Category: Nevin Manimala

JMIR Cardio. 2025 Aug 7;9:e76850. doi: 10.2196/76850.

ABSTRACT

BACKGROUND: Apolipoprotein B (APOB) rs676210 polymorphism has been associated with altered lipid metabolism and cardiovascular risk in various populations; however, data from Vietnamese populations remain limited.

OBJECTIVE: This study aimed to investigate the association of the APOB rs676210 variant with lipid profiles among Vietnamese individuals newly diagnosed with elevated low-density lipoprotein cholesterol (LDL-C).

METHODS: A cross-sectional study was conducted among 69 Vietnamese adults newly diagnosed with elevated LDL-C (≥130 mg/dL) at a tertiary hospital in Southern Vietnam. Participants were genotyped for APOB rs676210 using real-time polymerase chain reaction (PCR) with allele-specific probes. Lipid profile components, including LDL-C, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and ApoB, were compared across genotype groups (AA vs GA/GG) and alleles (A vs G). Statistical analyses involved t tests, chi-square tests, and multivariable linear regression adjusted for age, sex, the BMI, and diabetes. P<.05 was considered statistically significant.

RESULTS: Of the 69 participants, 32 (46.4%) carried the AA genotype, while 37 (53.6%) carried the GA or the GG genotype. The AA genotype was associated with significantly higher LDL-C (mean 5.19, SD 0.95, vs mean 4.37, SD 0.97, mmol/L; P<.001), non-HDL-C (mean 5.94, SD 1.08, vs mean 5.31, SD 1.22 mmol/L; P=.03), and ApoB (mean 149.5, SD 26.3, vs mean 136.9, SD 15.2, mg/dL; P=.02) and lower HDL-C (mean 1.26, SD 0.31, vs mean 1.44, SD 0.39, mmol/L; P=.03) compared to the GA/GG genotype. Allele-based analysis showed that carriers of the A allele (98/138, 71%) also had higher LDL-C (mean 4.91, SD 1.02, vs mean 4.36, SD 0.97, mmol/L; P=.004) and ApoB (mean 145.6, SD 23.2, vs mean 135.9, SD 16.0, mg/dL; P=.02) than G allele carriers (40/138, 29%). These associations remained significant after multivariate adjustment.

CONCLUSIONS: APOB rs676210 polymorphism is associated with significant differences in lipid profiles among Vietnamese adults with elevated LDL-C. Specifically, the A allele and the AA genotype confer a more atherogenic profile, suggesting potential utility as a genetic marker in lipid screening and personalized cardiovascular risk management in this population.

PMID:40773287 | DOI:10.2196/76850

Optom Vis Sci. 2025 Aug 8. doi: 10.1097/OPX.0000000000002284. Online ahead of print.

ABSTRACT

SIGNIFICANCE: This study adds to the understanding of how different factors affect quality of life in people with keratoconus.

PURPOSE: To evaluate how various demographic factors, clinical characteristics, and treatment modalities influence quality of life in people with keratoconus.

METHODS: This prospective survey study recruited adult participants (18 years and older) with a history of keratoconus. Demographic information, clinical characteristics, visual and surgical treatment history, and responses to the National Eye Institute 25-Item Visual Functioning Questionnaire (NEI-VFQ-25) were collected.

RESULTS: Between June 2022 and June 2023, 40 participants completed the study. The mean age was 40.9 ± 15.1 years, and 70.0% were male. All participants wore contact lenses (52.5% scleral lenses, 45.0% corneal lenses, and 2.5% soft lenses), and 17.5% had a history of corneal crosslinking. Compared to scleral lens wear, corneal lens wear was associated with worse quality of life on the NEI-VFQ-25 overall composite (p=0.015), general vision (p=0.02), and mental health (p=0.052) domains. History of corneal crosslinking was associated with worse quality of life in the NEI-VFQ-25 overall composite (p=0.002), mental health (p=0.010), role difficulty (p=0.045), and dependency (p=0.021) domains. The five lowest-scoring NEI-VFQ-25 domains in this sample were general health, general vision, ocular pain, mental health, and role difficulties.

