Chest X-ray Features of HIV-Associated Pneumocystis Pneumonia (PCP) in Adults: A Systematic Review and Meta-analysis.

Background: The performance of chest x-ray (CXR) features for Pneumocystis pneumonia (PCP) diagnosis has been evaluated in small studies. We conducted a systematic review and meta-analysis to describe CXR changes in adults with HIV-associated laboratory-confirmed PCP, comparing these with non-PCP respiratory disease. Methods: We searched databases for studies reporting CXR changes in people >15 years old with HIV and laboratory-confirmed PCP and those with non-PCP respiratory disease. CXR features were grouped using consensus terms. Proportions were pooled and odds ratios (ORs) generated using random-effects meta-analysis, with subgroup analyses by CD4 count, study period, radiology review method, and study region. Results: Fifty-one studies (with 1821 PCP and 1052 non-PCP cases) were included. Interstitial infiltrate (59%; 95% CI, 52%-66%; 36 studies, n = 1380; I2 = 85%) and ground-glass opacification (48%; 95% CI, 15%-83%; 4 studies, n = 57; I2 = 86%) were common in PCP. Cystic lesions, central lymphadenopathy, and pneumothorax were infrequent. Pleural effusion was rare in PCP (0%; 95% CI, 0%-2%). Interstitial infiltrate (OR, 2.3; 95% CI, 1.4-3.9; I2 = 60%), interstitial-alveolar infiltrate (OR, 10.2; 95% CI, 3.2-32.4; I2 = 0%), and diffuse CXR changes (OR, 7.3; 95% CI, 2.7-20.2; I2 = 87%) were associated with PCP diagnosis. There was loss of association with alveolar infiltrate in African studies. Conclusions: Diffuse CXR changes and interstitial-alveolar infiltrates indicate a higher likelihood of PCP. Pleural effusion, lymphadenopathy, and focal alveolar infiltrates suggest alternative causes. These findings could be incorporated into clinical algorithms to improve diagnosis of HIV-associated PCP.

Efficacy and Safety of Intensified Versus Standard Prophylactic Anticoagulation Therapy in Patients With Coronavirus Disease 2019: A Systematic Review and Meta-Analysis.

Background: Randomized controlled trials (RCTs) have reported inconsistent effects from intensified anticoagulation on clinical outcomes in coronavirus disease 2019 (COVID-19). We performed an aggregate data meta-analysis from available trials to quantify effect on nonfatal and fatal outcomes and identify subgroups who may benefit. Methods: We searched multiple databases for RCTs comparing intensified (intermediate or therapeutic dose) vs prophylactic anticoagulation in adults with laboratory-confirmed COVID-19 through 19 January 2022. We used random-effects meta-analysis to estimate pooled risk ratios for mortality, thrombotic, and bleeding events (at end of follow-up or discharge) and performed subgroup analysis for clinical setting and dose of intensified anticoagulation. Results: Eleven RCTs were included (N = 5873). Intensified vs prophylactic anticoagulation was not associated with a mortality reduction up to 45 days (risk ratio [RR], 0.93 [95% confidence interval {CI}, .79-1.10]). There was a possible signal of mortality reduction for non-intensive care unit (ICU) patients, although with low precision and high heterogeneity (5 studies; RR, 0.84 [95% CI, .49-1.44]; I 2 = 75%). Risk of venous thromboembolism was reduced (RR, 0.53 [95% CI, .41-.69]; I 2 = 0%), with effect driven by therapeutic rather than intermediate dosing (interaction P = .04). Major bleeding was increased with intensified anticoagulation (RR, 1.73 [95% CI, 1.17-2.56]) with no interaction for dosing and clinical setting. Conclusions: Intensified anticoagulation has no effect on mortality among hospitalized adults with COVID-19 and is associated with increased bleeding risk. The observed reduction in venous thromboembolism risk and trend toward reduced mortality in non-ICU settings requires exploration in additional RCTs. Clinical Trials Registration. CRD42021273449 (PROSPERO).

Efficacy and safety of intensified versus standard prophylactic anticoagulation therapy in patients with Covid-19: a systematic review and meta-analysis.

