Effects of neurostimulation for advanced Parkinson's disease patients on motor symptoms: A multiple-treatments meta-analysas of randomized controlled trials.
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ABSTRACT:
SUBMITTER: Xie CL
PROVIDER: S-EPMC4855136 | biostudies-other | 2016 May
REPOSITORIES: biostudies-other
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Project description:We conducted meta-analyses of findings from randomized, placebo-controlled, short-term trials for acute mania in manic or mixed states of DSM (III-IV) bipolar I disorder in 56 drug-placebo comparisons of 17 agents from 38 studies involving 10,800 patients. Of drugs tested, 13 (76%) were more effective than placebo: aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperdone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone. Their pooled effect size for mania improvement (Hedges' g in 48 trials) was 0.42 (confidence interval (CI): 0.36-0.48); pooled responder risk ratio (46 trials) was 1.52 (CI: 1.42-1.62); responder rate difference (RD) was 17% (drug: 48%, placebo: 31%), yielding an estimated number-needed-to-treat of 6 (all p<0.0001). In several direct comparisons, responses to various antipsychotics were somewhat greater or more rapid than lithium, valproate, or carbamazepine; lithium did not differ from valproate, nor did second generation antipsychotics differ from haloperidol. Meta-regression associated higher study site counts, as well as subject number with greater placebo (not drug) response; and higher baseline mania score with greater drug (not placebo) response. Most effective agents had moderate effect-sizes (Hedges' g=0.26-0.46); limited data indicated large effect sizes (Hedges' g=0.51-2.32) for: carbamazepine, cariprazine, haloperidol, risperidone, and tamoxifen. The findings support the efficacy of most clinically used antimanic treatments, but encourage more head-to-head studies and development of agents with even greater efficacy.
| S-EPMC3055677 | biostudies-other
Project description:ObjectivesExisting treatments for schizophrenia can improve positive symptoms, but it is unclear if they have any impact on negative symptoms. This meta-analysis was conducted to assess the efficacy of available treatments for negative symptoms in schizophrenia.MethodsAll randomized-controlled trials of interventions for negative symptoms in schizophrenia until December 2013 were retrieved; 168 unique and independent placebo-controlled trials were used. Negative symptom scores at baseline and follow-up, duration of illness, doses of medication, type of interventions, and sample demographics were extracted. Heterogeneity was addressed with the I (2) and Q statistic. Standardized mean difference in values of the Negative Symptom Rating Scale used in each study was calculated as the main outcome measure.Results6503 patients in the treatment arm and 5815 patients in the placebo arm were included. No evidence of publication biases found. Most treatments reduced negative symptoms at follow-up relative to placebo: second-generation antipsychotics: -0.579 (-0.755 to -0.404); antidepressants: -0.349 (-0.551 to -0.146); combinations of pharmacological agents: -0.518 (-0.757 to -0.279); glutamatergic medications: -0.289 (-0.478 to -0.1); psychological interventions: -0.396 (-0.563 to -0.229). No significant effect was found for first-generation antipsychotics: -0.531 (-1.104 to 0.041) and brain stimulation: -0.228 (-0.775 to 0.319). Effects of most treatments were not clinically meaningful as measured on Clinical Global Impression Severity Scale.Conclusions and relevanceAlthough some statistically significant effects on negative symptoms were evident, none reached the threshold for clinically significant improvement.
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Project description:Background: Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs). Methods and Findings: We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy ("ON" time without troublesome dyskinesia, "OFF" time, "ON" time, "UPDRS-III," and "UPDRS-II") and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of "ON" time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%). Conclusions: This network meta-analysis shows that apomorphine increased "ON" time without troublesome dyskinesia and decreased "OF" time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased "ON" time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.
