Category: Statistics

J Natl Cancer Inst. 2024 Aug 8:djae186. doi: 10.1093/jnci/djae186. Online ahead of print.

ABSTRACT

BACKGROUND: Ultraviolet radiation (UVR) exposure is the primary risk factor for melanoma although the relationship is complex. Compared to radiation from UVB wavelengths, UVA makes up a majority of the surface solar UVR, penetrates the skin more deeply, is the principal range emitted by tanning beds, and is less filtered by sunscreens and window glass. Few studies have examined the relationship between ambient UVA and UVB and melanoma risk.

METHODS: Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated for the association between satellite-based ambient (based on residential history) UVA, UVB and melanoma in non-Hispanic White participants using data from the United States Radiologic Technologists study, a large, nationwide prospective cohort. Associations of UVA and UVB quartile (Q) were examined in mutually adjusted and stratified models, additionally adjusted for demographic and sun sensitivity characteristics.

RESULTS: There were 837 incident melanoma cases among 62,785 participants. Incidence of melanoma was statistically significantly increased for the highest quartile of childhood UVA exposure after adjustment for UVB (IRR = 2.82; 95%CI:1.46,5.44), but not for higher childhood UVB after adjustment for UVA. Childhood UVA was associated with increased melanoma risk within strata of UVB. Childhood UVB was not associated with melanoma after adjustment for UVA, but there was some evidence of lower risk with increased lifetime ambient UVB after UVA adjustment.

CONCLUSIONS: Melanoma risk was elevated among participants living in locations with high annual childhood and lifetime UVA after controlling for UVB. With confirmation, these findings support increased protection from solar UVA for melanoma prevention.

PMID:39115885 | DOI:10.1093/jnci/djae186

Bioinformatics. 2024 Aug 8:btae498. doi: 10.1093/bioinformatics/btae498. Online ahead of print.

ABSTRACT

MOTIVATION: Generalized linear mixed models (GLMMs), such as the negative-binomial or Poisson linear mixed model, are widely applied to single-cell RNA sequencing data to compare transcript expression between different conditions determined at the subject level. However, the model is computationally intensive, and its relative statistical performance to pseudobulk approaches is poorly understood.

RESULTS: We propose offset-pseudobulk as a lightweight alternative to GLMMs. We prove that a count-based pseudobulk equipped with a proper offset variable has the same statistical properties as GLMMs in terms of both point estimates and standard errors. We confirm our findings using simulations based on real data. Offset-pseudobulk is substantially faster (>x10) and numerically more stable than GLMMs.

AVAILABILITY: Offset pseudobulk can be easily implemented in any generalized linear model software by tweaking a few options. The codes can be found at https://github.com/hanbin973/pseudobulk_is_mm.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:39115884 | DOI:10.1093/bioinformatics/btae498

J Cardiovasc Pharmacol. 2024 Aug 7. doi: 10.1097/FJC.0000000000001623. Online ahead of print.

ABSTRACT

Guidelines recommend intravenous (IV) loop diuretics as first-line therapy for patients hospitalized with acute heart failure (AHF) and volume overload. Additional agents can be utilized for augmentation but there is limited guidance on agent selection. The study objective was to determine if chlorothiazide or metolazone is associated with differences in diuretic efficacy or safety in loop diuretic-resistant patients with AHF and renal dysfunction. We conducted a multi-center, retrospective cohort study of patients hospitalized with AHF and renal dysfunction who received metolazone or chlorothiazide in addition to IV loop diuretics. The primary endpoint was a comparison of 24-hour urine output (UOP) between the 24 hours before and after thiazide administration. Secondary and safety endpoints included weight change, requirement for vasopressors or inotropes, electrolyte abnormalities, and changes in renal function. A total of 223 patients were included. The mean daily diuretic doses were chlorothiazide 632 mg and metolazone 7 mg. Mean 24-hour UOP increased more among chlorothiazide- (1668 to 3826 mL) versus metolazone-treated patients (1672 to 2834 mL) (p<0.001) after addition of the second diuretic. No statistically significant differences in weight or serum creatinine changes were observed. More hypomagnesemia was observed in the chlorothiazide group; no differences in other electrolytes or serum creatinine were observed. Chlorothiazide was associated with a greater increase in 24-hour UOP than metolazone without an excess of potassium or serum creatinine derangements. However, weight changes did not differ significantly between groups. Future prospective studies are needed to confirm potential differences in diuretic response and safety.

