Murad, M. Hassan

ABSTRACT Introduction Publication bias (PB) threatens the validity of meta‐analyses by distorting effect size estimates, potentially leading to misleading conclusions. With advanced pattern recognition and multimodal capabilities, large language models (LLMs) may be able to evaluate PB and make the systematic review process more efficient. Methods We evaluated the ability of two state‐of‐the‐art multimodal LLMs, GPT‐4o and Llama 3.2 Vision, to detect PB using funnel plots alone and in combination with quantitative inputs. We simulated meta‐analyses under varying conditions, including the absence of PB, different levels of presence of PB, varying total number of studies within a meta‐analysis, and differing degrees of between‐study heterogeneity. Results Neither GPT‐4o nor Llama 3.2 Vision consistently detected the presence of PB across various settings. Under no‐publication‐bias conditions, GPT‐4o achieved a higher specificity outperforming Llama 3.2 Vision, with the difference most shown in the meta‐analyses with 20 or more studies. The inclusion of quantitative inputs alongside funnel plots did not significantly improve performance. Additionally, between‐study heterogeneity and patterns of non‐reported studies had minimal impact on the models’ assessments. Conclusions The ability of LLMs to detect PB without fine‐tuning is limited at the present time. This study highlights the need for specialized model adaptation before LLMs can be effectively integrated into meta‐analysis workflows. Future research can focus on targeted refinements to enhance LLM performance and utility in evidence synthesis.

Abstract Context Data on diagnostic accuracy of dehydroepiandrosterone sulfate (DHEA-S) for mild autonomous cortisol secretion (MACS) and adrenal insufficiency (AI) are discrepant. Objective We conducted a systematic review and meta-analysis of published studies assessing the accuracy of DHEA-S in diagnosing MACS or AI. Methods From inception to January 8, 2024, we searched databases for original studies of at least 20 participants with MACS or AI. MACS was defined as postdexamethasone cortisol greater than 1.8 mcg/dL or postsurgical hypocortisolism. AI was defined by abnormal dynamic testing. QUADAS-2 was used to assess the risk of bias. Bivariate random effects meta-analysis was used to generate pooled diagnostic accuracy estimates. Results Seven studies on DHEA-S accuracy in diagnosing MACS (574 patients with MACS, 830 referent individuals), and 2 studies on DHEA-S accuracy in diagnosing AI (52 patients with AI, 59 referent individuals) were included. A meta-analysis of studies using DHEA-S cutoff between 60 and 70 mcg/dL to diagnose MACS demonstrated a sensitivity of 82% (95% CI, 64%-93%) and a specificity of 82% (95% CI, 74%-88%). In the 2 studies evaluating DHEA-S in diagnosing AI, the reference standard was a 1-mcg cosyntropin stimulation test. The sensitivity of DHEA-S for diagnosing AI ranged from 70.3% to 86.7%, and the specificity was 87.1%. Most studies were at a moderate risk of bias. Conclusion Based on limited heterogeneous evidence, measurement of DHEA-S provides additional value in diagnosing MACS, as well as AI.

ABSTRACT Background and Objectives The relevance of Cochrane systematic reviews depends on timely completion and updates. This study aimed to empirically assess the lifecycles of Cochrane reviews published from 2003 to 2024, including transitions from protocol to review, update patterns, and withdrawals. Methods We extracted data from Cochrane Library publications between 2003 and 2024. Each review topic was identified using a unique six‐digit DOI‐based ID. We recorded protocol publication, review publication, updates, and withdrawals (i.e., removed from the Cochrane Library for editorial or procedural reasons), calculating time intervals between stages and conducting subgroup analyses by review type. Results Of 8137 protocols, 71.9% progressed to reviews (median 25.7 months), 2.4% were updated during the protocol stage, and 10.0% were withdrawn. Among 8477 reviews, 64.3% were never updated by the time of our analysis; for those updated at least once, the median interval between updates was 57.2 months. Withdrawal occurred in 2.5% of reviews (median 67.6 months post‐publication). Subgroup analyses showed variation across review types; diagnostic and qualitative reviews tended to have longer protocol‐to‐review times than other types of reviews. Conclusions Cochrane reviews show long development and update intervals, with variation by review type. Greater use of automation and targeted support may improve review efficiency and timeliness.

