Sandeep Vijan

When Do Patients and Their Physicians Agree on Diabetes Treatment Goals and Strategies, and What Difference Does It Make?

BACKGROUND: For patients with chronic illnesses, it is hypothesized that effective patient-provider collaboration contributes to improved patient self-care by promoting greater agreement on patient-specific treatment goals and strategies. However, this hypothesis has not been tested in actual encounters of patients with their own physicians.OBJECTIVE: To assess the extent to which patients with type 2 diabetes agree with their primary care providers (PCPs) on diabetes treatment goals and strategies, the factors that predict agreement, and whether greater agreement is associated with better patient self-management of diabetes.DESIGN: One hundred twenty-seven pairs of patients and their PCPs in two health systems were surveyed about their top 3 diabetes treatment goals (desired outcomes) and strategies to meet those goals. Using several measures to evaluate agreement, we explored whether patient characteristics, such as education and attitudes toward treatment, and patient-provider interaction styles, such as shared decision making, were associated with greater agreement on treatment goals and strategies. We then examined whether agreement was associated with higher patient assessments of their diabetes care self-efficacy and self-management.RESULTS: Overall, agreement on top treatment goals and strategies was low (all κ were less than 0.40). In multivariable analyses, however, patients with more education, greater belief in the efficacy of their diabetes treatment, and who shared in treatment decision making with their providers were more likely to agree with their providers on treatment goals or strategies. Similarly, physician reports of having discussed more content areas of diabetes self-care were associated with greater agreement on treatment strategies. In turn, greater agreement on treatment goals and strategies was associated both with higher patient diabetes care self-efficacy and assessments of their diabetes self-management.CONCLUSION: Although patients and their PCPs in general had poor agreement on goals and strategies for managing diabetes, agreement was associated with higher patient self-efficacy and assessments of their diabetes self-management. This supports the hypothesis that enhancing patient-provider agreement on both overall treatment goals and specific strategies to meet these goals may lead to improved patient outcomes.

Treatment of Hypertension in Type 2 Diabetes Mellitus: Blood Pressure Goals, Choice of Agents, and Setting Priorities in Diabetes Care

