Hegazi, Moustafa

Objective: The objective of this investigation was to evaluate the agreement rate on judgments made using the Murad tool by different systematic review teams. Introduction: Evaluating the methodological quality of case reports and case series is challenging but some tools do exist for this purpose. We leveraged the presence of studies that have been evaluated by different systematic review teams to assess the inter-consensus agreement among different teams on Murad tool domains. Methods: Using a back-citation method, we identified systematic reviews that used the Murad tool and retrieved all the included primary studies. We selected studies that were assessed by more than 1 systematic review team. We calculated observed agreement and Gwet’s agreement coefficient on judgments made about each signaling question. Results: We identified 982 systematic reviews that cited the Murad tool and collectively cited 59,080 references. The final data comprised of 81 duplicated case reports and series assessed by more than 1 systematic review team. Overall, the signaling questions had very high observed agreement with 5 of the 8 questions having agreement over 75%. The signaling questions with the highest agreement addressed the adequacy of the ascertainment of the exposure (coefficient 0.959), ascertainment of the outcome (coefficient 0.829), presence of a dose-response gradient (perfect agreement), and clarity of reporting (coefficient 0.755). Conclusion: The current study demonstrates overall high agreement among different systematic review teams that used the Murad tool for appraisal of the same case series and case reports. Leveraging duplicated studies across systematic reviews is a feasible way to retrospectively assess the reliability of the tool.

Abstract Background Partial breast irradiation (PBI) is an effective treatment for early-stage breast cancer. However, evidence comparing different PBI modalities is limited. Methods This trial emulation uses electronic health records from a multi-state large tertiary health system. Three PBI modalities were compared: proton radiation therapy, photon radiation therapy, and applicator-based brachytherapy. Inverse probability weighting (IPW) was used to balance confounders. The primary outcome was ipsilateral breast recurrence (IBR). Results Between 2013 and 2023, 1041 women with early-stage breast cancer were treated with PBI. Of these, 1026 patients were included in the analyses. The median age was 66 years; 22.51% had ductal carcinoma in situ (DCIS), and 97.56% were estrogen receptor positive. With median follow-up of 38.2 months, the rate of IBR in the overall group was 3.05% (95% confidence interval [CI] = 1.99% to 4.65%) at 3 years. After IPW, compared with photon PBI, the hazard ratio for IBR for proton PBI was 2.11 (95% CI = 0.70 to 6.33) and for brachytherapy, 3.86 (95% CI = 1.39 to 10.69). Compared with proton PBI, the hazard ratio for IBR for brachytherapy was 1.83 (95% CI = 0.88 to 3.81). IBR risk was similar across PBI modalities for patients with tumor size ≤ 10 mm and in patients treated for DCIS. Among patients with tumor size >10 mm, the hazard ratio for IBR for brachytherapy was 7.64 (95% CI = 1.64 to 35.58) and 3.59 (95% CI = 1.22 to 10.56) relative to photons and protons, respectively. Conclusion PBI with applicator-based brachytherapy was associated with higher IBR than photon or proton PBI in patients with tumor size > 10 mm, suggesting the need for more careful PBI patient selection for this modality.

Background and Aims: With rapid changes in the management landscape of chronic hepatitis B (CHB), this technical systematic review addresses 4 critical Population, Intervention, Comparator, Outcome (PICO) questions to provide guidance to the formulation of recommendations to the 2025 AASLD practice guideline for management of CHB. Approach: The review was reported in accordance with PRISMA guidelines. Outcomes were evaluated across 4 key PICOs: (1) antiviral therapy for prevention of horizontal HBV transmission in high-risk groups, (2) antiviral therapy versus observation for persons in the immune-tolerant phase, (3) discontinuation versus continuation of nucleos(t)ide analogue therapy in HBeAg-negative individuals with undetectable HBV DNA, and (4) hepatocellular carcinoma (HCC) surveillance in non-cirrhotic individuals with HBsAg clearance or co-infections with HCV, HDV, or HIV. Results: For PICO 1, limited evidence suggests antiviral therapy may reduce horizontal transmission risk, though with low certainty. PICO 2 analyses reveal uncertain benefits of treating persons in the immune-tolerant phase, with very low certainty due to heterogeneity and bias. PICO 3 analyses demonstrate that discontinuing antiviral therapy in persons who are HBeAg negative with undetectable HBV DNA increases HBsAg loss rates (OR: 12.65, 95% CI: 1.58–101.51) but carries moderate risks of virologic relapse (OR: 47.17, 95% CI: 2.79–797.35) and clinical flares. PICO 4 analyses on several cohort studies showed that in patients co-infected with HCV, HBV, or HIV, the annual incidence of HCC was higher than the level where screening becomes cost-effective, suggesting that regular liver cancer screening could be beneficial for these patients. Conclusions: Despite low certainty, the findings support shared decision-making in high-risk horizontal transmission scenarios or in treating individuals in the immune tolerance phase, caution in discontinuing antiviral therapy in virologically suppressed individuals without HBsAg loss, and tailored HCC surveillance for those with co-infection or cirrhosis.

