Importance: Prior studies associate late-life community disadvantage with worse brain health. It is relatively unknown if childhood community disadvantage associates with late-life brain health.
Objective: To test associations between childhood residence in an economically disadvantaged community, individual income and education, and late-life cortical brain volumes and white matter integrity.
Design, setting, and participants: This cohort study was conducted in the ongoing harmonized cohorts KHANDLE (Kaiser Healthy Aging and Diverse Life Experiences Study; initiated 2017) and STAR (Study of Healthy Aging in African Americans; initiated 2018) using all available data collected out of a regional integrated health care delivery network in California between cohort initiation and analysis initiation in June 2023. Eligible participants were Kaiser Permanente Northern California member ages 65 years or older. Data were analyzed between June and November 2023.
Exposure: Residence at birth was geocoded and linked to historical Area Deprivation Indices (ADI). ADI is a nationally ranked percentile; community disadvantage was defined as ADI of 80 or higher.
Main outcomes and measures: Regional brain volumes and white matter integrity measures were derived from a random subset of participants who underwent 3T magnetic resonance imaging. Models adjusted for race and ethnicity, sex, and parental education.
Results: Of a total 2161 individuals in the combined cohort, 443 individuals were eligible for imaging (mean [SD] age, 76.3 [6.5] years; 253 female [57.1%]; 56 Asian [12.6%], 212 Black [47.9%], 67 Latino [15.1%], 109 White [24.6%]). Imaging participants had a mean (SD) 15.0 (2.5) years of education, and 183 (41.3%) earned $55 000 to $99 999 annually. Fifty-four participants (12.2%) resided in a disadvantaged childhood community. Childhood community disadvantage was associated with smaller gray matter volumes overall (-0.39 cm3; 95% CI, -0.65 to -0.10 cm3) and in the cerebellum (-0.39 cm3; 95% CI, -0.66 to -0.09 cm3), hippocampus (-0.37 cm3; 95% CI, -0.68 to -0.04 cm3), and parietal cortex (-0.25 cm3; 95% CI, -0.46 to -0.04 cm3) and larger mean lateral ventricle (0.44 cm3; 95% CI, 0.12 to 0.74 cm3), third ventricle (0.28 cm3; 95% CI, 0.03 to 0.55 cm3), and white matter hyperintensity volume (0.31 cm3; 95% CI, 0.06 to 0.56 cm3). Educational attainment and late-life income did not mediate these associations.
Conclusions and relevance: In this cohort study of racially and ethnically diverse health plan members, childhood community disadvantage was associated with worse late-life brain health independent of individual socioeconomic status. Future work should explore alternative pathways (eg, cardiovascular health) that may explain observed associations.
Importance: Barriers to divorce and reproductive health care can threaten the health and safety of pregnant and recently pregnant females.
Objective: To examine state laws about divorce, reproductive health care (access to contraception, family planning services, and abortion), and pregnancy-associated homicide rates in US states over a 4-year period (2018-2021).
Design, setting, and participants: In this cross-sectional study, bivariate tests and regressions were used to analyze crude rates of pregnancy-associated homicide from the National Violent Death Reporting System in 181 state-years for calendar years 2018 to 2021, with analyses conducted on September 8, 2024.
Exposures: Access to divorce while pregnant and reproductive health care over a 4-year period in the US.
Main outcomes and measures: Primary outcomes (pregnancy-associated homicide by intimate partners vs non-intimate partners and rates among younger Black, Hispanic, and White females) were assessed using the National Violent Death Reporting System. Negative binomial regression was used to test 2 hypotheses: access to divorce while pregnant and reproductive health care are associated with pregnancy-associated homicide rates.
Results: Individual level data, including exact sample size, were not available in this study of state-level homicide rates. Negative binomial regression analysis showed that, where finalizing divorce during pregnancy is prohibited, intimate partner homicide rates (incidence rate ratio [IRR], 2.11; 95% CI, 1.09-4.08; P = .03) and rates among younger (age 10-24 years) White females (IRR, 2.39; 95% CI, 1.12-5.09; P = .02) were significantly higher. In state-years with greater access to reproductive health care, rates were significantly lower for non-intimate partner homicide (IRR, 0.92; 95% CI, 0.87-0.98; P = .01) and for younger Black females (IRR, 0.91; 95% CI, 0.87-0.96; P < .001) and younger Hispanic females (IRR, 0.87; 95% CI, 0.79-0.96; P = .007).
Conclusions and relevance: In this cross-sectional study of pregnancy-associated homicide rates, barriers to divorce were associated with higher homicide rates and access to reproductive health care was associated with lower homicide rates. This study highlights the association between state legislation and pregnancy-associated homicide in the US, which is important information for policymakers.
Importance: Viloxazine is a novel nonstimulant medication approved for the treatment of attention-deficit/hyperactivity disorder (ADHD).
Objectives: To investigate the whether viloxazine is associated with effective and acceptable outcomes when treating children and adolescents with ADHD and to evaluate these outcomes' associations with viloxazine doses and duration of treatment.
Data sources: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, PsycINFO, and ClinicalTrial.gov databases were searched from database inception to June 23, 2024.
Study selection: Two reviewers independently screened for double-blind, fixed-dose randomized clinical trials (RCTs) that compared viloxazine with placebo for pediatric patients with ADHD.
Data extraction and synthesis: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. Data extraction was completed independently by 2 authors and cross-checked for errors. Random-effects pairwise and dose-response meta-analyses were conducted.