Type 2 diabetes mellitus is a common disease with substantial associated morbidity and mortality (1, 2). Most adverse diabetes outcomes are a result of vascular complications, both at a macrovascular level (coronary artery disease, cerebrovascular disease, or peripheral vascular disease) and a microvascular level (retinopathy, nephropathy, or neuropathy) (3). Macrovascular complications are more common; up to 80% of patients with type 2 diabetes will develop or die of macrovascular disease (4-12), and the costs associated with macrovascular disease are an order of magnitude greater than those associated with microvascular disease (13). Because diabetes is defined by blood glucose levels, much of the attention in diabetes care focuses on the management of hyperglycemia. This has been magnified by the causal link between hyperglycemia and microvascular outcomes (3, 14). However, while some observational evidence suggests that level of glycemia is a risk factor for macrovascular disease (15-18), experimental studies to date have not clearly shown a causal relationship between improved glycemic control and reductions in serious cardiovascular outcomes (3, 14). Given these results and the epidemiologic characteristics of diabetes complications, it would seem more logical to focus diabetes care on prevention of macrovascular complications rather than on glucose control and microvascular complications. Indeed, the importance of preventing the macrovascular complications of type 2 diabetes has started to receive greater attention. In particular, several trials have examined the benefit of management of highly prevalent risk factors, such as hypertension. Hypertension is extremely common in patients with type 2 diabetes, affecting up to 60% (2), and there are a growing number of pharmacologic treatment options. The goals of this paper are to review the literature to evaluate effects of management of hypertension on the complications of type 2 diabetes and, based on this literature, to determine optimal blood pressure goals and choice of agents. This will provide an evidence base to guide clinicians in setting hypertension treatment goals and priorities in patients with type 2 diabetes. Methods The literature review was limited to randomized, controlled trials that included patients with diabetes. Only studies that measured major clinical end points were included. We defined four classes of clinical end points: all-cause mortality, cardiovascular mortality, major cardiovascular events (that is, myocardial infarction or stroke), and advanced microvascular outcomes (photocoagulation or visual loss, nephropathy or end-stage renal disease, neuropathy, or amputation). We separated the literature review into two categories. The first category evaluated the effects of hypertension control if the comparison examined an antihypertensive drug versus placebo or the effects of different target blood pressure levels. The second category evaluated the effects of different classes of drugs. We used several sources to identify the relevant literature. For older literature, we started with the Cochrane Collaboration Diabetes Group report on treatment of hypertension in diabetes, which was published in 1997 (19). This report has now been withdrawn because it is out of date, but it served as a reasonable starting point to identify pre-1997 literature. We then performed a MEDLINE search in May 2000 and updated it in April 2002. We used the keywords exp diabetes mellitus and exp hypertension[therapy or prevention and control] and limited the search to randomized, controlled trials. The final search produced 322 results. Of these, most were discarded because they did not measure major clinical outcomes, were observational in nature, were reviews or editorials, or did not primarily address the issue of treatment of hypertension. We then updated the search through consultation with experts and through examining references from meta-analyses and review articles. Data were extracted from the primary study reports by the primary author and were reviewed by the senior author. Accuracy and quality of the abstraction were confirmed through reabstraction and comparison with the original abstraction. The outcomes were broken into categories as described, and data on absolute and relative risk reduction and numbers needed to treat for benefit were derived from the primary reports or were calculated in standard fashion (20). Results Benefits of Blood Pressure Control The results of the studies of blood pressure control versus placebo, or of different blood pressure targets, are outlined in Table 1. The Systolic Hypertension in the Elderly Program (SHEP) enrolled a diabetes subgroup totaling 583 patients and randomly assigned these patients to chlorthalidone plus atenolol or reserpine versus placebo and usual care (21). The intensive group had a 9.8mm Hg decrease in systolic blood pressure and a 2.2mm Hg decrease in diastolic blood pressure, as well as a significant decline in total cardiovascular events and a nonsignificant trend for lower all-cause mortality. Table 1. Primary Trials of Hypertension Control in Diabetes The Systolic Hypertension in Europe (Syst-Eur) study (22) randomly assigned elderly patients ( 60 years of age) with systolic hypertension to nitrendipine or placebo. The mean decreases in systolic blood pressure and diastolic blood pressure were 8.6 and 3.9 mm Hg in the intervention group compared with the placebo group. In the subgroup of 492 patients with diabetes, this led to an improvement in the risk for cardiovascular death, all cardiovascular events, and stroke. There was no significant difference in overall mortality in unadjusted analyses; however, after adjustment for baseline differences between groups, there was a 55% reduction in overall mortality in the active treatment group (P = 0.04). The Heart Outcomes and Prevention Evaluation (HOPE) study evaluated the cardiovascular effects of the angiotensin-converting enzyme (ACE) inhibitor ramipril (23, 24). Patients with diabetes and at least one other cardiovascular risk factor (n = 3577) were randomly assigned to the ACE inhibitor ramipril or placebo. The participants had only mild elevations in systolic blood pressure at baseline, and blood pressure differences at the final visit were small (systolic blood pressure, 2.4 mm Hg lower; diastolic blood pressure, 1 mm Hg lower). The ramipril group had significantly lower risks for cardiovascular outcomes, total mortality, and microvascular diabetes complications. The lower cardiovascular risk persisted after adjustment for blood pressure differences, suggesting that ACE inhibitors may confer a benefit independent of blood pressure control. Furthermore, several smaller or short-term studies suggest that ACE inhibitors may have a renoprotective effect in patients with type 2 diabetes compared with placebo; this effect may be independent of blood pressure control and may occur regardless of whether albuminuria is present (25-32). Several studies have also evaluated the effectiveness of angiotensin II receptor blockers on outcomes in patients with type 2 diabetes. In the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study (33), 1513 participants with type 2 diabetes and nephropathy were randomly assigned to losartan or placebo. There were minimal differences in blood pressure. Losartan led to a reduction in the risk for the primary end point of combined doubling of the creatinine concentration, end-stage renal disease, or death; there was no difference in combined cardiovascular end points. The Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IPDM) Study (34) randomly assigned 590 hypertensive patients with type 2 diabetes and microalbuminuria to irbesartan, 300 mg or 150 mg daily, or placebo. There were small but significant reductions in systolic blood pressure with irbesartan. Compared with the placebo group, systolic blood pressure was 3 mm Hg lower in the 300-mg group and 2 mm Hg lower in the 150-mg group. The risk for overt nephropathy was 0.30 (95% CI, 0.14 to 0.61) in the 300-mg group and 0.61 (CI, 0.34 to 1.08) in the 150-mg group. In both RENAAL and IPDM, the differences in outcomes persisted after adjustment for blood pressure differences and baseline level of microalbuminuria, suggesting a benefit that is independent of systemic blood pressure. Several studies have specifically compared the effects of different blood pressure targets on diabetes outcomes. The Hypertension Optimal Treatment (HOT) study included a subgroup of 1501 patients with diabetes; participants were randomly assigned into three groups with target diastolic blood pressures of 90, 85, and 80 mm Hg (35). There were substantial improvements in diastolic blood pressure in these groups (20.3, 22.3, and 24.3 mm Hg, respectively, with achieved diastolic blood pressure of 85.2, 83.2, and 81.1 mm Hg). In patients with diabetes, the group randomly assigned to a diastolic blood pressure target of 80 mm Hg had a significantly reduced risk for cardiovascular death and major cardiovascular events and a nonsignificant trend toward improved overall mortality compared with those who had a target diastolic blood pressure of 90 mm Hg. The United Kingdom Prospective Diabetes Study (UKPDS) of hypertension randomly assigned 1148 patients with newly diagnosed type 2 diabetes to a less tight target blood pressure of 180/105 mm Hg or to a tight control target of 150/85 mm Hg (36). The achieved blood pressure was 154/87 mm Hg in the less tight control group and 144/82 mm Hg in the tight control group. In the tight control group, there were substantial reductions in risk for any diabetes end point, deaths related to diabetes, and stroke but a nonsignificant change in all-cause mortality. There was also a significant reduction in risk for microvascular disease, most of which was due to reduction in retinal photocoagulation. I