PMID:39115872 | DOI:10.1097/FJC.0000000000001623

J Am Assoc Nurse Pract. 2024 Aug 6. doi: 10.1097/JXX.0000000000001062. Online ahead of print.

ABSTRACT

BACKGROUND: Despite updated American Heart Association guidelines, interventions designed to reduce telemetry misuse are uncommon.

LOCAL PROBLEM: There was a systemic failure within the institution to adopt the most recent guidelines, resulting in poor use of resources and downstream costs.

METHODS: Case-control. Pre-post educational intervention, quality-improvement (QI) project in an urban academic cancer institution. Baseline telemetry usage was observed in 2,984 nonintensive inpatients in 21 hospital services over 6 months. Outcome measures were weekly telemetry usage in total minutes and cost savings based on a cost-predicted algorithm. Performance was compared between the intervention group and a control group for 3 months. Measures were compared using QI control charts and inferential statistics.

INTERVENTION: Three high-using telemetry services primarily staffed by certified nurse practitioners (CNPs) were provided with a telemetry education intervention. The intervention consisted of four ten-minute educational sessions over 2 weeks delivered to the highest three telemetry using services.

RESULTS: Forty-five providers received the educational intervention (78% CNPs and physician assistants [PAs] and 22% medical doctors [MDs]) and 272 did not (57% CNPs and PAs and 43% MDs). Only the educational intervention group showed measurable decreases shown by shifts in QI control charts. Decreased usage in the intervention group produced greater cost savings per patient when compared with the control group ($71.98 vs. $60.68), resulting in an estimated total annual cost savings of $94,740.

CONCLUSIONS: Educational interventions for inpatient CNPs that reinforce national policies for telemetry discontinuation improve practice efficiency and potentially decrease health care costs.

PMID:39115863 | DOI:10.1097/JXX.0000000000001062

JAMA Netw Open. 2024 Aug 1;7(8):e2421731. doi: 10.1001/jamanetworkopen.2024.21731.

ABSTRACT

IMPORTANCE: In March 2021, Berkeley, California, became the world’s first jurisdiction to implement a healthy checkout policy, which sets nutrition standards for foods and beverages in store checkouts. This healthy checkout ordinance (HCO) has the potential to improve customers’ dietary intake if stores comply by increasing the healthfulness of foods and beverages at checkouts.

OBJECTIVES: To compare the percentage of checkout products that were HCO compliant and that fell into healthy and unhealthy food and beverage categories before and 1 year after HCO implementation in Berkeley relative to comparison cities.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study in which Berkeley implemented an HCO and other cities did not, a difference-in-differences analysis was conducted of 76 258 product facings at checkouts of 23 stores in Berkeley and 75 stores in 3 comparison cities in California. Data were collected in February 2021 (approximately 1 month before implementation of the HCO) and 1 year later in February 2022 and analyzed from October 2023 to May 2024.

EXPOSURE: The HCO, which permits only the following products at checkouts in large food stores: nonfood and nonbeverage products, unsweetened beverages, and foods with 5 g or less of added sugars per serving and 200 mg or less of sodium per serving in the following categories: sugar-free gum and mints, fruit, vegetables, nuts, seeds, legumes, yogurt or cheese, and whole grains.

MAIN OUTCOMES AND MEASURES: A product facing’s (1) HCO compliance and (2) category, including healthy compliant categories and unhealthy noncompliant categories, determined using a validated photograph-based tool to assess product characteristics.

