catabolism and cerebroside deposit in the lysosomes, which is due to a lack of glucocerebrosidase enzyme. Though GD shows a panethnic pattern of presentation, it particularly affects the Ashkenazi Jewish population. Several mutations have been defined among GD patients, and some genotypes related to neurologic affection have been described (L444P--most common mutation for neuropathic GD--188S, V394L and G377S). Lipid material storage or deposit exerts multiorganic affection. Enzyme replacement therapy (ERT) has demonstrable efficacy in reversing organic damage related to GD, though its capability to stop neurologic affection is currently under controversy and particular research. This paper portrays two GD cases of Mexican children treated with ERT at general zone hospitals of the Instituto Mexicano del Seguro Social in recent years, both of them depicting characteristic type 3 GD mutations, and comparing their clinical evolution with and without neurological features.

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

    Science.gov (United States)

    Kempke, Anna P; Leino, Abbie S; Daneshvar, Farzad; Lee, John Andrew; 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 data acquired from patients with acute and chronic kidney disease as well as healthy volunteers. These data and that obtained from drug package inserts were gathered for use in three published CRRT drug dosing equations. Doses calculated for a model patient using each method were compared to doses suggested in a commonly used dosing text. Results. Full pharmacokinetic data was available for 18, 31, and 40 agents using acute kidney injury, end stage renal disease, and normal patient data, respectively. On average, calculated doses differed by 30% or more from the doses recommended by the renal dosing text for >50% of the medications. Conclusion. Wide variability in dose recommendations for patients undergoing CRRT exists when these equations are used. Alternate, validated dosing methods need to be developed for this at-risk patient population.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Anna P. Kempke

    2016-01-01

    Full Text Available 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 data acquired from patients with acute and chronic kidney disease as well as healthy volunteers. These data and that obtained from drug package inserts were gathered for use in three published CRRT drug dosing equations. Doses calculated for a model patient using each method were compared to doses suggested in a commonly used dosing text. Results. Full pharmacokinetic data was available for 18, 31, and 40 agents using acute kidney injury, end stage renal disease, and normal patient data, respectively. On average, calculated doses differed by 30% or more from the doses recommended by the renal dosing text for >50% of the medications. Conclusion. Wide variability in dose recommendations for patients undergoing CRRT exists when these equations are used. Alternate, validated dosing methods need to be developed for this at-risk patient population.

  20. Experience with daptomycin daily dosing in ICU patients undergoing continuous renal replacement therapy.

    Science.gov (United States)

    Preiswerk, B; Rudiger, A; Fehr, J; Corti, N

    2013-04-01

    For critically ill patients undergoing continuous renal replacement therapy (CRRT), daptomycin dosing recommendations are scarce. We, therefore, retrospectively assessed routinely measured daptomycin plasma concentrations, daptomycin dose administered and microbiological data in 11 critically ill patients with Gram-positive infections that had received daptomycin once daily. The retrospective analysis included critically ill patients treated at the intensive care unit (ICU) who had daptomycin plasma concentrations measured. Daptomycin dose ranged from 3 to 8 mg/kg/q24 h in patients undergoing CRRT (n = 7) and 6 to 10 mg/kg/q24 h in patients without CRRT (n = 4). Peak and trough concentrations showed a high intra- and inter-patient variability in both groups, independent of the dosage per kg body weight. No drug accumulation was detected in CRRT patients with once-daily daptomycin dosing. Causative pathogens were Enterococcus faecium (n = 6), coagulase-negative Staphylococcus (n = 2), Staphylococcus aureus (n = 2) and unknown in one patient. Microbiological eradication was successful in 8 of 11 patients. Two of three patients with unsuccessful microbiological eradication and fatal outcome had an Enterococcus faecium infection. In critically ill patients undergoing CRRT, daptomycin exposure with once-daily dosing was similar to ICU patients with normal renal function, but lower compared to healthy volunteers. Our data suggest that daptomycin once-daily dosing is appropriate in patients undergoing CRRT.