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Objectives: To determine the influence of advanced age on anticoagulant use in subjects with atrial fibrillation and to explore the extent to which risk factors for stroke and contraindications to anticoagulant therapy predict subsequent use. Design: Retrospective cohort study. Setting: The Veterans Affairs Boston Healthcare System. Participants: A total of 2,217 subjects with nonvalvular atrial fibrillation. Measurements: Administrative databases were use to identify subject's age, anticoagulant use, and the presence of a diagnosis of atrial fibrillation, cerebrovascular accident, hypertension, diabetes mellitus, congestive heart failure, or gastrointestinal or cerebral hemorrhage. Results: Unadjusted analysis showed no difference in warfarin use between those aged 75 and older and younger subjects regardless of the presence (33.9% vs 35.7%, P=.37) or absence (33.4% vs 34.7%, P=.58) of contraindications to anticoagulant therapy. Multivariate modeling demonstrated a 14% reduction (95% confidence interval (CI)=4–22%) in anticoagulant use with each advancing decade of life. Intracranial hemorrhage was a significant deterrent (odds ratio (OR)=0.27 95% CI=0.06–0.85). History of hypertension (OR=2.90, 95% CI=2.15–3.89), congestive heart failure (OR=1.70, 95% CI=1.41–2.04), and cerebrovascular accident (OR=1.54, 95% CI=1.25–1.89) were significant independent predictors for anticoagulant use. Conclusion: Despite consensus guidelines to treat all atrial fibrillation patients aged 75 and older with anticoagulants, advancing age was found to be a deterrent to warfarin use. Better estimates of the risk:benefit ratio for oral anticoagulant therapy in older patients with atrial fibrillation are needed to optimize decision-making.

Purpose To identify systemic factors associated with the development of central serous chorioretinopathy (CSCR). Design Retrospective, case–control study. Participants and controls: 312 cases and 312 controls. Results By use of a multivariate analysis, the previously described risk factors, systemic steroid use (odds ratio [OR], 37.1; 95% confidence interval [CI], 6.2–221.8), and pregnancy (OR, 7.1; 95% CI, 1.0–50.7), were strongly associated with CSCR. Additional risk factors identified by this study include antibiotic use (OR, 6.2; 95% CI, 1.0–37.9), alcohol use (OR, 4.9; 95% CI, 1.5–16.3), untreated hypertension (OR, 3.3; 95% CI, 1.3–8.5), and allergic respiratory disease (OR, 2.5; 95% CI, 1.2–5.1). Conclusions A wide variety of systemic factors are associated with CSCR. Prospective studies are warranted to evaluate the nature and significance of these associations further.

BACKGROUND Low dietary vitamin K intake has been associated with an increased risk of hip fracture in men and women. Few data exist on the association between dietary vitamin K intake and bone mineral density (BMD). OBJECTIVE We studied cross-sectional associations between self-reported dietary vitamin K intake and BMD of the hip and spine in men and women aged 29-86 y. DESIGN BMD was measured at the hip and spine in 1112 men and 1479 women (macro x +/- SD age: 59 +/- 9 y) who participated in the Framingham Heart Study (1996-2000). Dietary and supplemental intakes of vitamin K were assessed with the use of a food-frequency questionnaire. Additional covariates included age, body mass index, smoking status, alcohol use, physical activity score, and menopause status and current estrogen use among the women. RESULTS Women in the lowest quartile of vitamin K intake (macro x: 70.2 microg/d) had significantly (P < or = 0.005) lower mean (+/- SEM) BMD at the femoral neck (0.854 +/- 0.006 g/cm(2)) and spine (1.140 +/- 0.010 g/cm(2)) than did those in the highest quartile of vitamin K intake (macro x: 309 microg/d): 0.888 +/- 0.006 and 1.190 +/- 0.010 g/cm(2), respectively. These associations remained after potential confounders were controlled for and after stratification by age or supplement use. No significant association was found between dietary vitamin K intake and BMD in men. CONCLUSIONS Low dietary vitamin K intake was associated with low BMD in women, consistent with previous reports that low dietary vitamin K intake is associated with an increased risk of hip fracture. In contrast, there was no association between dietary vitamin K intake and BMD in men.

Aim: Million Veteran Program (MVP) is the largest ongoing mega-cohort biobank program in the US with 570,131 enrollees as of May 2017. The primary aim is to describe demographics, military service, and major diseases and comorbidities of the MVP cohort. Our secondary aim is to examine body mass index (BMI), a proxy for general health, among enrollees. Materials and Method: The study population consists of Veterans who actively use the Veterans Health Administration in the US. Data evaluated in this paper combine health information from multiple sources to provide the most comprehensive demographic profile and information on height and weight of MVP enrollees. A standardized cleaning algorithm was used to curate the demographic variables for each participant in MVP. For height and weight, we derived a final data point for each participant to evaluate BMI. Statistical Analysis Used: Multivariable logistic regression was used to compare the differences in BMI categories across enrollment years adjusting for gender, race, and age. P < 0.05 was considered statistically significant. All analyses were conducted using Statistical Analysis System 9.2. Results: The MVP cohort consists of 90.4% of males with an average age of 61.9 years (standard deviation [SD] = 13.9). MVP is the largest multiethnic biobank cohort within the Veteran population with 73.9% White, 19.0% Black, and 6.5% Hispanic. The most common self-reported disease was hypertension (62.6%) for males and depression (47.5%) for females. Mean BMI was 29.7 kg/m2 (SD = 5.8) with 38.2% obese and 42.3% overweight. Conclusions: Our findings suggest that demographic representation in MVP is similar to the Veterans Health Administration population and contrasts with the overall National Health and Nutrition Examination Survey US population. The prevalence of overweight and obese is high among US Veterans, and future studies will examine the role of BMI and disease risk in the Veteran population.

