Madeline McCarren

Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes

BACKGROUND The effects of intensive glucose control on cardiovascular events in patients with long-standing type 2 diabetes mellitus remain uncertain. METHODS We randomly assigned 1791 military veterans (mean age, 60.4 years) who had a suboptimal response to therapy for type 2 diabetes to receive either intensive or standard glucose control. Other cardiovascular risk factors were treated uniformly. The mean number of years since the diagnosis of diabetes was 11.5, and 40% of the patients had already had a cardiovascular event. The goal in the intensive-therapy group was an absolute reduction of 1.5 percentage points in the glycated hemoglobin level, as compared with the standard-therapy group. The primary outcome was the time from randomization to the first occurrence of a major cardiovascular event, a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary disease, and amputation for ischemic gangrene. RESULTS The median follow-up was 5.6 years. Median glycated hemoglobin levels were 8.4% in the standard-therapy group and 6.9% in the intensive-therapy group. The primary outcome occurred in 264 patients in the standard-therapy group and 235 patients in the intensive-therapy group (hazard ratio in the intensive-therapy group, 0.88; 95% confidence interval [CI], 0.74 to 1.05; P=0.14). There was no significant difference between the two groups in any component of the primary outcome or in the rate of death from any cause (hazard ratio, 1.07; 95% CI, 0.81 to 1.42; P=0.62). No differences between the two groups were observed for microvascular complications. The rates of adverse events, predominantly hypoglycemia, were 17.6% in the standard-therapy group and 24.1% in the intensive-therapy group. CONCLUSIONS Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications with the exception of progression of albuminuria (P = 0.01) [added]. (ClinicalTrials.gov number, NCT00032487.)

Follow-up of Glycemic Control and Cardiovascular Outcomes in Type 2 Diabetes

BACKGROUND The Veterans Affairs Diabetes Trial previously showed that intensive glucose lowering, as compared with standard therapy, did not significantly reduce the rate of major cardiovascular events among 1791 military veterans (median follow-up, 5.6 years). We report the extended follow-up of the study participants. METHODS After the conclusion of the clinical trial, we followed participants, using central databases to identify procedures, hospitalizations, and deaths (complete cohort, with follow-up data for 92.4% of participants). Most participants agreed to additional data collection by means of annual surveys and periodic chart reviews (survey cohort, with 77.7% follow-up). The primary outcome was the time to the first major cardiovascular event (heart attack, stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or cardiovascular-related death). Secondary outcomes were cardiovascular mortality and all-cause mortality. RESULTS The difference in glycated hemoglobin levels between the intensive-therapy group and the standard-therapy group averaged 1.5 percentage points during the trial (median level, 6.9% vs. 8.4%) and declined to 0.2 to 0.3 percentage points by 3 years after the trial ended. Over a median follow-up of 9.8 years, the intensive-therapy group had a significantly lower risk of the primary outcome than did the standard-therapy group (hazard ratio, 0.83; 95% confidence interval [CI], 0.70 to 0.99; P=0.04), with an absolute reduction in risk of 8.6 major cardiovascular events per 1000 person-years, but did not have reduced cardiovascular mortality (hazard ratio, 0.88; 95% CI, 0.64 to 1.20; P=0.42). No reduction in total mortality was evident (hazard ratio in the intensive-therapy group, 1.05; 95% CI, 0.89 to 1.25; P=0.54; median follow-up, 11.8 years). CONCLUSIONS After nearly 10 years of follow-up, patients with type 2 diabetes who had been randomly assigned to intensive glucose control for 5.6 years had 8.6 fewer major cardiovascular events per 1000 person-years than those assigned to standard therapy, but no improvement was seen in the rate of overall survival. (Funded by the VA Cooperative Studies Program and others; VADT ClinicalTrials.gov number, NCT00032487.).

