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Serum angiotensin converting enzyme (ACE) levels are higher in patients with diabetes mellitus than in many others. Techniques are available to grade different degrees of diabetic retinopathy, which can demonstrate a relationship between ACE and diabetic retinopathy. In this study, patients with diabetic retinopathy had higher serum ACE levels (6.3 +/- 0.2) than nondiabetic patients (4.3 +/- 0.5) (p0.001). In addition, the mean serum ACE level in diabetic patients with nonproliferative retinopathy (5.55 +/- 0.4) was less than that in diabetic patients with proliferative retinopathy (6.63 +/- 0.25) (p = 0.02). Due to the variability in individual serum ACE levels and the frequent use of ACE inhibitors by hypertensive diabetics, these techniques are not suitable for retinopathy screening programs. However, the graded relationship demonstrated by these data may have relevance for the pathophysiology of diabetic retinopathy.

Background— The prompt administration of coronary reperfusion therapy for patients with an evolving acute myocardial infarction (AMI) is crucial in reducing mortality and the risk of serious clinical complications in these patients. However, long-term trends in extent of prehospital delay and factors affecting patient's care-seeking behavior remain relatively unexplored, especially in men and women of different ages. The objectives of this study were to examine the overall magnitude and 20-year trends (1986 to 2005) in duration of prehospital delay in middle-aged and elderly men and women hospitalized with AMI. Methods and Results— The study sample consisted of 5967 residents of the Worcester, Mass, metropolitan area hospitalized at all greater Worcester medical centers for AMI between 1986 and 2005 who had information available about duration of prehospital delay. Compared with men Conclusions— Our results suggest that duration of prehospital delay in persons with symptoms of AMI has remained essentially unchanged during the 20-year period under study and elderly individuals are more likely to delay seeking timely medical care than younger persons.

BACKGROUND: A limited number of studies have examined the age and sex differences, and potentially changing trends, in cardiac medication and procedure use in patients hospitalized with an acute coronary syndrome (ACS). METHODS: Using data from a large multinational study, we examined the age and sex differences, and changing trends (1999-2007) therein, in the hospital use of evidence-based therapies in patients hospitalized with an ACS using data from the Global Registry of Acute Coronary Events (n=50 096). RESULTS: After adjustment for several variables, in comparison with men below 65 years, patients in other age-sex strata had a significantly lower odds of receiving aspirin [odds ratios (ORs) for men 65-74, 75-84, and >or=85 years, women or=85 years were 0.86, 0.84, 0.72, 0.80, 0.86, 0.68 and 0.46, respectively], angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ORs, 1.08, 1.01, 0,71, 0.83, 0.90, 0.89, and 0.63), beta blockers (ORs, 0.66, 0.52, 0.53, 0.67, 0.54, 0.53, and 0.52), statins (ORs, 0.72, 0.49, 0.29, 0.82, 0.68, 0.44, and 0.22), and undergoing coronary artery bypass graft surgery or a percutaneous coronary intervention (ORs, 0.79, 0.53, 0.21, 0.64, 0.57, 0.38, and 0.13) during their acute hospitalization. Age and sex differences in the receipt of these therapies remained relatively unchanged during the period under study. CONCLUSION: Although there were increasing trends in the use of evidence-based medications and cardiac procedures over time, important gaps in the utilization of effective cardiac treatment modalities persist in elderly patients and younger women.

PURPOSE Colorectal cancer (CRC) screening remains underutilized. The objective of this study was to examine the impact of primary care and economic barriers to health care on CRC testing relative to the 2001 Medicare expansion of screening coverage. METHODS Medicare Current Beneficiary Survey data were use to study community-dwelling enrollees aged 65 to 80 years, free of renal disease and CRC, and who participated in the survey in 2000 (n = 8,330), 2003 (n = 7,889), or 2005 (n = 7,614). Three outcomes were examined: colonoscopy/sigmoidoscopy within 5 years (recent endoscopy), endoscopy more than 5 years previously, and fecal occult blood test (FOBT) within 2 years. RESULTS Endoscopy use increased and FOBT use decreased during the 6-year period, with no significant independent differences between those receiving care from primary care physicians and those receiving care from other physicians. Beneficiaries without a usual place of health care were the least likely to undergo CRC testing, and that gap widened with time: adjusted odds ratio (AOR) = 0.27 (95% confidence interval [CI], 0.19–0.39) for FOBT, and AOR = 0.35 (95% CI, 0.27–0.46) for endoscopy in 2000 compared with AOR = 0.18 (95% CI, 0.11–0.30) for FOBT and AOR = 0.22 (95% CI, 0.17–0.30) for endoscopy in 2005. Disparities in use of recent endoscopy by type of health insurance coverage in both 2000 and 2005 were greater for enrollees with a high school education or higher than they were for less-educated enrollees. There were no statistically significant differences by delayed care due to cost after adjustment for health insurance. CONCLUSION Despite expanding coverage for screening, complex CRC screening disparities persisted based on differences in the usual place and cost of health care, type of health insurance coverage, and level of education.