Importance The unprecedented increase in unintentional overdose events that has occurred in tandem with escalating sales of prescription opioids over the past 2 decades has raised concerns about whether the therapeutic use of opioids has contributed to increases in overdose injury. Few controlled studies have examined the extent to which ecologic measures of increases in opioid prescribing and overdose injuries reflect risk among patients prescribed opioids, let alone whether some opioid regimens are safer than others. Objective To examine whether the risk of unintentional overdose injury is associated with the duration of opioid action (ie, long-acting vs short-acting formulations). Design, Setting, and Participants A propensity score–adjusted cohort study was conducted using population-based health care utilization data from the Veterans Administration Healthcare System. The patients were veterans with chronic painful conditions who began therapy with opioid analgesics between January 1, 2000, and December 31, 2009. Main Outcomes and Measures Unintentional overdoses that are explicitly coded using International Classification of Disease, Ninth Revision codes as drug or medication poisonings of accidental intent (E850.x-860.x) or undetermined intent (E980.x or drug poisoning [960.x-980.x] without an accompanying external cause of injury code). Results A total of 319 unintentional overdose events were observed. Patients initiating therapy with long-acting opioids were more than twice as likely to overdose compared with persons initiating therapy with short-acting opioids. After adjustment for age, sex, opioid dose, and other clinical characteristics, patients receiving long-acting opioids had a significantly higher rate of overdose injury than did those receiving short-acting opioids (hazard ratio [HR], 2.33; 95% CI, 1.26-4.32). The risk associated with long-acting agents was particularly marked during the first 2 weeks after initiation of treatment (HR, 5.25; 1.88-14.72). Conclusions and Relevance To our knowledge, the findings of the present study provide the first evidence that the risk of unintentional overdose injury is related to the prescribed opioid’s duration of action. If replicated in other cohorts, our findings suggest that clinicians weighing the benefits and risks of initiating different opioid regimens should consider not only the daily dose prescribed but also the duration of opioid action, favoring short-acting agents whenever possible, especially during the first 2 weeks of therapy.

A genome-wide scan was performed in a randomly ascertained set of 330 extended families from the population-based Framingham Study to identify chromosomal regions possibly linked to bone mineral density (BMD). A set of 401 microsatellite markers was typed at a 10-centimorgan (cM) average density throughout the genome. BMD was measured at the femoral neck, trochanter, Ward's area, and lumbar spine in 1557 participants of both Framingham cohorts. BMDs were adjusted for age, body mass index (BMI), height, alcohol, caffeine, calcium and vitamin D intakes, smoking, physical activity, and estrogen use in women within each sex and cohort. Strong heritabilities (values between 0.543 and 0.633) were found for the adjusted BMD at all sites. Two-point and multipoint quantitative linkage analyses were performed for each BMD site using the maximum likelihood variance components method. By two-point screening, loci of suggestive linkage were identified on chromosomes 6 and 21, with the maximum log10 of the odds ratio (LOD) scores of 2.34 for the trochanter at D21S1446 and 2.93 for the femoral neck at D6S2427. Lumbar spine BMD had maxima at D6S2427 (LOD = 1.88) and at D12S395 (LOD = 2.08). Multipoint linkage analysis revealed suggestive linkage of trochanteric BMD at a broad (approximately 20 cM) interval on chromosome 21q, with the peak linkage close to D21S1446 (LOD = 3.14). LOD scores were 2.13 at 8q24 with Ward's BMD and 1.92 at 14q21.3 with lumbar spine BMD. This largest genome screen to date for genes underlying normal variation in BMD, adjusted for a large number of covariates, will help to identify new positional candidate genes, otherwise unrecognized.

Many late-onset diseases are caused by what appears to be a combination of a genetic predisposition to disease and environmental factors. The use of existing cohort studies provides an opportunity to infer genetic predisposition to disease on a representative sample of a study population, now that many such studies are gathering genetic information on the participants. One feature to using existing cohorts is that subjects may be censored due to death prior to genetic sampling, thereby adding a layer of complexity to the analysis. We develop a statistical framework to infer parameters of a latent variables model for disease onset. The latent variables model describes the role of genetic and modifiable risk factors on the onset ages of multiple diseases, and accounts for right-censoring of disease onset ages. The framework also allows for missing genetic information by inferring a subject's unknown genotype through appropriately incorporated covariate information. The model is applied to data gathered in the Framingham Heart Study for measuring the effect of different Apo-E genotypes on the occurrence of various cardiovascular disease events.

Background: Cigarette smoking potentiates the antiplatelet effect of clopidogrel. Guidelines recommend clopidogrel for 12 months after percutaneous coronary intervention (PCI) with bare-metal (BMS) or drug-eluting (DES) stents. Whether smoking affects the risk of ischemic events related to clopidogrel use beyond 12 months after PCI is unknown Methods: We identified all PCIs performed in the Veterans Affairs (VA) health system from 2002-2006 and linked the information with the VA pharmacy database. VA and non-VA clinical outcomes were identified by ICD-9 codes from the VA National Patient Care and CMS/Medicare databases. All patients who were event-free at 12 months were followed for death, myocardial infarction (MI), or target vessel revascularization (TVR) up to 4 years following PCI. Prolonged (i.e., > 12 months) vs. clopidogrel use for < 12 months was assessed for each outcome within each stent type using propensity score adjusted inverse probability of weighting (IPW) Cox-proportional hazards analyses. Results: From 2002-2006, 28,507 patients included in the study underwent PCI and were event free at 12 months. Of these, 42% were smokers (n = 11,989) at the index PCI, 51% received a DES (n = 14, 594) and 45% were treated with prolonged clopidogrel use (n = 12,968). Following a 12-month landmark period, 2,194 deaths, 2,288 death or MIs, and 2,010 TVRs occurred. In smokers, prolonged clopidogrel use was associated with a lower risk of death and death or MI with both stent types (interaction p ≤ 0.10). In non-smokers, prolonged clopidogrel use was associated with a lower risk of death (interaction p = 0.04) and death or MI (interaction p = 0.03) in patients receiving DES only (Table). Conclusions: Prolonging clopidogrel more than 12 months after PCI may lower the risk of death or MI in smokers irrespective of stent type and in non-smokers receiving DES only. This study suggests that the duration of clopidogrel use after PCI may be tailored to smoking status and stent-type.

