Engaging patients and stakeholders in research proposal review: the patient-centered outcomes research institute.

The inaugural round of merit review for the Patient-Centered Outcomes Research Institute (PCORI) in November 2012 included patients and other stakeholders, as well as scientists. This article examines relationships among scores of the 3 reviewer types, changes in scoring after in-person discussion, and the effect of inclusion of patient and stakeholder reviewers on the review process. In the first phase, 363 scientists scored 480 applications. In the second phase, 59 scientists, 21 patients, and 31 stakeholders provided a "prediscussion" score and a final "postdiscussion" score after an in-person meeting for applications. Bland-Altman plots were used to characterize levels of agreement among and within reviewer types before and after discussion. Before discussion, there was little agreement among average scores given by the 4 lead scientific reviewers and patient and stakeholder reviewers. After discussion, the 4 primary reviewers showed mild convergence in their scores, and the 21-member panel came to a much stronger agreement. Of the 25 awards with the best (and lowest) scores after phase 2, only 13 had ranked in the top 25 after the phase 1 review by scientists. Five percent of the 480 proposals submitted were funded. The authors conclude that patient and stakeholder reviewers brought different perspectives to the review process but that in-person discussion led to closer agreement among reviewer types. It is not yet known whether these conclusions are generalizable to future rounds of peer review. Future work would benefit from additional data collection for evaluation purposes and from long-term evaluation of the effect on the funded research.

PCORI at 3 years--progress, lessons, and plans.

The Patient-Centered Outcomes Research Institute (PCORI) has established distinctive pathways for funding and conducting practical research and has awarded over $318 million for studies covering a wide range of conditions, locations, and socioeconomic characteristics.

Screening for impaired fasting glucose and diabetes using available health plan data.

AIMS: To develop and validate prediction equations to identify individuals at high risk for type 2 diabetes using existing health plan data. METHODS: Health plan data from 2005 to 2009 from 18,527 members of a Midwestern HMO without diabetes, 6% of whom had fasting plasma glucose (FPG) ≥110mg/dL, and health plan data from 2005 to 2006 from 368,025 members of a West Coast-integrated delivery system without diabetes, 13% of whom had FPG ≥110mg/dL were analyzed. Within each health plan, we used multiple logistic regression to develop equations to predict FPG ≥110mg/dL for half of the population and validated the equations using the other half. We then externally validated the equations in the other health plan. RESULTS: Areas under the curve for the most parsimonious equations were 0.665 to 0.729 when validated internally. Positive predictive values were 14% to 32% when validated internally and 14% to 29% when validated externally. CONCLUSION: Multivariate logistic regression equations can be applied to existing health plan data to efficiently identify persons at higher risk for dysglycemia who might benefit from definitive diagnostic testing and interventions to prevent or treat diabetes.

Future directions for cardiovascular disease comparative effectiveness research: report of a workshop sponsored by the National Heart, Lung, and Blood Institute.

Comparative effectiveness research (CER) aims to provide decision makers with the evidence needed to evaluate the benefits and harms of alternative clinical management strategies. CER has become a national priority, with considerable new research funding allocated. Cardiovascular disease is a priority area for CER. This workshop report provides an overview of CER methods, with an emphasis on practical clinical trials and observational treatment comparisons. The report also details recommendations to the National Heart, Lung, and Blood Institute for a new framework for evidence development to foster cardiovascular CER, and specific studies to address 8 clinical issues identified by the Institute of Medicine as high priorities for cardiovascular CER.

Construction of a multisite DataLink using electronic health records for the identification, surveillance, prevention, and management of diabetes mellitus: the SUPREME-DM project.

