Dynamic Risk Prediction of Response to Ursodeoxycholic Acid Among Patients with Primary Biliary Cholangitis in the USA.

BACKGROUND: Ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC); however, inadequate treatment response (ITR) is common. The UK-PBC Consortium developed the modified UDCA Response Score (m-URS) to predict ITR (using alkaline phosphatase [ALP] > 1.67 times the upper limit of normal [*ULN]) at 12 months post-UDCA initiation). Using data from the US-based Fibrotic Liver Disease Consortium, we assessed the m-URS in our multi-racial cohort. We then used a dynamic modeling approach to improve prediction accuracy. METHODS: Using data collected at the time of UDCA initiation, we assessed the m-URS using the original formula; then, by calibrating coefficients to our data, we also assessed whether it remained accurate when using Paris II criteria for ITR. Next, we developed and validated a dynamic risk prediction model that included post-UDCA initiation laboratory data. RESULTS: Among 1578 patients (13% men; 8% African American, 9% Asian American/American Indian/Pacific Islander; 25% Hispanic), the rate of ITR was 27% using ALP > 1.67*ULN and 45% using Paris II criteria. M-URS accuracy was "very good" (AUROC = 0.87, sensitivity = 0.62, and specificity = 0.82) for ALP > 1.67*ULN and "moderate" (AUROC = 0.74, sensitivity = 0.57, and specificity = 0.70) for Paris II. Our dynamic model significantly improved accuracy for both definitions of ITR (ALP > 1.67*ULN: AUROC = 0.91; Paris II: AUROC = 0.81); specificity approached 100%. Roughly 9% of patients in our cohort were at the highest risk of ITR. CONCLUSIONS: Early identification of patients who will not respond to UDCA treatment using a dynamic prediction model based on longitudinal, repeated risk factor measurements may facilitate earlier introduction of adjuvant treatment.

The use of narrative electronic prescribing instructions in pharmacoepidemiology: A scoping review for the International Society for Pharmacoepidemiology.

Narrative electronic prescribing instructions (NEPIs) are text that convey information on the administration or co-administration of a drug as directed by a prescriber. For researchers, NEPIs have the potential to advance our understanding of the risks and benefits of medications in populations; however, due to their unstructured nature, they are not often utilized. The goal of this scoping review was to evaluate how NEPIs are currently employed in research, identify opportunities and challenges for their broader application, and provide recommendations on their future use. The scoping review comprised a comprehensive literature review and a survey of key stakeholders. From the literature review, we identified 33 primary articles that described the use of NEPIs. The majority of articles (n = 19) identified issues with the quality of information in NEPIs compared with structured prescribing information; nine articles described the development of novel algorithms that performed well in extracting information from NEPIs, and five described the used of manual or simpler algorithms to extract prescribing information from NEPIs. A survey of 19 stakeholders indicated concerns for the quality of information in NEPIs and called for standardization of NEPIs to reduce data variability/errors. Nevertheless, stakeholders believed NEPIs present an opportunity to identify prescriber's intent for the prescription and to study temporal treatment patterns. In summary, NEPIs hold much promise for advancing the field of pharmacoepidemiology. Researchers should take advantage of addressing important questions that can be uniquely answered with NEPIs, but exercise caution when using this information and carefully consider the quality of the data.

Ursodeoxycholic Acid Treatment Preferentially Improves Overall Survival Among African Americans With Primary Biliary Cholangitis.

BACKGROUND: We used data from the Fibrotic Liver Disease Consortium to evaluate the impact of ursodeoxycholic acid (UDCA) treatment across race/ethnicity, gender, and clinical status among patients with primary biliary cholangitis. METHODS: Data were collected from "index date" (baseline) through December 31, 2016. Inverse Probability of Treatment Weighting was used to adjust for UDCA treatment selection bias. Cox regression, focusing on UDCA-by-risk factor interactions, was used to assess the association between treatment and mortality and liver transplant/death. RESULTS: Among 4,238 patients with primary biliary cholangitis (13% men; 8% African American, 7% Asian American/American Indian/Pacific Island [ASINPI]; 21% Hispanic), 78% had ever received UDCA. The final multivariable model for mortality retained age, household income, comorbidity score, total bilirubin, albumin, alkaline phosphatase, and interactions of UDCA with race, gender, and aspartate aminotransferase/alanine aminotransferase ≥1.1. Among untreated patients, African Americans and ASINPIs had higher mortality than whites (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.08-1.67 and aHR = 1.40, 95% CI 1.11-1.76, respectively). Among treated patients, this relationship was reversed (aHR = 0.67, 95% CI 0.51-0.86 and aHR = 0.88, 95% CI 0.67-1.16). Patterns were similar for liver transplant/death. UDCA reduced the risk of liver transplant/death in all patient groups and mortality across all groups except white women with aspartate aminotransferase/alanine aminotransferase ≥1.1. As compared to patients with low-normal bilirubin at baseline (≤0.4 mg/dL), those with high-normal (1.0 > 0.7) and mid-normal bilirubin (0.7 > 0.4) had significantly higher liver transplant/death and all-cause mortality. DISCUSSION: African American and ASINPI patients who did not receive UDCA had significantly higher mortality than white patients. Among African Americans, treatment was associated with significantly lower mortality. Regardless of UDCA treatment, higher baseline bilirubin, even within the normal range, was associated with increased mortality and liver transplant/death compared with low-normal levels.

