A novel long-acting formulation of oral buprenorphine/naloxone produces prolonged decreases in fentanyl self-administration by rhesus monkeys.

BACKGROUND: Due to the poor oral bioavailability of buprenorphine, an oral formulation has not been thought possible. Lyndra Therapeutics is developing a once-weekly long-acting oral product containing buprenorphine. We evaluated the efficacy of this formulation in reducing intravenous (i.v.) fentanyl self-administration by three male and three female rhesus monkeys. METHODS: Buprenorphine HCl and naloxone HCl were co-formulated using an 11:1 ratio of buprenorphine:naloxone in a controlled-release gastric residence formulation administered in an oral capsule (LYN-013). Naloxone was included to determine the feasibility of combining naloxone with buprenorphine in the formulation as an abuse deterrent. Complete fentanyl dose-response functions were determined during each session. The efficacy of single doses of 56/5, 112/10 and 168/15 mg buprenorphine/naloxone in reducing fentanyl self-administration was examined over 13 days. RESULTS: LYN-013 significantly decreased the rate of responding for fentanyl for 3 days and significantly reduced total intake of fentanyl for 8 days. Time to maximal buprenorphine levels (Tmax) ranged between 56 and 68 h for all 3 doses. The maximal buprenorphine level (Cmax) following 168 mg was 2.3 ng/ml which was significantly greater that those observed for 56 mg (1.22 ng/ml) and 112 mg (1.35 ng/ml). Finally, the area-under-curves (AUCtau) were buprenorphine dose-dependently increased from 88 to 127-265 h*ng/ml. There were no signs of non-specific changes in behavior. CONCLUSIONS: A once-weekly oral buprenorphine/naloxone formulation produced sustained suppression of fentanyl self-administration in monkeys suggesting that oral delivery of buprenorphine with this formulation could provide a new opportunity to treat opioid use disorders (OUD).

Timed Bromocriptine-QR Therapy Reduces Progression of Cardiovascular Disease and Dysglycemia in Subjects with Well-Controlled Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control may reduce long-term CVD risk. However, other risk factors such as elevated vascular sympathetic tone and/or endothelial dysfunction may be stronger potentiators of CVD. This study evaluated the impact of bromocriptine-QR, a sympatholytic dopamine D2 receptor agonist, on progression of metabolic disease and CVD in T2DM subjects in good glycemic control (HbA1c ≤ 7.0%). METHODS: 1834 subjects (1219 bromocriptine-QR; 615 placebo) with baseline HbA1c ≤ 7.0% derived from the Cycloset Safety Trial (this trial is registered with ClinicalTrials.gov Identifier: NCT00377676), a 12-month, randomized, multicenter, placebo-controlled, double-blind study in T2DM, were evaluated. Treatment impact upon a prespecified composite CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for angina/congestive heart failure) and the odds of losing glycemic control (HbA1c >7.0% after 52 weeks of therapy) were determined. RESULTS: Bromocriptine-QR reduced the CVD endpoint by 48% (intention-to-treat; HR: 0.52 [0.28-0.98]) and 52% (on-treatment analysis; HR: 0.48 [0.24-0.95]). Bromocriptine-QR also reduced the odds of both losing glycemic control (OR: 0.63 (0.47-0.85), p = 0.002) and requiring treatment intensification to maintain HbA1c ≤ 7.0% (OR: 0.46 (0.31-0.69), p = 0.0002). CONCLUSIONS: Bromocriptine-QR therapy slowed the progression of CVD and metabolic disease in T2DM subjects in good glycemic control.

Erectile dysfunction diagnosis and treatment as a means to improve medication adherence and optimize comorbidity management.

