Harvey J. Murff

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.

Detecting Adverse Events Using Information Technology

CONTEXT Although patient safety is a major problem, most health care organizations rely on spontaneous reporting, which detects only a small minority of adverse events. As a result, problems with safety have remained hidden. Chart review can detect adverse events in research settings, but it is too expensive for routine use. Information technology techniques can detect some adverse events in a timely and cost-effective way, in some cases early enough to prevent patient harm. OBJECTIVE To review methodologies of detecting adverse events using information technology, reports of studies that used these techniques to detect adverse events, and study results for specific types of adverse events. DESIGN Structured review. METHODOLOGY English-language studies that reported using information technology to detect adverse events were identified using standard techniques. Only studies that contained original data were included. MAIN OUTCOME MEASURES Adverse events, with specific focus on nosocomial infections, adverse drug events, and injurious falls. RESULTS Tools such as event monitoring and natural language processing can inexpensively detect certain types of adverse events in clinical databases. These approaches already work well for some types of adverse events, including adverse drug events and nosocomial infections, and are in routine use in a few hospitals. In addition, it appears likely that these techniques will be adaptable in ways that allow detection of a broad array of adverse events, especially as more medical information becomes computerized. CONCLUSION Computerized detection of adverse events will soon be practical on a widespread basis.

Adverse Drug Events Occurring Following Hospital Discharge

OBJECTIVE: To describe the incidence of adverse drug events (ADEs), preventable ADEs, and ameliorable ADEs occurring after hospital discharge and their associated risk factors.DESIGN: Prospective cohort study.SETTING: Urban academic health sciences center.PATIENTS: Consecutive patients discharged home from the general medical service.INTERVENTIONS: We determined posthospital outcomes approximately 24 days following discharge by performing a chart review and telephone interview. Using the telephone interview, we identified new or worsening symptoms, the patient’s health system use, and recollection of processes of care. Posthospital outcomes were judged by 2 internists independently.RESULTS: Four hundred of 581 potentially eligible patients were evaluated. Of the 400 patients, 45 developed an ADE (incidence, 11%; 95% confidence interval [CI], 8% to 14%). Of these, 27% were preventable and 33% were ameliorable. Injuries were significant in 32 patients, serious in 6, and life threatening in 7. Patients were less likely to experience an ADE if they recalled having side effects of prescribed medications explained (OR, 0.4; 95% CI, 0.2 to 0.8). The risk of ADE per prescription was highest for corticosteroids, anticoagulants, antibiotics, analgesics, and cardiovascular medications. Risk increased with prescription number. Failure to monitor was an especially common cause of preventable and ameliorable ADEs.CONCLUSION: Following discharge, ADEs were common and many were preventable or ameliorable. Medication side effects should be discussed, and interventions should include better monitoring and target patients receiving specific drug classes or multiple medications.

Automated identification of postoperative complications within an electronic medical record using natural language processing.

CONTEXT Currently most automated methods to identify patient safety occurrences rely on administrative data codes; however, free-text searches of electronic medical records could represent an additional surveillance approach. OBJECTIVE To evaluate a natural language processing search-approach to identify postoperative surgical complications within a comprehensive electronic medical record. DESIGN, SETTING, AND PATIENTS Cross-sectional study involving 2974 patients undergoing inpatient surgical procedures at 6 Veterans Health Administration (VHA) medical centers from 1999 to 2006. MAIN OUTCOME MEASURES Postoperative occurrences of acute renal failure requiring dialysis, deep vein thrombosis, pulmonary embolism, sepsis, pneumonia, or myocardial infarction identified through medical record review as part of the VA Surgical Quality Improvement Program. We determined the sensitivity and specificity of the natural language processing approach to identify these complications and compared its performance with patient safety indicators that use discharge coding information. RESULTS The proportion of postoperative events for each sample was 2% (39 of 1924) for acute renal failure requiring dialysis, 0.7% (18 of 2327) for pulmonary embolism, 1% (29 of 2327) for deep vein thrombosis, 7% (61 of 866) for sepsis, 16% (222 of 1405) for pneumonia, and 2% (35 of 1822) for myocardial infarction. Natural language processing correctly identified 82% (95% confidence interval [CI], 67%-91%) of acute renal failure cases compared with 38% (95% CI, 25%-54%) for patient safety indicators. Similar results were obtained for venous thromboembolism (59%, 95% CI, 44%-72% vs 46%, 95% CI, 32%-60%), pneumonia (64%, 95% CI, 58%-70% vs 5%, 95% CI, 3%-9%), sepsis (89%, 95% CI, 78%-94% vs 34%, 95% CI, 24%-47%), and postoperative myocardial infarction (91%, 95% CI, 78%-97%) vs 89%, 95% CI, 74%-96%). Both natural language processing and patient safety indicators were highly specific for these diagnoses. CONCLUSION Among patients undergoing inpatient surgical procedures at VA medical centers, natural language processing analysis of electronic medical records to identify postoperative complications had higher sensitivity and lower specificity compared with patient safety indicators based on discharge coding.