Multiple sclerosis in a multi-ethnic population from Northern California: a retrospective analysis, 2010-2016.

BACKGROUND: Research is needed to examine differences in multiple sclerosis (MS) prevalence by race-ethnicity. The goal of this study was to quantify MS prevalence in a health care system in Northern California and examine differences in prevalence and phenotype by race-ethnicity. METHODS: We conducted a retrospective, observational cohort study of adults (2010-2016). MS prevalence estimates were standardised to distributions of gender and race-ethnicity for the underlying geographic region and stratified by gender and race-ethnicity with age adjustment. We performed a chart review of a racial-ethnic stratified sample of patients to examine disease phenotypes. RESULTS: 1,058,102 patients were identified, of which 3286 had MS. The overall direct-standardised prevalence was 288.0 cases per 100,000 population (95% confidence interval: 276.3-299.8). Age-adjusted prevalence ranged from 677.0 per 100,000 among non-Hispanic black women to 49.7 per 100,000 among non-Hispanic Asian men. Non-Hispanic blacks compared with other groups more often had primary-progressive (10.0% vs. 0.0-4.0%) or progressive-relapsing MS (6.0% vs. 0.0-2.0%). CONCLUSIONS: In this Northern Californian Cohort, between 2010 and 2016 the direct-standardised MS prevalence was estimated at 288.0 per 100,000 population, and increased over time. Non-Hispanic blacks, especially women, were disproportionately affected and had less common, earlier progressive MS phenotypes.

Glycemic Outcomes in Adults With Type 2 Diabetes Participating in a Continuous Glucose Monitor-Driven Virtual Diabetes Clinic: Prospective Trial.

BACKGROUND: The Onduo virtual diabetes clinic (VDC) for people with type 2 diabetes (T2D) combines a mobile app, remote personalized lifestyle coaching, connected devices, and live video consultations with board-certified endocrinologists for medication management and prescription of real-time continuous glucose monitoring (RT-CGM) devices for intermittent use. OBJECTIVE: This prospective single-arm study evaluated glycemic outcomes associated with participation in the Onduo VDC for 4 months. METHODS: Adults aged ≥18 years with T2D and a baseline glycated hemoglobin (HbA1c) of ≥8% to ≤12% were enrolled from 2 primary care centers from February 2019 to October 2019. Participants were asked to engage at ≥1 time per week with their care team and to participate in a telemedicine consultation with a clinic endocrinologist for diabetes medication review. Participants were asked to use a RT-CGM device and wear six 10-day sensors (total 60 days of sensor wear) intermittently over the course of 4 months. The primary outcome was change in HbA1c at 4 months from baseline. Other endpoints included change in weight and in RT-CGM glycemic metrics, including percent time <70, 70-180, 181-250, and >250 mg/dL. Changes in blood pressure and serum lipids at 4 months were also evaluated. RESULTS: Participants (n=55) were 57.3 (SD 11.6) years of age, body mass index 33.7 (SD 7.2), and 40% (22/55) female. HbA1c decreased significantly by 1.6% (SD 1%; P<.001). When stratified by baseline HbA1c of 8.0% to 9.0% (n=36) and >9.0% (n=19), HbA1c decreased by 1.2% (SD 0.6%; P<.001) and 2.4% (SD 1.3%; P<.001), respectively. Continuous glucose monitoring-measured (n=43) percent time in range (TIR) 70-180 mg/dL increased by 10.2% (SD 20.5%; P=.002), from 65.4% (SD 23.2%) to 75.5% (SD 22.7%), which was equivalent to a mean increase of 2.4 hours TIR per day. Percent time 181-250 mg/dL and >250 mg/dL decreased by 7.2% (SD 15.4; P=.005) and 3.0% (SD 9.4; P=.01), respectively. There was no change in percent time <70 mg/dL. Mean weight decreased by 9.0 lb (SD 10.4; P<.001). Significant improvements were also observed in systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and triglycerides (P=.04 to P=<.001). CONCLUSIONS: Participants in the Onduo VDC experienced significant improvement in HbA1c, increased TIR, decreased time in hyperglycemia, and no increase in hypoglycemia at 4 months. Improvements in other metabolic health parameters including weight and blood pressure were also observed. In conclusion, the Onduo VDC has potential to support people with T2D and their clinicians between office visits by increasing access to specialty care and advanced diabetes technology including RT-CGM. TRIAL REGISTRATION: ClinicalTrials.gov NCT03865381; https://clinicaltrials.gov/ct2/show/NCT03865381.