Estimated Benefits of Glycemic Control in Microvascular Complications in Type 2 Diabetes

Blindness and renal failure are two of the most feared complications of diabetes. These devastating outcomes frequently result from insidious progression of abnormalities in small blood vessels (microvascular disease) over many years. Although microvascular disease is associated with the level of glycemic control [1-3], the Diabetes Control and Complications Trial (DCCT) was the first study to convincingly show that in patients with type 1 diabetes, improved glycemic control can reduce the risk for early microvascular complications [4]. The DCCT settled many issues, but it also raised difficult questions about the management of diabetes. There is now nearly uniform agreement that intensive glycemic control should be attempted for most patients with type 1 diabetes. However, the implications of the DCCT for the treatment of type 2 diabetes remain controversial [5-8]. Cohort studies suggest that early microvascular disease is related to hemoglobin A1c level in both type 1 and type 2 diabetes [3, 9], but the incidence of end-stage complications is much lower in type 2 diabetes [10, 11], presumably because of the older age at onset and competing risks for death. Thus, the benefits of intensive therapy in type 2 diabetes seem less compelling. The perceived difficulty of treating patients with type 2 diabetes, the potential harms related to macrovascular complications, and concern about hypoglycemia further fuel the controversy. These concerns are important because roughly 90% of diabetic patients have type 2 disease. Although long-term benefit may result from improved glycemic control, economic costs may be increased [12]. For many patients, insulin injections, frequent laboratory monitoring, increased office visits, more restrictive diets, and intensive at-home monitoring of glucose levels are required. Thus, it is critical that the possible long-term benefits of aggressive glycemic control in type 2 diabetes be better quantified [7, 13]. Such information may facilitate the counseling of patients and could help health care systems prioritize and focus costly clinical interventions. We therefore created a model to calculate the risks for developing blindness and end-stage renal disease for patients at different ages of diabetes onset and levels of glycemic control. The base-case analysis used data from the DCCT for rates of early disease [4, 14] and used cohort data from patients with type 2 diabetes for rates of subsequent progression to end-stage disease [10, 11, 15, 16]. Methods Markov Model A Markov model was constructed to analyze the risk for retinopathy and nephropathy in patients with type 2 diabetes. The structure of the model is shown in the (Figure 1). Estimates for the two complications were modeled separately so that they were assumed not to interact. The simulated patients progressed sequentially through increasingly severe disease states; death could occur in any disease state (Figure 1). Incidence and progression of retinopathy were defined as in the DCCT [4, 17]. Blindness was defined as corrected visual acuity of 20/200 or worse and was restricted to blindness caused by retinopathy or its sequelae (for example, macular edema). Microalbuminuria was defined as an albumin level of 30 to 300 mg/g of creatinine, proteinuria was defined as a protein level greater than 300 mg/g of creatinine, and end-stage renal disease was defined as renal disease that required dialysis or transplantation. Figure 1. Structure of the model. Amputation was not modeled because of a lack of evidence on the relative contributions of microvascular and macrovascular disease to the risk for amputation. Moreover, the same patients who were identified in our analyses as being at high risk for retinal and renal complications (and who therefore will benefit more from intensified glycemic control) will have a similarly high risk for neuropathy and its associated outcomes [18]. Our study addressed clinical risks and benefits associated with glycemic control and did not directly evaluate costs. The costs of decreasing hemoglobin A1c levels are not well defined for patients with type 2 diabetes because glucose control can be improved by many methods. Each method has different implications for the costs to the patient, payers, and society. However, we present results in the form of expectation functions so that if the costs and effectiveness of a specific intervention are known, estimates of the cost per complication prevented can be calculated from our tables. Assumptions The construction of the model was based on the states defined in the DCCT, which provided estimates for the rates of early microvascular disease. Our review of the literature and input from diabetes experts consistently identified the Rochester, Minnesota, cohort study of diabetic patients and the Wisconsin Epidemiologic Study of Diabetic Retinopathy [3, 9-11, 15] as the best studies with which to provide estimates of the rates of progression to end-stage outcomes; thus, these studies were used in the base-case analysis. Further literature was identified by searching the MEDLINE database search with the keyword diabetes, cross-referenced with retinopathy, blindness, visual loss, nephropathy, kidney disease and failure, renal disease and failure, blood glucose, glycemic control, mortality, and hemoglobin A1c. We reviewed the abstracts of the identified articles and obtained the articles that were relevant to the model structure. Additional literature was identified by review of references in these articles and through discussion with national experts in the field. Patients were assumed to have no clinically detectable microvascular complications at the time of diagnosis of diabetes. Although up to 20% of patients have retinopathy at the time of diagnosis [19], we excluded this subgroup because data on the distribution of these patients across hemoglobin A1c levels are lacking. In addition, patients who present with complications have already declared themselves to be at high risk and thus should be considered for intensive control. We assumed that incidence and early progression of retinopathy and development of microalbuminuria were related to level of glycemic control at the rates of progression shown in the DCCT [4, 14]. Each 10% increase in hemoglobin A1c level is accompanied by a 20% increase in the rate of developing microalbuminuria, a 56% increase in the rate of developing retinopathy, and a 64% increase in the rate of progression of retinopathy [14]. Further progression (to renal disease beyond microalbuminuria and from retinopathy to blindness) was assumed not to be related to level of glycemic control [20-25]. Data for sensitivity analyses were derived from the 95% CIs in the DCCT and the range of estimates available in the literature (Table 1). Table 1. Model Components for the Base-Case and Sensitivity Analyses: Annual Rates of Transition between Disease States* Mortality estimates were based on U.S. data from the Department of Vital Statistics [40]. These estimates were modified to reflect the higher mortality rates in patients with type 2 diabetes [41-47]. Mortality was not adjusted for level of glycemic control. Some cohort studies show a relation between level of glycemic control and mortality, but it is not clear whether a causal relation exists [48]. Nephropathy, even at early stages, has been reported to be associated with increased rates of death, particularly death from cardiovascular disease [37, 49-52]. Much of this association may be due to confounding, but the effect persists after adjustment according to available severity and comorbidity measures [50]. The base-case model assumes that early nephropathy does not increase mortality rates. However, to evaluate the potential importance of this factor, we compared the mortality benefits of improved glycemic control by using half of or the full observed association between early renal disease and increased mortality rates. Model Structure and Implementation The model was run independently for each age of diabetes onset and level of glycemic control and was implemented by creating matrices of the probabilities of going from one health state to the next during a 1-year period (Figure 1). The percentage of patients developing each level of complication was tabulated annually, continuing through 90 years of age. Mortality rates were updated at 5-year intervals. This technique represents a standard implementation of a nonstationary Markov process [53, 54]. Average life expectancy was calculated by multiplying the proportion of patients dying during each year by the total number of years survived. Average time spent in each disease state was determined by dividing the total time spent in a state by the number of patients who develop that state. All calculations and modeling were performed by using Stata for Windows (Stata Corp., College Station, Texas). Sensitivity analyses were conducted by using varying estimates at all transition points (Table 1) [54]. We included the full range of estimates in the literature in one-way sensitivity analyses. However, because some studies had extreme values for the transition probabilities (most likely because of small sample sizes or atypical patient populations), three-way sensitivity analyses were conducted by using the midpoint between the base-case and extreme estimates. We also tested the validity of the model by modifying the simulated patients to fit the characteristics of the populations of various actual studies of natural history (for example, the mean values for age, hemoglobin A1c level, and initial prevalence of disease found in these studies were used to generate a limited set of results) and by comparing the predictions of the model (within one-way sensitivity analysis range) with the observed values from these studies. Using the model predictions and the characteristics of a population of patients with type 2 diabetes at a large staff-model health ma