CONCLUSIONS: Factors such as the type of contact lens wear may influence an individual’s quality of life. In categories like mental health, general vision, and the overall composite score, scleral lens wearers reported better quality of life. Similarly, surgical treatment history may influence quality of life. Specifically, those with a history of corneal crosslinking reported worse quality of life scores in the categories of mental health, role difficulty, dependency, and the overall composite score. Although these factors were found to be statistically significant, not all reached clinical significance. To determine whether the relationships found in this study are repeatable across different populations, additional studies must be performed. Additionally, eye care providers must consider how different treatment options impact not only a patient’s vision and ocular health but also their quality of life.

PMID:40773279 | DOI:10.1097/OPX.0000000000002284

Int J Surg. 2025 Aug 7. doi: 10.1097/JS9.0000000000003175. Online ahead of print.

NO ABSTRACT

PMID:40773259 | DOI:10.1097/JS9.0000000000003175

Proc Natl Acad Sci U S A. 2025 Aug 12;122(32):e2501435122. doi: 10.1073/pnas.2501435122. Epub 2025 Aug 7.

ABSTRACT

A quantitative understanding of local transmission dynamics is essential for designing effective prevention strategies. In this study, we developed a computational workflow to identify viral introductions and trace locally circulating clusters. We analyzed over 26,000 SARS-CoV-2 genomes and their associated metadata, collected between January and October 2021, to explore introduction and local dispersal patterns in Greater Houston, a major metropolitan area known for its demographic diversity. Our analysis identified more than 1,000 independent introduction events, resulting in clusters of varying sizes. The majority of introductions originated from domestic sources, while international introductions occurred earlier and were associated with larger cluster sizes. An analysis of locally circulating clusters revealed age-structured transmission dynamics. Geographic reconstruction of cluster spread identified Harris County as the primary viral source for surrounding areas. The outbreak in the source population was characterized by 1) a smaller proportion of new cases associated with external viral imports and 2) longer persistence times of circulating lineages. Overall, our high-resolution spatiotemporal reconstruction of the epidemic provides essential insights into the local-scale transmission landscape, supporting outbreak-specific, regional response strategies and public health planning.

PMID:40773234 | DOI:10.1073/pnas.2501435122

JAMA Otolaryngol Head Neck Surg. 2025 Aug 7. doi: 10.1001/jamaoto.2025.2049. Online ahead of print.

ABSTRACT

IMPORTANCE: Thyroid cancer incidence has tripled in the past 3 decades, largely driven by increased detection of small, indolent papillary thyroid cancers. Overuse of thyroid ultrasonography (TUS) contributes to overdiagnosis, leading to unnecessary biopsies, procedures, and potential patient harm.

OBJECTIVE: To evaluate the frequency of and factors associated with inappropriate TUS (iTUS) orders and assess related clinical outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed adult patients 18 years and older who underwent their first TUS from January 1, 2017, to December 30, 2021, at 4 Mayo Clinic sites. Patients with previous thyroid nodule, thyroid cancer, thyroid surgery, or TUS were excluded. Based on documented clinical indications, a validated natural language processing model classified TUS orders as appropriate or inappropriate. Data were analyzed from April 2024 to May 2025.

EXPOSURES: Baseline characteristics of patients, clinicians, and clinical encounters investigated for their association with an iTUS order.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of iTUS orders. Secondary outcomes included factors associated with iTUS (sociodemographic, clinical, order-specific, and clinician-related factors) and clinical outcomes following iTUS, including the detection of thyroid nodules, thyroid procedures, and thyroid cancer diagnoses.