Background: Randomised controlled trials (RCTs) have reported inconsistent effects from intensified anticoagulation on clinical outcomes in Covid-19. We performed an aggregate data meta-analysis from available trials to quantify effect on non-fatal and fatal outcomes and identify subgroups who may benefit. Methods: We searched multiple databases for RCTs comparing intensified (intermediate or therapeutic dose) versus standard prophylactic dose anticoagulation in adults with laboratory-confirmed Covid-19 through 19 January 2022. The primary efficacy outcome was all-cause mortality at end of follow-up or discharge. We used random effects meta-analysis to estimate pooled risk ratios for mortality, thrombotic, and bleeding events, and performed subgroup analysis for clinical setting and dose of intensified anticoagulation. Results: Eleven RCTs were included (n = 5873). Intensified anticoagulation was not associated with a reduction in mortality for up to 45 days compared with prophylactic anticoagulation: 17.5% (501/2861) died in the intensified anticoagulation group and 18.8% (513/2734) died in the prophylactic anticoagulation group, relative risk (RR) 0.93; 95%CI, 0.79 - 1.10. On subgroup analysis, there was a possible signal of mortality reduction for inpatients admitted to general wards, although with low precision and high heterogeneity (5 studies; RR 0.84; 95% CI, 0.49 - 1.44; I 2 = 75%) and not significantly different to studies performed in the ICU (interaction P = 0.51). Risk of venous thromboembolism was reduced with intensified anticoagulation compared with prophylaxis (8 studies; RR 0.53, 95%CI 0.41 - 0.69; I 2 = 0%). This effect was driven by therapeutic rather than intermediate dosing on subgroup analysis (interaction P =0.04). Major bleeding was increased with use of intensified anticoagulation (RR 1.73, 95% CI 1.17 - 2.56) with no interaction for dosing and clinical setting. Conclusion: Intensified anticoagulation has no effect on short term mortality among hospitalised adults with Covid-19 and is associated with increased risk of bleeding. The observed reduction in venous thromboembolism risk and trend towards reduced mortality in non-ICU hospitalised patients requires exploration in additional RCTs. Summary: In this aggregate data meta-analysis, use of intensified anticoagulation had no effect on short term mortality among hospitalised adults with Covid-19 and was associated with increased risk of bleeding.

The prevalence of laboratory-confirmed Pneumocystis jirovecii in HIV-infected adults in Africa: A systematic review and meta-analysis.

BACKGROUND: The epidemiology of Pneumocystis jirovecii, known to colonize the respiratory tract and cause a life-threatening HIV-associated pneumonia (PCP), is poorly described in Africa. We conducted a systematic review to evaluate P. jirovecii prevalence in African HIV-positive adults with or without respiratory symptoms. METHODS: We searched Medline, Embase, Cochrane library, Africa-Wide, and Web of Science for studies employing PCR and/or microscopy for P. jirovecii detection in respiratory samples from HIV-positive adults in Africa between 1995 and 2020. Prevalence with respiratory symptoms was pooled using random-effect meta-analysis, and stratified by laboratory method, sample tested, study setting, CD4 count, and trimethoprim/sulfamethoxazole prophylaxis. Colonization prevalence in asymptomatic adults and in adults with non-PCP respiratory disease was described, and quantitative PCR (qPCR) thresholds to distinguish colonization from microscopy-confirmed PCP reviewed. RESULTS: Thirty-two studies were included, with 27 studies (87%) at high risk of selection bias. P. jirovecii was detected in 19% [95% confidence interval (CI): 12-27%] of 3583 symptomatic and in 9% [95% CI: 0-45%] of 140 asymptomatic adults. Among symptomatic adults, prevalence was 22% [95% CI: 12-35%] by PCR and 15% [95% CI: 9-23%] by microscopy. Seven percent of 435 symptomatic adults had PCR-detected Pneumocystis colonization without evidence of PCP [95% CI: 5-10%, four studies]. One study established a qPCR cutoff of 78 copies/5µl of DNA in 305 induced sputum samples to distinguish Pneumocystis colonization from microscopy-confirmed PCP. CONCLUSION: Despite widened access to HIV services, P. jirovecii remains common in Africa. Prevalence estimates and qPCR-based definitions of colonization are limited, and overall quality of studies is low.

Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub-Saharan Africa (SSA). We performed a systematic review and meta-analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings. METHODS: We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized-controlled trials (RCTs) or investigator-managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short-term (in-hospital or two weeks), medium-term (up to 10 weeks) and long-term (up to six months). RESULTS AND DISCUSSION: Seventy-nine studies met inclusion criteria. In routine care settings, pooled short-term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole-based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short-term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short-term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized-controlled trials. Few studies evaluated long-term outcomes. CONCLUSIONS: Mortality rates from HIV-associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV-associated meningitis in the region.