Diabetes Control With Reciprocal Peer Support Versus Nurse Care Management: A Randomized Trial

BACKGROUND Resource barriers complicate diabetes care management. Support from peers may help patients manage their diabetes. OBJECTIVE To compare a reciprocal peer-support (RPS) program with nurse care management (NCM). DESIGN Randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00320112) SETTING 2 U.S. Department of Veterans Affairs health care facilities. PATIENTS 244 men with hemoglobin A(1c) (HbA(1c)) levels greater than 7.5% during the previous 6 months. MEASUREMENTS The primary outcome was 6-month change in HbA(1c) level. Secondary outcomes were changes in insulin therapy; blood pressure; and patient reports of medication adherence, diabetes-related support, and emotional distress. INTERVENTION Patients in the RPS group attended an initial group session to set diabetes-related behavioral goals, receive peer communication skills training, and be paired with another age-matched peer patient. Peers were encouraged to talk weekly using a telephone platform that recorded call occurrence and provided reminders to promote peer contact. These patients could also participate in optional group sessions at 1, 3, and 6 months. Patients in the NCM group attended a 1.5-hour educational session and were assigned to a nurse care manager. RESULTS Of the 244 patients enrolled, 216 (89%) completed the HbA(1c) assessments and 231 (95%) completed the survey assessments at 6 months. Mean HbA(1c) level decreased from 8.02% to 7.73% (change, -0.29%) in the RPS group and increased from 7.93% to 8.22% (change, 0.29%) in the NCM group. The difference in HbA(1c) change between groups was 0.58% (P = 0.004). Among patients with a baseline HbA(1c) level greater than 8.0%, those in the RPS group had a mean decrease of 0.88%, compared with a 0.07% decrease among those in the NCM group (between-group difference, 0.81%; P < 0.001). Eight patients in the RPS group started insulin therapy, compared with 1 patient in the NCM group (P = 0.020). Groups did not differ in blood pressure, self-reported medication adherence, or diabetes-specific distress, but the RPS group reported improvement in diabetes social support. LIMITATION The study included only male veterans and lasted only 6 months. CONCLUSION Reciprocal peer support holds promise as a method for diabetes care management.