INTRODUCTION: Optimal pharmacologic management of diseases comorbid with erectile dysfunction (ED), such as cardiovascular disease, depression, diabetes, dyslipidemia, hypertension, and benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), is dependent upon long-term treatment compliance and may be complicated by poor adherence to medication use. ED may contribute to poor adherence to medication use because poor quality erectile function may be an unwanted adverse effect of antihypertensives, antidepressants, and 5-α reductase inhibitors for treatment of BPH/LUTS. Diminished erectile spontaneity, rigidity, and/or sustaining capability also negatively affects mood, self-esteem, and confidence, which compromise motivation to be compliant with medications that treat diseases comorbid with ED. AIM: Literature review was performed to explore the role of ED diagnosis and effective treatment in enhancing overall management of selected ED comorbidities, highlighting the role of medication adherence. METHODS: Several PubMed searches were performed. RESULTS: Diagnosis and successful treatment of concomitant ED may promote improved adherence and management of comorbid diseases. Concomitant ED management may improve treatment outcome, decrease healthcare costs, and possibly prevent or even improve deterioration in medical conditions comorbid with ED. Because ED is a silent marker and predictor of comorbidities, especially cardiovascular disease, earlier diagnosis of ED may provide an opportunity to prevent future cardiovascular events. In men presenting with complaints of ED, screening for, monitoring, and appropriately treating diseases that are comorbid with ED is essential. Screening for and appropriately treating ED is important for enhanced life quality and improved motivation in men with existing ED comorbidities or risk factors. CONCLUSIONS: Appropriate management of ED and its risk factors may have beneficial effects on diseases that are comorbid with ED, and vice versa, most likely via shared pathophysiological pathways. Clinicians may need to consider men's health overall, of which sexual health is a central component, in order to provide optimal disease management.

Effect of bromocriptine-QR on glycemic control in subjects with uncontrolled hyperglycemia on one or two oral anti-diabetes agents.

OBJECTIVE: To investigate the effect of Bromocriptine-QR on glycemic control in patients with type 2 diabetes whose glycemia is poorly controlled on one or two oral anti-diabetes agents. METHODS: Five hundred fifteen Type 2 Diabetes Mellitus (T2DM) subjects (ages 18 to 80 and average body mass index [BMI] of 32.7) with baseline HbA1c ≥ 7.5 and on one or two oral anti-diabetes (OAD) medications (metformin, sulfonylurea, and/or thiazolidinediones) were randomized 2:1 to bromocriptine-QR (1.6 to 4.8 mg/day) or placebo for a 24 week treatment period. Study investigators were allowed to adjust, if necessary, subject anti-diabetes medications during the study to attempt to achieve glycemic control in case of glycemic deterioration. The impact of bromocriptine-QR treatment intervention on glycemic control was assessed in subjects on any one or two OADs (ALL treatment category) (N = 515), or on metformin with or without another OAD (Met/OAD treatment category) (N = 356), or on metformin plus a sulfonylurea (Met/SU treatment category) (N = 245) 1) by examining the between group difference in change from baseline a) concomitant OAD medication changes during the study, and b) HbA1c and 2) by determining the odds of reaching HbA1c of ≤ 7.0% on bromocriptine-QR versus placebo. RESULTS: Significantly more patients (approximately 1.5 to 2-fold more; P<.05) intensified concomitant anti-diabetes medication therapy during the study in the placebo versus the bromocriptine-QR arm. In subjects that did not change the intensity of the baseline diabetes therapy (72%), and that were on any one or two OADs (ALL), or on metformin with or without another OAD (Met/OAD), or on metformin plus sulfonylurea (Met/SU), the HbA1c change for bromocriptine-QR versus placebo was -0.47 versus +0.22 (between group delta of -0.69, P<.0001), -0.55 versus +0.26 (between group delta of -0.81, P<.0001) and -0.63 versus +0.20 (between group delta of -0.83, P<.0001) respectively, after 24 weeks on therapy. The odds ratio of reaching HbA1c of ≤ 7.0% was 6.50, 12.03 and 11.45 (P<.0002) for these three groups, respectively. CONCLUSION: In T2DM subjects whose hyperglycemia is poorly controlled on one or two oral agents, bromocriptine-QR therapy for 24 weeks can provide significant added improvement in glycemic control relative to adding placebo.

Statins and prostate cancer diagnosis and grade in a veterans population.

