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BMJ Open May 2022To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to... (Meta-Analysis)
Meta-Analysis
Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations.
OBJECTIVE
To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to prevent HIV.
METHODS
Databases (PubMed, Embase and the Cochrane Register of Controlled Trials) were searched up to 5 July 2020. Search terms for 'HIV' were combined with terms for 'PrEP' or 'tenofovir/emtricitabine'. RCTs were included that compared oral tenofovir-containing PrEP to placebo, no treatment or alternative medication/dosing schedule. The primary outcome was the rate ratio (RR) of HIV infection using a modified intention-to-treat analysis. Secondary outcomes included safety, adherence and risk compensation. All analyses were stratified a priori by population: men who have sex with men (MSM), serodiscordant couples, heterosexuals and people who inject drugs (PWIDs). The quality of individual studies was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was assessed using GRADE.
RESULTS
Of 2803 unique records, 15 RCTs met our inclusion criteria. Over 25 000 participants were included, encompassing 38 289 person-years of follow-up data. PrEP was found to be effective in MSM (RR 0.25, 95% CI 0.1 to 0.61; absolute rate difference (RD) -0.03, 95% CI -0.01 to -0.05), serodiscordant couples (RR 0.25, 95% CI 0.14 to 0.46; RD -0.01, 95% CI -0.01 to -0.02) and PWID (RR 0.51, 95% CI 0.29 to 0.92; RD -0.00, 95% CI -0.00 to -0.01), but not in heterosexuals (RR 0.77, 95% CI 0.46 to 1.29). Efficacy was strongly associated with adherence (p<0.01). PrEP was found to be safe, but unrecognised HIV at enrolment increased the risk of viral drug resistance mutations. Evidence for behaviour change or an increase in sexually transmitted infections was not found.
CONCLUSIONS
PrEP is safe and effective in MSM, serodiscordant couples and PWIDs. Additional research is needed prior to recommending PrEP in heterosexuals. No RCTs reported effectiveness or safety data for other high-risk groups, such as transgender women and sex workers.
PROSPERO REGISTRATION NUMBER
CRD42017065937.
Topics: Anti-HIV Agents; Emtricitabine; Female; HIV Infections; Humans; Male; Pre-Exposure Prophylaxis; Tenofovir; Treatment Outcome
PubMed: 35545381
DOI: 10.1136/bmjopen-2020-048478 -
Acta Neuropsychiatrica Apr 2023Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs) have evaluated the efficacy of different strategies to augment clozapine. This systematic review and meta-analysis reviewed the available RCTs that have evaluated the clinical efficacy of various pharmacological agents, non-pharmacological strategies (occupational therapy, cognitive behaviour therapy), and somatic treatment [electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, etc.)] as augmenting agents to clozapine.
METHODS
Data were extracted using standard procedures, and risk of bias was evaluated. Effect sizes were computed for the individual studies.
RESULTS
Forty-five clinical trials were evaluated. The pooled effect size for various antipsychotic medications was 0.103 (95% CI: 0.288-0.493, < 0.001); when the effect size was evaluated for specific antipsychotics for which more than one trial was available, the effect size for risperidone was -0.27 and that for aripiprazole was 0.57. The effect size for lamotrigine was 0.145, and that for topiramate was 0.392. The effect size for ECT was 0.743 (CI: 0.094-1.392). Risk of bias was low (mean Jadad score - 3.93). Largest effect sizes were seen for mirtazapine (effect size of 5.265). Most of the studies can be considered underpowered and limited by small sample sizes.
CONCLUSIONS
To conclude, based on the findings of the present systematic review and meta-analysis, it can be said that compared to other treatment strategies, clozapine non-responsive patients respond maximum to mirtazapine followed by ECT.
Topics: Humans; Clozapine; Schizophrenia; Mirtazapine; Antipsychotic Agents; Risperidone
PubMed: 36380513
DOI: 10.1017/neu.2022.30 -
Psychological Medicine Sep 2022Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants.... (Meta-Analysis)
Meta-Analysis Review
Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04-1.73 and 1.07-1.67, respectively] to 2.17 for risperidone (95% CrI 1.38-3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96-1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50-0.91), brexpiprazole (OR 0.69, 95% CrI 0.55-0.86), and cariprazine (OR 0.61, 95% CrI 0.46-0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25-1.07) and risperidone (OR 0.48, 95% CrI 0.10-2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.
Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Depressive Disorder, Major; Humans; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate; Risperidone
PubMed: 35993319
DOI: 10.1017/S0033291722001246 -
The Journal of International Medical... Mar 2023This study aimed to investigate the safety and efficacy of vericiguat in patients with heart failure (HF). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to investigate the safety and efficacy of vericiguat in patients with heart failure (HF).
METHODS
We conducted a comprehensive literature review of the PubMed, Embase, and Cochrane Library databases up to 14 December 2022 for studies comparing vericiguat with placebo in patients with HF. Clinical data were extracted and cardiovascular deaths, adverse effects, and HF-related hospitalization were analyzed using Review Manager software (version 5.3), after quality assessment of the enrolled studies.
RESULTS
Four studies (6705 patients) were included in this meta-analysis. There were no significant differences in the basic characteristics of the included studies. There was no significant difference in adverse effects between the vericiguat group and placebo group, and no significant differences between the groups in terms of cardiovascular death and HF hospitalization.
CONCLUSION
This meta-analysis indicated that vericiguat was not an effective drug for HF; however, more clinical trials are required to verify its efficacy.
Topics: Humans; Heart Failure; Hospitalization; Treatment Outcome; Heterocyclic Compounds, 2-Ring; Pyrimidines; Treatment Failure
PubMed: 36896460
DOI: 10.1177/03000605231159333 -
Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis.JMIR Public Health and Surveillance Jul 2023HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy.
OBJECTIVE
This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection.
METHODS
PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework.
RESULTS
We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs.
CONCLUSIONS
LA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate-emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.
Topics: Humans; Anti-HIV Agents; Emtricitabine; HIV Infections; HIV-1; Tenofovir
PubMed: 37498645
DOI: 10.2196/46767 -
Dermatologic Therapy May 2021Existing guidelines form no consensus for alopecia areata (AA) treatment due to the absence of a universal standard treatment and arbitrary selection of reference arms... (Meta-Analysis)
Meta-Analysis
Existing guidelines form no consensus for alopecia areata (AA) treatment due to the absence of a universal standard treatment and arbitrary selection of reference arms in randomized control trials (RCTs). The aim is to identify the best treatment and to rank treatments using systematic review and network meta-analysis. Data were extracted by the two investigators independently. Odds ratio (OR) of treatment success rate was pooled using the frequentist weighted least squares approach to random-model network meta-analysis. RCTs providing data of treatment success rate from PubMed, EMBASE, Web of Science, and manual search were included. About 54 RCTs consisting of 49 treatments and 3149 patients were included. Pentoxifylline plus topical corticosteroids had the highest treatment success rate compared with "no treatment," followed by pentoxifylline alone, topical calcipotriol plus narrowband ultraviolet radiation B phototherapy, topical calcipotriol, intralesional corticosteroids, systemic corticosteroids, minoxidil plus topical corticosteroids, topical bimatoprost, psoralen ultraviolet radiation A phototherapy, and tofacitinib. Even with the network meta-analysis, the best treatment because of independent loops and wide confidence intervals could not be identified. Treatment options above may be reasonable strategies, but further comparison is required.
Topics: Alopecia Areata; Humans; Minoxidil; Network Meta-Analysis; Phototherapy; Ultraviolet Therapy
PubMed: 33631058
DOI: 10.1111/dth.14916 -
International Journal of Colorectal... Oct 2021There is increasing evidence to support the use of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). However, its safety, efficacy and side effect... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is increasing evidence to support the use of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). However, its safety, efficacy and side effect profile is yet to be completely elucidated. This review aims to assess NAC regimens, duration, compare completion rates, intra-operative and post-operative complication profiles and oncological outcomes, in order to provide guidance for clinical practice and further research.