RESULTS: Of the 76 258 product facings at store checkouts, the percentage that were HCO compliant increased from 53% (4438 of 8425) to 83% (5966 of 7220) in Berkeley, a 63% increase relative to comparison cities (probability ratio [PR], 1.63; 95% CI, 1.41-1.87). The percentage of food and beverage checkout facings that were HCO compliant increased in Berkeley from 29% (1652 of 5639) to 62% (2007 of 3261), a 125% increase relative to comparison cities (PR, 2.25; 95% CI, 1.80-2.82). The percentage of Berkeley food and beverage facings consisting of candy, sugar-sweetened beverages, and other sweets significantly decreased (candy: from 30% [1687 of 5639] to 6% [197 of 3261]; PR, 0.21; 95% CI, 0.10-0.42; sugar-sweetened beverages: from 11% [596 of 5639] to 5% [157 of 3261]; PR, 0.41; 95% CI, 0.23-0.75; other sweets: from 7% [413 of 5639] to 3% [101 of 3261]; PR, 0.37; 95% CI, 0.15-0.88), while the percentage consisting of unsweetened beverages (from 4% [226 of 5639] to 19% [604 of 3261]; PR, 4.76; 95% CI, 2.54-8.91) and healthy foods (from 6% [350 of 5639] to 20% [663 of 3261]; PR, 2.90; 95% CI, 1.79-4.72) significantly increased.

CONCLUSIONS AND RELEVANCE: This cohort study of the first healthy checkout policy found substantial improvements in the healthfulness of food environments at checkouts 1 year after implementation of the policy. These results suggest that healthy checkout policies have the potential to improve the healthfulness of store checkouts.

PMID:39115848 | DOI:10.1001/jamanetworkopen.2024.21731

JAMA Netw Open. 2024 Aug 1;7(8):e2425593. doi: 10.1001/jamanetworkopen.2024.25593.

ABSTRACT

IMPORTANCE: Precise estimation of a patient’s drug metabolism capacity is important for antiseizure dose personalization.

OBJECTIVE: To quantify the differences in plasma concentrations for antiseizure drugs associated with variants of genes encoding drug metabolizing enzymes.

DATA SOURCES: PubMed, Clinicaltrialsregister.eu, ClinicalTrials.gov, International Clinical Trials Registry Platform, and CENTRAL databases were screened for studies from January 1, 1990, to September 30, 2023, without language restrictions.

STUDY SELECTION: Two reviewers performed independent study screening and assessed the following inclusion criteria: appropriate genotyping was performed, genotype-based categorization into subgroups was possible, and each subgroup contained at least 3 participants.

DATA EXTRACTION AND SYNTHESIS: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for data extraction and subsequent quality, validity, and risk-of-bias assessments. The results from the included studies were pooled with random-effect meta-analysis.

MAIN OUTCOMES AND MEASURES: Plasma concentrations of antiseizure drugs were quantified with the dose-normalized area under the concentration-time curve, the dose-normalized steady state concentration, or the concentrations after a single dose at standardized dose and sampling time. The ratio of the means was calculated by dividing the mean drug plasma concentrations of carriers and noncarriers of the pharmacogenetic variant.

RESULTS: Data from 98 studies involving 12 543 adult participants treated with phenytoin, valproate, lamotrigine, or carbamazepine were analyzed. Studies were mainly conducted within East Asian (69 studies) or White or European (15 studies) cohorts. Significant increases of plasma concentrations compared with the reference subgroup were observed for phenytoin, by 46% (95% CI, 33%-61%) in CYP2C9 intermediate metabolizers, 20% (95% CI, 17%-30%) in CYP2C19 intermediate metabolizers, and 39% (95% CI, 24%-56%) in CYP2C19 poor metabolizers; for valproate, by 12% (95% CI, 4%-20%) in CYP2C9 intermediate metabolizers, 12% (95% CI, 2%-24%) in CYP2C19 intermediate metabolizers, and 20% (95% CI, 2%-41%) in CYP2C19 poor metabolizers; and for carbamazepine, by 12% (95% CI, 3%-22%) in CYP3A5 poor metabolizers.

CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found that CYP2C9 and CYP2C19 genotypes encoding low enzymatic capacity were associated with a clinically relevant increase in phenytoin plasma concentrations, several pharmacogenetic variants were associated with statistically significant but only marginally clinically relevant changes in valproate and carbamazepine plasma concentrations, and numerous pharmacogenetic variants were not associated with statistically significant differences in plasma concentrations of antiseizure drugs.

PMID:39115847 | DOI:10.1001/jamanetworkopen.2024.25593

JAMA Netw Open. 2024 Aug 1;7(8):e2425987. doi: 10.1001/jamanetworkopen.2024.25987.

ABSTRACT

IMPORTANCE: Depression is a leading cause of disability. The timing and persistence of depression may be differentially associated with long-term mental health and psychosocial outcomes.

OBJECTIVE: To examine if depression symptoms during early and middle childhood and adolescence and persistent depression symptoms are associated with impaired young adult outcomes independent of early risk factors.

DESIGN, SETTING, AND PARTICIPANTS: Data for this prospective, longitudinal cohort study were from the Québec Longitudinal Study of Child Development, a representative population-based Canadian birth cohort. The cohort consists of infants born from October 1, 1997, to July 31, 1998. This is an ongoing study; data are collected annually or every 2 years and include those ages 5 months to 21 years. The end date for the data in this study was June 30, 2019, and data analyses were performed from October 4, 2022, to January 3, 2024.

EXPOSURES: Depression symptoms were assessed using maternal reports in early childhood (ages 1.5 to 6 years) from 1999 to 2004, teacher reports in middle childhood (ages 7 to 12 years) from 2005 to 2010, and self-reports in adolescence (ages 13 to 17 years) from 2011 to 2015.

MAIN OUTCOMES AND MEASURES: The primary outcome was depression symptoms at age 20 years, and secondary outcomes were indicators of psychosocial functioning (binge drinking; perceived stress; not being in education, employment, or training; social support; and experiencing online harrasment) at age 21 years. All outcomes were self-reported. Adult outcomes were reported by participants at ages 20 and 21 years from 2017 to 2019. Risk factors assessed when children were aged 5 months old were considered as covariates to assess the independent associations of childhood and adolescent depression symptoms with adult outcomes.

RESULTS: The cohort consisted of 2120 infants. The analytic sample size varied from 1118 to 1254 participants across outcomes (56.85% to 57.96% female). Concerning the primary outcome, adjusting for early risk factors and multiple testing, depression symptoms during adolescence were associated with higher levels of depression symptoms (β, 1.08 [95% CI, 0.84-1.32]; P < .001 unadjusted and Bonferroni adjusted) in young adulthood. Concerning the secondary outcomes, depression symptoms in adolescence were only associated with perceived stress (β, 3.63 [95% CI, 2.66-4.60]; P < .001 unadjusted and Bonferroni adjusted), while both middle-childhood (β, -1.58 [95% CI, -2.65 to -0.51]; P = .003 unadjusted and P < .001 Bonferroni adjusted) and adolescent (β, -1.97 [95% CI, -2.53 to -1.41]; P < .001 unadjusted and Bonferroni adjusted) depression symptoms were associated with lower levels of social support. There were no associations for binge drinking; not being in education, employment, or training; or experiencing online harrasment.

CONCLUSIONS AND RELEVANCE: In this cohort study of Canadian children and adolescents, childhood and adolescent depression symptoms were associated with impaired adult psychosocial functioning. Interventions should aim to screen and monitor children and adolescents for depression to inform policymaking regarding young adult mental health and psychosocial outcomes.

PMID:39115846 | DOI:10.1001/jamanetworkopen.2024.25987

JAMA Netw Open. 2024 Aug 1;7(8):e2426590. doi: 10.1001/jamanetworkopen.2024.26590.

ABSTRACT

IMPORTANCE: Traumatic brain injury (TBI), seizures, and dementia increase with age. There is a gap in understanding the associations of TBI, seizures, and medications such as antiseizure and antipsychotics with the progression of cognitive impairment across racial and ethnic groups.

