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Sexual Orientation and Cervical Cancer Screening Among Cisgender Women

JAMA Netw Open. 2024 May 1;7(5):e248886. doi: 10.1001/jamanetworkopen.2024.8886.

ABSTRACT

IMPORTANCE: Lesbian, gay, and bisexual populations face barriers accessing health care in Chicago, Illinois.

OBJECTIVE: To describe the prevalence of up-to-date cervical cancer screening among lesbian, gay, and bisexual vs heterosexual cisgender women in Chicago.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, cross-sectional, population-based study of cisgender women residing in Chicago was completed from 2020 to 2022 using data from the Healthy Chicago Survey, which is conducted annually by the Chicago Department of Public Health. Participants included cisgender women aged 25 to 64 years with no history of hysterectomy. Respondents who self-identified as lesbian, gay, or bisexual or other than straight, lesbian, or bisexual were coded as lesbian, gay, or bisexual (LGB). Respondents who self-identified as straight were coded as heterosexual. Those who reported having a Papanicolaou test within the past 3 years were considered up-to-date with cervical cancer screening. Data analysis was performed from June to October 2023.

EXPOSURES: The primary exposure was sexual orientation. Covariates included age, income level, race, ethnicity, having a primary care practitioner (PCP), and insurance coverage.

MAIN OUTCOMES AND MEASURES: Prevalence ratios (PRs), log-based regression models, and interaction analysis were used to describe the association of sexual orientation with up-to-date screening.

RESULTS: The sample included 5167 cisgender women (447 LGB and 4720 heterosexual), aged 25 to 64 years, with no history of hysterectomy. Among LGB cisgender women, 318 (71.14%) reported previous cervical cancer screening compared with 3632 (76.95%) heterosexual cisgender women. The prevalence of up-to-date screening was 10% lower in the LGB group compared with the heterosexual group (PR, 0.90; 95% CI, 0.82-1.00). In regression analysis, having a PCP (PR, 1.43; 95% CI, 1.29-1.59) was associated with up-to-date screening. In interaction analysis, LGB cisgender women with a PCP were 93% more likely to be up-to-date compared with those without a PCP (PR, 1.93; 95% CI, 1.37-2.72).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of cervical cancer screening rates between the heterosexual and LGB populations in Chicago, up-to-date cervical cancer screening was associated with having a PCP, regardless of sexual orientation, but this association was greater for LGB individuals. Although LGB populations were less likely to be screened, this disparity may be reduced with more consistent health care access and established care with PCPs.

PMID:38709536 | DOI:10.1001/jamanetworkopen.2024.8886

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Whole-Body Hypothermia vs Targeted Normothermia for Neonates With Mild Encephalopathy: A Multicenter Pilot Randomized Clinical Trial

JAMA Netw Open. 2024 May 1;7(5):e249119. doi: 10.1001/jamanetworkopen.2024.9119.

ABSTRACT

IMPORTANCE: Although whole-body hypothermia is widely used after mild neonatal hypoxic-ischemic encephalopathy (HIE), safety and efficacy have not been evaluated in randomized clinical trials (RCTs), to our knowledge.

OBJECTIVE: To examine the effect of 48 and 72 hours of whole-body hypothermia after mild HIE on cerebral magnetic resonance (MR) biomarkers.

DESIGN, SETTING, AND PARTICIPANTS: This open-label, 3-arm RCT was conducted between October 31, 2019, and April 28, 2023, with masked outcome analysis. Participants were neonates at 6 tertiary neonatal intensive care units in the UK and Italy born at or after 36 weeks’ gestation with severe birth acidosis, requiring continued resuscitation, or with an Apgar score less than 6 at 10 minutes after birth and with evidence of mild HIE on modified Sarnat staging. Statistical analysis was per intention to treat.

INTERVENTIONS: Random allocation to 1 of 3 groups (1:1:1) based on age: neonates younger than 6 hours were randomized to normothermia or 72-hour hypothermia (33.5 °C), and those 6 hours or older and already receiving whole-body hypothermia were randomized to rewarming after 48 or 72 hours of hypothermia.

