Tag: nevin manimala

Medicine (Baltimore). 2024 Jun 28;103(26):e38626. doi: 10.1097/MD.0000000000038626.

ABSTRACT

Primary sclerosing cholangitis (PSC), a chronic cholestatic liver condition, is frequently associated with inflammatory bowel disease. Specific immune cells have been implicated in PSC pathogenesis with the emergence of the “microbiota” and “gut lymphocyte homing” hypotheses, albeit their identities remain controversial. The first genome-wide association analysis leveraged nonoverlapping data from 3757 Europeans to evaluate 731 immunophenotypes. A genome-wide association analysis comprising 2871 cases and 12,019 controls yielded summary statistics for PSC. An inverse-variance weighted (IVW) analysis was performed to identify immunophenotypes causally related to PSC, and the results were validated using weighted mode, MR-Egger, and weighted median methods. Comprehensive sensitivity analyses were performed to verify the robustness, heterogeneity, and horizontal pleiotropy of the results. IVW analysis revealed 26 immune traits exhibiting causal associations with PSC. CD3 on HLA-DR+ CD4+ (IVW odds ratio [OR]: 0.904; 95% confidence interval [CI]: 0.828-0.986, P = .023) and CD3 on secreting Treg (IVW OR: 0.893; 95% CI: 0.823-0.969, P = .007) were negatively associated with PSC susceptibility and demonstrated high consistency across the 3 validation methods. Moreover, 7 other immune traits, including CD39+ resting Treg absolute cell (IVW OR = 1.083, 95% CI: 1.013-1.157, P = .019), CD39+ secreting Treg absolute cell (IVW OR = 1.063, 95% CI: 1.012-1.118, P = .015), CD3 on naive CD8br (IVW OR = 0.907, 95% CI: 0.835-0.986, P = .022), CD3 on CD39+ activated Treg (IVW OR = 0.927, 95% CI: 0.864-0.994, P = .034), CD28 on resting Treg (IVW OR = 0.724, 95% CI: 0.630-0.833, P = 5.95E-06), and CD39 on CD39+ CD4+ (IVW OR = 1.055, 95% CI: 1.001-1.112, P = .044) exhibited consistent results in the Weighted Median and Weighted Mode validation methods. Moreover, no significant heterogeneity or horizontal pleiotropy was observed across the single nucleotide polymorphisms. The leave-one-out results revealed that sequentially eliminating each single nucleotide polymorphism had no significant influence on model effect estimates or qualitative inference. This study evaluated potential causal links between 731 immune traits and PSC susceptibility. Twenty-six immune traits were identified using the IVW method. Verification across multiple methods revealed 9 immune traits with a plausible causal connection to PSC. These findings may uncover mechanistic pathways and novel therapeutic approaches.

PMID:38941430 | DOI:10.1097/MD.0000000000038626

JAMA Netw Open. 2024 Jun 3;7(6):e2418213. doi: 10.1001/jamanetworkopen.2024.18213.

ABSTRACT

IMPORTANCE: Unintended pregnancy is a major health risk for adolescents in the US, and adolescents face many barriers to obtaining effective and reliable contraception.

OBJECTIVE: To measure and describe the use of contraception, pregnancy risk index (PRI), and emergency contraception (EC) prescriptions among female adolescents accessing the emergency department (ED) for care.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study is a planned secondary analysis of a multicenter trial from April 2021 through April 2022 that used a tablet-based, content-validated, confidential sexual health survey at 6 urban, pediatric tertiary care EDs affiliated with the Pediatric Emergency Care Applied Research Network. Participants were individuals aged 15 to 21 years presenting to the ED who completed the confidential sexual health survey and indicated female sex assigned at birth and prior penile-vaginal sexual intercourse. Data analysis was performed from January 2023 to February 2024.

MAIN OUTCOMES AND MEASURES: The primary outcomes were the type and proportion of contraception use, the PRI, and provision of EC. Separate multivariable logistic regression models were performed to identify sociodemographic factors associated with these outcomes.