Introduction: Clopidogrel up to 12 months after an acute coronary syndrome (ACS) lowers the risk of major adverse coronary events. Guidelines recommend clopidogrel for 12 months after coronary intervention (PCI) with bare-metal (BMS) or drug-eluting (DES) stents. The value of prolonging clopidogrel beyond 12 months in PCI patients with ACS is unknown. Hypothesis: We hypothesize that prolonged clopidogrel differentially reduces adverse events in patients receiving DES compared with those receiving BMS for an ACS. Methods: We linked all PCIs in the national Veterans Affairs (VA) health system from 2002-2006 with the VA pharmacy database. VA and non-VA clinical outcomes were identified by ICD9 codes from the VA and CMS/Medicare databases. All patients who were event free at 12 months were followed for death, myocardial infarction (MI), and recurrent target vessel revascularization (TVR). The hazard ratio for prolonged clopidogrel use (more than 12 months) versus clopidogrel for less than or equal to 12 months was assessed for each outcome within each stent type, using Cox proportional hazards models. Multivariable models and propensity models were also used to adjust for confounding related to the propensity for prolonged clopidogrel treatment. Results: After exclusions, 28,507 patients had PCI and were event free at 12 months. Of these, 18,279 (64%) had an ACS at their index PCI including 9,336 (51%) who received a DES and 8,447 (46%) who received prolonged clopidogrel. Events occurring up to 4 years after PCI in these ACS patients included 1358 deaths, 1885 death or MIs, and 1335 TVRs. Prolonged clopidogrel was associated with lower risk of death (interaction p=0.04) and death or MI (interaction p=0.001) only in patients receiving DES (Table). Similar results were seen in multivariable and propensity models. Conclusions: Prolonging clopidogrel more than 12 months after PCI for ACS may lower the risk of death or MI in patients receiving DES but not in patients receiving BMS.

Purpose Quality improvements achieved by applying the systems approach to assess the clinical effectiveness, operational efficiency, and financial feasibility of a pharmacist-managed vancomycin dosing service are described. Summary Faced with increased patient volumes and resource demands, the pharmacy department at Tufts Medical Center conducted an evaluation of its adult inpatient vancomycin dosing service using the systems approach, which emphasizes multidisciplinary assessment of system inputs, processes, and outcomes and consensus-building methods to identify needed changes and recommended action steps. A multidisciplinary committee composed of representatives of the medical center’s pharmacy, internal medicine, infectious diseases, nursing, phlebotomy, and clinical laboratory services was assembled; in a series of three moderated monthly sessions, committee members deliberated and ultimately reached consensus on a list of action items. Relative to a concurrent intradepartmental assessment of the vancomycin dosing service based solely on pharmacist feedback, the systems approach identified a greater number and wider array of needed improvements in key program areas. Quality improvements implemented as a direct result of the systems-based analysis included a policy change authorizing pharmacists to order serum vancomycin determinations without physician cosignature and inclusion of a vancomycin dosing algorithm in the institutional antibiotic dosing guide. Future changes based on deliverable action items will result in a structured process to help direct program resources toward the patients most in need of pharmacist-managed vancomycin dosing services. Conclusion The systems approach allowed for a comprehensive multidisciplinary evaluation of the service, as indicated by the identification of process improvements not identified by the department of pharmacy alone.

Identify factors associated with chest illness and describe the relationship between chest illness and mortality in chronic spinal cord injury (SCI).Cross-sectional survey assessing chest illness and a prospective assessment of mortality.Between 1994 and 2005, 430 persons with chronic SCI (mean ± SD), 52.0 ± 14.9 years old, and ≥4 years post SCI (20.5 ± 12.5 years) underwent spirometry, completed a health questionnaire, and reported any chest illness resulting in time off work, indoors, or in bed in the preceding 3 years. Deaths through 2007 were identified. Outcome measures Logistic regression assessing relationships with chest illness at baseline and Cox regression assessing the relationship between chest illness and mortality.Chest illness was reported by 139 persons (32.3%). Personal characteristics associated with chest illness were current smoking (odds ratio =2.15; 95% confidence interval =1.25-3.70 per each pack per day increase), chronic obstructive pulmonary disease (COPD) (3.52; 1.79-6.92), and heart disease (2.18; 1.14-4.16). Adjusting for age, subjects reporting previous chest illness had a non-significantly increased hazard ratio (HR) for mortality (1.30; 0.88-1.91). In a multivariable model, independent predictors of mortality were greater age, SCI level and completeness of injury, diabetes, a lower %-predicted forced expiratory volume in 1 second, heart disease, and smoking history. Adjusting for these covariates, the effect of a previous chest illness on mortality was attenuated (HR = 1.15; 0.77-1.73).In chronic SCI, chest illness in the preceding 3 years was not an independent risk factor for mortality and was not associated with level and completeness of SCI, but was associated with current smoking, physician-diagnosed COPD, and heart disease history.

Prophylactic antibiotics (PRO) reduce the incidence of early-onset pneumonia in comatose patients with structural brain injury, but have not been examined in cardiac arrest survivors undergoing targeted temperature management (TTM). We investigated the effect of PRO on the development of pneumonia in that population.We conducted a retrospective cohort study comparing patients treated with PRO to those not receiving PRO (no-PRO) using Northern Hypothermia Network registry data. Cardiac arrest survivors ≥ 18 years of age with a GCS8 at hospital admission and treated with TTM at 32-34 °C were enrolled in the registry. Differences were analyzed in univariate analyses and with logistic regression models to evaluate independent associations of clinical factors with incidence of pneumonia and good functional outcome.416 of 1240 patients (33.5%) received PRO. Groups were similar in age, gender, arrest location, initial rhythm, and time from collapse to return of spontaneous circulation. PRO patients had less pneumonia (12.6% vs. 54.9%, p0.001) and less sepsis (1.2 vs. 5.7%, p0.001) compared to no-PRO patients. ICU length of stay (98 vs. 100 h, p = 0.2) and incidence of a good functional outcome (41.1 vs. 36.6%, p = 0.19) were similar between groups. Backwards stepwise logistic regression demonstrated PRO were independently associated with a lower incidence of pneumonia (OR 0.09, 95% 0.06-0.14, p0.001) and a similar incidence of good functional outcome.Prophylactic antibiotics were associated with a reduced incidence of pneumonia but a similar rate of good functional outcome.

A subset of human papillomaviruses (HPVs), known as the high-risk types, are the causative agents of cervical cancer and other malignancies of the anogenital region and oral mucosa. The capacity of these viruses to induce cancer and to immortalize cells in culture relies in part on a critical function of their E6 oncoprotein, that of promoting the poly-ubiquitination of the cellular tumor suppressor protein p53 and its subsequent degradation by the proteasome. Here, we describe a cellular assay to measure the p53-degradation activity of E6 from different HPV types. This assay is based on a translational fusion of p53 to Renilla luciferase (Rluc-p53) that remains sensitive to degradation by high-risk E6 and whose steady-state levels can be accurately measured in standard luciferase assays. The p53-degradation activity of any E6 protein can be tested and quantified in transiently transfected cells by determining the amount of E6-expression vector required to reduce by half the levels of RLuc-p53 luciferase activity (50 % effective concentration [EC50]). The high-throughput and quantitative nature of this assay makes it particularly useful to compare the p53-degradation activities of E6 from several HPV types in parallel.

