Current use of estrogen-containing oral contraceptives or hormone therapy and risk of COVID-19 infection and hospitalization: a population-based cohort study.

This population-based cohort study evaluated the association between current use of oral contraceptives (OC) among women under 50 years (n=306,541), and hormone therapy (HT) among women aged 50 or older (n=323,203), and COVID-19 infection and hospitalization. Current OC/HT use was recorded monthly using prescription dispensing data. COVID-19 infections were identified March 2020-February 2021. COVID-19 infection and hospitalization were identified through diagnosis codes and laboratory tests. Weighted generalized estimating equations models estimated multivariable-adjusted odds ratios (aORs) for COVID-19 infection associated with time-varying OC/HT use. Among women with COVID-19, logistic regression models evaluated OC/HT use and COVID-19 hospitalization. Over 12 months, 11,727 (3.8%) women <50 years and 8,661 (2.7%) women ≥50 years experienced COVID-19 infections. There was no evidence of an association between OC use and infection (aOR=1.05; 95%CI: 0.97, 1.12). There was a modest association between HT use and infection (aOR=1.19; 95%CI: 1.03, 1.38). Women using OC had a 39% lower risk of hospitalization (aOR=0.61; 95%CI: 0.38, 1.00), but there was no association of HT use with hospitalization (aOR=0.89; 95%CI: 0.51, 1.53). These findings do not suggest a meaningfully greater risk of COVID-19 infection associated with OC or HT use. OC use may be associated with lower COVID-19 hospitalization risk.

External Validation of the eRADAR Risk Score for Detecting Undiagnosed Dementia in Two Real-World Healthcare Systems.

BACKGROUND: Fifty percent of people living with dementia are undiagnosed. The electronic health record (EHR) Risk of Alzheimer's and Dementia Assessment Rule (eRADAR) was developed to identify older adults at risk of having undiagnosed dementia using routinely collected clinical data. OBJECTIVE: To externally validate eRADAR in two real-world healthcare systems, including examining performance over time and by race/ethnicity. DESIGN: Retrospective cohort study PARTICIPANTS: 129,315 members of Kaiser Permanente Washington (KPWA), an integrated health system providing insurance coverage and medical care, and 13,444 primary care patients at University of California San Francisco Health (UCSF), an academic medical system, aged 65 years or older without prior EHR documentation of dementia diagnosis or medication. MAIN MEASURES: Performance of eRADAR scores, calculated annually from EHR data (including vital signs, diagnoses, medications, and utilization in the prior 2 years), for predicting EHR documentation of incident dementia diagnosis within 12 months. KEY RESULTS: A total of 7631 dementia diagnoses were observed at KPWA (11.1 per 1000 person-years) and 216 at UCSF (4.6 per 1000 person-years). The area under the curve was 0.84 (95% confidence interval: 0.84-0.85) at KPWA and 0.79 (0.76-0.82) at UCSF. Using the 90th percentile as the cut point for identifying high-risk patients, sensitivity was 54% (53-56%) at KPWA and 44% (38-51%) at UCSF. Performance was similar over time, including across the transition from International Classification of Diseases, version 9 (ICD-9) to ICD-10 codes, and across racial/ethnic groups (though small samples limited precision in some groups). CONCLUSIONS: eRADAR showed strong external validity for detecting undiagnosed dementia in two health systems with different patient populations and differential availability of external healthcare data for risk calculations. In this study, eRADAR demonstrated generalizability from a research sample to real-world clinical populations, transportability across health systems, robustness to temporal changes in healthcare, and similar performance across larger racial/ethnic groups.

Association Between Diabetes Severity and Risks of COVID-19 Infection and Outcomes.