Statin Dosing Instructions, Medication Adherence, and Low-Density Lipoprotein Cholesterol: a Cohort Study of Incident Statin Users.

BACKGROUND: Robust evidence is lacking on optimal timing of statin administration and its impact on patient outcomes. OBJECTIVE: This study aims to evaluate among incident statin users the relationship between those prescribed evening vs. daily dosing instructions, medication adherence, and changes in low-density lipoprotein cholesterol (LDL-c). DESIGN: This is an observational cohort study at Sutter Health, a community-based healthcare system, 2010-2016. PARTICIPANTS: Patients were ≥ 35 years of age as of the first statin prescription (baseline), with 12 to 36 months of electronic health record activity before and after baseline. Incident use was defined as no statin prescription in 12 months prior to baseline. MAIN MEASURES: Differences in medication adherence (proportion of days covered ≥ 0.80) over 12 months from baseline and mean change in LDL-c between 12 and 24 months from baseline were measured using regression modeling, adjusting for baseline demographics and clinical, prescriber, and statin characteristics. KEY RESULTS: Among 31,252 patients with valid statin prescriptions between 2010 and 2016, 5099 eligible incident statin users (mean age, 63 years) were identified, of whom 53% were prescribed evening and 47% daily dosing instructions. No difference in likelihood of statin adherence over 12 months was observed for evening vs. daily dosing (adjusted odds ratio [OR] 0.90; 95% CI 0.75, 1.08). No differences were observed in mean change in LDL-c (adjusted mean difference 1.42 mg/dL; 95% CI - 1.02, 3.89) or likelihood of attaining LDL-c < 70 mg/dL (adjusted OR 0.83; 95% CI 0.67, 1.04) for evening vs. daily dosing over a mean of 19 months follow-up. CONCLUSIONS: Among incident statin users from a real-world clinical setting, those with daily and evening dosing instructions had similar adherence rates and mean changes in LDL-c. Given potential clinical equipoise for evening and daily dosing, clinicians should consider patient-tailored statin dosing instructions to reduce potentially unnecessary regimen complexity.

Racial and Ethnic Disparities in Opioid Prescribing for Long Bone Fractures at Discharge From the Emergency Department: A Cross-sectional Analysis of 22 Centers From a Health Care Delivery System in Northern California.

STUDY OBJECTIVE: We examine racial and ethnic differences in opioid prescribing and dosing for long bone fractures at emergency department (ED) discharge. METHODS: We conducted an electronic health records-based cross-sectional study of adults with long bone fractures who presented to the ED across 22 sites from a health care delivery system (2016 to 2017). We examined differences in opioid prescribing at ED discharge and, among patients with a prescription, differences in opioid dosing (measured as morphine milligram equivalents) by race/ethnicity, using regression modeling with statistical adjustment for patient, fracture, and prescriber characteristics. RESULTS: A total of 11,576 patients with long bone fractures were included in the study; 64.4% were non-Hispanic white; 16.4%, 7.3%, 5.8%, and 5.1%, respectively, were Hispanic, Asian, black, and of other or unknown race; and 65.6% received an opioid at discharge. After adjusting for other factors, rates of opioid prescribing were not different by race/ethnicity; however, among patients with an opioid prescription, total morphine milligram equivalent units prescribed were 4.3%, 6.0%, and 8.1% less for Hispanics, blacks, and Asians relative to non-Hispanic whites. CONCLUSION: Racial and ethnic minority groups with long bone fractures receive similar frequencies of opioid prescriptions at discharge, with a small potency difference. How this affects pain relief and why it happens is unclear.

Implementation of a group-based diabetes prevention program within a healthcare delivery system.