Replication of the human papillomavirus (HPV) double-stranded DNA genome is accomplished by the two viral proteins E1 and E2 in concert with host DNA replication factors. HPV DNA replication is an established model of eukaryotic DNA replication and a potential target for antiviral therapy. Assays to measure the transient replication of HPV DNA in transfected cells have been developed, which rely on a plasmid carrying the viral origin of DNA replication (ori) together with expression vectors for E1 and E2. Replication of the ori-plasmid is typically measured by Southern blotting or PCR analysis of newly replicated DNA (i.e., DpnI digested DNA) several days post-transfection. Although extremely valuable, these assays have been difficult to perform in a high-throughput and quantitative manner. Here, we describe a modified version of the transient DNA replication assay that circumvents these limitations by incorporating a firefly luciferase expression cassette in cis of the ori. Replication of this ori-plasmid by E1 and E2 results in increased levels of firefly luciferase activity that can be accurately quantified and normalized to those of Renilla luciferase expressed from a control plasmid, thus obviating the need for DNA extraction, digestion, and analysis. We provide a detailed protocol for performing the HPV type 31 DNA replication assay in a 96-well plate format suitable for small-molecule screening and EC50 determinations. The quantitative and high-throughput nature of the assay should greatly facilitate the study of HPV DNA replication and the identification of inhibitors thereof.

Background— Many patients with high blood pressure (BP) do not have antihypertensive medications appropriately intensified at clinician visits. We investigated whether an online spaced-education (SE) game among primary care clinicians can decrease time to BP target among their hypertensive patients. Methods and Results— A 2-arm randomized trial was conducted over 52 weeks among primary care clinicians at 8 hospitals. Educational content consisted of 32 validated multiple-choice questions with explanations on hypertension management. Providers were randomized into 2 groups: SE clinicians were enrolled in the game, whereas control clinicians received identical educational content in an online posting. SE game clinicians were e-mailed 1 question every 3 days. Adaptive game mechanics resent questions in 12 or 24 days if answered incorrectly or correctly, respectively. Clinicians retired questions by answering each correctly twice consecutively. Posting of relative performance among peers fostered competition. Primary outcome measure was time to BP target (P =0.018). The number of hypertensive episodes needed to treat to normalize one additional patient’s BP was 67.8. The number of clinicians needed to teach to achieve this was 0.43. Conclusions— An online SE game among clinicians generated a modest but significant reduction in the time to BP target among their hypertensive patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00904007.

With more than 5 million patient visits annually, certified nurse-midwives (CNMs) substantially contribute to women's health care in the United States. The objective of this study was to describe ambulatory visits and practices of CNMs, and compare them with those of obstetrician-gynecologists (OB/GYNs). Sources of population-based data used to compare characteristics of provider visits were three national surveys of CNMs and two National Ambulatory Medical Care Surveys of physicians. When a subset of 4,305 visits to CNMs in 1991 and 1992 were compared to 5,473 visits to OB/GYNs in similar office-based ambulatory care settings in 1989 and 1990, it was found that a larger proportion of CNM visits were made by women who were publicly insured and below age 25. The majority of visits to CNMs were for maternity care; the majority of visits to OB/GYNs were for gynecologic and/or family planning concerns. Face-to-face visit time was longer for CNMs, and involved more client education or counseling. This population-based comparison suggests that CNMs and OB/GYNs provide ambulatory care for women with diverse demographic characteristics and differing clinical service needs. Enhancing collaborative practice could improve health care access for women, which would be especially beneficial for those who are underserved and vulnerable.

This chapter describes ARIS, an open source tool for creating educational games, narratives, and field research activities on mobile devices. The tool is the result of years of design-based research into educational gaming, design pedagogy, and place-based learning. It has been used in a variety of educational contexts from after-school game-design workshops to university-level language courses. Deeply committed to open and democratic education, the project invites involvement at all levels and continues to innovate as a community of users matures.

Identification of persons with chronic obstructive pulmonary disease (COPD) at risk for acute exacerbations (AEs) targets them for close monitoring.We examined the ability of a novel index combining physical activity and systemic inflammation to identify persons at risk for AEs.In an observational cohort study of 167 persons with COPD, we assessed daily step count, a direct measure of physical activity, with the StepWatch Activity Monitor and measured plasma C-reactive protein (CRP) and IL-6 levels. AEs and COPD-related hospitalizations were assessed prospectively over a median of 16 months. Predictors of AEs and COPD-related hospitalizations were assessed using negative binomial models.Median daily step count was 5,203 steps (interquartile range, 3,627-7,024). Subjects with daily step count ≤ 5,203 and CRP3 mg/l had an increased rate of AEs (rate ratio [RR], 2.06; 95% confidence interval [CI], 1.30-3.27) and COPD-related hospitalizations (RR, 3.51; 95% CI, 1.73-7.11) compared with subjects with daily step count5,203 and CRP ≤ 3 mg/l, adjusting for FEV1% predicted and prednisone use for AE in the previous year. Similarly, subjects with daily step count ≤ 5,203 and IL-62 pg/ml had an increased rate of AEs (RR, 2.04; 95% CI, 1.14-3.63) and COPD-related hospitalizations (RR, 4.27; 95% CI, 1.56-11.7) compared with subjects with daily step count5,203 and IL-6 ≤ 2 pg/ml.An index combining daily step count and systemic inflammation can predict AEs and COPD-related hospitalizations. A validation study in a separate cohort is needed to confirm the utility of the proposed index as a clinical tool to risk stratify persons with COPD.

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).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), and150,000μL (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.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 hemoglobin10 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%).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.