MAIN OUTCOMES AND MEASURES: Thalamic N-acetyl aspartate (NAA) concentration (mmol/kg wet weight), assessed by cerebral MR imaging and thalamic spectroscopy between 4 and 7 days after birth using harmonized sequences.

RESULTS: Of 225 eligible neonates, 101 were recruited (54 males [53.5%]); 48 (47.5%) were younger than 6 hours and 53 (52.5%) were 6 hours or older at randomization. Mean (SD) gestational age and birth weight were 39.5 (1.1) weeks and 3378 (380) grams in the normothermia group (n = 34), 38.7 (0.5) weeks and 3017 (338) grams in the 48-hour hypothermia group (n = 31), and 39.0 (1.1) weeks and 3293 (252) grams in the 72-hour hypothermia group (n = 36). More neonates in the 48-hour (14 of 31 [45.2%]) and 72-hour (13 of 36 [36.1%]) groups required intubation at birth than in the normothermic group (3 of 34 [8.8%]). Ninety-nine neonates (98.0%) had MR imaging data and 87 (86.1%), NAA data. Injury scores on conventional MR biomarkers were similar across groups. The mean (SD) NAA level in the normothermia group was 10.98 (0.92) mmol/kg wet weight vs 8.36 (1.23) mmol/kg wet weight (mean difference [MD], -2.62 [95% CI, -3.34 to -1.89] mmol/kg wet weight) in the 48-hour and 9.02 (1.79) mmol/kg wet weight (MD, -1.96 [95% CI, -2.66 to -1.26] mmol/kg wet weight) in the 72-hour hypothermia group. Seizures occurred beyond 6 hours after birth in 4 neonates: 1 (2.9%) in the normothermia group, 1 (3.2%) in the 48-hour hypothermia group, and 2 (5.6%) in the 72-hour hypothermia group.

CONCLUSIONS AND RELEVANCE: In this pilot RCT, whole-body hypothermia did not improve cerebral MR biomarkers after mild HIE, although neonates in the hypothermia groups were sicker at baseline. Safety and efficacy of whole-body hypothermia should be evaluated in RCTs.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03409770.

PMID:38709535 | DOI:10.1001/jamanetworkopen.2024.9119

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Racial and Ethnic Disparities in Initiation of Direct Oral Anticoagulants Among Medicare Beneficiaries

JAMA Netw Open. 2024 May 1;7(5):e249465. doi: 10.1001/jamanetworkopen.2024.9465.

ABSTRACT

IMPORTANCE: The influence of race and ethnicity on initiation of direct oral anticoagulants (DOACs) is relatively understudied in Medicare data.

OBJECTIVE: To investigate disparities in the initiation of DOACs compared with warfarin by race, ethnicity, and social vulnerability.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used a 50% sample of Medicare fee-for-service data from January 1, 2010, to December 31, 2019 (mean patient enrollment duration, 7.7 years). Analysis took place between January 2023 and February 2024. A cohort of older adults (aged ≥65 years) with atrial fibrillation who newly initiated warfarin or DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) was identified.

EXPOSURE: Patients were classified as non-Hispanic White, non-Hispanic Black, and Hispanic.

MAIN OUTCOMES AND MEASURES: The likelihood of starting use of DOACs compared with warfarin was modeled, adjusting for race, ethnicity, age, sex, county-level social vulnerability, and other clinical factors.

RESULTS: Among 950 698 anticoagulation initiations, consisting of 680 974 DOAC users and 269 724 warfarin users (mean [SD] age, 78.5 [7.6] years; 52.6% female), 5.2% were Black, 4.3% were Hispanic, and 86.7% were White. During the 10-year study period, DOAC use increased for all demographic groups. After adjustment, compared with White patients, Black patients were 23% less likely (adjusted odds ratio [AOR, 0.77; 95% CI, 0.75-0.79) and Hispanic patients were 13% less likely (AOR, 0.87; 95% CI, 0.85-0.89) to initiate DOAC use. Disparities in DOAC initiation were greatest among Black patients in the earlier years but attenuated during the study period. For instance, in 2010, the OR of Black patients initiating DOACs was 0.54 (95% CI, 0.50-0.57), attenuating linearly over time to 0.69 by 2013 (95% CI, 0.65-0.74) and 0.83 (95% CI, 0.78-0.89) by 2017. By 2019, these differences became nonsignificant (OR, 1.08; 95% CI, 0.99-1.18).

