Prescription opioid dispensing patterns among patients with schizophrenia or bipolar disorder.

BACKGROUND: Patients with schizophrenia (SZ) or bipolar disorder (BD) may have increased risk of complications from prescribed opioids, including opioid-induced respiratory depression. We compared prescription opioid pain medication dispensing for patients with SZ or BD versus controls over 5 years to assess dispensing trends. METHODS: This retrospective, observational study analysed US claims data from the IBM® MarketScan® Commercial and Multi-State Medicaid databases for individuals aged 18-64 years with prevalent SZ or BD for years 2015-2019 compared with age- and sex-matched controls. Baseline characteristics, comorbidities, and medication use were assessed. Proportions of individuals dispensed prescription opioids chronically (ie, ≥70 days over a 90-day period or ≥ 6 prescriptions annually) or nonchronically (≥1 prescription, chronic definition not met) were assessed. RESULTS: In 2019, the Commercial and Medicaid databases contained records for 4773 and 30,179 patients with SZ and 52,780 and 63,455 patients with BD, respectively. Patients with SZ or BD had a higher prevalence of comorbidities, including pain, versus controls in each analysis year. From 2015 to 2019, among commercially insured patients with SZ, chronic opioid-dispensing proportions decreased from 6.1% (controls: 2.7%) to 2.3% (controls: 1.2%) and, for patients with BD, from 11.4% (controls: 2.7%) to 6.4% (controls: 1.6%). Chronic opioid dispensing declined in Medicaid-covered patients with SZ from 15.0% (controls: 14.7%) to 6.7% (controls: 6.0%) and, for patients with BD, from 27.4% (controls: 12.0%) to 12.4% (controls: 4.7%). Among commercially insured patients with SZ, nonchronic opioid dispensing decreased from 15.5% (controls: 16.4%) to 10.7% (controls: 11.0%) and, for patients with BD, from 26.1% (controls: 17.5%) to 20.0% (controls: 12.2%). In Medicaid-covered patients with SZ, nonchronic opioid dispensing declined from 22.5% (controls: 24.4%) to 15.1% (controls: 12.7%) and, for patients with BD, from 32.3% (controls: 25.9%) to 24.6% (controls: 13.6%). CONCLUSIONS: The proportions of individuals dispensed chronic or nonchronic opioid medications each year were similar between commercially and Medicaid-insured patients with SZ versus controls and were higher for patients with BD versus controls. From 2015 to 2019, the proportions of individuals who were dispensed prescription opioids chronically or nonchronically decreased for patients with SZ or BD and controls.

Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer trial study protocol: a randomised clinical trial of fibre-rich legumes targeting the gut microbiome, metabolome and gut transit time of overweight and obese patients with a history of noncancerous adenomatous polyps.

INTRODUCTION: Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC). METHODS/DESIGN: This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1-3 and one meal/day in months 4-6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1-2 pounds per week. ETHICS AND DISSEMINATION: The National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563). TRIAL REGISTRATION NUMBER: NCT04780477.

Describing the Shape of the Relationship Between Gestational Age at Birth and Cognitive Development in a Nationally Representative U.S. Birth Cohort.

BACKGROUND: Preterm children face higher risk of cognitive and academic deficits compared with their full-term peers. The objective of this study was to describe early childhood cognitive ability and kindergarten academic achievement across gestational age at birth in a population-based longitudinal cohort. METHODS: The study population included singletons born at 24-42 weeks gestation enrolled in the Early Childhood Longitudinal Study-Birth Cohort (n = 6150 for 2-year outcome, n = 4450 for kindergarten outcome). Home-based assessments measured cognitive ability at 2 years and reading and mathematics achievement at kindergarten age. Linear regression models estimated the association between gestational age and cognitive and academic scores using four different ways of modelling gestational age: continuous variable in linear and quadratic terms; categories for individual weeks; and clinical categories for early preterm, moderate preterm, late preterm, early term, full term, late term, and post-term. RESULTS: Children born at early preterm (24-27 weeks), moderate preterm (28-33 weeks), and late preterm (34-36 weeks) scored significantly worse than full-term (39-40 weeks) peers on 2-year and kindergarten assessments; however, no deficits were observed for early term (37-38 weeks). These categories were a clinically useful and parsimonious approach to stratifying risk of adverse cognitive and academic outcomes. CONCLUSIONS: This study estimated the relative performance of children born at 24-42 weeks in a population-based birth cohort using multiple approaches to modelling gestational age, providing a more rigorous understanding of the relationships between the full spectrum of gestational age and cognitive and academic outcomes in early childhood and at school age.