METHODS
PubMed, EMBASE and MEDLINE were searched for a systematic review of the literature from 2000 to 2020. Eight eligible studies were included, with a total of 1213 patients, 752 (62%) of whom received NAC. Of the eight studies analysed, two were randomised controlled trials comparing neoadjuvant chemotherapy followed by oncological resection to upfront surgery and adjuvant chemotherapy, three were prospective single-arm phase II trials analysing neoadjuvant chemotherapy followed by surgery only, one was a retrospective study comparing neoadjuvant chemotherapy followed by surgery versus surgery first followed by adjuvant chemotherapy and the remaining two were single-arm retrospective studies of neoadjuvant chemotherapy followed by surgery.
RESULTS
All cases of LACC were determined and staged by computed tomography; majority of the studies defined LACC as T3 with extramural depth of 5 mm or more, T4 and/or nodal positivity. NAC administered was either folinic acid, fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) with the exception of one study which utilised 5-fluorouracil and mitomycin. Most studies had NAC completion rates of above 83% with two notable exceptions being Zhou et al. and The Colorectal Cancer Chemotherapy Study Group of Japan who both recorded a completion rate of 52%. Time to surgery from completion of NAC ranged on average from 16 to 31 days. The anastomotic leak rate in the NAC group ranged from 0 to 4.5%, with no cases of postoperative mortality. The R0 resection rate in the NAC group was 96.1%. Meta-analysis of both RCTs included in this study showed that neoadjuvant chemotherapy increased the likelihood of a negative resection margin T3/4 advanced colon cancer (pooled relative risk of 0.47 with a 95% confidence interval) with no increase in adverse consequence of anastomotic leak, wound infection or return to theatre.
CONCLUSIONS
Our systematic review and meta-analysis show that NAC is safe with an acceptable side effect profile in the management of LACC. The current data supports an oncological benefit for tumour downstaging and increased in R0 resection rate.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Fluorouracil; Humans; Neoadjuvant Therapy; Neoplasm Staging; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 33945007
DOI: 10.1007/s00384-021-03945-3 -
Efficacy and safety of ruxolitinib in steroid-refractory graft-versus-host disease: A meta-analysis.Frontiers in Immunology 2022Ruxolitinib is an important treatment for steroid refractory graft-versus-host disease (SR-GVHD). Therefore, we reported the updated results of a systematic review and... (Meta-Analysis)
Meta-Analysis
Ruxolitinib is an important treatment for steroid refractory graft-versus-host disease (SR-GVHD). Therefore, we reported the updated results of a systematic review and meta-analysis of ruxolitinib as treatment for SR-GVHD. In addition, we wanted to compare the efficacy and safety between children and adults with SR-GVHD. Overall response rate (ORR) after ruxolitinib treatment was chosen as the primary end point. Complete response rate (CRR), infection, myelosuppression, and overall survival (OS) were chosen as secondary end points. A total of 37 studies were included in this meta-analysis, and 1,580 patients were enrolled. ORR at any time after ruxolitinib treatment was 0.77 [95% confidence interval (CI): 0.68-0.84] and 0.78 (95% CI: 0.74-0.81), respectively, for SR-aGVHD and SR-cGVHD. CRR at any time after ruxolitinib treatment was 0.49 (95% CI: 0.40-0.57) and 0.15 (95% CI: 0.10-0.23), respectively, for SR-aGVHD and SR-cGVHD. The ORRs at any time after treatment was highest in mouth SR-cGVHD, followed by skin, gut, joints and fascia, liver, eyes, esophagus, and lung SR-cGVHD. The incidence rate of infections after ruxolitinib treatment was 0.61 (95% CI: 0.45-0.76) and 0.47 (95% CI: 0.31-0.63), respectively, for SR-aGVHD and SR-cGVHD. The incidence rates of overall (grades I-IV) and severe (grades III-IV) cytopenia were 53.2% (95% CI: 16.0%-90.4%) and 31.0% (95% CI: 0.0-100.0%), respectively, for SR-aGVHD, and were 28.8% (95% CI:13.0%-44.6%) and 10.4% (95% CI: 0.0-27.9%), respectively, for SR-cGVHD. The probability rate of OS at 6 months after treatment was 63.9% (95% CI: 52.5%-75.2%) for SR-aGVHD. The probability rates of OS at 6 months, 1 year, and 2 years after treatment were 95% (95% CI: 79.5%-100.0%), 78.7% (95% CI: 67.2%-90.1%), and 75.3% (95% CI: 68.0%-82.7%), respectively, for SR-cGVHD. The ORR, CRR, infection events, and myelosuppression were all comparable between children and adults with SR-GVHD. In summary, this study suggests that ruxolitinib is an effective and safe treatment for SR-GVHD, and both children and adults with SR-GVHD could benefit from ruxolitinib treatment.