RESULTS: A total of 1063 participants (median [IQR] age, 17.5 [16.5-18.3] years) were included in this analysis; 219 (20.8%) identified as Hispanic, 464 (44.1%) identified as non-Hispanic Black, 308 (29.3%) identified as non-Hispanic White, and 61 (5.8%) identified as other races and ethnicities. In total, 756 participants (71.1%) reported contraception use during their last sexual encounter. Long-acting reversible contraception use (LARC) was the least used (164 participants [15.4%]), and 307 (28.9%) reported no contraception use. Sociodemographic factors associated with overall contraception use, and LARC use specifically, included insurance and race and ethnicity. The overall PRI was 7.89, or an expected 8 pregnancies per 100 female individuals per year. Although 108 participants (10.2%) were eligible for EC, EC was ordered for only 6 (5.6%) of those eligible.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of sexually active adolescents presenting to the ED, the majority of participants reported using at least 1 form of contraception; however, LARCs were the least used option, and 28.9% of participants reported no contraceptive use. The unintended pregnancy risk was almost 8% in the study population. Few patients eligible for EC received it. These data suggest a high need and potential opportunity for provision of contraception services in the ED setting.

PMID:38941097 | DOI:10.1001/jamanetworkopen.2024.18213

JAMA Netw Open. 2024 Jun 3;7(6):e2419029. doi: 10.1001/jamanetworkopen.2024.19029.

ABSTRACT

IMPORTANCE: Studies on the familial effects of body mass index (BMI) status have yielded a wide range of data on its heritability.

OBJECTIVE: To assess the heritability of obesity by measuring the association between the BMIs of fathers, mothers, and their offspring at the same age.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from population-wide mandatory medical screening before compulsory military service in Israel. The study included participants examined between January 1, 1986, and December 31, 2018, whose both parents had their BMI measurement taken at their own prerecruitment evaluation in the past. Data analysis was performed from May to December 2023.

MAIN OUTCOMES AND MEASURES: Spearman correlation coefficients were calculated for offsprings’ BMI and their mothers’, fathers’, and midparental BMI percentile (the mean of the mothers’ and fathers’ BMI cohort- and sex-specific BMI percentile) to estimate heritability. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% CIs of obesity compared with healthy BMI, according to parental BMI status.

RESULTS: A total of 447 883 offspring (235 105 male [52.5%]; mean [SD] age, 17.09 [0.34] years) with both parents enrolled and measured for BMI at 17 years of age were enrolled in the study, yielding a total study population of 1 343 649 individuals. Overall, the correlation between midparental BMI percentile at 17 years of age and the offspring’s BMI at 17 years of age was moderate (ρ = 0.386). Among female offspring, maternal-offspring BMI correlation (ρ = 0.329) was somewhat higher than the paternal-offspring BMI correlation (ρ = 0.266). Among trios in which both parents had a healthy BMI, the prevalence of overweight or obesity in offspring was 15.4%; this proportion increased to 76.6% when both parents had obesity and decreased to 3.3% when both parents had severe underweight. Compared with healthy weight, maternal (OR, 4.96; 95% CI, 4.63-5.32), paternal (OR, 4.48; 95% CI, 4.26-4.72), and parental (OR, 6.44; 95% CI, 6.22-6.67) obesity (midparent BMI in the ≥95th percentile) at 17 years of age were associated with increased odds of obesity among offspring.

CONCLUSIONS AND RELEVANCE: In this cohort study of military enrollees whose parents also underwent prerecruitment evaluations, the observed correlation between midparental and offspring BMI, coupled with a calculated narrow-sense heritability of 39%, suggested a substantive contribution of genetic factors to BMI variation at 17 years of age.

PMID:38941093 | DOI:10.1001/jamanetworkopen.2024.19029

JAMA Netw Open. 2024 Jun 3;7(6):e2419245. doi: 10.1001/jamanetworkopen.2024.19245.

ABSTRACT

IMPORTANCE: Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations. Consequently, professional bodies advise against the use of varenicline and bupropion and recommend caution with nicotine replacement therapy (NRT). Contemporary estimates of the use of smoking cessation pharmacotherapies during pregnancy are lacking.

OBJECTIVE: To quantify the proportion of individuals using prescribed smoking cessation pharmacotherapies during pregnancy and during the first trimester specifically, in 4 countries.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study used linked birth records, hospital admission records, and dispensing records of prescribed medications from all pregnancies resulting in birth between 2015 and 2020 in New South Wales, Australia; New Zealand; Norway; and Sweden. Data analyses were conducted in October and November 2023.

EXPOSURE: Prescribed smoking cessation pharmacotherapy use (varenicline, NRT, and bupropion) during pregnancy was defined as days’ supply overlapping the period from date of conception to childbirth.