Summary of relationships between exchangeability, biasing paths and bias.

Definitions and conceptualizations of confounding and selection bias have evolved over the past several decades. An important advance occurred with development of the concept of exchangeability. For example, if exchangeability holds, risks of disease in an unexposed group can be compared with risks in an exposed group to estimate causal effects. Another advance occurred with the use of causal graphs to summarize causal relationships and facilitate identification of causal patterns that likely indicate bias, including confounding and selection bias. While closely related, exchangeability is defined in the counterfactual-model framework and confounding paths in the causal-graph framework. Moreover, the precise relationships between these concepts have not been fully described. Here, we summarize definitions and current views of these concepts. We show how bias, exchangeability and biasing paths interrelate and provide justification for key results. For example, we show that absence of a biasing path implies exchangeability but that the reverse implication need not hold without an additional assumption, such as faithfulness. The close links shown are expected. However confounding, selection bias and exchangeability are basic concepts, so comprehensive summarization and definitive demonstration of links between them is important. Thus, this work facilitates and adds to our understanding of these important biases.

Oxidative balance score and risk for incident prostate cancer in a prospective U.S. cohort study.

PURPOSE: Oxidative stress is defined as an imbalance between pro-oxidants and antioxidants. Previous research found that a single comprehensive oxidative balance score (OBS) that includes individual pro- and anti-oxidant exposures may be associated with various conditions (including prostate cancer) in the absence of associations with the individual factors. We investigated an OBS-incident prostate cancer association among 43,325 men in the Cancer Prevention Study II Nutrition Cohort. METHODS: From 1999-2007, 3386 incident cases were identified. Twenty different components, used in two ways (unweighted or weighted based on literature reviews), were incorporated into the OBS, and the resulting scores were then expressed as three types of variables (continuous, quartiles, or six equal intervals). Multivariable-adjusted rate ratios were calculated using Cox proportional hazards models. RESULTS: We hypothesized that the OBS would be inversely associated with prostate cancer risk; however, the rate ratios (95% confidence intervals) comparing the highest with the lowest OBS categories ranged from 1.17 (1.04-1.32) to 1.39 (0.90-2.15) for all cases, 1.14 (0.87-1.50) to 1.59 (0.57-4.40) for aggressive disease (American Joint Committee on Cancer stage III/IV or Gleason score 8-10), and 0.91 (0.62-1.35) to 1.02 (1.02-1.04) for nonaggressive disease. CONCLUSIONS: Our findings are not consistent with the hypothesis that oxidative balance-related exposures collectively affect risk for prostate cancer.

Household emergency preparedness by housing type from a community assessment for public health emergency response (CASPER), Michigan.

OBJECTIVES: We examined the association between housing type and household emergency preparedness among households in Oakland County, Michigan. METHODS: We used interview data on household emergency preparedness from a cluster design survey in Oakland County, Michigan, in 2012. We compared survey-weighted frequencies of household demographics, medical conditions, and preparedness measures in single-detached homes versus multi-unit dwellings, and determined the unadjusted odds ratios (OR) and the income-level adjusted OR for each preparedness measure. RESULTS: Households had similar demographics and medical conditions between housing types. Unadjusted ORs were statistically significant for single detached homes having a generator (11.1), back-up heat source (10.9), way to cook without utilities (5.8), carbon monoxide (CO) detector (3.8), copies of important documents (3.4), evacuation routes (3.1), and 3-day supply of water (2.5). Income level adjusted ORs remained statistically significant except for owning a CO detector. CONCLUSIONS: Households in multi-unit dwellings were less likely to have certain recommended emergency plans and supplies compared to those in single detached homes. Further research is required to explore the feasibility, barriers, and alternatives for households in multi-unit dwellings in terms of complying with these measures.

