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JAMA Aug 2023A 2019 review for the US Preventive Services Task Force (USPSTF) found oral preexposure prophylaxis (PrEP) associated with decreased HIV infection risk vs placebo or no...
IMPORTANCE
A 2019 review for the US Preventive Services Task Force (USPSTF) found oral preexposure prophylaxis (PrEP) associated with decreased HIV infection risk vs placebo or no PrEP in adults at increased HIV acquisition risk. Newer PrEP regimens are available.
OBJECTIVE
To update the 2019 review on PrEP, to inform the USPSTF.
DATA SOURCES
Ovid MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Embase (January 2018 to May 16, 2022); surveillance through March 24, 2023.
STUDY SELECTION
Randomized clinical trials of PrEP vs placebo or no PrEP or newer vs older PrEP regimens and diagnostic accuracy studies of instruments for predicting incident HIV infection.
DATA EXTRACTION AND SYNTHESIS
Dual review of titles and abstracts, full-text articles, study quality, and data abstraction. Data were pooled using the DerSimonian and Laird random-effects model.
MAIN OUTCOMES AND MEASURES
HIV acquisition, mortality, and harms; and diagnostic test accuracy.
RESULTS
Thirty-two studies were included in the review (20 randomized clinical trials [N = 36 543] and 12 studies of diagnostic accuracy [N = 5 544 500]). Eleven trials in the 2019 review found oral PrEP associated with decreased HIV infection risk vs placebo or no PrEP (n = 18 172; relative risk [RR], 0.46 [95% CI, 0.33-0.66]). Higher adherence was associated with greater efficacy. One new trial (n = 5335) found oral tenofovir alafenamide/emtricitabine (TAF/FTC) to be noninferior to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in men who have sex with men (RR, 0.47 [95% CI, 0.19-1.14]). Two new trials found long-acting injectable cabotegravir associated with decreased risk of HIV infection vs oral TDF/FTC (RR, 0.33 [95% CI, 0.18-0.62] in cisgender men who have sex with men and transgender women [n = 4490] and RR, 0.11 [95% CI, 0.04-0.31] in cisgender women [n = 3178]). Discrimination of instruments for predicting incident HIV infection was moderate in men who have sex with men (5 studies; n = 25 488) and moderate to high in general populations of persons without HIV (2 studies; n = 5 477 291).
CONCLUSIONS AND RELEVANCE
In adults at increased HIV acquisition risk, oral PrEP was associated with decreased risk of acquiring HIV infection compared with placebo or no PrEP. Oral TAF/FTC was noninferior to oral TDF/FTC, and injectable cabotegravir reduced the risk of HIV infection compared with oral TDF/FTC in the populations studied.
Topics: Adult; Female; Humans; Male; Administration, Oral; Anti-HIV Agents; Emtricitabine; HIV Infections; Homosexuality, Male; Injections; Practice Guidelines as Topic; Pre-Exposure Prophylaxis; Randomized Controlled Trials as Topic; Risk; Sexual and Gender Minorities; Tenofovir
PubMed: 37606667
DOI: 10.1001/jama.2023.9865 -
Journal of Cosmetic Dermatology Jan 2024
Meta-Analysis
Topics: Humans; Nitriles; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome; Vitiligo; Pyrazoles
PubMed: 38161317
DOI: 10.1111/jocd.15921 -
JAMA Dermatology May 2024Sulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 5:1 ratio, are antibacterial sulfonamides commonly used for... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Sulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 5:1 ratio, are antibacterial sulfonamides commonly used for treating various diseases. A substantial prevalence of severe cutaneous adverse reactions (SCARs) following the administration of these drugs has been reported. However, the association between human leukocyte antigen (HLA) genotypes and SMX/CTX-induced SCARs has remained unclear.
OBJECTIVE
To investigate the association between HLA genotypes and SMX/CTX-induced SCARs.
DATA SOURCES
A comprehensive search was conducted in CENTRAL (Cochrane Library), MEDLINE, and Embase from inception to January 17, 2023.
STUDY SELECTION
Case-control studies that recruited patients who had experienced SCARs following SMX or CTX were included, and HLA alleles were analyzed.
DATA EXTRACTION AND SYNTHESIS
Two independent authors extracted data on study characteristics and outcome data. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. The Newcastle-Ottawa Scale for case-control studies was used to assess study quality. Odds ratios (ORs) were calculated using a random-effects model for meta-analysis.
