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The adverse consequences of untreated perinatal depression highlight the need to identify populations to target in order to increase treatment rates. The authors sought to evaluate treatment initiation for a new diagnosis of depression during pregnancy or postpartum and to describe racial-ethnic differences in initiation and type (psychotherapy, antidepressants) of treatment in a large health care system with universal perinatal depression screening.This retrospective cohort study included women who delivered a live birth in the Kaiser Permanente Northern California system between October 2012 and May 2017. Black, Latina, Asian, and White women ages ≥15 years were eligible. New depression diagnoses were defined by usingIn total, 13,637 women with a new depression diagnosis (prenatal: N=7,041, 51.6%; postpartum: N=6,596, 48.4%) were identified. Of the pregnant women, 31.4% initiated treatment, and of the postpartum women, 73.1% initiated treatment. Latina and Asian women were less likely than White women to initiate treatment postpartum. During pregnancy and postpartum, non-White women were more likely to initiate psychotherapy. White women were more likely to initiate antidepressant medication during pregnancy and postpartum or a combination of antidepressant medication and psychotherapy during the postpartum period.Research is warranted to identify patient-, provider-, and system-level barriers that contribute to racial-ethnic disparities in perinatal mental health care.

To describe the risk of multiple recurrences in intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) and their impact on progression. Prognostic studies of IR-NMIBC have focused on initial recurrences, yet little is known about subsequent recurrences and their impact on progression.IR-NMIBC patients from the Be-Well Study, a prospective cohort study of NMIBC patients diagnosed from 2015-2019 at Kaiser Permanente Northern California, were identified. The frequency of first, second, and third intravesical recurrences of urothelial carcinoma were characterized using conditional Kaplan-Meier analyses and random-effects shared-frailty models. The association of multiple recurrences with progression was examined.In 291 patients with IR-NMIBC (median follow-up 38 months), the 5-year risk of initial recurrence was 54.4%. After initial recurrence (n=137), 60.1% of patients had a second recurrence by 2 years. After second recurrence (n=70), 51.5% of patients had a third recurrence by 3 years. In multivariable analysis, female sex (Hazard Ratio 1.51, p0.01), increasing tumor size (HR 1.14, p0.01) and number of prior recurrences (HR 1.24, p0.01) were associated with multiple recurrences; whereas maintenance BCG (HR 0.66, p=0.03) was associated with reduced recurrences. The 5-year risk of progression varied significantly (p0.01) by number of recurrences: 9.5%, 21.9%, and 37.9% for patients with 1, 2, and 3+ recurrences, respectively.Multiple recurrences are common in IR-NMIBC and are associated with progression. Female sex, larger tumors, number of prior recurrences, and lack of maintenance BCG were associated with multiple recurrences. Multiple recurrences may prove useful as a clinical trial endpoint for IR-NMIBC.

Earlier puberty has been associated with numerous adverse mental, emotional, and physical health outcomes. Obesity is a known risk factor for earlier puberty in girls, but research with boys has yielded inconsistent findings. We examined sex- and race/ethnicity-specific associations between childhood obesity and puberty in a multiethnic cohort of 129,824 adolescents born at a Kaiser Permanente Northern California medical facility between 2003 and 2011. We used Weibull regression models to explore associations between childhood obesity and breast development onset (thelarche) in girls, testicular enlargement onset (gonadarche) in boys, and pubic hair development onset (pubarche) in both sexes, adjusting for important confounders. Clear dose-response relationships were observed. Boys with severe obesity had the greatest risk for earlier gonadarche (hazard ratio = 1.23, 95% confidence limit: 1.15, 1.32) and pubarche (hazard ratio = 1.44, 95% confidence limit: 1.34, 1.55), while underweight boys had delayed puberty compared with peers with normal body mass index. A similar dose-response relationship was observed in girls. There were significant interactions between childhood body mass index and race/ethnicity. Childhood obesity is associated with earlier puberty in both boys and girls, and the magnitude of the associations may vary by race/ethnicity. Prevention of childhood obesity may delay pubertal timing and mitigate health risks associated with both conditions.