BACKGROUND: Although prostate cancer is commonly diagnosed, few risk factors for high-grade prostate cancer are known and few prevention strategies exist. Statins have been proposed as a possible treatment to prevent prostate cancer. METHODS: Using electronic and administrative files from the Veterans Affairs New England Healthcare System, we identified 55,875 men taking either a statin or antihypertensive medication. We used age- and multivariable-adjusted Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer incidence among patients taking statins (n = 41,078) compared with patients taking antihypertensive medications (n = 14,797). We performed similar analyses for all lipid parameters including total cholesterol examining each lipid parameter as a continuous variable and by quartiles. All statistical tests were two-sided. RESULTS: Compared with men taking an antihypertensive medication, statin users were 31% less likely (HR = 0.69, 95% CI = 0.52 to 0.90) to be diagnosed with prostate cancer. Furthermore, statin users were 14% less likely (HR = 0.86, 95% CI = 0.62 to 1.20) to be diagnosed with low-grade prostate cancer and 60% less likely (HR = 0.40, 95% CI = 0.24 to 0.65) to be diagnosed with high-grade prostate cancer compared with antihypertensive medication users. Increased levels of total cholesterol were also associated with both total (HR = 1.02, 95% CI = 1.00 to 1.05) and high-grade (HR = 1.06, 95% CI = 1.02 to 1.10) prostate cancer incidence but not with low-grade prostate cancer incidence (HR = 1.01, 95% CI = 0.98 to 1.04). CONCLUSIONS: Statin use is associated with statistically significantly reduced risk for total and high-grade prostate cancer, and increased levels of serum cholesterol are associated with higher risk for total and high-grade prostate cancer. These findings indicate that clinical trials of statins for prostate cancer prevention are warranted.

Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes.

OBJECTIVE: Quick-release bromocriptine (bromocriptine-QR), a D2 dopamine receptor agonist, is indicated as a treatment for type 2 diabetes. The Cycloset Safety Trial, a 52-week, randomized, double-blind, multicenter trial, evaluated the overall safety and cardiovascular safety of this novel therapy for type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 3,095 patients with type 2 diabetes were randomized 2:1 to bromocriptine-QR or placebo in conjunction with the patient's usual diabetes therapy (diet controlled only or up to two antidiabetes medications, including insulin). The all-cause-safety end point was the occurrence of any serious adverse event (SAE), with a hazard ratio (HR) noninferiority margin of 1.5. In a prespecified analysis, the frequency of cardiovascular disease (CVD) events defined as a composite of myocardial infarction, stroke, coronary revascularization, and hospitalization for angina or congestive heart failure was evaluated using modified intent-to-treat analysis (clinicaltrials.gov, NCT00377676). RESULTS: In the bromocriptine-QR group, 176 (8.6%) people reported SAEs compared with 98 (9.6%) in the placebo group (HR 1.02 [96% one-sided CI 1.27]). Fewer people reported a CVD end point in the bromocriptine-QR group versus the placebo group (37 [1.8%] vs. 32 [3.2%], respecively) (HR 0.60 [95% two-sided CI 0.35-0.96]). Nausea was the most commonly reported adverse event in the bromocriptine-QR group. CONCLUSIONS: The frequency of SAEs was comparable between the treatment arms. Compared with patients in the placebo arm, fewer patients taking bromocriptine-QR experienced a cardiovascular end point.

Cardiovascular benefit of magnitude of low-density lipoprotein cholesterol reduction: a comparison of subgroups by age.