BACKGROUND: Group-based Diabetes Prevention Programs (DPP), aligned with recommendations from the Centers for Disease Control and Prevention, promote clinically significant weight loss and reduce cardio-metabolic risks. Studies have examined implementation of the DPP in community settings, but less is known about its integration in healthcare systems. In 2010, a group-based DPP known as the Group Lifestyle Balance (GLB) was implemented within a large healthcare delivery system in Northern California, across three geographically distinct regional administration divisions of the organization within 12 state counties, with varying underlying socio-demographics. The regional divisions implemented the program independently, allowing for natural variation in its real-world integration. We leveraged this natural experiment to qualitatively assess the implementation of a DPP in this healthcare system and, especially, its fidelity to the original GLB curriculum and potential heterogeneity in implementation across clinics and regional divisions. METHODS: Using purposive sampling, we conducted semi-structured interviews with DPP lifestyle coaches. Data were analyzed using mixed-method techniques, guided by an implementation outcomes framework consisting of eight constructs: acceptability, adoption, appropriateness, cost, feasibility, fidelity, penetration, and sustainability. RESULTS: We conducted 33 interviews at 20 clinics across the three regional administrative divisions. Consistencies in implementation of the program were found across regions in terms of satisfaction with the evidence base (acceptability), referral methods (adoption), eligibility criteria (fidelity), and strategies to increase retention and effectiveness (sustainability). Heterogeneity in implementation across regions were found in all categories, including: the number and frequency of sessions (fidelity); program branding (adoption); lifestyle coach training (adoption), and patient-facing cost (cost). Lifestyle coaches expressed differing attitudes about curriculum content (acceptability) and suitability of educational level (appropriateness). While difficulties with recruitment were common across regions (feasibility), strategies used to address these challenges differed (sustainability). CONCLUSIONS: Variation exists in the implementation of the DPP within a large multi-site healthcare system, revealing a dynamic and important tension between retaining fidelity to the original program and tailoring the program to meet the local needs. Moreover, certain challenges across sites may represent opportunities for considering alternative implementation to anticipate these barriers. Further research is needed to explore how differences in implementation domains impact program effectiveness.

Factors Associated With Prevalence and Treatment of Primary Biliary Cholangitis in United States Health Systems.

BACKGROUND & AIMS: Reported prevalence of primary biliary cholangitis (PBC) varies widely. Demographic features and treatment patterns are not well characterized in the United States (US). We analyzed data from the Fibrotic Liver Disease (FOLD) Consortium, drawn from 11 geographically diverse health systems, to investigate epidemiologic factors and treatment of PBC in the US. METHODS: We developed a validated electronic health record-based classification model to identify patients with PBC in the FOLD database from 2003 through 2014. We used multivariable modeling to assess the effects of factors associated with PBC prevalence and treatment with ursodeoxycholic acid (UDCA). RESULTS: We identified 4241 PBC cases among over 14.5 million patients in FOLD health systems; median follow-up was 5 years. Accuracy of the classification model was excellent, with an area under the receiver operating characteristic curve value of 93%, 94% sensitivity, and 87% specificity. The average patient age at diagnosis was 60 years; 21% were Hispanic, 8% were African American, and 7% were Asian American/American Indian/Pacific Islander. Half of the cohort (49%) had elevated levels of alkaline phosphatase, and overall, 70% were treated with UDCA. The estimated 12-year prevalence of PBC was 29.3 per 100,000 persons. Adjusted prevalence values were highest among women (42.8 per 100,000), White patients (29.6 per 100,000), and patients 60-70 years old (44.7 per 100,000). Prevalence was significantly lower among men and African Americans (10.7 and 19.7 per 100,000, respectively) than women and whites; men and African Americans were also less likely to receive UDCA treatment (odds ratios, 0.6 and 0.5, respectively; P < .05). CONCLUSIONS: In an analysis of a large cohort of patients with PBC receiving routine clinical care, we observed significant differences in PBC prevalence and treatment by gender, race, and age.

Increasing Prevalence of Primary Biliary Cholangitis and Reduced Mortality With Treatment.

BACKGROUND & AIMS: There are few data from longitudinal studies of trends in primary biliary cholangitis (PBC) among patients under routine clinical care in the United States. We collected data from the Fibrotic Liver Disease consortium to investigate changes in the incidence and prevalence of PBC and the effects of patient demographics, clinical features, and treatment on mortality. METHODS: We collected demographic and clinical data for the general patient population as well as PBC patients receiving care from 11 health systems in different regions of the United States (Northeast, Midwest, Northwest, and South) from January 1, 2003, through December 31, 2014. Annual percentage changes in PBC prevalence and incidence were estimated using join-point Poisson regression. Differences based on race, age, and gender were calculated with rate ratios. All-cause mortality was estimated using Cox regression with adjustment for patient characteristics and treatment with ursodeoxycholic acid (UDCA). Propensity scores were used to adjust for treatment selection bias. Analyses were adjusted by geographic regions. RESULTS: In our racially diverse cohort of 3488 patients with PBC (21% Hispanic, 8% African American, 7% Asian American), 70% had ever received UDCA. From 2006 through 2014, the prevalence of PBC increased from 21.7 to 39.2 per 100,000 persons. Adjusted annual percentage changes in prevalence differed among age groups (≤40 y, 41-50 y, 51-60 y, 61-70 y, and >70 y), ranging from 3.0% to 7.5% (P < .05). Incidence did not change significantly during the study period (4.2 vs 4.3 per 100,000 person-years in 2006 and 2014, respectively; P = .98). Ratios of prevalence for women vs men (3.9:1) and incidence for women vs men (3.2:1) were consistent over the study period. Among African Americans, the prevalence of PBC increased from 16.9 to 30.8 per 100,000 during the study period, and annual incidence ranged from 2.6 to 6.6 per 100,000 person-years. In adjusted analyses, an increased level of alkaline phosphatase at baseline was associated with significantly higher mortality (adjusted hazard ratios [aHR], 1.24; 95% CI, 1.04-1.48 for patients with levels 1-2 times the upper limit of normal and aHR, 2.27; 95% CI, 1.88-2.73 for patients with levels more than 3 times the upper limit of normal). UDCA treatment was associated with significantly reduced mortality (aHR, 0.57; 95% CI, 0.52-0.64). CONCLUSIONS: In an analysis of data from patients receiving routine clinical care in Fibrotic Liver Disease Consortium health systems, we found that the prevalence of PBC increased from 2004 through 2014, despite steady incidence. Patient demographic and clinical characteristics, as well as UDCA treatment, affected mortality.