OBJECTIVE: To investigate the association of TBI and seizures with the risk of cognitive impairment among cognitively normal older adults and the role of medications in moderating the association.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cohort study was a secondary analysis of the Uniform Data Set collected between June 1, 2005, and June 30, 2020, from the National Alzheimer’s Coordination Center. Statistical analysis was performed from February 1 to April 3, 2024. Data were collected from participants from 36 Alzheimer’s Disease Research Centers in the US who were 65 years or older at baseline, cognitively normal at baseline (Clinical Dementia Rating of 0 and no impairment based on a presumptive etiologic diagnosis of AD), and had complete information on race and ethnicity, age, sex, educational level, and apolipoprotein E genotype.

EXPOSURE: Health history of TBI, seizures, or both conditions.

MAIN OUTCOMES AND MEASURES: Progression to cognitive impairment measured by a Clinical Dementia Rating greater than 0.

RESULTS: Among the cohort of 7180 older adults (median age, 74 years [range, 65-102 years]; 4729 women [65.9%]), 1036 were African American or Black (14.4%), 21 were American Indian or Alaska Native (0.3%), 143 were Asian (2.0%), 332 were Hispanic (4.6%), and 5648 were non-Hispanic White (78.7%); the median educational level was 16.0 years (range, 1.0-29.0 years). After adjustment for selection basis using propensity score weighting, seizure was associated with a 40% higher risk of cognitive impairment (hazard ratio [HR], 1.40; 95% CI, 1.19-1.65), TBI with a 25% higher risk of cognitive impairment (HR, 1.25; 95% CI, 1.17-1.34), and both seizure and TBI were associated with a 57% higher risk (HR, 1.57; 95% CI, 1.23-2.01). The interaction models indicated that Hispanic participants with TBI and seizures had a higher risk of cognitive impairment compared with other racial and ethnic groups. The use of antiseizure medications (HR, 1.23; 95% CI, 0.99-1.53), antidepressants (HR, 1.32; 95% CI, 1.17-1.50), and antipsychotics (HR, 2.15; 95% CI, 1.18-3.89) was associated with a higher risk of cognitive impairment, while anxiolytic, sedative, or hypnotic use (HR, 0.88; 95% CI, 0.83-0.94) was associated with a lower risk.

CONCLUSIONS AND RELEVANCE: This study highlights the importance of addressing TBI and seizures as risk factors for cognitive impairment among older adults. Addressing the broader social determinants of health and bridging the health divide across various racial and ethnic groups are essential for the comprehensive management and prevention of dementia.

PMID:39115844 | DOI:10.1001/jamanetworkopen.2024.26590

JAMA Netw Open. 2024 Aug 1;7(8):e2426790. doi: 10.1001/jamanetworkopen.2024.26790.

ABSTRACT

IMPORTANCE: Climate change is a fundamental threat to human health, and industries, including health care, must assess their respective contribution to this crisis.

OBJECTIVE: To assess the change in knowledge of clinicians who completed a quality incentive program (QIP) measure on climate change and health care sustainability and to examine clinician attitudes toward climate change and their perception of clinical and individual relevance.

DESIGN, SETTING, AND PARTICIPANTS: The participants in this survey study included employed physicians and psychologists who were part of a hospital physician organization in an academic medical center (AMC) in Boston, Massachusetts. The hospital physician organization provides a QIP with different measures every 6 months and provides incentive payments on completion. The study is based on a survey of participants on completion of a QIP measure focused on climate change and health care sustainability offered from July 2023 through September 2023 at the AMC.

EXPOSURE: Structured educational video modules.

MAIN OUTCOMES AND MEASURES: After completion of the modules, the participants reported their baseline and postintervention knowledge on climate change impacts on health and health care sustainability, perceived relevance of the material, and attitudes toward the modules using 5-point Likert scales and free-text comments. Data were analyzed using univariate and multivariable analyses including participant age, gender, and practice specialty.

