Enhanced perceptual selection of predicted stimulus orientations following statistical learning.

Perception is influenced by predictions about the sensory environment. These predictions are informed by past experience and can be shaped by exposure to recurring patterns of sensory stimulation. Predictions can enhance perception of a predicted stimulus, but they can also suppress it by favoring novel and unexpected sensory information that is inconsistent with the predictions. Here we employed statistical learning to assess the effects of exposure to consistent sequences of oriented gratings on subsequent visual perceptual selection, as measured with binocular rivalry. Following statistical learning, the first portion of a learned sequence of stimulus orientations was presented to both eyes, followed by simultaneous presentation of the next grating in the sequence to one eye and an orthogonal unexpected orientation to the other eye. We found that subjects were more likely to perceive the grating that matched the orientation that was consistent with the predictive context. That is, observers were more likely to see what they expected to see, compared to the likelihood of perceiving the unexpected stimulus. Some other studies in the literature have reported the opposite effect of prediction on visual perceptual selection, and we suggest that these inconsistencies may be due to differences across studies in the level of the visual processing hierarchy at which competing perceptual interpretations are resolved.

A phase II study of cabozantinib alone or in combination with trastuzumab in breast cancer patients with brain metastases.

PURPOSE: To analyze the efficacy and tolerability of cabozantinib-a small molecule inhibitor of MET and VEGFR2-alone or with trastuzumab in patients with breast cancer brain metastases (BCBM). METHODS: This single-arm phase II study enrolled patients with new or progressive measurable BCBM into 3 cohorts: Cohort 1 (HER2-positive), Cohort 2 (hormone receptor-positive/HER2-negative), and Cohort 3 (triple-negative). Patients received cabozantinib 60-mg daily on a 21-day cycle. Cohort 1 added trastuzumab every 3 weeks and had a primary objective of central nervous system (CNS) objective response rate (ORR) by RECIST 1.1. Secondary objectives for all cohorts were progression-free survival, overall survival, toxicity, and changes in vascular parameters and circulating biomarkers. Cohorts 2 and 3 also had CNS ORR as a secondary objective. RESULTS: Thirty-six BCBM patients enrolled (cohort 1, n = 21; cohort 2, n = 7; cohort 3, n = 8), with a median age of 50. Patients had a median of 3 prior lines for metastatic disease (range 1-9). Treatments prior to enrollment included craniotomy (n = 4), whole brain radiation (n = 24) and stereotactic radiosurgery (n = 11). CNS ORR was 5% in cohort 1, 14% in cohort 2, and 0% in cohort 3. Most common grade 3/4 adverse events included elevations in lipase (11%), AST (8%), ALT (6%), hyponatremia (8%), and hypertension (6%). Cabozantinib increased plasma concentrations of CA-IX, soluble (s)MET, PlGF, sTIE-2, VEGF, and VEGF-D, and decreased sVEGFR2 and TNF-α and total tumor blood volume. CONCLUSIONS: Cabozantinib had insufficient activity in heavily pretreated BCBM patients. Biomarker analysis showed that cabozantinib had antiangiogenic activity and increased tissue hypoxia. TRIAL REGISTRATION: Clinicaltrial.gov registration: NCT02260531.

Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In-situ in Patients with Lobular Neoplasia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 020).

BACKGROUND: Lobular neoplasia (LN) represents a spectrum of atypical proliferative lesions, including atypical lobular hyperplasia and lobular carcinoma-in-situ. The need for excision for LN found on core biopsy (CB) is controversial. We conducted a prospective multi-institutional trial (TBCRC 20) to determine the rate of upgrade to cancer after excision for pure LN on CB. METHODS: Patients with a CB diagnosis of pure LN were prospectively identified and consented to excision. Cases with discordant imaging and those with additional lesions requiring excision were excluded. Upgrade rates to cancer were quantified on the basis of local and central pathology review. Confidence intervals and sample size were based on exact binomial calculations. RESULTS: A total of 77 of 79 registered patients underwent excision (median age 51 years, range 27-82 years). Two cases (3%; 95% confidence interval 0.3-9) were upgraded to cancer (one tubular carcinoma, one ductal carcinoma-in-situ) at excision per local pathology. Central pathology review of 76 cases confirmed pure LN in the CB in all but two cases. In one case, the tubular carcinoma identified at excision was also found in the CB specimen, and in the other, LN was not identified, yielding an upgrade rate of one case (1%; 95% CI 0.01-7) by central pathology review. CONCLUSIONS: In this prospective study of 77 patients with pure LN on CB, the upgrade rate was 3% by local pathology and 1% by central pathology review, demonstrating that routine excision is not indicated for patients with pure LN on CB and concordant imaging findings.

