Reproductive characteristics, menopausal status, race and ethnicity, and risk of breast cancer subtypes defined by ER, PR and HER2 status: the Breast Cancer Etiology in Minorities study.

BACKGROUND: Associations between reproductive factors and risk of breast cancer differ by subtype defined by joint estrogen receptor (ER), progesterone receptor (PR), and HER2 expression status. Racial and ethnic differences in the incidence of breast cancer subtypes suggest etiologic heterogeneity, yet data are limited because most studies have included non-Hispanic White women only. METHODS: We analyzed harmonized data for 2,794 breast cancer cases and 4,579 controls, of whom 90% self-identified as African American, Asian American or Hispanic. Questionnaire data were pooled from three population-based studies conducted in California and data on tumor characteristics were obtained from the California Cancer Registry. The study sample included 1,530 luminal A (ER-positive and/or PR-positive, HER2-negative), 442 luminal B (ER-positive and/or PR-positive, HER2-positive), 578 triple-negative (TN; ER-negative, PR-negative, HER2-negative), and 244 HER2-enriched (ER-negative, PR-negative, HER2-positive) cases. We used multivariable unconditional logistic regression models to estimate subtype-specific ORs and 95% confidence intervals associated with parity, breast-feeding, and other reproductive characteristics by menopausal status and race and ethnicity. RESULTS: Subtype-specific associations with reproductive factors revealed some notable differences by menopausal status and race and ethnicity. Specifically, higher parity without breast-feeding was associated with higher risk of luminal A and TN subtypes among premenopausal African American women. In contrast, among Asian American and Hispanic women, regardless of menopausal status, higher parity with a breast-feeding history was associated with lower risk of luminal A subtype. Among premenopausal women only, luminal A subtype was associated with older age at first full-term pregnancy (FTP), longer interval between menarche and first FTP, and shorter interval since last FTP, with similar OR estimates across the three racial and ethnic groups. CONCLUSIONS: Subtype-specific associations with reproductive factors overall and by menopausal status, and race and ethnicity, showed some differences, underscoring that understanding etiologic heterogeneity in racially and ethnically diverse study samples is essential. Breast-feeding is likely the only reproductive factor that is potentially modifiable. Targeted efforts to promote and facilitate breast-feeding could help mitigate the adverse effects of higher parity among premenopausal African American women.

Population-Level Identification of Patients With Lynch Syndrome for Clinical Care, Quality Improvement, and Research.

PURPOSE: Identification of those at risk of hereditary cancer syndromes using electronic health record (EHR) data sources is important for clinical care, quality improvement, and research. We describe diagnostic processes, previously seldom reported, for a common hereditary cancer syndrome, Lynch syndrome (LS), using EHR data within a community-based, multicenter, demographically diverse health system. METHODS: Within a retrospective cohort enrolled between 2015 and 2020 at Kaiser Permanente Northern California, we assessed electronic diagnostic domains for LS including (1) family history of LS-associated cancer; (2) personal history of LS-associated cancer; (3) LS screening via mismatch repair deficiency (MMRD) testing of newly diagnosed malignancy; (4) germline genetic test results; and (5) clinician-entered diagnostic codes for LS. We calculated proportions and overlap for each diagnostic domain descriptively. RESULTS: Among 5.8 million individuals, (1) 28,492 (0.49%) had a family history of LS-associated cancer of whom 3,635 (13%) underwent genetic testing; (2) 100,046 (1.7%) had a personal history of a LS-associated cancer; and (3) 8,711 (0.1%) were diagnosed with colorectal cancer of whom 7,533 (86%) underwent MMRD screening and of the positive screens (486), 130 (27%) underwent germline testing. One thousand seven hundred and fifty-seven (0.03%) were diagnosed with endometrial cancer of whom 1,613 (92%) underwent MMRD screening and of the 195 who screened positive, 55 (28%) underwent genetic testing. (4) 30,790 (0.05%) had LS germline genetic testing with 707 (0.01%) testing positive; and (5) 1,273 (0.02%) had a clinician-entered diagnosis of LS. CONCLUSION: It is feasible to electronically characterize the diagnostic processes of LS. No single data source comprehensively identifies all LS carriers. There is underutilization of LS genetic testing for those eligible and underdiagnosis of LS. Our work informs similar efforts in other settings for hereditary cancer syndromes.

Assessing the association between antibody status and symptoms of long COVID: A multisite study.