Main outcomes and measures: The primary outcome was the improvement of ADHD symptoms (measured by ADHD Rating Scale-5), and the secondary outcomes were all-cause discontinuation, dropout due to adverse effects, and serious adverse effects.
Results: A total of 5 dose-response RCTs were included, with 1560 participants (1011 [64.8%] male; mean [SD] age, 10.6 [6.7] years). Viloxazine was associated with better outcomes in ADHD treatment compared with placebo (mean difference, 5.47 points; 95% CI, 4.03-6.91 points). The dose-response curve was bell-shaped, suggesting that doses greater than 400 mg or greater than 7 mg/kg might not be associated with more efficacy. The temporal trends analysis showed ascent curves tapering off at approximately weeks 4 to 6. The curve for 100 mg/d declined more rapidly, while the curves for 200 mg/d and 400 mg/d declined more gradually. The overall discontinuation rate due to adverse effects was 4.15% in the viloxazine group (45 of 1084), while viloxazine compared with placebo was associated with 2.48-fold higher risk of discontinuation due to adverse effects (risk ratio, 2.48; 95% CI, 1.26-4.88).
Conclusions and relevance: In this meta-analysis, viloxazine was associated with better efficacy in treating children and adolescents with ADHD than placebo. A moderate dose (200-400 mg or 6-8 mg/kg) may provide optimal treatment outcomes. Future studies are warranted to assess the long-term effect of viloxazine. Viloxazine was relatively well tolerated for children and adolescents with ADHD.
Importance: The increased use of gabapentinoids has been most pronounced in older people who are also susceptible to hip fractures.
Objective: To investigate the overall association between gabapentinoids and the risk of hip fractures and the stratified association across age groups, frailty status, and history of chronic kidney disease.
Design, setting, and participants: This was a case-case-time-control study in patients hospitalized for hip fracture in Victoria, Australia, between March 1, 2013, and June 30, 2018, with at least 1 prescription for a gabapentinoid before fracture. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% CI for gabapentinoid dispensing in the index (1-60 days prefracture) compared with the reference (121-180 days prefracture) period. To adjust for the underlying time trend in gabapentinoid use, each index case was matched with up to 5 controls, selected from future cases of the same age and sex. Subgroup analyses were conducted in subgroups with or without chronic kidney disease (CKD), frailty scores less than 5, and frailty scores 5 and above. Frailty was computed using the Hospital Frailty Risk Score (HFRS). Data were analyzed from November 2023 to April 2024.
Exposure: Gabapentinoids (pregabalin or gabapentin).
Main outcome and measure: Hip fracture.
Results: Of 28 293 patients hospitalized for hip fractures, 2946 (1752 [59.5%] aged ≥80 years; 2099 [71.2%] female) were dispensed a gabapentinoid before hip fracture. Gabapentinoid dispensing was associated with increased odds of hip fractures (OR, 1.96; 95% CI, 1.66-2.32). After adjusting for the exposure-time trend and concomitant use of other central nervous system medications, the odds of hip fractures remained elevated (OR, 1.30; 95% CI, 1.07-1.57). The association between gabapentinoid dispensing and hip fracture was higher in patients with HFRS 5 and above (OR, 1.75; 95% CI, 1.31-2.33) and CKD (OR, 2.41; 95% CI, 1.65-3.52).
Conclusions and relevance: In this case-case-time-control study of Australian residents hospitalized for hip fracture, gabapentinoid use was associated with an increased risk of hip fractures, especially in patients who were frail or had chronic kidney disease. In addition to the known risk associated with kidney impairment, frailty status may be an important risk factor when considering use of gabapentinoids.
Importance: Ultrasonography-guided nerve blocks (UGNBs) have become a core component of multimodal analgesia for acute pain management in the emergency department (ED). Despite their growing use, national adoption of UGNBs has been slow due to a lack of procedural safety in the ED.
Objective: To assess the complication rates and patient pain scores of UGNBs performed in the ED.
Design, setting, and participants: This cohort study included data from the National Ultrasound-Guided Nerve Block Registry, a retrospective multicenter observational registry encompassing procedures performed in 11 EDs in the US from January 1, 2022, to December 31, 2023, of adult patients who underwent a UGNB.
Exposure: UGNB encounters.
Main outcomes and measures: The primary outcome of this study was complication rates associated with ED-performed UGNBs recorded in the National Ultrasound-Guided Nerve Block Registry from January 1, 2022, to December 31, 2023. The secondary outcome was patient pain scores of ED-based UGNBs. Data for all adult patients who underwent an ED-based UGNB at each site were recorded. The volume of UGNB at each site, as well as procedural outcomes (including complications), were recorded. Data were analyzed using descriptive statistics of all variables.
Results: In total, 2735 UGNB encounters among adult patients (median age, 62 years [IQR, 41-77 years]; 51.6% male) across 11 EDs nationwide were analyzed. Fascia iliaca blocks were the most commonly performed UGNBs (975 of 2742 blocks [35.6%]). Complications occurred at a rate of 0.4% (10 of 2735 blocks). One episode of local anesthetic systemic toxicity requiring an intralipid was reported. Overall, 1320 of 1864 patients (70.8%) experienced 51% to 100% pain relief following UGNBs. Operator training level varied, although 1953 of 2733 procedures (71.5%) were performed by resident physicians.
Conclusions and relevance: The findings of this cohort study of 2735 UGNB encounters support the safety of UGNBs in ED settings and suggest an association with improvement in patient pain scores. Broader implementation of UGNBs in ED settings may have important implications as key elements of multimodal analgesia strategies to reduce opioid use and improve patient care.
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