Tag: nevin manimala

JAMA Netw Open. 2025 Mar 3;8(3):e251540. doi: 10.1001/jamanetworkopen.2025.1540.

ABSTRACT

IMPORTANCE: Detecting and addressing potentially modifiable factors associated with healthy development is key to optimizing a child’s potential. When investigating the outcomes of child development, it is important to account for disparities in feeding practices and avoid confounding bias.

OBJECTIVES: To estimate the independent association between breastfeeding and attainment of developmental milestones or neurodevelopmental conditions.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from a national network for routine child development surveillance in Israel linked with national social insurance financial entitlements for neurodevelopmental deficiencies. Participants were children born between January 2014 and December 2020 after at least 35 weeks’ gestation without severe morbidity and with at least 1 follow-up surveillance visit at 2 to 3 years of age. Outcome data were collected in March 2023.

EXPOSURES: Duration and exclusivity of breastfeeding in infancy.

MAIN OUTCOMES AND MEASURES: The primary outcomes were delays in attainment of developmental milestones and diagnosis of prespecified neurodevelopmental conditions. Multivariable regression, matching, and within-family analyses were used to estimate adjusted odds ratios (AORs) after accounting for potential confounding factors related to the child (gestational age, birth weight, multiple gestation, and child order in the family) and mother (age, socioeconomic status, educational level, marital status, employment, nationality, and postpartum depression).

RESULTS: Of 570 532 children (291 953 [51.2%] male), 20 642 (3.6%) were preterm, 38 499 (6.7%) were small for gestational age, and 297 571 (52.1%) were breastfed for at least 6 months (123 984 [41.7%] were exclusively breastfed). Children who were breastfed for at least 6 months exhibited fewer delays in attaining language and social or motor developmental milestones compared with children exposed to less than 6 months of breastfeeding (AOR, 0.73 [95% CI, 0.71-0.76] for exclusive breastfeeding; AOR, 0.86 [95% CI, 0.83-0.88] for nonexclusive breastfeeding). Among 37 704 sibling pairs, children who were breastfed for at least 6 months were less likely to demonstrate milestone attainment delays (OR, 0.91 [95% CI, 0.86-0.97]) or be diagnosed with neurodevelopmental conditions (OR, 0.73 [95% CI, 0.66-0.82]) compared with their sibling with less than 6 months of breastfeeding or no breastfeeding.

CONCLUSIONS AND RELEVANCE: In this cohort study, exclusive or longer duration of breastfeeding was associated with reduced odds of developmental delays and language or social neurodevelopmental conditions. These findings may guide parents, caregivers, and public health initiatives in promoting early child development.

PMID:40126480 | DOI:10.1001/jamanetworkopen.2025.1540

JAMA Netw Open. 2025 Mar 3;8(3):e251665. doi: 10.1001/jamanetworkopen.2025.1665.

ABSTRACT

IMPORTANCE: Kidney transplantation offers survival benefits and superior quality of life compared with maintenance dialysis for patients with end-stage kidney disease (ESKD), but it is limited to approximately 25 000 patients annually in the United States. Expanding access to transplant could be accomplished by allowing more patients to join the waiting list or by increasing organ supply.

OBJECTIVE: To estimate how these interventions could affect transplant wait times.

DESIGN, SETTING, AND PARTICIPANTS: This decision-analytic study used a Markov model with a simulated cohort of transplant-eligible US patients over 10 years (2022-2032).

EXPOSURES: Three expansion strategies: waiting list expansion alone, waiting list expansion with deceased-donor transplant (DDT) expansion, and waiting list expansion with living-donor transplant (LDT) expansion. Relative 10%, 25%, 50%, and 100% expansions of the current deceased-donor organ supply and 25%, 50%, 100%, and 200% expansions of current living donation rates were simulated, modeling 2 degrees of waiting list expansion (10% and 50%) for each strategy.

MAIN OUTCOMES AND MEASURES: Median wait time to kidney transplant using Kaplan-Meier survival analysis.

RESULTS: There were a total of 662 190 transplant-eligible patients in the simulated cohort, with a mean (SD) age of 58.7 (14.7) years; 327 126 (49%) female individuals; and 269 082 (41%) Black, 163 028 (25%) Hispanic, 233 739 (35%) non-Hispanic White, and 78 496 (12%) Asian individuals and individuals with another race or ethnicity. Under the baseline strategy, median (IQR) wait time was 32.8 (13.1-66.4) months and increased to 36.8 (14.7-74.7) months and 52.6 (21.0-107.9) months for 10% and 50% waiting list expansion alone. DDT and LDT expansion strategies added 1911 to 20 035 organs. For 10% waiting list expansion, median (IQR) wait times ranged from 23.7 (9.3-47.8) months to 34.5 (13.9-74.7) months. For 50% waiting list expansion, median (IQR) wait times ranged from 34.2 (13.6-69.4) months to 49.4 (19.7-101.0) months.

