Dengue virus infection during pregnancy increased the risk of adverse fetal outcomes? An updated meta-analysis

ObjectiveTo evaluate the effect of maternal dengue virus (DENV) infection during pregnancy in premature birth, low birth weight, miscarriage and stillbirth.MethodsSystematic electronic literature searches were conducted including PubMed, Medline, Embase, Web of science, Scopus and the Cochrane Library database, up until July 5, 2017. Effect sizes were estimated by using the relative risk (RR) or odds ratio (OR) with theirs corresponding 95% confidence interval (CI). Subgroup analyses were conducted for study design (prospective or retrospective) and clinical symptom of participants (symptomatic or asymptomatic). Statistical analysis was conducted by STATA 12.0.ResultsThe initial systematic literature searches identified 1048 studies. After screening, fourteen studies were included. The pooled results did not suggest maternal DENV infection might increase the risk of adverse fetal outcomes with a pooled RR of 0.96 (95% CI: 0.85–1.09, I² = 49.6%) for premature birth, RR of 0.99 (95%CI: 0.87–1.12, I² = 35.1%) for low birth weight, OR of 1.77 (95% CI: 0.99–3.15, I² = 17.5%) for miscarriage and RR of 3.42 (95% CI: 0.76–15.49, I² = 54.8%) for stillbirth. Subgroup analysis of studies in symptomatic participants still did not indicate DENV infection appeared to be a risk factor for premature birth, low birth weight and miscarriage with pooled effect size of 0.99 (95% CI: 0.87–1.13, I² = 49.3%), 1.22 (95% CI: 0.827–1.80, I² = 55.1%) and 1.19 (95% CI: 0.56–2.55, I² = 4.7%), respectively.ConclusionsCurrent evidence did not suggest that maternal DENV infection during pregnancy might increase the risk of premature birth, low birth weight, miscarriage and stillbirth.     

Efficacy and safety of anti-interleukin-5 therapy in patients with chronic obstructive pulmonary disease: A meta-analysis of randomized,controlled trials

BackgroundAnti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear.MethodsA literature review was conducted to August 26th 2019. Only randomized controlled trials (RCTs) that investigated the clinical efficacy and adverse effects of anti-IL-5 therapy were included in the meta-analysis. The primary outcome was the risk of COPD exacerbation.ResultsA total of 3 articles containing 5 RCTs were included in the study. Overall, 2837 and 1442 patients received anti-IL-5 therapy (mepolizumab, n = 865; benralizumab, n = 1972) and placebo, respectively. In the pooled analysis, anti-IL-5 therapy was associated with a lower risk of COPD exacerbation compared with the placebo (rate ratio, 0.92; 95% CI, 0.86–0.97, I² = 0%). In addition, no significant differences in the changes in SGRQ scores and FEV₁ from baseline were found between the anti-IL-5 therapy and placebo (SGRQ, mean difference, ?0.86, 95% CI, ?1.92 – 0.19, I² = 0%; FEV₁, mean difference, 0.01, 95% CI, ?0.01 – 0.03, I² = 0%). Anti-IL-5 therapy had a similar risk of any adverse event (risk ratio, 1.02; 95% CI, 0.99–1.05), an event leading to treatment discontinuation (risk ratio, 1.04; 95% CI, 0.72–1.48) and any serious adverse events (risk ratio, 0.93; 95% CI, 0.85–1.01) when compared with the placebo.ConclusionAnti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.     

Mortality and clinical cure rates for pneumonia: a systematic review,meta-analysis,and trial sequential analysis of randomized control trials comparing bactericidal and bacteriostatic antibiotic treatments

