Wang, Zhen

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.

Objective: To compare postoperative complications between staged versus unstaged tympanoplasty and subtotal petrosectomy (STP) in adults undergoing cochlear implants with noncholesteatoma chronic otitis media (NCCOM) and tympanic membrane perforation. Databases reviewed: PubMed/MEDLINE, Cochrane CENTRAL, Embase, CINAHL, Web of Science, WHO Global Index Medicus, ClinicalTrials.gov, and WHO ICTRP. Materials and methods: A systematic search of databases was conducted by a research librarian from inception through November 18, 2024. Eligible studies for inclusion must have reported on adult cochlear implant recipients undergoing surgical management of NCCOM with perforation. Using a random effects model, complication rates were pooled and compared between staged and unstaged surgeries using relative risk (RR) with 95% CI. Results: Of 1265 studies identified, 19 met inclusion criteria (n = 84). Fifty three (63.1%) patients underwent unstaged surgery. Amongst all patients, STP was performed more than tympanoplasty (72.6%, 61/84 vs 27.4%, 23/84), and the overall complication rate was 11.9% (10/84). There was no significant difference in complication rates between combined staged and unstaged surgeries [RR: 1.13 (95% CI, 0.18-7.04)] as well staged and unstaged tympanoplasty [RR: 0.34 (95% CI, 0.11-0.1.01)]. However, complication rates were lower for staged than unstaged STP [RR: 0 (95% CI, 0.0-0.07)]. Conclusion: Staged and unstaged surgery for NCCOM and cochlear implant may result in comparable complication rates, however the wide CIs for RR statistics in comparisons between combined staged and unstaged procedures as well as staged and unstaged tympanoplasty indicate a need for similar studies of larger populations.

572 Background: Neoadjuvant endocrine therapy (NET) is sometimes used to shrink hormone receptor-positive (HR+) breast cancers to improve breast conservation rates and reduce axillary nodal burden. At the beginning of the COVID-19 pandemic, several organizations endorsed NET use to mitigate the harm of surgery delay when cancer operations were less available due to infection transmission concerns. However, the real-world patterns of NET during this period are understudied. This study investigated the alteration of NET utilization patterns during the COVID-19 pandemic in the United States using the National Cancer Database (NCDB). Methods: We identified patients diagnosed with stage I-III invasive HR+/human epidermal growth factor receptor 2-negative (HER2-) breast cancer between 2018-2022 in the NCDB. Estrogen receptor and/or progesterone receptor positivity was required for inclusion in the cohort. Receipt of NET was defined as initiation of endocrine therapy ≥ 14 days before the patient’s first surgical procedure. The study cohort generation and statistical analysis were conducted using Stata and R 4.4.3. A two-tailed p value < 0.05 was considered statistically significant. Results: 495,098 patients were included in the cohort, 195,371 in 2018-2019 (pre-pandemic), 91,686 in 2020 (early pandemic), 106,157 in 2021 (mid-pandemic), and 101,884 in 2022 (late pandemic). NET utilization was increased in the early pandemic compared to the pre-pandemic (seen in 5.8% vs 2.4% of the cohort, Chi-square p value < 0.001), but this use fell back to 3.4% in the mid-pandemic and 3.5% in the late-pandemic. The median (IQR) duration of NET was 15.7 (6.4-26.6) weeks in the pre-pandemic, 9.3 (5.4-18.7) weeks in the early pandemic, 13.2 (5.8-25.7) weeks in the mid-pandemic, and 12.0 (6-24.6) weeks in late pandemic (Kruskal-Wallis p value = 0.001). The transient increase in NET utilization during the early pandemic was more pronounced among patients with tumors < 5 cm and node-negative disease. Conclusions: Our study identified a significant shift in the utilization of NET for HR+/HER2- breast cancer during the COVID-19 pandemic. Pandemic-era NET policies produced a short-lived practice change that was only partially sustained once surgical access normalized. NET utilization (%) by subgroup and year for stage I-III HR+/HER2- breast cancer. Variable Category 2018-2019 2020 2021 2022 Overall NET Use 2.4 5.8 3.4 3.5 Age Group (years old) <50 2.2 4.9 3.9 4.0 >=50 2.4 6.0 3.3 3.4 Tumor Size <5 cm 2.0 5.5 2.9 3.1 >=5 cm 9.0 9.7 11.2 11.6 Histology Subtype Ductal 2.2 5.5 3.3 3.4 Lobular 3.6 7.1 4.4 4.8 Ductal/Lobular 2.6 6.2 4.3 3.6 Other 1.9 6.7 2.5 2.6 KI67 <20% 2.5 6.4 3.4 3.3 >=20% 2.3 5.5 3.5 3.7 Tumor Grade Well differentiated 1.9 5.8 2.4 2.6 Moderately differentiated 2.7 6.1 3.9 3.9 Poorly differentiated/undifferentiated 2.9 4.8 4.3 4.8 Node Positivity Positive 5.2 5.6 9.3 9.5 Negative 2.0 5.8 2.6 2.7