Hospital Workload and Adverse Events

Context:Hospitals are under pressure to increase revenue and lower costs, and at the same time, they face dramatic variation in clinical demand. Objective:We sought to determine the relationship between peak hospital workload and rates of adverse events (AEs). Methods:A random sample of 24,676 adult patients discharged from the medical/surgical services at 4 US hospitals (2 urban and 2 suburban teaching hospitals) from October 2000 to September 2001 were screened using administrative data, leaving 6841 cases to be reviewed for the presence of AEs. Daily workload for each hospital was characterized by volume, throughput (admissions and discharges), intensity (aggregate DRG weight), and staffing (patient-to-nurse ratios). For volume, we calculated an “enhanced” occupancy rate that accounted for same-day bed occupancy by more than 1 patient. We used Poisson regressions to predict the likelihood of an AE, with control for workload and individual patient complexity, and the effects of clustering. Results:One urban teaching hospital had enhanced occupancy rates more than 100% for much of the year. At that hospital, admissions and patients per nurse were significantly related to the likelihood of an AE (P < 0.05); occupancy rate, discharges, and DRG-weighted census were significant at P < 0.10. For example, a 0.1% increase in the patient-to-nurse ratio led to a 28% increase in the AE rate. Results at the other 3 hospitals varied and were mainly non significant. Conclusions:Hospitals that operate at or over capacity may experience heightened rates of patient safety events and might consider re-engineering the structures of care to respond better during periods of high stress.

Physician Satisfaction with Two Order Entry Systems

Objectives: In the wake of the Institute of Medicine report, To Err Is Human: Building a Safer Health System (LT Kohn, JM Corrigan, MS Donaldson, eds; Washington, DC: National Academy Press, 1999), numerous advisory panels are advocating widespread implementation of physician order entry as a means to reduce errors and improve patient safety. Successful implementation of an order entry system requires that attention be given to the user interface. The authors assessed physician satisfaction with the user interface of two different order entry systems—a commercially available product, and the Department of Veterans Affairs Computerized Patient Record System (CPRS). Design and Measurement: A standardized instrument for measuring user satisfaction with physician order entry systems was mailed to internal medicine and medicine-pediatrics house staff physicians. The subjects answered questions on each system using a 0 to 9 scale. Results: The survey response rates were 63 and 64 percent for the two order entry systems. Overall, house staff were dissatisfied with the commercial system, giving it an overall mean score of 3.67 (95 percent confidence interval [95%CI], 3.37–3.97). In contrast, the CPRS had a mean score of 7.21 (95% CI, 7.00–7.43), indicating that house staff were satisfied with the system. Overall satisfaction was most strongly correlated with the ability to perform tasks in a “straightforward” manner. Conclusions: User satisfaction differed significantly between the two order entry systems, suggesting that all order entry systems are not equally usable. Given the national usage of the two order entry systems studied, further studies are needed to assess physician satisfaction with use of these same systems at other institutions.