Patients with gestational diabetes mellitus and from racial/ethnic minority groups face disproportionate risk for type 2 diabetes. Lifestyle interventions, if accessible and acceptable to diverse patients, could advance diabetes prevention and mitigate racial/ethnic disparities. Here we describe overall and race/ethnicity-specific reach, acceptability, and perceived success from an effective telehealth diabetes prevention lifestyle program for patients with gestational diabetes mellitus, implemented in the Gestational Diabetes Effects on Moms (GEM) cluster-randomized controlled trial. GEM tested a program of 13 telephone sessions and behavior change techniques (BCTs, e.g., goal setting) in a healthcare system. We evaluated participation (completing ≥1 session), acceptability of BCTs, and perceived success reaching program goals. Among 1,087 patients (75.2% from minority groups), 50.3% participated. Participation rates were 61.7% among Black, 56.4% among Hispanic, 55.6% among multiracial/other, 53.0% among White, and 43.7% among Asian/Pacific Islander patients. Evaluation survey respondents (n = 433/547; 79.2%) largely rated BCTs as very helpful (range 40.9%–58.4%) or moderately helpful (27.3%–34.9%). Respondents from minority groups largely rated goal setting for weight management as very or moderately helpful, with fewer minority respondents rating it as only a little/not at all helpful than White respondents (p = .02). Black and White respondents reported more limited success reaching a healthy weight than Asian/Pacific Islander, Hispanic, and multiracial/other women (p = .005). A telehealth diabetes prevention lifestyle program demonstrated reach and acceptability across racial/ethnic groups. While perceived success can be improved among Black and White participants, such programs could promote access to preventive care and help mitigate disparities in diabetes risk.

ImportanceThe levels of glycemic control associated with the lowest risk of dementia in people with type 2 diabetes are unknown. This knowledge is critical to inform patient-centered glycemic target setting.ObjectiveTo examine the associations between cumulative exposure to various ranges of glycated hemoglobin (HbA1c) concentrations with dementia risk across sex and racial and ethnic groups and the association of current therapeutic glycemic targets with dementia risk.Design, Setting, and ParticipantsThis cohort study included members of the Kaiser Permanente Northern California integrated health care system with type 2 diabetes who were aged 50 years or older during the study period from January 1, 1996, to September 30, 2015. Individuals with fewer than 2 HbA1c measurements during the study period, prevalent dementia at baseline, or less than 3 years of follow-up were excluded. Data were analyzed from February 2020 to January 2023.ExposuresTime-updated cumulative exposure to HbA1c thresholds. At each HbA1c measurement, participants were categorized based on the percentage of their HbA1c measurements that fell into the following categories: less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, 9% to less than 10%, and 10% or more of total hemoglobin (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01).Main Outcomes and MeasuresDementia diagnosis was identified using International Classification of Diseases, Ninth Revision codes from inpatient and outpatient encounters. Cox proportional hazards regression models estimated the association of time-varying cumulative glycemic exposure with dementia, adjusting for age, race and ethnicity, baseline health conditions, and number of HbA1c measurements.ResultsA total of 253 211 participants were included. The mean (SD) age of participants was 61.5 (9.4) years, and 53.1% were men. The mean (SD) duration of follow-up was 5.9 (4.5) years. Participants with more than 50% of HbA1c measurements at 9% to less than 10% or 10% or more had greater risk of dementia compared with those who had 50% or less of measurements in those categories (HbA1c 9% to 1c≥10%: aHR, 1.74 [95% CI, 1.62-1.86]). By contrast, participants with more than 50% of HbA1c concentrations less than 6%, 6% to less than 7%, or 7% to less than 8% had lower risk of dementia (HbA1c1c 6% to 1c 7% to Conclusions and RelevanceIn this study dementia risk was greatest among adults with cumulative HbA1c concentrations of 9% or more. These results support currently recommended relaxed glycemic targets for older people with type 2 diabetes.

Supplementary Table 1. Estimates of lung cancer risk associated with metformin use in patient subgroups. Supplementary Table 2. Estimates of lung cancer risk associated with metformin use, by gender. Supplementary Table 3. Estimates of lung cancer risk associated with metformin use, by tumor stage

Supplementary Table S1. Descriptive factors for KP study population, broken down by study. Supplementary Table S2. Genome-wide significant SNPs found in our cohort. Supplementary Table S3. Cis-eQTL expression of rs4646284. Supplementary Table S4. Results at the 105 loci previously found to be associated with prostate cancer. Supplementary Table S5. Risk score of and variance explained by the 105 previously reported hits. Supplementary Figure S1. Manhattan and Q-Q plots of each race/ethnicity and meta-analysis. Supplementary Figure S2. Local plots of novel replicated rs4646284 and suggestive rs2659124. Supplementary Figure S3. Cis-eQTL of SLC22A1 and SLC22A3. Supplementary Figure S4. Comparison of ORs of KP to previous reports by race/ethnicity. Supplementary Figure S5. KP AUC estimates.