Which colon cancer screening test? A comparison of costs, effectiveness, and compliance

PURPOSE Recent media reports have advocated the use of colonoscopy for colorectal cancer screening. However, colonoscopy is expensive compared with other screening modalities, such as fecal occult blood testing and flexible sigmoidoscopy. We sought to determine the cost effectiveness of different screening strategies for colorectal cancer at levels of compliance likely to be achieved in clinical practice. METHODS A Markov decision model was used to examine screening strategies, including fecal occult blood testing alone, fecal occult blood testing combined with flexible sigmoidoscopy, flexible sigmoidoscopy alone, and colonoscopy. The timing and frequency of screening was varied to assess optimal screening intervals. Sensitivity analyses were conducted to assess the factors that have the greatest effect on the cost effectiveness of screening. RESULTS All strategies are cost effective versus no screening, at less than

Pharmacologic Lipid-Lowering Therapy in Type 2 Diabetes Mellitus: Background Paper for the American College of Physicians

20,000 per life-year saved. Direct comparison suggests that the most effective strategies are twice-lifetime colonoscopy and flexible sigmoidoscopy combined with fecal occult blood testing. Assuming perfect compliance, flexible sigmoidoscopy combined with fecal occult blood testing is slightly more effective than twice-lifetime colonoscopy (at ages 50 and 60 years) but is substantially more expensive, with an incremental cost effectiveness of

Projections of demand and capacity for colonoscopy related to increasing rates of colorectal cancer screening in the United States.

390,000 per additional life-year saved. However, compliance with primary screening tests and colonoscopic follow-up for polyps affect screening decisions. Colonoscopy at ages 50 and 60 years is the preferred test regardless of compliance with the primary screening test. However, if follow-up colonoscopy for polyps is less than 75%, then even once-lifetime colonoscopy is preferred over most combinations of flexible sigmoidoscopy and fecal occult blood testing. Costs of colonoscopy and proportion of cancer arising from polyps also affect cost effectiveness. CONCLUSIONS Colonoscopic screening for colorectal cancer appears preferable to current screening recommendations. Screening recommendations should be tailored to the compliance levels achievable in different practice settings.