Abstract Background Preexisting diabetes (PDM) increases the risk of maternal and perinatal mortality and morbidity. Reduction of maternal hyperglycemia prior to and during pregnancy can reduce these risks. Despite compelling evidence that preconception care (PCC), which includes achieving strict glycemic goals, reduces the risk of congenital malformations and other adverse pregnancy outcomes, only a minority of individuals receive PCC. Suboptimal pregnancy outcomes demonstrated in real-world data highlight the need to further optimize prenatal glycemia. New evolving technology shows promise in helping to achieve that goal. Dysglycemia is not the only driver of poor pregnancy outcomes in PDM. The increasing impact of obesity on pregnancy outcomes underscores the importance of optimal nutrition and management of insulin sensitizing medications during prenatal care for PDM. Objective To provide recommendations for the care of individuals with PDM that lead to a reduction in maternal and neonatal adverse outcomes. Methods The Guideline Development Panel (GDP) composed of a multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 10 clinically relevant questions related to the care of individuals with diabetes before, during and after pregnancy. The GDP prioritized randomized controlled trials (RCTs) evaluating the effects of different interventions (eg, PCC, nutrition, treatment options, delivery) during the reproductive life cycle of individuals with diabetes, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Systematic reviews queried electronic databases for publications related to these 10 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and develop recommendations. The approach incorporated perspectives from 2 patient representatives and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. Results In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest asking a screening question about pregnancy intention at every reproductive, diabetes, and primary care visit. Screening for pregnancy intent is also suggested at urgent care/emergency room visits when clinically appropriate (2 | ⊕OOO). This was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced glycated hemoglobin (HbA1c) at the first prenatal visit and congenital malformations. In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest use of contraception when pregnancy is not desired (2 | ⊕⊕OO). This was suggested based on indirect evidence in women with diabetes, where PCC—including contraception as a key component—showed a clinically significant association with improvements in first-trimester HbA1c and the rate of congenital malformations, together with indirect evidence from the general population regarding the reduction of unplanned pregnancies and pregnancy terminations with the use of contraception. In individuals with T2DM, we suggest discontinuation of glucagon-like peptide-1 receptor agonist (GLP-1RA) before conception rather than discontinuation between the start of pregnancy and the end of the first trimester (2 | ⊕OOO). This was suggested based on limited data on risk of exposure to GLP-1RA receptor agonists during pregnancy. In pregnant individuals with T2DM already on insulin, we suggest against routine addition of metformin (2 | ⊕OOO). This was suggested based on the GDP judgment that the benefit of adding metformin to insulin to achieve decrease in rates of large for gestational age infants did not outweigh the potential harm of increasing the risk of small for gestational age infants or adverse childhood outcomes related to changes in body composition. In individuals with PDM, we suggest either a carbohydrate-restricted diet (<175 g/day) or usual diet (>175 g/day) during pregnancy (2 | ⊕OOO). This was suggested based on the GDP judgment that the available evidence was limited and very indirect, resulting in significant uncertainty about the net benefits or harms. As such, the evidence was insufficient to support a recommendation either for or against a carbohydrate intake cutoff of 175 g/day. In pregnant individuals with T2DM, we suggest either the use of a continuous glucose monitor (CGM) or self-monitoring of blood glucose (SMBG) (2 | ⊕OOO). There is lack of direct evidence supporting superiority of CGM use over SMBG for T2DM during pregnancy. There is indirect evidence supporting improved glucometrics with the use of CGM for individuals with T2DM outside of pregnancy, substantial improvements in neonatal outcomes for individuals with T1DM using CGM during pregnancy and the potential for decreasing adverse pregnancy outcomes with improved glucometrics in individuals with T2DM. In individuals with PDM using a CGM, we suggest against the use of a single 24-hour CGM target <140 mg/dL (7.8 mmol/L) in place of standard-of-care pregnancy glucose targets of fasting <95 mg/dL (5.3 mmol/L), 1-hour postprandial <140 mg/dL (7.8 mmol/L), and 2-hour postprandial < 120 mg/dL (6.7 mmol/L) (2 | ⊕OOO). This was suggested based on indirect evidence that associated adverse pregnancy outcomes with a fasting glucose > 126 mg/dL (7 mmol/L). In individuals with T1DM who are pregnant, we suggest the use of a hybrid closed-loop pump (pump adjusting automatically based on CGM) rather than an insulin pump with CGM (without an algorithm) or multiple daily insulin injections with CGM (2 | ⊕OOO). This was suggested based on a meta-analysis of RCTs which demonstrated improvement in glucometrics with increased time in range (MD +3.81%; CI −4.24 to 11.86) and reduced time below range (MD −0.85%; CI −1.98 to 0.28) with the use of hybrid closed-loop pump technology. In individuals with PDM, we suggest early delivery based on risk assessment rather than expectant management (2 | ⊕OOO). This was suggested based on indirect evidence that risks may outweigh benefits of expectant management beyond 38 weeks gestation and that risk assessment criteria may be useful to inform ideal delivery timing. In individuals with PDM (including those with pregnancy loss or termination), we suggest postpartum endocrine care (diabetes management), in addition to usual obstetric care (2 | ⊕OOO). As the postpartum period frequently overlaps with preconception, this was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced HbA1c at the first prenatal visit and congenital malformations. Conclusion The data supporting these recommendations were of very low to low certainty, highlighting the urgent need for research designed to provide high certainty evidence to support the care of individuals with diabetes before, during, and after pregnancy. Investment in implementation science for PCC is crucial to prevent significant mortality and morbidity for individuals with PDM and their children. RCTs to further define glycemic targets in pregnancy and refinement of emerging technology to achieve those targets can lead to significant reduction of harm and in the burden of diabetes care. Data on optimal nutrition and obesity management in pregnancy are lacking. More research on timing of delivery in women with PDM is also needed.