Methodologic biases may explain why observational studies examining metformin use in relation to lung cancer risk have produced inconsistent results. We conducted a cohort study to further investigate this relationship, accounting for potential biases. For 47,351 patients with diabetes ages ≥40 years, who completed a health-related survey administered between 1994 and 1996, data on prescribed diabetes medications were obtained from electronic pharmacy records. Follow-up for incident lung cancer occurred from January 1, 1997, until June 30, 2012. Using Cox regression, we estimated lung cancer risk associated with new use of metformin, along with total duration, recency, and cumulative dose (all modeled as time-dependent covariates), adjusting for potential confounding factors. During 428,557 person-years of follow-up, 747 patients were diagnosed with lung cancer. No association was found with duration, dose, or recency of metformin use and overall lung cancer risk. Among never smokers, however, ever use was inversely associated with lung cancer risk [HR, 0.57; 95% confidence interval (CI), 0.33–0.99], and risk appeared to decrease monotonically with longer use (≥5 years: HR, 0.48; 95% CI, 0.21–1.09). Among current smokers, corresponding risk estimates were >1.0, although not statistically significant. Consistent with this variation in effect by smoking history, longer use was suggestively associated with lower adenocarcinoma risk (HR, 0.69; 95% CI, 0.40–1.17), but higher small cell carcinoma risk (HR, 1.82; 95% CI, 0.85–3.91). In this population, we found no evidence that metformin use affects overall lung cancer risk. The observed variation in association by smoking history and histology requires further confirmation. Cancer Prev Res; 8(2); 174–9. ©2014 AACR.

Background: Given the limited literature, we conducted a study to examine the epidemiology of herpes zoster (HZ) among newly diagnosed cancer patients.Methods: We identified adult health plan members of Kaiser Permanente Northern California diagnosed with invasive cancer from 2001 to 2005. Electronic health records with inpatient and outpatient diagnoses, laboratory tests, and antiviral medications were used to identify HZ diagnoses from 2001 to 2006. HZ diagnoses and associated complications were confirmed by medical chart review. Treatment with chemotherapy and corticosteroids was used to classify patients by immunosuppression level.Results: Among 14,670 cancer patients, 424 were diagnosed with HZ during follow-up (median 22 months). The incidence of HZ was 31/1,000 person-year (PY) in patients with hematologic malignancies and 12/1,000 PY in patients with solid tumors. The corresponding 2-year cumulative incidence of HZ was approximately 6% and 2%, respectively. Compared with incidence rates of HZ reported in a general US population, the age- and sex-standardized rates of HZ were 4.8 times higher [95% confidence interval (CI), 4.0–5.6] in patients with hematologic malignancies and 1.9 times higher (95% CI, 1.7–2.1) in those with solid tumors. HZ risk increased with increasing level of immunosuppression. Among HZ cases, 19% with hematologic malignancies and 14% with solid tumors had HZ-associated pain for at least 30 days. The corresponding numbers for nonpain-related complications were 30% and 18%, respectively.Conclusions: Cancer patients are at substantially increased risk of HZ and among those with HZ, complications are relatively common.Impact: Better HZ prevention and treatment options for cancer patients are needed. Cancer Epidemiol Biomarkers Prev; 22(1); 82–90. ©2012 AACR.

Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival.Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan–Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I–III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer–specific mortality (CRCsM).Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09–1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05–2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and 2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity.Conclusions: Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker.Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008–15. ©2017 AACR.