BACKGROUND: Little is known about whether diabetes increases the risk of COVID-19 infection and whether measures of diabetes severity are related to COVID-19 outcomes. OBJECTIVE: Investigate diabetes severity measures as potential risk factors for COVID-19 infection and COVID-19 outcomes. DESIGN, PARTICIPANTS, MEASURES: In integrated healthcare systems in Colorado, Oregon, and Washington, we identified a cohort of adults on February 29, 2020 (n = 1,086,918) and conducted follow-up through February 28, 2021. Electronic health data and death certificates were used to identify markers of diabetes severity, covariates, and outcomes. Outcomes were COVID-19 infection (positive nucleic acid antigen test, COVID-19 hospitalization, or COVID-19 death) and severe COVID-19 (invasive mechanical ventilation or COVID-19 death). Individuals with diabetes (n = 142,340) and categories of diabetes severity measures were compared with a referent group with no diabetes (n = 944,578), adjusting for demographic variables, neighborhood deprivation index, body mass index, and comorbidities. RESULTS: Of 30,935 patients with COVID-19 infection, 996 met the criteria for severe COVID-19. Type 1 (odds ratio [OR] 1.41, 95% CI 1.27-1.57) and type 2 diabetes (OR 1.27, 95% CI 1.23-1.31) were associated with increased risk of COVID-19 infection. Insulin treatment was associated with greater COVID-19 infection risk (OR 1.43, 95% CI 1.34-1.52) than treatment with non-insulin drugs (OR 1.26, 95% 1.20-1.33) or no treatment (OR 1.24; 1.18-1.29). The relationship between glycemic control and COVID-19 infection risk was dose-dependent: from an OR of 1.21 (95% CI 1.15-1.26) for hemoglobin A1c (HbA1c) < 7% to an OR of 1.62 (95% CI 1.51-1.75) for HbA1c ≥ 9%. Risk factors for severe COVID-19 were type 1 diabetes (OR 2.87; 95% CI 1.99-4.15), type 2 diabetes (OR 1.80; 95% CI 1.55-2.09), insulin treatment (OR 2.65; 95% CI 2.13-3.28), and HbA1c ≥ 9% (OR 2.61; 95% CI 1.94-3.52). CONCLUSIONS: Diabetes and greater diabetes severity were associated with increased risks of COVID-19 infection and worse COVID-19 outcomes.

Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.

AIM: The aim of this study was to identify skeletal muscle relaxant (SMR) drug-drug-drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury. METHODS: We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self-controlled case series study for each drug triad consisting of an SMR base-pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base-pair. We included patients aged ≥16 years with an injury occurring during base-pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base-pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base-pair alone. RESULTS: Among 58 478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI = 1.01-1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02-4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. CONCLUSION: We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.

Use of a mobile app to capture supplemental health information during pregnancy: Implications for clinical research.

PURPOSE: Mobile applications ("apps") may be efficient tools for improving the quality of clinical research among pregnant women, but evidence is sparse. We assess the feasibility and generalizability of a mobile app for capturing supplemental data during pregnancy. METHODS: In 2017, we conducted a pilot study of the FDA MyStudies mobile app within a pregnant population identified through Kaiser Permanente Washington (KPWA), an integrated healthcare delivery system. We ascertained health conditions, medications, and substance use through app-based questionnaires. In a post-hoc analysis, we utilized electronic health records (EHR) to summarize sociodemographic and health characteristics of pilot participants and, for comparison, a pregnant population identified using similar methods. RESULTS: Six percent (64/1070) of contacted women enrolled in the pilot study. Nearly half (23/53) reported taking medication for headaches and one-fourth for constipation (13/53) and nausea (12/53) each. Few instances (2/92) of over-the-counter medication use were identified in electronic dispensing records. One-quarter to one-third of participants with depression and anxiety/panic, respectively, reported recently discontinuing medications for these conditions. Eighty-eight percent of pilot participants reported White race (95%CI: 81-95%), versus 67% of the comparison population (N = 2065). More pilot participants filled ≥1 prescription for antianxiety medication (22% [95%CI: 13-35%]) and antidepressants (19% [95%CI 10-31%]) pre-pregnancy than the comparison population (10 and 9%, respectively). CONCLUSIONS: Mobile apps may be a feasible tool for capturing health data not routinely available in EHR. Pregnant women willing to use a mobile app for research may differ from the general pregnant population, but confirmation is needed.

Validation of diagnosis codes to identify hospitalized COVID-19 patients in health care claims data.