CONCLUSIONS AND RELEVANCE: In this decision-analytic model, expansion strategies without additional organ supply increased the median time to kidney transplant by nearly 2 years; 10% waiting list expansion required at least 2850 additional organs to shorten wait times. However, 50% waiting list expansion required at least 11 000 additional organs to approximate current wait times. Reduction in the deceased-donor organ nonuse rate alone is unlikely to meet the shortfall. Systems-level efforts to significantly increase deceased and living donation should be prioritized alongside increased access to the transplant waiting list.

PMID:40126479 | DOI:10.1001/jamanetworkopen.2025.1665

JAMA Netw Open. 2025 Mar 3;8(3):e251689. doi: 10.1001/jamanetworkopen.2025.1689.

ABSTRACT

IMPORTANCE: Dapagliflozin reduces the urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) decline at a population level, but individuals show a large variation in responses. The n-of-1 trial design allows for direct assessment of treatment effects within an individual, and digital technologies and remote study assessments can reduce clinic visits, ease participant burden, and improve trial efficiency.

OBJECTIVE: To assess individual UACR responses to dapagliflozin treatment in a decentralized clinical trial and the feasibility of remote data collection.

DESIGN, SETTING, AND PARTICIPANTS: This decentralized, randomized, double-blind, placebo-controlled crossover trial using an n-of-1 approach was conducted using data from the Dutch primary and secondary health care systems between May 2021 and September 2022. Participants included adults with type 2 diabetes, a UACR greater than 20 mg/g, and an eGFR greater than 30 mL/min/1.73 m2. Statistical analyses were performed between June and August 2023.

INTERVENTIONS: Participants were assigned to two 1-week treatment periods with dapagliflozin, 10 mg/d, and two 1-week treatment periods with placebo in random order, with 1-week washout periods in between.

MAIN OUTCOMES AND MEASURES: The primary outcome was the difference in the change in UACR from start to end of treatment between dapagliflozin and placebo in the per-protocol population. A post hoc exploratory analysis assessed the feasibility of remote data collection, including the proportion of urine and capillary blood samples successfully delivered to the central laboratory.

RESULTS: In total, 20 participants (mean [SD] age, 64.9 [8.7] years; 17 [85.0%] male) with a mean (SD) eGFR of 70.2 (20.3) mL/min/1.73 m2 and a median UACR of 94.7 (IQR, 29.8-242.6) mg/g were included in the study. They experienced a relative change in UACR with dapagliflozin compared with placebo of -15.1% (95% CI, -28.2% to -3.3%; P = .01). UACR changes showed considerable variation during both dapagliflozin and placebo treatment (first treatment period: median, -12.8% [range, -56.3% to 36.2%] and 2.9% [range, -86.7% to 35.1%], respectively). UACR changes correlated significantly between the first and second dapagliflozin exposure (r = 0.50; P = .03), with no correlation observed between the placebo exposure periods (r = 0.09; P = .69). With regard to remote data collection, 811 of 816 urine samples (99.4%) and 433 of 440 capillary blood samples (98.4%) were successfully delivered to the central laboratory.

CONCLUSIONS AND RELEVANCE: In this crossover trial, individual UACR responses to dapagliflozin reflected a pharmacological response. Remote data collection proved to be reliable, supporting its use in future studies and clinical practice for monitoring individual dapagliflozin responses.

TRIAL REGISTRATION: EudraCT identifier: 2020-004929-23.

PMID:40126478 | DOI:10.1001/jamanetworkopen.2025.1689

Postgrad Med J. 2025 Mar 24:qgaf037. doi: 10.1093/postmj/qgaf037. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has significantly impacted global health, making it essential to understand its genetic effects on various traits.

METHOD: Leveraging the extensive FinnGen dataset comprising 500 000 individuals, we performed a Mendelian randomization (MR) phenome-wide association study. COVID-19-related phenotypes obtained from the COVID-19 Host Genetics Initiative GWAS (release 7). We employed four distinct approaches, including MR-Egger, weighted median, random-effect inverse variance weighted (IVW), and weighted mode, to conduct the MR analysis.