Objective: To estimate the relative risk of meningitis after repair of spontaneous lateral skull base cerebrospinal fluid (CSF) leaks through meta-analysis of published studies. Databases Reviewed: PubMed, Medline, Embase, Cochrane, SCI-EXPANDED, ESCI, Epistemonikos, and WHO Global Index Medicus were queried for terms including and related to meningitis, CSF leak, surgery, and spontaneous from inception to April 02, 2024. Methods: Prospective and retrospective studies in any language reporting either preoperative or postoperative rates of meningitis in adults with spontaneous lateral skull base CSF leaks were included. Two reviewers independently screened 2,564 studies and extracted data and evaluated risk of bias in 57 studies that met inclusion criteria. A random effects generalized linear mixed model was used to pool and compare logit transformed risk of meningitis before and after repair. Results: Of 1,310 patients who met inclusion criteria, 1,239 underwent CSF leak repair. Fifty-two studies reported rates of preoperative meningitis, and 27 studies reported rates of postoperative meningitis. Twenty-two studies with a total of 511 patients reported both rates. The average follow-up period of 17 studies reporting duration of follow-up was 23.1 months. The preoperative pooled risk of meningitis was 0.16 (95% CI: 0.13–0.25, I 2 = 40.57%). The postoperative pooled risk was considerably lower at 0.01 (95% CI: 0.01–0.14, I 2 = 4.16%). With substantial heterogeneity (I 2 = 62.94%), we observed a relative risk of meningitis after repair of 0.02 (95% CI: 0.00–0.79, p = 0.04). Conclusion: Surgical repair of spontaneous lateral skull base CSF leaks may significantly reduce the risk of adult meningitis.

Importance Suicide is a leading cause of death among young people and an escalating public health crisis. Objective To assess the effectiveness and harms of available treatments for suicidal thoughts and behaviors among youths at heightened risk for suicide. Evidence Review A systematic review was conducted searching databases including MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and various gray literature sources from January 1, 2000, to September 26, 2024. We included randomized clinical trials, comparative observational studies, and before-after studies of psychosocial interventions, pharmacologic interventions, neurotherapeutics, emerging therapies, and combination therapies. Eligible patients were youths (aged 5-24 years) with heightened risk for suicide, adolescents from racial and ethnic minority groups known to be at increased risk of suicide, or those exposed to crime or violence. Pairs of independent reviewers selected and appraised studies. Findings This review included 65 studies (33 randomized clinical trials, 13 comparative observational studies, and 19 before-after studies) reporting on 14 534 patients (median age, 15.1 years; 75.1% female patients). Psychosocial interventions comprised psychotherapy interventions (33 studies; cognitive behavioral therapy, dialectical behavioral therapy, collaborative assessment and management of suicidality, dynamic deconstructive psychotherapy, attachment-based family therapy, and family-focused therapy), acute (ie, 1-4 sessions or contacts) psychosocial interventions (19 studies; safety planning, family-based crisis management, motivational interviewing crisis interventions, continuity of care after crisis, and brief adjunctive treatments), and school- or community-based psychosocial interventions (13 studies; social network interventions, school-based skills interventions, suicide awareness or gatekeeper programs, and community-based, culturally tailored adjunct programs). Dialectical behavior therapy showed moderate strength of evidence for reducing suicidal ideation. Other categories of psychosocial treatments showed insufficient to low strength of evidence for reducing suicidal outcomes. None of the studies evaluated adverse events. The evidence base on pharmacologic treatment for youths at risk of suicide was largely nonexistent. Conclusions and Relevance This systematic review found that the current evidence on available interventions targeting youths at heightened risk of suicide is uncertain. Medication, neurotherapeutics, and emerging therapies remain unstudied among this population. The limited evidence base calls for the development of novel, developmentally and trauma-informed treatments, as well as multilevel interventions to target the increasing suicide risk among youths.

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.