The association between SARS-CoV-2 humoral immunity and post-acute sequelae of COVID-19 (long COVID) remains uncertain. The objective of this population-based cohort study was to assess the association between SARS-CoV-2 seropositivity and symptoms consistent with long COVID. English and Spanish-speaking members ≥ 18 years old with SARS-CoV-2 serologic testing conducted prior to August 2021 were recruited from Kaiser Permanente Southern California and Kaiser Permanente Colorado. Between November 2021 and April 2022, participants completed a survey assessing symptoms, physical health, mental health, and cognitive function consistent with long COVID. Survey results were linked to SARS-CoV-2 antibody (Ab) and viral (RNA) lab results in electronic health records. Weighted descriptive analyses were generated for five mutually exclusive patient groups: (1) +Ab/+RNA; (2) +Ab/- or missing RNA; (3) -Ab/+RNA; (4a) -Ab/-RNA reporting no prior infection; and (4b) -Ab/-RNA reporting prior infection. The proportions reporting symptoms between the +Ab/+RNA and -Ab/+RNA groups were compared, adjusted for covariates. Among 3,946 participants, the mean age was 52.1 years old (SD 15.6), 68.3% were female, 28.4% were Hispanic, and the serologic testing occurred a median of 15 months prior (IQR = 12-18). Three quarters (74.5%) reported having had COVID-19. Among people with laboratory-confirmed COVID-19, there was no association between antibody positivity (+Ab/+RNA vs. -Ab/+RNA) and any symptoms, physical health, mental health, or cognitive function. As expected, physical health, cognitive function, and fatigue were worse, and palpitations and headaches limiting the ability to work were more prevalent among people with laboratory-confirmed prior infection and positive serology (+Ab/+RNA) compared to those without reported or confirmed prior infection and negative serology (-Ab/-RNA/no reported COVID-19). Among people with laboratory-confirmed COVID-19, SARS-CoV-2 serology from practice settings were not associated with long COVID symptoms and health status suggesting limited utility of serology testing for long COVID.

Sleep Problems and Health Outcomes Among Urban American Indian and Alaska Native Adolescents.

Importance: Adolescent sleep problems are prevalent, particularly among racial and ethnic minority groups, and can increase morbidity. Despite the numerous strengths of their racial and ethnic group, urban American Indian and Alaska Native adolescents face significant health disparities but are rarely included in health research. Understanding how sleep problems are associated with health outcomes among American Indian and Alaska Native adolescents may elucidate novel targets for interventions to promote health equity. Objective: To assess whether baseline sleep problems are associated with changes in behavioral and cardiometabolic health outcomes among urban American Indian and Alaska Native adolescents 2 years later. Design, Setting, and Participants: American Indian and Alaska Native adolescents were recruited via flyers and community events for an observational cohort study in California. Baseline assessments were conducted among 142 adolescents from March 1, 2018, to March 31, 2020, and follow-ups were conducted among 114 adolescents from December 1, 2020, to June 30, 2022. Exposures: Baseline actigraphy-assessed sleep duration and efficiency and self-reported sleep disturbances and social jet lag (absolute value of the difference in sleep midpoint on weekends vs weekdays; indicator of circadian misalignment). Main Outcomes and Measures: Main outcome measures included self-reported depression (measured using the Patient Health Questionnaire), anxiety (measured using the Generalized Anxiety Disorder 7-item scale), past year alcohol and cannabis use, body mass index, systolic blood pressure (SBP) and diastolic blood pressure (DBP), waist circumference, and glycosylated hemoglobin (HbA1c). Analyses examined whether baseline sleep was associated with health outcomes at follow-up, controlling for age, sex, and baseline outcome measures. Results: The baseline sample included 142 urban American Indian and Alaska Native adolescents (mean [SD] age, 14.0 [1.4] years; 84 girls [59%]), 80% of whom (n = 114; mean [SD] age, 14.1 [1.3] years; 71 girls [62%]) completed follow-ups. Linear or logistic regressions showed significant negative associations between shorter sleep duration and depression (ß = -1.21 [95% CI, -2.19 to -0.24]), anxiety (ß = -0.89 [95% CI, -1.76 to -0.03]), DBP (ß = -2.03 [95% CI, -3.79 to -0.28]), and HbA1c level (ß = -0.15 [95% CI, -0.26 to -0.04]) and likelihood of alcohol (odds ratio [OR], 0.57 [95% CI, 0.36-0.91]) and cannabis use (full week: OR, 0.59 [95% CI, 0.35-0.99]) at follow-up. Greater social jet lag was associated with significantly higher SBP (ß = 0.06 [95% CI, 0.01-0.11]) at follow-up. Conclusions and Relevance: This cohort study found significant associations between poor sleep and adverse changes in health outcomes. Findings highlight the importance of developing culturally responsive interventions that target sleep as a key modifiable risk factor to improve the health of American Indian and Alaska Native adolescents.