BACKGROUND: We examined the effect of the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction across subjects of various ages in a retrospective cohort study. METHODS AND RESULTS: We selected 20,132 male veterans at high risk for an acute cardiovascular event and who had 2 or more LDL-C measurements before their first documented acute myocardial infarction, revascularization, death, or censoring date. LDL-C reduction was categorized as no reduction (<10 mg/dL; reference), small reduction (between 10 and 40 mg/dL), moderate reduction (between 40 and 70 mg/dL), or large reduction (> or =70 mg/dL). The primary outcome was combined acute myocardial infarction or revascularization. The first and last LDL-C levels in the databases were used to calculate the LDL-C reduction in patients who experienced no outcome or who died. Within each age quartile and in a subgroup of patients > or =80 years of age, a Cox proportional hazards model was used to determine hazard ratios for each category of LDL-C reduction compared with the reference category, with adjustment for age, body mass index, current smoking status, medications, and comorbidities. In all age groups, the magnitude of LDL-C reduction was proportional to the magnitude of cardiovascular risk reduction. Risk reduction for the combined outcome in patients who achieved a large LDL-C reduction was similar in all age quartiles, with multivariate-adjusted hazard ratios of approximately 0.30. CONCLUSIONS: In a cohort of veterans at high risk for cardiovascular events, patients of all ages, including those 80 years or older, benefitted the most from large reductions in LDL-C.

Low-density lipoprotein reduction and magnitude of cardiovascular risk reduction.

The authors examined the relationship between the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction and the magnitude of cardiovascular risk reduction. From the Veterans Integrated Service Network 1 databases, the authors selected 54,611 patients with prevalent ischemic heart disease, peripheral vascular disease or diabetes mellitus, and >or=2 documented LDL-C levels who were followed between 1997 and 2006. The outcome was defined as acute myocardial infarction or revascularization. Preoutcome LDL-C reduction was categorized as follows: <10 mg/dL, reference; >or=10 but <40 mg/dL, small reduction; >or=40 but <70 mg/dL, moderate reduction; >or=70 mg/dL, large reduction. Proportional hazards were used to determine the hazard ratio for the outcome for each LDL-C reduction category compared with the reference. Results revealed a graded relationship between the magnitude of reduction in LDL-C and cardiovascular risk reduction. Stratified analyses demonstrated these findings to be robust regardless of initial LDL-C levels or whether patients achieved "target" final LDL-C values of <100 mg/dL.

Lack of cholesterol awareness among physicians who smoke.

Cigarette use is a known risk factor for the development of coronary artery disease (CAD) as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR) and 95% confidence intervals (CI) of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively), as did the diagnosis of diabetes (2.40 to 7.79%). Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively), however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol at both time points if they were current smokers (1982 OR 1.44, CI 1.4-1.7; 1997 OR 1.71, CI 1.48-1.97), past smokers (1982 OR 1.12, CI 1.05-1.18; 1997 OR 1.13, CI 1.06-1.20), overweight (BMI 25 kg/m2) or sedentary. In addition, physicians who never quit smoking were likely to be unaware of their cholesterol throughout the study (OR 1.42, CI 1.21-1.67). Cholesterol awareness in general and among those with CAD risk factors improved after 14-years of follow-up. However, the likelihood of being unaware was greater among smokers at both time points. Therefore, smokers do not appear to take advantage of other preventive strategies that would minimize their risk of developing CAD.

Cost impact of diagnostic imaging for lower extremity peripheral vascular occlusive disease.

OBJECTIVE: The evaluation of peripheral vascular disease in the primary care setting is routinely performed by contrast-enhanced magnetic resonance angiography (CE-MRA) and digital subtraction angiography (DSA). However, limited data are available on the relative costs and clinical outcomes following these diagnostic procedures. The objective of this study is to assess and compare costs associated with diagnostic imaging in peripheral vascular occlusive disease (PAOD). METHODS: US veterans (n = 19,209) with CE-MRA or DSA for the assessment of PAOD from fiscal year (FY) 1999 to FY 2004. Main outcome measure(s) using the Department of Veterans Affairs' (VA) costing algorithms, cost, and log-cost of interventions (e.g., revascularization, stent, angioplasty), amputations or mortality rates within 30/90 days and 1 year of DSA or CE-MRA were compared, and adjusted for patient characteristics and disease severity using multivariate regression. Imaging modality selection bias was evaluated with propensity score, instrumental variables, and Heckman methods using untransformed costs and log-costs with smearing retransformation. RESULTS: Initial CE-MRA imaging was significantly more likely among patients with prior renal disease or bypass surgery [odds ratio (OR) > 2; P < 0.001], and less likely among patients with prior amputation, peripheral vascular disease (PVD), claudication, or other cardiovascular disease (OR < 0.7; P < 0.001). After adjusting for endogenous choice of initial imaging modality, 30-day treatment costs were US$3500-$4300 lower (P < 0.001) for patients with initial CE-MRA. Eighty-two percent of DSA imaging patients had no additional procedures or events within 30 days, and 65% at 90 days. Less than 3.2% (3.6%) of patients had any repeat imaging within 30 (90) days of initial imaging. CONCLUSIONS: Relative to DSA, CE-MRA imaging was associated with substantial treatment episode savings, beyond the US$950 direct savings in imaging cost per procedure. Substituting CE-MRA for DSA among those not planning or requiring any follow-up procedures within 30 days, could have reduced outpatient imaging costs by up to 55%, and reduced VA system costs by US$13.2 million over the six-year period.