PURPOSE: Health plan claims may provide complete longitudinal data for timely, real-world population-level COVID-19 assessment. However, these data often lack laboratory results, the standard for COVID-19 diagnosis. METHODS: We assessed the validity of ICD-10-CM diagnosis codes for identifying patients hospitalized with COVID-19 in U.S. claims databases, compared to linked laboratory results, among six Food and Drug Administration Sentinel System data partners (two large national insurers, four integrated delivery systems) from February 20-October 17, 2020. We identified patients hospitalized with COVID-19 according to five ICD-10-CM diagnosis code-based algorithms, which included combinations of codes U07.1, B97.29, general coronavirus codes, and diagnosis codes for severe symptoms. We calculated the positive predictive value (PPV) and sensitivity of each algorithm relative to laboratory test results. We stratified results by data source type and across three time periods: February 20-March 31 (Time A), April 1-30 (Time B), May 1-October 17 (Time C). RESULTS: The five algorithms identified between 34 806 and 47 293 patients across the study periods; 23% with known laboratory results contributed to PPV calculations. PPVs were high and similar across algorithms. PPV of U07.1 alone was stable around 93% for integrated delivery systems, but declined over time from 93% to 70% among national insurers. Overall PPV of U07.1 across all data partners was 94.1% (95% CI, 92.3%-95.5%) in Time A and 81.2% (95% CI, 80.1%-82.2%) in Time C. Sensitivity was consistent across algorithms and over time, at 94.9% (95% CI, 94.2%-95.5%). CONCLUSION: Our results support the use of code U07.1 to identify hospitalized COVID-19 patients in U.S. claims data.

Association of Antidepressant Continuation in Pregnancy and Infant Birth Weight.

PURPOSE: The aim of the study was to evaluate the association of antidepressant continuation in pregnancy with infant birth weight among women using antidepressants before pregnancy. METHODS: This retrospective cohort study used electronic health data linked with state birth records. We identified singleton live births (2001-2014) to enrolled women with 1 or more antidepressant prescriptions filled 6 months or less before pregnancy, including "continuers" (≥1 antidepressant fills during pregnancy, n = 1775) and "discontinuers" (no fill during pregnancy, n = 1249). We compared birth weight, small or large for gestational age (SGA or LGA), low birth weight (LBW; <2500 g), and macrosomia (>4500 g) between the 2 groups, using inverse probability of treatment weighting to account for pre-pregnancy characteristics, including mental health conditions. RESULTS: After weighting, infants born to antidepressant continuers weighed 71.9 g less than discontinuers' infants (95% confidence interval [CI], -115.5 to -28.3 g), with a larger difference for female infants (-106.4 g; 95% CI, -164.6 to -48.1) than male infants (-48.5 g; 95% CI, -107.2 to 10.3). For female infants, SGA risk was greater in continuers than discontinuers (relative risk [RR],1.54; 95% CI, 1.02 to 2.32). Low birth weight risk was greater in continuers with 50% or more of days covered (RR, 1.69; 95% CI, 1.11 to 2.58) and exposure in the second trimester (RR, 1.53; 95% CI, 1.02 to 2.29), as compared with discontinuers. CONCLUSIONS: Depending on infant sex, as well as duration and timing of use, continuation of antidepressant use during pregnancy may be associated with lower infant birth weight, with corresponding increases in LBW and SGA.

Prevalence of prescription opioid use during pregnancy in eight US health plans during 2001-2014.

PURPOSE: To estimate prevalence of prescription opioid use during pregnancy in eight US health plans during 2001-2014. METHODS: We conducted a cohort study of singleton live birth deliveries. Maternal characteristics were ascertained from health plan and/or birth certificate data and opioids dispensed during pregnancy from health plan pharmacy records. Prevalence of prescription opioid use during pregnancy was calculated for any use, cumulative days of use, and number of dispensings. RESULTS: We examined prevalence of prescription opioid use during pregnancy in each health plan. Tennessee Medicaid had appreciably greater prevalence of use compared to the seven other health plans. Thus, results for the two groups were reported separately. In the seven health plans (n = 587 093 deliveries), prevalence of use during pregnancy was relatively stable at 9%-11% throughout 2001-2014. In Tennessee Medicaid (n = 256 724 deliveries), prevalence increased from 29% in 2001 to a peak of 36%-37% in 2004-2010, and then declined to 28% in 2014. Use for ≥30 days during pregnancy was stable at 1% in the seven health plans and increased from 2% to 7% in Tennessee Medicaid during 2001-2014. Receipt of ≥5 opioid dispensings during pregnancy increased in the seven health plans (0.3%-0.6%) and Tennessee Medicaid (3%-5%) during 2001-2014. CONCLUSION: During 2001-2014, prescription opioid use during pregnancy was more common in Tennessee Medicaid (peak prevalence in late 2000s) compared to the seven health plans (relatively stable prevalence). Although a small percentage of women had opioid use during pregnancy for ≥30 days or ≥ 5 dispensings, they represent thousands of women during 2001-2014.

