Tag: nevin manimala

JAMA Netw Open. 2025 Oct 1;8(10):e2536771. doi: 10.1001/jamanetworkopen.2025.36771.

ABSTRACT

IMPORTANCE: Narcolepsy is a sleep disorder potentially affecting mortality, yet evidence on this association remains sparse.

OBJECTIVE: To examine whether narcolepsy is associated with an increased risk of all-cause and cause-specific mortality.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2021, with patients followed up until death or December 31, 2022. Patients were aged 6 years or older with 2 or more narcolepsy diagnoses from psychiatrists or neurologists. Controls were selected from the NHIRD as a population-based sample. Controls without narcolepsy were matched in a 1:4 ratio on sex and birth date (±6 months). Sibling controls were siblings without narcolepsy. Statistical analysis was performed from January to April 2025.

EXPOSURES: Clinical narcolepsy diagnosis, confirmed via NHIRD records (International Classification of Diseases, Ninth Revision, Clinical Modification code 347 or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification code G47.4).

MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality, measured as hazard ratios (HRs) using Cox proportional hazards regression, adjusted for birth year, sex, income, urbanization, and Charlson Comorbidity Index. Secondary outcomes included cause-specific mortality (natural, unnatural, accidents, suicides).

RESULTS: Of 3187 patients with narcolepsy (mean [SD] age, 29.5 [16.1] years; 1674 male patients [52.5%]) and 12 748 controls (mean [SD] age, 29.5 [16.1] years; 6696 male patients [52.5%]), 132 patients with narcolepsy and 456 controls died. Psychiatric comorbidities, especially depression (1167 of 3187 [36.6%] vs 861 of 12 748 [6.8%]) and anxiety (1054 of 3187 [33.1%] vs 853 of 12 748 [6.7%]), were more common in the narcolepsy group than in the control group. Crude all-cause mortality rates were 44.3 per 10 000 person-years among patients with narcolepsy and 38.1 per 10 000 person-years among controls. All-cause mortality was not increased among patients with narcolepsy (HR, 0.96; 95% CI, 0.79-1.17). There was no increase among patients with narcolepsy in cause-specific mortality for natural causes (HR, 0.90; 95% CI, 0.73-1.11), unnatural causes, (HR, 1.41; 95% CI, 0.83-2.40), accidents (HR, 1.37; 95% CI, 0.64-2.95), and suicides (HR, 1.41; 95% CI, 0.62-3.22). The sibling cohort analysis similarly demonstrated no significantly increased risk among patients with narcolepsy of all-cause mortality (HR, 1.14; 95% CI, 0.63-2.06) or cause-specific mortality from natural causes (HR, 0.66; 95% CI, 0.28-1.56), unnatural causes (HR, 2.08; 95% CI, 0.87-4.98), accidents (HR, 1.61; 95% CI, 0.48-5.37), or suicides (HR, 3.43; 95% CI, 0.88-13.28).

CONCLUSIONS AND RELEVANCE: In this cohort study of Taiwanese residents, narcolepsy was not associated with excess all-cause or cause-specific mortality. These findings reduce immediate clinical concern, but the wide 95% CIs suggest that a modest increase in risk cannot be excluded; replication in other populations with longer follow-up is warranted.

PMID:41066120 | DOI:10.1001/jamanetworkopen.2025.36771

Surg Laparosc Endosc Percutan Tech. 2025 Oct 9. doi: 10.1097/SLE.0000000000001410. Online ahead of print.

ABSTRACT

BACKGROUND: We designed a study to determine the impact of transversalis fascia repair (TFR) during TEP surgery for inguinal hernias on hospital stay duration, recurrence rates, quality of life, and related adverse outcomes in a randomized, double-blinded, controlled clinical trial. We screened patients presenting with inguinal hernias requiring elective surgery.

METHODS: Eligible patients were randomly allocated into 2 groups: the TFR group, whose inguinal ring defect was narrowed; and the Routine Treatment Group (RTG) group, whose defect left unchanged. The prespecified primary outcomes were the length of hospital stay and the time of surgery. Patients were followed for 6 months to be evaluated regarding the Visual Analogue Scale (VAS), the rate of recurrence and seroma formation, and their Carolina Comfort Scale (CCS) hernia-specific quality of life.