First-trimester maternal plasma cytokine levels, pre-pregnancy body mass index, and spontaneous preterm delivery.

OBJECTIVE: To examine associations between first-trimester plasma cytokines and spontaneous preterm delivery (sPTD). DESIGN: A case-control study was nested within the Danish National Birth Cohort, a cohort of women with 101,042 pregnancies from 1997 to 2002 who were recruited during pregnancy and followed prospectively. SAMPLE: Subjects included 107 women delivering singleton infants at 24-29 weeks, 353 at 30-33 weeks, 422 at 34-36 weeks, and 1,372 at > or =37 weeks. METHODS: Maternal plasma interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured at a median of eight weeks gestation using multiplex flow cytometry. Adjusted odds ratios (ORs) were obtained using polytomous logistic regression. MAIN OUTCOME MEASURES: sPTD categorized as: 24-29 weeks, 30-33 weeks, 34-36 weeks, and > or =37 weeks (controls). RESULTS: Elevated TNF-alpha and GM-CSF were associated with an increased risk of delivery at 34-36 weeks. In underweight women, sPTD <34 weeks was associated with elevated (>75th percentile) IL-6 (OR=5.62, 95% confidence interval (CI): 1.73, 18.26) and TNF-alpha (OR=3.02, CI: 1.02, 8.91) compared with term delivery. Conversely, among obese women, elevated IL-2 (OR=0.30, CI: 0.11, 0.78) and TNF-alpha (OR=0.15, CI: 0.05, 0.47) were associated with a reduced risk of delivering at <34 weeks. Cytokines were not related to delivery at <34 weeks in normal-weight and overweight women. CONCLUSIONS: These findings suggest that the association between first-trimester plasma cytokine levels and sPTD may depend on pre-pregnancy body mass index.

TGF-alpha expression as a potential biomarker of risk within the normal-appearing colorectal mucosa of patients with and without incident sporadic adenoma.

BACKGROUND: Transforming growth factor-alpha (TGF-alpha), a stimulatory growth factor and member of the epidermal growth factor family, is a mediator of oncogenesis and malignant progression in colorectal carcinogenesis. Limited evidence suggests its utility as a growth-related biomarker of risk for colorectal cancer. METHODS: We measured expression of TGF-alpha in biopsies of normal-appearing colorectal mucosa using automated immunohistochemistry and quantitative image analysis in a subsample of 29 cases and 31 controls from a colonoscopy-based case-control study (n = 203) of biomarkers of risk for incident sporadic colorectal adenoma. Diet, lifestyle, and medical history were assessed with validated questionnaires. RESULTS: TGF-alpha expression in the rectum was 51% higher in cases compared with controls (P = 0.05) and statistically significantly associated with accepted risk factors for colorectal neoplasms (36% lower among nonsteroidal anti-inflammatory drug users, 49% lower among women using hormone replacement therapy, 79% higher among persons with a family history of colorectal cancer). CONCLUSIONS: TGF-alpha expression in the normal-appearing rectal mucosa shows promise as an early, potentially modifiable biomarker of risk for colorectal cancer.

Physical activity and depressive symptoms among Norwegian adults aged 20-50.

