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:BackgroundThe synthetic tetrahydrocannabinol analogue nabilone improved overall non-motor symptom (NMS) burden in Parkinson's disease (PD) patients in comparison to placebo.ObjectivesTo characterize the effects of nabilone on different sleep outcomes in PD patients.MethodsWe performed a post-hoc analysis of the controlled, double-blind, enriched enrollment randomized withdrawal NMS-Nab study to assess the effects of nabilone on sleep outcomes in study participants who reported clinically-relevant sleep problems (MDS-UPDRS-1.7 ≥ 2 points).ResultsAfter open-label nabilone administration, 77.4% reported no relevant sleep problem. In the withdrawal phase of the trial, the MDS-UPDRS-1.7. and the NMS-Scale Domain 2 (i.e., Sleep/Fatigue) significantly worsened only in PD patients in the placebo group, which was mostly driven by a significant worsening of insomnia (question 5 of the NMS-Scale Domain 2).ConclusionsThis post-hoc analysis of the NMS-Nab trial suggests that nabilone has beneficial effects on sleep outcomes in PD patients experiencing sleep problems at baseline.The original trial was registered with ClinicalTrials.gov (NCT03769896, https://clinicaltrials.gov/ct2/show/NCT03769896) and EudraCT (2017-000192-86).
| S-EPMC9346252 | biostudies-literature
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:Previous studies have shown less access to deep brain stimulation (DBS) for Parkinson's disease (PD) in women compared to men raising concerns about a potential gender gap resulting from nonclinical factors or gender differences in clinical efficacy for postoperative quality of life (QoL), motor, and nonmotor symptoms (NMS) outcomes. This was a cross-sectional and a longitudinal, prospective, observational, controlled, quasi-experimental, international multicenter study. A total sample size of 505 consisted of 316 consecutively referred patients for DBS indication evaluation at the University Hospital Cologne (01/2015-09/2020) and 189 consecutively treated patients at DBS centers in the University Hospitals Cologne and Marburg, Salford's Royal Hospital Manchester, and King's College Hospital London. In the cross-sectional cohort, we examined gender proportions at referral, indication evaluations, and DBS surgery. In the longitudinal cohort, clinical assessments at preoperative baseline and 6-month follow-up after surgery included the PD Questionnaire-8, NMSScale, Scales for Outcomes in PD-motor scale, and levodopa-equivalent daily dose. Propensity score matching resulted in a pseudo-randomized sub-cohort balancing baseline demographic and clinical characteristics between women with PD and male controls. 316 patients were referred for DBS. 219 indication evaluations were positive (women n = 102, respectively n = 82). Women with PD were disproportionally underrepresented in referrals compared to the general PD population (relative risk [RR], 0.72; 95%CI, 0.56-0.91; P = 0.002), but more likely to be approved for DBS than men (RR, 1.17; 95%CI, 1.03-1.34; P = 0.029). Nonetheless, their total relative risk of undergoing DBS treatment was 0.74 (95%CI, 0.48-1.12) compared to men with PD. At baseline, women had longer disease duration and worse dyskinesia. Exploring QoL domains, women reported worse mobility and bodily discomfort. At follow-up, all main outcomes improved equally in both genders. Our study provides evidence of a gender gap in DBS for PD. Women and men with PD have distinct preoperative nonmotor and motor profiles. We advocate that more focus should be directed toward the implementation of gender equity as both genders benefit from DBS with equal clinical efficacy. This study provides Class II evidence of beneficial effects of DBS in women with PD compared to male controls.