Risk Factors for Hydroxychloroquine Retinopathy and Its Subtypes.

Importance: The major toxic effect of hydroxychloroquine is retinopathy. Thus, current guidelines recommend limiting the dose and screening annually for retinopathy among all long-term users, but individual patient factors may be associated with retinopathy risk. Objective: To identify risk factors beyond hydroxychloroquine dose and duration of use for hydroxychloroquine retinopathy. Design, Setting, and Participants: This cohort study of 4677 patients in the Kaiser Permanente Northern California integrated health network who initiated hydroxychloroquine, continued treatment, and underwent retinopathy screening after 5 years of use was conducted from July 1, 1997, to December 31, 2020, with up to 15 years of follow-up. Statistical analysis was performed in August 2023. Exposure: Candidate risk factors included age at hydroxychloroquine initiation, sex, race and ethnicity, indications, chronic kidney disease (CKD), liver disease, diabetes, tamoxifen use, and medications that interact with hydroxychloroquine metabolism. Hydroxychloroquine dose was assessed from pharmacy dispensing records. Main Outcome and Measures: Incident hydroxychloroquine retinopathy was adjudicated from masked review of guideline-recommended screening studies and classified as parafoveal or pericentral pattern. Multivariable Cox proportional hazards regression was used to assess potential risk factors for hydroxychloroquine retinopathy within 15 years of initiation. Results: Of 4677 long-term hydroxychloroquine users (mean [SD] age at initiation, 52.4 [14.1] years; 3877 women [82.9%]), 125 patients developed hydroxychloroquine retinopathy within 15 years (102 parafoveal, 23 pericentral). Older age at time of hydroxychloroquine initiation was associated with retinopathy risk, with adjusted hazard ratios (HRs) of 2.48 (95% CI, 1.28-4.78) for those aged 45 to 54 years, 3.82 (95% CI, 2.05-7.14) for those aged 55 to 64 years, and 5.68 (95% CI, 2.99-10.79) for those aged 65 years or older compared with those younger than 45 years. The risk of retinopathy was higher among females than males (HR, 3.83 [95% CI, 1.86-7.89]), among patients with CKD stage 3 or greater (HR, 1.95 [95% CI, 1.25-3.04]), and among individuals with tamoxifen use (HR, 3.43 [95% CI, 1.08-10.89]). The likelihood of pericentral retinopathy was higher among Asian patients (HR, 15.02 [95% CI, 4.82-46.87]) and Black patients (HR, 5.51 [95% CI, 1.22-24.97]) compared with non-Hispanic White patients. Conclusions and Relevance: This study suggests that increasing age, female sex, CKD stage 3 or greater, and tamoxifen use were associated with a higher risk of hydroxychloroquine retinopathy, whereas being younger than 45 years at hydroxychloroquine initiation and male sex were associated with a lower risk. Race and ethnicity were also associated with the pattern of retinopathy. These factors should be incorporated into hydroxychloroquine dosing decisions.

California's COVID-19 Vaccine Equity Policy: Cases, Hospitalizations, And Deaths Averted In Affected Communities.

In March 2021, California implemented a vaccine equity policy that prioritized COVID-19 vaccine allocation to communities identified as least advantaged by an area-based socioeconomic measure, the Healthy Places Index. We conducted quasi-experimental and counterfactual analyses to estimate the effect of this policy on COVID-19 vaccination, case, hospitalization, and death rates. Among prioritized communities, vaccination rates increased 28.4 percent after policy implementation. Furthermore, an estimated 160,892 COVID-19 cases, 10,248 hospitalizations, and 679 deaths in the least-advantaged communities were averted by the policy. Despite these improvements, the share of COVID-19 cases, hospitalizations, and deaths in prioritized communities remained elevated. These estimates were robust in sensitivity analyses that tested exchangeability between prioritized communities and those not prioritized by the policy; model specifications; and potential temporal confounders, including prior infections. Correcting for disparities by strategically allocating limited resources to the least-advantaged or most-affected communities can reduce the impacts of COVID-19 and other diseases but might not eliminate health disparities.

CalScope: methodology and lessons learned for conducting a remote statewide SARS-CoV-2 seroprevalence study in California using an at-home dried blood spot collection kit and online survey.