BackgroundBactericidal antibiotics are generally assumed to be superior to bacteriostatic antibiotics as first-line treatment for pneumonia.ObjectivesWe performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of randomized controlled trials (RCTs) of bactericidal versus bacteriostatic antibiotics to ascertain clinical superiority. Clinical cure rate was the primary outcome. Secondary outcomes included all-cause mortality, microbiological eradication, treatment failure, and relapse rates.Data sourcesPubMed, Cochrane Library, Embase, and MedRxivStudy eligibility criteriaRandomized control trials.ParticiapantsAdult patients with bacterial pneumonia treated with antibiotics in the community or in-hospital.InterventionsBacteriostatic versus bactericidal antibiotics.Assessment of risk of biasThe Cochrane Collaboration assessing risk of bias 2 tool.Methods of data synthesisData on dichotomous outcomes are presented as risk ratio (RR). A random-effects model with the generic Mantel–Haenszel method was used for integrating RRs for generalizability of findings. The I² method was used to assess the magnitude of variation secondary to heterogeneity.ResultsForty-three RCTs involving 10 752 patients met the eligibility criteria. The clinical cure rate (42 studies, 10 312 patients; RR: 1.02; 95% CI, 0.99–1.05; I²: 37%; TSA-adjusted CI, 0.99–1.05), all-cause mortality (25 studies, 8302 patients; RR: 1.07; 95% CI, 0.81–1.42; I²: 57%), microbiological eradication (24 studies, 2776 patients; RR: 1.00; 95% CI, 0.97–1.03; I²: 0%), treatment failure (31 studies, 7296 patients; RR: 0.96; 95% CI, 0.83–1.11; I²: 42%), and relapse rate (5 studies, 1111 patients; RR: 1.15; 95% CI, 0.50–2.63; I²: 0%) were similar between bactericidal and bacteriostatic antibiotic treatments.ConclusionsBactericidal agents are not associated with any statistical difference in clinical cure rates, mortality, microbiological eradication, treatment failure, or relapse rates compared with bacteriostatic antibiotics in the treatment of pneumonia.     

Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides receiving rituximab: A meta-analysis

IntroductionThe efficacy of rituximab (RTX) for remission induction and maintenance in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is now established, but the safety, particularly concerning severe infection risk, is not well known.ObjectiveThe purpose of this meta-analysis is to assess the prevalence and incidence of severe infections and the factors explaining heterogeneity in AAV patients treated with RTX.MethodsPubMed and Embase were searched up to December 2017. Prevalence and incidence was pooled using a random-effects model in case of significant heterogeneity (I² > 50%). Severe infection was defined as severe when it led to hospitalization, intravenous antibiotics therapy, and/or death. The heterogeneity was explored by subgroup analyses and meta-regression.ResultsThe included studies encompassed 1434 patients with a median age of 51.9 years. The overall prevalence and incidence of severe infections was 15.4% (95% CI [8.9; 23.3], I² = 90%, 33 studies) and 6.5 per 100 person-years (PY) (95% CI [2.9; 11.4], I² = 76%, 18 studies), respectively. The most common infections were bacterial (9.4%, 95% CI [5.1; 14.8]). The prevalence of opportunistic infection was 1.5% (95% CI [0.5; 3.1], I² = 58%) including pneumocytis jirovecii infections (0.2%, 95% CI [0.0; 0.6], I² = 0), irrespective of prophylaxis administration. Mortality related to infection was estimated at 0.7% (95% CI [0.2; 1.2], I² = 27%). The RTX cumulative dose was positively associated with prevalence of infections (13 studies, prevalence increase of 4% per 100 mg, p < .0001). The incidence of infection was negatively associated with duration of follow-up (8 studies, incidence decrease of 9% per year, p = .03).ConclusionPrevalence and incidence of severe infections, mainly bacterial ones, were high in AAV patients treated with RTX. This meta-analysis highlights the need for prospective studies to stratify infectious risk and validate cumulative RTX dose and duration of follow-up as modifying factors.     

Clinical efficacy and safety of baloxavir marboxil in the treatment of influenza: A systematic review and meta-analysis of randomized controlled trials

PurposeThe aim of this meta-analysis is to compare the clinical efficacy and safety of baloxavir with other anti-influenza agents or placebo in the treatment of influenza.MethodsPubMed, Embase, Web of Science, Google Scholar, Scopus, CINAHL, Cochrane databases and clinical registration were searched from inception until February 15 2021 for relevant randomized controlled trials (RCTs). Only phase 3 RCTs evaluating the usefulness of baloxavir in the treatment of influenza were included.ResultsThree RCTs enrolling 3771 patients (baloxavir group, n = 1451; oseltamivir group, n = 1288; placebo group, n = 1032) were included. Compared with oseltamivir, baloxavir had an insignificantly shorter time to the alleviation of symptoms (mean difference [MD], −1.29 h; 95% CI, −6.80 to 4.21; I² = 0%). In contrast, baloxavir had a significantly shorter time to the alleviation of symptoms than placebo (MD, −26.32 h; 95% CI, −33.78 to −18.86; I² = 0%). Baloxavir was associated with a significant decline in influenza virus titers and viral RNA load compared to oseltamivir and placebo. Baloxavir was associated with a lower risk of any adverse events than oseltamivir (OR, 0.82; 95% CI, 0.69–0.98; I² = 0%) and placebo (OR, 0.79; 95% CI, 0.66–0.96; I² = 0%).ConclusionsThe findings of this meta-analysis suggested that baloxavir is superior to placebo in the treatment of influenza in both clinical outcome and virological response. Moreover, baloxavir was found to have a better virological response than oseltamivir and to be as effective as oseltamivir clinically. Compared with oseltamivir and placebo, baloxavir appears to be a relatively safe anti-influenza agent.     