| S-EPMC9021281 | biostudies-literature
Project description:IntroductionThe DYSCOVER study was a phase 3b, open-label, randomized trial (NCT02799381) that evaluated levodopa-carbidopa intestinal gel (LCIG) versus optimized medical treatment (OMT) in patients with Parkinson's disease (PD) and a high burden of dyskinesia at baseline (defined as Unified Dyskinesia Rating Scale [UDysRS] total score ≥ 30). At week 12, patients receiving LCIG versus OMT experienced significant improvements in dyskinesia, pain, and health-related outcomes. The objective of this analysis was to examine correlations between dyskinesia, pain, and health-related outcomes in PD.MethodsThis post hoc analysis assessed correlations between UDysRS, King's Parkinson's Disease Pain Scale (KPPS), 8-item Parkinson's Disease Questionnaire (PDQ-8), Unified Parkinson's Disease Rating Scale part II, Clinical Global Impression of Severity (CGI-S) or Change (CGI-C), and "On" time without troublesome dyskinesia at baseline and after 12 weeks of LCIG or OMT. Correlations were assessed by Pearson correlation coefficients (categorization: weak, r = 0.20-0.39; moderate, r = 0.40-0.59; strong, r ≥ 0.60).ResultsAmong 61 patients, moderate-to-strong positive and significant correlations were observed between UDysRS and KPPS scores (baseline, r = 0.47; week 12 change from baseline [CFB], r = 0.63; all p < 0.001). UDysRS and KPPS scores had moderate-to-strong positive and highly significant correlations with PDQ-8 scores (baseline, r = 0.45 and 0.46, respectively; CFB, r = 0.54 and 0.64, respectively; all p < 0.001). Moderate positive and significant correlations were observed between UDysRS and CGI-S/CGI-C scores (baseline, r = 0.41; CFB, r = 0.47; all p < 0.001).ConclusionsIn patients with high dyskinesia burden, positive correlations were observed between dyskinesia, pain, and health-related quality of life (HRQoL) at baseline. Improvements in dyskinesia and pain were associated with improvements in HRQoL, demonstrating the clinical burden of troublesome dyskinesia.Trial registration numberClinicaltrials.gov identifier NCT02799381.
| S-EPMC10951158 | biostudies-literature
Project description:BackgroundAlzheimer'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.MethodsParticipants 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.ResultsThe 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.ConclusionMild-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:Safinamide is a selective, reversible, monoamine oxidase B inhibitor for the treatment of patients with Parkinson's disease (PD) and motor fluctuations. This was a post hoc analysis of the SETTLE study, in which patients with PD and motor fluctuations were randomly assigned to 24-week treatment with safinamide (50 mg/day for 2 weeks, increased to 100 mg/day if tolerated) or placebo. In the present analysis, responders were defined according to their treatment responses at Week 2 and Week 24 based on changes in ON-time without troublesome dyskinesia from baseline with cutoffs of 1 hour. It was found that 81% (103/127) of the responders at Week 2 maintained the response through Week 24 in the safinamide group. Other outcomes did not necessarily coincide with the ON-time response; however, "Early" responders who showed a treatment response at both Week 2 and Week 24 had substantial improvements from baseline in OFF-time, UPDRS Part II and III scores, and PDQ-39 summary index scores through Week 24. The safinamide group had a higher proportion of early responders than the placebo group (39% vs 20%, p < 0.0001). At baseline, early responders in the safinamide group had significantly higher UPDRS Part II and III scores, shorter ON-time, and longer OFF-time than the other responder populations. In conclusion, the results of the present post hoc analysis suggest that patients with a short ON-time, severe motor symptoms, and highly compromised activities of daily living can benefit from safinamide early in treatment and over the long term.
| S-EPMC10083404 | biostudies-literature
Project description:ObjectiveSafinamide is a selective, reversible monoamine oxidase B inhibitor with demonstrated efficacy and tolerability in placebo-controlled studies and is clinically useful for patients with motor fluctuations. This study evaluated the efficacy and safety of safinamide as a levodopa adjunct therapy in Asian patients with Parkinson's disease.MethodsData from 173 Asian and 371 Caucasian patients from the international Phase III SETTLE study were included in this post hoc analysis. The safinamide dose was increased from 50 mg/day to 100 mg/day if no tolerability issues occurred at week 2. The primary outcome was the change from baseline to week 24 in daily ON-time without troublesome dyskinesia (i.e., ON-time). Key secondary outcomes included changes in Unified Parkinson's Disease Rating Scale (UPDRS) scores.ResultsSafinamide significantly increased daily ON-time relative to placebo in both groups (least-squares mean: 0.83 hours, p = 0.011 [Asians]; 1.05 hours, p < 0.0001 [Caucasians]). Motor function relative to placebo (UPDRS Part III) improved significantly in Asians (-2.65 points, p = 0.012) but not Caucasians (-1.44 points, p = 0.0576). Safinamide did not worsen Dyskinesia Rating Scale scores in either subgroup, regardless of the presence or absence of dyskinesia at baseline. Dyskinesia was largely mild for Asians and moderate for Caucasians. None of the Asian patients experienced adverse events leading to treatment discontinuation.ConclusionSafinamide as a levodopa adjunct is well tolerated and effective in reducing motor fluctuations in both Asian and Caucasian patients. Further studies to investigate the real-world effectiveness and safety of safinamide in Asia are warranted.
| S-EPMC10236023 | biostudies-literature