			Home About us Contact

Mean Change (mean + change)

Distribution by Scientific Domains

Medical Sciences	90%
Mathematics and Statistics	3%
Life Sciences	3%

Distribution within Medical Sciences

Psychiatry	15%
Diabetes	7%
Neurology	5%
Geriatric Medicine	3%
23 Other Subdomains	70%

Selected Abstracts

Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorder

DEPRESSION AND ANXIETY, Issue 3 2009
Lenard A. Adler M.D.
Abstract Background: To evaluate the effect of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD) and comorbid social anxiety disorder in adults. Methods: Randomized, double-blind, placebo-controlled, conducted in adults with ADHD and social anxiety disorder. Patients received 40,100,mg ATX (n=224) or placebo (n=218) for 14 weeks following a 2-week placebo lead-in period. Efficacy measures included the Conners' Adult ADHD Rating Scale: Investigator-Rated: Screening Version (CAARS:Inv:SV), Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression-Overall-Severity (CGI-O-S), State-Trait Anxiety Inventory (STAI), Social Adjustment Scale-Self Report (SAS), and Adult ADHD Quality of Life Scale-29 (AAQoL). Safety and tolerability were also assessed. Results: ATX mean change (,8.7±10.0) from baseline (29.6±10.4) on CAARS:Inv:SV Total ADHD Symptoms score was significantly greater than placebo mean change (,5.6±10.2) from baseline (31.2±9.4; P<.001). ATX mean change (,22.9±25.3) from baseline (85.3±23.6) on LSAS Total score was significant compared to placebo mean change (,14.4±20.3) from baseline (82.1±21.3; P<.001). The visit-wise analysis revealed greater improvement on the CAARS:Inv:SV Total ADHD Symptoms score and LSAS Total score for ATX at every time point throughout the study (P values ,.012). Mean changes in CGI-O-S, STAI-Trait Anxiety scores, and AAQoL Total score were significantly greater for ATX compared to placebo. Mean change for both groups on STAI-State Anxiety scores was comparable. Improvement on SAS for ATX compared to placebo was not significant. Rates of insomnia, nausea, dry mouth, and dizziness were higher with ATX than with placebo. Discontinuation rates due to treatment-emergent adverse events were similar between groups. Conclusions: ATX monotherapy effectively improved symptoms of ADHD and comorbid social anxiety disorder in adults and was well tolerated. Depression and Anxiety, 2009. Published 2009 Wiley-Liss, Inc. [source]

Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trials

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2005
James I. Hudson
Abstract Objective To examine the safety and tolerability of the antidepressant duloxetine across multiple studies for major depressive disorder (MDD). Method Safety data were integrated from the acute phases of eight double-blind, placebo-controlled trials in which patients were randomized to duloxetine (40,120,mg/d; n,=,1139) or placebo (n,=,777) for up to 9 weeks. This data set included all acute-phase clinical trials that formed the basis of the New Drug Application (United States) or European Union submission package for duloxetine in the treatment of MDD. Two studies included continuation phases in which acute treatment responders received duloxetine or placebo for an additional 26 weeks. Safety assessments included serious adverse event reports, rates of discontinuation, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory values, and electrocardiograms. Results The rates of serious adverse events for duloxetine- and placebo-treated patients were 0.3% and 0.6%, respectively (p,=,0.282). Adverse events led to discontinuation in 9.7% of duloxetine-treated patients, compared with 4.2% of patients receiving placebo (p,<,0.001). Treatment-emergent adverse events with an incidence for duloxetine ,,5.0% and significantly greater than placebo were nausea, dry mouth, constipation, insomnia, dizziness, fatigue, somnolence, increased sweating and decreased appetite. Mean changes in blood pressure and heart rate were small, and the incidence of increases above normal ranges was low. Duloxetine-treated patients had a mean decrease in weight of 0.5,kg compared with an increase of 0.2,kg for patients receiving placebo (p,<,0.001). No significant differences were found between duloxetine and placebo in the incidence of potentially clinically significant laboratory values at anytime while on treatment. Conclusion These results are consistent with those obtained previously from smaller pooled data sets, and suggest that duloxetine is safe and well tolerated in patients with MDD. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Botulinum neurotoxins for post-stroke spasticity in adults: A systematic review,,

MOVEMENT DISORDERS, Issue 6 2009
Antonio Emanuele Elia MD
Abstract The aim of this systematic review was to determine whether botulinum neurotoxin (BoNT) reduce spasticity or improve function in adult patients after stroke. Eleven double-blind randomized placebo-controlled trials met inclusion criteria. They encompassed 782 patients, 767 (98%) of whom received BoNT/A, and 15 (2%) BoNT/B. Most studies used the Ashworth scale as primary outcome measure. Differences between treated and control groups were assessed as categorical or continuous comparisons. The overall effect on upper limb spasticity was in favor of BoNT/A. A significantly higher number of patients had a reduction of upper limb spasticity at 4-week and 8-week evaluations in the treatment group compared with placebo. Mean changes in joint spasticity revealed improvement 3 to 6 weeks and 9 to 12 weeks after treatment. There were insufficient data to establish BoNT/A efficacy on lower limb spasticity or the effect of BoNT/B on the upper and lower limbs. Because of inconsistency and heterogeneity of the available data, it was not possible to perform a meta-analysis on disability and patients' reported outcomes. There was an overlapping safety profile between the treatment and the placebo groups. BoNT/A reduces upper limb spasticity in patients post-stroke, but the improvement in functional ability remains to be established. This gap needs to be filled by new studies to assess the effect of BoNT in the context of multidisciplinary patient management. © 2009 Movement Disorder Society [source]

Anti-androgens increase N-terminal pro-BNP levels in men with prostate cancer

CLINICAL ENDOCRINOLOGY, Issue 1 2008
Frances Dockery
Summary Objective, The aim of this study was to determine the effects of anti-androgens on left ventricular (LV) function and levels of N-terminal proB-type natriuretic peptide (NT-proBNP), a sensitive cardiac risk marker, in men with prostate cancer as these are widely used drugs in this condition, and evidence suggests that endogenous androgens are cardioprotective in men. Design and patients, Forty-three men (mean age 70·7 ± 6·2 years) with prostate cancer were randomized to goserelin (an LH-releasing hormone analogue) or bicalutamide (an androgen-receptor blocker) for 6 months; 20 men with a history of prostate cancer on no treatment were studied in parallel. Results, Mean changes in testosterone and oestradiol, respectively, from baseline to 6 months were ,88% and ,46% with goserelin, +50% and +44% with bicalutamide, and ,1% and ,9% for the ,no-treatment' group. Bicalutamide significantly increased NT-proBNP from baseline to 3 and 6 months (median value at baseline, 3 and 6 months: 55, 101 and 118 ng/l, respectively). Goserelin caused a significant increase from baseline to 3 months but not to 6 months (median value at baseline, 3 and 6 months: 66, 87 and 72 ng/l, respectively). No significant changes occurred in the ,no-treatment' cohort (median value at baseline 3 and 6 months: 60, 53 and 60 ng/l, respectively). No significant changes in LV function, blood pressure (BP), body mass index or waist,hip ratio occurred to account for the changes in NT-proBNP. Conclusion, Androgen receptor blockade and, to a lesser extent, androgen suppression cause an increase in NT-pro-BNP in men with prostate cancer. The significance is not clear but could imply an adverse effect on cardiovascular risk following hormonal manipulation. [source]

Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder,

DEPRESSION AND ANXIETY, Issue 5 2010
Vladimir Coric M.D.
Abstract Background: Antagonism of corticotropin-releasing factor (CRF) receptors has been hypothesized as a potential target for the development of novel anxiolytics. This study was designed to determine the safety and efficacy of pexacerfont, a selective CRF-1 receptor antagonist, in the treatment of generalized anxiety disorder (GAD). Method: This was a multicenter, randomized, double-blind, placebo-controlled and active comparator trial. Two hundred and sixty patients were randomly assigned to pexacerfont 100,mg/day (after a 1 week loading dose of 300,mg/day), placebo or escitalopram 20,mg/day in a 2:2:1 ratio. The primary outcome was the mean change from baseline to end point (week 8) in the Hamilton Anxiety Scale total score. Results: Pexacerfont 100,mg/day did not separate from placebo on the primary outcome measure. The half-powered active comparator arm, escitalopram 20,mg/day, demonstrated efficacy with significant separation from placebo at weeks 1, 2, 3, 6, and 8 (P<.02). Response rates for pexacerfont, placebo, and escitalopram were 42, 42, and 53%, respectively. Genetic and psychometric rating scale data was obtained in 175 randomized subjects. There was a significant association between a single nucleotide polymorphism (SNP) of the gene encoding plexin A2 (PLXNA2-2016) with the HAM-A psychic subscale score for the entire cohort at baseline (FDR-adjusted P=.015). Conclusions: Pexacerfont did not demonstrate efficacy compared to placebo for the treatment of GAD. Whether these findings are generalizable to this class of agents remains to be determined. Our preliminary genetic finding of an association between a SNP for the gene encoding plexin A2 and an anxiety phenotype in this study merits further exploration. The trial was registered at clinicaltrials.gov (NCT00481325) before enrollment. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [source]

Atomoxetine treatment in adults with attention-deficit/hyperactivity disorder and comorbid social anxiety disorder

Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial

DEPRESSION AND ANXIETY, Issue 3 2008
Moira Rynn M.D.
Abstract Generalized anxiety disorder (GAD), a prevalent and chronic illness, is associated with dysregulation in both serotonergic and noradrenergic neurotransmission. Our study examined the efficacy, safety, and tolerability of duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, for short-term treatment of adults with GAD. In a 10-week, double-blind, progressive-titration, flexible-dose trial, 327 adult outpatients with a DSM-IV,defined GAD diagnosis were randomized to duloxetine 60,120,mg (DLX, N=168) or placebo (PLA, N=159) treatment. The primary efficacy measure was mean change from baseline to endpoint in Hamilton Anxiety Scale (HAMA) total score. Secondary outcome measures included response rate (HAMA total score reduction ,50% from baseline), Clinician Global Impression,Improvement (CGI-I) scores, and Sheehan Disability Scale (SDS) scores. Patients who received duloxetine treatment demonstrated significantly greater improvement in HAMA total scores (P=.02); a higher response rate (P=.03), and greater improvement (P=.04) than patients who received placebo. Duloxetine-treated patients were also significantly more improved than placebo-treated patients on SDS global functional (P<.01) and work, social, and family/home impairment scores (P<.05). The rate of discontinuation due to adverse events (AEs) was higher for the duloxetine group compared with the placebo group (P=.002). The AEs most frequently associated with duloxetine were nausea, dizziness, and somnolence. Duloxetine was an efficacious, safe, and well-tolerated treatment that resulted in clinically significant improvements in symptom severity and functioning for patients with GAD. Depression and Anxiety 0:1,8, 2007. © 2007 Wiley-Liss, Inc. [source]

Robust improvements in fasting and prandial measures of ,-cell function with vildagliptin in drug-naïve patients: analysis of pooled vildagliptin monotherapy database

DIABETES OBESITY & METABOLISM, Issue 10 2008
R. E. Pratley
Aim:, To assess the effects of 24-week treatment with vildagliptin on measures of ,-cell function in a broad spectrum of drug-naïve patients with type 2 diabetes (T2DM). Methods:, Data from all double-blind, multicentre, randomized, placebo- or active-controlled trials conducted in drug-naïve patients with T2DM were pooled from all patients receiving monotherapy with vildagliptin (100 mg daily: 50 mg twice daily or 100 mg once daily, n = 1855) or placebo (n = 347). Fasting measures of ,-cell function [homeostasis model assessment of ,-cell function (HOMA-B) and proinsulin : insulin ratio] were assessed in the overall pooled monotherapy population. Standard meal tests were performed at baseline and week 24 in a subset of patients, and effects of vildagliptin (100 mg daily, n = 227) on dynamic (meal test,derived) measures of ,-cell function [insulin secretion rate relative to glucose (ISR/G) and insulinogenic indices] were assessed relative to baseline and vs. placebo (n = 29). Results:, In the overall population, vildagliptin significantly increased HOMA-B both relative to baseline [adjusted mean change (AM,) = 10.3 ± 1.5] and vs. placebo (between-treatment difference in AM, = 11.5 ± 4.5, p = 0.01) and significantly decreased the proinsulin : insulin ratio relative to baseline (AM, = ,0.05 ± 0.01) and vs. placebo (between-treatment difference in AM, = ,0.09 ± 0.02, p < 0.001). Relative to baseline, vildagliptin monotherapy significantly increased all meal test,derived parameters, and ISR/G (between-treatment difference in AM, = 9.8 ± 2.8 pmol/min/m2/mM, p < 0.001) and the insulinogenic index0,peak glucose (between-treatment difference in AM, = 0.24 ± 0.05 pmol/mmol, p = 0.045) were significantly increased vs. placebo. Conclusions:, Vildagliptin monotherapy consistently produced robust improvements in both fasting and meal test,derived measures of ,-cell function across a broad spectrum of drug-naïve patients with T2DM. All Phase III trials described (NCT 00099905, NCT 00099866, NCT 00099918, NCT 00101673, NCT 00101803 and NCT 00120536) are registered with ClinicalTrials.gov. [source]

