Robert A. Greevy

Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus: A Cohort Study

BACKGROUND The effects of sulfonylureas and metformin on outcomes of cardiovascular disease (CVD) in type 2 diabetes are not well-characterized. OBJECTIVE To compare the effects of sulfonylureas and metformin on CVD outcomes (acute myocardial infarction and stroke) or death. DESIGN Retrospective cohort study. SETTING National Veterans Health Administration databases linked to Medicare files. PATIENTS Veterans who initiated metformin or sulfonylurea therapy for diabetes. Patients with chronic kidney disease or serious medical illness were excluded. MEASUREMENTS Composite outcome of hospitalization for acute myocardial infarction or stroke, or death, adjusted for baseline demographic characteristics; medications; cholesterol, hemoglobin A1c, and serum creatinine levels; blood pressure; body mass index; health care utilization; and comorbid conditions. RESULTS Among 253 690 patients initiating treatment (98 665 with sulfonylurea therapy and 155 025 with metformin therapy), crude rates of the composite outcome were 18.2 per 1000 person-years in sulfonylurea users and 10.4 per 1000 person-years in metformin users (adjusted incidence rate difference, 2.2 [95% CI, 1.4 to 3.0] more CVD events with sulfonylureas per 1000 person-years; adjusted hazard ratio [aHR], 1.21 [CI, 1.13 to 1.30]). Results were consistent for both glyburide (aHR, 1.26 [CI, 1.16 to 1.37]) and glipizide (aHR, 1.15 [CI, 1.06 to 1.26]) in subgroups by CVD history, age, body mass index, and albuminuria; in a propensity score-matched cohort analysis; and in sensitivity analyses. LIMITATION Most of the veterans in the study population were white men; data on women and minority groups were limited but reflective of the Veterans Health Administration population. CONCLUSION Use of sulfonylureas compared with metformin for initial treatment of diabetes was associated with an increased hazard of CVD events or death. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality and the U.S. Department of Health and Human Services.

Association Between Intensification of Metformin Treatment With Insulin vs Sulfonylureas and Cardiovascular Events and All-Cause Mortality Among Patients With Diabetes

IMPORTANCE Preferred second-line medication for diabetes treatment after metformin failure remains uncertain. OBJECTIVE To compare time to acute myocardial infarction (AMI), stroke, or death in a cohort of metformin initiators who added insulin or a sulfonylurea. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort constructed with national Veterans Health Administration, Medicare, and National Death Index databases. The study population comprised veterans initially treated with metformin from 2001 through 2008 who subsequently added either insulin or sulfonylurea. Propensity score matching on characteristics was performed, matching each participant who added insulin to 5 who added a sulfonylurea. Patients were followed through September 2011 for primary analyses or September 2009 for cause-of-death analyses. MAIN OUTCOMES AND MEASURES Risk of a composite outcome of AMI, stroke hospitalization, or all-cause death was compared between therapies with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, cholesterol level, hemoglobin A1c level, creatinine level, blood pressure, body mass index, and comorbidities. RESULTS Among 178,341 metformin monotherapy patients, 2948 added insulin and 39,990 added a sulfonylurea. Propensity score matching yielded 2436 metformin + insulin and 12,180 metformin + sulfonylurea patients. At intensification, patients had received metformin for a median of 14 months (IQR, 5-30), and hemoglobin A1c level was 8.1% (IQR, 7.2%-9.9%). Median follow-up after intensification was 14 months (IQR, 6-29 months). There were 172 vs 634 events for the primary outcome among patients who added insulin vs sulfonylureas, respectively (42.7 vs 32.8 events per 1000 person-years; adjusted hazard ratio [aHR], 1.30; 95% CI, 1.07-1.58; P = .009). Acute myocardial infarction and stroke rates were statistically similar, 41 vs 229 events (10.2 and 11.9 events per 1000 person-years; aHR, 0.88; 95% CI, 0.59-1.30; P = .52), whereas all-cause death rates were 137 vs 444 events, respectively (33.7 and 22.7 events per 1000 person-years; aHR, 1.44; 95% CI, 1.15-1.79; P = .001). There were 54 vs 258 secondary outcomes: AMI, stroke hospitalizations, or cardiovascular deaths (22.8 vs 22.5 events per 1000 person-years; aHR, 0.98; 95% CI, 0.71-1.34; P = .87). CONCLUSIONS AND RELEVANCE Among patients with diabetes who were receiving metformin, the addition of insulin vs a sulfonylurea was associated with an increased risk of a composite of nonfatal cardiovascular outcomes and all-cause mortality. These findings require further investigation to understand risks associated with insulin use in these patients.