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Project description:Although some trials assessed the effectiveness of aerobic exercise for Parkinson's disease (PD), the role of aerobic exercise in the management of PD remained controversial.The purpose of this systematic review is to evaluate the evidence about whether aerobic exercise is effective for PD.Seven electronic databases, up to December 2013, were searched to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. Standardised mean difference (SMD) and 95% confidence intervals (CI) of random-effects model were calculated. And heterogeneity was assessed based on the I2 statistic.18 randomized controlled trials (RCTs) with 901 patients were eligible. The aggregated results suggested that aerobic exercise should show superior effects in improving motor actions (SMD, -0.57; 95% CI -0.94 to -0.19; p?=?0.003), balance (SMD, 2.02; 95% CI 0.45 to 3.59; p?=?0.01), and gait (SMD, 0.33; 95% CI 0.17 to 0.49; p<0.0001) in patients with PD, but not in quality of life (SMD, 0.11; 95% CI -0.23 to 0.46; p?=?0.52). And there was no valid evidence on follow-up effects of aerobic exercise for PD.Aerobic exercise showed immediate beneficial effects in improving motor action, balance, and gait in patients with PD. However, given no evidence on follow-up effects, large-scale RCTs with long follow-up are warrant to confirm the current findings.
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Project description:Background: We provided a comprehensive evaluation of efficacy of available treatments for coronavirus disease 2019 (COVID-19). Methods: We searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database up to August 19, 2021. Randomized controlled trials for suspected or confirmed COVID-19 patients published on peer-reviewed journals were included, regardless of demographic characteristics. Outcome measures included mortality, mechanical ventilation, hospital discharge and viral clearance. Bayesian network meta-analysis with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs). Odds ratio (OR) was used as the summary measure for treatment effect. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by the treatment classifications. Results: We identified 222 eligible studies with a total of 102,950 patients. Compared with the standard of care, imatinib, intravenous immunoglobulin and tocilizumab led to lower risk of death; baricitinib plus remdesivir, colchicine, dexamethasone, recombinant human granulocyte colony stimulating factor and tocilizumab indicated lower occurrence of mechanical ventilation; tofacitinib, sarilumab, remdesivir, tocilizumab and baricitinib plus remdesivir increased the hospital discharge rate; convalescent plasma, ivermectin, ivermectin plus doxycycline, hydroxychloroquine, nitazoxanide and proxalutamide resulted in better viral clearance. From the treatment class level, we found that the use of antineoplastic agents was associated with fewer mortality cases, immunostimulants could reduce the risk of mechanical ventilation and immunosuppressants led to higher discharge rates. Conclusions: This network meta-analysis identified superiority of several COVID-19 treatments over the standard of care in terms of mortality, mechanical ventilation, hospital discharge and viral clearance. Tocilizumab showed its superiority compared with SOC on preventing severe outcomes such as death and mechanical ventilation as well as increasing the discharge rate, which might be an appropriate treatment for patients with severe or mild/moderate illness. We also found the clinical efficacy of antineoplastic agents, immunostimulants and immunosuppressants with respect to the endpoints of mortality, mechanical ventilation and discharge, which provides valuable information for the discovery of potential COVID-19 treatments.
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Project description:ObjectivesHeart Failure is a chronic syndrome affecting over 5.7 million in the US and 26 million adults worldwide with nearly 50% experiencing depressive symptoms. The objective of the study is to compare the effects of two evidence-based treatment options for adult patients with depression and advanced heart failure, on depressive symptom severity, physical and mental health related quality of life (HRQoL), heart-failure specific quality of life, caregiver burden, morbidity, and mortality at 3, 6 and 12-months.MethodsTrial design. Pragmatic, randomized, comparative effectiveness trial. Interventions. The treatment interventions are: (1) Behavioral Activation (BA), a patient-centered psychotherapy which emphasizes engagement in enjoyable and valued personalized activities as selected by the patient; or (2) Antidepressant Medication Management administered using the collaborative care model (MEDS). Participants. Adults aged 18 and over with advanced heart failure (defined as New York Heart Association (NYHA) Class II, III, and IV) and depression (defined as a score of 10 or above on the PHQ-9 and confirmed by the MINI International Neuropsychiatric Interview for the DSM-5) selected from all patients at Cedars-Sinai Medical Center who are admitted with heart failure and all patients presenting to the outpatient programs of the Smidt Heart Institute at Cedars-Sinai Medical Center. We plan to randomize 416 patients to BA or MEDS, with an estimated 28% loss to follow-up/inability to collect follow-up data. Thus, we plan to include 150 in each group for a total of 300 participants from which data after randomization will be collected and analyzed.ConclusionsThe current trial is the first to compare the impact of BA and MEDS on depressive symptoms, quality of life, caregiver burden, morbidity, and mortality in patients with depression and advanced heart failure. The trial will provide novel results that will be disseminated and implemented into a wide range of current practice settings.RegistrationClinicalTrials.Gov Identifier: NCT03688100.