Efficacy of early treatment with hydroxychloroquine in people with mild to moderate COVID-19: a systematic review and meta-analysis

IntroductionNo early treatment intervention for COVID-19 has proven effective to date. We systematically reviewed the efficacy of hydroxychloroquine as early treatment for COVID-19.Material and methodsRandomized controlled trials (RCTs) evaluating hydroxychloroquine for early treatment of COVID-19 were searched in five engines and preprint websites until September 14, 2021. Primary outcomes were hospitalization and all-cause mortality. Secondary outcomes included COVID-19 symptom resolution, viral clearance, and adverse events. Inverse variance random-effects meta-analyses were performed and quality of evidence (QoE) per outcome was assessed with GRADE methods.ResultsFive RCTs (n = 1848) were included. The comparator was placebo in four RCTs and usual care in one RCT. The RCTs used hydroxychloroquine total doses between 1,600 and 4,400 mg and had follow-up times between 14 and 90 days. Compared to the controls, early treatment with hydroxychloroquine did not reduce hospitalizations (RR = 0.80, 95% CI: 0.47–1.36, I² = 2%, 5 RCTs, low QoE), all-cause mortality (RR = 0.77, 95% CI: 0.16–3.68, I² = 0%, 5 RCTs, very low QoE), symptom resolution (RR = 0.94, 95% CI: 0.77–1.16, I² = 71%, 3 RCTs, low QoE) or viral clearance at 14 days (RR = 1.02, 95% CI: 0.82–1.27, I² = 65%, 2 RCTs, low QoE). There was a larger non-significant increase of adverse events with hydroxychloroquine vs. controls (RR = 2.17, 95% CI: 0.86–5.45, I² = 92%, 5 RCTs, very low QoE).ConclusionsHydroxychloroquine was not efficacious as early treatment for COVID-19 infections in RCTs with low to very low quality of evidence for all outcomes. More RCTs are needed to elucidate the efficacy of hydroxychloroquine as early treatment intervention.     

Dietary intakes of monounsaturated fatty acids and risk of mortality from all causes,cardiovascular disease and cancer: A systematic review and dose-response meta-analysis of prospective cohort studies

BackgroundFindings on the link between dietary intakes of monounsaturated fatty acids (MUFA) and risk of mortality are conflicting. This study aimed to summarize existing literature regarding the association between MUFA intake and risk of mortality from all causes, cardiovascular diseases (CVDs), and cancer.MethodsPubMed, Scopus, and ISI Web of Science was systematically searched up to December 2020. Prospective cohort studies which investigated MUFA intake in relation to mortality from all causes, CVD, or cancer were eligible for this systematic review. Publications that had reported risk ratios (RRs) or hazard ratios (HRs) and 95% confidence intervals (CIs) as effect size, were considered.ResultsA total of 17 prospective cohort studies were included. These studies included 1022,321 participants aged ≥ 20 years in total, and 191,283 all-cause deaths, 55,437 CVD deaths, and 64,448 cancer deaths were totally reported. Combining 15 effect sizes from 11 studies, MUFA intake was inversely associated with risk of all-cause mortality (RR: 0.94; 95% CI: 0.90, 0.98; I² =55.5; P = 0.005). Based on 17 effect sizes from 11 studies, we found no significant association between MUFA intake and risk of CVD mortality (RR: 0.95; 95% CI: 0.89, 1.01; I² =37.0; P = 0.06). Combining 10 effect sizes from 6 studies, MUFA intake was not significantly associated with cancer mortality (RR: 0.99; 95% CI: 0.96, 1.03, I² =13.3%, P = 0.32). Also, an additional 5% of energy from MUFA was associated with a 3% reduced risk of all-cause mortality (RR: 0.97; 95%CI: 0.96, 0.98), but not with CVD (RR: 0.98; 95%CI: 0.95, 1.01) and cancer mortality (RR: 0.99; 95%CI: 0.97, 1.01).ConclusionsMUFA intake was found to be inversely associated with risk of all-cause mortality. However, no link was found between MUFA consumption and mortality from CVD or cancer.     