RESULTS: A total of 60 patients were allocated to study arms with no significant differences in the baseline characteristics. The intervention did not have a significant impact on the duration of hospitalization. However, the operation time in the TFR group was significantly longer than in the RTG group (Cohen’s d=-1.13, 95% CI: -1.67 to -0.58, P<0.001). In contrast, no statistically or clinically significant differences were noted between the groups concerning postoperative pain, analgesic usage, or rates of acute and chronic pain. Furthermore, the TFR group had a much lower risk of seroma formation during the first week after surgery compared with the routine nonclosing defect group, showing an almost 80% lower risk of seroma formation. However, this finding did not reach statistical significance.

CONCLUSION: Although the defect-closing approach resulted in longer operation times, our study did not demonstrate any beneficial effects on hospital stay duration, postoperative pain, or quality of life. However, this approach may reduce seroma formation in the first week postsurgery, which should be confirmed in future meta-analyses.

TRIAL REGISTRATION: This trial was prospectively registered on the Iranian Registry of Clinical Trials on February 29, 2024 (IRCT20180312039067N2).

PMID:41066116 | DOI:10.1097/SLE.0000000000001410

JAMA Oncol. 2025 Oct 9. doi: 10.1001/jamaoncol.2025.3875. Online ahead of print.

ABSTRACT

IMPORTANCE: Inherited pathogenic variants (PVs) in known predisposition genes can greatly increase breast cancer risk, but the combined impact of PV status, family history, and other factors on breast cancer risk in the general US population has not been well described.

OBJECTIVE: To evaluate population-based breast cancer risk estimates for those with established PVs overall and stratified by first-degree family history of breast cancer and other factors.

DESIGN, SETTING, AND PARTICIPANTS: This study used pooled data from 13 US-based breast cancer case-control studies participating in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Enrollment for individual studies occurred between 1976 and 2013, and results are based on data released March 2023, with analyses conducted from June 2022 to July 2025.

EXPOSURES: PVs, breast cancer family history, self-reported race and ethnicity, and established risk factors.

MAIN OUTCOMES AND MEASURES: Breast cancer rate ratios for PVs in 7 genes were estimated from the CARRIERS consortium. PV status and incidence and mortality statistics were combined using the Individualized Coherent Absolute Risk Estimation (iCARE) model to estimate conditional cumulative breast cancer risks and 95% CIs, stratified by family history and standardized to the US population. Models that incorporated population-based data and published estimates for established epidemiologic risk factors were also evaluated.

RESULTS: A total of 67 692 women were studied, including 33 841 who were diagnosed with breast cancer. PVs in ATM, BRCA1, BRCA2, CHEK2, and PALB2 were strongly associated with breast cancer risk, with BRCA1 and PALB2 PVs showing evidence of heterogeneity by family history. In models considering PVs, family history, and established risk factors, the estimated cumulative risks of breast cancer by age 50 years ranged from 2.4% (95% CI, 2.4-2.4) in women with no PVs and no family history to 35.5% (95% CI, 21.6-55.1) in PALB2 PV carriers with a family history. Among women who have not been diagnosed with breast cancer by age 50 years, the cumulative risk of breast cancer by age 80 years ranged from 11.1% (95% CI, 11.0-11.2) in noncarriers with no family history to 70.5% (95% CI, 52.8-83.5) for PALB2 carriers with a family history. PV-specific cumulative risk estimates varied across subgroups defined by race and ethnicity and potentially modifiable epidemiologic risk factors.

CONCLUSIONS AND RELEVANCE: In this study, population-based estimates of cumulative breast cancer risk for established PVs, as informed by the CARRIERS case-control sample, varied by family history and potentially modifiable risk factors. These estimates provide guidance for identifying individuals who will most benefit from enhanced screening and prevention strategies.

PMID:41066089 | DOI:10.1001/jamaoncol.2025.3875

Stat Med. 2025 Oct;44(23-24):e70207. doi: 10.1002/sim.70207.