Background— Data from clinical trials suggest that short-term mortality in outpatients presenting with pulmonary embolism (PE) is low and that outpatient therapy may be appropriate. However, subjects enrolled in these studies may not be representative of patients seen in the community setting. Methods and Results— The medical records of residents from Worcester, Mass, with International Classification of Disease, Ninth Edition , codes consistent with potential venous thromboembolism during 1999, 2001, and 2003 were independently validated and reviewed by trained abstractors. A total of 305 patients presented with PE from the outpatient setting. The rates of recurrent PE, major bleeding, mortality, or occurrence of any 1 of these end points at 90 days were 1.4%, 9.5%, 11.1%, and 20.1%, respectively. Patients with a history of congestive heart failure, recent intensive care unit discharge, cancer, severe infection, systolic blood pressure Conclusions— In the present population-based study, morbidity and mortality after outpatient PE were much higher than what was observed in clinical studies. Our findings raise questions about broad-based outpatient treatment of PE in the community setting. In our study, comorbid conditions and recent illness were important determinants of adverse outcomes, suggesting that these variables should be carefully considered before embarking on outpatient therapy of PE.

Objective.To develop and validate a modified version of the Disease Activity Score with 28 joint count (mDAS28), for use in epidemiological research, when acute-phase reactant values are unavailable.Methods.In a cross-sectional development cohort (5729 patients), statistically significant predictors of the logarithm of erythrocyte sedimentation rate (lnESR) were identified. After computation of the mDAS28, a cross-sectional validation cohort (5578 patients) was used to evaluate internal, criterion, and construct validities. The ability of the mDAS28 to discriminate between disease states was also assessed. A second validation cohort (longitudinal, 336 pairs of patient visits) was used to assess sensitivity to change.Results.Significant predictors of lnESR included tender and swollen joints with 28 counts, patient’s and physician’s assessments of global health, and patient’s assessment of pain (visual analog scale 0–100 mm) and a physical function (modified Health Assessment Questionnaire 0–3; mHAQ). Satisfactory internal validity (α = 0.72) and strong criterion validity compared to the DAS28, the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI) (r = 0.87–0.96) were found. Predictive validity was demonstrated by good correlation with the mHAQ (r = 0.58). The mDAS28 showed substantial agreement with the DAS28, SDAI, and CDAI in discriminating between disease states (κ = 0.70–0.77) and moderate to substantial agreement between response levels (κ = 0.52–0.73). Both mDAS28 and DAS28 measures classified patients similarly in remission compared to the SDAI and CDAI. The mDAS28 was superior in detecting change (standardized response mean = 0.58) followed by the DAS28, CDAI, and SDAI.Conclusion.The mDAS28 is a valid and sensitive tool to assess disease activity in epidemiological research, as an alternative to the DAS28, when acute-phase reactant values are unavailable.

Objective Liver function test (LFT) elevations are reported with the use of tumour necrosis factor inhibitors (TNF-Is). The aim of this study was to compare LFT elevations in patients with rheumatoid arthritis receiving adalimumab (ADA), etanercept (ETN) or infliximab (INF) enrolled in the Consortium of Rheumatology Researchers of North America from October 2001 to March 2007. Methods Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels >1× upper limit of normal (ULN) were considered elevations and ALT/AST levels >2× ULN were considered abnormalities. Treatments included TNF-Is, methotrexate (MTX), leflunomide and other disease-modifying antirheumatic agents (DMARDs). Patients were censored after their first LFT elevation. Three analytical models were evaluated: (1) individual TNF-I vs non-biological DMARDs (primary model); (2) individual TNF-I plus MTX vs MTX monotherapy; and (3) limited to new users of individual TNF-I vs non-biological DMARDs. ORs for LFT elevations were estimated using generalised estimating equation logistic regression. Results 6861 patients (ADA: 849; ETN: 1383; INF: 1449) with 22 522 determinations were analysed. LFT elevations >1× ULN with TNF-I use were seen in 5.9% of AST/ALT determinations and abnormalities >2× ULN in 0.77%. In the primary model the adjusted ORs for LFT elevations >1× ULN were ADA 1.35 (95% CI 1.09 to 1.66), ETN 1.00 (95% CI 0.83 to 1.21) and INF 1.58 (95% CI 1.35 to 1.86). For 2× ULN, adjusted ORs were ADA 1.72 (95% CI 0.99 to 3.01), ETN 1.10 (95% CI 0.64 to 1.88) and INF 2.40 (95% CI 1.53 to 3.76). Similar results were obtained in other models. Conclusion The overall incidence of LFT elevations >1× ULN with TNF-I use was uncommon and abnormalities >2× ULN were rarely observed. Significant differences were most consistently observed with INF, less commonly with ADA and were not observed with ETN compared with comparator DMARDs.