The association between statins and cancer incidence in a veterans population.

BACKGROUND: Meta-analyses of trials of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors or statins for cardiovascular disease prevention have failed to show any statistically significant benefit of statins for cancer prevention. However, these trials included relatively young participants, who develop few cancers, and their follow-up periods may have been too short to detect an association between statin use and cancer incidence. We investigated this association in a population of veterans. METHODS: We identified patients using antihypertensive medications but no cholesterol-lowering medications (n = 25,594) and patients using statins (n = 37,248) who were enrolled in the Veterans Affairs New England Healthcare System between January 1, 1997, and December 31, 2005. Age- and multivariable-adjusted Cox proportional hazards models were used to calculate the hazard ratio (HR) and its 95% confidence interval (CI) for cancer incidence, excluding nonmelanoma skin cancer, among patients taking statins compared with patients taking antihypertensive medications and among patients grouped by statin dose (as equivalent simvastatin dose). All statistical tests were two-sided. RESULTS: The absolute incidence of total cancers was 9.4% among statin users and 13.2% among nonusers (difference = 3.8%, 95% CI = 3.3% to 4.3%, P(difference) < .001). Statin users had a statistically significant lower risk for total cancer than nonusers after adjustment for age (HR = 0.76, 95% CI = 0.73 to 0.80) and multiple potential confounders (HR = 0.74, 95% CI = 0.70 to 0.78). After multivariable adjustment, a statistically significantly decreased risk of all cancers was also associated with increasing statin use (P(trend) < .001). CONCLUSIONS: Patients using statins may be at lower risk for developing cancer. Additional observational studies and randomized trials of statins for cancer prevention are warranted.

A six-year study of diagnostic lower extremity imaging practice patterns and outcomes in the Veterans Affairs health care system.

BACKGROUND: The use of diagnostic imaging in the United States continues to increase, while investigations of the clinical implications following testing are lacking. The objectives of the present study are to describe the practice patterns and clinical outcomes that follow lower extremity diagnostic imaging. This is a retrospective cohort study with six years of data (1999 to 2004). METHODS: The sources of data for the present study were Veterans Affairs Hospital administrative and clinical databases. The study population included 19,209 American veterans who had either contrast-enhanced magnetic resonance angiography (MRA) or digital subtraction angiography (DSA) for the assessment of peripheral artery occlusive disease. Descriptive statistics of the characteristics were provided, as well as adjusted ORs for having interventions or complications following an imaging procedure. RESULTS: The number of patients initially imaged with a contrast-enhanced MRA increased from 1999 to 2004, while those imaged with DSA decreased. The overall imaging rate remained relatively constant. In the multivariate model adjusted for the risk of complications within 30 days of the initial imaging procedure, the risk of complications following DSA increased 2.29-fold (95% CI 1.60 to 3.30). More patients had an intervention following DSA (DSA 41% versus MRA 23%, P<0.0001) but were also twice as likely to have an intervention with an amputation (adjusted OR 2.36, 95% CI 1.79 to 3.12). CONCLUSIONS: The present study illustrates the need for prospective evaluation of diagnostic imaging to determine how best to employ screening strategies that will optimize diagnostic imaging and treatment in patients diagnosed with peripheral artery occlusive disease.