Preventive visit among older adults with Medicare's introduction of Annual Wellness Visit: Closing gaps in underutilization.

Preventive visit rates are low among older adults in the United States. We evaluated changes in preventive visit utilization with Medicare's introduction of Annual Wellness Visits (AWVs) in 2011. We further assessed how coverage expansion differentially affected older adults who were previously underutilizing the service. The study included Medicare beneficiaries aged 65 to 85 from a mixed-payer multispecialty outpatient healthcare organization in northern California between 2007 and 2016. Data from the electronic health records were used, and the unit of analysis was patient-year (N = 456,281). Multivariable logistic regression models were used to assess determinants of "any preventive visit" use. Prior to the AWV coverage (2007-2010), Medicare beneficiaries who were older, with serious chronic conditions, and with a fee-for-services (FFS) plan underutilized preventive visits such that odds ratio (OR) for age groups (vs. age 65-69) ranges from 0.826 (age 70-74) to 0.522 (age 80-85); for Charlson comorbidity index (CCI) (vs. 0 CCI) ranges from 0.77 (1 CCI) to 0.65 (≥2 CCI); and for FFS (vs. HMO) is 0.236. With the Medicare coverage (2011-2016), the age-based gap reduced substantially, but the difference persisted, e.g., OR for age 80-85 (vs. 65-69) is 0.628, and FFS (vs. HMO) beneficiaries still have far lower odds of using a preventive visit (OR = 0.278). The gap based on comorbidity was not reduced. Medicare's coverage expansion facilitated the use of preventive visit particularly for older adults with more advanced age or with FFS, thereby reducing disparities in preventive visit use.

Provider and Patient Determinants of Generic Levothyroxine Prescribing: An Electronic Health Records-Based Study.

BACKGROUND: Despite the availability of generic levothyroxine products for more than a decade, uptake of these products is poor. OBJECTIVE: We sought to evaluate determinants of generic prescribing of levothyroxine. METHODS: In a cross-sectional analysis of electronic health records data between 2010 and 2013, we identified adult patients with a levothyroxine prescription from a primary-care physician (PCP) or endocrinologist. We used mixed-effect logistic regression models with random intercepts for prescribing provider to examine predictors of generic levothyroxine prescribing. Models include patient, prescription, and provider fixed-effect covariates. Odds ratios (ORs) and 95% CIs were generated. Between-provider random variation was quantified by the intraclass correlation coefficient (ICC). RESULTS: Study patients (n = 63 838) were clustered among 941 prescribing providers within 25 ambulatory care clinics. The overall prevalence of generic prescribing of levothyroxine was 73%. In the multivariable mixed-effect model, patients were significantly less likely to receive generic levothyroxine from an endocrinologist than a PCP (OR = 0.43; 95% CI = 0.33-0.55; P < 0.001). Women were less likely to receive generic levothyroxine than men from endocrinologists (OR = 0.68; 95% CI = 0.59-0.78; P < 0.001) but not from PCPs. Between-provider variation in generic prescribing was 18.3% in the absence of fixed-effect covariates and could be explained marginally by patient, prescription, and provider factors (ICC = 15.9%). CONCLUSIONS: Generic levothyroxine prescribing differed by PCPs and endocrinologists. Residual variation in generic prescribing, after accounting for measurable factors, indicates the need for provider interventions or patient education aimed at improving levothyroxine generic uptake.

Diabetes Prevention and Weight Loss with a Fully Automated Behavioral Intervention by Email, Web, and Mobile Phone: A Randomized Controlled Trial Among Persons with Prediabetes.