MAIN OUTCOMES AND MEASURES
The prespecified outcome was the OR comparing SMX/CTX-induced SCARs with healthy or SMX/CTX-tolerant controls based on different HLA alleles.
RESULTS
Six studies involving 322 patients with SCAR were included, including 236 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis, 86 with drug reaction with eosinophilia and systemic symptoms, 8448 healthy controls, and 229 tolerant controls. Significant associations were found in HLA-A*11:01 (OR, 2.10; 95% CI, 1.11-4.00), HLA-B*13:01 (OR, 5.96; 95% CI, 1.58-22.56), HLA-B*15:02 (OR, 2.23; 95% CI, 1.20-4.14), HLA-B*38:02 (OR, 3.47; 95% CI, 1.42-8.48), and HLA-C*08:01 (OR, 2.63; 95% CI, 1.07-6.44) compared with tolerant controls. In the Stevens-Johnson syndrome/toxic epidermal necrolysis subgroup, significant associations were found in HLA-B*15:02 (OR, 3.01; 95% CI, 1.56-5.80) and HLA-B*38:02 (OR, 5.13; 95% CI, 1.96-13.47). In the drug reaction with eosinophilia and systemic symptoms subgroup, significant associations were found in HLA-A*68:01 (OR, 12.86; 95% CI, 1.09-151.34), HLA-B*13:01 (OR, 23.09; 95% CI, 3.31-161.00), HLA-B*39:01 (OR, 4.56; 95% CI, 1.31-15.82).
CONCLUSIONS AND RELEVANCE
The results of this systematic review and meta-analysis suggest that multiple HLA alleles (HLA-A*11:01, HLA-B*13:01, HLA-B*15:02, HLA-B*38:02, and HLA-C*0801) are associated with SMX/CTX-induced SCARs.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; HLA Antigens; Drug Eruptions; Sulfamethoxazole; Genotype; Severity of Illness Index; Anti-Bacterial Agents; Case-Control Studies
PubMed: 38568509
DOI: 10.1001/jamadermatol.2024.0210 -
Journal of Cardiovascular Medicine... Jul 2024We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients. (Meta-Analysis)
Meta-Analysis
AIMS
We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients.
METHODS
A systematic review and meta-analysis was conducted, and efficacy [changes in postexercise left ventricular outflow tract (LVOT) gradient, left ventricular ejection fraction (LVEF), peak oxygen consumption (pVO 2 ), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), and the proportion of patients exhibiting an improvement of at least one New York Heart Association (NYHA) functional class from baseline)], safety (total count of treatment-emergent adverse events and SAEs, as well as the proportion of patients experiencing at least one adverse event or SAE), and cardiac biomarkers (NT-proBNP and cTnI) outcomes were evaluated.
RESULTS
We incorporated data from four randomized controlled trials, namely EXPLORER-HCM, VALOR-HCM, MAVERICK-HCM, and EXPLORER-CN. Mavacamten demonstrated significant efficacy in reducing the postexercise LVOT gradient by 49.44 mmHg ( P = 0.0001) and LVEF by 3.84 ( P < 0.0001) and improving pVO 2 by 0.69 ml/kg/min ( P = 0.4547), KCCQ CSS by 8.11 points ( P < 0.0001), and patients with at least one NYHA functional class improvement from baseline by 2.20 times ( P < 0.0001). Importantly, mavacamten increased 1.11-fold adverse events ( P = 0.0184) 4.24-fold reduced LVEF to less than 50% ( P = 0.0233) and 1.06-fold SAEs ( P = 0.8631). Additionally, mavacamten decreased NT-proBNP by 528.62 ng/l ( P < 0.0001) and cTnI by 8.28 ng/l ( P < 0.0001).
CONCLUSION
Mavacamten demonstrates both safety and efficacy in patients with HCM, suggesting its potential as a promising therapeutic strategy for this condition. Further research is warranted to confirm these results and explore its long-term effects.
Topics: Humans; Cardiomyopathy, Hypertrophic; Treatment Outcome; Randomized Controlled Trials as Topic; Ventricular Function, Left; Stroke Volume; Middle Aged; Male; Female; Natriuretic Peptide, Brain; Pyrimidines; Exercise Tolerance; Biomarkers; Adult; Recovery of Function; Oxygen Consumption; Aged; Benzylamines; Uracil
PubMed: 38814051
DOI: 10.2459/JCM.0000000000001638 -
Yonsei Medical Journal Jan 2024There are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe... (Meta-Analysis)
Meta-Analysis
PURPOSE
There are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe combination and whether such regimens have differences in safety. We compared the lipid-modifying efficacy and safety of 5 mg rosuvastatin/10 mg ezetimibe to those of 20 mg rosuvastatin.