RESULTS: Two hundred fifty-five potential causal effects of COVID-19 were observed for a diverse range of outcomes using the IVW method, including cardiovascular disorders, respiratory conditions, autoimmune diseases, and metabolic disorders. Apart from a few that can be classified as “other traits,” the majority of the traits are disease-related traits. We have also identified 31 traits, wherein all four distinct MR analyses yielded a P-value of less than 0.05. Only one trait remained statistically significant after multiple testing correction using the conservative Bonferroni threshold (P < 2.2E-5).

CONCLUSIONS: This phenome-wide MR study provides valuable insights into the genetically predicted effects of COVID-19 on a comprehensive range of traits. The identified associations contribute to our understanding of the complex interplay between the impact of the post-COVID-19 era on healthcare and may have implications for the development of targeted therapeutic strategies and public health interventions. Key messages What is already known on this topic – COVID-19 has a high mortality rate, and patients often have many sequelae, including myocarditis, acute respiratory distress syndrome, and neurological and hematologic complications. What this study adds Most of the current relevant studies lack large-scale phenotype-group ranging Mendelian randomization (MR) studies on the outcome of COVID-19 due to their small sample sizes. Therefore, this study performed a full phenotypic group MR analysis in the FinnGen dataset to investigate the relationship between COVID-19 and thousands of outcome variables. How this study might affect research, practice or policy- The study identified a set of traits that are strongly associated with genetic susceptibility to the long-term effects of COVID-19.

PMID:40126442 | DOI:10.1093/postmj/qgaf037

Hepatol Commun. 2025 Mar 21;9(4):e0648. doi: 10.1097/HC9.0000000000000648. eCollection 2025 Apr 1.

ABSTRACT

BACKGROUND: To identify clinical characteristics and serological biomarkers that predicted subsequent nosocomial infection in ATTIRE trial patients.

METHODS: We identified 360 patients at hospitalization without infection and not prescribed antibiotics and compared clinical characteristics between those who subsequently developed a nosocomial infection and not. In a 68-patient subcohort, we compared plasma biomarkers of bacterial translocation, infection, and inflammation at hospitalization between those who developed a nosocomial infection and not. In a 56-patient subcohort, we investigated plasma lipidomic profiles in those who did and did not develop nosocomial infection using Lipotype Shotgun platform analysis and multivariate statistical techniques. To further investigate lipid pathways, we compared outcomes in patients taking statins or not at hospitalization.

RESULTS: Serum bilirubin >188 µmol/L at hospitalization predicted subsequent nosocomial infection in univariate and multivariate analyses, with 80% specificity. The most common nosocomial infections were respiratory tract (29%) and those developing infection had significantly greater 28 and 90-day mortality than those not (p=9.34E-05 and 0.014). Serological biomarkers of bacterial translocation, infection, and inflammation did not predict subsequent infection. Partial least squares discriminatory analyses identified cholesterol esters (CEs) (CE.18.1.2, CE.18.1.0, and CE.16.0.0) as important predictors of infection but provided only a small improvement in predictive ability over bilirubin alone. RNA-sequencing analyses suggest this is mediated by a downregulation of the cellular cholesterol esterification enzyme sterol O-acyltransferase 1. Statin use was not associated with nosocomial infection prevention.

CONCLUSIONS: In ATTIRE, elevated serum bilirubin at hospitalization was the only clinical characteristic that predicted subsequent development of nosocomial infection. Considering the rising incidence of antimicrobial resistance, these data could be used to limit antibiotic prophylaxis or aid trial design for investigating use in high-risk patients.

PMID:40126412 | DOI:10.1097/HC9.0000000000000648

J Med Econ. 2025 Mar 24:1-15. doi: 10.1080/13696998.2025.2484073. Online ahead of print.

ABSTRACT

INTRODUCTION: Hepatocellular carcinoma (HCC), which accounts for about 90% of all primary liver cancer cases, is the fifth most common malignancy and the second leading cause of cancer-related mortality worldwide. This study aims to analyse the differential costs of HCC-related hospital admissions compared to the general population in Spain.

METHODS: A retrospective multicenter study analyzed inpatient admissions from a Spanish national discharge database, covering 90% of hospitals between 2010 and 2022. HCC-related admissions were identified using ICD-9 and ICD-10 codes, while control admissions were selected from the general population in the same database without an HCC diagnosis. The direct hospitalization cost was included, covering medical examinations, procedures, medications, surgeries, personnel and equipment. Statistical methods, including nearest-neighbor matching, propensity score matching, and a generalized linear model, were used to estimate differential costs and to ensure comparability based on age, gender, and Charlson Comorbidity Index (CCI).