Effect of the immunosuppressive regimen on the incidence of cytomegalovirus infection in 378 heart transplant recipients: A single centre,prospective cohort study

BackgroundCytomegalovirus (CMV) infection is a major complication of immunosuppression after heart transplant. Recent studies suggest the actual immunosuppressive regimen may affect the risk of CMV infection.ObjectivesTo evaluate incidence, risk factors and clinical consequences of CMV infection and assess the possible differential effect of distinct immunosuppressive protocols.Study designSingle centre, prospective cohort study of 378 consecutive heart transplant recipients undergoing CMV monitoring. Preemptive treatment was the standard of care. Patients were grouped as follows: group A, without any CMV infection; group B, with CMV infection not requiring pre-emptive treatment; group C, treated for CMV infection or disease.ResultsMost recipients never required antiviral therapy because of no CMV infection/disease (group A, 31%) or CMV levels below the cut-off for pre-emptive treatment (group B, 28%). Group C recipients (41%) were significantly older than group A patients (49.1 ± 13.2 vs. 44.8 ± 15.1 years; p = 0.028). Most cases occurred within the second month post-transplant. CMV viremia was detected in 77% and 62% of patients primed with thymoglobulin or ATG Fresenius, respectively, (OR 2.06, 95% C.I. 1.27–3.34; p = 0.0034). Use of everolimus was associated with a significantly lower rate of CMV infection compared to azathioprine or mycophenolate (OR 0.19, 95% C.I. 0.09–0.39; p < 0.0001). Major opportunistic infections were significantly more common in groups B and C.ConclusionIn a large and homogeneous cohort of heart transplant recipients, we observed a strong relationship between the immune suppressive regimen and CMV infection, as well as an increased incidence of other opportunistic infections in recipients with CMV infection/disease.     

Efficacy of different antifungal drugs as initial treatment for patients with talaromycosis: A systematic review and meta-analysis

There are no standard choices on antifungal drugs for talaromycosis due to various factors, and related studies are also limited. This study summarizes and analyzes efficacy of different antifungal drugs for patients with talaromycosis, which can provide more reference evidence for drugs’ choices in practice. We conducted a meta-analysis on prognostic impacts of different antifungal drugs against talaromycosis, and primary outcome was all-cause mortality. A total of 975 patients from 8 studies were included. One of the 8 studies was a randomized controlled trial and the others were retrospective studies. Among these patients, 582 cases were initiated with amphotericin B, 31 cases died (9.28%). The other 393 cases were initiated with itraconazole, and 54 cases died (14.00%). The initial use of amphotericin B for talaromycosis significantly reduced mortality compared with itraconazole (risk ratio (RR): 0.61; 95% confidence interval (CI): 0.41–0.90; P = 0.01; I² = 4%). Initial treatment with amphotericin B for talaromycosis in different regions (internal and external) and studies (sample size < 100) had no obvious prognostic advantages over itraconazole (RR: 0.60, 95% CI: 0.32–1.13; P = 0.11; I² = 44%; RR: 0.61, 95% CI: 0.37– 1.00; P = 0.05; I² = 0%; RR: 0.71, 95% CI: 0.39–1.29; P = 0.26; I² = 0%, respectively). However, when study's sample size was ≥ 100, the mortality of amphotericin B group was significantly reduced (RR: 0.54, 95% CI: 0.32– 0.92; P = 0.02; I² = 46%). In conclusion, amphotericin B is a better choice as initial therapeutic drug for talaromycosis.     