Design of the cooperative study on glycemic control and complications in diabetes mellitus type 2 Veterans Affairs Diabetes Trial

INTRODUCTION Long-term glycemic control trials in type 2 diabetes show as the main clinical benefit a difference in retinal photocoagulation (3/1000 in the UK Prospective Diabetes Study [UKPDS]), but no effect on visual acuity or renal failure. No intensive glycemic control trial has yet affected cardiovascular (CV) events, the main cause of morbidity and mortality. By contrast, modest blood pressure reduction has protective effects on visual acuity, renal function, CV events, and mortality. Optimal glycemic control goals are not established in elderly, obese persons with advanced complications, the most common patients in the Veterans Affairs (VA) system. The earlier feasibility trial in such patients (VA-CSDM) suggested potentially worse CV outcomes with lower attained hemoglobin A1c (HbA1c) levels. OBJECTIVES The primary objective of the Veterans Affairs Diabetes Trial (VADT) is the assessment of the effect of intensive glycemic treatment on CV events. Other objectives are effects on microangiopathy, quality of life, and cost effectiveness. RESEARCH DESIGN AND METHODS The VADT, started in December 2000, is enrolling 1700 men and women previously uncontrolled on insulin or maximum doses of oral agents at 20 VA medical centers. Accrual is 2 years and follow-up is 5-7 years, with visits every 1.5 months. The study has a power of 86% to detect a 21% relative reduction in major CV events (CV death, myocardial infarction [MI], cerebrovascular accident [CVA], congestive heart failure [CHF], revascularization and amputation for ischemia). Subjects are randomized to an intensive arm aiming at normal HbA1c levels or to a standard arm with usual, improved glycemic control. An HbA1c separation of >1.5% is to be maintained (expected 2%). Both arms receive step therapy: glimepiride or metformin plus rosiglitazone and addition of insulin or other oral agents to achieve goals. Strict control of blood pressure and dyslipidemia, daily aspirin, diet, and education are identical in both arms. Plasma fibrinogen, plasminogen-activating inhibitor I (PAI-I), lipids, renal function parameters, and ECG are measured throughout. Stereo retinal photographs are obtained at entry and 5 years, eye examinations yearly, and intervention as needed to prevent visual deterioration. Recruitment is proceeding on schedule: the current mean HbA1c at entry is 9.4+/-1.6% and mean duration of diagnosed diabetes 11+/-8 years.

Patient Satisfaction with an Emergency Department Chest Pain Observation Unit

STUDY OBJECTIVE Patient satisfaction is an essential outcome measure in the diagnosis and treatment of acute chest pain in the emergency department. We compared patient satisfaction with the diagnostic protocol of a chest pain observation unit (CPOU) and standard inpatient hospitalization. METHODS We prospectively studied patients who presented to the ED with chest pain and were found to have a low risk of acute myocardial infarction (AMI) but who still might have benefited from a diagnostic protocol to rule out AMI. Consenting patients (N = 104) were randomized to the CPOU (experimental) arm or the hospital inpatient (control) arm and assessed for satisfaction by means of an interview before hospital discharge. RESULTS The CPOU protocol scored higher on four summary ratings of overall patient satisfaction. Correlations between overall satisfaction, number, and type of problems with care, and patient characteristics demonstrated content validity and revealed strengths and improvements that might be made in CPOUs. CONCLUSION Patients were more satisfied with rapid diagnosis in the CPOU than with inpatient stays for acute chest pain. Our findings add important information to the standard practice of weighing clinical and cost outcomes between two medical care alternatives.

Emergency Department Observation Unit versus hospital inpatient care for a chronic asthmatic population: a randomized trial of health status outcome and cost.

OBJECTIVES This study was designed to determine if an accelerated treatment protocol administered to acute asthmatics presenting to a Hospital Emergency Department Observation Unit (EDOU) can offset the need for inpatient admissions and reduce total cost per episode of care without sacrificing patient quality of life. METHODS The authors used a prospective randomized controlled trial comparing postintervention patient quality of life for EDOU care versus standard inpatient care as measured by the standardized Medical Outcomes Study (MOS) SF-36 instrument. Other measures reported include: clinical status as measured by peak flow rates, total cost per treatment arm using microcosting techniques, and relapse-free survival 8 weeks after treatment. Eligible patients (n = 113) were assigned randomly to an EDOU or inpatient care from a consecutive sample of 250 acute asthmatic patients presenting to an urban hospital emergency department who could not resolve their acute asthma exacerbation after 3 hours of emergency department therapy. RESULTS Patients assigned to the EDOU had lower mean costs of treatment (EDOU =