OBJECTIVE: The goal was to characterize the early course of nicotine dependence. METHODS: Data were collected from 1246 sixth-graders in a 4-year (2002–2006) prospective study using 11 individual interviews. Subjects were monitored for 10 symptoms of dependence by using the Hooked on Nicotine Checklist. The bidirectional prospective relationship between the intensity of dependence (number of symptoms) and smoking frequency was examined by using cross-lagged analyses. RESULTS: Of the 370 subjects who had inhaled from a cigarette, 62% smoked at least once per month, 53% experienced dependence symptoms, and 40% experienced escalation to daily smoking. Smoking frequency predicted the number of dependence symptoms at the next interview, and the number of symptoms predicted reciprocally the observed escalation in smoking frequency. Monthly smoking was a strong risk factor for the development of symptoms (adjusted hazard ratio: 9.9 [95% confidence interval: 6.6–14.8]). A strong desire to smoke was the most common presenting symptom, typically followed by the appearance of symptoms of nicotine withdrawal, escalation to daily smoking, and then reports of feeling addicted or difficulty controlling smoking. The appearance of any dependence symptom increased the risk for daily smoking (hazard ratio: 6.81 [95% confidence interval: 4.4–10.5]). CONCLUSIONS: Nondaily tobacco use triggers the emergence of nicotine dependence. Early dependence symptoms promote escalation in smoking frequency and, reciprocally, more-frequent smoking accelerates the appearance of additional symptoms of dependence. As this positive feedback progresses, the symptoms of nicotine dependence present in a typical sequence, with some individual variation.

Compared to screening for partner violence, screening for childhood physical and sexual abuse among adult patients has received little attention, despite associated adverse health consequences. The objective of this exploratory study was to describe the practices, skills, attitudes, and perceived barriers of a large sample of family physicians in screening adult patients for childhood sexual or physical abuse.Surveys were mailed to the 833 members of the Massachusetts Academy of Family Physicians in 2007 eliciting information about screening practices. Factors associated with routine or targeted screening among adult primary care patients were evaluated.Less than one-third of providers reported usually or always screening for childhood trauma and correctly estimated childhood abuse prevalence rates; 25% of providers reported that they rarely or never screen patients. Confidence in screening, perceived role, and knowledge of trauma prevalence were associated with routine and targeted screening. Women and physicians reporting fewer barriers were more likely to routinely screen adult patients.Despite the 20%-50% prevalence of child abuse exposure among adult primary care patients, screening for childhood abuse is not routine practice for most physicians surveyed; a large subgroup of physicians never screen patients. Study findings draw attention to a largely unexplored experience associated with considerable health care costs and morbidity. Results highlight the need to develop training programs about when to suspect trauma histories and how to approach adult patients.

The present study was undertaken to determine whether an acute physiological increase in plasma cortisol level had significant effects on alanine metabolism and gluconeogenesis within 3 hours in conscious, overnight-fasted dogs. Each experiment consisted of an 80-minute tracer and dye equilibration period, a 40-minute basal period, and a 3-hour experimental period. A primed, continuous infusion of [3-3H]glucose and continuous infusions of [U-14C]alanine and indocyanine green dye were initiated at the start of the equilibration period and continued throughout the experiment. Dogs were studied with (1) a hydrocortisone infusion ([CORT] 3.0 micrograms.kg-1.min-1, n = 5), (2) hydrocortisone infused as in CORT, but with pancreatic hormones clamped using somatostatin and basal intraportal replacement of insulin and glucagon (CLAMP+CORT, n = 5), or (3) saline infusion during a pancreatic clamp (CLAMP, n = 5). Glucose production and gluconeogenesis were determined using tracer and arteriovenous difference techniques. During CLAMP, all parameters were stable except for a modest 67% +/- 6% increase in gluconeogenic conversion of alanine to glucose and a 53% +/- 26% increase in gluconeogenic efficiency. When plasma cortisol levels were increased fourfold during CLAMP+CORT, there was no change in the concentration, production, or clearance of glucose. Gluconeogenic conversion of alanine to glucose increased 10% +/- 34% and gluconeogenic efficiency increased 65% +/- 43%, while net hepatic alanine uptake (NHAU) increased 60% +/- 19% and hepatic fractional extraction of alanine increased 38% +/- 12%. Cortisol did not cause an increase in the arterial glycerol level or net hepatic glycerol uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study we used a whole-room indirect calorimeter to evaluate the accuracy of self-reported food intake. Daily measured energy expenditure was compared with 2 weeks of self-reported food intake. Additionally, oxidation of each macronutrient was compared with its self-$$$reported intake to assess the accuracy of self-reported dietary composition. Participants (23 through 60 years old) were eight dietitians, eight subjects who were trained in keeping dietary records, and eight subjects who were not trained. Physical activity in the calorimeter was matched to usual daily physical activity. Overall, measured energy expenditure was approximately 200 kcal/day higher than reported metabolizable energy intake. However, this was the result primarily of a few subjects whose self-reported food intake was considerably below measured energy expenditure Subjects who were trained in record keeping did not differ from untrained subjects. Dietitians had the lowest difference between intake and expenditure; none of them had the large discrepancies between intake and expenditure seen in the other groups. In all groups, there was a much greater discrepancy between self-reported intake and oxidation of each macronutrient than between self-reported total energy intake and expenditure.