INTRODUCTION: Electronic health record (EHR) data enhance opportunities for conducting surveillance of diabetes. The objective of this study was to identify the number of people with diabetes from a diabetes DataLink developed as part of the SUPREME-DM (SUrveillance, PREvention, and ManagEment of Diabetes Mellitus) project, a consortium of 11 integrated health systems that use comprehensive EHR data for research. METHODS: We identified all members of 11 health care systems who had any enrollment from January 2005 through December 2009. For these members, we searched inpatient and outpatient diagnosis codes, laboratory test results, and pharmaceutical dispensings from January 2000 through December 2009 to create indicator variables that could potentially identify a person with diabetes. Using this information, we estimated the number of people with diabetes and among them, the number of incident cases, defined as indication of diabetes after at least 2 years of continuous health system enrollment. RESULTS: The 11 health systems contributed 15,765,529 unique members, of whom 1,085,947 (6.9%) met 1 or more study criteria for diabetes. The nonstandardized proportion meeting study criteria for diabetes ranged from 4.2% to 12.4% across sites. Most members with diabetes (88%) met multiple criteria. Of the members with diabetes, 428,349 (39.4%) were incident cases. CONCLUSION: The SUPREME-DM DataLink is a unique resource that provides an opportunity to conduct comparative effectiveness research, epidemiologic surveillance including longitudinal analyses, and population-based care management studies of people with diabetes. It also provides a useful data source for pragmatic clinical trials of prevention or treatment interventions.

Clinical, epidemiologic, histopathologic and molecular features of an unexplained dermopathy.

BACKGROUND: Morgellons is a poorly characterized constellation of symptoms, with the primary manifestations involving the skin. We conducted an investigation of this unexplained dermopathy to characterize the clinical and epidemiologic features and explore potential etiologies. METHODS: A descriptive study was conducted among persons at least 13 years of age and enrolled in Kaiser Permanente Northern California (KPNC) during 2006-2008. A case was defined as the self-reported emergence of fibers or materials from the skin accompanied by skin lesions and/or disturbing skin sensations. We collected detailed epidemiologic data, performed clinical evaluations and geospatial analyses and analyzed materials collected from participants' skin. RESULTS: We identified 115 case-patients. The prevalence was 3.65 (95% CI = 2.98, 4.40) cases per 100,000 enrollees. There was no clustering of cases within the 13-county KPNC catchment area (p = .113). Case-patients had a median age of 52 years (range: 17-93) and were primarily female (77%) and Caucasian (77%). Multi-system complaints were common; 70% reported chronic fatigue and 54% rated their overall health as fair or poor with mean Physical Component Scores and Mental Component Scores of 36.63 (SD = 12.9) and 35.45 (SD = 12.89), respectively. Cognitive deficits were detected in 59% of case-patients and 63% had evidence of clinically significant somatic complaints; 50% had drugs detected in hair samples and 78% reported exposure to solvents. Solar elastosis was the most common histopathologic abnormality (51% of biopsies); skin lesions were most consistent with arthropod bites or chronic excoriations. No parasites or mycobacteria were detected. Most materials collected from participants' skin were composed of cellulose, likely of cotton origin. CONCLUSIONS: This unexplained dermopathy was rare among this population of Northern California residents, but associated with significantly reduced health-related quality of life. No common underlying medical condition or infectious source was identified, similar to more commonly recognized conditions such as delusional infestation.

Lactation intensity and postpartum maternal glucose tolerance and insulin resistance in women with recent GDM: the SWIFT cohort.

OBJECTIVE: To examine the association between breastfeeding intensity in relation to maternal blood glucose and insulin and glucose intolerance based on the postpartum 2-h 75-g oral glucose tolerance test (OGTT) results at 6-9 weeks after a pregnancy with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We selected 522 participants enrolled into the Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT), a prospective observational cohort study of Kaiser Permanente Northern California members diagnosed with GDM using the 3-h 100-g OGTT by the Carpenter and Coustan criteria. Women were classified as normal, prediabetes, or diabetes according to American Diabetes Association criteria based on the postpartum 2-h 75-g OGTT results. RESULTS: Compared with exclusive or mostly formula feeding (>17 oz formula per 24 h), exclusive breastfeeding and mostly breastfeeding (≤6 oz formula per 24 h) groups, respectively, had lower adjusted mean (95% CI) group differences in fasting plasma glucose (mg/dL) of -4.3 (-7.4 to -1.3) and -5.0 (-8.5 to -1.4), in fasting insulin (µU/mL) of -6.3 (-10.1 to -2.4) and -7.5 (-11.9 to -3.0), and in 2-h insulin of -21.4 (-41.0 to -1.7) and -36.5 (-59.3 to -13.7) (all P < 0.05). Exclusive or mostly breastfeeding groups had lower prevalence of diabetes or prediabetes (P = 0.02). CONCLUSIONS: Higher intensity of lactation was associated with improved fasting glucose and lower insulin levels at 6-9 weeks' postpartum. Lactation may have favorable effects on glucose metabolism and insulin sensitivity that may reduce diabetes risk after GDM pregnancy.