CONCLUSIONS AND RELEVANCE: In this cohort study of Medicare patients with atrial fibrillation, Black and Hispanic patients were less likely to initiate DOACs for atrial fibrillation, although these differences diminished over time. Identifying the factors behind these early disparities is crucial for ensuring equitable access to novel therapies as they emerge for Black and Hispanic populations.

PMID:38709533 | DOI:10.1001/jamanetworkopen.2024.9465

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Consumption of Olive Oil and Diet Quality and Risk of Dementia-Related Death

JAMA Netw Open. 2024 May 1;7(5):e2410021. doi: 10.1001/jamanetworkopen.2024.10021.

ABSTRACT

IMPORTANCE: Age-standardized dementia mortality rates are on the rise. Whether long-term consumption of olive oil and diet quality are associated with dementia-related death is unknown.

OBJECTIVE: To examine the association of olive oil intake with the subsequent risk of dementia-related death and assess the joint association with diet quality and substitution for other fats.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study examined data from the Nurses’ Health Study (NHS; 1990-2018) and Health Professionals Follow-Up Study (HPFS; 1990-2018). The population included women from the NHS and men from the HPFS who were free of cardiovascular disease and cancer at baseline. Data were analyzed from May 2022 to July 2023.

EXPOSURES: Olive oil intake was assessed every 4 years using a food frequency questionnaire and categorized as (1) never or less than once per month, (2) greater than 0 to less than or equal to 4.5 g/d, (3) greater than 4.5 g/d to less than or equal to 7 g/d, and (4) greater than 7 g/d. Diet quality was based on the Alternative Healthy Eating Index and Mediterranean Diet score.

MAIN OUTCOME AND MEASURE: Dementia death was ascertained from death records. Multivariable Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% CIs adjusted for confounders including genetic, sociodemographic, and lifestyle factors.

RESULTS: Of 92 383 participants, 60 582 (65.6%) were women and the mean (SD) age was 56.4 (8.0) years. During 28 years of follow-up (2 183 095 person-years), 4751 dementia-related deaths occurred. Individuals who were homozygous for the apolipoprotein ε4 (APOE ε4) allele were 5 to 9 times more likely to die with dementia. Consuming at least 7 g/d of olive oil was associated with a 28% lower risk of dementia-related death (adjusted pooled HR, 0.72 [95% CI, 0.64-0.81]) compared with never or rarely consuming olive oil (P for trend < .001); results were consistent after further adjustment for APOE ε4. No interaction by diet quality scores was found. In modeled substitution analyses, replacing 5 g/d of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8% (95% CI, 4%-12%) to 14% (95% CI, 7%-20%) lower risk of dementia mortality. Substitutions for other vegetable oils or butter were not significant.

CONCLUSIONS AND RELEVANCE: In US adults, higher olive oil intake was associated with a lower risk of dementia-related mortality, irrespective of diet quality. Beyond heart health, the findings extend the current dietary recommendations of choosing olive oil and other vegetable oils for cognitive-related health.

PMID:38709531 | DOI:10.1001/jamanetworkopen.2024.10021

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Doubly Robust Causal Modeling to Evaluate Device Implantation

JAMA Intern Med. 2024 May 6. doi: 10.1001/jamainternmed.2024.1181. Online ahead of print.

NO ABSTRACT

PMID:38709499 | DOI:10.1001/jamainternmed.2024.1181

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Learning Morphological, Spatial, and Dynamic Models of Cellular Components

Methods Mol Biol. 2024;2800:231-244. doi: 10.1007/978-1-0716-3834-7_16.