Thrombotic Microangiopathy Associated with Sirolimus Level after Allogeneic Hematopoietic Cell Transplantation with Tacrolimus/Sirolimus-Based Graft-versus-Host Disease Prophylaxis

Posttransplantation thrombotic microangiopathy (TMA) is a multifactorial complication of allogeneic hematopoietic cell transplantation (allo-HCT) whose incidence is increased with the use of a sirolimus plus tacrolimus (SIR/TAC) regimen for acute graft-versus-host disease (aGVHD) prophylaxis. We evaluated the incidence and possible risk factors for TMA in a case series of 177 patients who received allo-HCT using SIR/TAC-based GVHD prophylaxis. The patients received either a sibling donor graft (n = 82) or a matched unrelated donor graft (n = 95). Within the first 100 days post-HCT, 30 patients (17%) were diagnosed with TMA, and an additional 9 patients (5%) were classified as probable TMA cases. The median time to onset of TMA was 4.6 weeks (range, 1.6-10.6 weeks). Thirty-four patients developed both TMA and aGVHD, with the majority (81%) developing aGVHD first. Multivariate analysis identified the following factors as associated with increased risk of TMA: day 14 serum sirolimus level ≥9.9 ng/mL (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.13-4.27; P = .02), presence of previous aGVHD grade II-IV (HR, 3.04; 95% CI, 1.38-6.71; P < .01), and fully myeloablative conditioning (HR, 3.47; 95% CI, 1.60-7.53; P < .01). These risk factors for TMA suggest that when using a SIR/TAC regimen for GVHD prophylaxis, careful monitoring and adjustment of the sirolimus dosage is critical, particularly in patients with active aGVHD.     

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for ATL with HTLV-1 Antibody-Positive Donors

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is the only available curative treatment option for patients with aggressive adult T cell leukemia-lymphoma (ATL). Donor human T cell leukemia virus (HTLV) 1 seropositivity is a critical concern when choosing relative donors, as they are not usually recommended due solely to the occurrence of donor-derived ATL. A previous report suggested that allo-HCT with an HTLV-1-seropositive donor increased ATL-related mortality. We updated the risk assessment for choosing an HTLV-1-seropositive allo-HCT donor for ATL. Our current registry data, which include larger numbers of HTLV-1-seropositive donors and longer observation periods, revealed no significant difference in overall survival (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.70-1.24; P = .61) or cumulative incidence of either ATL-related (HR, 0.96; 95% CI, 0.64 to 1.45; P = .80) or non-ATL-related mortality (HR, 0.91; 95% CI, 0.61 to 1.37; P = .66). Similarly, when considering only patients with ATL in complete remission, there was no significant difference in overall survival (HR, 1.02; 95% CI, 0.70 to 1.49; P = .91) or cumulative incidence of either ATL-related (HR, 1.20; 95% CI, 0.66 to 2.20; P=0.54) or non-ATL-related mortality (HR, 0.86; 95% CI, 0.52-1.42; P = .66). These data indicate that selecting HTLV-1-seropositive donors might not be contraindicated for patients with ATL receiving allo-HCT if alternative donors are unavailable. Further risk assessment remains to be performed.     

Current weight of evidence of viruses associated with peri‐implantitis and peri‐implant health: A systematic review and meta‐analysis

The pathological role of human herpesviruses (HHVs) (Epstein‐Barr virus [EBV], Human cytomegalovirus [CMV], and Herpes simplex virus [HSV]) in peri‐implant health needs clarification quantitatively. To determine the weight of evidence for HHVs in patients with peri‐implantitis (PI) and substantiate the significance of HHVs in peri‐implant inflammation, electronic databases including EMBASE, MEDLINE, Cochrane Oral Health Group Trials Register, and Cochrane Central Register of Controlled Trials were searched from 1964 up to and including November 2018. Meta‐analyses were conducted for prevalence of HHVs in PI and healthy controls. Forest plots were generated that recorded risk difference (RD) of outcomes and 95% confidence intervals (CI). Five clinical studies were considered and included. Four clinical studies reported data on EBV while three clinical studies reported data on CMV. Considering the risk of these viruses in PI, significant heterogeneity for CMV (χ² = 53.37, p < 0.0001, I² = 96.25%) and EBV (χ² = 14.14, p = 0.002, I² = 78.79%) prevalence was noticed between PI and healthy control sites. The overall RD for only EBV (RD = 0.20, 95% CI, 0.01‐0.40, p = 0.03) was statistically significant between both groups. Frequencies of the viruses were increased in patients with PI compared with healthy nondiseased sites. However, the findings of the present study should be interpreted with caution because of significant heterogeneity and small number of included studies.     