BACKGROUND: To describe the methodology for conducting the CalScope study, a remote, population-based survey launched by the California Department of Public Health (CDPH) to estimate SARS-CoV-2 seroprevalence and understand COVID-19 disease burden in California. METHODS: Between April 2021 and August 2022, 666,857 randomly selected households were invited by mail to complete an online survey and at-home test kit for up to one adult and one child. A gift card was given for each completed survey and test kit. Multiple customized REDCap databases were used to create a data system which provided task automation and scalable data management through API integrations. Support infrastructure was developed to manage follow-up for participant questions and a communications plan was used for outreach through local partners. RESULTS: Across 3 waves, 32,671 out of 666,857 (4.9%) households registered, 6.3% by phone using an interactive voice response (IVR) system and 95.7% in English. Overall, 25,488 (78.0%) households completed surveys, while 23,396 (71.6%) households returned blood samples for testing. Support requests (n = 5,807) received through the web-based form (36.3%), by email (34.1%), and voicemail (29.7%) were mostly concerned with the test kit (31.6%), test result (26.8%), and gift card (21.3%). CONCLUSIONS: Ensuring a well-integrated and scalable data system, responsive support infrastructure for participant follow-up, and appropriate academic and local health department partnerships for study management and communication allowed for successful rollout of a large population-based survey. Remote data collection utilizing online surveys and at-home test kits can complement routine surveillance data for a state health department.

Positive psychosocial factors may protect against perceived stress in people with systemic lupus erythematosus with and without trauma history.

OBJECTIVE: Trauma history is associated with SLE onset and worse patient-reported outcomes; perceived stress is associated with greater SLE disease activity. Stress perceptions vary in response to life events and may be influenced by psychosocial factors. In an SLE cohort, we examined whether stressful events associated with perceived stress, whether psychosocial factors affected perceived stress, and whether these relationships varied by prior trauma exposure. METHODS: This is a cross-sectional analysis of data from the California Lupus Epidemiology Study, an adult SLE cohort. Multivariable linear regression analyses controlling for age, gender, educational attainment, income, SLE damage, comorbid conditions, glucocorticoids ≥7.5 mg/day and depression examined associations of recent stressful events (Life Events Inventory) and positive (resilience, self-efficacy, emotional support) and negative (social isolation) psychosocial factors with perceived stress. Analyses were stratified by lifetime trauma history (Brief Trauma Questionnaire (BTQ)) and by adverse childhood experiences (ACEs) in a subset. RESULTS: Among 242 individuals with SLE, a greater number of recent stressful events was associated with greater perceived stress (beta (95% CI)=0.20 (0.07 to 0.33), p=0.003). Positive psychosocial factor score representing resilience, self-efficacy and emotional support was associated with lower perceived stress when accounting for number of stressful events (-0.67 (-0.94 to -0.40), p<0.0001); social isolation was associated with higher stress (0.20 (0.14 to 0.25), p<0.0001). In analyses stratified by BTQ trauma and ACEs, associations of psychosocial factors and perceived stress were similar between groups. However, the number of recent stressful events was significantly associated with perceived stress only for people with BTQ trauma (0.17 (0.05 to 0.29), p=0.0077) and ACEs (0.37 (0.15 to 0.58), p=0.0011). CONCLUSION: Enhancing positive and lessening negative psychosocial factors may mitigate deleterious perceived stress, which may improve outcomes in SLE, even among individuals with a history of prior trauma who may be more vulnerable to recent stressful events.

Racial and Ethnic Disparities in the Incidence of Anti-NMDA Receptor Encephalitis.

OBJECTIVES: To estimate the incidence of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHODS: We conducted a retrospective cohort study of >10 million person-years of observation from members of Kaiser Permanente Southern California, 2011-2022. The electronic health record of individuals with text-string mention of NMDA and encephalitis were reviewed to identify persons who met diagnostic criteria for anti-NMDAR encephalitis. Age-standardized and sex-standardized incidences stratified by race and ethnicity were estimated according to the 2020 US Census population. RESULTS: We identified 70 patients who met diagnostic criteria for anti-NMDAR encephalitis. The median age at onset was 23.7 years (IQR = 14.2-31.0 years), and 45 (64%) were female patients. The age-standardized and sex-standardized incidence of anti-NMDAR encephalitis per 1 million person-years was significantly higher in Black (2.94, 95% CI 1.27-4.61), Hispanic (2.17, 95% CI 1.51-2.83), and Asian/Pacific Island persons (2.02, 95% CI 0.77-3.28) compared with White persons (0.40, 95% CI 0.08-0.72). Ovarian teratomas were found in 58.3% of Black female individuals and 10%-28.6% in other groups. DISCUSSION: Anti-NMDA receptor encephalitis disproportionately affected Black, Hispanic, or Asian/Pacific Island persons. Ovarian teratomas were a particularly common trigger in Black female individuals. Future research should seek to identify environmental and biological risk factors that disproportionately affect minoritized individuals residing in the United States.