MAIN OUTCOMES AND MEASURES: Prevalence of use among all pregnancies and pregnancies with maternal smoking were calculated. Among women who used a pharmacotherapy, the proportion of women with use during the first trimester of pregnancy was also calculated.

RESULTS: Among 1 700 638 pregnancies in 4 countries, 138 033 (8.1%) had maternal smoking and 729 498 (42.9%) were younger than 30 years. The prevalences ranged from 0.02% to 0.14% for varenicline, less than 0.01% to 1.86% for prescribed NRT, and less than 0.01% to 0.07% for bupropion. Among pregnant individuals who smoked, use of pharmacotherapies was up to 10 times higher, with maximum prevalences of 1.25% for varenicline in New South Wales, 11.39% for NRT in New Zealand, and 0.39% for bupropion in New Zealand. Use in the first trimester occurred among more than 90% of individuals using varenicline, approximately 60% among those using NRT, and 80% to 90% among those using bupropion.

CONCLUSIONS AND RELEVANCE: In this cohort study of pregnant individuals in 4 high-income countries, the low prevalence of varenicline and bupropion use during pregnancy and higher prevalence of NRT use aligned with current clinical guidelines. As most use occurred in the first trimester, there is a need for evidence on the risk of congenital malformations for these medications.

PMID:38941092 | DOI:10.1001/jamanetworkopen.2024.19245

JAMA Netw Open. 2024 Jun 3;7(6):e2419250. doi: 10.1001/jamanetworkopen.2024.19250.

ABSTRACT

IMPORTANCE: Although existing research has found daily heat to be associated with dementia-related outcomes, there is still a gap in understanding the differing associations of nighttime and daytime heat with dementia-related deaths.

OBJECTIVES: To quantitatively assess the risk and burden of dementia-related deaths associated with short-term nighttime and daytime heat exposure and identify potential effect modifications.

DESIGN, SETTING, AND PARTICIPANTS: This case-crossover study analyzed individual death records for dementia across all mainland China counties from January 1, 2013, to December 31, 2019, using a time-stratified case-crossover approach. Statistical analysis was conducted from January 1, 2013, to December 31, 2019.

EXPOSURES: Two novel heat metrics: hot night excess (HNE) and hot day excess (HDE), representing nighttime and daytime heat intensity, respectively.

MAIN OUTCOMES AND MEASURES: Main outcomes were the relative risk and burden of dementia-related deaths associated with HNE and HDE under different definitions. Analysis was conducted with conditional logistic regression integrated with the distributed lag nonlinear model.

RESULTS: The study involved 132 573 dementia-related deaths (mean [SD] age, 82.5 [22.5] years; 73 086 women [55.1%]). For a 95% threshold, the median hot night threshold was 24.5 °C (IQR, 20.1 °C-26.2 °C) with an HNE of 3.7 °C (IQR, 3.1 °C-4.3 °C), and the median hot day threshold was 33.3 °C (IQR, 29.9 °C-34.7 °C) with an HDE of 0.6 °C (IQR, 0.5 °C-0.8 °C). Both nighttime and daytime heat were associated with increased risk of dementia-related deaths. Hot nights’ associations with risk of dementia-related deaths persisted for 6 days, while hot days’ associations with risk of dementia-related deaths extended over 10 days. Extreme HDE had a higher relative risk of dementia-related deaths, with a greater burden associated with extreme HNE at more stringent thresholds. At a 97.5% threshold, the odds ratio for dementia-related deaths was 1.38 (95% CI, 1.22-1.55) for extreme HNE and 1.46 (95% CI, 1.27-1.68) for extreme HDE, with an attributable fraction of 1.45% (95% empirical confidence interval [95% eCI], 1.43%-1.47%) for extreme HNE and 1.10% (95% eCI, 1.08%-1.11%) for extreme HDE. Subgroup analyses suggested heightened susceptibility among females, individuals older than 75 years of age, and those with lower educational levels. Regional disparities were observed, with individuals in the south exhibiting greater sensitivity to nighttime heat and those in the north to daytime heat.

CONCLUSIONS AND RELEVANCE: Results of this nationwide case-crossover study suggest that both nighttime and daytime heat are associated with increased risk of dementia-related deaths, with a greater burden associated with nighttime heat. These findings underscore the necessity of time-specific interventions to mitigate extreme heat risk.

PMID:38941091 | DOI:10.1001/jamanetworkopen.2024.19250

J Autism Dev Disord. 2024 Jun 28. doi: 10.1007/s10803-024-06436-w. Online ahead of print.