BACKGROUND: One-third of US adults, 86 million people, have prediabetes. Two-thirds of adults are overweight or obese and at risk for diabetes. Effective and affordable interventions are needed that can reach these 86 million, and others at high risk, to reduce their progression to diagnosed diabetes. OBJECTIVE: The aim was to evaluate the effectiveness of a fully automated algorithm-driven behavioral intervention for diabetes prevention, Alive-PD, delivered via the Web, Internet, mobile phone, and automated phone calls. METHODS: Alive-PD provided tailored behavioral support for improvements in physical activity, eating habits, and factors such as weight loss, stress, and sleep. Weekly emails suggested small-step goals and linked to an individual Web page with tools for tracking, coaching, social support through virtual teams, competition, and health information. A mobile phone app and automated phone calls provided further support. The trial randomly assigned 339 persons to the Alive-PD intervention (n=163) or a 6-month wait-list usual-care control group (n=176). Participants were eligible if either fasting glucose or glycated hemoglobin A1c (HbA1c) was in the prediabetic range. Primary outcome measures were changes in fasting glucose and HbA1c at 6 months. Secondary outcome measures included clinic-measured changes in body weight, body mass index (BMI), waist circumference, triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio, and Framingham diabetes risk score. Analysis was by intention-to-treat. RESULTS: Participants' mean age was 55 (SD 8.9) years, mean BMI was 31.2 (SD 4.4) kg/m(2), and 68.7% (233/339) were male. Mean fasting glucose was in the prediabetic range (mean 109.9, SD 8.4 mg/dL), whereas the mean HbA1c was 5.6% (SD 0.3), in the normal range. In intention-to-treat analyses, Alive-PD participants achieved significantly greater reductions than controls in fasting glucose (mean -7.36 mg/dL, 95% CI -7.85 to -6.87 vs mean -2.19, 95% CI -2.64 to -1.73, P<.001), HbA1c (mean -0.26%, 95% CI -0.27 to -0.24 vs mean -0.18%, 95% CI -0.19 to -0.16, P<.001), and body weight (mean -3.26 kg, 95% CI -3.26 to -3.25 vs mean -1.26 kg, 95% CI -1.27 to -1.26, P<.001). Reductions in BMI, waist circumference, and TG/HDL were also significantly greater in Alive-PD participants than in the control group. At 6 months, the Alive-PD group reduced their Framingham 8-year diabetes risk from 16% to 11%, significantly more than the control group (P<.001). Participation and retention was good; intervention participants interacted with the program a median of 17 (IQR 14) of 24 weeks and 71.1% (116/163) were still interacting with the program in month 6. CONCLUSIONS: Alive-PD improved glycemic control, body weight, BMI, waist circumference, TG/HDL ratio, and diabetes risk. As a fully automated system, the program has high potential for scalability and could potentially reach many of the 86 million US adults who have prediabetes as well as other at-risk groups. TRIAL REGISTRATION: Clinicaltrials.gov NCT01479062; https://clinicaltrials.gov/ct2/show/NCT01479062 (Archived by WebCite at http://www.webcitation.org/6bt4V20NR).

Predictors of statin compliance after switching from branded to generic agents among managed-care beneficiaries.

OBJECTIVES: To identify patient demographics and characteristics associated with compliance to statin therapy after switching from branded to generic agents DESIGN: Retrospective cohort study using electronic health records and pharmacy claims data from Sutter Health's ambulatory-care medical network PATIENTS: Managed-care beneficiaries, ≥ 18 years of age, who were switched from branded to generic statins between 1 January 2003 and 31 December 2012 MAIN MEASURES: Compliance was calculated as days of therapy dispensed divided by days from first to last generic prescription fill over 6 months, and was defined as a medication possession ratio ≥ 0.80. We used multivariable logistic regression to assess factors associated with compliance. Adjusted ORs and 95% CI were generated. KEY RESULTS: We identified 5,156 patients who were switched from branded to generic statins; 73% of patients were compliant in the 6 months after switching. After statistical adjustment, higher compliance was associated with each 10-year increase in age (OR: 1.13; 95% CI: 1.07, 1.19; p < 0.001), receipt of a generic statin equivalent in potency to the prior branded statin (OR: 1.41; 95% CI: 1.16, 1.70; p < 0.001), and compliance with prior branded statin (OR: 4.68; 95% CI: 4.07, 5.39; p < 0.001). Lower compliance was seen among Hispanic patients compared to non-Hispanic white patients (OR: 0.68; 95% CI: 0.52, 0.91; p = 0.009). Also, a switch to a higher potency generic statin, regardless of prior dose/potency, was negatively associated with compliance after switching (OR: 0.87; 95% CI: 0.80, 0.94; p = 0.001). CONCLUSIONS: The majority of patients switched from branded to generic agents were compliant with therapy in the first 6 months after switching. The potential for non-compliance to generic statin therapy, particularly among younger or Hispanic patients or when dose/potency changes are made, should be considered prior to switching. For these patients, counseling or close monitoring may be required to optimize generic interchange.