Relative Cost and Infectious Days Averted Associated With Rapid Gonorrhea and Chlamydia Testing Among Men Who Have Sex With Men.

BACKGROUND: Standard-of-care nucleic acid amplification tests (routine NAATs) for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) can take several days to result and therefore delay treatment. Rapid point-of-care GC/CT NAAT (rapid NAAT) could reduce the time to treatment and therefore onward transmission. This study evaluated the incremental cost per infectious day averted and overall cost of implementation associated with rapid compared with routine NAAT. METHODS: Prospective sexually transmitted infection (STI) treatment data from men who have sex with men and transgender women in San Diego who received rapid NAAT between November 2018 and February 2021 were evaluated. Historical time from testing to treatment for routine NAAT was abstracted from the literature. Costs per test for rapid and routine NAAT were calculated using a micro-costing approach. The incremental cost per infectious day averted comparing rapid to routine NAAT and the costs of rapid GC/CT NAAT implementation in San Diego Public Health STI clinics were calculated. RESULTS: Overall, 2333 individuals underwent rapid NAAT with a median time from sample collection to treatment of 2 days compared with 7 to 14 days for routine NAAT equating to a reduction of 5 to 12 days. The cost of rapid and routine GC/CT NAAT was $57.86 and $18.38 per test, respectively, with a cost-effectiveness of between $2.43 and $5.82 per infectious day averted. The incremental cost of rapid NAAT improved when at least 2000 tests were performed annually. CONCLUSIONS: Although rapid GC/CT NAAT is more expensive than routine testing, the reduction of infectious days between testing and treatment may reduce transmission and provide improved STI treatment services to patients.

Water Fluoridation and Birth Outcomes in California.

BACKGROUND: There is a lack of research on the relationship between water fluoridation and pregnancy outcomes. OBJECTIVES: We assessed whether hypothetical interventions to reduce fluoride levels would improve birth outcomes in California. METHODS: We linked California birth records from 2000 to 2018 to annual average fluoride levels by community water system. Fluoride levels were collected from consumer confidence reports using publicly available data and public record requests. We estimated the effects of a hypothetical intervention reducing water fluoride levels to 0.7 ppm (the current level recommended by the US Department of Health and Human Services) and 0.5 ppm (below the current recommendation) on birth weight, birth-weight-for-gestational age z-scores, gestational age, preterm birth, small-for-gestational age, large-for-gestational age, and macrosomia using linear regression with natural cubic splines and G-computation. Inference was calculated using a clustered bootstrap with Wald-type confidence intervals. We evaluated race/ethnicity, health insurance type, fetal sex, and arsenic levels as potential effect modifiers. RESULTS: Fluoride levels ranged from 0 to 2.5 ppm, with a median of 0.51 ppm. There was a small negative association on birth weight with the hypothetical intervention to reduce fluoride levels to 0.7 ppm [-2.2g; 95% confidence interval (CI): -4.4, 0.0] and to 0.5 ppm (-5.8g; 95% CI: -10.0, -1.6). There were small negative associations with birth-weight-for-gestational-age z-scores for both hypothetical interventions (0.7 ppm: -0.004; 95% CI: -0.007, 0.000 and 0.5 ppm: -0.006; 95% CI: -0.013, 0.000). We also observed small negative associations for risk of large-for-gestational age for both the hypothetical interventions to 0.7 ppm [risk difference (RD)=-0.001; 95% CI: -0.002, 0.000 and 0.5 ppm (-0.001; 95% CI: -0.003, 0.000)]. We did not observe any associations with preterm birth or with being small for gestational age for either hypothetical intervention. We did not observe any associations with risk of preterm birth or small-for-gestational age for either hypothetical intervention. CONCLUSION: We estimated that a reduction in water fluoride levels would modestly decrease birth weight and birth-weight-for-gestational-age z-scores in California. https://doi.org/10.1289/EHP13732.

Mixed methods approach to examining the implementation experience of a phone-based survey for a SARS-CoV-2 test-negative case-control study in California.