Joule for joule, dietary fat may promote obesity more than protein or carbohydrate. In this study we determined whether the addition of 50 g dietary fat to a standard breakfast would increase energy expenditure or fat oxidation during the immediate 6-h postprandial period or over the ensuing 18 h. We also determined whether subjects with a high level of aerobic physical fitness would show a greater increase in fat oxidation after the ingestion of the extra fat than would less fit subjects. Adding fat did not increase fat oxidation or energy expenditure either during the immediate 6-h postprandial period or over the following 18 h. This was true regardless of the subject's fitness level. Acutely, dietary fat ingested in excess of its usual rate of oxidation appears to be stored in the body. Being physically fit does not appear to provide an advantage in avoiding short-term storage of excess dietary fat.

To study the influence of diet composition on regulation of body weight, we fed 21 weight-stable subjects (11 lean, 10 obese) high-carbohydrate (HC) and high-fat (HF) diets for 1 wk each. Although diet composition was fixed, total energy intake was unrestricted. Subjects had a higher energy intake on the HF (11,039 +/- 2700 kJ/d) than on the HC (10,672 +/- 2617 kJ/d) diet (P less than 0.05), but energy expenditure was not different between diets. On day 7 of the HC diet, carbohydrate (CHO) oxidation was significantly related to CHO intake with the slope of the regression line 0.99, suggesting that overall CHO balance was near zero. However, the slope of the regression line was greater for obese than for lean subjects. On day 7 of the HF diet, fat oxidation was significantly related to fat intake but the slope of the line was 0.50, suggesting that overall fat balance was positive. However, this relationship was due entirely to lean subjects, with obese subjects showing no relationship between fat intake and oxidation.

SummaryBleeding is the most frequent complication of antithrombotic therapy for venous thromboembolism (VTE). However, little attention has been paid to the impact of bleeding after VTE in the community setting. The purpose of this investigation was to describe the incidence rate of bleeding after VTE, to characterize patients most at risk for bleeding, and to assess the impact of bleeding on rates of recurrent VTE and all-cause mortality. The medical records of residents of the Worcester (MA, USA) metropolitan area diagnosed with ICD-9 codes consistent with potential VTE during 1999, 2001, and 2003 were individually validated and reviewed by trained data abstracters. Clinical characteristics, acute treatment, and outcomes (including VTE recurrence rates, bleeding rates, and mortality) over follow-up (up to 3 years maximum) were evaluated. Bleeding occurred in 228 (12%) of 1,897 patients with VTE during our follow-up. Of these, 115 (58.8%) had evidence of early bleeding occurring within 30 days of VTE diagnosis. Patient characteristics associated with bleeding included impaired renal function and recent trauma. Other than a history of prior VTE, the occurrence of bleeding was the strongest predictor of recurrent VTE (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.54–3.09) and was also a predictor of total mortality (HR 1.97; 95%CI 1.57–2.47). The occur-rence of bleeding following VTE is associated with an increased risk of recurrent VTE and mortality. Future study of antithrombotic strategies for VTE should be informed by this finding. Advances that result in decreased bleeding rates may paradoxically decrease the risk of VTE recurrence.

Objectives. To evaluate composite measures of response without acute-phase reactants in RA patients. Specifically, Clinical Disease Activity Index (CDAI)-derived response criteria were compared with the European League Against Rheumatism (EULAR) response criteria, and the modified ACR (mACR) response criteria were compared to the ACR response criteria. Methods. Data from 10 108 RA patients enrolled in the Consortium of Rheumatology Researchers of North America registry were examined, including 649 patients initiating DMARD therapy. CDAI cut-off points for disease activity levels and responses were derived using receiver operating characteristic curves with the DAS28 and EULAR response criteria as gold standards. The κ-statistics were applied to assess agreement between CDAI-derived and EULAR-defined responses, as well as ACR20 and ACR50 with mACR20- and mACR50-defined responses, respectively. Results. For the components of the EULAR response, the derived CDAI cut-off points for DAS28 levels of 3.2 and 5.1 were 7.6 and 19.6, respectively. The derived CDAI cut-off points were 4.3 and 10.0 for DAS28 changes of 0.6 and 1.2, respectively. There were moderate to substantial agreements between CDAI-derived and EULAR responses (κ = 0.57–0.71). Agreement of ACR20 and ACR50 with mACR20 and mACR50 responses, respectively, was excellent (κ = 0.88–0.95). Conclusions. Agreement between composite measures of response without acute-phase reactants and standard measures ranged from moderate to excellent. The mACR20 and mACR50 criteria as well as CDAI-derived response criteria, can serve as composite measures of response in clinical practice and research settings without access to acute-phase reactants.