Study of Women, Infant Feeding, and Type 2 diabetes mellitus after GDM pregnancy (SWIFT), a prospective cohort study: methodology and design.

BACKGROUND: Women with history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes within 5 years after delivery. Evidence that lactation duration influences incident type 2 diabetes after GDM pregnancy is based on one retrospective study reporting a null association. The Study of Women, Infant Feeding and Type 2 Diabetes after GDM pregnancy (SWIFT) is a prospective cohort study of postpartum women with recent GDM within the Kaiser Permanente Northern California (KPNC) integrated health care system. The primary goal of SWIFT is to assess whether prolonged, intensive lactation as compared to formula feeding reduces the 2-year incidence of type 2 diabetes mellitus among women with GDM. The study also examines whether lactation intensity and duration have persistent favorable effects on blood glucose, insulin resistance, and adiposity during the 2-year postpartum period. This report describes the design and methods implemented for this study to obtain the clinical, biochemical, anthropometric, and behavioral measurements during the recruitment and follow-up phases. METHODS: SWIFT is a prospective, observational cohort study enrolling and following over 1, 000 postpartum women diagnosed with GDM during pregnancy within KPNC. The study enrolled women at 6-9 weeks postpartum (baseline) who had been diagnosed by standard GDM criteria, aged 20-45 years, delivered a singleton, term (greater than or equal to 35 weeks gestation) live birth, were not using medications affecting glucose tolerance, and not planning another pregnancy or moving out of the area within the next 2 years. Participants who are free of type 2 diabetes and other serious medical conditions at baseline are screened for type 2 diabetes annually within the first 2 years after delivery. Recruitment began in September 2008 and ends in December 2011. Data are being collected through pregnancy and early postpartum telephone interviews, self-administered monthly mailed questionnaires (3-11 months postpartum), a telephone interview at 6 months, and annual in-person examinations at which a 75 g 2-hour OGTT is conducted, anthropometric measurements are obtained, and self- and interviewer-administered questionnaires are completed. DISCUSSION: This is the first, large prospective, community-based study involving a racially and ethnically diverse cohort of women with recent GDM that rigorously assesses lactation intensity and duration and examines their relationship to incident type 2 diabetes while accounting for numerous potential confounders not assessed previously.

Correlates of depression among people with diabetes: The Translating Research Into Action for Diabetes (TRIAD) study.

AIM: The broad objective of this study was to examine multiple dimensions of depression in a large, diverse population of adults with diabetes. Specific aims were to measure the association of depression with: (1) patient characteristics; (2) outcomes; and (3) diabetes-related quality of care. METHODS: Cross-sectional analyses were performed using survey and chart data from the Translating Research Into Action for Diabetes (TRIAD) study, including 8790 adults with diabetes, enrolled in 10 managed care health plans in 7 states. Depression was measured using the Patient Health Questionnaire (PHQ-8). Patient characteristics, outcomes and quality of care were measured using validated survey items and chart data. RESULTS: Nearly 18% of patients had major depression, with prevalence 2-3 times higher among patients with low socioeconomic status. Pain and limited mobility were strongly associated with depression, controlling for other patient characteristics. Depression was associated with slightly worse glycemic control, but not other intermediate clinical outcomes. Depressed patients received slightly fewer recommended diabetes-related processes of care. CONCLUSIONS: In a large, diverse cohort of patients with diabetes, depression was most prevalent among patients with low socioeconomic status and those with pain, and was associated with slightly worse glycemic control and quality of care.