OBJECTIVE: To describe the implementation of a test-negative design case-control study in California during the Coronavirus Disease 2019 (COVID-19) pandemic. STUDY DESIGN: Test-negative case-control study. METHODS: Between February 24, 2021 - February 24, 2022, a team of 34 interviewers called 38,470 Californians, enrolling 1,885 that tested positive for SARS-CoV-2 (cases) and 1,871 testing negative for SARS-CoV-2 (controls) for 20-minute telephone survey. We estimated adjusted odds ratios for answering the phone and consenting to participate using mixed effects logistic regression. We used a web-based anonymous survey to compile interviewer experiences. RESULTS: Cases had 1.29-fold (95% CI: 1.24-1.35) higher adjusted odds of answering the phone and 1.69-fold (1.56-1.83) higher adjusted odds of consenting to participate compared to controls. Calls placed from 4pm to 6pm had the highest adjusted odds of being answered. Some interviewers experienced mental wellness challenges interacting with participants with physical (e.g., food, shelter, etc.) and emotional (e.g., grief counseling) needs, and enduring verbal harassment from individuals called. CONCLUSIONS: Calls placed during afternoon hours may optimize response rate when enrolling controls to a case-control study during a public health emergency response. Proactive check-ins and continual collection of interviewer experience(s) and may help maintain mental wellbeing of investigation workforce. Remaining adaptive to the dynamic needs of the investigation team is critical to a successful study, especially in emergent public health crises, like that represented by the COVID-19 pandemic.

Stomach Cancer Prediction Model (SCoPM): An approach to risk stratification in a diverse U.S. population.

BACKGROUND AND AIMS: Population-based screening for gastric cancer (GC) in low prevalence nations is not recommended. The objective of this study was to develop a risk-prediction model to identify high-risk patients who could potentially benefit from targeted screening in a racial/ethnically diverse regional US population. METHODS: We performed a retrospective cohort study from Kaiser Permanente Southern California from January 2008-June 2018 among individuals age ≥50 years. Patients with prior GC or follow-up <30 days were excluded. Censoring occurred at GC, death, age 85 years, disenrollment, end of 5-year follow-up, or study conclusion. Cross-validated LASSO regression models were developed to identify the strongest of 20 candidate predictors (clinical, demographic, and laboratory parameters). Records from 12 of the medical service areas were used for training/initial validation while records from a separate medical service area were used for testing. RESULTS: 1,844,643 individuals formed the study cohort (1,555,392 training and validation, 289,251 testing). Mean age was 61.9 years with 53.3% female. GC incidence was 2.1 (95% CI 2.0-2.2) cases per 10,000 person-years (pyr). Higher incidence was seen with family history: 4.8/10,000 pyr, history of gastric ulcer: 5.3/10,000 pyr, H. pylori: 3.6/10,000 pyr and anemia: 5.3/10,000 pyr. The final model included age, gender, race/ethnicity, smoking, proton-pump inhibitor, family history of gastric cancer, history of gastric ulcer, H. pylori infection, and baseline hemoglobin. The means and standard deviations (SD) of c-index in validation and testing datasets were 0.75 (SD 0.03) and 0.76 (SD 0.02), respectively. CONCLUSIONS: This prediction model may serve as an aid for pre-endoscopic assessment of GC risk for identification of a high-risk population that could benefit from targeted screening.

Changes in injecting versus smoking heroin, fentanyl, and methamphetamine among people who inject drugs in San Diego, California, 2020-2023.

BACKGROUND: Amidst an increasingly toxic drug supply in North America, people who inject drugs may be transitioning to smoking them. We aimed to assess changes in injecting and smoking opioids and methamphetamine among a cohort of people who inject drugs from San Diego, California. METHODS: Over five six-month periods spanning October 2020-April 2023, we assessed prevalence of injecting and smoking opioids or methamphetamine and whether participants used these drugs more frequently by smoking than injecting. Multivariable Poisson regression via generalized estimating equations was used to examine time trends. RESULTS: Of 362 participants, median age was 40 years; a minority were female (29%), Hispanic/Latinx/Mexican (45%), and housed (33%). Among this cohort, of whom 100% injected (and 84% injected and smoked) in period one (October 2020-April 2021), by period five (November 2022-April 2023), 34% only smoked, 59% injected and smoked, and 7% only injected. By period five, the adjusted relative risk (aRR) of injecting opioids was 0.41 (95% Confidence Interval [CI]: 0.33, 0.51) and the aRR for injecting methamphetamine was 0.50 (95% CI: 0.39, 0.63) compared to period one. Risks for smoking fentanyl rose significantly during period three (aRR=1.44, 95% CI: 1.06, 1.94), four (aRR=1.65, 95% CI: 1.24, 2.20) and five (aRR=1.90, 95% CI: 1.43, 2.53) compared to period one. Risks for smoking heroin and methamphetamine more frequently than injecting these drugs increased across all periods. CONCLUSIONS: Opioid and methamphetamine injection declined precipitously, with notable increases in smoking these drugs. Research is needed to understand the health consequences of these trends.

Did a workplace sugar-sweetened beverage sales ban reduce anxiety-related sugar-sweetened beverage consumption during the COVID-19 pandemic?

