The "gender factor" in wearing-off among patients with Parkinson's disease: a post hoc analysis of DEEP study.
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ABSTRACT:
SUBMITTER: Colombo D
PROVIDER: S-EPMC4320843 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Pain is a troublesome non-motor symptom of Parkinson's disease (PD). The RECOVER (Randomized Evaluation of the 24-hour Coverage: Efficacy of Rotigotine; Clintrials.gov: NCT00474058) study demonstrated significant improvements in early-morning motor function (UPDRS III) and sleep disturbances (PDSS-2) with rotigotine transdermal system. Improvements were also reported on a Likert pain scale (measuring any type of pain). This post hoc analysis of RECOVER further evaluates the effect of rotigotine on pain, and whether improvements in pain may be attributable to benefits in motor function or sleep disturbance.PD patients with unsatisfactory early-morning motor impairment were randomized to optimal-dose (up to 16 mg/24 h) rotigotine or placebo, maintained for 4 weeks. Pain was assessed in the early-morning using an 11-point Likert pain scale (rated average severity of pain (of any type) over the preceding 12 hours from 0 [no pain] to 10 [worst pain ever experienced]). Post hoc analyses for patients reporting 'any' pain (pain score ?1) at baseline, and subgroups reporting 'mild' (score 1-3), and 'moderate-to-severe' pain (score ?4) were performed. Likert pain scale change from baseline in rotigotine-treated patients was further analyzed based on a UPDRS III/PDSS-2 responder analysis (a responder defined as showing a ?30% reduction in early morning UPDRS III total score or PDSS-2 total score). As post hoc analyses, all p values presented are exploratory.Of 267 patients with Likert pain data (178 rotigotine, 89 placebo), 187 (70%) reported 'any' pain; of these 87 (33%) reported 'mild', and 100 (37%) 'moderate-to-severe' pain. Change from baseline pain scores decreased with rotigotine compared with placebo in patients with 'any' pain (-0.88 [95% CI: -1.56, -0.19], p?=?0.013), and in the subgroup with 'moderate-to-severe' pain (-1.38 [-2.44, -0.31], p?=?0.012). UPDRS III or PDSS-2 responders showed greater improvement in pain than non-responders.The results from this post hoc analysis of the RECOVER study suggest that pain was improved in patients with PD treated with rotigotine; this may be partly attributable to benefits in motor function and sleep disturbances. Prospective studies are warranted to investigate this potential benefit and the clinical relevance of these findings.
| S-EPMC4016269 | biostudies-literature
Project description:BackgroundIn the REMoxTB study of 4-month treatment-shortening regimens containing moxifloxacin compared to the standard 6-month regimen for tuberculosis, the proportion of unfavourable outcomes for women was similar in all study arms, but men had more frequent unfavourable outcomes (bacteriologically or clinically defined failure or relapse within 18 months after randomisation) on the shortened moxifloxacin-containing regimens. The reason for this gender disparity in treatment outcome is poorly understood.MethodsThe gender differences in baseline variables were calculated, as was time to smear and culture conversion and Kaplan-Meier plots were constructed. In post hoc exploratory analyses, multivariable logistic regression modelling and an observed case analysis were used to explore factors associated with both gender and unfavourable treatment outcome.ResultsThe per-protocol population included 472/1548 (30%) women. Women were younger and had lower rates of cavitation, smoking and weight (all p?<?0.05) and higher prevalence of HIV (10% vs 6%, p?=?0.001). They received higher doses (mg/kg) than men of rifampicin, isoniazid, pyrazinamide and moxifloxacin (p???0.005). There was no difference in baseline smear grading or mycobacterial growth indicator tube (MGIT) time to positivity. Women converted to negative cultures more quickly than men on Lowenstein-Jensen (HR 1.14, p?=?0.008) and MGIT media (HR 1.19, p?<?0.001). In men, the presence of cavitation, positive HIV status, higher age, lower BMI and 'ever smoked' were independently associated with unfavourable treatment outcome. In women, only 'ever smoked' was independently associated with unfavourable treatment outcome. Only for cavitation was there a gender difference in treatment outcomes by regimen; their outcome in the 4-month arms was significantly poorer compared to the 6-month treatment arm (p?<?0.001). Women, with or without cavities, and men without cavities had a similar outcome on all treatment arms (p?=?0.218, 0.224 and 0.689 respectively). For all other covariate subgroups, there were no differences in treatment effects for men or women.ConclusionsGender differences in TB treatment responses for the shorter regimens in the REMoxTB study may be explained by poor outcomes in men with cavitation on the moxifloxacin-containing regimens. We observed that women with cavities, or without, on the 4-month moxifloxacin regimens had similar outcomes to all patients on the standard 6-month treatment. The biological reasons for this difference are poorly understood and require further exploration.