This study examined a wide array of clinical factors to evaluate their influence on fracture risk and T scores in women with rheumatoid arthritis (RA) and determine if women with RA who are at risk for osteoporosis (OP) are adequately treated with OP medications.Data from 8419 female RA patients participating in the Consortium of Rheumatology Researchers of North America registry from March 02, 2006 to August 15, 2006 was evaluated. Covariates included medication subgroups, demographic, and clinical parameters. Lumbar spine and hip T scores and fracture rates were studied in relation to the variables. Use of OP medications in patients with OP risk factors was also evaluated.Postmenopausal status and higher modified health assessment questionnaire score (mHAQ) had a negative effect on lumbar spine score,while marriage, education, and body mass index had a positive effect. A similar trend was found with hip T scores. Increase in overall fracture risk correlated with postmenopausal status, mHAQ, and prednisone use, while tumor necrosis factor monotherapy was associated with decreased overall fracture risk. mHAQ was also associated with nonhip/nonspine fractures. Eighty percent of patients had at least 1 risk factor for OP, but only 32% were on OP medications. Only 54% of patients with 3 risk factors were on OP medication.In RA, postmenopausal status, mHAQ, and prednisone use were associated with a higher overall fracture risk. Women with RA who were at risk for OP may have been inadequately treated with OP medications.

Objective:To examine the association of methotrexate (MTX) and tumour necrosis factor (TNF) antagonists with the risk of infectious outcomes including opportunistic infections in patients with rheumatoid arthritis (RA).Methods:Patients with RA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry prescribed MTX, TNF antagonists or other disease-modifying antirheumatic drugs (DMARDs) were included. The primary outcomes were incident overall and opportunistic infections. Incident rate ratios were calculated using generalised estimating equation Poisson regression models adjusted for demographics, comorbidities and RA disease activity measures.Results:A total of 7971 patients with RA were followed. The adjusted rate of infections per 100 person-years was increased among users of MTX (30.9, 95% CI 29.2 to 32.7), TNF antagonists (40.1, 95% CI 37.0 to 43.4) and a combination of MTX and TNF antagonists (37.1, 95% CI 34.9 to 39.3) compared with users of other non-biological DMARDs (24.5, 95% CI 21.8 to 27.5). The adjusted incidence rate ratio (IRR) was increased in patients treated with MTX (IRR 1.30, 95% CI 1.12 to 1.50) and TNF antagonists (IRR 1.52, 95% CI 1.30 to 1.78) compared with those treated with other DMARDs. TNF antagonist use was associated with an increased risk of opportunistic infections (IRR 1.67, 95% CI 0.95 to 2.94). Prednisone use was associated with an increased risk of opportunistic infections (IRR 1.63, 95% CI 1.20 to 2.21) and an increased risk of overall infection at doses >10 mg daily (IRR 1.30, 95% CI 1.11 to 1.53).Conclusions:MTX, TNF antagonists and prednisone at doses >10 mg daily were associated with increased risks of overall infections. Low-dose prednisone and TNF antagonists (but not MTX) increased the risk of opportunistic infections.

Objectives. We developed a method to evaluate geographic and temporal variations in community-level obesity prevalence and used that method to identify communities in Massachusetts that should be considered high priority communities for obesity control. Methods. We developed small-area estimation models to estimate community-level obesity prevalence among community-living adults 18 years or older. Individual-level data from the Behavioral Risk Factors Surveillance System from 1999 to 2005 were integrated with community-level data from the 2000 US Census. Small-area estimation models assessed the associations of obesity (body mass index ≥ 30 kg/m2) with individual- and community-level characteristics. A classification system based on level and precision of obesity prevalence estimates was then used to identify high-priority communities. Results. Estimates of the prevalence of community-level obesity ranged from 9% to 38% in 2005 and increased in all communities from 1999 to 2005. Fewer than 7% of communities met the Healthy People 2010 objective of prevalence rates below 15%. The highest prevalence rates occurred in communities characterized by lower income, less education, and more blue-collar workers. Conclusions. Similar to the rest of the nation, Massachusetts faces a great challenge in reaching the national obesity control objective. Targeting high-priority communities identified by small-area estimation may maximize use of limited resources.