RESULTS: Of 11 442 included patients, 8422 (73.6%) were female, and the mean (SD) age was 57.3 (15.8) years with a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 29.7 (7.0). Among 11 442 TUS orders, 866 (7.6%) were classified as inappropriate. In multivariable analysis, younger age (age of 18 to 54 years vs older than 65 years; odds ratio [OR], 1.86; 95% CI, 1.56-2.22), hyperthyroidism (OR, 9.04; 95% CI, 6.75-12.11), ordering by nonendocrinology specialties (eg, oncology/hematology; OR, 3.43; 95% CI, 2.47-4.76), and orders not linked to an in-person appointment (eg, portal messages; OR, 2.42; 95% CI, 2.08-2.82) were strongly associated with increased odds of iTUS. Compared with appropriate TUS, iTUS led to lower rates of thyroid nodule detection (202 of 866 [23.3%] vs 6885 of 10 576 [65.1%]; OR, 0.16; 95% CI, 0.14-0.19), biopsies (89 [10.3%] vs 2647 [25.0%]; OR, 0.34; 95% CI, 0.27-0.43), partial thyroidectomies (14 [1.6%] vs 424 [4.0%]; OR, 0.39; 95% CI, 0.23-0.67), and confirmed thyroid cancer cases (16 [1.8%] vs 425 [4.0%]; OR, 0.45; 95% CI, 0.27-0.74).

CONCLUSIONS AND RELEVANCE: In this cohort study, approximately 1 in 13 TUS orders were inappropriate. iTUS was more common in younger patients, those with thyroid dysfunction, those not seen in person, and in those referred by nonendocrinology specialties. These findings highlight the need for targeted strategies to optimize TUS use and mitigate overdiagnosis and overtreatment.

PMID:40773204 | DOI:10.1001/jamaoto.2025.2049

JAMA Netw Open. 2025 Aug 1;8(8):e2525789. doi: 10.1001/jamanetworkopen.2025.25789.

ABSTRACT

IMPORTANCE: Most children and adolescents with kidney and ureteral stones are treated with ureteroscopy, despite the uncertainty and equal weight of guideline recommendations for ureteroscopy or shockwave lithotripsy.

OBJECTIVE: To compare stone clearance and patient-reported outcomes among children and adolescents after ureteroscopy or shockwave lithotripsy.

DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized clinical trial enrolled patients between March 16, 2020, and July 31, 2023, at 31 medical centers in the US and Canada. Patients aged 8 to 21 years with kidney stones, ureteral stones, or both were included. Follow-up was completed on October 15, 2023.

INTERVENTIONS: Ureteroscopy or shockwave lithotripsy.

MAIN OUTCOMES AND MEASURES: The primary outcome was stone clearance assessed by standardized ultrasonography 6 (±2) weeks after surgery. Using inverse probability weighting and random intercepts for site, stone clearance was evaluated per kidney or ureter using logistic regression and estimated stone clearance rates were generated for each procedure.

RESULTS: This study included 1142 patients (690 females [60.4%]), with a median age of 15.6 years (IQR, 12.6-17.3 years). In terms of race and ethnicity, 41 patients (3.6%) were Black, 130 (11.4%) were Hispanic, and 884 (77.4%) were White. A total of 124 urologists treated 1069 and 197 kidneys or ureters with ureteroscopy and shockwave lithotripsy (n = 953 and n = 189 patients), respectively, with a median stone size of 6.0 mm (IQR, 4.0-9.0 mm). Ureteral stents were placed at time of index surgery for 841 procedures for 767 patients (80.4%) receiving ureteroscopy and for 6 procedures for 5 patients (2.6%) receiving shockwave lithotripsy. Stone clearance occurred in 474 patients who underwent ureteroscopy (71.2% [95% CI, 63.8%-78.5%]) and in 105 patients who underwent shockwave lithotripsy (67.5% [95% CI, 61.0%-74.1%]), a difference that was not statistically significant (risk difference, 3.6% [95% CI, -6.2% to 13.5%]). Compared with shockwave lithotripsy, ureteroscopy resulted in greater pain interference (T-score difference, 5.0 [95% CI, 2.3-7.8]) and urinary symptoms (symptom score difference, 3.9 [95% CI, 1.2-6.7]) 1 week after surgery. Patients who had ureteroscopy missed more school (risk difference, 21.3% [95% CI, 9.7%-32.8%]) and caregivers missed more work (risk difference, 23.0% [95% CI, 11.0%-35.0%]) in the week after surgery.