Patient and caregiver perspectives on a tool to increase recognition of undiagnosed dementia: a qualitative study.

BACKGROUND: Early detection of dementia may improve patient care and quality of life, yet up to half of people with dementia are undiagnosed. Electronic health record (EHR) data could be used to help identify individuals at risk of having undiagnosed dementia for outreach and assessment, but acceptability to people with dementia and caregivers is unknown. METHODS: We conducted five focus groups at Kaiser Permanente Washington (KPWA), an integrated healthcare system in Washington State, to explore people's feelings about timing of dementia diagnosis, use of EHR-based tools to predict risk of undiagnosed dementia, and communication about risk. We recruited people enrolled in KPWA who had dementia or mild cognitive impairment, people enrolled in KPWA who had neither diagnosis, and caregivers (i.e., loved ones of people with dementia who assist with various tasks of daily life). People who were non-white or Hispanic were oversampled. Two team members analyzed transcripts using thematic coding. RESULTS: Forty people (63% women; 59% non-white or Hispanic) participated in the focus groups. Themes that arose included: perceived pros and cons of early dementia diagnosis; questions and concerns about a potential tool to assess risk of undiagnosed dementia; and preferences related to patient-provider conversations disclosing that a person was at high risk to have undiagnosed dementia. Participants supported early diagnosis, describing benefits such as time to adjust to the disease, plan, involve caregivers, and identify resources. They also acknowledged the possible psychosocial toll of receiving the diagnosis. Participants supported use of an EHR-based tool, but some people worried about accuracy and privacy. Participants emphasized that information about risk of undiagnosed dementia should be communicated thoughtfully by a trusted provider and that the conversation should include advice about prognosis, treatment options and other resources when a new dementia diagnosis was made. CONCLUSION: People with dementia or mild cognitive impairment, people with neither diagnosis, and caregivers of people with dementia supported using EHR-based tools to help identify individuals at risk of having undiagnosed dementia. Such tools must be implemented carefully to address concerns and ensure that people living with dementia and their caregivers are adequately supported.

Maternal Gestational Weight Gain in Relation to Antidepressant Continuation in Pregnancy.

OBJECTIVE: Both excessive and inadequate gestational weight gain (GWG) are associated with adverse health outcomes for the woman and her child. Antidepressant use in pregnancy could affect GWG, based on evidence in nonpregnant women that some antidepressants may cause weight gain and others weight loss. Previous studies of antidepressant use and GWG were small with limited ability to account for confounding, including by maternal mental health status and severity. We assessed the association of antidepressant continuation in pregnancy with GWG among women using antidepressants before pregnancy. STUDY DESIGN: Our retrospective cohort study included singleton livebirths from 2001 to 2014 within Kaiser Permanente Washington, an integrated health care system. Data were obtained from electronic health records and linked Washington State birth records. Among women with ≥1 antidepressant fill within 6 months before pregnancy, women who filled an antidepressant during pregnancy were considered "continuers;" women without a fill were "discontinuers." We calculated mean differences in GWG and relative risks (RR) of inadequate and excessive weight gain based on Institute of Medicine guidelines. Using inverse probability of treatment weighting with generalized estimating equations, we addressed differences in maternal characteristics, including mental health conditions. RESULTS: Among the 2,887 births, 1,689 (59%) were to women who continued antidepressants in pregnancy and 1,198 (42%) were to discontinuers. After accounting for confounding, continuers had similar weight gain to those who discontinued (mean difference: 1.3 lbs, 95% confidence interval [CI]: -0.1 to 2.8 lbs) and similar risks of inadequate and excessive GWG (RR: 0.95, 95% CI: 0.80-1.14 and RR: 1.06, 95% CI: 0.98-1.14, respectively). Findings were comparable for specific antidepressants and trimesters of exposure. CONCLUSION: We did not find evidence that continuation of antidepressants in pregnancy led to differences in GWG. KEY POINTS: · Antidepressant use is associated with weight change in nonpregnant populations.. · Prior evidence on whether antidepressant use in pregnancy affects gestational weight gain is sparse.. · We accounted for confounding by characteristics such as mental health conditions and their severity.. · We found no association between pregnancy antidepressant continuation and gestational weight gain..

