Murad, M. Hassan

AbstractBackgroundCytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients (SOTRs). Secondary prophylaxis (SP) is not routinely recommended by guidelines on the management of CMV in SOTR but may be considered in certain higher‐risk situations.MethodsA comprehensive search of English language publications up to September 2023 was performed. The primary outcome was CMV relapse, defined as the recurrence of DNAemia or disease. Secondary outcomes included graft loss, mortality, and hematological toxicity. Meta‐analysis used the random‐effects model. The study protocol is registered in PROSPERO (no. CRD42022357028).ResultsSix retrospective comparative studies were included. A total of 520/727 (72%) of SOTR received SP with valganciclovir. The meta‐analysis did not demonstrate a significant difference in CMV relapse (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.79–2.63). Heterogeneity between the studies was low (I2 = 0%, p = 0.57). SP was significantly associated with a reduction in mortality (OR 0.2, 95% CI 0.07–0.54) but not graft loss (OR 0.67, 0.17–2.63). There was no significant difference in CMV relapse among kidney‐specific SOTR (OR 1.38, 95% CI 0.65–2.96).ConclusionEvidence from six nonrandomized studies is limited and cannot support a recommendation for or against routine SP in SOTR treated for CMV infection. Awaiting prospective‐controlled trials, the decision about SP should depend on individualized risk‐profile assessments by experienced clinicians. image

Summary Background There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. Aims The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. Methods We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population‐based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random‐effects meta‐analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). Results We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21–1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06–1.53]) and non‐Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20–1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27–1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09–1.35]) (p for interaction = 0.026). Meta‐regression demonstrated that mean age of patients, study year, mean study follow‐up duration, and percentages of immunomodulators and biologics use did not influence study outcome. Conclusions The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non‐Hodgkin's lymphoma.

Abstract Recent work in causally interpretable meta-analysis (CIMA) has bridged the gap between traditional meta-analysis and causal inference. Whereas traditional meta-analysis results generally do not apply to any well-defined population, CIMA approaches specify a target population to which meta-analytic treatment effect estimates are transported. Although theoretically attractive, these approaches currently have some practical limitations. Most assume that all studies in the meta-analysis have individual participant data (IPD), which is rare in practice because most trials share only aggregate data. We propose a method to perform CIMA using a combination of aggregate data and IPD. This method borrows information from studies with IPD to augment the aggregate data and create aggregate-matched synthetic IPD (AMSIPD), which can be used readily in the existing CIMA framework. By allowing use of both aggregate data and IPD, the method opens CIMA to more applications and can avoid biases arising from using only studies with IPD. We present a case study and simulations showing the AMSIPD approach is promising and merits further investigation as an advancement of CIMA.

Objective Recalcitrant palatal fistulas in patients with cleft palate history sometimes require free flap reconstruction. This study reviews the literature on described flaps and outcomes. Design A systematic review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Setting All study designs were included. Non-English articles were excluded. Patients and Participants Patients with a history of cleft palate who underwent free flap reconstruction for a oronasal fistula. Interventions Free tissue transfer for a palatal fistula repair. Main outcomee measures Information regarding defect and flap characteristics were reviewed. Surgical outcomes such as flap loss rates, rates of recurrent fistula formation, and speech outcomes were also obtained. Results Our search returned 894 articles, of which 23 were included. All studies were retrospective case series and reports. A total of 65 patients were described with an average age of 19.3 (range 3–55) years and a median fistula size of 8.00 cm 2 (range 2.54 cm 2 – 24 cm 2 ). The most common flap was the radial forearm flap (n = 37). Nine patients (13.8%) had recurrent fistula formation with surgical revision successful in all cases in which the patient returned to the operating room. There were two partial flap losses and no total flap losses. Speech outcomes showed improvement in 27 patients across 10 studies. Conclusions Palatal fistula repair with free tissue transfer is safe with an acceptable risk profile and low flap loss rate. Early recurrence due to partial flap necrosis and dehiscence are successfully managed with flap readvancement.