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Project description:Non-motor symptoms (NMS) including sleep disorders, anxiety, depression, fatigue, and cognitive decline can significantly impact quality of life in people with PD. Qigong exercise is a mind-body exercise that shows a wide range of benefits in various medical conditions. The purpose of this study was to investigate the effect of Qigong exercise on NMS with a focus on sleep quality. Seventeen participants completed a 12-week intervention of Qigong (n = 8) or sham Qigong (n = 9). Disease severity, anxiety and depression levels, fatigue, cognition, quality of life, and other NMS of the participants were evaluated prior to the intervention and at the end of the 12-week intervention. After the intervention, both Qigong and sham-Qigong group showed significant improvement in sleep quality (p < 0.05) and overall NMS (p < 0.05). No significant difference was found between groups. Qigong exercise has the potential as a rehabilitation method for people with PD, specifically alleviating NMS in PD. However, this finding needs to be carefully considered due to the small sample size and potentially low intervention fidelity of this study.
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Project description:BackgroundDepression is a major nonmotor symptom of Parkinson's disease (PD). However, few treatments exist for PD depression. Monoamine oxidase-B inhibitors (MAOB-Is) provide symptomatic relief for the motor symptoms of PD and exert antidepressive effects. The present meta-analysis of randomized controlled trials (RCTs) investigated the effects of MAOB-Is on depressive symptoms in patients with PD.MethodsArticles on PD-management-related RCTs using one of three MAOB-Is approved by the US Food and Drug Administration, that is, selegiline, rasagiline, and safinamide, were identified. The primary outcomes were the benefits of MAOB-Is for depressive symptoms. Subgroup analysis included the effects of MAOB-Is on patients in the early versus middle-to-late stages of PD and the effect of short-term versus long-term treatment.ResultsOverall, six studies were included, four of which were conducted on patients with early stage PD. Overall, MAOB-Is significantly reduced the severity of depressive symptoms [standardized mean difference (SMD): -0.14, 95% confidence interval (CI): -0.21 to -0.06, p < 0.001]. Subgroup analysis indicated that the positive effect of MAOB-Is was significant in patients with early stage PD (SMD: -0.20, 95% CI: -0.31 to -0.09, p < 0.001), but not in those with middle-to-late-stage PD (SMD: -0.07, 95% CI: -0.17 to 0.03, p = 0.18). The antidepressive effect was significant for short-term treatment, that is, 90-120 days (SMD: -0.23, 95% CI: -0.35 to -0.10, p < 0.001), but not long-term treatment, that is, 24 weeks to 18 months (SMD: -0.08, 95% CI: -0.18 to 0.01, p = 0.09).ConclusionIn addition to the treatment of PD motor symptoms, MAOB-Is may help reduce the severity of depressive symptoms in PD, especially in patients with early stage PD. Considering the tolerability and simultaneous benefits of MAOB-Is, further RCTs are warranted to confirm their therapeutic effects in moderate-to-severe PD depression.