Getting heavier, younger: Trajectories of obesity over the life course

Type 2 diabetes mellitus is a common disease that is increasing to near epidemic levels in industrialized nations (1, 2). Diabetes is associated with substantial risk for morbidity and premature mortality (3, 4). Most adverse diabetes outcomes are due to vascular complications, either at a macrovascular level (that is, coronary artery disease, cerebrovascular disease, or peripheral vascular disease) or a microvascular level (that is, retinopathy, nephropathy, or neuropathy) (5). Macrovascular complications are more common and severe; up to 80% of patients with type 2 diabetes will develop or die of macrovascular disease, and the costs associated with macrovascular disease are an order of magnitude greater than those for microvascular disease (6). Given the epidemiology of diabetes complications, management of cardiovascular risk has been emphasized in people with diabetes. Modifying cardiovascular risk by treating hypertension or by using lipid-lowering agents is of tremendous importance and may be more effective and cost-effective than treating hyperglycemia (7, 8). This paper focuses on the evidence behind the use of lipid-lowering agents in type 2 diabetes. Patients with diabetes typically have low high-density lipoprotein (HDL) cholesterol levels, high triglyceride levels, and average low-density lipoprotein (LDL) cholesterol levels; LDL cholesterol particles in people with diabetes tend to be smaller, denser, and possibly more atherogenic (9, 10). The elevated cardiovascular risk in patients with type 2 diabetes makes these patients strong candidates for treatment with lipid-lowering medications. Methods The literature review was limited to randomized, controlled trials of drug therapy that included patients with diabetes. Only studies that measured major clinical end points were included. Major clinical end points were defined as major cardiovascular events (for example, cardiovascular mortality, myocardial infarction, stroke), cardiovascular mortality, and total mortality. Of note, many of the trials reported somewhat different clinical end points in the patients with diabetes. All included cardiovascular mortality and myocardial infarction in their composite end point; some included stroke and revascularization, and one included unstable angina. We used the primary reported data directly from the published study in our review. We also subdivided the literature review into 2 categories. The first category evaluated the effects of lipid management in primary prevention (that is, patients without known cardiovascular disease); the second evaluated the effects in secondary prevention. We used several sources to identify the relevant literature. We started with a search of the Cochrane Library. We then performed a MEDLINE search in September 2002. We used the keywords exp diabetes mellitus and exp lipids [therapy or prevention and control] and limited the search to randomized, controlled trials and human studies. The final search produced 919 results. Of these, most were discarded because they did not measure major clinical end points, did not report outcomes for patients with diabetes, were observational in nature, or were reviews or editorials. We then updated the search through consultation with experts and through references from the identified articles, meta-analyses, and review articles. The primary author extracted data from the primary study reports. Accuracy and quality of the abstraction were confirmed through reabstraction and comparison with the original abstraction. The outcomes were broken into categories as described earlier, and data on absolute and relative risk reduction and numbers needed to treat for benefit were derived from the primary reports or were calculated in standard fashion (11). The results of the studies were then combined by using meta-analytic techniques. We pooled data for both relative and absolute risks. A MantelHaenszel test was done to test for heterogeneity. In the analyses of secondary prevention, the data had substantial heterogeneity, so the pooled risk ratios and differences were calculated by using the DerSimonian and Laird method with a random-effects model. Sensitivity analyses were done by excluding studies that appeared to be outliers to ascertain the source of the heterogeneity. All analyses were done by using the statistical package Stata (Stata Corp., College Station, Texas). There were no sources of direct funding for this manuscript. Dr. Vijan was a Veterans Affairs Career Development Awardee during preparation, and the American College of Physicians provided an honorarium to the authors. Data Synthesis No studies of lipid-lowering therapy that reported cardiovascular outcomes were conducted solely in patients with diabetes, but several studies reported diabetes subgroup analyses. Sample sizes of participants with diabetes were often small, so most of the studies presented data only on combined