ABSTRACT

PURPOSE: Many individuals with autism spectrum disorder (ASD) experience challenges with facial emotion recognition (FER), which may exacerbate social difficulties in ASD. Few studies have examined whether FER can be experimentally manipulated and improved for autistic people. This study utilized a randomized controlled trial design to examine acceptability and preliminary clinical impact of a novel mixed reality-based neurofeedback program, FER Assistant, using EEG brain computer interface (BCI)-assisted technology to improve FER for autistic adolescents and adults.

METHODS: Twenty-seven autistic male participants (M age: 21.12 years; M IQ: 105.78; 85% white) were randomized to the active condition to receive FER Assistant (n = 17) or waitlist control (n = 10). FER Assistant participants received ten sessions utilizing BCI-assisted neurofeedback training in FER. All participants, regardless of randomization, completed a computerized FER task at baseline and endpoint.

RESULTS: Results partially indicated that FER Assistant was acceptable to participants. Regression analyses demonstrated that participation in FER Assistant led to group differences in FER at endpoint, compared to a waitlist control. However, analyses examining reliable change in FER indicated no reliable improvement or decline for FER Assistant participants, whereas two waitlist participants demonstrated reliable decline.

CONCLUSION: Given the preliminary nature of this work, results collectively suggest that FER Assistant may be an acceptable intervention. Results also suggest that FER may be a potential mechanism that is amenable to intervention for autistic individuals, although additional trials using larger sample sizes are warranted.

PMID:38941048 | DOI:10.1007/s10803-024-06436-w

EJNMMI Phys. 2024 Jun 28;11(1):53. doi: 10.1186/s40658-024-00655-x.

ABSTRACT

BACKGROUND: For dosimetry, the demand for whole-body SPECT/CT imaging, which require long acquisition durations with dual-head Anger cameras, is increasing. Here we evaluated sparsely acquired projections and assessed whether the addition of deep-learning-generated synthetic intermediate projections (SIPs) could improve the image quality while preserving dosimetric accuracy.

METHODS: This study included 16 patients treated with ¹⁷⁷Lu-DOTATATE with SPECT/CT imaging (120 projections, 120P) at four time points. Deep neural networks (CUSIPs) were designed and trained to compile 90 SIPs from 30 acquired projections (30P). The 120P, 30P, and three different CUSIP sets (30P + 90 SIPs) were reconstructed using Monte Carlo-based OSEM reconstruction (yielding 120P_rec, 30P_rec, and CUSIP_recs). The noise levels were visually compared. Quantitative measures of normalised root mean square error, normalised mean absolute error, peak signal-to-noise ratio, and structural similarity were evaluated, and kidney and bone marrow absorbed doses were estimated for each reconstruction set.

RESULTS: The use of SIPs visually improved noise levels. All quantitative measures demonstrated high similarity between CUSIP sets and 120P. Linear regression showed nearly perfect concordance of the kidney and bone marrow absorbed doses for all reconstruction sets, compared to the doses of 120P_rec (R² ≥ 0.97). Compared to 120P_rec, the mean relative difference in kidney absorbed dose, for all reconstruction sets, was within 3%. For bone marrow absorbed doses, there was a higher dissipation in relative differences, and CUSIP_recs outperformed 30P_rec in mean relative difference (within 4% compared to 9%). Kidney and bone marrow absorbed doses for 30P_rec were statistically significantly different from those of 120_rec, as opposed to the absorbed doses of the best performing CUSIP_rec, where no statistically significant difference was found.

CONCLUSION: When performing SPECT/CT reconstruction, the use of SIPs can substantially reduce acquisition durations in SPECT/CT imaging, enabling acquisition of multiple fields of view of high image quality with satisfactory dosimetric accuracy.

PMID:38941040 | DOI:10.1186/s40658-024-00655-x

J Assist Reprod Genet. 2024 Jun 28. doi: 10.1007/s10815-024-03177-8. Online ahead of print.

ABSTRACT

PURPOSE: To examine outcomes of oocyte retrievals completed by Reproductive Endocrinology and Infertility (REI) fellows versus faculty physicians.

METHODS: This retrospective cohort study examined patients who underwent oocyte retrievals at Mayo Clinic from July 15, 2009, to December 15, 2016. The primary outcome was the oocyte retrieval rate (ORR) calculated per retrieval as the number of oocytes retrieved per follicles aspirated. The Wilcoxon signed-rank test was used to compare follicle and oocyte counts and ORR between fellows and faculty during the same bilateral retrieval.