Risk of incident dementia following metformin initiation compared with noninitiation or delay of antidiabetic medication therapy.

PURPOSE: Emerging evidence suggests metformin compared with sulfonylurea is associated with an 8% to 10% lower risk for dementia. Guidelines recommend metformin as initial diabetes treatment, but there is still the question of treatment timing. Thus, the risk of dementia associated with initiating metformin compared with not initiating or delaying treatment was examined. METHODS: A retrospective cohort study (1996 to 2015) was conducted with electronic health records from Veteran Health Affairs (VHA; n = 112 845) and Kaiser Permanente Washington (KPW; n = 14 333) healthcare systems. Patients were aged ≥50 years, had a hemoglobin A1c (HbA1c) between 6.5 and <9.5 mg/dL, and did not have dementia or fills for antidiabetic medications before cohort entry. Initiators started metformin monotherapy and noninitiators used no antidiabetic medications in the 6 months after the first qualifying HbA1c. The primary outcome was incident dementia. Propensity scores and inverse probability of treatment weighting (IPTW) controlled for confounding in Cox proportional hazards models. RESULTS: During a median follow-up of 6.2 years in VHA and 6.8 years in KPW, there were 7547 new dementia cases in VHA and 1090 in KPW. After IPTW, there was no association between initiation of metformin (vs no initial treatment) and incident dementia in VHA (HR = 1.04; 95% confidence interval [CI]: 0.95-1.13) or KPW (HR = 0.81; 95% CI: 0.51-1.28). Results did not differ by age, baseline HbA1c, or race. CONCLUSIONS: Results do not support initiating metformin earlier to prevent cognitive decline and, thus, may dampen enthusiasm for metformin as a potential antidementia drug. Randomized clinical trials could help clarify the relationship between metformin and cognitive decline.

Validity of diagnosis and procedure codes for identifying neural tube defects in infants.

PURPOSE: The use of validated criteria to identify birth defects in electronic healthcare databases can avoid the cost and time-intensive efforts required to conduct chart reviews to confirm outcomes. This study evaluated the validity of various case-finding methodologies to identify neural tube defects (NTDs) in infants using an electronic healthcare database. METHODS: This analysis used data generated from a study whose primary aim was to evaluate the association between first-trimester maternal prescription opioid use and NTDs. The study was conducted within the Medication Exposure in Pregnancy Risk Evaluation Program. A broad approach was used to identify potential NTDs including diagnosis and procedure codes from inpatient and outpatient settings, death certificates and birth defect flags in birth certificates. Potential NTD cases were chart abstracted and confirmed by clinical experts. Positive predictive values (PPVs) and 95% confidence intervals (95% CI) are reported. RESULTS: The cohort included 113 168 singleton live-born infants: 55 960 infants with opioid exposure in pregnancy and 57 208 infants unexposed in pregnancy. Seventy-three potential NTD cases were available for the validation analysis. The overall PPV was 41% using all diagnosis and procedure codes plus birth certificates. Restricting approaches to codes recorded in the infants' medical record or to birth certificate flags increased the PPVs (72% and 80%, respectively) but missed a substantial proportion of confirmed NTDs. CONCLUSIONS: Codes in electronic healthcare data did not accurately identify confirmed NTDs. These results indicate that chart review with adjudication of outcomes is important when conducting observational studies of NTDs using electronic healthcare data.

Association Between Metformin Initiation and Incident Dementia Among African American and White Veterans Health Administration Patients.