Weight gain on antipsychotic medication is associated with sustained use among veterans with schizophrenia.

OBJECTIVE: Continuous antipsychotic treatment is important in schizophrenia, and studies have shown that rates of discontinuation are high. Some studies suggest that weight gain may lead schizophrenic patients to discontinue treatment, whereas other studies show smaller effects of weight gain on medication discontinuation, and some find weight gain associated with symptom improvement. Our retrospective cohort study investigated the effect of weight change on the continued use for 1 year (persistence) of all antipsychotics, then among users of first-generation antipsychotics and second-generation antipsychotics (SGAs), and lastly subgroups of SGAs. METHODS: We identified 2130 patients with schizophrenia starting an antipsychotic that had not used 1 in the prior year. Using multivariable logistic regression adjusted for demographic and clinical variables, we determined the odds of remaining persistent on medication among patients who either gained weight or did not gain weight in the following year. RESULTS: For all antipsychotics combined, weight change was not associated with persistence. Among SGAs, weight gain was associated with a 23% increase in the adjusted odds ratio (OR) for persistence (OR, 1.23; 95% confidence interval [CI], 1.00-1.51), whereas there was a nonsignificant decrease in the adjusted odds of persistence among first-generation antipsychotic users (OR, 0.74; 95% CI, 0.43-1.28). When SGAs were divided into subgroups (clozapine/olanzapine, risperidone/quetiapine), both had increases in the likelihood of persistence, but only the association for clozapine/olanzapine was significant at a trend level (adjusted OR, 1.46; 95% CI, 0.99-2.16). CONCLUSIONS: These findings are supportive of other research that shows weight gain does not invariably lead to medication discontinuation and may be associated with clinical improvement.

Prescription opioid analgesics increase the risk of depression.

BACKGROUND: Prescription opioid analgesic use has quintupled recently. Evidence linking opioid use with depression emanates from animal models and studies of persons with co-occurring substance use and major depression. Little is known about depressogenic effects of opioid use in other populations. OBJECTIVE: The purpose of this study was to determine whether prescription opioids are associated with increased risk of diagnosed depression. DESIGN: Retrospective cohort study, new user design. PATIENTS: Medical record data from 49,770 US Department of Veterans Affairs (VA) health care system patients with no recent (24-month) history of opioid use or a diagnosis of depression in 1999 and 2000. MAIN MEASURES: Propensity scores were used to control for bias by indication, and the data were weighted to balance the distribution of covariates by duration of incident opioid exposure. Cox proportional hazard models with adjustment for painful conditions were used to estimate the association between duration of prescription opioid use and the subsequent risk of development of depression between 2001 and 2007. KEY RESULTS: Of 49,770 patients who were prescribed an opioid analgesic, 91 % had a prescription for < 90 days, 4 % for 90-180 days, and 5 % for > 180 days. Compared to patients whose prescription was for < 90 days, the risk of depression increased significantly as the duration of opioid prescription increased (HR = 1.25; 95 % CI: 1.05-1.46 for 90-180 days, and HR = 1.51; 95 % CI:1.31-1.74 for > 180 days). CONCLUSIONS: In this sample of veterans with no recent (24-month) history of depression or opioid analgesic use, the risk of development of depression increased as the duration of opioid analgesic exposure increased. The potential for depressogenic effect should be considered in risk-benefit discussions, and patients initiating opioid treatment should be monitored for development of depression.

Incident severe thrombocytopenia in veterans treated with pegylated interferon plus ribavirin for chronic hepatitis C infection.