BACKGROUND AND OBJECTIVES: Aneurysm risk prediction remains an imprecise science that places patients at risk for either over or undertreatment. Machine learning (ML) models may improve clinical practice by adding precision to risk assessment. This study aims to comprehensively assess the current landscape of ML applications in predicting the risk of aneurysm rupture and compare the performance with the widely used PHASES score. METHODS: A systematic review of PubMed, Scopus, and Web of Science was conducted. All studies using ML tools to predict the rupture risk of intracranial aneurysms were included. Meta-analysis was conducted with consideration to the ML algorithms and compared with the PHASES score. RESULTS: Thirty-six studies involving 22 462 patients were included in the final analysis. ML techniques, including 124 models using 25 algorithms, were employed. Among various ML models, while they had comparable diagnostic performance, deep learning exhibited a slightly better performance profile (sensitivity = 0.792, specificity = 0.788, and accuracy = 0.778 in external validation). Based on our analysis, ML, regardless of the algorithm, provides comparable sensitivity (0.743 vs 0.771, P = .60) and higher specificity (0.763 vs 0.507, P < .01) compared with the PHASES score. Consistently, pooling the area under the receiver operating characteristic curve (AUC) for 60 ML models and 5 PHASES score data, ML models exhibited higher AUC (0.84 vs 0.64, P < .01). Using hemodynamic parameters as input for models improved specificity ( P < .01) in the test sets without any significant changes in the sensitivity. The later improvement was not observed in the external validation sets. CONCLUSION: ML techniques have the potential to enhance the prediction of intracranial aneurysm rupture compared with traditional approaches, like the PHASES score. Incorporating hemodynamic parameters may further enhance the accuracy of ML models. Feature prospective studies are required to validate the utility of ML models for clinical integration.

Abstract Objective To examine the effectiveness of treatment strategies for medication‐overuse headache (MOH) in children and adolescents. Background There are no guidelines for the treatment of adult or pediatric patients with MOH. However, research pertaining to MOH in adults is far outpacing research in children and adolescents. Methods A systematic review of evidence on treatment for MOH in children and adolescents was performed via PubMed, Embase, Web of Science, PsycINFO, and Cochrane from database inception to October 2024 for articles with the subject headings and keywords for MOH and pediatric, children, and/or adolescent. Inclusion criteria were: (i) randomized controlled trials and retrospective and prospective observational studies, (ii) children and adolescents aged <18 years with chronic headaches and with medication overuse (MO) or MOH, and (iii) interventions addressing MO or MOH, including pharmacologic and behavioral interventions. At least two independent reviewers screened citations and full‐text articles independently. Results A total of 16 studies (one randomized control trial, six prospective observational studies and nine retrospective observational studies) were identified as meeting final inclusion criteria, resulting in 7978 total participants with a subset of those having MO, MOH or probable MOH. Participants ranged in mean age from 10 to 14.7 years, with 7.1%–46.2% male participants. All the studies recruited patients from an outpatient setting. Interventions used in the studies included withdrawal of the overused acute medication, initiation of preventive medication, patient education, physiotherapy and psychological treatment, and motivational interviewing. Multimodal therapy was studied more than single therapeutic intervention. There was vast heterogeneity across the studies, including study design, diagnostic criteria, intervention type, and outcomes. Conclusion From the data available, there does not seem to be a singular superior treatment approach. Accordingly, the most appropriate treatment modality will need to be tailored to the patient and their caregivers. Further research is required regarding management of MOH in children and adolescents.

OBJECTIVE Patients with autosomal dominant polycystic kidney disease (ADPKD) have been identified to have a significantly increased risk of developing intracranial aneurysms (IAs). These patients are diagnosed at younger ages and are also at increased risk for IA rupture. The objective of this systematic review and meta-analysis was to identify risk factors associated with IA detection during screening of asymptomatic ADPKD patients. METHODS The authors searched for studies reporting the prevalence of IA among patients with ADPKD screened using MRA, CTA, or DSA on PubMed, Embase, Google Scholar, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov prior to August 2023 by using individualized standardized search strategies. Eligibility of all retrieved studies was assessed according to the PRISMA guidelines. Risk of bias of the included observational studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using a random-effects model. RESULTS Twenty-four observational studies involving 5907 patients with ADPKD were identified for quantitative analysis. The authors observed an overall prevalence of IA of 12.6%. They identified several risk factors for IA with statistically significantly increased odds for unruptured IA (UIA) detection, including female sex (18 studies, OR 1.63, 95% CI 1.37–1.94, I 2 = 0%), family history of either IA or subarachnoid hemorrhage (SAH) (12 studies, OR 2.17, 95% CI 1.68–2.81, I 2 = 0%), family history of SAH (3 studies, OR 2.67, 95% CI 1.25–5.71, I 2 = 66.0%), stage 3 or greater chronic kidney disease (CKD) (4 studies, OR 2.55, 95% CI 1.84–3.54, I 2 = 0%), and hypertension (13 studies, OR 1.41, 95% CI 1.04–1.91, I 2 = 34%). Age > 45 years, family history of ADPKD, smoking status, and presence of liver cysts did not reach statistical significance as risk factors during this meta-analysis. CONCLUSIONS The results of the authors’ meta-analysis suggest increased risk of UIA detection in screening of ADPKD patients who are female, have a family history of IA or SAH, have hypertension, or have moderate or more severe CKD. Given the increased prevalence of IA in ADPKD patients with these risk factors, these patients may stand to benefit from screening for IA early in treatment or at time of diagnosis, even if neurologically asymptomatic.