PURPOSE: African American patients are more likely to experience cognitive decline after type 2 diabetes mellitus onset than white patients. Metformin use has been associated with a lower risk of dementia compared with sulfonylureas. Evidence for whether this association differs by race is sparse. METHODS: Veterans Health Administration (VHA) medical record data were obtained for 73,761 African American and white patients aged ≥50 years who used the VHA from fiscal years 2000 to 2015. Patients were free of dementia and diabetes medications during fiscal years 2000 and 2001 and subsequently initiated metformin or sulfonylurea monotherapy. For race and age subgroups, Cox proportional hazards models using propensity scores and inverse probability of treatment weighting to control for confounding were computed to measure the association between metformin vs sulfonylurea initiation and incident dementia. RESULTS: After controlling for confounding, among patients aged ≥50 years, metformin vs sulfonylurea use was associated with a significantly lower risk of dementia in African American patients (hazard ratio [HR] = 0.73; 95% CI, 0.6-0.89) but not white patients (HR = 0.96; 95% CI, 0.9-1.03). The strongest magnitude of association between metformin and dementia was observed among African American patients aged 50 to 64 years (HR = 0.6; 95% CI, 0.45-0.81). Among those aged 65 to 74 years, metformin was significantly associated with lower risk of dementia in both races. Metformin was not associated with dementia in patients aged ≥75 years. CONCLUSIONS: Metformin vs sulfonylurea initiation was associated with a substantially lower risk of dementia among younger African American patients. These results may point to a novel approach for reducing the risk of dementia in African Americans with type 2 diabetes mellitus.

Antidepressant continuation in pregnancy and risk of gestational diabetes.

PURPOSE: Previous studies observed modestly higher risk of gestational diabetes (GDM) associated with antidepressant use in pregnancy, potentially due to confounding by indication. We assessed the association of antidepressant continuation in pregnancy with GDM, as well as blood glucose levels, after accounting for confounding. METHODS: We conducted a retrospective cohort study of singleton live births from 2001 to 2014 to women enrolled in Kaiser Permanente Washington, an integrated health care delivery system, utilizing electronic health data and linked Washington State birth records. We required that women have ≥1 antidepressant prescription fills ≤6 months before pregnancy. Women with an antidepressant fill during pregnancy were categorized as "continuers" (n = 1634); those without a fill were "discontinuers" (n = 1211). We calculated relative risks (RRs) for GDM and mean differences in screening blood glucose levels using generalized estimating equations with inverse probability of treatment weighting to account for baseline characteristics, including mental health conditions and indicators of mental health severity. RESULTS: Compared with discontinuers, antidepressant continuers had comparable risk of GDM (RR: 1.10; 95% confidence interval [CI], 0.84-1.44) and blood glucose levels (mean difference: 2.3 mg/dL; 95% CI, -1.5 to 6.1 mg/dL). We observed generally similar results for specific antidepressants, with the potential exceptions of risk of GDM associated with sertraline (RR: 1.30; 95% CI, 0.90-1.88) and venlafaxine (RR: 1.52; 95% CI, 0.87-2.68), but neither association was statistically significant. CONCLUSIONS: Our study suggests that overall, women who continue antidepressants in pregnancy are not at increased risk for GDM or higher blood glucose, although further study may be warranted for sertraline and venlafaxine.

Impact of initiatives to reduce prescription opioid risks on medically attended injuries in people using chronic opioid therapy.

PURPOSE: The purpose of the study is to determine whether initiatives to improve the safety of opioid prescribing decreased injuries in people using chronic opioid therapy (COT). METHODS: We conducted an interrupted time series analysis using data from Group Health (GH), an integrated health care delivery system in the United States. In 2007, GH implemented initiatives which substantially reduced daily opioid dose and increased patient monitoring. Among GH members age 18 or older receiving COT between 2006 and 2014, we compared injury rates for patients in GH's integrated group practice (IGP; exposed to the initiatives) vs patients cared for by contracted providers (not exposed). Injuries were identified using a validated algorithm. We calculated injury incidence during the baseline (preintervention) period from 2006 to 2007; the dose reduction period, 2008 to 2010; and the risk stratification and monitoring period, 2010 to 2014. Using modified Poisson regression, we estimated adjusted relative risks (RRs) representing the relative change per year in injury rates. RESULTS: Among 21 853 people receiving COT in the IGP and 8260 in contracted care, there were 2679 injuries during follow-up. The baseline injury rate was 1.0% per calendar quarter in the IGP and 0.9% in contracted care. Risk reduction initiatives did not decrease injury rates: Within the IGP, the RR in the dose reduction period was 1.01 (95% CI, 0.95-1.07) and in the risk stratification and monitoring period, 0.99 (95% CI, 0.95-1.04). Injury trends did not differ between the two care settings. CONCLUSIONS: Risk reduction initiatives did not decrease injuries in people using COT.