Population trends in the incidence and outcomes of acute myocardial infarction.

BACKGROUND: Few studies have characterized recent population trends in the incidence and outcomes of myocardial infarction. METHODS: We identified patients 30 years of age or older in a large, diverse, community-based population who were hospitalized for incident myocardial infarction between 1999 and 2008. Age- and sex-adjusted incidence rates were calculated for myocardial infarction overall and separately for ST-segment elevation and non-ST-segment elevation myocardial infarction. Patient characteristics, outpatient medications, and cardiac biomarker levels during hospitalization were identified from health plan databases, and 30-day mortality was ascertained from administrative databases, state death data, and Social Security Administration files. RESULTS: We identified 46,086 hospitalizations for myocardial infarctions during 18,691,131 person-years of follow-up from 1999 to 2008. The age- and sex-adjusted incidence of myocardial infarction increased from 274 cases per 100,000 person-years in 1999 to 287 cases per 100,000 person-years in 2000, and it decreased each year thereafter, to 208 cases per 100,000 person-years in 2008, representing a 24% relative decrease over the study period. The age- and sex-adjusted incidence of ST-segment elevation myocardial infarction decreased throughout the study period (from 133 cases per 100,000 person-years in 1999 to 50 cases per 100,000 person-years in 2008, P<0.001 for linear trend). Thirty-day mortality was significantly lower in 2008 than in 1999 (adjusted odds ratio, 0.76; 95% confidence interval, 0.65 to 0.89). CONCLUSIONS: Within a large community-based population, the incidence of myocardial infarction decreased significantly after 2000, and the incidence of ST-segment elevation myocardial infarction decreased markedly after 1999. Reductions in short-term case fatality rates for myocardial infarction appear to be driven, in part, by a decrease in the incidence of ST-segment elevation myocardial infarction and a lower rate of death after non-ST-segment elevation myocardial infarction.

Meaningful variation in performance: what does variation in quality tell us about improving quality?

BACKGROUND: Variance reduction is sometimes considered as a goal of clinical quality improvement. Variance among physicians, hospitals, or health plans has been evaluated as the proportion of total variance (or intraclass correlation, ICC) in a quality measure; low ICCs have been interpreted to indicate low potential for quality improvement at that level. However, the absolute amount of variation, expressed in clinically meaningful units, is less frequently reported. Moreover, changes in variance components have not been studied as quality improves. OBJECTIVES: To examine changes in variance components at primary care physician and medical facility levels as performance improved for 4 quality indicators: systolic blood pressure levels in hypertension; low-density lipoprotein-cholesterol levels in hyperlipidemia; patient-reported care experience scores after primary care visits; and mammography screening rates. POPULATION: Adult members (n = 62,596-410,976) of Kaiser Permanente in Northern California, served by more than 1000 primary care physicians in 35 facilities, from 2001 to 2006. METHODS: Multilevel linear and logistic regression to examine the interphysician and interfacility variances in 4 quality indicators over 6 years, after case-mix adjustment. RESULTS: ICCs were low for all 4 indicators at both levels (0.0021-0.086). Nevertheless, variances at both levels were statistically and clinically significant. For systolic blood pressure and the care experience score, interfacility and interphysician variance as well as ICCs decreased further as quality improved; declines were greater at the facility level. For low-density lipoprotein-cholesterol, variability at both levels increased with quality improvement; and for screening mammography, small declines were not statistically significant for either physicians or facilities. CONCLUSIONS: Low proportions of variance do not predict low potential for quality improvement. Despite low ICCs for facilities, quality improvement efforts directed primarily at facilities improved quality for all 4 indicators.

Meaningful variation in performance: a systematic literature review.