ABSTRACT

Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants and to use resources efficiently. Adaptive clinical trials are often more efficient and ethical than standard or non-adaptive trials because they can require fewer participants, target more promising treatments, and stop early with sufficient evidence of effectiveness or harm. The design of adaptive trials is usually undertaken via simulation, which requires assumptions about the data-generating process to be specified a priori. Unfortunately, if such assumptions are misspecified, then the resulting trial design may not perform as expected, leading to, for example, reduced statistical power or an increased Type I error. Motivated by a clinical trial of a vaccine to protect against gastroenteritis in infants, we propose an approach to design adaptive clinical trials with time-to-event outcomes without needing to explicitly define the data-generating process. To facilitate this, we consider trial design within a general Bayesian framework where inference about the treatment effect is based on the partial likelihood. As a result, inference is robust to the form of the baseline hazard function, and we exploit this property to undertake trial design when the data-generating process is only implicitly defined. The benefits of this approach are demonstrated via an illustrative example and via redesigning our motivating clinical trial.

PMID:41066086 | DOI:10.1002/sim.70207

J Comput Biol. 2025 Oct 9. doi: 10.1177/15578666251383561. Online ahead of print.

ABSTRACT

Metacell partitioning is a common preprocessing step in single-cell data analysis, used to reduce sparsity by aggregating similar cells. However, existing metacell partitioning algorithms may inadvertently group heterogeneous cells, potentially biasing downstream analyses. The resulting metacell partitions can vary substantially with different hyperparameter settings, leaving users uncertain about which result to trust. The mcRigor R package offers a statistical method for evaluating and optimizing metacell partitioning in single-cell data analysis. This article provides instructions for installing and using mcRigor to support more rigorous and interpretable metacell-based workflows.

PMID:41066085 | DOI:10.1177/15578666251383561

Stat Med. 2025 Oct;44(23-24):e70275. doi: 10.1002/sim.70275.

ABSTRACT

Identifying and quantifying predictive biomarkers is a critical issue of Precision Medicine approaches and patient-centric clinical development strategies. Early phase adaptive designs can improve trial efficiency by allowing for adaptations during the course of the trial. In this work, we are interested in adaptations based on interim analysis permitting a refinement of the existing study population according to their predictive biomarkers. At an early stage, the goal is not to precisely define the target population, but to not miss an efficacy signal that might be limited to a biomarker subgroup. In this work, we propose a one-arm two-stage early phase biomarker-guided design in the setting of an oncology trial where at the time of the interim analysis, several decisions can be made regarding stopping the entire trial early or continuing to recruit patients from the full or a selected patient population. Via simulations, we show that, although the sample size is limited, the proposed design leads to better decision-making compared to a classical design that does not consider an enrichment expansion.

PMID:41066076 | DOI:10.1002/sim.70275

J Palliat Med. 2025 Oct 9. doi: 10.1177/10966218251386947. Online ahead of print.

ABSTRACT

Background: Palliative care is essential yet underutilized in Canada. Inconsistent definitions and fee codes across provinces/territories hinder effective comparative analysis. Aim: Explore palliative care definitions and fee codes in Canada by examining the provincial/territorial schedules of benefits. Design: We conducted a narrative review of provincial/territorial schedules of benefits, focusing on palliative care definitions and fee codes. Qualitative comparative analysis was performed on the definitions, and descriptive statistical analysis was conducted on the fee codes. Setting/Participants: The study reviewed schedules of benefits from 11 Canadian provinces and territories, excluding Quebec and Nunavut. Results: About 7/11 (64%) provinces/territories published definitions for palliative care, typically characterizing it as terminal, focusing on comfort, and providing a time-based prognosis. The number of specific palliative care fee codes varied from 4 to 32. Conclusions: There is substantial variability in the definition and fee codes used for physician-delivered palliative care across Canada. A standardized national framework for palliative care definitions and fee codes could improve access and care delivery.

PMID:41066074 | DOI:10.1177/10966218251386947

Indian Pediatr. 2025 Oct 9. doi: 10.1007/s13312-025-00192-5. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare module-based versus conventional lectures for undergraduate teaching in pediatrics.