PURPOSE: We sought to determine the incidence and risks for severe thrombocytopenia (platelets < 50,000/µL) in United States Veteran patients treated with pegylated interferon (PEG-IFN) plus ribavirin for hepatitis C virus-positive (HCV) chronic liver disease (CLD). METHODS: Using a retrospective, observational cohort study design to analyze databases from the New England Veterans Healthcare System, we identified 979 patients diagnosed with HCV-positive CLD treated solely with PEG-IFN plus ribavirin. The cohort was stratified by pre-treatment platelet counts of 50,000-100,000/µL (N = 90), >100,000-150,000/µL (N = 162), and >150,000µL (N = 727). The cumulative incidence of severe thrombocytopenia and major bleeding events were determined for each baseline platelet group for 48 weeks following treatment initiation. Multivariable Cox regression was used to identify risk factors for incident severe thrombocytopenia. RESULTS: Overall, severe thrombocytopenia occurred in 6.1% (N = 60), but in 41.1% of patients with pre-treatment platelet counts 50, 000-100,000/µL compared with 11.7% (p < 0.001) and 0.55% (p < 0.001) in the two higher pre-treatment platelet groups. Most episodes occurred within the first 12 weeks of treatment. Median nadir count for these 60 patients was 35,000/µL (inter-quartile range 28,000, 44,000). Baseline platelet counts of 50,000-100,000/µL [adjusted hazard ratio (HR) = 3.81; 95%CI = 2.07-7.00] and hemoglobin <10 g/dL (adjusted HR = 3.39; 95%CI = 1.45-7.960) associated with severe thrombocytopenia. Major bleeding events during the 48-week observation period were rare (N = 5, 0.51%). CONCLUSIONS: The incidence of severe thrombocytopenia in a large, observational cohort of veteran patients with HCV CLD treated with PEG-IFN plus ribavirin was 6.1%. Low pre-treatment platelet counts and hemoglobin levels associated with early, incident severe thrombocytopenia.

Thrombocytopenia and bleeding in veterans with non-hepatitis C-related chronic liver disease.

BACKGROUND: Thrombocytopenia in chronic liver disease (CLD) typically reflects disease severity and may indicate an increased risk for bleeding. AIMS: To describe the longitudinal course of thrombocytopenia and risks for bleeding in veteran patients with non-hepatitis C-related CLD. METHODS: We identified 2,349 patients with non-hepatitis C-related CLD from databases of the New England Veterans Healthcare System between 1999 and 2008. The cohort was stratified by baseline platelet counts of <50,000, 50-100,000, > 100,000-150,000, and >150,000/µl. Primary outcomes were the incidence and hazard rates for bleeding episodes requiring hospitalization and incident severe thrombocytopenia (<50,000/µl). RESULTS: Over a median follow-up of 3.3 years (IQR 1.2, 6.3), incident major bleeds, predominantly gastrointestinal, occurred in 254 patients (10.8 % of the cohort) and in 19.9 % of those with baseline platelets <50,000/µl. Incident severe thrombocytopenia occurred in 315 patients (13.4 % of cohort) and in 40.7 % of those with baseline platelet counts between 50,000 and 100,000/µl. Baseline platelet counts between 50,000 and 100,000/µl independently predicted bleeding [adjusted HR 2.89 (1.76, 4.73) p < 0.001] as did esophageal varices, hemoglobin ≤ 9.9 g %, and INR 1.4-2.0. Incident severe thrombocytopenia and minimum platelet counts <25,000/µl each associated with bleeding episodes, but the average of minimum platelet counts recorded for those who bled was 76,000/µl. CONCLUSIONS: Among veteran patients with non-hepatitis C-related CLD, baseline platelet counts of 50,000 to 100,000/µl increased subsequent risks for both incident severe thrombocytopenia and major bleeding events. Whereas associations between severe thrombocytopenia and bleeding most likely reflect CLD severity, liver-related coagulopathies, and co-morbid bleeding risks, interventions to enhance platelet production may be beneficial for such patients.

Risk of community-acquired pneumonia in veteran patients to whom proton pump inhibitors were dispensed.