| S-EPMC6192317 | biostudies-literature
Project description:Transdermal delivery of rotigotine maintains stable plasma concentrations for 24 hours. Three phase 3 studies of rotigotine as add-on to levodopa in advanced Parkinson's disease showed a significant reduction in "off" time from baseline to end of maintenance (EoM). However, detailed analyses over the range of a day have not yet been performed. The objective was to examine the time course of the efficacy profile of rotigotine throughout the day.Post hoc analysis of diary data from 3 double-blind, placebo-controlled studies of rotigotine in patients with advanced Parkinson's disease inadequately controlled with levodopa, with average "off" time of ?2.5 h/d (CLEOPATRA-PD [NCT00244387], 16-week maintenance; PREFER, 24-week maintenance; SP921 [NCT00522379], 12-week maintenance). Patients marked 30-minute intervals as "off," "on without troublesome dyskinesia," "on with troublesome dyskinesia," or "sleep." Diaries completed on the 3 days before EoM were analyzed. A 2-sample t test was performed for comparison of rotigotine + levodopa versus placebo + levodopa for mean percentage of time per status during four 6-hour periods: 12:00AM (midnight) to 6:00AM, 6:00AM to 12:00PM (noon), noon to 6:00PM, and 6:00PM to midnight.Data were available for 967 patients (placebo + levodopa, 260; rotigotine + levodopa, 707). During the 24-hour period at EoM, an advantage in mean percentage time spent "off" and "on without troublesome dyskinesia" was observed with rotigotine + levodopa versus placebo + levodopa during the three 6-hour periods from 6:00AM to midnight (P < 0.05; exploratory analysis).These exploratory analyses of patients with motor fluctuations suggest that the efficacy of rotigotine transdermal patch, as captured by diary data, in reducing "off" time and increasing "on time without troublesome dyskinesia" may cover the full waking day.
| S-EPMC4791317 | biostudies-literature
Project description:BACKGROUND:Alzheimer's disease (AD) is characterized by progressive cognitive decline, often associated with Behavioral and Psychological Symptoms of Dementia (BPSD). Acetylcholinesterase inhibitors (ChEi) may attenuate cognitive decline and mitigate BPSD. The EVOLUTION group found that the switch from oral ChEi to transdermal rivastigmine patch formulation resulted in improvement/stabilization in the frequency of clinically relevant BPSD, but gender-specific subgroup analyses were not reported. METHODS:Participants underwent Neuropsychiatric Inventory to assess the frequency and severity of neuropsychiatric symptoms at baseline and 3 and 6 months after the switch from oral ChEi to transdermal rivastigmine patch. A descriptive post hoc analysis was conducted to assess whether there were gender-based differences in BPSD profile during the 6 months after the switch. RESULTS:The entire sample consisted of 475 patients, 274 women and 201 men. Women were on average slightly older and with poorer cognitive performance (60.6% of the women had moderate-AD, defined as Mini-Mental State Examination [MMSE] score of 10-17, vs. 43.8% of men). In mild-AD patients (MMSE score 18-26), the frequency of BPSD did not change significantly over time and an association was found between gender and depression (odds ratio; OR [95% confidence interval; CI] female vs. male?=?3.32 [1.44-7.67]), anxiety (2.42 [1.23-4.79]), apathy (2.25 [1.07-4.70]), nighttime behavior disturbances (3.97 [1.66-9.49]), and appetite/eating abnormalities (2.39 [1.10-5.18]). Moderate-AD female patients had euphoria more frequently than male patients (OR [95% CI] female vs. male?=?3.67 [1.25-10.74]). The frequency of delusions, anxiety, and irritability decreased during the first 3 months after the switch, independently of gender. CONCLUSION:Mild-AD women tended to suffer more frequently from BPSD than men; in the 3 months after treatment switch, moderate-AD patients showed a decrease in delusions, anxiety, and irritability, with no significant differences between genders. Ad hoc studies to investigate this potential gender effect in AD could be well worthwhile.