OBJECTIVE To report a case of tremors and agitation associated with the administration of low doses of intravenous hydromorphone in a patient with acute kidney injury in the setting of chronic kidney disease. CASE SUMMARY A 91-year-old man was admitted for a left intertrochanteric hip fracture. On hospital days 1 and 2, the patient received hydromorphone 1 mg intravenously for pain. By hospital day 3, the patient had received a total of 3.5 mg of hydromorphone. He then became tremulous and agitated, which worsened as the dose was increased. During hospital day 4, the hydromorphone dosage was increased to 0.5 mg intravenously every 4 hours for what was perceived to be inadequate pain control, manifesting as tremors and agitation. On hospital day 5, hydromorphone, now considered a potential cause of the tremors and agitation, was discontinued. The total amount of hydromorphone administered was 8 mg over 5 days. By hospital day 6, the tremors and agitation had decreased in severity and had resolved by hospital day 7. DISCUSSION Previous reports suggest that hydromorphone-induced neurotoxicity is more likely to occur following high doses over extended periods, especially in patients with kidney dysfunction. There is a paucity of evidence suggesting that neurotoxicity can occur following low doses for short periods of time. Morphine-3-glucuronide has neuroexcitatory properties including myoclonus, allodynia, agitation, or tremors. Structural similarities between morphine-3-glucuronide and hydromorphone-3-glucuronide suggest that neuroexcitatory effects with hydromorphone are feasible. The Naranjo probability scale indicated that hydromorphone-induced tremors were possible. Our case is distinct because the patient received low doses of hydromorphone over a short period. CONCLUSIONS Neurotoxicity can occur in patients with kidney dysfunction while they receive low doses of intravenous hydromorphone over short periods. Diligent monitoring and reporting of such effects are necessary to better understand risk factors and a mechanism.

Growing evidence suggests that Alzheimer’s disease and other types of dementia are underdiagnosed and poorly documented. In our study, we describe patterns of dementia coding and treatment in the Veteran’s Administration New England Healthcare System. We conducted a retrospective cohort study with new outpatient ICD-9 codes for several types of dementia between 2002 and 2009. We examined healthcare utilization, medication use, initial dementia diagnoses, and changes in diagnoses over time by provider type. 8,999 veterans received new dementia diagnoses during the study period. Only 18.3% received a code for cognitive impairment other than dementia, most often “memory loss” (65.2%) prior to dementia diagnosis. Two-thirds of patients received their initial code from a PCP. The etiology of dementia was often never specified by ICD-9 code, even by specialists. Patients followed up exclusively by PCPs had lower rates of neuroimaging and were less likely to receive dementia medication. Emergency room visits and hospitalizations were frequent in all patients but highest in those seen by dementia specialists. Dementia medications are commonly used off-label. Our results suggest that, for the majority the patients, no prodrome of the dementia syndrome is documented with diagnostic code, and patients who do not see dementia specialists have less extensive diagnostic assessment and treatment.

Purpose.The goal of the study was to characterize the dietary patterns of adult men and women.Design.The study used a cross-sectional analysis of food consumption behaviors and nutrient intake measured from 1984 through 1988.Setting.The Framingham Offspring/Spouse Study, Framingham, Massachusetts.Subjects.The population-based sample comprised 1831 men and 1828 women between 20 and 70 years of age.Measures.Dietary patterns were defined by cluster analyses, which used the estimates of usual daily food intake from food frequency questionnaires, and the patterns were compared with Food Guide Pyramid recommendations. Nutrient intakes were independently estimated from 24-hour recalls and compared with Year 2000 nutrition recommendations.Results.Cluster analyses identified five groups of men and five groups of women with distinctive dietary patterns. Men differed on intakes of all food groups except vegetables and snacks plus sweetened beverages. Specific dietary behaviors, including low intakes of whole grains, fruits, vegetables, and other complex carbohydrates; high intakes of beer and liquor; and high intakes of high-fat animal foods warrant targeted intervention messages for men. Women's patterns differed across all food groups except red meats and fattier poultry and beer. Dietary behaviors of women that deserve attention include low fruit, vegetable, starch, and dairy intakes; chronic dieting; high alcohol intake; and sources of hidden fats. No cluster met the current recommendations for food and nutrient intake.Conclusions.Distinct dietary patterns in Framingham men and women vary in compliance with national nutrition and health policy objectives and provide insights for developing behavioral interventions to improve food and nutrient intake.

Objective—To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). Animals—11 healthy parrots. Procedures—Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Results—Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Conclusions and Clinical Relevance—Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

Background: Interaction in clinical trials presents challenges for design and appropriate sample size estimation. Here we considered interaction between treatment assignment and a dichotomous prognostic factor with a continuous outcome. Our objectives were to describe differences in power and sample size requirements across alternative distributions of a prognostic factor and magnitudes of the interaction effect, describe the effect of misspecification of the distribution of the prognostic factor on the power to detect an interaction effect, and discuss and compare three methods of handling the misspecification of the prognostic factor distribution. Methods: We examined the impact of the distribution of the dichotomous prognostic factor on power and sample size for the interaction effect using traditional one-stage sample size calculation. We varied the magnitude of the interaction effect, the distribution of the prognostic factor, and the magnitude and direction of the misspecification of the distribution of the prognostic factor. We compared quota sampling, modified quota sampling, and sample size re-estimation using conditional power as three strategies for ensuring adequate power and type I error in the presence of a misspecification of the prognostic factor distribution. Results: The sample size required to detect an interaction effect with 80% power increases as the distribution of the prognostic factor becomes less balanced. Misspecification such that the actual distribution of the prognostic factor was more skewed than planned led to a decrease in power with the greatest loss in power seen as the distribution of the prognostic factor became less balanced. Quota sampling was able to maintain the empirical power at 80% and the empirical type I error at 5%. The performance of the modified quota sampling procedure was related to the percentage of trials switching the quota sampling scheme. Sample size re-estimation using conditional power was able to improve the empirical power under negative misspecifications (i.e. skewed distributions) but it was not able to reach the target of 80% in all situations. Conclusions: Misspecifying the distribution of a dichotomous prognostic factor can greatly impact power to detect an interaction effect. Modified quota sampling and sample size re-estimation using conditional power improve the power when the distribution of the prognostic factor is misspecified. Quota sampling is simple and can prevent misspecification of the prognostic factor, while maintaining power and type I error.