BACKGROUND: Observational studies linking proton pump inhibitor (PPI) exposure with community-acquired pneumonia (CAP) have reported either modest or no associations. Accordingly, we studied PPI exposure and CAP in veteran patients, using a retrospective, nested case-control design. METHODS: From linked pharmacy and administrative databases of the New England Veterans Healthcare System, we identified 71985 outpatients newly prescribed PPIs between 1998 and 2007; 1544 patients met criteria for CAP subsequent to PPI initiation; 15440 controls were matched through risk-set sampling by age and time under observation. Crude and adjusted odds ratios comparing current with past PPI exposures, as well as tests for interactions, were conducted for the entire and stratified samples. RESULTS: Current PPI use associated with CAP (adjusted odds ratio [OR], 1.29 [95% confidence interval {CI}, 1.15-1.45]). Risks were not substantially altered by age or year of diagnosis. Dementia (n = 85; P = .062 for interaction) and sedative/tranquilizer use (n = 224; P = .049 for interaction) were likely effect modifiers increasing a PPI-CAP association; conversely, for some chronic medical conditions, PPI-associated CAP risks were reversed. PPI exposures between 1 and 15 days increased CAP risks, compared with longer exposures, but PPI initiation also frequently occurred shortly after CAP diagnoses. Prescribed PPI doses >1 dose/day also increased PPI-associated CAP risks. CONCLUSIONS: Among the veterans studied, current compared with past PPI exposures associated modestly with increased risks of CAP. However, our observations that recent treatment initiation and higher PPI doses were associated with greater risks, and the inconsistent PPI-CAP associations between patient subgroups, indicate that further inquiries are needed to separate out coincidental patterns of associations.

Veterans and suicide: a reexamination of the National Death Index-linked National Health Interview Survey.

OBJECTIVES: We assessed the risk of suicide among veterans compared with nonveterans. METHODS: Cox proportional hazards models estimated the relative risk of suicide, by self-reported veteran status, among 500,822 adult male participants in the National Death Index (NDI)-linked National Health Interview Survey (NHIS), a nationally representative cohort study. RESULTS: A total of 482 male veterans died by suicide during 1,837,886 person-years of follow-up (76% by firearm); 835 male nonveterans died by suicide during 4,438,515 person-years of follow-up (62% by firearm). Crude suicide rates for veterans and nonveterans were, respectively, 26.2 and 18.8 per 100,000 person-years. The risk of suicide was not significantly higher among veterans, compared with nonveterans, after adjustment for differences in age, race, and survey year (hazard ratio = 1.11; 95% confidence interval = 0.96, 1.29). CONCLUSIONS: Consistent with most studies of suicide risk among veterans of conflicts before Operation Iraqi Freedom/Operation Enduring Freedom, but in contrast to a previous study using the NDI-linked NHIS data, we found that male veterans responding to the NHIS were modestly, but not significantly, at higher risk for suicide compared with male nonveterans.

The association between height and prostate cancer grade in the Early Stage Prostate Cancer Cohort Study.

OBJECTIVE: We examined the relationship between height and prostate cancer grade. METHODS: The Early Stage Prostate Cancer Cohort Study is an observational cohort of 1,037 men diagnosed with early-stage prostate cancer, T(0-3)N(x)M(0). High-grade prostate cancer was defined as a biopsy Gleason score ≥ 7 (4 + 3). Logistic regression models were created to calculate odds ratios (OR) and 95% confidence intervals (CI) for the cross-sectional relationship between height and prostate cancer grade in the overall cohort and subpopulations. RESULTS: We identified 939 participants with a biopsy Gleason score. High-grade prostate cancer was diagnosed in 138 participants. Overall, participants in the highest quartile of height were more than twice as likely to have a Gleason score ≥ 7 (4 + 3) than participants in the lowest quartile of height, OR 2.14 (95% CI 1.11, 4.14), after multivariate adjustment. Participants in the highest quartile of height were more likely to be diagnosed with high-grade prostate cancer than participants in the lowest quartile of height among participants who were black, OR 8.00 (95% CI 1.99, 32.18), and participants who had diabetes mellitus, OR 5.09 (95% CI 1.30, 19.98). CONCLUSIONS: Height is associated with increased risk of high-grade prostate cancer overall and perhaps among certain subpopulations.

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen.