RESULTS: Of the 2559 eligible clinicians, 2417 (94.5%) (mean [SD] age, 48.9 [11.5] years; range, 29-85 years; 1244 males [51.5%]) participated in the measure and completed the survey. Among these participants, 1767 (73.1%) thought the modules were relevant or very relevant to their lives and 1580 (65.4%) found the modules relevant or very relevant to their clinical practice. Age was not associated with responses. Practitioners in specialties classified as climate facing were more likely to think that the education was relevant to their clinical practice compared with those in non-climate-facing specialties (mean [SD] score, 3.76 [1.19] vs 3.61 [1.26]; P = .005). Practitioners identifying as female were also more likely to consider this education as relevant to their clinical practice compared with male practitioners (mean [SD] score, 3.82 [1.17] vs 3.56 [1.27]; P < .001).

CONCLUSIONS AND RELEVANCE: In this survey study, a high proportion of clinicians expressed positive attitudes toward education in climate change and health and health care sustainability, with some demographic and specialty variability. These data support that climate and health education in AMCs provides information that practitioners see as relevant and important.

PMID:39115843 | DOI:10.1001/jamanetworkopen.2024.26790

JAMA Netw Open. 2024 Aug 1;7(8):e2426795. doi: 10.1001/jamanetworkopen.2024.26795.

ABSTRACT

IMPORTANCE: Evidence on the association of early intervention services (EISs) with self-harm and suicide among patients with first-episode schizophrenia (FES) at older than 25 years is lacking.

OBJECTIVE: To examine changes in self-harm and suicide rates among patients with FES before and after the implementation of an EIS program.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study conducted among 37 040 patients aged 15 to 64 years with FES between January 1, 2001, and March 31, 2020, used electronic medical records from the Hong Kong Clinical Data Analysis and Reporting System. All patients were followed up from the first diagnosis of schizophrenia (the index date) until the date of their death or the end of the study period (March 31, 2021), whichever came first. Statistical analysis was performed from July to November 2023.

EXPOSURE: The EIS extended the Early Assessment Service for Young People With Early Psychosis (EASY) program from patients aged 15 to 25 years to those aged 15 to 64 years (EASY Plus). The exposure was the implementation of the EASY Plus program in April 2011. The exposure period was defined as between April 2012 and March 2021 for the 1-year-time-lag analysis.

MAIN OUTCOMES AND MEASURES: The outcomes were monthly rates of self-harm and suicide among patients with FES before and after the implementation of the EASY Plus program. Interrupted time series analysis was used for the main analysis.

RESULTS: This study included 37 040 patients with FES (mean [SD] age at onset, 39 [12] years; 82.6% older than 25 years; 53.0% female patients). The 1-year-time-lag analysis found an immediate decrease in self-harm rates among patients aged 26 to 44 years (rate ratio [RR], 0.77 [95% CI, 0.59-1.00]) and 45 to 64 years (RR, 0.70 [95% CI, 0.49-1.00]) and among male patients (RR, 0.71 [95% CI, 0.56-0.91]). A significant long-term decrease in self-harm rates was found for all patients with FES (patients aged 15-25 years: RR, 0.98 [95% CI, 0.97-1.00]; patients aged 26-44 years: RR, 0.98 [95% CI, 0.97-0.99]; patients aged 45-64 years: RR, 0.97 [95% CI, 0.96-0.98]). Suicide rates decreased immediately after the implementation of the EASY Plus program among patients aged 15 to 25 years (RR, 0.33 [95% CI, 0.14-0.77]) and 26 to 44 years (RR, 0.38 [95% CI, 0.20-0.73]). Compared with the counterfactual scenario, the EASY Plus program might have led to 6302 fewer self-harm episodes among patients aged 26 to 44 years.

CONCLUSIONS AND RELEVANCE: This cohort study of the EASY Plus program suggests that the extended EIS was associated with reduced self-harm and suicide rates among all patients with FES, including those older than 25 years. These findings emphasize the importance of developing tailored interventions for patients across all age ranges to maximize the benefits of EISs.

PMID:39115842 | DOI:10.1001/jamanetworkopen.2024.26795