Effect of treating erectile dysfunction on management of systolic hypertension.

Erectile dysfunction (ED) is a prevalent condition and a predictor of future cardiovascular events. Screening and treatment of ED may improve management of cardiovascular risk factors. We evaluated the potential beneficial effect of newly treating ED on the management of hypertension in men in the New England Veteran Affairs Healthcare System. We conducted a retrospective cohort study using medical record data to identify patients diagnosed with and treated at any time for hypertension who received a prescription for a phosphodiesterase type 5 inhibitor (PDE5i) before February 1, 2003. Fifty percent of 6,768 men (mean +/- SD 61.6 +/- 9.9 years of age) had a systolic blood pressure (BP) > or =140 mm Hg before PDE5i administration. Overall, there was a decrease in systolic BP by 1.43 mm Hg (95% confidence interval -1.69 to -1.18) after initiation of PDE5i. The decrease in systolic BP was most pronounced in men with a systolic BP > or =160 mm Hg at baseline (-17.8 mm Hg, 95% confidence interval -18.8 to -16.8). After initiating therapy with PDE5i, patients were more likely to start an antihypertensive medication (17.3%) versus stop therapy (2.3%) and add additional antihypertensive medication to their existing therapy (42.2%) versus decrease the number of medications (17.3%). Surveillance also increased with total number of systolic BP measurements increasing by 42%. In conclusion, men with high systolic BP who initiated ED therapy had improvements in systolic BP control that may be related to clinically relevant behaviors, such as more aggressive monitoring and treatment with antihypertensive medications.

A randomized, double-blind, placebo-controlled trial to assess safety and tolerability during treatment of type 2 diabetes with usual diabetes therapy and either Cycloset or placebo.

BACKGROUND: Cycloset is a quick-release formulation of bromocriptine mesylate, a dopamine agonist, which in animal models of insulin resistance and type 2 diabetes acts centrally to reduce resistance to insulin- mediated suppression of hepatic glucose output and tissue glucose disposal. In such animals, bromocriptine also reduces hepatic triglyceride synthesis and free fatty acid mobilization, manifesting decreases in both plasma triglycerides and free fatty acids. In clinical trials, morning administration of Cycloset either as monotherapy or adjunctive therapy to sulfonylurea or insulin reduces HbA1c levels relative to placebo by 0.55-1.2. Cycloset therapy also reduces plasma triglycerides and free fatty acid by approximately 25% and 20%, respectively, among those also receiving sulfonylurea therapies. The effects of once-daily morning Cycloset therapy on glycemic control and plasma lipids are demonstrable throughout the diurnal portion of the day (7 a.m. to 7 p.m.) across postprandial time points. METHODS/DESIGN: 3,095 individuals were randomized in a 2:1 ratio into a one year trial aimed to assess the safety and efficacy of Cycloset compared to placebo among individuals receiving a variety of treatments for type 2 diabetes. Eligibility criteria for this randomized placebo controlled trial included: age 30-80, HbA1c

Health care utilization and receipt of cholesterol testing by veterans with and those without mental illness.

OBJECTIVE: We examined the relationship between mental illness, health care utilization and rates of cholesterol testing. METHODS: We conducted a retrospective cohort study using Veterans Affairs (VA) administrative data on 64,490 United States veterans who used VA New England Health Care System outpatient services between January 1998 and June 2001. A total of 10,100 veterans (15.7%) had a mental illness treated with medication. We examined the interaction between mental illness and outpatient service utilization with respect to the likelihood of receiving a cholesterol test, adjusting for major demographic and clinical covariates. RESULTS: Among veterans using VA outpatient services infrequently, those with mental illness were less likely than non-mentally ill control subjects to receive a cholesterol test during the study period (first quartile adjusted OR=0.45, 95% CI=0.37-0.54; second quartile adjusted OR=0.50, 95% CI=0.45-0.57). Mentally ill subjects with more frequent utilization of VA services were as likely as (third quartile adjusted OR=1.01, 95% CI=0.91-1.13) or more likely than (fourth quartile adjusted OR=2.73, 95% CI=2.46-3.03) non-mentally ill subjects to receive cholesterol testing. CONCLUSIONS: Mental illness was associated with a lower likelihood of cholesterol testing in subjects who used fewer VA outpatient services. The observed disparity attenuated at higher levels of service utilization.