Risk of failure in dual therapy versus triple therapy in naïve HIV patients: a systematic review and meta-analysis

ObjectivesSeveral attempts have been made to test different drug-sparing strategies to reduce the drug-burden and drug-related toxicities. The objective of this meta-analysis was to evaluate the relative risk (RR) of failure of dual therapies compared to triple therapies in HIV-naïve patients.MethodsWe searched MEDLINE, Google Scholar and the Cochrane Library. The following criteria were used: present data from original articles comparing the two treatment regimens; published from January 2007 up to January, 2020. No language or study design restriction was applied. Subjects were HIV-positive naïve patients treated with dual or triple antiretroviral therapy (ART). A systematic review and meta-analysis was performed. Treatment failure (TF) was the primary outcome evaluated; heterogeneity was assessed using the Q statistic and I².ResultsFourteen studies were included, allowing a meta-analysis on 5205 patients. The meta-analysis performed on studies that presented data at 48 weeks showed that the RR of TF (RR > 1 favouring triple therapy) in 10 studies was 1.20 (95% confidence interval (CI): 0.91–1.59, I²: 49.2%); the RR of virological failure (VF) in eight studies was 1.54 (95% CI: 0.84–2.86, I²: 54%); the RR of adverse drug reaction leading to discontinuation of the regimen at 48 weeks in eight studies was 0.76 (95% CI: 0.43–1.33, I²: 17.7%). In patients with less than 200 CD4+, the RR of TF in two studies without maraviroc was 2.09 (95% CI: 1.05–4.17, I²: 0.0%). Regarding the studies at 96 weeks there was no difference except in rate of development of resistance, RR 1.94 (95% CI: 1.06–3.53, I²: 6.2%).ConclusionDual therapies are as effective as those with three drugs, showing no difference according to the different dual therapies, except in patients with less than 200 CD4; however, they are associated with a higher selection of resistance-associated mutations at 96 weeks of therapy.     

No difference in myocardial iron concentration and serum ferritin with deferasirox and deferiprone in pediatric patients with hemoglobinopathies: A systematic review and meta-analysis

ObjectivesIron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders.Material and methodsPubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12 months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model.ResultsA total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: ?0.92; 95% CI [?3.35, 1.52]; p = 0.46; I² = 0). Moreover, there has been no significant difference noted in SF levels at both 6 months (WMD: 97.31; 95% CI [?236.16, 430.77]; p = 0.57; I² = 0) and 12 months (WMD: 46.99; 95% CI [?191.42, 285.40]; p = 0.70; I² = 0) respectively.ConclusionOur analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.     

The efficacy and safety of hydroxychloroquine (HCQ) in treatment of COVID19 –a systematic review and meta-analysis

IntroductionThe treatment of SARS CoV2 (Severe Acute Respiratory Syndrome corona virus 2) also known as COVID-19 (corona virus disease 2019) continues to remain an enigma even after six months of the pandemic. Hydroxychloroquine (HCQ) has been one of the most widely tested drugs for SARS CoV2 on account of its antiviral properties. However the results so far have been far from categorical. The meta-analyses conducted till date are also lacking in precision and appropriateness. This systematic review and meta-analysis addresses the efficacy and safety of HCQ in SARS CoV2 by overcoming the limitations of earlier meta-analysis.MethodsA total of 5 prominent medical databases were searched and fourteen studies (n = 12455) were included in the systematic review and meta-analyses. The data on survival, alleviation of symptoms, conversion of RT PCR positivity to negativity, use and efficacy in presence of co-morbidities (Hypertension, diabetes and heart disease) and cardiac and gastrointestinal side effects were extracted. Meta-analysis was applied to calculate the pooled estimates. Fixed-effects model results were chosen since I² was <25%.Meta-analysis was conducted using STATA version 13 (StataCorp LP, College Station, TX, USA).ResultsThe pooled estimates showed that HCQ treatment did not significantly affect survival at 14 and 28 days in COVID-19 patients with respect to the control population (RR: 1.003, 95% CI: 0.983–1.022), alleviation of symptoms at day 10 (RR: 1.044, 95% CI: 0.911 1.196), success in presence of co-morbidities (RR: 1.058, 95% CI: 1.035–1.082) and conversion from RT PCR positive to RT PCR negative on day 6 (RR:1.123, 95% CI: 1.041 1.212). There was higher risk for cardiac side effects (RR: 2.012, 95% CI: 1.428 2.833) and gastrointestinal side effects (RR: 1.318, 95% CI: 0.730 2.380) in HCQ recipients.ConclusionThere is no evidence on the safety and efficacy of HCQ either alone or in combination with other drugs in SARS CoV2 infection.     