RESULTS: The study cohort included the first bilateral retrieval from 845 unique patients completed by 11 fellows and seven faculty. The median ORR was not statistically different for fellows and faculty (0.79 versus 0.80, p = 0.46). To assess for a learning curve, the outcomes of seven fellows who completed at least 80 retrievals in their first year were examined as four chronologically ordered sets of 20. When these sets were compared to the faculty physician mean ORR, no significant differences were found (p-values of 0.69, 0.69, 0.81, and 0.81, respectively).

CONCLUSION: There were no significant differences in oocyte retrieval rates between fellows versus faculty over a 7-year period, with no significant learning curve observed. These findings suggest that fellows possess the requisite skills for successful oocyte retrieval upon entering REI fellowship following their OB/GYN residency. However, this does not diminish the critical role of comprehensive fellowship training and close supervision, especially in initial and complex cases.

PMID:38941004 | DOI:10.1007/s10815-024-03177-8

Intern Emerg Med. 2024 Jun 28. doi: 10.1007/s11739-024-03681-w. Online ahead of print.

ABSTRACT

During the COVID-19 pandemic, there was a notable undersupply of respiratory support devices, especially in low- and middle-income countries. As a result, many hospitals turned to alternative respiratory therapies, including the use of gas-operated ventilators (GOV). The aim of this study was to describe the use of GOV as a noninvasive bridging respiratory therapy in critically ill COVID-19 patients and to compare clinical outcomes achieved with this device to conventional respiratory therapies. Retrospective cohort analysis of critically ill COVID-19 patients during the first local wave of the pandemic. The final analysis included 204 patients grouped according to the type of respiratory therapy received in the first 24 h, as follows: conventional oxygen therapy (COT), n = 28 (14%); GOV, n = 72 (35%); noninvasive ventilation (NIV), n = 49 (24%); invasive mechanical ventilation (IMV), n = 55 (27%). In 72, GOV served as noninvasive bridging respiratory therapy in 42 (58%) of these patients. In the other 30 patients (42%), 20 (28%) presented clinical improvement and were discharged; 10 (14%) died. In the COT and GOV groups, 68% and 39%, respectively, progressed to intubation (P ≤ 0.001). Clinical outcomes in the GOV and NIV groups were similar (no statistically significant differences). GOV was successfully used as a noninvasive bridging respiratory therapy in more than half of patients. Clinical outcomes in the GOV group were comparable to those of the NIV group. These findings support the use of GOV as an emergency, noninvasive bridging respiratory therapy in medical crises when alternative approaches to the standard of care may be justifiable.

PMID:38940989 | DOI:10.1007/s11739-024-03681-w

Arch Orthop Trauma Surg. 2024 Jun 28. doi: 10.1007/s00402-024-05411-5. Online ahead of print.

ABSTRACT

INTRODUCTION: High tibial osteotomy (HTO) is a surgery performed to treat the symptoms and prevent the progression of medial osteoarthritis. Post-operative bleeding has led to early returns to hospital following surgery. Intrafocal injection of tranexamic acid (TXA) could reduce this bleeding complication. The objective of the study was to evaluate the effect of TXA during HTO on the incidence of post-operative complications and early returns to hospital.

MATERIALS AND METHODS: This retrospective study included 251 cases of HTO performed between May 2012 and October 2021, with the use of TXA introduced in May 2017. The experimental (n = 102) and control (n = 149) groups were compared as to the rate of post-operative early returns. The influence of confounding factors was evaluated, including age, sex, body mass index (BMI), tobacco use, grade of medial femorotibial osteoarthritis (MFTO), magnitude of angular correction (MAC), and surgery duration.

RESULTS: No statistically significant difference was found between the groups with regards to all variables except age. The experimental group was significantly older (54.4 years; σ = 7.5) than the control group (50.4 years; σ = 7.9; p < 0.001). We observed a decrease in emergency department (ED) visits in the experimental group (15.7%) compared to the control (30.2%; p = 0.008) and a decrease in early returns in the experimental group (28.4%) compared to the control (40.5%; p = 0.049). No statistically significant difference in demographic data, MFTO, or MAC was found among patients with and without an early return, in both the experimental and control groups.

CONCLUSION: The intrafocal injection of TXA during HTO decreases early returns to hospital.

PMID:38940983 | DOI:10.1007/s00402-024-05411-5