Abstract Background Risk of bias (RoB) tools are critical in systematic reviews and affect subsequent decision‐making. RoB tools should have adequate interrater reliability and interconsensus agreement. We present an approach of post hoc evaluation of RoB tools using duplicated studies that overlap systematic reviews. Methods Using a back‐citation approach, we identified systematic reviews that used the Risk Of Bias In Nonrandomized Studies‐of Interventions (ROBINS‐I) tool and retrieved all the included primary studies. We selected studies that were appraised by more than one systematic review and calculated observed agreement and unweighted kappa comparing the different systematic reviews' assessments. Results We identified 903 systematic reviews that used the tool with 51,676 cited references, from which we eventually analyzed 171 duplicated studies assessed using ROBINS‐I by different systematic reviewers. The observed agreement on ROBINS‐I domains ranged from 54.9% (missing data domain) to 70.3% (deviations from intended interventions domain), and was 63.0% for overall RoB assessment of the study. Kappa coefficient ranged from 0.131 (measurement of outcome domain) to 0.396 (domains of confounding and deviations from intended interventions), and was 0.404 for overall RoB assessment of the study. Conclusion A post hoc evaluation of RoB tools is feasible by focusing on duplicated studies that overlap systematic review. ROBINS‐I assessments demonstrated considerable variation in interconsensus agreement among various systematic reviewes that assessed the same study and outcome, suggesting the need for more intensive upfront work to calibrate systematic reviewers on how to identify context‐specific information and agree on how to judge it.

Abstract Objectives Breast milk is the recommended nutritional source for newborns and has been associated with decreased morbidity in low‐birth‐weight and preterm infants. In situations where breast milk is not available, donor breast milk is an alternative. Milk banking is becoming increasingly common worldwide to meet this need. Although the benefits of donor breast milk for the recipient infant are well established, the health impact on the breast milk donor and the infant of the breast milk donor is an area of current research. We aim to synthesize and evaluate the available evidence regarding the impact of donating breast milk on the health, lactation, and well‐being of the breast milk donor, and the health and growth of the infant of the breast milk donor. Methods We will search electronic databases, grey literature, and the websites of relevant international organizations. We will include studies that involve lactating women and their infants, healthy or with health conditions, who donate breast milk, without restrictions on study date, language, or study design. If sufficient homogeneity exists between studies, we will complete meta‐analyses. We will evaluate the risk of bias using the Risk of Bias tool or the Cochrane Risk of Bias in Non‐Randomized Studies tool. We will evaluate the overall certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Conclusion In this systematic review and meta‐analysis, we will summarize the current literature regarding the effects of human milk donation on human milk donors and their infants.

Abstract Objectives Human milk has been shown to reduce severe morbidity in preterm/low‐birth‐weight infants and is therefore the recommended nutritional source. When infants cannot receive maternal milk, donor human milk (DHM) is recommended. The use of human milk banking facilities is increasing to meet the need for DHM. DHM is unique compared to maternal milk as it must be processed and stored. The processing and storage of animal milk has been more rigorously studied than human milk and can serve as proxy to create DHM banking guidelines. Methods and Analysis We will search electronic databases, grey literature, and the websites of relevant international organizations. We will include studies that evaluated the impact of storage, handling, and treatment on the nutritional quality and safety of animal milk. We will not restrict study date, language, or design. If sufficient homogeneity exists between studies, we will conduct a meta‐analysis. We will evaluate the methodological quality of each study using the SYRCLE's (Systematic Review Centre for Laboratory Animal Experimentation) risk of bias tool. (1) We will evaluate the overall certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. Conclusion In this systematic review and meta‐analysis, commissioned by the World Health Organization, we will synthesize the available literature regarding the impact of various storage, handling, and treatment practices on the nutritional quality and safety of animal milk.