MATERIALS AND METHODS
A literature search was conducted using the PubMed, EMBASE, Cochrane, Web of Sciences, and SCOPUS databases up to December 2021. Human studies investigating the two aforementioned regimens with a randomized controlled design were selected. Outcome variables included the percentage reduction in LDL-C and other lipid parameters and rates of composite adverse events (AEs), including muscle-related symptoms. A random-effects meta-analysis was performed after heterogeneity testing between studies.
RESULTS
Seven studies were included in this meta-analysis. The percentage LDL-C reduction did not differ between the combination and monotherapy groups [standardized mean difference (SMD) 0.08; 95% confidence interval (CI) -0.09 to 0.26; =0.35]. The risk of composite AEs (odds ratio 0.50; 95% CI 0.15 to 1.72; =0.27) of the combination was not different compared to the monotherapy group. The percentage of total cholesterol reduction was greater in the combination group (SMD 0.22; =0.02), whereas that of triglyceride reduction and high-density lipoprotein cholesterol elevation did not differ between the two groups.
CONCLUSION
This meta-analysis showed that 5 mg rosuvastatin/10 mg ezetimibe had largely comparable lipid-modifying efficacy and tolerability as 20 mg rosuvastatin.
Topics: Humans; Rosuvastatin Calcium; Ezetimibe; Cholesterol, LDL; Anticholesteremic Agents; Hypercholesterolemia; Drug Therapy, Combination; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Treatment Outcome
PubMed: 38154476
DOI: 10.3349/ymj.2023.0285 -
Cardiology in the Young Nov 2023The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare... (Meta-Analysis)
Meta-Analysis
The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare the efficacy and safety of pulmonary vasodilators in PAH-CHD. PubMed and EMBASE databases were searched through May 2022 and a network meta-analysis was conducted. The primary outcomes were mean difference of changes in 6-minute walk distance, NYHA functional class, and N-terminal pro-brain natriuretic peptide. The secondary outcomes included pulmonary vascular resistance, mean pulmonary arterial pressure, and resting oxygen saturation. We identified 14 studies, yielding 807 patients with PAH-CHD. Bosentan and sildenafil were associated with a significant increase in 6-minute walk distance from baseline compared with placebo (MD 48.92 m, 95% CI 0.32 to 97.55 and MD 59.70 m, 95% CI 0.88 to 118.53, respectively). Bosentan, sildenafil, and combination of bosentan and sildenafil were associated with significant improvement in NYHA functional class compared with placebo (MD -0.33, 95% CI -0.51 to -0.14, MD -0.58, 95% CI -0.75 to -0.22 and MD -0.62, 95% CI -0.92 to -0.31, respectively). Bosentan and sildenafil were also associated with significant improvements in secondary outcomes. These findings were largely confirmed in the subgroup analysis. Various adverse events were reported; however, serious adverse event rates were relatively low (4.8-8.7%), including right heart failure, acute kidney injury, respiratory failure, hypotension, and discontinuation of pulmonary vasodilators. In conclusion, bosentan and sildenafil were the most effective in improving prognostic risk factor such as 6-minute walk distance and NYHA class. Overall, pulmonary vasodilators were well tolerated in PAH-CHD.
Topics: Humans; Vasodilator Agents; Bosentan; Sildenafil Citrate; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Antihypertensive Agents; Sulfonamides; Network Meta-Analysis; Treatment Outcome; Familial Primary Pulmonary Hypertension
PubMed: 36721907
DOI: 10.1017/S1047951123000124 -
Transplant Immunology Dec 2023The selection of antiviral therapy for BK polyomavirus (BKPyV) infection has been extensively debated. Our study aimed to assess the efficacy and safety of various... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The selection of antiviral therapy for BK polyomavirus (BKPyV) infection has been extensively debated. Our study aimed to assess the efficacy and safety of various treatments for BKPyV infection.
METHODS
We searched PubMed, EMBASE, and Web of Science databases for relevant studies regarding drug treatments for BKPyV viremia/DNAemia published between January 1, 1970 and September 30, 2022. Two independent authors screened the published studies, extracted pertinent data, and evaluated their methodological quality. A meta-analysis was performed using the RevMan software version 4.2.2.