| S-EPMC6247376 | biostudies-literature
Project description:BackgroundIdentifying the factors that influence health-related quality of life (HRQoL) is of great scientific interest, but a potential causal relationship between treatment and HRQoL has yet to be fully elucidated. Japanese patients reported better HRQoL outcomes on the Parkinson's Disease Questionnaire (PDQ-39) emotional well-being domain, a 6-question subset of the PDQ-39 which is considered to reflect the emotional aspects of the disease-specific HRQoL, when treated with rasagiline, than placebo, in both a monotherapy clinical trial (NCT02337725) and an adjunctive therapy clinical trial in patients with wearing-off phenomena (NCT02337738).ObjectiveTo investigate how rasagiline exerts its effect on the PDQ-39 emotional well-being domain in Japanese patients with Parkinson's disease.MethodsA path analysis was performed to assess the direct treatment effects of rasagiline on the PDQ-39 emotional well-being domain and the effects mediated indirectly through the influence on items related to motor symptoms by a post-hoc analysis of two clinical trials in Japan.ResultsIn the monotherapy trial, the PDQ-39 emotional well-being domain was mainly affected indirectly through items related to motor symptoms (80.7%) composed of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II (67.2%) and Part III (13.5%). In the adjunctive therapy trial, the PDQ-39 emotional well-being domain was also mainly influenced indirectly through effects on items related to motor symptoms (1 mg/day: 54.7%, 0.5 mg/day: 57.6%) composed of MDS-UPDRS Part II (1 mg/day: 35.6%, 0.5 mg/day: 40.9%), Part III (1 mg/day: 8.0%, 0.5 mg/day: 8.3%) and mean daily OFF-time (1 mg/day: 11.1%, 0.5 mg/day: 8.4%).ConclusionsThe effects of rasagiline on the PDQ-39 emotional well-being domain were mediated primarily by influence on the subjective aspects of motor experiences of daily living.
| S-EPMC8789184 | biostudies-literature
Project description:Background and Aims:This GEMINI 1 post hoc analysis evaluated vedolizumab efficacy for inducing deep remission in patients with ulcerative colitis and correlation between vedolizumab trough concentrations and deep remission rates. Methods:Week 6 vedolizumab responders were re-randomized to placebo or vedolizumab every 8 or 4 weeks. Deep remission at Week 52 was measured using four different definitions [from most to least stringent]: [1] Mayo Clinic endoscopic score = 0, rectal bleeding score = 0 and decrease or no change from baseline in stool frequency score; [2] endoscopic score ?1, rectal bleeding score = 0 and stool frequency score = 0; [3] endoscopic score ?1, rectal bleeding score = 0, decrease or no change from baseline stool frequency score, and total score [endoscopic score + rectal bleeding score + stool frequency score] ?1; and [4] endoscopic score ?1, rectal bleeding score = 0 and stool frequency score ?1. Steady-state trough vedolizumab serum concentrations were evaluated. Results:At Week 6, 373 vedolizumab responders were re-randomized to maintenance placebo [n = 126] or vedolizumab every 8 [n = 122] or 4 [n = 125] weeks. Significantly more vedolizumab patients achieved deep remission at Week 52 for the most (placebo 8.7%, every 8 weeks 27.0% [p = 0.0001], every 4 weeks 28.0% [p < 0.0001]) and least (placebo 15.9%, every 8 weeks 43.4% [p < 0.0001], every 4 weeks 43.2% [p < 0.0001]) stringent definitions. Patients with higher vedolizumab trough concentration quartiles had higher deep remission rates [all definitions] compared with those with the lowest quartile or who received placebo. Conclusion:Vedolizumab was associated with significantly higher deep remission rates than placebo at Week 52, regardless of deep remission definition [NCT00783718].
| S-EPMC6357899 | biostudies-other
Project description:BACKGROUND:The burden of chronic obstructive lung disease (COPD) is increasing in women, with recent evidence suggesting gender differences in disease characteristics and potentially in treatment outcomes. METHODS:FLAME was a 52-week randomized controlled trial in patients with severe-to-very-severe COPD and a history of exacerbations. In this post-hoc analysis, gender-based baseline differences and treatment outcomes between indacaterol/glycopyrronium 110/50??g once daily (IND/GLY) and salmeterol/fluticasone 50/500 twice daily (SFC) were assessed in terms of rate of exacerbations, time-to-first exacerbation, lung function, health status, and rescue medication use. RESULTS:This post-hoc analysis included 2557 men and 805 women. Baseline characteristics differed between genders, with women being younger, having better lung function and more often experiencing ?2 exacerbations in the previous year. Compared with SFC, IND/GLY treatment was associated with reductions in the annualized rates of moderate/severe exacerbations (rate ratio [95% CI]: 0.81 [0.73-0.91], 0.89 [0.74-1.07] in men and women, respectively). Similarly, time-to-first moderate/severe exacerbation was also delayed (hazard ratio [95% CI]: 0.79 [0.70-0.89] and 0.76 [0.63-0.91] in men and women, respectively). Results were similar for all (mild/moderate/severe) exacerbations. Improvements in lung function, health status and rescue medication use with IND/GLY vs SFC were comparable between men and women. The smaller sample size for women may account for some observed discrepancies in treatment responses. CONCLUSIONS:Although there were gender differences in baseline characteristics, IND/GLY demonstrated similar trends for exacerbation prevention and lung function improvement in men and women with moderate-to-very-severe COPD and a history of exacerbations compared with SFC. Small differences in the effects seen between genders may be attributed to the different sizes of the two groups and need to be further evaluated in randomized trials that are appropriately powered for gender analysis. TRIAL REGISTRATION:Post hoc analysis of the FLAME study. ClinicalTrials.gov number: NCT01782326 . Registered 1 February 2013.