Patterns of antihypertensive and statin adherence prior to dementia: findings from the adult changes in thought study.

BACKGROUND: Detecting patients with undiagnosed dementia is an important clinical challenge. Changes in medication adherence might represent an early sign of cognitive impairment. We sought to examine antihypertensive and statin adherence trajectories in community-dwelling older adults, comparing people who went on to develop dementia to those who did not. METHODS: We analyzed data from Adult Changes in Thought (ACT), a population-based cohort study embedded within an integrated healthcare delivery system. Analyses included 4368 participants aged ≥65 years who had at least one follow-up visit. Research-quality dementia diagnoses were used to identify cases. We selected non-dementia control visits matched on age, sex, and study cohort that occurred at similar ACT follow-up time as the case's dementia onset; we treated this as the index date. Participants were included if they were prevalent users of either a statin or antihypertensive medication on the first day of follow up - 3 years prior to the index date. Using prescription fill dates and days supply, we calculated daily binary medication availability measures for each participant ('days covered') over 3 years leading up to the index date. We used group-based trajectory models to identify patterns of antihypertensive and statin adherence, and used conditional logistic regression to examine associations between adherence trajectories and dementia. RESULTS: Four trajectories were identified for antihypertensive users (292 cases, 3890 control visits), including near perfect (n = 1877, 36.6% cases, 45.5% controls), high (n = 1840, 43.2% cases, 44.1% controls), moderate (n = 365, 18.5% cases, 8.0% controls) and early poor adherence (n = 100, 1.7% cases, 2.4% controls). Odds of dementia was 3 times greater for those with moderate antihypertensive adherence compared to those with near perfect adherence (adjusted OR 3.0, 95% CI 2.0, 4.3). Four trajectories were identified for statin users (148 cases, 1131 control visits), including high (n = 1004, 75.0% cases, 79.0% controls), moderate (n = 192, 19.6% cases, 14.4% controls), early poor (n = 43, 2.0% cases, 3.5% controls), and delayed poor adherence (n = 40, 3.4% cases, 3.1% controls). No association was detected between statin adherence trajectories and dementia. CONCLUSIONS: Patterns of medication adherence may be useful to identify a subset of people at higher likelihood of developing dementia.

Early Pregnancy Hemoglobin A1C and Pregnancy Outcomes: A Population-Based Study.

OBJECTIVE: Women with prediabetes are identified from screening for overt diabetes in early pregnancy, but the clinical significance of prediabetes in pregnancy is unclear. We examined whether prediabetes in early pregnancy was associated with risks of adverse outcomes. STUDY DESIGN: We conducted a retrospective cohort study of pregnant women enrolled in Kaiser Permanente Washington from 2011 to 2014. Early pregnancy hemoglobin A1C (A1C) values, covariates, and outcomes were ascertained from electronic medical records and state birth certificates. Women with prediabetes (A1C of 5.7-6.4%) were compared with those with normal A1C levels (<5.7%) for risk of gestational diabetes mellitus (GDM) and other outcomes including preeclampsia, primary cesarean delivery, induction of labor, large/small for gestational age, preterm birth, and macrosomia. We used modified Poisson's regression to calculate adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Of 7,020 women, 239 (3.4%) had prediabetes. GDM developed in 48% of prediabetic women compared with 11% of women with normal A1C levels (adjusted RR: 2.8, 95% CI: 2.4-3.3). Prediabetes was not associated with all other adverse maternal and neonatal outcomes. CONCLUSION: Prediabetes in early pregnancy is a risk factor for GDM. Future research is needed to elucidate whether early intervention may reduce this risk.

Proton pump inhibitor use and the risk of fractures among an older adult cohort.