BACKGROUND: Recommendations for directing quality improvement initiatives at particular levels (eg, patients, physicians, provider groups) have been made on the basis of empirical components of variance analyses of performance. OBJECTIVE: To review the literature on use of multilevel analyses of variability in quality. RESEARCH DESIGN: Systematic literature review of English-language articles (n = 39) examining variability and reliability of performance measures in Medline using PubMed (1949-November 2008). RESULTS: Variation was most commonly assessed at facility (eg, hospital, medical center) (n = 19) and physician (n = 18) levels; most articles reported variability as the proportion of total variation attributable to given levels (n = 22). Proportions of variability explained by aggregated levels were generally low (eg, <19% for physicians), and numerous authors concluded that the proportion of variability at a specific level did not justify targeting quality interventions to that level. Few articles based their recommendations on absolute differences among physicians, hospitals, or other levels. Seven of 12 articles that assessed reliability found that reliability was poor at the physician or hospital level due to low proportional variability and small sample sizes per unit, and cautioned that public reporting or incentives based on these measures may be inappropriate. CONCLUSIONS: The proportion of variability at levels higher than patients is often found to be "low." Although low proportional variability may lead to poor measurement reliability, a number of authors further suggested that it also indicates a lack of potential for quality improvement. Few studies provided additional information to help determine whether variation was, nevertheless, clinically meaningful.

Validation of an algorithm for categorizing the severity of hospital emergency department visits.

BACKGROUND: Differentiating between appropriate and inappropriate resource use represents a critical challenge in health services research. The New York University Emergency Department (NYU ED) visit severity algorithm attempts to classify visits to the ED based on diagnosis, but it has not been formally validated. OBJECTIVE: To assess the validity of the NYU algorithm. RESEARCH DESIGN: A longitudinal study in a single integrated delivery system from January 1999 to December 2001. SUBJECTS: A total of 2,257,445 commercial and 261,091 Medicare members of an integrated delivery system. MEASURES: ED visits were classified as emergent, nonemergent, or intermediate severity, using the NYU ED algorithm. We examined the relationship between visit-severity and the probability of future hospitalizations and death using a logistic model with a general estimating equation approach. RESULTS: Among commercially insured subjects, ED visits categorized as emergent were significantly more likely to result in a hospitalization within 1-day (odds ratio = 3.37, 95% CI: 3.31-3.44) or death within 30-days (odds ratio = 2.81, 95% CI: 2.62-3.00) than visits categorized as nonemergent. We found similar results in Medicare patients and in sensitivity analyses using different probability thresholds. ED overuse for nonemergent conditions was not related to socio-economic status or insurance type. CONCLUSIONS: The evidence presented supports the validity of the NYU ED visit severity algorithm for differentiating ED visits based on need for hospitalization and/or mortality risk; therefore, it can contribute to evidence-based policies aimed at reducing the use of the ED for nonemergencies.

Characteristics of insured patients with persistent gaps in diabetes care services: the Translating Research into Action for Diabetes (TRIAD) study.

BACKGROUND: Although preventing diabetes complications requires long-term management, little is known about which patients persistently fail to get recommended care. OBJECTIVE: To determine the frequency and correlates of persistent, long-term gaps in diabetes care. METHOD: : The study population included 8392 patients with diabetes. Patient surveys and medical records from 10 health plans over 3 years provided data on socioeconomic characteristics, access to care, social support, and mental and physical health, and diabetes preventive care services. We defined a "persistent gap" as a participant's missing a preventive care service for the entire 3 years. Services considered included hemoglobin A1c, cholesterol, and albuminuria tests, and foot and dilated eye examinations. RESULTS: Thirty percent of participants had at least 1 persistent gap. The most common gaps were lipid testing (11.6%), microalbuminuria testing (9.7%), and eye examinations (9.0%). Persistent gaps were 18% to 42% higher for young patients, lean persons, those with low income, employed persons, smokers, those with diabetes less than 5 years, and patients with none or 1 comorbid conditions. Sex, education, marital status, family demands, transportation, trust in physicians, and mental health were not associated with gaps in care. CONCLUSIONS: Persistent gaps in diabetes care are common even among insured patients. Patients with lower income, younger age, fewer years of diabetes, having fewer comorbidities, taking fewer medications, and poor health behaviors are vulnerable to persistent gaps in care and a group who warrant targeted interventions to improve preventive diabetes care.