Behavioral therapy and serotonin reuptake inhibitor pharmacotherapy in the treatment of obsessive-compulsive disorder: a systematic review and meta-analysis of head-to-head randomized controlled trials.

BACKGROUND: Effective treatments for obsessive-compulsive disorder (OCD) include behavioral therapy (exposure and response/ritual prevention and cognitive behavioral therapy) and serotonin-reuptake inhibitors (SRIs); however, the relative efficacy of these treatments is not well established. We sought to review evidence from head-to-head randomized-controlled trials (RCTs) of behavioral therapy and SRIs in the treatment of OCD. METHODS: A systematic search of multiple databases was conducted from first available date to June 30, 2012, for RCTs in the treatment of OCD among outpatients, comparing behavioral therapy and SRIs, alone or combined. Two independent reviewers evaluated studies for eligibility and risk of bias. The main outcome measure was posttreatment mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) score. RESULTS: We identified 2,186 unique articles. Fifteen articles were included, describing 13 RCTs. Pooled standardized mean difference (SMD; 95% confidence intervals) in YBOCS score significantly favored behavioral therapy over SRIs (0.37; 0.10, 0.64; P = .007), but not in a subset of trials that used selective SRIs (0.22; -0.02, 0.47; P = .070). Within individual trials, effect sizes significantly favored the combination of behavioral therapy plus an SRI over an SRI, but not behavioral therapy, alone. CONCLUSIONS: This review provides evidence that, among outpatients with OCD, behavioral therapy is more effective than SRIs, overall, but not selective SRIs. Furthermore, the combination of behavioral therapy plus an SRI is more effective than an SRI alone. These data may be used to inform the development of evidence-based treatment guidelines; however, more studies are also needed to further evaluate the relative efficacy of these interventions.

Compliance after switching from branded to generic statins.

PURPOSE: The purpose of this study was to evaluate the impact of switching from branded to generic statins on medication compliance. METHODS: In this historic cohort study, we identified patients taking branded statins between January 2003 and December 2012 from Sutter Health's electronic health records in Northern California. Patients with ≥2 consecutive pharmacy claims for generic statins after initiating branded statins were classified as switchers. Switchers and non-switchers were matched 1:1 on the propensity for switching. Medication possession ratio (MPR) was calculated as the sum of days supply of therapy divided by treatment duration. We assessed between-group differences in compliance (MPR ≥ 0.80) by logistic regression. RESULTS: Among 16,364 patients meeting eligibility criteria, 8470 were retained in the matched cohort. No significant differences in compliance with statin therapy were observed for non-switchers versus switchers, overall, or versus patients switched from a branded to generic statin of the same agent (generic substitutions). Patients switched from a branded to generic statin of a different agent (therapeutic substitutions) more frequently received less potent statin dosing relative to those with generic substitutions (42.2% vs. <2%, respectively) and were significantly less compliant with statin therapy in the first 6 months after switching (73.9% vs. 77.6%; p = 0.011); however, compliance significantly improved among patients with therapeutic substitutions relative to generic substitutions more than 12 months after switching (66.2% vs. 61.3%; p = 0.021). CONCLUSIONS: Compliance with statin therapy was largely similar among patients who switch to generic statins and those remaining on branded statins. Dosing should be reviewed when changing therapy to optimize clinical outcomes.

Regional and Local Inequalities in Disability Status by Sexual Orientation and Gender Identity: A Cross-Sectional Ecological Analysis of the 2021 Census of England and Wales.

Purpose: To examine regional differences in disability status by sexual orientation and gender identity and to explore local factors that are associated with levels of inequalities for people who identify as lesbian, gay, bisexual, or other sexual orientations (LGB+) or transgender. Methods: This was a cross-sectional ecological analysis of 2021 Census data from England and Wales. The main outcome variable was disability status. The main explanatory variables were sexual orientation and gender identity. Weighed linear regression was used to examine differences in disability status by sexual orientation (LGB+ vs. heterosexual) and gender identity (transgender vs. cisgender). The magnitude of between-group differences was explored by region and, in England, local authority-level urbanization and socioeconomic deprivation. Results: Among 48.5 million census respondents within 331 local authority districts (LADs) across England and Wales, LGB+ and transgender groups were more likely to report having a disability than their heterosexual and cisgender counterparts. Inequalities were prevalent across regions of England and Wales, but were smallest in the Greater London area and largest in the southwest of England. Inequalities were also larger within English LADs that were relatively less urbanized and relatively more socioeconomically deprived. Conclusions: This study identified disparities in disability status by sexual orientation and gender identity, which varied by region and local socioeconomic deprivation and urbanization. More research is needed to better understand how to support disabled LGBT+ people, especially those in less urbanized and more socioeconomically deprived areas.