Topics: Adult; Child; Graft vs Host Disease; Humans; Nitriles; Pyrazoles; Pyrimidines; Steroids
PubMed: 35990629
DOI: 10.3389/fimmu.2022.954268 -
Nutrients Jan 2023Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive impairment is a staggering personal and societal burden; accordingly, there is a strong interest in potential strategies for its prevention and treatment. Nutritional supplements have been extensively investigated, and citicoline seems to be a promising agent; its role in clinical practice, however, has not been established. We systematically reviewed studies on the effect of citicoline on cognitive performance.
METHODS
We searched the PubMed and Cochrane Library databases for articles published between 2010 and 2022. Relevant information was extracted and presented following the PRISMA recommendations. Data were pooled using the inverse-variance method with random effects models.
RESULTS
We selected seven studies including patients with mild cognitive impairment, Alzheimer's disease or post-stroke dementia. All the studies showed a positive effect of citicoline on cognitive functions. Six studies could be included in the meta-analysis. Overall, citicoline improved cognitive status, with pooled standardized mean differences ranging from 0.56 (95% CI: 0.37-0.75) to 1.57 (95% CI: 0.77-2.37) in different sensitivity analyses. The overall quality of the studies was poor.
DISCUSSION
Available data indicate that citicoline has positive effects on cognitive function. The general quality of the studies, however, is poor with significant risk of bias in favor of the intervention. Other: PubMed and the Cochrane Library.
Topics: Humans; Cytidine Diphosphate Choline; Alzheimer Disease; Cognitive Dysfunction; Cognition Disorders; Cognition
PubMed: 36678257
DOI: 10.3390/nu15020386 -
Journal of Psychiatric Research Jun 2020We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of... (Meta-Analysis)
Meta-Analysis Review
We performed a network meta-analysis to build clear hierarchies of efficacy and tolerability of pharmacological interventions for the treatment and prevention of delirium. Electronic databases including PubMed, Google Scholar, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and MEDLINE were searched published up to February 22, 2019. A total of 108 randomized controlled trials (RCTs) investigating pharmacotherapy on delirium were included for analysis, and the strength of evidence (SoE) was evaluated for critical outcomes. In terms of treatment, quetiapine (low SoE), morphine (low SoE), and dexmedetomidine (moderate SoE) were effective in the intensive care unit (ICU) patients. In terms of prevention, dexmedetomidine (high SoE) and risperidone (high SoE) significantly reduced the incidence of delirium in ICU surgical patients, while ramelteon (high SoE) reduced the incidence of delirium in ICU medical patients. Despite the efficacy, dexmedetomidine and risperidone demonstrated higher drop-out rate (moderate to high SoE). Haloperidol and other antipsychotics, except for quetiapine and risperidone, showed no benefit. None of the agents showed benefit in non-ICU patients. In conclusion, dexmedetomidine may be a drug of choice for both treating and preventing delirium of the ICU and postsurgical patients. However, it may be less tolerable, and side-effects should be adequately managed. Current evidence does not support the routine use of antipsychotics. For medical patients, oral ramelteon might be useful for prevention.
Topics: Antipsychotic Agents; Delirium; Haloperidol; Humans; Network Meta-Analysis; Risperidone
PubMed: 32302794
DOI: 10.1016/j.jpsychires.2020.03.012