INTRODUCTION: To analyze the association between physical activity (PA) and occurrence of depressive symptoms in The Nord-Trøndelag Health Survey (HUNT 1 1984-1986, HUNT 2 1995-1997). METHODS: In this prospective follow-up study, we studied men and women who were 21-40 years old in HUNT 1, and participated in HUNT 2. The sample consisted of 3,353 women and 3,308 men. We used logistic regression and calculated odds ratios (OR) to assess the association between physical activity and depression (Hospital Anxiety and Depression Scale depression subscale [HADS-D]). Confounding was addressed by excluding those with relevant health conditions and adjustment. RESULTS: Among women 272 (8.1%) and among men 293 (8.9%) scored higher than 8 on the HADS-D scale. We found a higher mean on HADS-D in men and women who were inactive. Men participating in low PA had significantly lower scores on depression (OR=0.63, confidence interval [CI]=0.43-0.93, p=.02) than inactive men. Women participating in medium PA had significantly lower scores on depression (OR=0.69, CI=0.49-0.97, p=.03) than inactive women. CONCLUSIONS: Young men and women who exercised were less likely to have a high depression score, compared with inactive people. Our prospective, observational study included a large population and indicated some significant associations between physical activity and depression.

Occurrence of and mortality from childhood neuronal ceroid lipofuscinoses in norway.

The aim of this study was to estimate the prevalence of, incidence of, and survival from childhood neuronal lipofuscinoses in Norway. All children with neuronal ceroid lipofuscinoses living in Norway are referred to the Tambartun National Resource Centre for the Visually Impaired. We based the data collection on the medical records at Tambartun. We identified 70 children with neuronal ceroid lipofuscinoses who were born in Norway from 1957 to 1998. Seven had a diagnosis of late infantile neuronal ceroid lipofuscinoses, and 63 had the juvenile form of neuronal ceroid lipofuscinoses. In 2005, the prevalence of childhood neuronal ceroid lipofuscinoses was 8.3 per million inhabitants in Norway, and all children were diagnosed with the juvenile form. The average annual incidence rate of childhood neuronal ceroid lipofuscinoses was 1.8 per 100,000 live births using the years from 1957 to 1978 and 3.9 using the years from 1978 to 1999. The trend in incidence increased at an annual rate of about 3.3% per year (P = .001), averaged over this period. Restricted to the most recent period (1967-1998), the trend was much weaker (1.4% increase per year; P = .3), and confidence intervals included the possibility of no trend. The median age at death of children diagnosed with late infantile neuronal ceroid lipofuscinoses was 12 years (95% confidence interval 9-14) and 26 years (95% confidence interval 25-30) for children diagnosed with the juvenile form. The results did not support the hypothesis that children with neuronal ceroid lipofuscinoses born in 1975 or later lived longer than those born from 1957 to 1975 (relative risk 1.0, 95% confidence interval 0.36-2.8). Mortality was similar for both genders (hazard ratio 0.97, 95% confidence interval 0.4-2.2).

Healthy postmenopausal women- physical activity and forearm bone mineral density: the Nord-Trøndelag health survey.

UNLABELLED: The aim of this study was to analyze the association between Physical Activity (PA) and forearm bone mineral density (BMD) in healthy postmenopausal women. During 1984-1986, a population-based health survey (HUNT-1) was conducted in Nord-Trøndelag county, Norway. The second follow-up survey (HUNT-2) was conducted during 1995-1997. The subjects consist of all healthy postmenopausal women (N = 2,924). Higher intensity of recreational PA in HUNT-1 was associated with higher BMD ultradistally (slope = +0.0084, p = 0.0009). The summary score of duration, frequency and intensity of recreational PA in HUNT-1 was associated with lower risk of being below the 20th percentile ultradistally (OR = 0.90, p = 0.01, after adjustment for covariates). The trends for mean distal and ultradistal BMD and percent low BMD lacked statistical significance when we used the PA score that combined the recreational and occupational PA in HUNT-1 and HUNT-2. CONCLUSION: Higher intensity of prior recreational PA (HUNT-1) was associated with a protective effect on BMD measured in the forearm (HUNT- 2).