BACKGROUND: Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care. PURPOSE: We describe a novel randomized clinical trial that uses the informatics and statistics infrastructure of the Veterans Affairs Healthcare System (VA) to illustrate one key component (called the point-of-care clinical trial - POC-CT) of a 'learning healthcare system,' and settles a clinical question of interest to the VA. METHODS: This study is an open-label, randomized trial comparing sliding scale regular insulin to a weight-based regimen for control of hyperglycemia, using the primary outcome length of stay, in non-ICU inpatients within the northeast region of the VA. All non-ICU patients who require in-hospital insulin therapy are eligible for the trial, and the VA's automated systems will be used to assess eligibility and present the possibility of randomization to the clinician at the point of care. Clinicians will indicate their approval for informed consent to be obtained by study staff. Adaptive randomization will assign up to 3000 patients, preferentially to the currently 'winning' strategy, and all care will proceed according to usual practices. Based on a Bayesian stopping rule, the study has acceptable frequentist operating characteristics (Type I error 6%, power 86%) against a 12% reduction of median length of stay from 5 to 4.4 days. The adaptive stopping rule promotes implementation of a successful treatment strategy. LIMITATIONS: Despite clinical equipoise, individual healthcare providers may have strong treatment preferences that jeopardize the success and implementation of the trial design, leading to low rates of randomization. Unblinded treatment assignment may bias results. In addition, generalization of clinical results to other healthcare systems may be limited by differences in patient population. Generalizability of the POC-CT method depends on the level of informatics and statistics infrastructure available to a healthcare system. CONCLUSIONS: The methods proposed will demonstrate outcome-based evaluation of control of hyperglycemia in hospitalized veterans. By institutionalizing a process of statistically sound and efficient learning, and by integrating that learning with automatic implementation of best practice, the participating VA Healthcare Systems will accelerate improvements in the effectiveness of care.

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.

Posttraumatic stress disorder and completed suicide.

Most research regarding posttraumatic stress disorder (PTSD) and suicide has focused on suicidal ideation or attempts; no known study of the association between PTSD and completed suicide in a population-based sample has been reported. This study examined the association between PTSD and completed suicide in a population-based sample. Data were obtained from the nationwide Danish health and administrative registries, which include data on all 5.4 million residents of Denmark. All suicides between January 1, 1994, and December 31, 2006, were included, and controls were selected from a sample of all Danish residents. Using this nested case-control design, the authors examined 9,612 suicide cases and 199,306 controls matched to cases on gender, date of birth, and time. Thirty-eight suicide cases (0.40%) and 95 controls (0.05%) were diagnosed with PTSD. The odds ratio associating PTSD with suicide was 9.8 (95% confidence interval: 6.7, 15). The association between PTSD and completed suicide remained after controlling for psychiatric and demographic confounders (odds ratio = 5.3, 95% confidence interval: 3.4, 8.1). Additionally, persons with PTSD and depression had a greater rate of suicide than expected based on their independent effects. In conclusion, a registry-based diagnosis of PTSD based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, is a risk factor for completed suicide.

Change in use of gadolinium-enhanced magnetic resonance studies in kidney disease patients after US Food and Drug Administration warnings: a cross-sectional study of Veterans Affairs Health Care System data from 2005-2008.

BACKGROUND: Exposure to gadolinium in patients with kidney disease has been linked to risk of developing nephrogenic systemic fibrosis. The US Food and Drug Administration (FDA) has issued warnings against the use of gadolinium in this population. We studied the impact of these warnings on the use of gadolinium-enhanced magnetic resonance (GE-MR) studies in patients with decreased estimated glomerular filtration rate (eGFR) and the practice of measuring serum creatinine before gadolinium exposure. STUDY DESIGN: Cross-sectional study of patients who had undergone MR studies from October 2002 to September 2008. SETTING & PARTICIPANTS: Patients receiving medical care in the US Department of Veterans Affairs Health Care System. PREDICTOR: Date of MR imaging, serum creatinine level, and eGFR using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. OUTCOMES & MEASUREMENTS: The rate of MR studies performed with and without gadolinium from July 2005 to September 2008 in patients with different stages of kidney disease, defined using eGFR. The proportion of GE-MR studies with a screening serum creatinine level. RESULTS: There was a 71% decrease in the rate of GE-MR use in patients with GFR<30 mL/min/1.73 m2 2 years after the release of the first public health advisory, although studies continued to be performed in patients with stages 4 and 5 chronic kidney disease. The proportion of GE-MR studies with serum creatinine measured within 1 month before the study increased by 99%. LIMITATIONS: Data available up to September 30, 2008. Indications for the GE-MR studies were not assessed. The accuracy of Current Procedural Terminology and International Classification of Diseases, Ninth Revision coding was not assessed. CONCLUSION: There was a large decrease in the use of GE-MR studies in patients with GFR<30 mL/min/1.73 m2 and a large but not universal increase in the practice of measuring serum creatinine before GE-MR after the release of the FDA warnings.