cardiovascular events (for example, cardiovascular mortality, nonfatal myocardial infarction, stroke, and coronary revascularization). In several cases, diabetes was an exclusion criterion or very few patients with diabetes were included; for example, in the West of Scotland Coronary Prevention Study, about 1% of patients (76 of 6595) had diabetes, and results were not presented for this subgroup (12). We found a total of 12 lipid-lowering studies that presented diabetes-specific data and reported clinical outcomes. Of these studies, 4 were focused on primary prevention, 6 were focused on secondary prevention, and 2 presented data on both. The general study characteristics, including the effect of interventions of lipid levels, are presented in Table 1. Table 1. Studies of Lipid-Lowering Therapy in Type 2 Diabetes Mellitus: Intervention, Lipid Goals, and Achieved Lipid Levels Primary Prevention Trials We identified 6 studies that evaluated primary prevention for patients with diabetes. The Air Force Coronary Atherosclerosis Prevention Study/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) randomly assigned patients with average cholesterol levels to receive lovastatin, 20 mg/d, or placebo (13). The daily dose of lovastatin was increased to 40 mg if the LDL cholesterol level was above 2.84 mmol/L (>110 mg/dL). One hundred fifty-five patients had diagnosed diabetes at study entry. Lovastatin therapy led to a relative risk of 0.56 (95% CI, 0.17 to 1.92) for any coronary heart disease (CHD) event and an absolute risk reduction of 0.04 (CI, 0.04 to 0.12), neither of which was statistically significant. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack TrialLipid-Lowering Trial (ALLHAT-LLT) randomly assigned patients who were 55 years of age or older and who had hypertension and at least one other CHD risk factor to pravastatin, 40 mg/d, or placebo (14). Only 14% of patients had known CHD at baseline; thus, this was essentially a trial of primary prevention. In the subgroup of 3638 patients with type 2 diabetes, the relative risk for CHD events was 0.89 (CI, 0.71 to 1.10); the absolute risk reduction was not reported. Some have criticized this trial because the difference in LDL cholesterol levels between the intervention and control groups was smaller than in other studies (17%, or 0.62 mmol/L [24 mg/dL] at 4 years). This was due in part to contamination of the control arm caused by publication of several other lipid-lowering studies during the trial. The Helsinki Heart Study was a randomized, controlled primary prevention trial of gemfibrozil in patients with elevated non-HDL cholesterol levels (primarily triglyceride and LDL cholesterol levels) (15). One hundred thirty-five patients in the study had diabetes. The incidence of CHD was 3.4% in the gemfibrozil group and 10.5% in the placebo group (relative risk, 0.32 [CI, 0.07 to 1.46]; absolute risk reduction, 0.07 [CI, 0.01 to 0.15]) (16). Given the small sample size, these differences were not statistically significant. The Heart Protection Study (HPS) included data on both primary and secondary prevention in patients with diabetes (17). The goal of this large study was to examine the effects of LDL cholesterollowering therapy across a broad range of lipid levels and risk factors. In the primary prevention group, 3982 patients had diabetes. Treatment with simvastatin led to reduced risks for CHD events (relative risk, 0.74 [CI, 0.64 to 0.85]; absolute risk reduction, 0.05 [CI, 0.03 to 0.07]). The Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) randomly assigned elderly patients (age 70 to 82 years) to pravastatin, 40 mg/d, or placebo (18). This study also evaluated both primary and secondary prevention. In total, 623 patients had diabetes; of these, 396 were in the primary prevention group. In this group, pravastatin led to trend toward harm, with a relative risk of 1.23 (CI, 0.77 to 1.95) and an absolute risk reduction of 0.03 (CI, 0.10 to 0.04) (Shepherd J, Blauw GJ, Murphy MG. Personal communication). This contrasted with the primary results of the trial, which showed a positive effect of pravastatin. Indeed, the interaction between the diabetes and treatment groups was statistically significant, suggesting that patients with diabetes did substantially worse than those without diabetes. The Anglo-Scandinavian Cardiac Outcomes TrialLipid-Lowering Arm (ASCOT-LLA) randomly assigned patients without CHD but with hypertension and at least 3 other cardiovascular risk factors to atorvastatin, 10 mg/d, or placebo (19). A total of 2532 patients with diabetes who also had hypertension and 2 or more other risk factors participated in the study. The patients with diabetes had surprisingly low event rates of 3.6% in the control group and 3.0% in the intervention group. Lipid-lowering treatment, with a relative risk of 0.84 (CI, 0.55 to 1.29) and an absolute risk reduction of 0.006 (CI, 0.008 to 0.019), did not lead to statistically significant improvements in outcomes