Electronically Screening Discharge Summaries for Adverse Medical Events

Objective: Detecting adverse events is pivotal for measuring and improving medical safety, yet current techniques discourage routine screening. The authors hypothesized that discharge summaries would include information on adverse events, and they developed and evaluated an electronic method for screening medical discharge summaries for adverse events. Design: A cohort study including 424 randomly selected admissions to the medical services of an academic medical center was conducted between January and July 2000. The authors developed a computerized screening tool that searched free-text discharge summaries for trigger words representing possible adverse events. Measurements: All discharge summaries with a trigger word present underwent chart review by two independent physician reviewers. The presence of adverse events was assessed using structured implicit judgment. A random sample of discharge summaries without trigger words also was reviewed. Results: Fifty-nine percent (251 of 424) of the discharge summaries contained trigger words. Based on discharge summary review, 44.8% (327 of 730) of the alerted trigger words indicated a possible adverse event. After medical record review, the tool detected 131 adverse events. The sensitivity and specificity of the screening tool were 69% and 48%, respectively. The positive predictive value of the tool was 52%. Conclusion: Medical discharge summaries contain information regarding adverse events. Electronic screening of discharge summaries for adverse events using keyword searches is feasible but thus far has poor specificity. Nonetheless, computerized clinical narrative screening methods could potentially offer researchers and quality managers a means to routinely detect adverse events.

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.

Primary care physician attitudes concerning follow-up of abnormal test results and ambulatory decision support systems

OBJECTIVES Failures to follow-up abnormal test results are common in ambulatory care. Information systems could assist providers with abnormal test result tracking, yet little is known about primary care providers attitudes toward outpatient decision support systems. METHODS A cross-sectional survey of 216 primary care physicians (PCPs) that utilize a single electronic medical record (EMR) without computer-based clinical decision support. RESULTS The overall response rate was 65% (140/216). Less than one-third of the respondents were satisfied with their current system to manage abnormal laboratory, radiographs, Pap smear, or mammograms results. Only 15% of providers were satisfied with their system to notify patients of abnormal results. Over 90% of respondents felt automated systems to track abnormal test results would be useful. Seventy-nine percent of our respondents believed that they could comply better with guidelines through electronic clinical reminders. CONCLUSIONS Most PCPs were not satisfied with their methods for tracking abnormal results. Respondents believed that clinical decision support systems (CDSS) would be useful and could improve their ability to track abnormal results.

Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: A prospective cohort study

Breast cancer is the most common cancer in women. Controversy exists regarding the role of dietary fat in breast cancer etiology. We investigated the association of dietary polyunsaturated fatty acids (PUFAs) and the ratio of n‐6 PUFAs to marine‐derived n‐3 PUFAs with breast cancer risk in the Shanghai Womens Health Study, a prospective cohort study including 72,571 cancer‐free participants at baseline. Dietary fatty acid intake was determined using food frequency questionnaires. We used Cox proportional hazards analysis to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for the association of breast cancer risk with dietary fatty acids consumption. In 583,998 person‐years of follow‐up, we identified 712 breast cancer cases. We found no association of breast cancer risk to dietary intake of linoleic acid, arachidonic acid, α‐linolenic acid or marine‐derived n‐3 PUFA. We found a statistically significant interaction between n‐6 PUFA intake, marine‐derived n‐3 PUFA intake and breast cancer risk (p = 0.008). Women with lower intake (the lowest tertile) of marine‐derived n‐3 PUFA and higher intake (the highest tertile) of n‐6 PUFA had an increase risk for breast cancer (RR = 2.06; 95% CI = 1.27–3.34) compared to women with higher intake (the highest tertile) of marine‐derived n‐3 PUFAs and lower intake (the lowest tertile) of n‐6 PUFAs after adjusting for potential confounders. The relative amounts of n‐6 PUFA to marine‐derived n‐3 PUFAs may be more important for breast cancer risk than individual dietary amounts of these fatty acids.