CONCLUSIONS AND RELEVANCE: In this study of 1142 children and adolescents with kidney and ureteral stones, there was no clinically meaningful difference in stone clearance with ureteroscopy vs shockwave lithotripsy. Shockwave lithotripsy was associated with better patient-reported outcomes. These findings raise questions about the preference for ureteroscopy in practice.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04285658.

PMID:40773197 | DOI:10.1001/jamanetworkopen.2025.25789

JAMA Netw Open. 2025 Aug 1;8(8):e2525801. doi: 10.1001/jamanetworkopen.2025.25801.

ABSTRACT

IMPORTANCE: Left bundle branch block (LBBB) might play a causative role in the progression to heart failure (HF), but the association of LBBB with HF in asymptomatic individuals with structurally normal hearts has not yet been investigated.

OBJECTIVES: To examine the association of LBBB with the risk of HF in community-dwelling individuals.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study used data from 4 US sites participating in the Cardiovascular Health Study (1989-1990), collected from 1989 to 2013. Adults aged 65 years and older with a normal left ventricular ejection fraction (LVEF) and no history of HF at baseline were included. Data were analyzed from February 2018 to October 2024.

EXPOSURE: The presence of LBBB as confirmed by 12-lead electrocardiograms obtained on all participants at baseline.

MAIN OUTCOMES AND MEASURES: Multivariable Cox proportional hazards models were used to estimate the associations of LBBB with the risk of incident HF, hospital admission for HF with reduced EF or HF with preserved EF, 5-year LVEF decline, and death.

RESULTS: Among 4541 individuals (mean [SD] age, 72.6 [5.5] years; 2697 female [59.4%]), 44 (1.0%) exhibited LBBB at baseline, and 1321 (29.1%) received a diagnosis of HF over a median (IQR) follow-up of 14.6 (8.4-18.3) years. In the adjusted model, those with baseline LBBB had an increased risk of incident HF (hazard ratio, 4.98; 95% CI, 2.18-11.39; P < .001) and greater odds of 5-year LVEF decline (odds ratio, 4.73; 95% CI, 1.70-13.70; P = .003), but no statistically significant increased risk of death was observed (hazard ratio, 1.39; 95% CI, 0.99-1.94; P = .05).

CONCLUSIONS AND RELEVANCE: In this cohort study of individuals with structurally normal hearts, LBBB was associated with an increased risk of HF and a decrease in LVEF, suggesting that LBBB could be a potential target for early interventions to prevent deterioration of cardiac function and, ultimately, progression to HF.

PMID:40773196 | DOI:10.1001/jamanetworkopen.2025.25801

JAMA Netw Open. 2025 Aug 1;8(8):e2526067. doi: 10.1001/jamanetworkopen.2025.26067.

ABSTRACT

IMPORTANCE: Donation physicians (DPs) are usually critical care specialists whose responsibilities may include assessment of donation eligibility, care of potential donors, death determination, education, and advocacy. While DP programs have been implemented in some countries with the aim of optimizing the organ donation process, there are few studies evaluating their effectiveness.

OBJECTIVE: To assess the association of a DP program with key performance metrics.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used interrupted time series analysis to compare baseline data from intensive care units and emergency departments in a Canadian province (December 2019 to February 2020 and March 2021 to May 2021) with data following the initial 3 years of a DP program (July 2021 to June 2024). Donation data included consecutive deceased critically ill patients with various forms of brain injury who received mechanical ventilation in the last 12 hours of life.