| S-EPMC6325763 | biostudies-literature
Project description:Safinamide is a novel ?-aminoamide with dopaminergic and non-dopaminergic properties developed as adjunctive therapy for patients with PD. Results from a 24-month double-blind controlled study suggested that as add-on to levodopa (and other PD medications) the benefits of safinamide on dyskinesia may be related to severity of dyskinesia at baseline.This post-hoc analysis further characterized the effects of safinamide on dyskinesia in mid- to late-stage PD patients.Patients were stratified by the presence or absence of dyskinesia at baseline, and by whether or not the dose of levodopa had been changed during the 24-month treatment period. Differences between safinamide and placebo were evaluated using the Wilcoxon rank-sum test.For the overall treated population (with or without baseline dyskinesia), safinamide 100?mg/day significantly improved the dyskinesia rating scale score, compared with placebo, in the subgroup of patients with no change in levodopa dose (p?=?0.0488). For patients with baseline dyskinesia, improvements over placebo were also significant (p?=?0.0153) in patients with or without changes in levodopa dose, and nearly significant (p?=?0.0546) in patients with no change in levodopa dose, suggesting that these improvements were not due to levodopa dose reductions.While no statistically significant difference in mean DRS scores was seen between safinamide and placebo in the original study population, the present post-hoc analysis helps to provide a meaningful interpretation of the long-term effects of safinamide on dyskinesia. These results may be related to safinamide state- and use-dependent inhibition of sodium channels and stimulated glutamate release, and are unlikely due to reduced dopaminergic stimulation.
| S-EPMC4923744 | biostudies-literature
Project description:The given data set is the first deep sequencing transcriptome-wide data set of human Parkinson's disease (PD) patients RNA. The data set was produced from blood leukocytes of PD patients, from the same patients following deep brain stimulation (DBS), and from matched healthy control volunteers. Post-DBS samples were taken from the patients while being on electrical stimulation (ON-Stim), and following one hour off of electrical stimulation (OFF-Stim state). We have previously shown that gene expression changes, and in particular, alternative splicing changes, are observed in blood leukocytes and may contribute to PD and being subjected to regulation following DBS. Here, SOLiD RNA-Seq was applied to study the transcriptome of PD patients. Exon- and junction-level analyses revealed deep insight into both differential expression and alternative splicing regulation in PD blood leukocytes prior to and following DBS both on and off electrical stimulation. This transcriptome genome-wide data obtained through high-throughput sequencing of RNA produced from human Parkinson's disease (PD) patients blood leukocytes prior to treatment and following deep brain stimulation (DBS) neurosurgical treatment may yield insights into the molecular mechanisms that underlie the pathogenesis of PD and treatment efficacy. It may further enable the development of future diagnostics and therapeutics for PD.
2014-07-16 | GSE42608 | GEO
Project description:The given data set is the first deep sequencing transcriptome-wide data set of human Parkinson's disease (PD) patients RNA. The data set was produced from blood leukocytes of PD patients, from the same patients following deep brain stimulation (DBS), and from matched healthy control volunteers. Post-DBS samples were taken from the patients while being on electrical stimulation (ON-Stim), and following one hour off of electrical stimulation (OFF-Stim state). We have previously shown that gene expression changes, and in particular, alternative splicing changes, are observed in blood leukocytes and may contribute to PD and being subjected to regulation following DBS. Here, SOLiD RNA-Seq was applied to study the transcriptome of PD patients. Exon- and junction-level analyses revealed deep insight into both differential expression and alternative splicing regulation in PD blood leukocytes prior to and following DBS both on and off electrical stimulation. This transcriptome genome-wide data obtained through high-throughput sequencing of RNA produced from human Parkinson's disease (PD) patients blood leukocytes prior to treatment and following deep brain stimulation (DBS) neurosurgical treatment may yield insights into the molecular mechanisms that underlie the pathogenesis of PD and treatment efficacy. It may further enable the development of future diagnostics and therapeutics for PD. Blood leukocyte RNA was analyzed from 3 healthy control volunteers, and from 3 PD patients pre-DBS, ON-Stim, and OFF-Stim.
2014-07-16 | E-GEOD-42608 | biostudies-arrayexpress