RESULTS: A total of 199,670 HCC-related hospital admissions and 200,000 control admissions were analyzed. Most HCC-related admissions involved male patients (78%) aged 66-85 years, with an average CCI of 5.18. HCC-related admissions incurred significantly higher costs, with an estimated differential cost of €1,303.68 using GLM, €1,804.25 via propensity score matching, and €1,767.77 using nearest-neighbor matching. Total costs per HCC admission ranged between €1,000 and €31,000.

CONCLUSIONS: HCC-related hospital admissions impose a significantly higher economic burden due to the complexity of care. Given the high mortality and resource utilization, advancements in early detection, treatment, and cost-effective interventions are needed to improve patient outcomes and reduce healthcare costs.

PMID:40126406 | DOI:10.1080/13696998.2025.2484073

J Minim Access Surg. 2025 Mar 24. doi: 10.4103/jmas.jmas_271_24. Online ahead of print.

ABSTRACT

BACKGROUND: Due to the lack of a validated instrument to measure fatphobia, its epidemiology in India remains unknown. This study aimed to culturally adapt and validate the Fat Phobia Scale-Short Form (FPS-SF) in Hindi.

PATIENTS AND METHODS: A cross-sectional study using a purposive sampling technique was conducted in the metabolic surgery clinic of a tertiary care teaching institution. We followed the World Health Organization’s procedure for cultural adaptation and validation of an instrument. The study was biphasic. The phase-1 entailed forward translation, formation of an expert panel, backward translation and cognitive interviewing with the two groups of seven individuals, each with severe obesity. During phase-2, 175 participants (students [n = 120], patients [n = 55]) were recruited after written informed consent. Hindi-FPS-SF was administered to students twice, 1 week apart. All participants completed Hindi-FPS-SF, Modified Weight Bias Internalization Scale (Hindi-WBIS-M), Patient Health Questionnaire (Hindi-PHQ-9) and Generalised Anxiety Disorder Questionnaire (Hindi-GAD-7). Statistical analysis was done.

RESULTS: Several items of forward-translated Hindi-FPS-SF underwent culture-specific modifications in Phase-1. Content or curricular validity and face validity were assessed. In Phase-2, the reliability and validity of Hindi-FPS-SF were evaluated. The internal consistency (Cronbach’s alpha), intra-class correlation type-A coefficient (ICC) and cross-cultural reliability were α =0.902 (P < 0.001), 0.799 (95% CI = 0.753-0.840) (P < 0.001) and (ICC: 0.865-0.992) (P < 0.001), respectively. The convergent-construct validity assessed by correlations between total scores of Hindi-WBIS-M and Hindi-FPS-SF was significant. Criterion validity measured through correlations with original FPS-SF, Hindi-WBIS-M, PHQ-9 and GAD-7 was significant.

CONCLUSIONS: The Hindi-FPS-SF demonstrated good psychometric properties and may be used to measure fat phobia and its correlates in India for epidemiological purposes.

PMID:40126402 | DOI:10.4103/jmas.jmas_271_24

Prehosp Emerg Care. 2025 Mar 24:1-10. doi: 10.1080/10903127.2025.2476196. Online ahead of print.

ABSTRACT

OBJECTIVES: Neonates, infants 30 days of age or younger, are understudied in prehospital emergencies. Our objective was to describe prehospital assessment and care for patients <30 days of age at the San Diego-Tijuana Point of Entry (POE). Additional objectives included describing assessments, care, frequency, and level of care for newborns brought to the border by Mexican ambulances.

METHODS: This was a retrospective analysis from January 1, 2014 to January 01, 2020 of all 9-1-1 calls involving patients <30 days of age at the San Diego POEs. The 9-1-1 responses to newly delivered patients were “newborns”. Patients who were not immediately post-delivery were “neonates.” Patient demographics, response intervals, clinician interventions, and dispositional data were collected from electronic patient records. Descriptive statistics applied.