BACKGROUND: COPD is characterized by variability in exercise capacity and physical activity (PA), and acute exacerbations (AEs). Little is known about the relationship between daily step count, a direct measure of PA, and the risk of AEs, including hospitalizations. METHODS: In an observational cohort study of 169 persons with COPD, we directly assessed PA with the StepWatch Activity Monitor, an ankle-worn accelerometer that measures daily step count. We also assessed exercise capacity with the 6-minute walk test (6MWT) and patient-reported PA with the St. George's Respiratory Questionnaire Activity Score (SGRQ-AS). AEs and COPD-related hospitalizations were assessed and validated prospectively over a median of 16 months. RESULTS: Mean daily step count was 5804±3141 steps. Over 209 person-years of observation, there were 263 AEs (incidence rate 1.3±1.6 per person-year) and 116 COPD-related hospitalizations (incidence rate 0.56±1.09 per person-year). Adjusting for FEV1 % predicted and prednisone use for AE in previous year, for each 1000 fewer steps per day walked at baseline, there was an increased rate of AEs (rate ratio 1.07; 95%CI = 1.003-1.15) and COPD-related hospitalizations (rate ratio 1.24; 95%CI = 1.08-1.42). There was a significant linear trend of decreasing daily step count by quartiles and increasing rate ratios for AEs (P = 0.008) and COPD-related hospitalizations (P = 0.003). Each 30-meter decrease in 6MWT distance was associated with an increased rate ratio of 1.07 (95%CI = 1.01-1.14) for AEs and 1.18 (95%CI = 1.07-1.30) for COPD-related hospitalizations. Worsening of SGRQ-AS by 4 points was associated with an increased rate ratio of 1.05 (95%CI = 1.01-1.09) for AEs and 1.10 (95%CI = 1.02-1.17) for COPD-related hospitalizations. CONCLUSIONS: Lower daily step count, lower 6MWT distance, and worse SGRQ-AS predict future AEs and COPD-related hospitalizations, independent of pulmonary function and previous AE history. These results support the importance of assessing PA in patients with COPD, and provide the rationale to promote PA as part of exacerbation-prevention strategies.

Kaplan-Meier curves provide descriptors of survival information for different subgroups within a data set. Investigators frequently use these figures for descriptive comparison of the effect of a particular measure upon survival. When subjects enter a study at different ages and age is associated with survival, it is often desirable to adjust survival information for age differences in the subgroups. This report discusses several methods for age-adjustment of survival curves, including direct age-adjustment and proportional hazard modelling with age as a covariate.

Importance Traumatic intracranial bleeding, which is most commonly attributable to falls, is a common concern among health care professionals, who are hesitant to prescribe oral anticoagulants to older adults with atrial fibrillation. Objective To describe the incidence of and risk factors for traumatic intracranial bleeding in a large cohort of older adults who were newly prescribed warfarin sodium. Design, Setting, and Participants Retrospective cohort study at the US Department of Veterans Affairs (VA). Participants included 31 951 veterans with atrial fibrillation 75 years or older who were new referrals to VA anticoagulation clinics (for warfarin therapy) between January 1, 2002, and December 31, 2012. The dates of the core analysis were March 2014 through May 2015, and subsequent ad hoc analyses were performed through December 2015. Patients with comorbid conditions requiring warfarin were excluded. Main Outcomes and Measures The primary outcome was hospitalization for traumatic intracranial bleeding. Secondary outcomes included hospitalization for any intracranial bleeding or ischemic stroke. We used International Classification of Diseases , Ninth Revision , Clinical Modification codes to identify the incidence rates of these outcomes after warfarin initiation using VA administrative data (in-system hospitalizations) and Medicare fee-for-service claims data (out-of-system hospitalizations). Clinical characteristics, laboratory results, and pharmacy data were extracted from the VA electronic medical record. For traumatic intracranial bleeding, Cox proportional hazards regression was used to determine predictors of interest selected a priori based on prior known associations. Results The study population comprised 31 951 participants. The mean (SD) patient age was 81.1 (4.1) years, and 98.1% were male. Comorbidities were common, including hypertension (82.5%), coronary artery disease (42.6%), and diabetes mellitus (33.8%). During the study period, the incidence rate of hospitalization for traumatic intracranial bleeding was 4.80 per 1000 person-years. In unadjusted models, significant predictors of traumatic intracranial bleeding included dementia, fall within the past year, anemia, depression, abnormal renal or liver function, anticonvulsant use, labile international normalized ratio, and antihypertensive use. After adjusting for potential confounders, the remaining significant predictors for traumatic intracranial bleeding were dementia (hazard ratio [HR], 1.76; 95% CI, 1.26-2.46), anemia (HR, 1.23; 95% CI, 1.00-1.52), depression (HR, 1.30; 95% CI, 1.05-1.61), anticonvulsant use (HR, 1.35; 95% CI, 1.04-1.75), and labile international normalized ratio (HR, 1.33; 95% CI, 1.04-1.72). The incidence rates of hospitalization for any intracranial bleeding and ischemic stroke were 14.58 and 13.44, respectively, per 1000 person-years. Conclusions and Relevance Among patients 75 years or older with atrial fibrillation initiating warfarin therapy, the risk factors for traumatic intracranial bleeding are unique from those for ischemic stroke. The high overall rate of intracranial bleeding in our sample supports the need to more systematically evaluate the benefits and harms of warfarin therapy in older adults.

Heart failure (HF) with preserved ejection fraction (HFpEF) is difficult to curate in a large database of electronic medical records since it requires verification of HF diagnosis and left ventricular ejection fraction (LVEF) values to be consistently ≥ 50%. We used national Veterans Affairs

Objective In this study we examined changes in dietary intake and risk factors for cardiovascular disease that occurred over three decades in a US-population-based sample. Design Secular trends in dietary profiles and risk factors were studied in cross-sectional samples of subjects from the Framingham Study in 1957–1960, 1966–1969, and 1984–1988. Results Dietary levels of cholesterol appeared to have declined considerably, whereas macronutrient and fatty acid intakes appeared to change only slightly. Men appeared to increase their saturated fat intakes from 16.4% in 1966–1969 to 17.0% in 1984–1988 ( P Conclusions The observed secular trends in diet and risk factor levels for cardiovascular disease in the Framingham population are important to guide the development and implementation of population-based strategies for promoting cardiovascular health, including nutrition interventions. J Am DietAssoc. 1995; 95:171–179.

Background Many foot pathologies are associated with specific foot types. If foot structure and function are related, measurement of either could assist with differential diagnosis of pedal pathologies. Hypothesis Biomechanical measures of foot structure and function are related in asymptomatic healthy individuals. Methods Sixty-one healthy subjects’ left feet were stratified into cavus (n = 12), rectus (n = 27) and planus (n = 22) foot types. Foot structure was assessed by malleolar valgus index, arch height index, and arch height flexibility. Anthropometrics (height and weight), age, and walking speed were measured. Foot function was assessed by center of pressure excursion index, peak plantar pressure, maximum force, and gait pattern parameters. Foot structure and anthropometric variables were entered into stepwise linear regression models to identify predictors of function. Results Measures of foot structure and anthropometrics explained 10–37% of the model variance (adjusted R2) for gait pattern parameters. When walking speed was included, the adjusted R2 increased to 45–77% but foot structure was no longer a factor. Foot structure and anthropometrics predicted 7–47% of the model variance for plantar pressure and 16–64% for maximum force parameters. All multivariate models were significant (p Discussion and conclusion Foot structure and function are related in asymptomatic healthy individuals. The structural parameters employed are basic measurements that do not require ionizing radiation and could be used in a clinical setting. Further research is needed to identify additional predictive parameters (plantar soft tissue characteristics, skeletal alignment, and neuromuscular control) and to include individuals with pathology.