METHODS: This quasi-experimental study was conducted among phase III part II MBBS students during their pediatric posting at a tertiary care teaching center in Southern India. Fifty students each in the experimental and control group were taught using module-based and conventional lectures, respectively. The learning outcome was evaluated by pre-, and post-test scores and analyzed by ‘paired t test’, ‘unpaired t test’ and ‘repeated measure ANOVA’. Perception was assessed using five-point Likert scale.

RESULTS: The gain of marks for module-based teaching was statistically significant compared to conventional lecture (P < 0.001). Regarding perception, 72% of students ‘strongly agreed’ (40%) and ‘agreed’ (32%) to the different characteristics of modular teaching whereas in conventional lecture, 34% were neutral, 32% disagreed, and 12% strongly disagreed.

CONCLUSION: The knowledge outcome and perception level in module-based teaching are superior to that of conventional lectures.

PMID:41066067 | DOI:10.1007/s13312-025-00192-5

Updates Surg. 2025 Oct 9. doi: 10.1007/s13304-025-02352-5. Online ahead of print.

ABSTRACT

Anastomotic leakage (AL) is a serious complication in colorectal surgery, particularly after laparoscopic intersphincteric resection (LsISR) for ultra-low rectal cancer. This study evaluates the effectiveness of ICG fluorescence laparoscopic (FL) resection in reducing AL and improving recovery, especially in high-BMI patients. A retrospective cohort study was conducted on patients undergoing LsISR for ultra-low rectal adenocarcinoma from January 2012 to July 2023, comparing FL (n = 133) and non-FL groups (n = 266). The primary endpoint was the incidence of anastomotic leakage, including symptomatic AL. Secondary endpoints included intraoperative blood loss, lymph node yield, and short-term recovery parameters such as bowel function recovery, soft diet initiation, and hospital stay.Propensity score matching (PSM) was used to reduce baseline differences. In the PSM cohort, the FL group had a significantly lower AL rate (3.0%) compared to the non-FL group (9.4%) (P = 0.035). Severe symptomatic anastomotic leaks (SSAL) were also reduced in the FL group (0.8% vs. 5.6%, P = 0.045). Subgroup analysis showed that FL significantly reduced AL in normal BMI patients (2.4% vs. 8.5%, P = 0.041). In high-BMI patients, FL reduced AL (3.9% vs. 10.8%, P = 0.063), but the difference was not statistically significant. FL also reduced blood loss, improved lymph node yield, and accelerated recovery, including earlier return of bowel function, quicker soft diet initiation, and shorter hospital stays. ICG FL reduces AL and enhances recovery, particularly in normal BMI patients, with a potential benefit for high-BMI patients. Further studies are needed to confirm its effect in this group.

PMID:41066064 | DOI:10.1007/s13304-025-02352-5

Neurol Sci. 2025 Oct 9. doi: 10.1007/s10072-025-08554-4. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe causes, clinical manifestations, imaging features and prognosis of reversible splenial lesion syndrome (RESLES) in children.

METHODS: A total of 36 patients with RESLES hospitalized in Children’s Hospital of Chongqing Medical University between January 1, 2017 and Mar 31, 2024 were included. The clinical features including the causes, clinical manifestations and prognosis were statistically analyzed.

RESULTS: The patients’ ages ranged from 16 to 170 months with a median age of 49 months. Of the 36 patients, 24 patients were RESLES type-1 (the lesions were limited to SCC) and 12 patients were RESLES type-2(the lesions spread to other parts of the corpus callosum, extensive brain white matter, or both). The participating causes included infection, chemotherapy, immunoglobulin A vasculitis, autoimmune glial fibrillary acidic protein astrocytopathy, hypertension and hypoparathyroidism. The common neurological symptoms were seizures(n = 27), headache(n = 10), dizziness(n = 6), altered consciousness(n = 8), and psychologico-behavioral abnormalities(n = 14). Most patients had a good prognosis except 1 patient remained in a state of minimal consciousness during the follow-up.

CONCLUSION: This research demonstrates some possible causes of RESLES. Patients with RESLES present with a variety of nonspecific symptoms and most of them had a good prognosis.

SIGNIFICANCE: These findings are groundbreaking to a deeper understanding of RESLES.

PMID:41066056 | DOI:10.1007/s10072-025-08554-4