Effect of Smoking on Outcomes of Allogeneic Transplantation: A Single-Center Analysis

Pulmonary complications are fatal adverse events after allogeneic hematopoietic cell transplantation (allo-HCT). On the other hand, smoking is a well-known risk factor for various pulmonary diseases and also increases the incidence of pulmonary complications and overall mortality in allo-HCT recipients. In this study, we retrospectively assessed the impact of smoking intensity on survival outcomes. This study included consecutive allo-HCT recipients at our center between June 2007 and May 2019 whose smoking profiles were available (n = 408); they were divided into high (pack-years >10, n = 171) and low (pack-years ≤10, n = 231) pack-years groups. In univariate analyses, nonrelapse mortality (NRM) and overall survival (OS) were significantly inferior in the high pack-years group (1-year NRM 26.6% versus 13.9%, P < .001; 1-year OS 58.4% versus 70.1%, P = .0067). However, this association was not observed in multivariate analyses. In subgroup analyses according to sex, the survival outcomes in the high pack-years group were significantly inferior in males (NRM hazard ratio [HR], 2.24 [95% confidence interval (CI), 1.23 to 4.07], P = .0082; OS HR, 1.54 [95% CI, 1.04 to 2.28], P = .031), but not in females (NRM HR, 0.587 [95% CI, 0.241 to 1.43], P = .24; OS HR, 0.689 [95% CI, 0.400 to 1.19], P = .18). In summary, high pack-years were associated with inferior survival of allo-HCT recipients, especially in males.     

Antibacterial prophylaxis with ciprofloxacin for patients with multiple myeloma and lymphoma undergoing autologous haematopoietic cell transplantation: a quasi-experimental single-centre before-after study

ObjectivesWe aimed to study whether ciprofloxacin prophylaxis reduces infectious complications in patients undergoing autologous haematopoietic cell transplantation (AHCT).MethodsThis is a quasi-experimental, retrospective, before-after study. We compared the incidence of bacterial-related complications among 356 patients with multiple myeloma (MM) (n = 202) and lymphoma (n = 154) who underwent AHCT with (n = 177) or without (n = 179) ciprofloxacin prophylaxis between 03/2007 and 10/2012 and between 10/2012 and 07/2016, respectively, at a single centre.ResultsFebrile neutropaenia, bacteraemia, and pneumonia were significantly more common among patients who underwent AHCT during the second study period and did not receive antibacterial prophylaxis compared with patients who underwent AHCT during the first study period and received antibacterial prophylaxis (89.9% (161/179) vs. 83.1% (147/177), difference 6.9%, 95% CI 0-14.1%, P = 0.002; 15.1% (27/179) vs. 4.5% (8/177), difference 10.6%, 95% CI 4.4-16.9%, p < 0.0001; 12.3% (22/179) vs. 6.2% (11/177), difference 6.1%, 95% CI 0-12.3%, p = 0.04, respectively). The number-needed-to-treat to prevent one episode of bacteraemia, pneumonia, and febrile neutropaenia was 8.6, 8.5, and 13.7, respectively. Patients with ciprofloxacin prophylaxis had higher rates of ciprofloxacin-resistant bacteraemia (62.5% (5/8) vs. 18.5% (5/27), difference 44%, 95% CI 7-70%, p = 0.01). In multivariate analysis, ciprofloxacin prophylaxis significantly decreased the odds of bacteraemia (OR 0.19, 95% CI 0.07-0.52; p < 0.0001) and pneumonia (OR 0.37, 95% CI 0.16-0.85, p = 0.02).ConclusionAccording to our single-centre experience, patients with MM and lymphoma undergoing AHCT may benefit from antibacterial prophylaxis with ciprofloxacin.     