Thrombocytopenia in chronic liver disease (CLD) typically reflects disease severity and may indicate an increased risk for bleeding.To describe the longitudinal course of thrombocytopenia and risks for bleeding in veteran patients with non-hepatitis C-related CLD.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 of50,000, 50-100,000,100,000-150,000, and150,000/μl. Primary outcomes were the incidence and hazard rates for bleeding episodes requiring hospitalization and incident severe thrombocytopenia (50,000/μl).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 platelets50,000/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) p0.001] as did esophageal varices, hemoglobin ≤ 9.9 g %, and INR 1.4-2.0. Incident severe thrombocytopenia and minimum platelet counts25,000/μl each associated with bleeding episodes, but the average of minimum platelet counts recorded for those who bled was 76,000/μl.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.

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 contrastenhanced 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 contrastenhanced 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

LaAlO[sub 3] was chemically modified in order to ascertain the effects of substitution of larger cations on the compound's slight rhombohedral distortion from cubic symmetry--a property that often degrades the performance of LaAlO[sub 3] substrates for epitaxial high-temperature superconducting films. La[sub 1[minus]x]Sr[sub x]Al[sub 1[minus]x]Ti[sub x]O[sub 3] (x = 0.05, 0.10, 0.15, 0.25), La[sub 1[minus]x]Sr[sub x]Al[sub 1[minus]x]Zr[sub x]O[sub 3], La[sub 1[minus]x]Sr[sub x]Al[sub 1[minus]x]Mg[sub x]O[sub 3[minus]2x]F[sub 2x] and La[sub 1[minus]x]Sr[sub x]Al[sub 1[minus]x]Sc[sub x]O[sub 3[minus]x]F[sub x] (x = 0.05, 0.10, 0.15) were prepared in polycrystalline form and 1--2 mm single crystals of the Sr, Ti- and Sr,Zr-substituted systems were grown using a PbO-PbF[sub 2]-B[sub 2]O[sub 3]-PbO[sub 2] flux. Shifts in the peak positions of the X-ray powder diffraction patterns confirmed substitution of the larger cations. The diffraction patterns were also typified by line-broadening and a decrease in the rhombohedral splitting at all doping levels. The dielectric constant of LaAlO[sub 3] was unchanged for all of the fluoride-containing systems and for the 5% Sr,Ti- and Sr,Zr-systems.

BACKGROUND Sinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein (a). Although prospective data suggest that increased plasma lipoprotein (a) is an independent risk factor for coronary heart disease in men, no prospective studies are available in women. METHODS AND RESULTS From 1968 through 1975, sinking prebeta lipoprotein was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease. A sinking prebeta lipoprotein band was detectable in 434 of the women (14%) studied. The median follow-up interval was approximately 12 years. Incident cardiovascular disease was associated with band presence using a proportional hazards model that included age, smoking, body mass index, systolic blood pressure, glucose intolerance, low- and high-density lipoprotein cholesterol, and ECG left ventricular hypertrophy. Multivariable adjusted relative risk estimates (with 95% confidence intervals) for outcomes in the band present versus absent groups were as follows: myocardial infarction (82 events), 2.37 (1.48 to 3.81); intermittent claudication (62 events), 1.94 (1.07 to 3.50); cerebrovascular disease (83 events), 1.88 (1.12 to 3.15); total coronary heart disease (174 events), 1.61 (1.13 to 2.29); and total cardiovascular disease (305 events), 1.44 (1.09 to 1.91). A subset analysis indicated that band presence was 50.9% sensitive and 95.4% specific for detecting plasma lipoprotein (a) levels of > 30 mg/dL, the threshold value linked to increased cardiovascular disease risk in men. CONCLUSIONS Sinking prebeta lipoprotein was a valid surrogate for elevated lipoprotein (a) levels in Framingham Heart Study women. Band presence and, equivalently, elevated plasma lipoprotein (a), was a strong, independent predictor of myocardial infarction, intermittent claudication, and cerebrovascular disease. Confirmation of these findings in other longitudinal studies of women is needed.

We examined the relationship between the risk of CVD mortality and morbidity and HCT over a period of 34 years of follow-up in the 5209 men and women in the Framingham cohort. There was an increased risk of all-cause death as well as morbidity and mortality due to CVD in subjects with HCT values in the highest quintile. There was no evidence of a decreased risk of CVD in men with lower than median HCT values, and women actually showed increased risk of CVD events with lower HCT values, indicating a J- or U-shaped relationship between HCT and CVD events. The impact of HCT on CVD events appears to differ for different age groups and by sex. HCT is significantly related to the incidence of CVD, including CHD, MI, angina pectoris, stroke, and IC in younger men. In younger women, HCT is related to the incidence of CVD, CHD, MI, and mortality from CVD and CHD. A negative association with CHF incidence and stroke death is noted in elderly women. These results support the hypothesis that HCT is an important risk factor for some CVD events, an association that merits further investigation.

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.

To evaluate the relationship between systemic inflammation and pulmonary function in persons with chronic spinal cord injury (SCI).Cross-sectional study.Veterans Affairs Medical Center.Fifty-nine men with chronic SCI participating in a prior epidemiologic study.Standardized assessment of pulmonary function and measurement of plasma C-reactive protein (CRP) and interleukin-6 (IL-6).Forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC).Persons with the highest values of IL-6 had the lowest %-predicted FEV(1) and FVC. There was a significant inverse linear trend between quartile of IL-6 and %-predicted FEV(1) (P.001) and FVC (P.006), unadjusted and adjusted for SCI level and completeness of injury, obstructive lung disease history, smoking, and body mass index (P = .010-.039). Although not as strong as for IL-6, there also were similar trends for %-predicted FEV(1) and FVC with CRP.In chronic SCI, higher levels of IL-6 and CRP were associated with a lower FEV(1) and FVC, independent of level and completeness of injury. These results suggest that the reduction of pulmonary function after SCI is related not only to neuromuscular impairment but also to factors that promote systemic inflammation.