,-Blocker use and diabetes symptom score: results from the GEMINI study

DIABETES OBESITY & METABOLISM, Issue 3 2007
J. B. McGill
Aim:, The Glycemic Effect in Diabetes Mellitus: Carvedilol,Metoprolol Comparison in Hypertensives (GEMINI) trial compared the metabolic effects of two ,-blockers in people with type 2 diabetes and hypertension treated with renin,angiotensin system (RAS) blockade and found differences in metabolic outcomes. In this paper, we report the results of a prespecified secondary analysis of GEMINI that sought to determine the effect of these two ,-blockers on commonly reported symptoms. Methods:, The Diabetes Symptom Checklist (DSC), a self-report questionnaire measuring the occurrence and perceived burden of diabetes-related symptoms, was completed by GEMINI participants at baseline and at the end of the study (maintenance month 5). The DSC assessed symptoms in eight domains: psychology (fatigue), psychology (cognitive), neuropathy (pain), neuropathy (sensory), cardiology, ophthalmology, hyperglycaemia and hypoglycaemia. Results:, Comparison of the mean change in self-reported diabetes-related symptoms indicated a significant treatment difference favouring carvedilol over metoprolol tartrate in overall symptom score (,0.08; 95% CI ,0.15, ,0.01; p = 0.02) and in the domains for hypoglycaemia symptoms (,0.12; 95% CI ,0.23, ,0.02; p = 0.02) and hyperglycaemia symptoms (,0.16; 95% CI ,0.27, ,0.05; p = 0.005). Carvedilol resulted in fewer perceived diabetes-related symptoms in patients with diabetes and hypertension. Conclusion:, Carvedilol resulted in a lower perceived burden of diabetes-related symptoms in patients with type 2 diabetes and hypertension. The addition of a well-tolerated ,-blocker to RAS blockade may improve hypertension treatment and quality of life in patients with diabetes. [source]

No significant effect of uridine or pravastatin treatment for HIV lipoatrophy in men who have ceased thymidine analogue nucleoside reverse transcriptase inhibitor therapy: a randomized trial,

HIV MEDICINE, Issue 8 2010
A Calmy
Background Lipoatrophy can complicate thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI)-based antiretroviral therapy (ART). Lipoatrophy may be less likely with ART including ritonavir-boosted lopinavir (LPV/r). Small, placebo-controlled studies found that uridine (in tNRTI recipients) and pravastatin improved HIV lipoatrophy over 12 weeks. Today, most patients with lipoatrophy receive non-tNRTI-based ART; the effect of uridine in such patients is unknown. Methods We performed a prospective, randomized trial in lipoatrophic adults with plasma HIV RNA<50 HIV-1 RNA copies/mL on tNRTI-sparing ART including LPV/r. Patients received uridine [36 g three times a day (tid) on 10 consecutive days per month; n=10], pravastatin [40 mg every night (nocte); n=12], uridine plus pravastatin (n=11) or neither (n=12) for 24 weeks. The primary endpoint was mean change in limb fat mass as assessed by dual-energy X-ray absorptiometry (DEXA). With 20 patients per intervention, the study had 80% power to detect a mean difference between a treatment and the control of 0.5 kg, assuming a standard deviation of 0.9 and an alpha threshold equal to 5% (two-sided). Results Of 45 participants (all men, with median age 49.5 years and median limb fat 2.6 kg), two discontinued pravastatin and one participant stopped both pravastatin and uridine. The difference between the mean changes in limb fat mass for uridine vs. no uridine was 0.03 kg [95% confidence interval (CI) ,0.35, +0.28; P=0.79]. The respective difference for pravastatin was ,0.03 kg (95% CI ,0.29, +0.34; P=0.84). Pravastatin slightly decreased total cholesterol (0.44 mmol/L; P=0.099). Visceral adipose tissue measured by computed tomography did not change significantly. Conclusion In this population and at the doses used, neither uridine nor pravastatin for 24 weeks significantly increased limb fat mass. [source]

Effects of memantine on cognition in patients with moderate to severe Alzheimer's disease: post-hoc analyses of ADAS-cog and SIB total and single-item scores from six randomized, double-blind, placebo-controlled studies

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2009
Patrizia Mecocci
Abstract Objectives The post-hoc analyses reported here evaluate the specific effects of memantine treatment on ADAS-cog single-items or SIB subscales for patients with moderate to severe AD. Methods Data from six multicentre, randomised, placebo-controlled, parallel-group, double-blind, 6-month studies were used as the basis for these post-hoc analyses. All patients with a Mini-Mental State Examination (MMSE) score of less than 20 were included. Analyses of patients with moderate AD (MMSE: 10,19), evaluated with the Alzheimer's disease Assessment Scale (ADAS-cog) and analyses of patients with moderate to severe AD (MMSE: 3,14), evaluated using the Severe Impairment Battery (SIB), were performed separately. Results The mean change from baseline showed a significant benefit of memantine treatment on both the ADAS-cog (p,<,0.01) and the SIB (p,<,0.001) total score at study end. The ADAS-cog single-item analyses showed significant benefits of memantine treatment, compared to placebo, for mean change from baseline for commands (p,<,0.001), ideational praxis (p,<,0.05), orientation (p,<,0.01), comprehension (p,<,0.05), and remembering test instructions (p,<,0.05) for observed cases (OC). The SIB subscale analyses showed significant benefits of memantine, compared to placebo, for mean change from baseline for language (p,<,0.05), memory (p,<,0.05), orientation (p,<,0.01), praxis (p,<,0.001), and visuospatial ability (p,<,0.01) for OC. Conclusion Memantine shows significant benefits on overall cognitive abilities as well as on specific key cognitive domains for patients with moderate to severe AD. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Randomized, Placebo-Controlled Trial of the Cognitive Effect, Safety, and Tolerability of Oral Extended-Release Oxybutynin in Cognitively Impaired Nursing Home Residents with Urge Urinary Incontinence

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2008
Thomas E. Lackner PharmD
OBJECTIVES: Determine the cognitive effect, safety, and tolerability of oral extended-release oxybutynin in cognitively impaired older nursing home residents with urge urinary incontinence. DESIGN: Randomized, double-blinded, placebo-controlled trial. SETTING: Twelve skilled nursing homes. PARTICIPANTS: Fifty women aged 65 and older with urge incontinence and cognitive impairment. INTERVENTION: Four-week treatment with once-daily oral extended-release oxybutynin 5 mg or placebo. MEASUREMENTS: Withdrawal rates and delirium or change in cognition from baseline at 1, 3, 7, 14, 21, and 28 days after starting treatment using the Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and Severe Impairment Battery (SIB). The Brief Agitation Rating Scale, adverse events, falls incidence, and serum anticholinergic activity change with treatment were also assessed. RESULTS: Participants' mean age ±standard deviation was 88.6±6.2, and MMSE baseline score was 14.5±4.3. Ninety-six percent of subjects receiving oxybutynin (n=26) and 92% receiving placebo (n=24) completed treatment (P=.50). The differences in mean change in CAM score from baseline to all time points were equivalent between the oxybutynin and placebo groups. Delirium did not occur in either group. One participant receiving oxybutynin was withdrawn because of urinary retention, which resolved without treatment. Mild adverse events occurred in 38.5% of participants receiving oxybutynin and 37.5% receiving placebo (P=.94). CONCLUSION: Short-term treatment using oral extended-release oxybutynin 5 mg once daily was safe and well tolerated, with no delirium, in older female nursing home participants with mild to severe dementia. Future research should investigate different dosages and long-term treatment. [source]