Statin use and fracture risk: study of a US veterans population.

BACKGROUND: Whether statins reduce the risk of fractures is still contested. Several studies support a favorable association, whereas post hoc analyses of statin-randomized trials have failed to find a benefit. We sought to assess this possible relationship in a large population of elderly, predominantly male veterans. METHODS: We established the study population using all health care encounters and services from patients who received care in the New England Veterans Affairs health care system between January 1998 and June 2001. According to evidence from the literature, covariates that would affect the risk of fractures were included in the final model, as were medications that were clinically meaningful and significant in univariate models and the Charlson Comorbidity Index as a surrogate for general health. We also conducted a similar analysis among new statin users. We used pooled logistic regression to assess for significant associations. RESULTS: Of the 91 052 patients in the final cohort, 28 063 were prescribed statins and 2195 were prescribed nonstatin lipid-lowering medications. In the adjusted analyses, statin use was associated with a 36% (odds ratio, 0.64; 95% confidence interval, 0.58-0.72) reduction in fracture risk when compared with no lipid-lowering therapy and a 32% (odds ratio, 0.67; 95% confidence interval, 0.50-0.91) reduction when compared with nonstatin lipid-lowering therapy. Similar findings were found for the new statin user group. CONCLUSIONS: We have provided yet another study in a unique population of mostly male veterans that found a significant reduction in fractures among statin users. More studies need to be performed to confirm or refute our findings.

Performance of a rheumatoid arthritis records-based index of severity.

OBJECTIVE: To assess the performance of a rheumatoid arthritis (RA) records-based index of severity (RARBIS) developed by a Delphi panel process in a cohort of patients with RA. METHODS: We reviewed the medical records of 120 RA patients from the New England Veteran's Administration (VA) Healthcare System and collected data on markers of RA disease severity. Markers were refined through a Delphi panel process before developing the RARBIS based on chart review. The RARBIS includes 5 subscales on surgery, radiography, extraarticular manifestations, clinical status, and laboratory values. Factors that were regarded by the Delphi panel as highly related to severity of RA were assigned higher points on the index. We assessed the validity of the RARBIS by comparing it to the intensity of the actual RA treatment that these patients received: low, neither biologic nor disease modifying antirheumatic drug (DMARD) use; moderate, therapy with DMARD such as hydroxychloroquine, gold, or sulfasalazine; high, treatment with stronger DMARD such as methotrexate, azathioprine, leflunomide, and cyclosporine; and very high, use of any biologics. RESULTS: The RARBIS had a range of 0 to 8. All subscales except extraarticular manifestations were statistically significantly related to intensity of RA treatment (chi-square test p

Characteristics associated with differences in reported versus measured total cholesterol among male physicians.

We studied 4,543 male physicians to assess accuracy of self-reported cholesterol level. The rate of accurate reporting improved over 14 years (25% to 62%), while failing to report a cholesterol level decreased. Overweight, current or past smoking, and physical inactivity were significantly associated with not reporting or inaccurately reporting cholesterol level. Though an increasing proportion of physicians accurately reported their cholesterol level over time, those at increased risk for developing cardiovascular disease tended to underestimate or fail to report their cholesterol level. Knowledge may be a critical factor in empowering physicians and patients to advocate for and adopt healthier lifestyles. EDITORS' STRATEGIC IMPLICATIONS: Rates of sedentary behavior and obesity in the U.S. continue to rise. In this promising study with a large sample, a longitudinal design, and multi-method assessments, we find that--even among this sample of highly educated medical professionals--those individuals who are at greatest cardiovascular risk might require different types of monitoring, motivational interventions, or health education.