Introduction:Potential hepatotoxicity associated with disease-modifying antirheumatic drugs (DMARDs) requires laboratory monitoring. In patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA), the incidence of elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) enzymes associated with methotrexate (MTX), leflunomide (LEF) and MTX+LEF versus other DMARDs was examined.Methods:Patients with RA and PsA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) initiating DMARDs were identified. Abnormalities were identified when either was 1- or 2-fold times above the upper limits of normal (ULN). Odds ratios (OR) between MTX/LEF dose and elevated ALT/AST enzymes were estimated using generalised estimating equations. Interaction terms for use of MTX+LEF quantified the incremental risk of the combination compared with each individually.Results:Elevated ALT/AST levels (>1× ULN) occurred in 22%, 17%, 31% and 14% of patients with RA receiving MTX, LEF, MTX+LEF or neither, respectively; elevations were 2.76-fold (95% CI 1.84 to 4.15) more likely in patients with PsA. Elevations >2× ULN occurred in 1–2% of patients on MTX or LEF monotherapy compared with 5% with the combination. After multivariable adjustment and compared with either monotherapy, the combination of MTX and LEF was associated with a greater risk according to MTX dose used as part of the combination: MTX 10–17.5 mg/week, OR 2.91 (95% CI 1.23 to 6.90); MTX ⩾20 mg/week, OR 3.98 (95% CI 1.72 to 9.24).Conclusions:Abnormal ALT/AST levels developed in 14–35% of patients with RA or PsA initiating DMARD therapy. The risks were incrementally greater in those with PsA and in those receiving MTX (⩾10 mg/day) + LEF. These findings should help inform monitoring for potential hepatotoxicity in these patient populations.

The purpose of this study was to examine the effect of alterations in diet composition on energy expenditure and nutrient balance in humans. Eight adults (three men, five women) ate a high-carbohydrate (60% of calories from carbohydrate) and a high-fat (60% of calories from fat) diet for 7 d each according to a randomized, crossover design. Six subjects were studied for an additional week on a mixed diet (45% of calories from fat). For each subject, total caloric intake was identical on all diets and was intended to provide the subject's maintenance energy requirements. All subjects spent days 3 and 7 of each week in a whole-room indirect calorimeter. Diet composition did not affect total daily energy expenditure but did affect daily nutrient oxidation by rapidly shifting substrate oxidation to more closely reflect the composition of the diet. These results show that diet composition can affect substrate oxidation without producing measurable effects on total energy expenditure.

The objective of this study was to determine the short- and long-term radiographic, physiologic and histologic changes elicited in the lung of rabbits following the aspiration of commonly used radiographic contrast agents. All agents used, including nonionic agents, caused radiographically evident pulmonary edema which cleared by 24 hours. The contrast materials with higher osmolality, viscosity, and iodine content elicited the greatest physiologic and pathologic changes. No differences were found between an ionic and a nonionic agent with similar viscosities and iodine content, despite a lower osmolality in the nonionic agent. No contrast agent is innocuous when introduced into the lung.

Twenty-five patients with cancer of the uterus underwent transvaginal sonography (TVS) to assess depth of myometrial invasion. All scans were performed with a 5.0-MHz curvilinear array probe (Toshiba, Inc., Tustin, CA) within 1 week of hysterectomy. In 21 cases (84%) sonography correctly predicted the depth of invasion (within 15% of actual). Only one of three cases with cervical involvement was detected. Transvaginal sonography can accurately detect depth of myometrial invasion and is well suited as a screening test to detect high-risk patients for consultation or referral.

Objective The study objective was to investigate responsiveness according to whether patients satisfy eligibility criteria from randomized controlled trials of tumor necrosis factor (TNF) antagonists in a multicentered US cohort. Methods Biologic-naive patients with rheumatoid arthritis who were prescribed TNF antagonists (n = 465) in the Consortium of Rheumatology Researchers of North America registry were included. Patients were stratified by whether they met eligibility criteria from 3 major TNF antagonist trials. Two cohorts were examined: Cohort A (n = 336) included patients with complete American College of Rheumatology response criteria except acute phase reactants, and cohort B (n = 129) included patients with complete response criteria. Study outcomes included modified American College of Rheumatology 20% and 50% improvement responses (cohort A) and standard American College of Rheumatology improvement (cohort B). Results A minority of patients (5.4%-19.4%) prescribed TNF antagonists met trial eligibility criteria and predominantly had high disease activity (78.5%-100%). For patients who met eligibility criteria in cohort A, rates of 20% improvement (52.3%-63.6%) and 50% improvement (30.8%-45.5%) were achieved. Among patients failing to meet eligibility criteria, rates of 20% improvement (16.2%-20.4%) and 50% improvement (8.9%-10.8%) were consistently inferior (P Conclusion This multicentered US cohort study demonstrates that the majority of patients receiving TNF antagonists would not meet trial eligibility criteria and achieve lower clinical responses. These findings highlight the tradeoff between defining treatment responsive populations and achieving results that can be generalized for broader patient populations.