ABSTRACT

In this chapter, we describe protocols for using the CellOrganizer software on the Jupyter Notebook platform to analyze and model cell and organelle shape and spatial arrangement. CellOrganizer is an open-source system for using microscope images to learn statistical models of the structure of cell components and how those components are organized relative to each other. Such models capture the statistical variation in the organization of cellular components by jointly modeling the distributions of their number, shape, and spatial distributions. These models can be created for different cell types or conditions and compared to reflect differences in their spatial organizations. The models are also generative, in that they can be used to synthesize new cell instances reflecting what a model learned and to provide well-structured cell geometries that can be used for biochemical simulations.

PMID:38709488 | DOI:10.1007/978-1-0716-3834-7_16

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Author Correction: Discovering trends of social interaction behavior over time: An introduction to relational event modeling

Behav Res Methods. 2024 May 6. doi: 10.3758/s13428-024-02423-2. Online ahead of print.

NO ABSTRACT

PMID:38709453 | DOI:10.3758/s13428-024-02423-2

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Influence of UGT2B7, UGT1A4 and ABCG2 Polymorphisms on the Pharmacokinetics and Therapeutic Efficacy of Lamotrigine in Patients with Epilepsy

Eur J Drug Metab Pharmacokinet. 2024 May 6. doi: 10.1007/s13318-024-00894-4. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: A substantial inter-individual variability has been observed in the pharmacokinetics of lamotrigine. The aim of the study was to investigate the impact of genetic polymorphism of the metabolizing enzymes (UGT2B7, UGT1A4) and transporter (ABCG2) on the pharmacokinetics and therapeutic efficacy of lamotrigine in patients with epilepsy.

METHODS: The genetic analysis of single-nucleotide polymorphisms was conducted using polymerase chain reaction sequence. High-performance liquid chromatography/tandem mass spectrometry was employed to measure the plasma concentrations of lamotrigine. The efficacy of lamotrigine was assessed by evaluating the reduction rate of epileptic seizure frequency.

RESULTS: This study included a cohort of 331 patients who were treated with lamotrigine as monotherapy. A linear correlation was observed between the lamotrigine concentration and daily dose taken (r = 0.58, p < 2.2e-16). Statistically significant differences were found in both the median plasma concentration and dose-adjusted concentration (C/D ratio) when comparing the ineffective to the effective group (p < 0.05). Multivariate analysis showed that UGT1A4 rs2011425, ABCG2 rs2231142 polymorphisms and age had a significant relationship with the lamotrigine concentrations (p < 0.05). Age was a predictive factor for C/D ratio (p < 0.001). Lamotrigine concentration and weight were good predictive factors for effective seizure outcomes (odds ratio [OR] = 0.715, 95% CI 0.658-0.776, p < 0.001; OR = 0.926, 95% CI 0.901-0.951, p < 0.001, respectively). The cut-off values of lamotrigine trough concentrations for clinical outcomes in the age-related groups were determined as 2.49 μg/ml (area under the receiver-operating characteristic curve [AUC]: 0.828, 95% CI 0.690-0.966), 2.70 μg/ml (AUC: 0.805, 95% CI 0.745-0.866) and 3.25 μg/ml (AUC: 0.807, 95% CI 0.686-0.928) for the adult group, adolescent group, and toddler and school-age group, respectively.

CONCLUSIONS: UGT1A4 rs2011425 and ABCG2 rs2231142 were correlated with lamotrigine concentrations. Lower lamotrigine trough concentration was found in the ineffective group and the troughs were associated with seizure outcomes.

PMID:38709450 | DOI:10.1007/s13318-024-00894-4

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Real-World Clinical Burden of Newly Diagnosed Heart failure in Thai Patients

Cardiol Ther. 2024 May 6. doi: 10.1007/s40119-024-00366-5. Online ahead of print.