A Single-Dose Placebo-Controlled Study of AMG 162, a Fully Human Monoclonal Antibody to RANKL, in Postmenopausal Women

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2004
Pirow J Bekker
Abstract The safety and bone antiresorptive effect of a single subcutaneous dose of AMG 162, a human monoclonal antibody to RANKL, was investigated in 49 postmenopausal women. AMG 162 is a potent antiresorptive agent for diseases such as osteoporosis. Introduction: RANKL is an essential osteoclastic differentiation and activation factor. Materials and Methods: The bone antiresorptive activity and safety of AMG 162, a fully human monoclonal antibody to RANKL, were evaluated in postmenopausal women in this randomized, double-blind, placebo-controlled, single-dose, dose escalation study. Six cohorts of eight to nine women were randomly assigned to receive a single subcutaneous injection of either AMG 162 or placebo (3:1 ratio). AMG 162 doses were 0.01, 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg. Subjects were followed up to 6 months in all cohorts and 9 months in the three highest dose cohorts. Second morning void urinary N-telopeptide/creatinine (NTX; Osteomark), serum NTX, and serum bone-specific alkaline phosphatase (BALP, Ostase) were assessed as bone turnover markers. Results and Conclusions: Forty-nine women were enrolled. A single subcutaneous dose of AMG 162 resulted in a dose-dependent, rapid (within 12 h), profound (up to 84%), and sustained (up to 6 months) decrease in urinary NTX. At 6 months, there was a mean change from baseline of ,81% in the 3.0 mg/kg AMG 162 group compared with ,10% in the placebo group; serum NTX changes were ,56% and 2%, respectively. BALP levels did not decrease remarkably until after 1 month, indicating that the effect of AMG 162 is primarily antiresorptive. Intact parathyroid hormone (PTH) levels increased up to ,3-fold after 4 days in the 3.0 mg/kg dose group, but returned toward baseline with follow-up. Albumin-adjusted serum calcium did not decrease >10% on average in any group, and no subject had values below 2 mmol/liter. AMG 162 was well tolerated. No related serious adverse events occurred. No clinically meaningful laboratory changes, other than those described above, were observed. In summary, a single subcutaneous dose of AMG 162 resulted in a dose-dependent rapid and sustained decrease from baseline in bone turnover and could be an effective and convenient treatment for osteoporosis. [source]

Efficacy of progressive muscle relaxation training in reducing anxiety in patients with acute schizophrenia

JOURNAL OF CLINICAL NURSING, Issue 15 2009
Wen-Chun Chen
Aim and objectives., The objective of this study was to examine the efficacy of progressive muscle relaxation training on anxiety in patients with acute schizophrenia. Background., Many empirical studies have found progressive muscle relaxation training beneficial in reducing the psychological effects of anxiety. Progressive muscle relaxation training is also effective in reducing the distress symptoms associated with the symptomatology of schizophrenia. Design., An experimental randomised controlled trial using repeated measures. Method., The study was designed to examine the effects of progressive muscle relaxation training on patients diagnosed with schizophrenia. Study participants were acute psychiatric inpatients in Taiwan. Eighteen patients were block randomised and then assigned to an experimental or control group. The experimental group received progressive muscle relaxation training and the control group received a placebo intervention. Results from the Beck anxiety inventory were compared between groups as a pretest before intervention, on day 11 of intervention and one week post-test after the intervention was completed. Changes in finger temperature were measured throughout the experiment. Results., The degree of anxiety improvement was significantly higher in the progressive muscle relaxation training group than in the control group after progressive muscle relaxation training intervention (p < 0·0001) and at follow-up (p = 0·0446; the mean BAI score fell from 16·4 pretest to ,5·8 post-test. After adjusting for the change in patient finger temperature, the mean change in temperature was significantly different between the two patient groups. The average body temperature increased significantly after applying the progressive muscle relaxation training to patients with schizophrenia. Conclusion., This study demonstrated that progressive muscle relaxation training can effectively alleviate anxiety in patients with schizophrenia. Relevance to clinical practice., Progressive muscle relaxation training is potentially an effective nursing intervention in the reduction of anxiety in patients diagnosed with schizophrenia, depending on the quality of their mental status at the time of intervention. Progressive muscle relaxation training is a useful intervention as it is proven to reduce anxiety levels across a spectrum of psychiatric disorders. [source]

Clinical effects of a new mouthrinse containing chlorhexidine, cetylpyridinium chloride and zinc-lactate on oral halitosis