Validity of surrogate endpoints assessing central venous catheter-related infection: evidence from individual- and study-level analyses

ObjectivesThe prevention of catheter-related bloodstream infection (CRBSI) has been an area of intense research, but the heterogeneity of endpoints used to define catheter infection makes the interpretation of randomized controlled trials (RCTs) problematic. The aim of this study was to determine the validity of different endpoints for central venous catheter infections.Data sources(a) Individual-catheter data were collected from 9428 catheters from four large RCTs; (b) study-level data from 70 RCTs were identified with a systematic search. Eligible studies were RCTs published between January 1987 and October 2018 investigating various interventions to reduce infections from short-term central venous catheters or short-term dialysis catheters. For each RCT the prevalence rates of CRBSI, quantitative catheter tip colonization, catheter-associated infection (CAI) and central line-associated bloodstream infection (CLABSI) were extracted for each randomized study arm.MethodsCRBSI was used as the gold-standard endpoint, for which colonization, CAI and CLABSI were evaluated as surrogate endpoints. Surrogate validity was assessed as (1) the individual partial coefficient of determination (individual-pR²) using individual catheter data; (2) the coefficient of determination (study-R²) from mixed-effect models regressing the therapeutic effect size of the surrogates on the effect size of CRBSI, using study-level data.ResultsColonization showed poor agreement with CRBSI at the individual-patient level (pR² = 0.33 95% CI 0.28–0.38) and poor capture at the study level (R² = 0.42, 95% CI 0.21–0.58). CAI showed good agreement with CRBSI at the individual-patient level (pR² = 0.80, 95% CI 0.76–0.83) and moderate capture at the study level (R² = 0.71, 95% CI 0.51–0.85). CLABSI showed poor agreement with CRBSI at the individual patient level (pR² = 0.34, 95% CI 0.23–0.46) and poor capture at the study level (R² = 0.28, 95% CI 0.07–0.76).ConclusionsCAI is a moderate to good surrogate endpoint for CRBSI. Colonization and CLABSI do not reliably reflect treatment effects on CRBSI and are consequently more suitable for surveillance than for clinical effectiveness research.     

Impact of Preemptive Therapy for Cytomegalovirus on Toxicities after Allogeneic Hematopoietic Cell Transplantation in Clinical Practice: A Retrospective Single-Center Cohort Study

(Val)ganciclovir (vGCV) or foscarnet (FCN) as preemptive therapy (PET) for cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT) is associated with myelosuppression and nephrotoxicity, respectively. We analyzed a cohort of CMV-seropositive (R⁺) HCT recipients managed preemptively at a single center. The objectives of our study were to (1) quantify the frequencies of neutropenia and acute kidney injury (AKI) through day +100 (D100) post-HCT and at PET discontinuation and (2) assess the impact of PET on neutropenia and AKI in multivariate models. This was a retrospective cohort study of adult CMV R⁺ recipients who underwent allo-HCT at Memorial Sloan Kettering Cancer Center from March 18, 2013, through December 31, 2017, and were managed with PET. Patients were grouped by receipt of PET (PET and no PET). Neutropenia and AKI were defined by Common Terminology Criteria for Adverse Events version 4. Frequencies of toxicities by D100 were compared between relevant groups. The impact of PET on toxicities was examined in univariate and multivariate Poisson/negative binomial regression models. Of 368 CMV R⁺ HCT recipients, 208 (56.5%) received PET. Neutropenia by D100 occurred in 41.8% and 28.6% patients in PET and no PET, respectively (P = .0009). PET increased the risk of neutropenia (adjusted relative risk = 1.81; 95% confidence interval [CI], 1.48 to 2.21; P < .0001) in multivariate analyses. AKI by D100 occurred in 12.0% and 7.8% patients in PET and no PET, respectively (P = .19). PET increased the risk of AKI by 2.75-fold (95% CI, 1.71 to 4.42; P < .0001). When PET recipients were grouped by first antiviral, neutropenia by D100 occurred in 34.8% and 48.9% of vGCV and FCN recipients, respectively, (P = .08), and AKI occurred in 13.0% and 34.0% of vGCV and FCN recipients, respectively (P = .001). At discontinuation of vGCV or FCN, neutropenia was present in 11.2% versus 2.1% patients, respectively (P = .08), and AKI was present in 1.9% of versus 12.8% patients respectively (P = .005). Preemptive therapy for CMV increased the risk of neutropenia and AKI in the first 100 days post-HCT by 1.8-fold and 2.8-fold, respectively. Our results underscore the need for safer antivirals for CMV management in HCT recipients.