Abstract Context Women with preexisting diabetes mellitus (PDM) are at increased risk of pregnancy-related complications. Objective To summarize the available supporting evidence for the Endocrine Society guidelines about management of PDM in pregnancy. Data Sources MEDLINE, EMBASE, Scopus, and other sources through February 2025. Study Selection Studies were selected by pairs of independent reviewers. Data Extraction Data were extracted by pairs of independent reviewers. Data Synthesis We included 17 studies. Meta-analysis showed no significant difference between hybrid closed-loop insulin pump (HCL) and standard of care regarding time in range (TIR), time above range (TAR), and time below range (TBR). HCL had better overnight TIR and TBR. For women with type 2 diabetes mellitus (T2DM), intermittent use of continuous glucose monitoring (CGM) was not associated with a significant change in the risk of large for gestational age (LGA) neonates (2 randomized controlled trials [RCTs], 102 patients). Adding metformin to insulin was associated with a lower risk of LGA (2 RCTs, 1126 patients). Three retrospective studies (1724 patients) suggested increased neonatal complications when delivery was induced before 39 weeks of gestation (particularly before 38 weeks) in women with preexisting type 1 (T1DM) and T2DM, although this evidence was subject to likely confounding. One retrospective study showed no increase in neonatal complications with periconceptional exposure to glucagon-like peptide-1 receptor agonists. We could not identify comparative studies assessing a screening question about the possibility of pregnancy or a carbohydrate restrictive diet. Conclusion This systematic review addresses various aspects of managing PDM in pregnancy and will support the development of the Endocrine Society guidelines.

Abstract Background Although the choice of dialysis technique is based on several factors, patient survival is undoubtedly one of the most relevant. In a context where randomization to either peritoneal dialysis (PD) or hemodialysis (HD) proved to be extremely challenging, previous meta-analyses were greatly limited due to the inclusion of historical studies. Methods We performed a systematic review by searching multiple databases up to April 22nd, 2022. The primary outcome was the association between dialysis modality (PD vs HD) and mortality assessed via hazard ratios (HR). Subgroup analyses were conducted to explore potential sources of heterogeneity, including sex, age, diabetes, dialysis vintage, geographical location, HD access, and study cohort inclusion period. Results Database search yielded 5317 citations, from which, 27 observational studies met the eligibility criteria, including 1 033 362 incident dialysis patients. The pooled mortality HR for PD versus HD was 1.01 (95% CI 0.93–1.10). Heterogeneity was substantial ( I 2 = 94%) and was largely explained by different baseline features of the included populations. A statistically significant subgroup effect was demonstrated for age (> 65 vs.<65 years; p = 0.01), geographical location of the studies (Oceania vs. Europe vs. Asia vs. North America; p < 0.01), and HD vascular access (central venous catheter vs. arteriovenous fistula; p < 0.01, only one study included). Conclusions This meta-analysis suggests that overall PD and incentre HD likely carry equivalent survival benefits. However, differences were detected among subgroups based on age, geographic location, HD access type, but not on sex, diabetes status, dialysis vintage and study cohort inclusion period.

Objectives: To compare thresholds and accuracies of FIB-4, vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2D shear wave elastography (2D-SWE), and MR elastography (MRE) for detecting hepatic fibrosis in patients with MASLD. Materials and Methods: Systematic searching of MEDLINE, EMBASE, Cochrane Library, Scopus, and the gray literature from inception to March 2024 was performed. Studies evaluating accuracies of FIB-4, VCTE, 2D-SWE, pSWE, and/or MRE for detecting significant (≥F2) and/or advanced (≥F3) hepatic fibrosis in MASLD patients compared to histology were identified. Full-text review and data extraction were performed independently by two reviewers. Multivariate meta-analysis and subgroup analyses were performed using index test and fibrosis grading. Risk of bias was assessed using QUADAS-2. Results: 207 studies with over 80,000 patient investigations were included. FIB-4 1.3 threshold sensitivity was 71% (95% CI 66–75%) for detecting advanced hepatic fibrosis, which improved to 88% (85–91%) using a <0.75 threshold. FIB-4 specificity using a 2.67 threshold was 96% (94–97%). Sensitivities of 88–91% were achieved using thresholds of 3.2 kPa for pSWE, 4.92 kPa for 2D-SWE, 7.18 kPa for VCTE, and 2.32 kPa for MRE. No significant differences were identified for sensitivities in subgroup analysis with thresholds between 7 and 9 kPa. Most imaging-based studies were high risk of bias for the index test. Conclusions: A FIB-4 threshold of <0.75 and modality-dependent thresholds (VCTE < 7 kPa; pSWE <3 kPa; 2D-SWE <5 kPa; and MRE <2.5 kPa) would achieve sensitivities of around 90% when defining low-risk MASLD in population screening. A modified two-tier algorithm aligning with existing Society of Radiologists in Ultrasound guidelines would improve risk stratification accuracies compared to existing guidelines by European and American liver societies.