This study compares methods for analyzing correlated survival data from physician-randomized trials of health care quality improvement interventions. Several proposed methods adjust for correlated survival data; however the most suitable method is unknown. Applying the characteristics of our study example, we performed three simulation studies to compare conditional, marginal, and non-parametric methods for analyzing clustered survival data. We simulated 1000 datasets using a shared frailty model with (1) fixed cluster size, (2) variable cluster size, and (3) non-lognormal random effects. Methods of analyses included: the nonlinear mixed model (conditional), the marginal proportional hazards model with robust standard errors, the clustered logrank test, and the clustered permutation test (non-parametric). For each method considered we estimated Type I error, power, mean squared error, and the coverage probability of the treatment effect estimator. We observed underestimated Type I error for the clustered logrank test. The marginal proportional hazards method performed well even when model assumptions were violated. Nonlinear mixed models were only advantageous when the distribution was correctly specified.

The clustered logrank test is a nonparametric method of significance testing for correlated survival data. Examples of its application include cluster randomized trials where groups of patients rather than individuals are randomized to either a treatment or a control intervention. We describe a SAS macro that implements the 2-sample clustered logrank test for data where the entire cluster is randomized to the same treatment group. We discuss the theory and applications behind this test as well as details of the SAS code.

The 1984-1988 dietary and cardiovascular disease risk factor profiles of the Framingham Offspring-Spouse population (n = 3787 Framingham males and females, 22-79 years) were compared to earlier estimates from the 1976-1980 NHANES II and 1977-1978 USDA Nationwide Food Consumption surveys. The goals were to assess whether differences exist among population estimates, to determine whether national population-based nutrition recommendations for cardiovascular disease risk reduction are appropriately targeted, and to identify focus areas for future preventive nutrition interventions. Overall, population mean levels of cardiovascular disease risk factors were high but mean total cholesterol and blood pressure levels and rates of dyslipidaemia were lower in Framingham men and women and hypertension appeared higher in Framingham compared with NHANES II. Severe overweight appeared more prevalent in Framingham men but similar in Framingham women in comparison with NHANES. Population estimates of total fat (36-41% of calories) and saturated fat (12.5-13.7% of calories) intakes were higher and carbohydrate intakes were lower (40-46% of calories) than current recommended levels. Dietary cholesterol and sodium intakes in Framingham women appeared to have reached recommended levels but were high in men. While the goals of current nutrition recommendations remain appropriate, future population-based preventive nutrition interventions to lower cardiovascular disease risk need to emphasize weight reduction, lowering intakes of foods rich in animal and plant fats, increases in dietary sources of complex carbohydrates, fibre and micronutrients, and lower sodium intakes, particularly in adult men.

Objective: This study examined static and time-varying risk factors for perpetration of intimate partner violence (IPV) among men in treatment for alcohol use disorders. Method: Participants were 178 men diagnosed with alcohol abuse or dependence and their partners. Most (85%) of the men were European American; their average age was 41.0 years. Participants completed measures assessing initial alcohol problem severity, baseline beliefs related to alcohol use, antisocial personality characteristics, alcohol and drug use, relationship adjustment, and IPV. Results: According to couples' reconciled reports, 42% of participants perpetrated IPV at baseline. Among this group, the IPV recurrence rate was 43% at 6-month follow-up and 36% at 12-month follow-up. For participants without IPV perpetration at baseline, new incidence of IPV was 15% and 7% at the 6-month and 12-month follow-up points, respectively. Fixed marker predictors of IPV rates included baseline alcohol problem severity variables, baseline beliefs related to alcohol use, and antisocial personality characteristics. Variable risk factor predictors included alcohol and drug use variables, relationship adjustment factors, and anger. Alcohol use variables and anger were associated with new incidents of IPV among those without reported IPV at baseline only. Conclusions: Findings suggest that assessing and monitoring IPV occurrence by both partners is important for men in treatment for alcohol use disorders. Results indicate vulnerability factors that may identify individuals at risk for IPV and provide targets for IPV prevention among those with alcohol use disorders. These findings can aid in the development of more comprehensive models that more precisely predict IPV. (PsycINFO Database Record (c) 2010 APA, all rights reserved). Language: en

Chest illnesses commonly cause morbidity in persons with chronic spinal cord injury. Risk factors remain poorly characterized because previous studies have not accounted for factors other than spinal cord injury.Between 1994 and 2005, 403 participants completed a respiratory questionnaire and underwent spirometry. Participants were contacted at a median of 1.7 yrs [interquartile range: 1.3-2.5 yrs] apart over a mean (SD) of 5.1 +/- 3.0 yrs and asked to report chest illnesses that had resulted in time off work, spent indoors, or in bed since prior contact.In 97 participants, there were 247 chest illnesses (0.12/person-year) with 54 hospitalizations (22%). Spinal cord injury level, completeness of injury, and duration of injury were not associated with illness risk. Adjusting for age and smoking history, any wheeze (relative risk = 1.92; 95% confidence interval: 1.19, 3.08), pneumonia or bronchitis since spinal cord injury (relative risk = 2.29; 95% confidence interval: 1.40, 3.75), and physician-diagnosed chronic obstructive pulmonary disease (relative risk = 2.17; 95% confidence interval: 1.08, 4.37) were associated with a greater risk of chest illness. Each percent-predicted decrease in forced expiratory volume in 1 sec was associated with a 1.2% increase in risk of chest illness (P = 0.030).In chronic spinal cord injury, chest illness resulting in time spent away from usual activities was not related to the level or completeness of spinal cord injury but was related to reduced pulmonary function, wheeze, chronic obstructive pulmonary disease, a history of pneumonia and bronchitis, and smoking.

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

We have developed an on-line game, built around a simple simulator, as an innovative approach to mitigate the time and budget constraints that hinder the development of engineering expertise within a typical one-semester course. Students playing the game, as an alternative to calculation-based homework sets, develop a rich empirical understanding of the engineering principles of interest. A variety of gaming features such as real-life role-playing, competition, and graphically amplified results transform a Matlab-based simulator from being merely a sophisticated calculator into a learning tool that motivates exploration and provides rapid meaningful feedback to real-life engineering design challenges. As with many engineering projects, solutions are obtained by adjusting a variety of interrelated parameters within a set of physical constraints to satisfy a threshold condition. A comparison of a player's solution to an optimal solution provides a quantitative mechanism through which feedback can be easily provided, a competitive factor for either personal accomplishment or group bragging rights, and motivation to pursue the optimal solution. Decisions required during the game engage learning at the advanced level of comparisons and analyses. A digital record of the students' interaction with the game enables an innovative mechanism for learning assessment.