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2003
A dual-center, double-blind placebo-controlled study
Abstract Objectives:, The aim of this double-blind, parallel study was to test the clinical efficacy of a newly developed mouthrinse in the treatment of oral halitosis in patients without periodontitis. Material and methods:, Forty volunteers, recruited in two centers, participated in this study. Patients were selected on the basis of (1) halitosis of oral origin, (2) full-mouth organoleptic score>1, using an arbitrary 0,5 scale, (3) level of volatile sulfur compounds (VSC)>170 parts per billion (ppb) and (4) Winkel tongue coating index (WTCI)>4 (0,12). Intervention included gargling with a mouthrinse containing chlorhexidine (0.05%), cetylpyridinium chloride (0.05%) and zinc-lactate (0.14%) or with a placebo mouthrinse without active ingredients. At days 0 and 14 clinical variables were assessed in order of performance: (1) organoleptic assessments, (2) levels of VSC, and (3) WTCI. Results:, Treatment with the active mouthrinse resulted in a significant mean reduction in the organoleptic score from 2.8 to 1.5 (p<0.005). In the placebo group, no significant reduction in the mean organoleptic score occurred. Consequently, this resulted, after 2 weeks, in a greater change of the organoleptic scores in the test group in comparison to the placebo group (p<0.005). The mean VSC scores were reduced from 292 to 172 ppb in the test group (p<0.005), whereas no reduction was observed in the placebo group. At the 2-week examination, the mean change of the VSC scores in the test group was significantly greater than the mean change in the placebo group (p<0.005). Neither in the test nor in the placebo group a significant reduction in tongue coating was observed. Conclusions:, In conclusion, the tested mouthrinse is effective in the treatment of oral halitosis. Zusammenfassung Klinischer Effekt einer neuartigen Chlorhexidin, Cetylpyridiniumchlorid und Zinklaktat enthaltenden Mundspüllösung auf Mundgeruch. Eine bizentrische plazebokontrollierte Doppelblindstudie Zielsetzung: Untersuchung der klinischen Wirksamkeit einer neu entwickelten Mundspüllösung für die Behandlung von Mundgeruch bei Patienten, die keine Parodontitis haben, mittels einer parallelarmigen Doppelblindstudie. Material und Methoden: 40 Freiwillige, die an 2 Zentren rekrutiert wurden, nahmen an dieser Studie teil. Die Patienten wurden nach folgenden Kriterien ausgewählt: 1) Mundgeruch, 2) organoleptischer Wert der gesamten Mundhöhle > 1 auf einer arbiträren Skala von 0 bis 5, 3) Spiegel flüchtiger Schwefelverbindungen (VSC) > 170 parts per billion (ppb), 4) Winkel Zungenbelagsindex (WTCI) > 4 (0-12). Die Therapie umfasste Gurgeln mit einer Mundspüllösung, die Chlorhexidin (0,05%), Cetylpyridiniumchlorid (0,05%) und Zinklaktat (0.14%) enthielt oder mit einer Plazebospüllösung, die keine aktiven Bestandteile aufwies. Am Tag 0 und 14 wurden klinische Parameter in folgender Reihenfolge erhoben: 1) organoleptische Messungen, 2) VSC-Spiegel, 3) WTCI. Ergebnisse: Die Behandlung mit der aktiven Spüllösung resultierte in einer signifikanten mittleren Reduktion des organoleptischen Werts von 2,8 auf 1,5 (p<0,005), während in der Plazebogruppe keine signifikante Verringerung des mittleren organoleptischen Werts beobachtet wurde. Konsequenterweise ergab sich nach 2 Wochen in der Testgruppe eine stärkere Veränderung des organoleptischen Werts als in der Plazebogruppe (p<0,005). Der mittlere VSC-Wert wurde in der Testgruppe von 292 auf 172 ppb reduziert (p<0,005), während in der Plazebogruppe keine Veränderung auftrat. Nach 2 Wochen wurde in der Testgruppe eine signifikant stärkere Veränderung des VSC-Werts beobachtet als in der Kontrollgruppe (p<0,005). Weder in der Test- noch in der Plazebogruppe wurde eine signifikante Reduktion des Zungenbelags beobachtet. Schlussfolgerung: Die untersuchte Mundspüllösung ist wirksam zur Behandlung von Mundgeruch. Résumé Effets cliniques d'un nouveau bain de bouche contenant de la chlorhexidine, du chlorure de cetylpyridinium et du lactate de zinc sur l'halitose buccale. Une étude bi-centrique contrôlée par placebo en double aveugle. Objectifs: Le but de cette étude bi-centrique en double aveugle en parallèle était de tester l'efficacité clinique d'un bain de bouche récemment développé pour le traitement de l'halitose buccale sans parodontite. Matériel & Méthodes: 40 volontaires recrutés dans deux centres ont participéà cette étude. Les patients ont été sélectionnés sur les critères suivants : 1) halitose d'origine buccale, 2) score organoleptique de la bouche complète > 1, en utilisant une échelle arbitraire allant de 0 à 5, 3) un niveau de composés volatiles sulfurés (VSC) > 170 portions par billion (ppb) 4) un indice de recouvrement de la langue de Winkel (WTCI) > 4 (0,12). L'intervention comprenait un gargarisme avec un bain de bouche contenant de la chlorhexidine (0.05%), du chlorure de cetylpyridinium (0.05%) et du lactate de zinc (0.14%) ou avec un placebo sans ingrédients actifs. Au jours 0 et 14 les paramètres cliniques furent relevés pour l'ordre d'exécution 1) estimation organoleptique 2)niveaux de VSC, 3) WTCI. Résultats: le traitement avec le bain de bouche actif résultait en une réduction moyenne significative du score organoleptique de 2.8 à 1.5 (p < 0.005). Dans le groupe placebo, aucune réduction significative du score moyen organoleptique n'était par contre relevée. En consequence, ceci impliquait après 2 semaines un changement plus grand des scores organoleptiques dans le groupe test par rapport par rapport au groupe placebo (p < 0.005). Les scores moyens de VSC étaient réduits de 292 à 172 ppb dans le groupe test (p < 0.005), alors qu'aucune diminution n'était observée dans le groupe placebo. Lors de l'examen à 2 semaines, le changement moyen des scores de VSC dans le groupe test était significativement plus importants que le changement moyen dans le groupe placebo. (p < 0.005). Aucune réduction significative du recouvrement de la langue n'était par contre observée, ni dans le groupe test, ni dans le groupe placebo. Conclusions: En conclusion, Le bain de bouche testé est efficace pour le traitement de l'halitose. [source]

Altered Thyroid Hormones and Behavioural Change in a Sub-Population of Rats Following Chronic Constriction Injury

JOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2010
E. Kilburn-Watt
Hypothyroidism is associated with a disturbance of behaviour and mood. There are also individuals, not classified as hypothyroid, with low to ,low normal' thyroid hormone levels and normal thyroid-stimulating hormone (TSH) levels who have mood and behavioural changes. As the peripheral thyroid hormones decrease, TSH is expected to increase. However, there are a number of physiological mechanisms known to suppress TSH. In the present study, we report on thyroid hormone regulation in a rat model of neuropathic pain and altered social behaviour that is usually transient, but is persistent in a sub-group of the population. Following ligation of the sciatic nerve, male Sprague-Dawley rats were assessed for social dominance towards an intruder: 20% showed persistently decreased social dominance. Plasma levels of thyroid hormones, TSH and corticosterone were measured before and on days 2, 3, 4, 5 and 6 after injury in 21 rats. The mean plasma thyroxine (T4), free thyroxine (fT4) and triiodothyronine (T3) levels decreased significantly post-injury in rats with persistently changed behaviour compared to rats with unchanged behaviour (P , 0.002). There was no significant difference between groups for mean change in free triiodothyronine (fT3) or TSH. There was a correlation between decreased dominance behaviour and decrease in both T4 (r = 0.62, P = 0.009) and fT4 (r = 0.71, P = 0.001), but no correlation with TSH. In a sub-population of rats, decreased thyroid hormones did not result in the expected increased levels of TSH to restore pre-injury levels, nor did they show increased hypothalamic thyrotrophin-releasing hormone mRNA expression, indicating altered hypothalamic-pituitary-thyroid axis regulation. Because T3 availability to the brain is dependent on both circulating T3 and T4, decreased peripheral thyroid hormones may result in changed neural function, as expressed in altered complex behaviours in this sub-population of rats. [source]

