Robert Romanelli

A Fully Automated Diabetes Prevention Program, Alive-PD: Program Design and Randomized Controlled Trial Protocol

Background In the United States, 86 million adults have pre-diabetes. Evidence-based interventions that are both cost effective and widely scalable are needed to prevent diabetes. Objective Our goal was to develop a fully automated diabetes prevention program and determine its effectiveness in a randomized controlled trial. Methods Subjects with verified pre-diabetes were recruited to participate in a trial of the effectiveness of Alive-PD, a newly developed, 1-year, fully automated behavior change program delivered by email and Web. The program involves weekly tailored goal-setting, team-based and individual challenges, gamification, and other opportunities for interaction. An accompanying mobile phone app supports goal-setting and activity planning. For the trial, participants were randomized by computer algorithm to start the program immediately or after a 6-month delay. The primary outcome measures are change in HbA1c and fasting glucose from baseline to 6 months. The secondary outcome measures are change in HbA1c, glucose, lipids, body mass index (BMI), weight, waist circumference, and blood pressure at 3, 6, 9, and 12 months. Randomization and delivery of the intervention are independent of clinic staff, who are blinded to treatment assignment. Outcomes will be evaluated for the intention-to-treat and per-protocol populations. Results A total of 340 subjects with pre-diabetes were randomized to the intervention (n=164) or delayed-entry control group (n=176). Baseline characteristics were as follows: mean age 55 (SD 8.9); mean BMI 31.1 (SD 4.3); male 68.5%; mean fasting glucose 109.9 (SD 8.4) mg/dL; and mean HbA1c 5.6 (SD 0.3)%. Data collection and analysis are in progress. We hypothesize that participants in the intervention group will achieve statistically significant reductions in fasting glucose and HbA1c as compared to the control group at 6 months post baseline. Conclusions The randomized trial will provide rigorous evidence regarding the efficacy of this Web- and Internet-based program in reducing or preventing progression of glycemic markers and indirectly in preventing progression to diabetes. Trial Registration ClinicalTrials.gov NCT01479062; http://clinicaltrials.gov/show/NCT01479062 (Archived by WebCite at http://www.webcitation.org/6U8ODy1vo).

Improving diet, activity and wellness in adults at risk of diabetes: randomized controlled trial.

Objective:The purpose of this analysis is to examine the effect of an algorithm-driven online diabetes prevention program on changes in eating habits, physical activity and wellness/productivity factors.Methods:The intervention, Alive-PD, used small-step individually tailored goal setting and other features to promote changes in diet and physical activity. A 6-month randomized controlled trial was conducted among patients from a healthcare delivery system who had confirmed prediabetes (n =339). Change in weight and glycemic markers were measured in the clinic. Changes in physical activity, diet and wellness/productivity factors were self-reported. Mean age was 55 (s.d. 8.9) years, mean body mass index was 31 (s.d. 4.4) kg m−2, 68% were white and 69% were male.Results:The intervention group increased fruit/vegetable consumption by 3.71 (95% confidence interval (CI) 2.73, 4.70) times per week (effect size 0.62), and decreased refined carbohydrates by 3.77 (95% CI 3.10, 4.44) times per week both significantly (P<0.001) greater changes than in the control group. The intervention group also reported a significantly greater increase in physical activity than in the control group, effect size 0.49, P<0.001. In addition, the intervention group reported a significant increase in self-rated health, in confidence in ability to make dietary changes and in ability to accomplish tasks, and a decrease in fatigue, compared with the control group. These changes paralleled the significant treatment effects on glycemic markers and weight.Conclusions:In addition to promoting improvements in weight and glycemic markers, the Alive-PD program appears to improve eating habits and physical activity, behaviors important not just for diabetes prevention but for those with diagnosed diabetes or obesity. The improvements in wellness/productivity may derive from the diet and activity improvements, and from the satisfaction and self-efficacy of achieving goals.

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.

Comparative effectiveness of early versus delayed metformin in the treatment of type 2 diabetes

AIM The purpose of this study was to evaluate the effectiveness of early versus delayed initiation of metformin in type 2 diabetes. METHODS We identified 2925 new users of metformin with type 2 diabetes between 2005 and 2012 in the electronic health records of an integrated health system in Northern California. Patients were matched 1:1 on the propensity for receiving early treatment (defined as ≤6 months from first evidence of diabetes). We evaluated the effectiveness of early versus delayed metformin treatment on intermediate clinical outcomes indicated by changes in hemoglobin A1c (HbA1c) and body mass index (BMI), as well as the incidence of therapy intensification (addition or substitution of a second antihyperglycemic agent). RESULTS A total of 2144 propensity-score matched patients were included in the early or delayed treatment group (n=1072, in each). Early treatment was associated with significantly larger decreases in HbA1c (-0.36%; 95% confidence intervals [CI]: -0.44 to -0.27%; P<0.001) and BMI (-0.46 kg/m(2); 95% CI: -0.64 to -0.29 kg/m(2); P<0.001) relative to delayed treatment. Patients receiving early treatment also had a greater likelihood of attaining an HbA1c<7% (<53 mmol/mol) (odds ratio: 2.00; 95% CI: 1.63-2.45; P<0.001) and a reduced risk of therapy intensification (hazard ratio: 0.72; 95% CI: 0.61-0.85; P<0.001). CONCLUSIONS Treatment with metformin earlier in the course of type 2 diabetes is associated with better glycemic control, more pronounced weight reduction, and a lower risk for therapy intensification than delayed treatment. Antihyperglycemic therapy should be initiated early after diagnosis to achieve optimal outcomes.