Identifying risk factors for racial disparities in diabetes outcomes: the translating research into action for diabetes study.

BACKGROUND: Versus whites, blacks with diabetes have poorer control of hemoglobin A1c (HbA1c), higher systolic blood pressure (SBP), and higher low-density lipoprotein (LDL) cholesterol as well as higher rates of morbidity and microvascular complications. OBJECTIVE: To examine whether several mutable risk factors were more strongly associated with poor control of multiple intermediate outcomes among blacks with diabetes than among similar whites. DESIGN: Case-control study. SUBJECTS: A total of 764 blacks and whites with diabetes receiving care within 8 managed care health plans. MEASURES: Cases were patients with poor control of at least 2 of 3 intermediate outcomes (HbA1c > or =8.0%, SBP > or =140 mmHg, LDL cholesterol > or =130 mg/dL) and controls were patients with good control of all 3 (HbA1c <8.0%, SBP <140 mmHg, LDL cholesterol <130 mg/dL). In multivariate analyses, we determined whether each of several potentially mutable risk factors, including depression, poor adherence to medications, low self-efficacy for reducing cardiovascular risk, and poor patient-provider communication, predicted case or control status. RESULTS: Among blacks but not whites, in multivariate analyses depression (odds ratio: 2.28; 95% confidence interval: 1.09-4.75) and having missed medication doses (odds ratio: 1.96; 95% confidence interval: 1.01-3.81) were associated with greater odds of being a case rather than a control. None of the other risk factors were associated for either blacks or whites. CONCLUSIONS: Depression and missing medication doses are more strongly associated with poor diabetes control among blacks than in whites. These 2 risk factors may represent important targets for patient-level interventions to address racial disparities in diabetes outcomes.

Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus.

CONTEXT: Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older patients with type 2 diabetes. OBJECTIVE: To determine if hypoglycemic episodes severe enough to require hospitalization are associated with an increased risk of dementia in a population of older patients with type 2 diabetes followed up for 27 years. DESIGN, SETTING, AND PATIENTS: A longitudinal cohort study from 1980-2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who are members of an integrated health care delivery system in northern California. MAIN OUTCOME MEASURE: Hypoglycemic events from 1980-2002 were collected and reviewed using hospital discharge and emergency department diagnoses. Cohort members with no prior diagnoses of dementia, mild cognitive impairment, or general memory complaints as of January 1, 2003, were followed up for a dementia diagnosis through January 15, 2007. Dementia risk was examined using Cox proportional hazard regression models, adjusted for age, sex, race/ethnicity, education, body mass index, duration of diabetes, 7-year mean glycated hemoglobin, diabetes treatment, duration of insulin use, hyperlipidemia, hypertension, cardiovascular disease, stroke, transient cerebral ischemia, and end-stage renal disease. RESULTS: At least 1 episode of hypoglycemia was diagnosed in 1465 patients (8.8%) and dementia was diagnosed in 1822 patients (11%) during follow-up; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95%). Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk with fully adjusted hazard ratios (HRs): for 1 episode (HR, 1.26; 95% confidence interval [CI], 1.10-1.49); 2 episodes (HR, 1.80; 95% CI, 1.37-2.36); and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). The attributable risk of dementia between individuals with and without a history of hypoglycemia was 2.39% per year (95% CI, 1.72%-3.01%). Results were not attenuated when medical utilization rates, length of health plan membership, or time since initial diabetes diagnosis were added to the model. When examining emergency department admissions for hypoglycemia for association with risk of dementia (535 episodes), results were similar (compared with patients with 0 episodes) with fully adjusted HRs: for 1 episode (HR, 1.42; 95% CI, 1.12-1.78) and for 2 or more episodes (HR, 2.36; 95% CI, 1.57-3.55). CONCLUSIONS: Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.