The purpose of this study is to determine the effect at 48 months of a screening and brief patient-centered physician- and nurse practitioner-delivered intervention implemented during a routine primary care visit on the reduction of alcohol consumption by high-risk drinkers.Participants seen in primary care practices previously randomized to special intervention (SI) or usual care (UC) were reconsented for long-term follow-up. From the initial cohort, 63% reconsented to participate and provided follow-up at 48 months between November 1996 and March 2002. The data for this paper were analyzed in June 2004.At 48 months, SI participants maintained significant reductions in drinks per week seen at 6 and 12 months. However, there were no longer significant differences in drinks per week, binges per month, percentage of low-risk drinking, relapse rates, and new quits between the SI and UC groups at 48 months that had been seen at earlier follow-up. There was a significant effect of prior low-risk drinking status at 12 months; those who were low-risk drinkers at 12 months were more likely to stay low-risk drinkers at 48 months regardless of treatment group.With a single brief intervention, SI participants had significantly greater reductions in their drinking levels at 6 and 12 months compared to UC participants and maintained the lower-risk levels at 48 months resulting in a reduction in health risk exposure time. However, the significant group differences in treatment effect seen in earlier follow-ups were not maintained.

Background:Results from a statewide telephone survey of walking showed that the average adult in Colorado takes 6804 steps/d, and that steps/d were negatively associated with body mass index. No similar data exist for children.Methods:As part of the Colorado survey, demographic information was obtained from parents for 116 children. A subsample of 59 children and adolescents (age 10 to 17 y) agreed to wear a step counter for four consecutive days.Results:The youth reported taking an average of 7902 steps/d. There was a trend for children’s steps/d to be positively associated with parents’ steps/d and negatively associated with TV watching.Conclusion:This sample of children is not large enough to be considered a representative sample of Colorado youth, but this cross-sectional study provides some much needed information about steps/d in children and generates some interesting hypotheses about steps/d and other measures of health and overweight.

The relative efficacy of anti-IL-2 receptor antibodies (IL2R Abs) and antilymphocyte antibodies in preventing acute rejection and improving graft survival after renal transplantation is poorly defined. In particular, the benefits of these agents in specific subgroups, such as recipients with different degrees of HLA mismatch, are unknown. Using the SRTR database, we compared IL2R Abs to no induction and to antilymphocyte antibody induction in 48 948 first renal transplant recipients in the United States between 1998 and 2003 with respect to acute rejection and graft failure. IL2R Abs decreased acute rejection at 6 months (OR: 0.81(0.75-0.87)), and reduced graft failure (HR: 0.90(0.84-0.95)), compared to no induction over a follow-up of 1059 days. Compared to IL2R Abs, antilymphocyte Abs were associated with decreased acute rejection (OR: 0.90(0.83-0.99)) at 1 year, but were not associated with improved graft survival (OR: 1.08(1.00-1.18)) over a follow-up of 732 days. The benefit of IL2R Abs in reducing acute rejection increased significantly with greater HLA mismatch (p = 0.007). IL2R Abs remain an important option in the management of renal transplant patients, and may be particularly useful in specific patient subsets.

Is anti-tumor necrosis factor therapy effective in reducing uveitis flares in patients with spondyloarthropathies?

In the United States, tobacco treatment specialists are professionals from a variety of backgrounds trained to deliver moderate to intensive evidence-based tobacco treatment in a variety of settings across the country. This paper reports the results of a study that examined the extent to which specialists participating in a larger study adhered to clinical practice guidelines for tobacco dependence using standardized patient assessments. A total of 64 tobacco treatment specialists completed a survey and two audiotaped standardized patient interviews. Overall, 41% and 31% of tobacco treatment specialists demonstrated 80% or more of session content and interviewing skills assessed, respectively, when required to demonstrate the skill in both standardized patient interactions. These rates increased to 85% and 56%, respectively, when using the less stringent criteria of demonstrating the skill in at least one of the two standardized patient interactions. Tobacco treatment specialists who had attended a greater number of types of tobacco treatment training exhibited both greater coverage of session content (p