Dyslipidemia in Special Ethnic Populations

This article reviews racial/ethnic differences in dyslipidemia-prevalence of dyslipidemia, its relation to coronary heart disease (CHD) and stroke mortality rates, response to lipid-lowering agents, and lifestyle modification. Asian Indians, Filipinos, and Hispanics are at higher risk for dyslipidemia, which is consistent with the higher CHD mortality rates in these groups. Statins may have greater efficacy for Asians, but the data are mixed. Lifestyle modifications are recommended. Culturally-tailored prevention and intervention should be provided to the minority populations with elevated risk for dyslipidemia and considerably more research is needed to determine the best approaches to helping specific subgroups.

Forces influencing generic drug development in the United States: a narrative review

BackgroundThe United States (U.S.) Food and Drug Administration, as protectors of public health, encourages generic drug development and use so that patients can access affordable medications. The FDA, however, has limited mechanisms to encourage generic drug manufacturing.Main resultsGeneric drug manufacturers make decisions regarding development of products based on expected profitability, influenced by market forces, features of the reference listed drug, and manufacturing capabilities, as well as regulatory restrictions. Barriers to the development of generic drugs include the challenge of demonstrating bioequivalence of some products, particularly those that are considered to be complex generics.ConclusionsWe present here a focused review describing the influences on generic manufacturers who are prioritizing drugs for generic development. We also review proposed strategies that regulators may use to incentivize generic drug development.

Estimating generic drug use with electronic health records data from a health care delivery system: Implications for quality improvement and research

BACKGROUND Generic drug use in the outpatient setting is typically measured with adjudicated pharmacy claims; however, not all delivery systems have access to these data for their clinical populations. OBJECTIVE To develop an algorithm to estimate generic drug use in an outpatient setting using electronic health records (EHR) data. METHODS Twenty-five therapeutic classes were chosen with the potential for low generic use that were prescribed to managed care beneficiaries in a health care system in Northern California. An algorithm was developed to estimate generic drug use based on medication names and dispense-as-written requests from electronic prescriptions, as well as information on generic availability at the time the prescriptions were written. The algorithm was used to quantify a generic utilization rate (GUR) across therapeutic classes and was validated by comparing the estimated GUR to the true GUR, using pharmacy claims corresponding to prescriptions in the same patient cohort. RESULTS Among managed care beneficiaries, 104,859 prescriptions were identified for drugs in the therapeutic classes of interest with corresponding pharmacy claims. The algorithm estimated a GUR of 73.7% across 25 unique classes. The actual GUR based on pharmacy claims was 73.1%. Sensitivity (97%) and specificity (89%) of the algorithm were high, and total percentage of agreement was 95%. CONCLUSIONS An algorithm that estimates generic drug use performed well in a population of managed care beneficiaries. Health care delivery systems may apply methods described in this article to quantify generic drug use in their ambulatory populations for quality improvement and research initiatives, particularly when pharmacy claims are unavailable. DISCLOSURES This study was funded by a grant from the U.S. Food and Drug Administration in cooperative agreement with the Johns Hopkins School of Medicine and the Palo Alto Medical Foundation Research Institute (1U01FD005267-01). Romanelli has received research grant support from Pfizer and Janssen Scientific Affairs. Authors have no other conflicts to disclose. Romanelli and Segal contributed the study concept and design. Nimbal took the lead in data collection, assisted by Romanelli. All authors were involved with data interpretation and revision of the manuscript. The manuscript was written by Romanelli and Nimbal.

A Shared Medical Appointment on the Benefits and Risks of Opioids Is Associated With Improved Patient Confidence in Managing Chronic Pain

Objectives: To evaluate a shared medical appointment (SMA) on opioids in the treatment of chronic pain. Research design: This prospective study was conducted at an ambulatory clinic within a health-care delivery system. The SMA is a single 90-minute encounter, led by a physician. We included adult patients who attended the SMA and completed an immediate pre–post survey. Survey items were measured on a scale from 0 (worst) to 5 (best). Mean differences in pre–post responses were assessed by a paired t test. Results: A total of 130 patients were included in the analysis. Patients showed improvements in confidence in self-managing pain (+0.44; 95% confidence interval [CI]: 0.29-0.59; P < .001) and their providers’ ability to help manage pain (+0.28; 95% CI: 0.14-0.43; P < .001). Most patients (81%) were very/extremely satisfied with the SMA. Conclusions: An SMA on the benefits and risks of opioids was associated with prompt improvements in patients’ confidence in self-managing pain and in their health-care providers’ ability to help manage pain. Such confidence can lay the foundation for increased patient engagement and activation in pain management.

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.

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.