Cognitive Impairment in Sexual and Gender Minority Groups: A Scoping Review of the Literature.

Purpose: The purpose of this review was to synthesize evidence on differences in cognitive impairment by sexual orientation/gender identity (SOGI) status. Methods: A scoping review of the literature was conducted. Five databases (PubMed/Medline, Cumulated Index to Nursing and Allied Health Literature, Web of Science, PsycInfo, and Embase) were searched for primary articles comparing incidence or prevalence of cognitive impairment among sexual and gender minority (SGM) groups versus non-SGM groups. Two reviewers independently screened articles and conducted risk-of-bias assessment on eligible articles. Results: Fifteen primary studies were eligible. Most studies (n = 13) were cross-sectional, with moderate to critical risk of bias. Among eight studies examining self-reported cognitive impairment, seven reported a higher prevalence among some SGM groups versus non-SGM groups. Among seven studies using objective measures of cognitive impairment, three examined prevalence of clinician-documented diagnosis of dementia, of which two reported a higher prevalence specifically among transgender versus cisgender individuals. Among the other four studies examining objective measures, two reported poorer cognitive performance or memory, one reported better performance, and another reported no difference. Comparisons across studies were challenging due to inconsistencies in how SOGI and cognitive impairment were operationalized, and the factors used for statistical adjustment; some studies adjusted for putative intermediary factors that potentially explain differences in cognitive impairment. Conclusions: Whereas most published studies identified a positive relationship between SOGI status and self-reported cognitive impairment, evidence is mixed with regard to objective cognitive performance. Well-designed longitudinal, observational studies are needed, using objective measures of cognitive function, with careful consideration of confounding versus intermediary risk factors.

Changes in Healthcare Utilization After Lifestyle Intervention for Weight Loss.

INTRODUCTION: This study evaluates the real-world impact of a lifestyle change program (LCP) on healthcare utilization in a large health system. METHODS: Using electronic health record data from a large health system in northern California, U.S., LCP participant and propensity-score-matched nonparticipant outcomes were compared in the second year post-participation: (1) overall healthcare utilization and (2) utilization and medications related to cardiometabolic conditions and obesity. Adult LCP participants between 2010 and 2017 were identified and matched 1:1 with replacement to comparable nonparticipants. Participants without electronic health record activity in the 12-36 months before baseline, or with conditions or procedures associated with substantial weight change, were excluded. Statistical analysis and modeling were performed in 2021-22. RESULTS: Compared to matched nonparticipants, LCP participants in the 12-24 months post-baseline were more likely to have specialty-care visits (+4.7%, 95% CI +1.8%, +7.6%), electronic communications (8.6%, 95% CI +5.6%, +11.7%), and urgent-care visits (+6.5%, 95% CI +3.0%, 10.0%). Participants also had more office visits for cardiometabolic conditions and obesity (+1.72 visits/patient, 95% CI +1.05, +2.39). CONCLUSIONS: Compared with matched nonparticipants, LCP participation was associated with higher utilization of outpatient services post-participation. Additional research could assess whether this indicates an increase in preventive care that could lead to improved future outcomes.

Drivers of Variation in Opioid Prescribing after Common Surgical Procedures in a Large Multihospital Healthcare System.

BACKGROUND: Misuse of prescription opioids is a well-established contributor to the United States opioid epidemic. The primary objective of this study was to identify which level of care delivery (i.e. patient, prescriber, or hospital) produced the most unwarranted variation in opioid prescribing after common surgical procedures. STUDY DESIGN: Electronic health record (EHR) data from a large multihospital healthcare system was used in conjunction with random-effect models to examine variation in opioid prescribing practices following similar inpatient and outpatient surgical procedures between October 2019 and September 2021. Unwarranted variation was conceptualized as variation resulting from prescriber behavior unsupported by evidence. Covariates identified as drivers of warranted variation included characteristics known to influence pain levels or patient safety. All other model variables, including prescriber specialty and patient race, ethnicity, and insurance status were characterized as potential drivers of unwarranted variation. RESULTS: Among 25,188 procedures with an opioid prescription at hospital discharge, 53.5% exceeded guideline recommendations, corresponding to 13,228 patients receiving the equivalent of >140,000 excess 5mg oxycodone tablets following surgical procedures. Prescribing variation was primarily driven by prescriber-level factors, with approximately half of the total variation in morphine milligram equivalents (MMEs) prescribed observed at the prescriber level and not explained by any measured variables. Unwarranted covariates associated with higher prescribed opioid quantity included non-Hispanic black race, Medicare insurance, smoking history, later hospital discharge times, and prescription by a surgeon rather than a hospitalist or primary care provider. CONCLUSION: Given the large proportion of unexplained variation observed at the provider level, targeting prescribers through education and training may be an effective strategy for reducing postoperative opioid prescribing.