PURPOSE: The purpose of the study is to determine if the use of a proton pump inhibitor (PPI) is associated with an increased fracture risk, as some prior studies have suggested. METHODS: This retrospective cohort study included data on 4438 participants aged 65 and older who had no fracture in the year prior to baseline and had ≥5 years of enrollment history in Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, WA, during 1994 to 2014. Time-varying cumulative exposure to PPIs was determined from automated pharmacy data by summing standard daily doses (SDDs) across fills, and patients were categorized as no use (reference group, ≤30 SDD), light use (31-540 SDD), moderate use (541-1080 SDD), and heavy use (≥1081 SDD). Incident fractures were assessed using International Classification of Diseases, Ninth Revision codes from electronic medical records. Potential confounders, chosen a priori, were assessed at baseline and at each 2-year follow-up visit. Fracture risk was analyzed using a Cox proportional hazards model. RESULTS: Over a mean follow-up of 6.1 years, 802 (18.1%) participants experienced a fracture. No overall association was found between PPI use and fracture risk. Adjusted hazard ratios comparing users to the referent category were 1.08 (95% CI 0.83-1.40) for light users, 1.31 (95% CI 0.86-1.95) for moderate users, and 0.95 (95% CI 0.68-1.34) for heavy users. Among patients with SSD > 30, no appreciable increase in fracture risk was present in persons with recent versus distant use (adjusted hazard ratio of 1.14 [95% CI 0.91-1.42]). CONCLUSIONS: No association was observed between PPI use and fracture risk among older adults.

Impact of Opioid Dose Reduction and Risk Mitigation Initiatives on Chronic Opioid Therapy Patients at Higher Risk for Opioid-Related Adverse Outcomes.

Objective: We aimed to determine if opioid risk reduction initiatives including dose reduction and risk mitigation strategies for chronic noncancer pain patients receiving chronic opioid therapy (COT) had a differential impact on average daily opioid doses of COT patients at higher risk for opioid-related adverse outcomes compared with lower-risk patients. Design: Interrupted time series. Setting: Group Health Cooperative (GH), a health care delivery system and insurance within Washington State, between 2006 and 2014. Population: GH enrollees on COT defined as receiving a supply of 70 or more days of opioids within 90 days using electronic pharmacy data for filled prescriptions. Methods: We compared the average daily morphine equivalent doses (MED) of COT patients with and without each of the following higher-risk characteristics: mental disorders, substance use disorders, sedative use, and male gender. Results: In all four pairwise comparisons, the higher-risk subgroup had a higher average daily MED than the lower-risk subgroup across the study period. Adjusted for covariates, modest differences in the annual rate of reduction in average daily MED were noted between higher- and lower-risk subgroups in three pairwise comparisons: those with mental disorders vs without (-8.2 mg/y vs -5.2 mg/y, P = 0.005), with sedative use vs without (-9.2 mg/y vs -5.8 mg/y, P = 0.004); mg), in men vs women (-8.8 mg/y vs -5.9 mg/y, P = 0.01). Conclusion: Using clinical policy initiatives in a health care system, dose reductions were achieved among COT patients at higher risk for opioid-related adverse outcomes that were at least as large as those among lower-risk patients.

Getting through the day: a pilot qualitative study of U.S. women's experiences making decisions about anti-nausea medication during pregnancy.

BACKGROUND: Nausea during pregnancy affects 80% of pregnant women and can severely affect women's functioning and quality of life. Women often have difficulty deciding whether to take anti-nausea medications due to concern about medication risks. This paper foregrounds U.S. women's voices as they share their experiences making decisions about anti-nausea medication use. METHODS: As a pilot study, we conducted two focus groups including 20 women who had filled at least one prescription for an anti-nausea medication during pregnancy. Topics included deciding about and taking anti-nausea medications. Transcripts were analyzed by two medical anthropologists using an inductive or open coding approach. RESULTS: Women in our pilot study carefully considered whether to take anti-nausea medications. Most women preferred not to take medications, in general, but were willing to do so for severe symptoms. When considering medications, they expressed concerns about risks to fetal health. They considered information from internet research, their health care provider, and the experiences of friends and family. While some women in our study decided against taking medications, many did take a prescription medication, and they reported substantial improvement in their symptoms and sense of well-being. CONCLUSIONS: Women weighed various sources of evidence to assess the risks and benefits of taking anti-nausea medication and ultimately made a range of choices. More research is needed about the effectiveness and risks of anti-nausea medication, to help support women in their decision-making process, and also about the best methods to communicate scientific evidence to women.