A Double-Blind, Placebo-Controlled Study With Quetiapine as Adjunct Therapy With Lithium or Divalproex in Bipolar I Patients With Coexisting Alcohol Dependence

ALCOHOLISM, Issue 10 2010
Mary Stedman
Background:, This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence. Methods:, Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12-week, placebo-controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions-Severity of Illness score. Results:, Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was ,0.36 with quetiapine and ,0.36 with placebo (p = 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine. Conclusions:, The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence. [source]

Dopaminergic Neurons in the Ventral Tegmental Area of C57BL/6J and DBA/2J Mice Differ in Sensitivity to Ethanol Excitation

ALCOHOLISM, Issue 7 2000
Mark S. Brodie
Background: The mesolimbic dopamine pathway that originates in the ventral tegmental area (VTA) is important for the rewarding effects of ethanol. Ethanol has been shown to excite dopaminergic neurons of the VTA, both in vivo and in vitro, in rats. Behavioral differences in the rewarding effects of ethanol have been observed between C57BL/6J and DBA/2J mice. The present electrophysiological study examined the effect of ethanol on individual dopaminergic VTA neurons from these two inbred mouse strains. Methods: Extracellular single unit recordings of spontaneous action potentials were made from dopaminergic VTA neurons in brain slices from either C57BL/6J or DBA/2J mice. Ethanol (10 to 160 mM) was administered in the superfusate and the mean change in firing rate produced by ethanol was measured. Results: There was no significant difference in basal spontaneous firing rate of dopaminergic VTA neurons between these two mouse strains. Ethanol caused a concentration-dependent increase in the firing rate of neurons from both mouse strains. Ethanol excited dopaminergic VTA neurons from DBA/2J mice more potently than those from C57BL/6J mice. Conclusions: The difference in sensitivity to ethanol excitation of dopaminergic VTA neurons in C57BL/6J and DBA/2J mice may contribute to differences in their behavioral response to ethanol. The fact that a given concentration of ethanol causes greater excitation of dopaminergic VTA (reward) neurons in DBA/2J mice than in C57BL/6J mice could explain why DBA/2J mice show much stronger place preference conditioning with ethanol. The higher voluntary intake of ethanol by C57BL/6J mice may be partly due to the insensitivity of their dopaminergic VTA neurons that requires them to drink a lot of ethanol to achieve sufficient excitation of reward neurons, whereas DBA/2J mice avoid oral ingestion of ethanol, despite its rewarding effect, because of their aversion to its taste. [source]

Reproducibility of Airway Responsiveness in Horses Using Flowmetric Plethysmography and Histamine Bronchoprovocation

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009
R. D. Nolen-Walston
Background: Inflammatory airway disease has a high prevalence in horses, but is often a diagnostic challenge. Flowmetric plethysmography and histamine bronchoprovocation (FP/HBP) is a simple and effective tool for diagnosis, but reproducibility of these measurements made over time has not been established. Hypothesis: We hypothesize that the measurement of airway responsiveness in horses using FP/HBP is consistent over both short and long periods of time. Animals: Twenty-nine healthy adult horses from 2 university herds. Methods: In this prospective experimental study, airway responsiveness was determined in each horse at day 0 (baseline [BL]) with FP/ HBP, using PC35 (provocative concentration of histamine needed to increase ,flow by 35%) as a measure of airway responsiveness. Each horse was re-tested 1,4 weeks after BL (short-term [ST]) and again at 3,12 months after BL (long-term [LT]). Results: In the ST period, 23/27 (85%) of the horses had a PC35 that was within 1 doubling concentration of histamine of their BL value, with a mean change of 0.52 doubling concentrations (95% CI 0.26,0.79, range 0,2.06). For the LT data, 19/26 (73%) of horses were within 1 doubling concentration of their BL value, with a mean change of 0.81 doubling concentrations (95% CI 0.45,1.17, range 0.14,3.10). There was no significant difference in reproducibility between the 2 groups of subjects. Conclusions and Clinical Importance: Repeated measurements of airway responsiveness obtained with FP/HBP show acceptable reproducibility over time periods up to a year. However, caution must be used when testing horses when ambient air temperature is low. [source]

Treatment of essential tremor with the barbiturate t2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid)

MOVEMENT DISORDERS, Issue 5 2007
Calvin Melmed MD
Abstract The effect of the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid; DMMDPB) on essential tremor, given in twice daily doses of 400 and 300 mg, was assessed in two brief, randomized, placebo-controlled, parallel-group, double-blinded, single-center trials in 12 and 22 patients, respectively. These trials represent the first clinical use of T2000 for a specific indication. The primary endpoint was the change in the mean scores of the treated and control groups based on the Fahn-Tolosa-Marin tremor scale. In the first study of 12 patients treated with 400 mg or placebo twice daily for 14 days, the mean change from baseline at day 14 was 19.3 (P < 0.0001) in the treated group and 9.0 (P = 0.0121) in the control group. Using a two-factor mixed ANOVA model to evaluate within group and between group changes, the effect of T2000 was significantly different from that of the placebo group (P = 0.03). In the second study of 22 patients treated with 300 mg of T2000 or placebo twice daily for 20 days, statistically significant changes were seen in treated patients compared to baseline, but the ANOVA model did not demonstrate a significant treatment effect of T2000 compared to placebo. When the treated groups from each study are compared, the 800-mg daily group is significantly different from the 600-mg daily group (P = 0.02). Some treated patients in each study, but no placebo patients, experienced marked improvement. These results support further evaluation of T2000 in the treatment of essential tremor. © 2006 Movement Disorder Society [source]

Macular pigment optical density at four retinal loci during 120 days of lutein supplementation

OPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 4 2007
Adam J. Wenzel
Abstract Background:, Increased consumption of lutein and zeaxanthin has been shown to increase macular pigment optical density (MPOD) in some individuals. Most interventions either obtained infrequent measures of MPOD or measured MPOD at a single retinal locus. Purpose:, The aim of this study was to measure acute changes in MPOD at four retinal loci during lutein intervention. Methods:, For 120 days, three subjects consumed 30 mg of lutein and 2.7 mg of zeaxanthin supplement per day. MPOD was measured with heterochromatic flicker photometry at 20,, 30,, 60, and 120, eccentricity three or four times per week. High-performance liquid chromatography was used to measure serum carotenoid concentrations in blood samples collected at baseline and at 30-day intervals. Results:, At the two most central loci, MPOD significantly increased in all three subjects with a mean change of approximately 0.09 log units at 20, eccentricity and 0.08 log units at 30, eccentricity. MPOD significantly increased in two subjects at 60, eccentricity, and in one subject at 120, eccentricity. The increases in MPOD appeared to be linear and continued after treatment was ended. In all three subjects, log sensitivity at the reference locus decreased linearly. Serum lutein and serum zeaxanthin increased from baseline, reaching peak concentrations after 30 days of supplementation. Conclusion:, The changes in MPOD suggest that carotenoid deposition occurs linearly and may be biased towards the central retina. Further, carotenoid deposition may occur outside the central fovea in interventions with pharmacological doses of carotenoid, resulting in underestimations of psychophysical measures of MPOD. [source]