EXPOSURE: Implementation of a province-wide DP program coupled with regular audit and feedback aimed at identifying and minimizing missed donation opportunities.

MAIN OUTCOMES AND MEASURES: Missed organ donation opportunities, defined as occurring when families of eligible potential donors were not given the option of donation. Secondary outcomes included appropriate notification of the provincial donation organization, donors per million population, and median number of organs transplanted per donor.

RESULTS: Over 42 months, there were 1072 eligible potential donors, including 635 (59%) following death by neurologic criteria and 437 (41%) following death by circulatory criteria. The median (IQR) age was 44.6 (30.8-58.3) years, 662 (62%) were male, and the most common cause of death was hypoxic-ischemic brain injury. During the initial 36 months of the DP program, 129 of 942 (14%) eligible potential donors were missed, compared with 43 of 123 (33%) during 6 months of baseline data (P < .001). The monthly proportion of missed cases decreased by 10.9% (95% CI, -22.0% to 0.3%; P = .06) immediately following the start of the program and then declined -0.7% (95% CI, -0.9% to -0.5%; P < .001) per month. Appropriate notification of the provincial organ donation organization increased 0.9% (95% CI, 0.6% to 1.3%, P < .001) per month. The annual donation rate increased from 14.0 to 23.7 donors per million. The median (IQR) number of organs transplanted per donor did not change (4 [3-5]; P = .69). Missed opportunities occurred in 3% of eligible potential donors when the most responsible physician was a DP and 17% when it was not (P < .001).

CONCLUSIONS: In this cohort study of consecutive eligible potential organ donors, implementation of a novel DP program was associated with a sustained reduction in missed organ donation opportunities, increased referrals, and a higher deceased donation rate.

PMID:40773195 | DOI:10.1001/jamanetworkopen.2025.26067

JAMA Netw Open. 2025 Aug 1;8(8):e2526077. doi: 10.1001/jamanetworkopen.2025.26077.

ABSTRACT

IMPORTANCE: The emergence of fentanyl and other high-potency synthetic opioids (HPSOs) has not only been underlying overdose deaths, but has complicated initiation of methadone and buprenorphine for opioid use disorder (OUD) treatment, including in the hospital. In response, clinicians with addiction expertise have developed novel initiation practices, yet no studies have characterized initiation practices nationally.

OBJECTIVE: To assess the use of novel hospital-based practices for initiating methadone and buprenorphine.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study of directors of hospital-based addiction consult services (ACS) associated with addiction medicine and addiction psychiatry fellowships in hospitals in the US was conducted using a REDcap anonymous survey from October 2023 to April 2024.

EXPOSURE: Predefined methadone and buprenorphine initiation practices. Standard methadone initiation was defined as 40 mg oral maximum on day 1 with up-titration of 5 to 10 mg every 3 days. Rapid methadone initiation was defined as any initiation regimen more rapid than standard. Buprenorphine initiation practices included low dose, high dose, traditional, and rescue.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of ACS directors using predefined methadone and buprenorphine initiation practices. Perceived impact of the drug supply on methadone and buprenorphine initiation was assessed through a 5-point Likert scale ranging from strongly disagree to strongly agree. Typical selection of buprenorphine initiation practices was assessed using 7 case-based scenarios intended to represent common hospital scenarios.