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Project description:Background: Melasma is an acquired pigmentation disorder with challenges in treatment because of its refractory nature and high risk of recurrence. Objectives: This study aimed to compare the efficacy and side effects of 14 common therapies for melasma using a systematic review and network meta-analysis (NMA). Methods: The PubMed, Embase, and Cochrane Library databases were searched till December 2020 using the melasma area and severity index as a therapeutic index. A total of 59 randomized controlled trials (RCTs) met the inclusion criteria and were selected. Results: The ranking of relative efficacy compared with placebo in descending order was Q-switched Nd:Yag 1,064-nm laser (QSND), intense pulsed light, ablative fractional laser (AFL), triple combined cream (TCC), topical vitamin C, oral tranexamic acid (oTA), peeling, azelaic acid, microneedles (MNs), topical tranexamic acid (tTA), tretinoin, picosecond laser, hydroquinone (HQ), and non-AFL. Moreover, QSND was more effective than HQ and tTA against melasma. The ranking of percentage (%) of side effects in ascending order for each of 14 therapies with more than 80 participants was tretinoin (10.1%), oTA (17.6%), HQ (18.2%), AFL (20.0%), QSND (21.5%), TCC (25.7%), tTA (36.75%), peeling (38.0%), and MN (52.3%). Taking both efficacy and safety into consideration, TCC was found to be the most favorable selection among the topical drugs for melasma. QSND and AFL were still the best ways to treat melasma among photoelectric devices. oTA as system administration was a promising way recommended for melasma. Among 31 studies, 87% (27/31) studies showed that the efficacy of combination therapies is superior to that of single therapy. The quality of evidence in this study was generally high because of nearly 50% of split-face RCTs. Conclusions: Based on the published studies, this NMA indicated that QSND, AFL, TCC, and oTA would be the preferred ways to treat melasma for dermatologists. However, more attention should be paid to the efficacy and safety simultaneously during the clinical application. Most of the results were in line with those of the previous studies, but a large number of RCTs should be included for validation or update. Systematic Review Registration: identifier: CRD42021239203.
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Project description:Background No network meta-analysis has considered the relative efficacy of cilostazol, home exercise therapy, supervised exercise therapy (SET), endovascular revascularization (ER), and ER plus SET (ER+SET) in improving maximum walking distance (MWD) over short- (<1 year), moderate- (1 to <2 years), and long-term (≥2 years) follow-up in people with intermittent claudication. Methods and Results A systematic literature search was performed to identify randomized controlled trials testing 1 or more of these 5 treatments according to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The primary outcome was improvement in MWD assessed by a standardized treadmill test. Secondary outcomes were adverse events and health-related quality of life. Network meta-analysis was performed using the gemtc R statistical package. The Cochrane collaborative tool was used to assess risk of bias. Forty-six trials involving 4256 patients were included. At short-term follow-up, home exercise therapy (mean difference [MD], 89.4 m; 95% credible interval [CrI], 20.9-157.7), SET (MD, 186.8 m; 95% CrI, 136.4-237.6), and ER+SET (MD, 326.3 m; 95% CrI, 222.6-430.6), but not ER (MD, 82.5 m; 95% CrI, -2.4 to 168.2) and cilostazol (MD, 71.1 m; 95% CrI, -24.6 to 167.9), significantly improved MWD (in meters) compared with controls. At moderate-term follow-up, SET (MD, 201.1; 95% CrI, 89.8-318.3) and ER+SET (MD, 368.5; 95% CrI, 195.3-546.9), but not home exercise therapy (MD, 99.4; 95% CrI, -174.0 to 374.9) or ER (MD, 84.2; 95% CrI, -35.3 to 206.4), significantly improved MWD (in meters) compared to controls. At long-term follow-up, none of the tested treatments significantly improved MWD compared to controls. Adverse events and quality of life were reported inconsistently and could not be meta-analyzed. Risk of bias was low, moderate, and high in 4, 24, and 18 trials respectively. Conclusions This network meta-analysis suggested that SET and ER+SET are effective at improving MWD over the moderate term (<2 year) but not beyond this. Durable treatments for intermittent claudication are needed.
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