Supplemental Tables 1-3

PDF file - 83K, This supplementary document describes methods used to create an algorithm for classifying patients' level of immunosuppression

Supplementary Figure 1 from CYP1A1/2 Haplotypes and Lung Cancer and Assessment of Confounding by Population Stratification

Supplementary Tables 1-4 from CYP1A1/2 Haplotypes and Lung Cancer and Assessment of Confounding by Population Stratification

Prior studies of lung cancer and CYP1A1/2 in African-American and Latino populations have shown inconsistent results and have not yet investigated the haplotype block structure of CYP1A1/2 or addressed potential population stratification. To investigate haplotypes in the CYP1A1/2 region and lung cancer in African-Americans and Latinos, we conducted a case-control study (1998–2003). African-Americans (n = 535) and Latinos (n = 412) were frequency matched on age, sex, and self-reported race/ethnicity. We used a custom genotyping panel containing 50 single nucleotide polymorphisms in the CYP1A1/2 region and 184 ancestry informative markers selected to have large allele frequency differences between Africans, Europeans, and Amerindians. Latinos exhibited significant haplotype main effects in two blocks even after adjusting for admixture [odds ratio (OR), 2.02; 95% confidence interval (95% CI), 1.28–3.19 and OR, 0.55; 95% CI, 0.36–0.83], but no main effects were found among African-Americans. Adjustment for admixture revealed substantial confounding by population stratification among Latinos but not African-Americans. Among Latinos and African-Americans, interactions between smoking level and haplotypes were not statistically significant. Evidence of population stratification among Latinos underscores the importance of adjusting for admixture in lung cancer association studies, particularly in Latino populations. These results suggest that a variant occurring within the CYP1A2 region may be conferring an increased risk of lung cancer in Latinos. [Cancer Res 2009;69(6):2340–8]

Supplementary Figure 3 from CYP1A1/2 Haplotypes and Lung Cancer and Assessment of Confounding by Population Stratification

Supplementary Figure 2 from CYP1A1/2 Haplotypes and Lung Cancer and Assessment of Confounding by Population Stratification

Background: National guidelines recommend physical activity (PA) during pregnancy for optimal cardiovascular and overall health. Yet most individuals do not engage in sufficient PA and motivation for PA during pregnancy is poorly understood. Methods: We examined intrinsic motivation for PA (i.e., engaging in activity for enjoyment or satisfaction) and its cross-sectional associations with PA, by intensity level, in the first trimester of pregnancy. Data come from the Pregnancy, Lifestyle and Environment Study (PETALS), a population-based cohort study set in an integrated health system. Following recruitment at 10-13 weeks’ gestation, participants ( N =472; 71% from racial/ethnic groups other than White) completed the validated Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2, intrinsic subscale); and Pregnancy Physical Activity Questionnaire (PPAQ) to estimate typical PA in the prior 2 months, as expressed in MET [metabolic equivalent] hours/week (by intensity and, for MVPA, by domain—i.e., limited to intentional activity such as sports, walking, aerobic exercise, etc.). Data were collected in 2017-18. Results: As hypothesized, intrinsic motivation was higher among those who met ( n =192, 40.7%) vs. did not meet national guidelines for 150 minutes/week of moderate-to-vigorous intensity PA (MVPA; mean BREQ-2 scores [SD]: 2.84 [0.89] vs. 1.94 [1.02], p n =131, 27.8%) vs. below the sample-specific 75 th percentile for vigorous PA (2.86 [0.93] vs. 2.09 [1.03], p n =119, 25.2%) vs. below the 75 th percentile for sedentary behavior (1.99 [1.14] vs. 2.41 [1.01], p =0.0005). Intrinsic motivation was not associated with reaching the 75 th percentiles for total, light, or moderate PA. In modified Poisson regression models adjusted for age, pre-pregnancy body mass index, race/ethnicity, education, and parity, a 1-unit increase in BREQ-2 score was associated with an increased probability of meeting or exceeding MVPA guidelines (rate ratio [95% CI]: 1.66 [1.48, 1.86]) and scoring at or above the 75 th percentile for vigorous PA (1.70 [1.44, 1.99]). A 1-unit increase in BREQ-2 score decreased the probability of scoring at or above the 75 th percentile for sedentary behavior (0.79 [0.67, 0.92]). Conclusions: Only 4 in 10 participants met national guidelines for MVPA in the first trimester of pregnancy. Intrinsic motivation was associated with greater MVPA and vigorous PA, and less sedentary behavior, in this diverse sample. Intrinsic motivation is potentially modifiable and thus a promising target for new behavioral interventions to improve maternal cardiovascular health.