RESULTS
A total of 33 published studies involving 986 patients were included in the meta-analysis. Overall, therapeutic interventions comprised immunosuppression reduction alone or in combination with leflunomide, intravenous immunoglobulin (IVIG), cidofovir, or mTOR inhibitor (mTORi) therapy. The meta-analysis revealed that the efficacy of immunosuppression reduction alone for serum BKPyV clearance was 68% (95% confidence interval [CI]: 0.58-0.77; I = 78%). Moreover, the efficacy of immunosuppression reduction in combination with leflunomide, cidofovir, IVIG, or mTORi therapy for serum BKPyV clearance was 61% (95% CI: 0.47-0.74; I = 83%), 71% (95% CI: 0.63-0.78; I = 0), 87% (95% CI: 0.82-0.93; I = 45%), and 80% (95% CI: 0.59-1.00; I = 58%), respectively. Compared to immunosuppression reduction alone, immunosuppression reduction combined with IVIG therapy offered a statistically significant benefit in serum BKPyV clearance (P < 0.01) with minimal adverse reactions, whereas other adjunctive drug treatments did not demonstrate considerable effects.
CONCLUSIONS
Reducing immunosuppression remains the primary approach for treating BKPyV infection. Although the combination treatment with IVIG proved to be most effective, other agents might offer varied antiviral advantages of high heterogeneity, which should be substantiated in future long-term randomized controlled trials.
Topics: Humans; Kidney Transplantation; Cidofovir; Leflunomide; Immunoglobulins, Intravenous; Polyomavirus Infections; BK Virus; Tumor Virus Infections; Transplant Recipients
PubMed: 37931665
DOI: 10.1016/j.trim.2023.101953 -
Plastic and Reconstructive Surgery Jun 2024Keloids and hypertrophic scars cause physical and psychosocial problems. A combination of 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC) may enhance the... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparing Combination Triamcinolone Acetonide and 5-Fluorouracil with Monotherapy Triamcinolone Acetonide or 5-Fluorouracil in the Treatment of Hypertrophic Scars: A Systematic Review and Meta-Analysis.
BACKGROUND
Keloids and hypertrophic scars cause physical and psychosocial problems. A combination of 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC) may enhance the treatment of pathologic scars, although the evidence base is limited. The authors compared the efficacy and complication rates of combination intralesional TAC and 5-FU with those of monotherapy intralesional TAC or 5-FU for the treatment of keloids and hypertrophic scars.
METHODS
Embase, MEDLINE, and CENTRAL were searched by two independent reviewers. The primary outcome was treatment efficacy (51% to 100% improvement). Study quality and risk of bias were assessed using the Cochrane risk of bias tool.
RESULTS
Of 277 articles screened, 13 studies were included, comprising 12 randomized control trials and one nonrandomized study. Six studies compared combination intralesional therapy versus monotherapy 5-FU, and nine studies compared combination intralesional therapy versus monotherapy TAC. The combined group demonstrated superior objective treatment efficacy compared with the monotherapy TAC group (OR, 3.45; 95% CI, 2.22 to 5.35; I 2 = 0%; P < 0.00001) and monotherapy 5-FU group (OR, 4.17; 95% CI, 2.21 to 7.87; I 2 = 0%; P < 0.0001). Telangiectasia was less frequent in combination therapy (OR, 0.24; 95% CI, 0.11 to 0.52; I 2 = 0%; P = 0.0003) compared with monotherapy TAC.
CONCLUSIONS
Combined intralesional TAC and 5-FU administration demonstrated superior treatment efficacy outcomes compared with monotherapy TAC or 5-FU. Patient-reported outcome measures should be incorporated in the design of future research to justify clinical recommendations.
CLINICAL RELEVANCE STATEMENT
Combined TAC and 5-FU has demonstrated superior treatment efficacy outcomes compared to monotherapy TAC or 5-FU in the treatment of hypertrophic scars and keloids.
Topics: Humans; Fluorouracil; Cicatrix, Hypertrophic; Triamcinolone Acetonide; Drug Therapy, Combination; Injections, Intralesional; Treatment Outcome; Keloid; Glucocorticoids
PubMed: 37337341
DOI: 10.1097/PRS.0000000000010867 -
Annals of Clinical Microbiology and... Mar 2024Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Infections caused by Stenotrophomonas maltophilia are clinically important due to its intrinsic resistance to a broad range of antibiotics. Therefore, selecting the most appropriate antibiotic to treat S. maltophilia infection is a major challenge.