Plasma ghrelin concentration is a signal of decreased fat free mass in healthy elderly females

AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2009
Jaak Jürimäe
This study aimed to evaluate whether circulating ghrelin is associated with changes in different body composition parameters over a 12-month prospective study period in healthy older females. On 41 postmenopausal women (mean age: 71.0 ± 6.5 years), ghrelin, leptin, insulin resistance (IR), and body composition parameters were assessed before and after the study period. Trunk fat: leg fat ratio (+3.6%), fat free mass (FFM) (,4.1%), glucose (+5.8%), and IR (+7.0%) were significantly changed (P < 0.05), whereas no changes in height, body mass, body mass index, fat mass (FM), %FM, trunk fat, leptin, ghrelin, and insulin were observed as a result of study period. At baseline, ghrelin correlated negatively (r > ,0.306; P < 0.05) with body mass, FM, %FM, trunk fat, FFM, leptin, insulin, and IR. Multivariate linear regression analysis demonstrated that baseline ghrelin concentration was significantly associated only with the mean change in FFM value over the 12-month study period. In conclusion, basal ghrelin concentration predicted the loss of FFM in healthy elderly females. In addition, these results suggest that circulating ghrelin concentration could be regarded as a signal of decreased FFM in healthy elderly females. Am. J. Hum. Biol., 2009. © 2009 Wiley-Liss, Inc. [source]

Burden of Medical Illness in Drug- and Alcohol-dependent Persons Without Primary Care

THE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2004
Israel De Alba M.D., M.P.H.
Little is known about the frequency, severity, and risk factors for disease in drug- and alcohol-dependent persons without primary medical care. Our aims are to assess the burden of medical illness, identify patient and substance dependence characteristics associated with worse physical health, and compare measures of illness burden in this population. This was accomplished through a cross-sectional study among alcohol-, heroin- or cocaine-dependent persons without primary medical care who were admitted to an urban inpatient detoxification unit. The mean age of these patients was 35.7 (SD 7.8) years; 76% were male and 46% were Black. Forty-five percent reported being diagnosed with a chronic illness, and 80% had prior medical hospitalizations. The mean age-adjusted SF-36 Physical Component Summary (PCS) score was lower than the general U.S. population norm (44.1 vs 50.1; p < 0.001). In multivariable analysis, female gender (adjusted mean change in PCS score: ,3.71 points, p = .002), problem use of hallucinogens (,3.51, p = 0.013), heroin (,2.94, p = 0.008), other opiates (,3.20, p = .045), living alone (,3.15, p = .023), having medical insurance (,2.26, p = 0.014) and older age (,.22 points per year, p = 0.001) were associated with worse health. From these data, it seems that alcohol- and drug-dependent persons without primary medical care have a substantial burden of medical illness compared to age- and gender-matched U.S. population controls. While the optimal measure of medical illness burden in this population is unclear, a variety of health measures document this medical illness burden in addicted persons. [source]

Sexuality and Management of Benign Prostatic Hyperplasia with Alfuzosin: SAMBA Thailand

THE JOURNAL OF SEXUAL MEDICINE, Issue 9 2010
Somboon Leungwattanakij MD
ABSTRACT Introduction., Benign prostatic hyperplasia (BPH) is a common condition among elderly men. The aim of therapy is to improve lower urinary tract symptoms (LUTS) and quality of life (QoL) and to prevent complications. Aim., The primary objective was to assess the effect on ejaculatory dysfunction (EjD) of 6 months treatment with alfuzosin (XATRAL) 10 mg once daily (OD) in men with LUTS suggestive of BPH in Thailand. Secondary objectives were to evaluate the efficacy of alfuzosin on LUTS, bother score (International Prostate Symptom Score [IPSS] 8th question), erectile dysfunction (ED), onset of action, and tolerability. Methods., Overall, 99 men with moderate to severe LUTS suggestive of BPH (mean IPSS 18.9, bother score 4.3) were enrolled in an open-label study. Sexual function was evaluated at baseline and after 6 months treatment, using the International Index of Erectile Function-5 and the Male Sexual Health Questionnaire (MSHQ) ejaculation score, a new validated questionnaire assessing seven EjD symptoms. Main Outcome Measure., The main outcome measure is mean change from baseline to the end of treatment in the MSHQ Ejaculation score. Results., MHSQ ejaculation score significantly improved from 23.09 at baseline to 21.54 at 6 months (P = 0.022). Overall, 70% of patients perceived an improvement in LUTS within 1 week (36.3% within 3 days). IPSS total score significantly improved from 18.93 at baseline to 9.59 at 6 months (P < 0.001). IPSS voiding and irritative subscores also significantly improved. The percentage of patients with moderate or severe ED decreased from 35.3% at baseline to 21.8% at 6 months. Most adverse events were dizziness (3%) and orthostatic hypotension (1%) with minor intensity. No significant change in blood pressure and heart rate was observed. Conclusions., Alfuzosin 10 mg OD administered for 6 months provides a marked and rapid (within 1 week) improvement in LUTS and bother score while improving both ED and EjD. Leungwattanakij S, Watanachote D, Noppakulsatit P, Petchpaibuol T, Choeypunt N, Tongbai T, Wanamkang T, Lojanapiwat B, Permpongkosol S, Tantiwong A, Pripatnanont C, Akarasakul D, Kongwiwatanakul S, and Chotikawanich E. Sexuality and management of benign prostatic hyperplasia with alfuzosin: SAMBA Thailand. J Sex Med 2010;7:3115,3126. [source]

A Randomized Trial to Assess the Impact of Early Steroid Withdrawal on Growth in Pediatric Renal Transplantation: The TWIST Study