To compare survival among patients with head and neck cancer before and after implementing a weekly multidisciplinary clinic and case conference.A retrospective cohort study with chart review was conducted of 3081 patients (1431 preimplementation, 1650 postimplementation) diagnosed with stage I-IVB tumors in the oral cavity, oropharynx, hypopharynx, nasopharynx, or larynx. Pre- and postimplementation differences in overall and disease-specific survival 1, 2, and 3 years after diagnosis were assessed with unadjusted Kaplan-Meier curves and multivariable Cox proportional hazard regression models adjusted for demographic characteristics, comorbidity burden, smoking status, tumor site and stage, p16 status for oropharyngeal squamous cell cancer, and initial treatment modality.Patients less commonly presented with oropharyngeal squamous cell cancer and advanced tumors (III-IVB) and received primary treatment with surgery alone or with adjuvant therapy preimplementation than postimplementation. Overall survival at 3 years was 77.1% and 79.9% (A multidisciplinary clinic and case conference were associated with improved outcomes among patients with head and neck cancer, especially those with advanced tumors.All patients with head and neck cancer should receive multidisciplinary team management, especially those with advanced tumors.

ImportanceTobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear.ObjectiveTo examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non–muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions.Design, Setting, and ParticipantsThe Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.4 months in the Kaiser Permanente Northern and Southern California integrated health care system. Eligibility criteria were age at least 21 years, first NMIBC diagnosis (stages Ta, Tis, or T1), alive, and not in hospice care. Exclusion criteria were previous diagnosis of bladder cancer or other cancer diagnoses within 1 year prior to or concurrent with NMIBC diagnosis. Data were analyzed from April 1 to October 4, 2022.ExposuresUse of cigarettes, pipes, cigars, e-cigarettes, and marijuana was reported in the baseline interview. Use of smoking cessation interventions (counseling and medications) was derived from electronic health records.Main Outcomes and MeasuresHazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression.ResultsA total of 1472 patients (mean [SD] age at diagnosis, 70.2 [10.8%] years; 1129 [76.7%] male patients) with NMIBC were enrolled at a mean (SD) of 2.3 (1.3) months after diagnosis, including 874 patients (59.4%) who were former smokers and 111 patients (7.5%) who were current cigarette smokers; 67 patients (13.7%) smoked pipes and/or cigars only, 65 patients (4.4%) used e-cigarettes, 363 patients (24.7%) used marijuana. Longer cigarette smoking duration and more pack-years were associated with higher risk of recurrence in a dose-dependent manner, with the highest risks for patients who had smoked for 40 or more years (HR, 2.36; 95% CI, 1.43-3.91) or 40 or more pack-years (HR, 1.97; 95% CI, 1.32-2.95). There was no association of having ever smoked, being a former or current cigarette smoker, and years since quit smoking with recurrence risk. No associations with pipes, cigars, e-cigarettes, or marijuana were found. Of 102 patients offered a smoking cessation intervention, 57 (53.8%) received an interventions after diagnosis, with female patients more likely than male patients to engage in such interventions (23 of 30 female patients [76.7%] vs 34 of 76 male patients [44.7%]; P = .003).Conclusions and RelevanceThese findings suggest that longer duration and more pack-years of cigarette smoking were associated with higher risk of NMIBC recurrence. Cigarette smoking remains a critical exposure before and after diagnosis in survivors of NMIBC.

Environmental phenols are ubiquitous endocrine disruptors and putatively diabetogenic. However, data during pregnancy are scant. We investigated the prospective associations between pregnancy phenols concentrations and gestational diabetes (GDM) risk. In a nested matched case-control study of 111 individuals with GDM and 222 non-GDM controls within the prospective PETALS cohort, urinary bisphenol A (BPA), BPA substitutes (bisphenol F, bisphenol S [BPS]), benzophenone-3, and triclosan were quantified during the first and second trimesters. Cumulative concentrations across the two times were calculated using the area under the curve (AUC). Multivariable conditional logistic regression examined the associations of individual phenols with GDM risk. We conducted mixture analysis using Bayesian kernel machine regression. We a priori examined effect modification by Asians/Pacific Islanders (A/PI) race/ethnicity due to the case-control matching and highest GDM prevalence among A/PI. Overall, first-trimester urinary BPS was positively associated with an increased risk of GDM [adjusted odds ratio comparing the highest versus lowest tertile aORT3 vs. T1 (95% CI)=2.12 (1.00-4.50)]. We identified associations among non-A/P, who had higher phenols concentrations than A/PI. Among non-A/PI, first-trimester BPA, BPS, and triclosan were positively associated with GDM risk [aORT3 vs. T1 (95% CI)=2.91 (1.05-8.02), 4.60 (1.55-13.70), 2.88 (1.11-7.45), respectively]. Triclosan in the second trimester and AUC were positively associated with GDM risk among non-A/PI (P