Optimal Nonbipartite Matching and Its Statistical Applications

Matching is a powerful statistical tool in design and analysis. Conventional two-group, or bipartite, matching has been widely used in practice. However, its utility is limited to simpler designs. In contrast, nonbipartite matching is not limited to the two-group case, handling multiparty matching situations. It can be used to find the set of matches that minimize the sum of distances based on a given distance matrix. It brings greater flexibility to the matching design, such as multigroup comparisons. Thanks to improvements in computing power and freely available algorithms to solve nonbipartite problems, the cost in terms of computation time and complexity is low. This article reviews the optimal nonbipartite matching algorithm and its statistical applications, including observational studies with complex designs and an exact distribution-free test comparing two multivariate distributions. We also introduce an R package that performs optimal nonbipartite matching. We present an easily accessible web application to make nonbipartite matching freely available to general researchers.

Computer-based Insulin Infusion Protocol Improves Glycemia Control over Manual Protocol

OBJECTIVE Hyperglycemia worsens clinical outcomes in critically ill patients. Precise glycemia control using intravenous insulin improves outcomes. To determine if we could improve glycemia control over a previous paper-based, manual protocol, authors implemented, in a surgical intensive care unit (SICU), an intravenous insulin protocol integrated into a care provider order entry (CPOE) system. DESIGN Retrospective before-after study of consecutive adult patients admitted to a SICU during pre (manual protocol, 32 days) and post (computer-based protocol, 49 days) periods. MEASUREMENTS Percentage of glucose readings in ideal range of 70-109 mg/dl, and minutes spent in ideal range of control during the first 5 days of SICU stay. RESULTS The computer-based protocol reduced time from first glucose measurement to initiation of insulin protocol, improved the percentage of all SICU glucose readings in the ideal range, and improved control in patients on IV insulin for > or =24 hours. Hypoglycemia (<40 mg/dl) was rare in both groups. CONCLUSION The CPOE-based intravenous insulin protocol improved glycemia control in SICU patients compared to a previous manual protocol, and reduced time to insulin therapy initiation. Integrating a computer-based insulin protocol into a CPOE system achieved efficient, safe, and effective glycemia control in SICU patients.

Organisational culture: variation across hospitals and connection to patient safety climate

Context Bureaucratic organisational culture is less favourable to quality improvement, whereas organisations with group (teamwork) culture are better aligned for quality improvement. Objective To determine if an organisational group culture shows better alignment with patient safety climate. Design Cross-sectional administration of questionnaires. Setting 40 Hospital Corporation of America hospitals. Participants 1406 nurses, ancillary staff, allied staff and physicians. Main outcome measures Competing Values Measure of Organisational Culture, Safety Attitudes Questionnaire (SAQ), Safety Climate Survey (SCSc) and Information and Analysis (IA). Results The Cronbach alpha was 0.81 for the group culture scale and 0.72 for the hierarchical culture scale. Group culture was positively correlated with SAQ and its subscales (from correlation coefficient r=0.44 to 0.55, except situational recognition), ScSc (r=0.47) and IA (r=0.33). Hierarchical culture was negatively correlated with the SAQ scales, SCSc and IA. Among the 40 hospitals, 37.5% had a hierarchical dominant culture, 37.5% a dominant group culture and 25% a balanced culture. Group culture hospitals had significantly higher safety climate scores than hierarchical culture hospitals. The magnitude of these relationships was not affected after adjusting for provider job type and hospital characteristics. Conclusions Hospitals vary in organisational culture, and the type of culture relates to the safety climate within the hospital. In combination with prior studies, these results suggest that a healthcare organisations culture is a critical factor in the development of its patient safety climate and in the successful implementation of quality improvement initiatives.

The Comprehensiveness of Family Cancer History Assessments in Primary Care

Background: Accurate family history information is required for adequate breast and colorectal cancer risk assessments. Few studies have examined the comprehensiveness of the family medical history interview in primary care. Methods: We compared family cancer history information collected through a self-completed survey with that documented within medical charts for 310 patients. Results: Forty-three percent (18/42) of individuals at increased risk for breast or colorectal cancer based on their family history had documentation of this risk within their chart. Age of cancer diagnosis was recorded for 40% (50/124) of affected relatives identified by chart review compared with 81% (203/252) identified through the survey (p < 0.0001). Conclusions: Over half of the individuals at increased risk for breast or colorectal cancer based on their family history did not have documentation of this risk within their medical record, and the age of relatives at diagnosis was frequently missing.

Comparative effectiveness of incident oral antidiabetic drugs on kidney function.

Diabetes is a major cause of chronic kidney disease, and oral antidiabetic drugs are the mainstay of therapy for most patients with Type 2 diabetes. Here we evaluated their role on renal outcomes by using a national Veterans Administration database to assemble a retrospective cohort of 93,577 diabetic patients who filled an incident oral antidiabetic drug prescription for metformin, sulfonylurea, or rosiglitazone, and had an estimated glomerular filtration rate (eGFR) of 60 ml/min or better. The primary composite outcome was a persistent decline in eGFR from baseline of 25% or more (eGFR event) or a diagnosis of end-stage renal disease (ESRD). The secondary outcome was an eGFR event, ESRD, or death. Sensitivity analyses included using a more stringent definition of the eGFR event requiring an eGFR <60 ml/min per 1.73 m2 in addition to the 25% or more decline; controlling for baseline proteinuria thereby restricting data to 15,065 patients; and not requiring persistent treatment with the initial oral antidiabetic drug. Compared to patients using metformin, sulfonylurea users had an increased risk for both the primary and the secondary outcome, each with an adjusted hazard ratio of 1.20. Results of sensitivity analyses were consistent with the main findings. The risk associated with rosiglitazone was similar to metformin for both outcomes. Thus, compared to metformin, oral antidiabetic drug treatment with sulfonylureas increased the risk of a decline in eGFR, ESRD, or death.