OBJECTIVE: Workplace sugar-sweetened beverage (SSB) sales bans can reduce SSB consumption. Because stress and anxiety can promote sugar consumption, we examined whether anxiety among hospital employees during the COVID-19 pandemic was associated with changes in SSB consumption and explored whether this relationship varied by exposure to a workplace SSB sales ban. DESIGN: In a prospective, controlled trial of workplace SSB sales bans, we examined self-reported anxiety (generalised anxiety disorder-7) and self-reported SSB consumption (fluid ounces/d) before (July 2019) and during (May 2020) the COVID-19 pandemic. SETTING: Hospital sites in two conditions (four with SSB sales bans and three without sales bans) in Northern California. PARTICIPANTS: We sampled 580 participants (hospital employees) from a larger trial of sales bans; all were regular consumers of SSB (minimum 3/week at main trial enrollment). This subsample was chosen based on having appropriately timed data for our study questions. RESULTS: Across conditions, participants reduced SSB consumption over the study period. However, participants with higher pandemic-era anxiety scores experienced smaller reductions in SSB consumption after 9 months compared with those with lower anxiety scores (ß = 0·65, P < 0·05). When the sample was disaggregated by sales ban condition, this relationship held for participants in the control group (access to SSB at work, ß = 0·82, P < 0·05), but not for those exposed to an SSB sales ban (ß = 0·42, P = 0·25). CONCLUSIONS: SSB sales bans likely reduce SSB consumption through multiple pathways; buffering stress-related consumption may be one mechanism.

Maternal residential exposure to solvents from industrial sources during pregnancy and childhood cancer risk in California.

BACKGROUND: Maternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer. METHODS: The present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy. RESULTS: 1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74). CONCLUSIONS: Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

Factors associated with suicidal ideation among people with HIV engaged in care.

BACKGROUND: People with HIV (PWH) are at elevated risk for suicidal ideation (SI), yet few studies have examined how substance use, clinical and sociodemographic factors are associated with SI among PWH. METHOD: We used substance use (Tobacco, Alcohol, Prescription Medication, and Other Substance Use [TAPS]) and depression (PHQ-9) data from computerized screening of adult PWH in primary care clinics in Northern California, combined with health record data on psychiatric diagnoses, HIV diagnosis, treatment, and control (HIV RNA, CD4), insurance, and neighborhood deprivation index (NDI) to examine factors associated with SI (PHQ-9 item 9 score > 0). Adjusted odds ratios (aOR) for SI were obtained from logistic regression models. RESULTS: Among 2829 PWH screened (92 % male; 56 % white; mean (SD) age of 54 (13) years; 220 (8 %) reported SI. Compared with no problematic use, SI was higher among those reporting one (aOR = 1.65, 95 % CI = 1.17, 2.33), two (aOR = 2.23, 95 % CI = 1.42, 3.49), or ≥ 3 substances (aOR = 4.49, 95 % CI = 2.41, 8.39). SI risk was higher for those with stimulant use (aOR = 3.55, 95 % CI = 2.25, 5.59), depression (aOR = 4.18, 95 % CI = 3.04, 5.74), and anxiety diagnoses (aOR = 1.67, 95 % CI = 1.19, 2.34), or Medicaid (aOR = 2.11, 95%CI = 1.24, 3.60) compared with commercial/other insurance. SI was not associated with HIV-related measures or NDI. LIMITATIONS: SI was assessed with a single PHQ-9 item. Simultaneous SI and exposure data collection restricts the ability to establish substance use as a risk factor. CONCLUSIONS: HIV care providers should consider multiple substance use, stimulant use, depression or anxiety, and public insurance as risk factors for SI and provide interventions when needed.

Risk of Adverse Neonatal Outcomes After Combined Prenatal Cannabis and Nicotine Exposure.