The Cost-Effectiveness of CT Colonography in Screening for Colorectal Neoplasia

Background : There is debate about the optimal colorectal cancer screening test, partly because of concerns about colonoscopy demand.

BRIEF REPORT: The Burden of Diabetes Therapy: Implications for the Design of Effective Patient-centered Treatment Regimens

Context:Although recent trends in obesity have been well documented, generational patterns of obesity from early childhood through adulthood across birth cohorts, which account for the recent epidemic of childhood obesity, have not been well described. Such trends may have implications for the prevalence of obesity-associated conditions among population subgroups, including type 2 diabetes.Objective:Our objective was to evaluate trajectories of obesity over the life course for the US population, overall and by gender and race.Design, Setting and Participants:We conducted an age, period and birth cohort analysis of obesity for US individuals who participated in the National Health and Nutrition Examination Surveys (NHANES) (1971–2006).Main Outcome Measures:Obesity was defined as a body mass index ⩾95th percentile for individuals aged 2–16 years or ⩾30 kg  m–2 among individuals older than 16 years. Age was represented by the age of the individual at each NHANES, period was defined by the year midpoint of each survey, and cohort was calculated by subtracting age from period.Results:Recent birth cohorts are becoming obese in greater proportions for a given age, and are experiencing a greater duration of obesity over their lifetime. For example, although the 1966–1975 and 1976–1985 birth cohorts had reached an estimated obesity prevalence of at least 20% by 20–29 years of age, this level was only reached by 30–39 years for the 1946–1955 and 1956–1965 birth cohorts, by 40–49 years for the 1936–1945 birth cohort and by 50–59 years of age for the 1926–1935 birth cohort. Trends are particularly pronounced for female compared with male, and black compared with white cohorts.Conclusions:The increasing cumulative exposure to excess weight over the lifetime of recent birth cohorts will likely have profound implications for future rates of type 2 diabetes, and mortality within the US population.