RESULTS: Among 80 consult services, 58 directors (72.5%; median [IQR] age, 41 [38-50] years; 27 of 57 [47.3%] women) completed surveys, one of which was partially completed. Of 57 ACS directors, specialties included addiction medicine (41 respondents [71.9%]), addiction psychiatry (11 respondents [19.3%]), general or consult liaison psychiatry (11 respondents [19.3%]), and toxicology (2 respondents [3.5%]). Among those who reported initiating methadone (47 of 58 respondents [81.0%]), 33 (70.2%) agreed that HPSOs changed their methadone initiation practices. Of 46 respondents, 40 (87.0%) reported rapid initiation of methadone, and of those, 26 (65.0%) reported using rapid initiation for more than 50% of initiations. Full-agonist opioids were used by 31 of 46 ACS directors (67.4%) to treat withdrawal during methadone initiation. Of 58 respondents, 54 (93.1%) agreed that HPSOs changed their buprenorphine initiation practices. All 58 ACS directors reported that their initiation practices offered buprenorphine initiation, including 53 of 57 (92.9%) offering low dose, 50 of 57 (87.7%) offering traditional, 43 of 57 (75.4%) offering high dose , and 20 of 57 (35.1%) offering rescue. For 7 clinical cases provided, low-dose initiation was the most commonly endorsed method of buprenorphine initiation, except in the case of a person presenting in significant withdrawal 2 days after last fentanyl use.

CONCLUSIONS AND RELEVANCE: The findings of this survey study of hospital-based academic ACS directors suggest that methadone and buprenorphine initiation has adapted to a shifting opioid supply, often outpacing research and changes in clinical guidelines.

PMID:40773194 | DOI:10.1001/jamanetworkopen.2025.26077

JAMA Netw Open. 2025 Aug 1;8(8):e2526089. doi: 10.1001/jamanetworkopen.2025.26089.

ABSTRACT

IMPORTANCE: Hippocampal sclerosis (HS), defined as severe neuronal loss and astrogliosis in coronal sections of the midhippocampus cornu ammonis 1 or subiculum, is an important pathology associated with limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy neuropathological change (LATE-NC), Alzheimer disease, and dementia. The association of diet with HS or HS with LATE-NC in humans remains underexplored.

OBJECTIVE: To investigate the association of the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet with HS and HS with LATE-NC.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included autopsied participants from the ongoing Rush Memory and Aging Project cohort study. Participants with dietary and neuropathological data from 2004 to 2024 were included. Data were analyzed from April 3, 2024, to May, 13, 2025.

EXPOSURES: Mean MIND diet scores (range, 0-15; higher score indicates better diet), computed from all validated food frequency questionnaires administered annually for up to 18 years before death.

MAIN OUTCOMES AND MEASURES: The outcomes of interest were presence of HS, assessed using hematoxylin and eosin staining, and presence of LATE-NC, detected by TDP-43 immunohistochemistry in 8 brain regions. For a subset of 300 participants, hippocampal neuronal loss severity was scored using a semiquantitative scale from 0, indicating none, to 5, severe, and categorized as none to mild, moderate, and severe neuronal loss.

RESULTS: Among 809 participants (mean [SD] age at death, 91.3 [6.1] years; 538 [72%] female; mean [SD] follow-up, 7.2 [4.4] years), HS was present in 82 (10.1%) participants; 71 participants (9%) had both HS and LATE-NC, and in the scored subset, 43 participants (14%) had moderate and 35 participants (12%) had severe hippocampal neuronal loss. Higher MIND diet scores were associated with lower odds of HS (odds ratio [OR], 0.78; 95% CI, 0.65 to 0.95) and HS with LATE-NC (OR, 0.79; 95% CI, 0.64 to 0.97) after controlling for age at death, sex, education, total calories, APOE-ε4 status, AD, and vascular pathologies. In mediation analyses, the MIND diet was associated with less dementia at the time of death (β = -0.26; 95% CI, -0.36 to -0.15; P < .001), with an indirect association of 21% through HS (β = -0.05; 95% CI, -0.10 to -0.01; P = .02). A higher MIND diet score was associated with less hippocampal neuronal loss (P for trend = .01).

CONCLUSIONS AND RELEVANCE: This cohort study of autopsied participants found that MIND diet adherence during follow-up was associated with a lower likelihood of HS, HS with LATE-NC, and hippocampal neuronal loss. The association of diet with dementia was partially mediated by its association with HS. These findings suggest that the MIND diet may reduce adverse brain health outcomes.

PMID:40773193 | DOI:10.1001/jamanetworkopen.2025.26089