Prediction of relapse within eight weeks after an acute asthma exacerbation in adults

1,202 versus Hospital Inpatient =

A twin study of the association of post-traumatic stress disorder and combat exposure with long-term socioeconomic status in Vietnam veterans

2,247) and higher quality of life outcomes after intervention in five of eight domains measured by the MOS SF-36: Physical Functioning, Role Functioning-Emotional, Social Functioning, Mental Health, and Vitality. No differences were found in clinical outcomes as measured by peak flow rates or postintervention relapse-free survival. Univariate comparative findings were re-examined and confirmed through multivariable analysis when baseline SF-36 scores and postintervention peak expiratory flow rates clinical status were used as covariates. CONCLUSIONS The study showed that the EDOU was a lower cost and more effective treatment alternative for a refractory asthmatic population presenting to the Emergency Department. Several baseline MOS SF-36 domains proved useful in predicting or validating posttreatment clinical status, relapse, and total costs of care. Outcome SF-36 domain scores were also useful in identifying patients with the most favorable clinical, cost, and relapse rate outcomes at the study endpoint.

Control of cardiovascular risk factors in the Veterans Affairs Diabetes Trial in advanced type 2 diabetes.

Associations between historical, presenting, and treatment-related characteristics and relapse within 8 weeks after a moderate to severe asthma exacerbation were studied in a cohort of 284 adult asthmatics. Data were collected prospectively, and a multivariate model was developed and internally validated. Within 10 days, only 8% had relapsed, increasing to 45% by 8 weeks. Three variables that could be identified at the time of discharge were independently associated with relapse. These included: having made three or more visits to an emergency department in the prior 6 months (hazard ratio (HR) = 2.3, 95% CI = 1.6-3.4); difficulty performing work or activities as a result of physical health in the 4 weeks prior (HR = 2.7, 95% CI = 1.6-4.3); discontinuing hospital-based treatment for the exacerbation within 24 hours without having achieved a peak expiratory flow rate of at least 50% of predicted (HR = 2.6, 95% CI = 1.6-4.1). These risk factors may help to identify patients with poorly controlled asthma in need of more intensive and comprehensive management.

An evaluation of a chest pain diagnostic protocol to exclude acute cardiac ischemia in the emergency department

This study examines the association between post-traumatic stress disorder (PTSD) and combat exposure with the socioeconomic status of 2210 male monozygotic veteran twin pairs in 1987. In the unadjusted analysis on individuals, modest correlations indicated that those with PTSD were more likely to have been divorced, and less likely to be currently employed or to achieve high status in income, education or occupation. In the crude analysis of veterans not suffering from PTSD, there were small positive correlations between combat level experienced and the likelihood of ever being married, ever being divorced, and the number of years employed at the current job. However, when we examined identical twins discordant for PTSD, and adjusted for pre-military and military service factors, only unemployment remained significant. Likewise, in combat-discordant twins, no significant effects on the socioeconomic indicators were seen. We conclude that PTSD and combat experience in Southeast Asia have not had a major impact on the socioeconomic status of veterans.

A comparison between emergency diagnostic and treatment unit and inpatient care in the management of acute asthma.

OBJECTIVE To present a status report on the Veterans Affairs Diabetes Trial (VADT), a multisite long-term study examining the effect of glucose control on cardiovascular (CV) complications in older patients with established, poorly controlled type 2 diabetes. METHODS We review the rationale, objectives, and design of the VADT and summarize the baseline data and the results achieved thus far. RESULTS The main objective of this 20-site, 1,792-patient study is to ascertain whether intensive glucose control can reduce major CV events in patients with difficult-to-control type 2 diabetes. The study design consists of a standard treatment arm and an intensive treatment arm, with a goal of 1.5% difference in hemoglobin A1c values between the two groups. The trial is now in its fifth year, with completion expected in December 2007. The planned glucose separation has been achieved and maintained to this point. Blood pressure and hemoglobin A1c levels have been reduced from baseline values, and established CV risk factors are within recommended ranges. CONCLUSION The current results of the VADT show that excellent control of glucose and CV risk factors can be achieved and maintained in the population studied. The results of these interventions on CV outcomes will ultimately have important implications for the clinical care of older patients with advanced type 2 diabetes.