Background: Increasing maternal body mass index (BMI) represents a risk factor for Gestational Diabetes Mellitus (GDM) and adverse obstetrical and perinatal outcomes. Objective: To stratify clinical outcomes for pregnancies affected by GDM according to maternal BMI. Methods: Retrospective cohort study including individuals ≥18 years of age who were diagnosed with GDM from 2018 to 2022. Universal GDM screening was employed with a 50 g oral glucose challenge test ± a 100 g oral glucose tolerance test. Maternal demographics, preexisting medical conditions, and selected obstetric and neonatal morbidities were evaluated. Results: A total of 2193 pregnancies in 2110 women affected by GDM were identified. This included 506 (23.0%) with normal baseline maternal BMI, 596 (27.2%) with overweight, and 1091 (49.7%) with obese BMI. Adverse maternal outcomes were more frequent in the obese compared to overweight or normal BMI categories (cesarean delivery: normal 26.9% vs. overweight 28.5% vs. obese 40.9%; p < 0.001; hypertensive disorders of pregnancy: normal 8.7% vs. overweight 12.1% vs. obese 16.8%; p < 0.001). Postpartum glucose intolerance was higher in women with obesity (normal 7.3% vs. overweight 5.9% vs. obese 14.9%; p < 0.001). Infants born to mothers with obesity had higher birthweights (normal 3.3 kg vs. overweight 3.4 kg vs. obese 3.5 kg; p < 0.001), were more likely to have neonatal hypoglycemia (normal 29.4% vs. overweight 24.3% vs. obese 41.9%; p < 0.001) and require intensive care unit admission (normal 8.1% vs. overweight 5.9% vs. obese 11.9%; p < 0.001). Conclusions: Patients with GDM and baseline BMI in the obese range experienced the highest rate of adverse outcomes, while those with overweight BMI had similar outcomes to individuals who had normal BMI at baseline.

Abstract Context Primary aldosteronism (PA) is a leading endocrine cause of secondary hypertension. Objective To support the development of the Endocrine Society Clinical Practice Guideline on managing PA. Data Source MEDLINE, Embase, Scopus, and others were searched on October 4, 2024. Study Selection Studies were selected by pairs of independent reviewers. Data Extraction Data were extracted and appraised by pairs of independent reviewers. Data Synthesis We included 95 studies (7 randomized trials and 88 observational studies). We did not identify trials that evaluated the outcomes of PA screening. One observational study suggested that screening was associated with higher rates of using PA-specific medical therapies and better blood pressure control. Patients managed with adrenal venous sampling (vs computed tomography alone) may have a better post-adrenalectomy biochemical cure rate, but with an increased risk of adrenal hemorrhage. Two small observational studies suggested that PA-specific medical or surgical therapy was likely associated with better blood pressure control than nonspecific therapy. Small randomized trials suggested that surgical therapy may be associated with better blood pressure control than medical therapy, with a lower number and dosage of antihypertensive medications. Compared to eplerenone, spironolactone may be associated with better control of hypokalemia and a lower number and dosage of antihypertensive agents. Unsuppressed plasma renin activity was associated with better control of hypokalemia, while suppression was associated with higher risk of mortality, atrial fibrillation, and stroke (very low certainty). Conclusion This systematic review addresses various aspects of managing PA and will support the development of the Endocrine Society guidelines.