ABSTRACT

INTRODUCTION: There are limited data on the burden of newly diagnosed patients with heart failure (HF) in Thailand. Thus, this study aimed to fully understand the hospitalization, rehospitalization, mortality rates, demographics and characteristics, and quality of care in these patients.

METHOD: A retrospective review of all eligible adult patients’ medical records from 2018 and 2019 was conducted at five hospitals. The patients were newly diagnosed with HF, as indicated by the International Classification of Diseases (ICD)-10 code “I50.” Descriptive statistics was used to investigate patients’ hospital burden and clinical outcome data.

RESULTS: There were 1134 patients newly diagnosed with HF, classified as HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and HF with mildly reduced ejection fraction (HFmrEF) (44.0, 40.0, and 16.0%, respectively). The male-to-female ratios in HFmrEF and HFpEF were similar. In contrast, the proportion of men with HFrEF was greater. The mean age of all patients was 66.0 years. The hospitalization rate was 1.3. Rehospitalization rates for HF-related issues were 0.1, 0.2, 0.4, and 0.5 at 30 days, 60 days, 180 days, and 1 year, respectively. The percentage of deaths from all causes among these patients was 9.8%, while the percentage of deaths from cardiovascular-related causes was 8.5%. Only a small proportion of patients received a target dose of guideline-directed medical therapy (GDMT).

CONCLUSIONS: The study revealed that the characteristics, hospitalization rate for HF, and in-hospital mortality rate among newly diagnosed patients with HF were higher compared to similar studies conducted in Thailand and other countries. Moreover, a high quality of care is needed to improve the morbidity and mortality associated with HF in Thailand.

PMID:38709436 | DOI:10.1007/s40119-024-00366-5

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Efficacy and Safety of Monoclonal Antibodies for the Treatment of Eosinophilic Esophagitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Dig Dis Sci. 2024 May 6. doi: 10.1007/s10620-024-08413-w. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Monoclonal antibodies (MAbs) have clinical benefits for treating several atopic diseases. However, consensus on its use for eosinophilic esophagitis (EoE) is lacking. The present meta-analysis aimed to compare the efficacy and safety of MAbs versus placebo for treating EoE.

METHODS: We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcomes were changes in peak esophageal eosinophils count/high power field (HPF) and mean esophageal eosinophils count/HPF. The secondary outcomes were changes in the EoE-Histology Scoring System (EoE-HSS), Endoscopic Reference Score (EREFS), dysphagia score, and adverse events (AEs). We compared binary outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD) or standardized mean difference (SMD), with 95% confidence interval (CI). Considering the diversity of mechanistic properties of MAbs, a pre-specified subgroup analysis by MAb mechanism of action was performed for all outcomes, provided that at least two studies were in each subgroup. Heterogeneity was assessed using Cochran’s Q test and I2 statistics.

RESULTS: 6 RCTs were included (533 patients). Compared to placebo, MAbs led to a significant reduction in peak esophageal eosinophils count/HPF (MD -0.78; CI 95% -0.87, -0.6801) and mean esophageal eosinophils count/HPF (SMD -0.79; CI 95% -1.5, -0.08). Moreover, MAbs significantly reduced EoE-HSS scores (grade score: SMD -9.31; 95% CI -13.95, -4.6701; stage score: SMD -10.18; 95% CI -15.06, -5.31), EREFS (SMD -5.95; CI 95% -9.19, -2.71) and dysphagia score (SMD -1.79; CI 95% -3.36, -0.23) without increasing AEs compared to placebo. Among those MAbs whose mechanism of action includes the blockage of the receptor for IL-13 (Dupilumab, QAX576, and RPC4046), the scores of EoE-HSS grade, EoE-HSS stage, EREFS, and dysphagia were significantly reduced, and they presented a similar risk of overall and serious AEs compared to placebo.

CONCLUSION: MAbs seem effective and safe in reducing esophageal eosinophil infiltrate, EoE-HSS score, EREFS score, and dysphagia symptoms in patients with EoE. However, further evidence is needed to establish its place in EoE management.

PMID:38709421 | DOI:10.1007/s10620-024-08413-w