Evaluation of hospital glycemic control at US academic medical centers.

OBJECTIVE To evaluate contemporary hospital glycemic management in US academic medical centers. DESIGN This retrospective cohort study was conducted on patients discharged from 37 academic medical centers between July 1 and September 30, 2004; 1,718 eligible adult patients met at least 1 of the inclusion criteria: 2 consecutive blood glucose readings >180 mg/dL within 24 hours, or insulin treatment at any time during hospitalization. We assessed 3 consecutive measurement days of glucose values, glycemic therapy, and additional clinical and laboratory characteristics. RESULTS In this diverse cohort, 79% of patients had a prior diagnosis of diabetes, and 84.6% received insulin on the second measurement day. There was wide variation in hospital performance of recommended hospital diabetes care measures such as glycosylated hemoglobin (A1C) assessment (range, 3%-63%) and timely admission laboratory glucose measurement (range, 39%-97%). Median glucose was significantly lower for patients in the intensive care unit (ICU) compared to ward/intermediate care. ICU patients treated with intravenous insulin had significantly lower median glucose when compared to subcutaneous insulin. Only 25% of ICU patients on day 3 had estimated 6 AM glucose <or=110 mg/dL. Hyperglycemia was common, 50% of all patients had >or=1 glucose measurement >or=180 mg/dL on measurement days 2 and 3. Severe hypoglycemia (<50 mg/dL) occurred in 2.8% of all patient days. CONCLUSIONS Despite frequent insulin use, glucose control was suboptimal. Academic medical centers have opportunities to improve care to meet current American Diabetes Association hospital diabetes care standards.

Measuring and Comparing Safety Climate in Intensive Care Units

Background:Learning about the factors that influence safety climate and improving the methods for assessing relative performance among hospital or units would improve decision-making for clinical improvement. Objectives:To measure safety climate in intensive care units (ICU) owned by a large for-profit integrated health delivery systems; identify specific provider, ICU, and hospital factors that influence safety climate; and improve the reporting of safety climate data for comparison and benchmarking. Research Design:We administered the Safety Attitudes Questionnaire (SAQ) to clinicians, staff, and administrators in 110 ICUs from 61 hospitals. Subjects:A total of 1502 surveys (43% response) from physicians, nurses, respiratory therapists, pharmacists, mangers, and other ancillary providers. Measures:The survey measured safety climate across 6 domains: teamwork climate; safety climate; perceptions of management; job satisfaction; working conditions; and stress recognition. Percentage of positive scores, mean scores, unadjusted random effects, and covariate-adjusted random effect were used to rank ICU performance. Results:The cohort was characterized by a positive safety climate. Respondents scored perceptions of management and working conditions significantly lower than the other domains of safety climate. Respondent job type was significantly associated with safety climate and domain scores. There was modest agreement between ranking methodologies using raw scores and random effects. Conclusions:The relative proportion of job type must be considered before comparing safety climate results across organizational units. Ranking methodologies based on raw scores and random effects are viable for feedback reports. The use of covariate-adjusted random effects is recommended for hospital decision-making.

Effect of Short Call Admission on Length of Stay and Quality of Care for Acute Decompensated Heart Failure

Background— In response to residency work hour restrictions, programs restructured call schedules, increasing the use of short call (daytime admitting teams). Few data exist on the effect of short call on quality of patient care. Our objective was to examine the effect of short call admission on length of stay and quality of care for patients with acute decompensated heart failure. Methods and Results— We conducted a retrospective cohort study of 218 patients admitted with acute decompensated heart failure to the Nashville VA Medical Center between July 1, 2003, and June 30, 2005. The primary exposure was short call, and the primary outcome was length of stay. The secondary outcomes—diuretic dosing, weight monitoring, and hospital complications—were determined through a combination of administrative data and chart review. Patients admitted to short call had a longer median length of stay than patients admitted to long call (5.2 days [25% to 75%, 3.2 to 8 days] versus 3.9 days [interquartile range, 2.7 to 6.5 days]; P=0.0004). After adjustment for covariates, short call had a 44% increase in length of stay (95% CI, 15 to 80) compared with long call. Short call patients received fewer diuretic doses in the first 24 hours of hospitalization (1.80 versus 2.12; P=0.014) and had a longer median time to the second dose of loop diuretics compared with long call patients (17.9 hours versus 16.2 hours; P=0.044). Conclusions— Admission to short call is predictive of increased length of stay, a decreased number of diuretic doses, and delays in the timing of diuretics among patients with acute decompensated heart failure. Additional studies are needed to clarify the impact of short call admission on inpatient quality of care.