Abstract Introduction Case reports and series are critical to guide initial decision-making in a pandemic, but may have lower rigor because of the need to publish them quickly. This meta-epidemiologic study compares the methodological quality of case series that described the acute coronavirus disease 2019 (COVID-19) pandemic in 2020 versus those that described long-haul cases. Methods We conducted a systematic review in multiple databases for long-haul case series and reports. We identified early cases of acute COVID-19 synthesized in published systematic reviews. We evaluated the methodological quality by pairs of independent reviewers using a tool dedicated for appraising case series. Results We included 239 original case series (81 published in the first year of the pandemic and 158 published later describing long-haul COVID). The methodological quality of both groups of case series was very good (80–100% of series satisfying quality items) except for two items, the selection approach of cases included in the series and ruling out other causes that can explain the main finding described in the series. The appraisal tool demonstrated high agreement and reliability between reviewers. Conclusion The methodological quality of modern case series is high, except for two quality items that represent an area for potential for improvement for authors of case series describing future pandemics.

Abstract Context The risk of gestational diabetes mellitus (GDM) in twin pregnancies is more than double that of singleton pregnancies. Although twin pregnancies present unique challenges for fetal growth and prenatal management, the approach to GDM diagnosis and treatment is the same regardless of plurality. Data on pregnancy outcomes for individuals with GDM and a twin pregnancy are limited and conflicting. Objective To describe the maternal characteristics associated with GDM in twin pregnancies and to assess the associated pregnancy outcomes compared to twin pregnancies unaffected by GDM. Methods A retrospective cohort study was conducted at Mayo Clinic, Rochester, Minnesota, USA, and included predominantly Causasian women aged 18 to 45 years who received prenatal care for a twin pregnancy from 2017-2022. Maternal characteristics and a broad spectrum of pregnancy outcomes were evaluated. Universal GDM screening involved a 50 g oral glucose challenge test +/− a 100 g oral glucose tolerance test. Results GDM was diagnosed in 23% pregnancies (n = 104/452). Compared to those without, women with GDM had known risk factors including a higher prepregnancy body mass index (31.1vs 26.3 kg/m2; P &lt; .01) and a prior history of GDM (21.7 vs 5.9%; P &lt; .01). There were no differences in maternal pregnancy complications or neonatal outcomes between groups. Attendance at postpartum glucose testing among women with GDM was poor at 27.9% (29/104). Conclusion These data suggest that women with twin pregnancies share a similar GDM risk profile to those with singleton pregnancies and provide reassuring evidence that current management for GDM twin pregnancies produces similar outcomes to twin pregnancies without GDM.

Introduction D-dimer levels, which originate from the lysis of cross-linked fibrin, are serially measured during coronavirus disease 2019 illness to rule out hypercoagulability as well as a septic marker. Methods This multicenter retrospective study was carried out in two tertiary care hospitals in Karachi, Pakistan. The study included adult patients admitted with a laboratory-confirmed coronavirus disease 2019 infection, with at least one measured d-dimer within 24 h following admission. Discharged patients were compared with the mortality group for survival analysis. Results The study population of 813 patients had 68.5% males, with a median age of 57.0 years and 14.0 days of illness. The largest d-dimer elevation was between 0.51–2.00 mcg/ml (tertile 2) observed in 332 patients (40.8%), followed by 236 patients (29.2%) having values greater than 5.00 mcg/ml (tertile 4). Within 45 days of hospital stay, 230 patients (28.3%) died, with the majority in the ICU (53.9%). On multivariable logistic regression between d-dimer and mortality, the unadjusted (Model 1) had a higher d-dimer category (tertile 3 and tertile 4) associated with a higher risk of death (OR: 2.15; 95% CI: 1.02–4.54, P=0.044) and (OR: 4.74; 95% CI: 2.38–9.46, P<0.001). Adjustment for age, sex, and BMI (Model 2) yields only tertile 4 being significant (OR: 4.27; 95% CI: 2.06–8.86, P<0.001). Conclusion: Higher d-dimer levels were independently associated with a high risk of mortality. The added value of d-dimer in risk stratifying patients for mortality was not affected by invasive ventilation, ICU stays, length of hospital stays, or comorbidities.