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010
R. Grenda
Minimizing steroid exposure in pediatric renal transplant recipients can improve linear growth and reduce metabolic disorders. This randomized multicenter study investigated the impact of early steroid withdrawal on mean change in height standard deviation score (SDS) and the safety and efficacy of two immunosuppressive regimens during the first 6 months after transplantation. Children received tacrolimus, MMF, two doses of daclizumab and steroids until day 4 (TAC/MMF/DAC, n=98) or tacrolimus, MMF and standard-dose steroids (TAC/MMF/STR, n=98). Mean change in height SDS was 0.16 ± 0.32 with TAC/MMF/DAC and 0.03 ± 0.32 with TAC/MMF/STR. The mean treatment group difference was 0.13 (p < 0.005 [95% CI 0.04,0.22]), 0.21 in prepubertal (p = 0.009 [95% CI 0.05,0.36]) and 0.05 in pubertal children (p = ns). Frequency of biopsy-proven acute rejection was 10.2%, TAC/MMF/DAC, and 7.1%, TAC/MMF/STR. Patient and graft survival and renal function were similar. Significantly greater reductions in total cholesterol and triglycerides but significantly higher incidences of infection and anemia were found with TAC/MMF/DAC (p < 0.05 all comparisons). Early steroid withdrawal significantly aided growth at 6 months more so in prepubertal than pubertal children. This was accompanied by significantly better lipid and glucose metabolism profiles without increases in graft rejection or loss. [source]

Fate of the Mate: The Influence of Delayed Graft Function in Renal Transplantation on the Mate Recipient

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009
J. F. Johnson
Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time. Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of ,11.2 mL/min, while the control group had a mean change of ,0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these,at-risk'recipients should be developed and tested. [source]

Effectiveness of rituximab treatment in primary Sjögren's syndrome: A randomized, double-blind, placebo-controlled trial,

ARTHRITIS & RHEUMATISM, Issue 4 2010
J. M. Meijer
Objective To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sjögren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial. Methods Patients with active primary SS, as determined by the revised American,European Consensus Group criteria, and a rate of stimulated whole saliva secretion of ,0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables. Results Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean ± SD age of the patients receiving rituximab was 43 ± 11 years and the disease duration was 63 ± 50 months, while patients in the placebo group were age 43 ± 17 years and had a disease duration of 67 ± 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness,like disease. Conclusion These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS. [source]

Results of a two-year followup study of patients with rheumatoid arthritis who received a combination of abatacept and methotrexate,

ARTHRITIS & RHEUMATISM, Issue 4 2008
Joel M. Kremer
Objective To evaluate the efficacy, radiographic changes, and safety of abatacept and methotrexate therapy through 2 years in a long-term extension of a previously published 1-year study. Methods Patients who received placebo during year 1 were switched to abatacept. Patients taking abatacept continued to take it. Efficacy and safety were assessed through 2 years. Results Of 539 patients enrolled in the initial 1-year study, 488 completed 1 year of the long-term extension (2% discontinued for lack of efficacy). At 2 years, patients taking abatacept had maintained their responses on the American College of Rheumatology (ACR) improvement criteria and the Disease Activity Score in 28 joints (DAS28; using the C-reactive protein [CRP] level), as well as their physical function (according to the Health Assessment Questionnaire [HAQ] disability index [DI]) and health-related quality of life (HRQOL; assessed with the Short Form 36 [SF-36] health survey), that were observed at the end of the double-blind period (year 1 versus year 2 values were 81.9% versus 80.3% for ACR 20% improvement, 25.4% versus 30.9% for a DAS28 [CRP] of <2.6, 71.8% versus 66.8% for the HAQ DI, and 9.7 versus 10.6 and 7.3 versus 7.2, respectively, for the mean change in the physical and mental components summary scores of the SF-36). In the abatacept group, post hoc analysis demonstrated further inhibition of radiographic progression during year 2 (57% reduction in mean change of total score in year 2 versus year 1; P < 0.0001), and minimal radiographic progression was observed (mean change in total score from baseline was 1.1 and 1.6 at year 1 and 2, respectively). Rates of adverse events (AEs) and severe AEs were consistent throughout the cumulative period. Conclusion The improvements in signs and symptoms, physical function, and HRQOL observed after 1 year of abatacept treatment were maintained through 2 years of treatment. This durability was accompanied by a safety profile consistent with that in the double-blind portion of the study. Radiographic progression was further inhibited in year 2 compared with year 1, suggesting an increasing effect of abatacept on the inhibition of structural damage in year 2. [source]

Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials

BIPOLAR DISORDERS, Issue 1 2006
Stuart F Kushner
Objective:, To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder. Methods:, In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of ,1 previous manic or mixed episodes, and ,20 Young Mania Rating Scale (YMRS) score were randomized to double-blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9-week double-blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study. Results:, Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, ,5.1 to ,8.4). Mean YMRS reductions in lithium-treated groups were significantly greater (p , 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo. Conclusions:, These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression. Lithium was confirmed as an effective therapy in this population. [source]

Duloxetine compared with placebo for treating women with symptoms of overactive bladder

BJU INTERNATIONAL, Issue 2 2007
William D. Steers
OBJECTIVE To evaluate duloxetine (a serotonin-noradrenaline reuptake inhibitor) in women with symptoms of overactive bladder (OAB), as it has been shown to increase the bladder capacity in an animal model. PATIENTS AND METHODS In all, 306 women (aged 21,84 years) were recruited and randomly assigned to placebo (153) or duloxetine (80-mg/day for 4 weeks increased to 120-mg/day for 8 weeks; 153). Symptoms of OAB were defined as bothersome urinary urgency and/or urge urinary incontinence (UI) for ,3 months. Participants were also required to have a mean daytime voiding interval (VI) of ,2 h and urodynamic observations of either detrusor overactivity (DOA) or urgency which limited bladder capacity to <400 mL, both with no stress UI (SUI). The primary efficacy analysis compared the treatment effects on mean change from baseline to endpoint in the mean number of voiding episodes (VE)/24 h. The secondary efficacy analyses compared the treatment effects on the number of UI episodes (IE)/24 h, in the Incontinence Quality of Life questionnaire (I-QOL) score, and on the mean daytime VI. Safety was assessed with vital signs, adverse event reporting, routine laboratory testing, electrocardiogram, and the measurement of postvoid residual urine volumes (PVR). RESULTS Patients randomized to duloxetine had significant improvements over those randomized to placebo for decreases in VE and IE, for increases in the daytime VI, and for improvements in I-QOL scores at both doses of duloxetine. Urodynamic studies showed no significant increases in maximum cystometric capacity or in the volume threshold for DOA. The most common treatment-emergent adverse events with duloxetine (nausea, 31%; dry mouth, 16%; dizziness, 14%; constipation, 14%; insomnia, 13%; and fatigue, 11%) were the same as those reported by women with SUI and were significantly more common with duloxetine than placebo. Laboratory assessments, vital signs and electrocardiograms were stable relative to baseline, with no relevant differences detected between groups. There was a significant difference in the change in PVR with duloxetine (<5 mL mean increase) but no patient reported hesitancy or retention. CONCLUSION In this trial, duloxetine was better than placebo for treating women with ,wet' and ,dry' symptoms of OAB associated with DOA or a bladder capacity of <400 mL. [source]