Importance: The prevalence of cannabis use in pregnancy is rising and is associated with adverse perinatal outcomes. In parallel, combined prenatal use of cannabis and nicotine is also increasing, but little is known about the combined impact of both substances on pregnancy and offspring outcomes compared with each substance alone. Objective: To assess the perinatal outcomes associated with combined cannabis and nicotine exposure compared with each substance alone during pregnancy. Design, Setting, and Participants: This retrospective population-based cohort study included linked hospital discharge data (obtained from the California Department of Health Care Access and Information) and vital statistics (obtained from the California Department of Public Health) from January 1, 2012, through December 31, 2019. Pregnant individuals with singleton gestations and gestational ages of 23 to 42 weeks were included. Data were analyzed from October 14, 2023, to March 4, 2024. Exposures: Cannabis-related diagnosis and prenatal nicotine product use were captured using codes from International Classification of Diseases, Ninth Revision, Clinical Modification, and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification. Main Outcome and Measures: The main outcomes were infant and neonatal death, infants small for gestational age, and preterm delivery. Results were analyzed by multivariable Poisson regression models. Results: A total of 3 129 259 pregnant individuals were included (mean [SD] maternal age 29.3 [6.0] years), of whom 23 007 (0.7%) had a cannabis-related diagnosis, 56 811 (1.8%) had a nicotine-use diagnosis, and 10 312 (0.3%) had both in pregnancy. Compared with nonusers, those with cannabis or nicotine use diagnoses alone had increased rates of infant (0.7% for both) and neonatal (0.3% for both) death, small for gestational age (14.3% and 13.7%, respectively), and preterm delivery (<37 weeks) (12.2% and 12.0%, respectively). Moreover, risks in those with both cannabis and nicotine use were higher for infant death (1.2%; adjusted risk ratio [ARR], 2.18 [95% CI, 1.82-2.62]), neonatal death (0.6%; ARR, 1.76 [95% CI, 1.36-2.28]), small for gestational age (18.0%; ARR, 1.94 [95% CI, 1.86-2.02]), and preterm delivery (17.5%; ARR, 1.83 [95% CI, 1.75-1.91]). Conclusions and Relevance: These findings suggest that co-occurring maternal use of cannabis and nicotine products in pregnancy is associated with an increased risk of infant and neonatal death and maternal and neonatal morbidity compared with use of either substance alone. Given the increasing prevalence of combined cannabis and nicotine use in pregnancy, these findings can help guide health care practitioners with preconception and prenatal counseling, especially regarding the benefits of cessation.

Impacts of heat and wildfire on preterm birth.

BACKGROUND: Climate change continues to increase the frequency, intensity, and duration of heat events and wildfires, both of which are associated with adverse pregnancy outcomes. Few studies simultaneously evaluated exposures to these increasingly common exposures. OBJECTIVES: We investigated the relationship between exposure to heat and wildfire smoke and preterm birth (PTB). METHODS: In this time-stratified case-crossover study, participants consisted of 85,806 California singleton PTBs (20-36 gestational weeks) from May through October of 2015-2019. Birthing parent ZIP codes were linked to high-resolution daily weather, PM2.5 from wildfire smoke, and ambient air pollution data. Heat day was defined as a day with apparent temperature >98th percentile within each ZIP code and heat wave was defined as ≥2 consecutive heat days. Wildfire-smoke day was defined as a day with any exposure to wildfire-smoke PM2.5. Conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI) comparing exposures during a hazard period (lags 0-6) compared to control periods. Analyses were adjusted for relative humidity, fine particles, and ozone. RESULTS: Wildfire-smoke days were associated with 3.0% increased odds of PTB (ORlag0: 1.03, CI: 1.00-1.05). Compared with white participants, associations appeared stronger among Black, Hispanic, Asian, and American Indians/Alaskan Native participants. Heatwave days (ORlag2: 1.07, CI: 1.02-1.13) were positively associated with PTB, with stronger associations among those simultaneously exposed to wildfire smoke days (ORlag2: 1.19, CI: 1.11-1.27). Similar findings were observed for heat days and when other temperature metrics (e.g., maximum, minimum) were used. DISCUSSION: Heat and wildfire increased PTB risk with evidence of synergism. As the occurrence and co-occurrence of these events increase, exposure reduction among pregnant people is critical, especially among racial/ethnic minorities.

Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

BACKGROUND: Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts. METHODS AND RESULTS: CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function. Outcomes were myocardial infarction or coronary death for FHS hard coronary heart disease function; and myocardial infarction, stroke, or coronary death for American College of Cardiology/American Heart Association and FHS hard CVD function. We calculated regression coefficients and assessed discrimination and calibration by sex; predicted to observed risk of outcome was also compared. In the combined cohort of 9412, 158 (1.7%) had a coronary heart disease event, and 309 (3.3%) had a CVD event. Among women, CVD risk was generally underestimated by all 3 risk functions. Among men, CVD risk was underestimated by the American College of Cardiology/American Heart Association and FHS hard CVD function, but overestimated by the FHS hard coronary heart disease function. Calibration was poor for women using the FHS hard CVD function and for men using all functions. Discrimination in all functions was good for women (c-statistics ranging from 0.78 to 0.90) and moderate for men (c-statistics ranging from 0.71 to 0.72). CONCLUSIONS: Established CVD risk prediction functions generally underestimate risk in people with HIV. Differences in model performance by sex underscore the need for both HIV-specific and sex-specific functions. Development of CVD risk prediction models tailored to HIV will enhance care for aging people with HIV.