AIM
The current meta-analysis aimed to investigate the global prevalence of antibiotic resistance among S. maltophilia isolates to the develop more effective therapeutic strategies.
METHOD
A systematic literature search was performed using the appropriate search syntax after searching Pubmed, Embase, Web of Science and Scopus databases (May 2023). Statistical analysis was performed using Pooled and the random effects model in R and the metafor package. A total of 11,438 articles were retrieved. After a thorough evaluation, 289 studies were finally eligible for inclusion in this systematic review and meta-analysis.
RESULT
Present analysis indicated that the highest incidences of resistance were associated with doripenem (97%), cefoxitin (96%), imipenem and cefuroxime (95%), ampicillin (94%), ceftriaxone (92%), aztreonam (91%) and meropenem (90%) which resistance to Carbapenems is intrinsic. The lowest resistance rates were documented for minocycline (3%), cefiderocol (4%). The global resistance rate to TMP-SMX remained constant in two periods before and after 2010 (14.4% vs. 14.6%). A significant increase in resistance to tigecycline and ceftolozane/tazobactam was observed before and after 2010.
CONCLUSIONS
Minocycline and cefiderocol can be considered the preferred treatment options due to low resistance rates, although regional differences in resistance rates to other antibiotics should be considered. The low global prevalence of resistance to TMP-SMX as a first-line treatment for S. maltophilia suggests that it remains an effective treatment option.
Topics: Humans; Trimethoprim, Sulfamethoxazole Drug Combination; Minocycline; Stenotrophomonas maltophilia; Microbial Sensitivity Tests; Anti-Bacterial Agents; Cefiderocol; Drug Resistance, Microbial; Gram-Negative Bacterial Infections
PubMed: 38504262
DOI: 10.1186/s12941-024-00685-4 -
Critical Reviews in Oncology/hematology Aug 2023Aflibercept; a decoy receptor for vascular endothelial growth factors (VEGFs) and placental growth factor (PLGF), in combination with FOLFIRI (leucovorin calcium,... (Meta-Analysis)
Meta-Analysis Review
A systemic review and meta-analysis of Aflibercept plus FOLFIRI regimen as a second-line treatment for metastatic colorectal cancer: A PRISMA compliant pooled analysis of randomized controlled trials and single arm studies to assess efficacy and safety.
BACKGROUND AND OBJECTIVE
Aflibercept; a decoy receptor for vascular endothelial growth factors (VEGFs) and placental growth factor (PLGF), in combination with FOLFIRI (leucovorin calcium, fluorouracil, irinotecan hydrochloride) chemotherapy regime, was FDA approved in 2012 as second-line salvage chemotherapy for metastatic colorectal cancer (mCRC). This is the first systematic review, and meta-analysis-based evidence to determine the efficacy and safety of Aflibercept plus FOLFIRI regimen pooling randomized controlled trials and single-arm studies.
METHOD
PubMed, Cochrane library, Embase, and Clinical trial.gov were systematically searched for published randomized controlled trials, single-arm studies, and national patient programs on aflibercept plus FOLFIRI chemotherapy for the treatment of mCRC till 11/10/2022.
RESULT
Ten studies met the inclusion criteria comprising 1075 patients for efficacy studies and 2027 patients for safety studies. The pooled prevalences were 18% (95% CI, 5%-37%, p = 0.00) for 12 m PFS and 61% (95% CI, 53-68%, p = 0.00) for 12 m OS. The pooled prevalences were 69% (95% CI, 55-82%, p = 0.00) for any grade 3-4 toxicities, 10% (95% CI, 5-16%, p = 0.00) for grade 3-4 diarrhea, 13% (95% CI, 5-24%, p = 0.00) for grade 3-4 hypertension, 31% (95% CI, 22-40%, p = 0.00) for grade 3-4 neutropenia and 5% (95% CI, 2-7%, p = 0.00) for grade 3-4 venous thromboembolic event.
CONCLUSION
Our meta-analysis shows that the aflibercept plus FOLFIRI combination shows better survival efficacies however; it is also associated with more high-grade adverse events.
Topics: Humans; Female; Colorectal Neoplasms; Camptothecin; Placenta Growth Factor; Randomized Controlled Trials as Topic; Colonic Neoplasms; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Rectal Neoplasms; Fluorouracil; Leucovorin; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37257732
DOI: 10.1016/j.critrevonc.2023.104034