Background: While racial–ethnic disparities in cesarean delivery rates among nulliparous women delivering a term singleton in the vertex position (NTSV) exist, it remains unclear the extent to whic...

PURPOSE: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. METHODS: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2,152 HR+ BC patients diagnosed from 2006–2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at six-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture. RESULTS: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although

Background Lactation is associated with lower risks for cardiovascular disease in women. Organ-related adiposity, which plays significant roles in the development of cardiometabolic diseases, could help explain this observation. We evaluated the association of lactation duration with visceral (VAT) and pericardial (PAT) fat volumes in women. Methods Data were obtained from 910 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study (1985-1986) without diabetes prior to pregnancy who had ≥1 birth during 25 years of follow-up and had VAT and PAT measured from computed tomographic scans in 2010-2011. Cumulative lactation duration across all births since baseline was calculated from self-reports collected at periodic exams. Results At baseline, the average age of women (48% black, 52% white) was 24 ± 3.7 years. After controlling for baseline age, race, smoking status, body mass index, fasting glucose, family history of diabetes, fat intake, total cholesterol, physical activity, and follow-up covariates (parity, gestational diabetes), the mean fat volumes across categories of lactation [none (n = 221), 1-5 months (n = 306), 6-11 months (n = 210), and ≥12 months (n = 173)] were 122.0, 113.7 105.0, and 110.1 cm3 for VAT and 52.2, 46.7, 44.5, and 43.4 cm3 for PAT, respectively. Changes in body weight from the first post-baseline birth to the end of follow-up mediated 21% and 18% of the associations of lactation with VAT and PAT, respectively. Conclusions In this prospective study, longer cumulative lactation duration was associated with lower VAT and PAT volumes, with weight gain partially mediating these associations.

Patients with versus without atopic dermatitis may have a greater risk of cardiovascular events, and the risk increases with severity of atopic dermatitis. The incidence of cardiovascular events in the population of patients with moderate-to-severe atopic dermatitis is largely unknown. This retrospective study evaluates incidence rates of cardiovascular events in patients aged ≥12 years with moderate-to-severe atopic dermatitis in a cohort of Kaiser Permanente Northern California health care system members without recognized risk factors for adverse events. Patients with moderate-to-severe atopic dermatitis, as defined by dermatologist-rendered code and prescription history between 2007 and 2018, were included. Major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolisms were identified via International Classification of Diseases codes. Stratification variables included age, sex, race, smoking history, and diabetes. Incidence rates per 1000 person-years were calculated by the number of patients with an incident event divided by the total person-years of observation. Among 8197 patients with moderate-to-severe atopic dermatitis, incidence rates per 1000 person-years (95% confidence interval) for major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolism were: 2.6 (2.1–3.2), 2.0 (1.5–2.5), 1.6 (1.2–2.1), and 0.7 (0.5–1.0), respectively. Incidence rates for all events were higher for older versus younger patients, patients with versus without diabetes, former smokers versus patients who had never smoked, and men versus women, except for pulmonary embolisms, which were higher in women. This study estimated the incidence of cardiovascular events in patients with moderate-to-severe atopic dermatitis and provides valuable information for clinicians.