Initiation of anaemia management in patients with chronic kidney disease not on dialysis in the Veterans Health Administration.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are frequently used to treat anaemia of chronic kidney disease (CKD) in the dialysis setting; however, few data are available regarding factors influencing initiation of ESAs and other therapies in non-dialysis patients. METHODS: A retrospective cohort study of Veterans Health Administration data from 2003 to 2005 for 89 585 patients identified as having CKD and anaemia based on two outpatient estimated glomerular filtration rates <60 ml/min/1.73 m(2) and at least one outpatient haemoglobin (Hb) <11 g/dL. Hb levels, patient demographics, clinical and provider characteristics and procedures predicted ESA treatment initiation over 1 year of follow-up. Multivariable logistic and pooled logistic survival models identified predictors of ESA initiation. RESULTS: Overall, 6381 subjects (7.1%) initiated ESAs within 1 year of the index Hb; initiation was more common (8.6%) for patients with Hb <10 g/dL. Iron therapy use varied by initial Hb levels (27.6% to 52.4%) as did transfusions (12.5% to 42.8%); each was more common at lower Hb levels. Hbs rose to above 11 g/dL for 25-50% of patients in the absence of any treatment or by transfusion/iron therapy. Factors predicting time to ESA initiation included: nephrologist [odds ratio (OR = 2.3)] or haematologist care (OR = 2.2) and iron therapy (OR = 1.6). Transfusions increased for patients with increasing follow-up time. CONCLUSION: Iron therapy is more common than ESA treatment in patients with CKD and Hbs <11 g/dL in the VA. Correction of anaemia in the absence of any ESA treatment was common at higher Hbs levels, but much less so when Hb levels fell below 10 g/dL.

Suicide among US veterans: A prospective study of 500,000 middle-aged and elderly men.

Expert opinion is divided about whether US military veterans, the vast majority of whom are middle-aged or older, are at increased risk of suicide. To assess the risk of suicide associated with veteran status, the authors conducted a prospective cohort study of 499,356 male participants in the Cancer Prevention Study II. Participants reported their veteran status and other characteristics in 1982 and were followed for mortality through 2004. The relative risk of mortality from suicide according to veteran status at baseline was estimated by using Cox proportional hazards models. During follow-up, 1,248 veterans and 614 nonveterans died by suicide. In age-adjusted analyses, the risk of suicide did not differ by veteran status. Additional adjustment for several sociodemographic, behavioral, and clinical factors had little effect on hazard ratios. The authors concluded that the risk of death from suicide among middle-aged and older US males is independent of veteran status and suggest that policies to prevent veteran suicide should focus on factors that may heighten suicide risk rather than on veteran status per se.

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.

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.

Practitioner-level determinants of inappropriate prostate-specific antigen screening.

BACKGROUND: None of the major clinical practice guidelines recommend that prostate-specific antigen (PSA) screening be routinely performed in asymptomatic men older than 75 years or younger than 40 years. We investigated the practitioner-level determinants of inappropriate PSA screening in 7 Veterans Health Administration (VHA) hospitals. METHODS: Data on PSA test use from 1997 to 2004 were obtained from VHA databases for 181 139 male patients and the 4823 health care providers who ordered their tests. Patients were excluded from the study population if they underwent PSA testing for nonscreening reasons, as indicated by prostate cancer-specific medications, diagnoses, and procedures. Inappropriate PSA test use was defined as PSA screening in patients older than 75 years or younger than 40 years. Univariate and multivariate Poisson regressions were performed. RESULTS: The mean +/- SD percentage of inappropriate tests by health care provider was 19.3% +/- 15.0%, with 18.4% +/- 14.9% in patients older than 75 years and 0.8% +/- 3.0% in patients younger than 40 years. Practitioners who were urology specialists, male, infrequent PSA test orderers, and affiliated with specific hospitals had significantly higher levels of inappropriate PSA screening. Compared with attending physicians, nurses and physician assistants had significantly lower levels of inappropriate screening. Under multivariate modeling, infrequent PSA test ordering and hospital affiliation retained statistical significance. The percentage of inappropriate PSA screening increased significantly with the age of male health care providers (P<.001). CONCLUSIONS: This study elucidates several important provider-level determinants of PSA screening misuse and substantiates that PSA screening is frequently performed counter to evidence-based guidelines. Further work is needed to determine the degree to which "prostatempathy" contributes to PSA misuse by older male providers.