RESULTS: A total of 57 patients <30 days of age were included. With 27 newborn patients, 15 were delivered by EMS personnel (27, 55.6%). Initial APGARs scores were 8-10 in 44.4% and 5-7 in 29.6%. Procedures include newborn care (88.9%), advanced life support (ALS) assessment (63.0%), and warming (59.3%). There were 5 patients that had stimulation, 7 received oxygen, and 3 received Bag-Valve-Mask (BVM) ventilation. No serial heart rates were documented. Regarding 30 neonates, the predominant method of transport to the POE was Mexican ambulance (n 16, 53.3%). Medications administered included oxygen (n 16, 53.3%) and albuterol/ipratropium (n 1, 3.3%). Procedures included ALS assessment (n 19, 63.3%), pulse oximetry (n 22, 73.3%) and 3-lead electrocardiogram (n 8, 26.7%). Three patients (10%) received BVM. Mexican Ambulances brought 16 neonates. A physician or nurse was present in 37.5% transfers, 50% incubated, 25% intubated, 37.5% on supplemental oxygen, and 71% had preexisting intravenous access. These were not interfacility transfers but were 9-1-1 activations by U.S. border agents; And 14 neonates did not arrive via Mexican ambulance. Their complaints were respiratory distress (n 7, 50%) and Brief Resolved Unexplained Episode (n 4, 28.6%).

CONCLUSIONS: We found that 9-1-1 transports at the San Diego-Tijuana POE for patients <30 days were few and involved resuscitation, neonates in Mexican ambulances with specialized equipment, physicians, and unfamiliar medications. Neonates arriving via private transport had respiratory distress and BRUE.

PMID:40126385 | DOI:10.1080/10903127.2025.2476196

Clin Pediatr (Phila). 2025 Mar 24:99228251321597. doi: 10.1177/00099228251321597. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the relationship between the type 2 inflammatory response associated with asthma and lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV).

METHODS: Sixty-seven children with RSV infection hospitalized in our hospital from October 2023 to December 2023 and 27 healthy children undergoing medical examination were included. The study population was divided into the RSV LRTI group (n = 67) and the control group (n = 27). Interleukin-13 (IL-13), serum total immunoglobulin E (IgE), mucin 5AC (MUC5AC), and blood eosinophil count (EOS) were tested and compared between the two groups. The presence or absence of specificity between the two groups was analyzed using the rank sum test and subject operating characteristic curves (Receiver Operating Characteristic curves, ROC curves).

RESULTS: The levels of IL-13, IgE, MUC5AC, and EOS were higher in children with RSV LRTI compared to healthy children. These differences were statistically significant (P < .05). The ROC curve analysis results showed that IL-13, IgE, MUC5AC, and EOS predicted type 2 inflammation with areas under the curve of 0.687, 0.762, 0.764, and 0.646, respectively.

CONCLUSION: A type 2 inflammatory response associated with asthma may be observed after RSV-induced LRTIs.

PMID:40126358 | DOI:10.1177/00099228251321597

Noncoding RNA. 2025 Mar 17;11(2):26. doi: 10.3390/ncrna11020026.

ABSTRACT

Colorectal cancer (CRC) is the third most diagnosed cancer and a leading cause of cancer-related mortality in Morocco, often detected at late stages. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for CRC detection, with miR-21, miR-29a, and miR-92a showing significant diagnostic potential. This study aimed to evaluate the expression levels of these miRNAs in a Moroccan population and their efficacy as diagnostic biomarkers.

METHODS: A prospective study was conducted using blood samples from 50 CRC patients and 50 healthy controls. Circulating miRNA expression levels were quantified through reverse transcription quantitative PCR (RT-qPCR), with normalization to miR-1228-3p. Statistical analyses, including the Mann-Whitney U test, Receiver Operating Characteristic (ROC) curve analysis, sensitivity (Sen), and specificity (Spe) evaluations, were performed to assess the diagnostic accuracy of individual miRNAs and their combined performance as panels.

RESULTS: The expression levels of miR-21, miR-29a, and miR-92a were significantly elevated in CRC patients compared to healthy controls (all p < 0.001). ROC analysis demonstrated that miR-92a exhibited the highest individual diagnostic performance (AUC: 0.938), followed by miR-21 (AUC: 0.907) and miR-29a (AUC: 0.898). Sensitivity and specificity were 88% and 90%, 92% and 56%, and 76% and 94%, respectively. Combinatorial analysis revealed that the miR-29a and miR-92a panel achieved the highest diagnostic accuracy (AUC: 0.976), surpassing individual miRNAs and other combinations, highlighting its potential as a robust, non-invasive biomarker panel for CRC.

CONCLUSIONS: This study highlights the potential of the miR-29a and miR-92a combination, which achieved excellent diagnostic efficiency (AUC: 0.976). These findings underscore miRNA utility in enhancing early detection and reducing CRC-related mortality in Morocco.

PMID:40126350 | DOI:10.3390/ncrna11020026