Evidence is limited characterizing sociodemographically diverse patient populations with lung cancer in relation to smoking status.In a cross-sectional analysis of adults diagnosed with lung cancer at ages ≥30 years from 2007-2018 within an integrated healthcare system, overall and sex-specific prevalence of never smoking were estimated according to sociodemographic and clinical characteristics. Adjusted prevalence ratio (aPR) and 95% confidence interval (CI) were also estimated using modified Poisson regression to identify patient characteristics associated with never smoking, overall and by sex. Similar analyses were conducted to explore whether prevalence and association patterns differed between non-Hispanic White and Asian/Pacific Islander patients.Among 17,939 patients with lung cancer, 2,780 (15.5%) never smoked and 8,698 (48.5%) had adenocarcinoma. Overall prevalence of never smoking was higher among females than males (21.2%Our findings suggest that patterns of never-smoking status associated with sociodemographic and clinical characteristics are different across sex and race/ethnicity among patients with lung cancer. Such data are critical to increasing awareness and expediting diagnosis of this disease.

Gestational diabetes (GDM) predisposes pregnant individuals to perinatal complications and long-term diabetes and cardiovascular diseases. We developed and validated metabolomic markers for GDM in a prospective test-validation study. In a case-control sample within the PETALS cohort (91 GDM, 180 non-GDM; discovery set), a random PETALS subsample (42 GDM, 372 non-GDM; validation set 1), and a case-control sample within the GLOW trial (35 GDM, 70 non-GDM; validation set 2), fasting serum untargeted metabolomics were measured by gas chromatography/time-of-flight mass spectrometry. Multivariate enrichment analysis examined metabolites-GDM associations. Ten-fold cross-validated LASSO regression identified predictive metabolomic markers at gestational weeks (GW) 10-13 and 16-19 for GDM. The purinone metabolites at GW 10-13 and 16-19, and the amino acids, amino alcohols, hexoses, indoles, and pyrimidines metabolites at GW 16-19 were positively associated with GDM risk (FDR P

Histone deacetylase inhibitors, including valproic acid, selectively induce cellular differentiation and apoptosis in melanoma cells. No published pharmacoepidemiologic studies have explored the association between valproic acid use and melanoma risk. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n = 2,213,845) from 1997 to 2012 to examine the association between valproic acid use and melanoma risk. Melanoma hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, adjusted for age, sex, calendar year, and healthcare use. Melanoma incidence was lower among exposed individuals (64.0 exposed vs. 96.2 unexposed per 100,000 person-years, P0.001). Exposed individuals had a lower incident melanoma risk (HR = 0.64; 95% CI = 0.51-0.79) in unadjusted analysis, and the estimate was attenuated but significant in adjusted analysis (HR = 0.76, 95% CI = 0.61-0.94). Cumulative exposure based on the number of fills revealed a biologically implausible inverse dose-effect. Exposed individuals were more likely to present with local than regional or distant disease at diagnosis (80/82; 97.6% exposed vs. 12,940/13,971; 92.6% unexposed). Our findings suggest that valproic acid exposure may be associated with decreased melanoma risk and progression, but the cumulative exposure analyses suggest that the observation may be owing to residual confounding.

Background Associations of excessive gestational weight gain (GWG) with greater birthweight and childhood obesity may be confounded by shared familial environment or genetics. Sibling comparisons can minimize variation in these confounders because siblings grow up in similar environments and share the same genetic predisposition for weight gain. Methods We identified 96 289 women with live births in 2008–2014 at Kaiser Permanente Northern California. Fifteen percent of women (N = 14 417) had at least two births during the study period for sibling analyses. We assessed associations of GWG according to the Institute of Medicine (IOM) recommendations with birthweight and obesity at age 3 years, using conventional analyses comparing outcomes between mothers and sibling analyses comparing outcomes within mothers, which control for stable within-family unmeasured confounders such as familial environment and genetics. We used generalized estimating-equations and fixed-effects models. Results In conventional analyses, GWG above the IOM recommendations was associated with 88% greater odds of large-for-gestational age birthweight [95% confidence interval (CI): 1.80, 1.97] and 30% greater odds of obesity at 3 years old (95% CI: 1.24, 1.37) compared with GWG within the IOM recommendations. In sibling analyses, GWG above the IOM recommendations was also associated with greater odds of large-for-gestational age [odds ratio (OR): 1.36; 95% CI: 1.20, 1.54], but was not associated with obesity at 3 years old (OR = 0.98; 95% CI: 0.84, 1.15). Conclusions GWG likely has a direct impact on birthweight; however, shared environmental and lifestyle factors within families may play a larger role in determining early-childhood weight status and obesity risk than GWG.