Background Among patients who have failed a prior TNF agent, there is little data to inform prescribing decisions for the next biologic. Objectives We sought to perform a head to head comparison of the effectiveness of tocilizumab (TCZ) versus abatacept (ABA) among RA patients with previous anti-TNF exposure using data from a multi-center observational registry within the United States (Corrona, LLC). Methods We identified RA patients between 4/2/2009 through 5/2/14 who had discontinued at least 1 anti-TNF and initiated either TCZ or ABA, with no prior use of either of these two drugs, were not in remission or low disease activity based on the Clinical Disease Activity Index (CDAI) at the time of initiation, and had follow-up at 6 months (TCZ=266; ABA=663). Propensity score (PS) matching (1:1 match) based on demographics, comorbid conditions and RA disease characeristics was utilized to control for imbalances between treatment groups stratified by the number of prior anti-TNF agents. This resulted in 266 matched (TCZ:ABA) pairs of which 45% had 1 and 55% ≥2 prior TNFs. Treatment response was measured at 6 months after initiation based on mean change in disease activity using the CDAI, and change in mHAQ. Secondary analyses included achievement of low disease activity (CDAI ≤10). For any patients who switched from ABA or TCZ to a new biologic, last observation carried forward (LOCF) prior to the switch was applied. Change in prednisone use was well as initiation or discontinuation of a nonbiologic disease modifying anti-rheumatic drug (DMARD) over the study period was also examined. Regression analysis was performed with the matched pairs as a random effect. Results There were 266 TCZ initiators matched to 266 ABA initiators. Most patients were female (74-75%) with a mean age of 57 years, mean disease duration of 10-11 years and mean CDAI of 28. There were no standardized differences >0.10 between the 2 groups for demographics, insurance, comorbidities, RA disease characteristics, disease activity, functional status, medication use, concomitant prednisone use, and number of prior biologics. There were no significant differences between the two groups in terms of the primary and secondary outcomes (Table). Additionally there were no significant differences between TCZ vs. ABA in terms of prednisone use (dose escalation [14.0% vs. 12.5%]) and dose reduction [18.9% vs. 18.6%]) and nonbiologic DMARD use (rates of initiation [11.3% vs. 14.3%] and discontinuation [13.1% vs. 15.0%]). Conclusions Both TCZ and ABA were associated with substantial improvements in disease activity at 6 months and had comparable effectiveness in this difficult to treat population of RA patents. Longer term outcomes will be needed in order to determine best strategies in TNF inadequate responder patients with RA in the US. Acknowledgements This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Astra Zeneca, BMS, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest L. Harrold Grant/research support from: Corrona, LLC., G. Reed Employee of: Corrona, LLC., D. Solomon Grant/research support from: Amgen, Lilly and Corrona, J. Curtis Grant/research support from: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, Abb Vie, Consultant for: Roche/Genentech, UCB, Janssen, Corrona, Amgen, Pfizer, BMS, Crescendo, Abb Vie, M. Liu Employee of: Corrona, LLC., J. Greenberg Shareholder of: Corrona, LLC., Consultant for: AstraZeneca, Celgene, Novartis and Pfizer, Employee of: Corrona, LLC., J. Kremer Shareholder of: Corrona, LLC., Consultant for: AbbVie, Amgen, BMS, Genentech, Lilly, Pfizer, Employee of: Corrona, LLC.

Background Current treatment recommendations recommend accelerating therapy when rheumatoid arthritis (RA) patients (pts) reach moderate to severe disease activity. Objectives To assess whether initiating biologics among pts with moderate RA results in better clinical outcomes compared with pts with severe RA. Methods Data (10/2001–03/2013) were from the Corrona RA registry. The study population included RA pts who initiated a biologic for the first time and had 1 and 2 years (yrs) of follow-up and a Clinical Disease Activity Index (CDAI) score >10 at the time of biologic initiation. For analysis, pts were divided into 2 groups: those with moderate disease activity (10 22). Clinical outcomes were percent of pts in remission (CDAI≤2.8), percent of pts with low disease activity (CDAI≤10), mean change in CDAI and modified HAQ (mHAQ), and mean cumulative CDAI and mHAQ (area under the curve standardized by length of follow-up computed for each pt). Outcomes were compared using Mann-Whitney-Wilcoxon rank tests and Fisher9s exact test. A mixed-effects linear regression model was used to estimate mean CDAI and mHAQ over time for both groups. Results 1596 (moderate:779;severe:817) and 1269 (moderate:634;severe:635) RA pts with 1 and 2 yrs of follow-up, respectively, were identified. Baseline characteristics (eg. age, sex, duration of RA, yr of initiation) for the 1-yr cohort were similar between moderate and severe disease activity initiators except for measures related to disease activity: median CDAI (16.1 vs 31.1), mHAQ (0.30 vs 0.60), tender joint count (4.0 vs 11.0), and swollen joint count (5.0 vs. 11.0); all P Conclusions This real-world analysis showed that pts with moderate disease activity who initiate treatment with biologics achieve lower levels of disease activity significantly more than those with severe disease. This information will be helpful to clinicians in a T2T setting where achieving a target is the desired outcome. Acknowledgements The Corrona LLC RA registry has been supported through contracted subscriptions in the last 2 yrs by AbbVie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Lilly, Novartis, Pfizer and UCB. The design, study conduct, and financial support for the study was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. Joann Hettasch PhD of Arbor Communications Inc provided medical writing and editing services in the development of this abstract. Financial support for these services was provided by AbbVie. Disclosure of Interest A. Kavanaugh Grant/research support from: AbbVie, Amgen, Janssen, L.P., UCB, J. Greenberg Shareholder of: Corrona, LLC., Consultant for: Astra Zeneca, Celgene, Pfizer, Novartis, Employee of: Corrona, LLC., G. Reed Employee of: Corrona, LLC., J. Griffith Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc., A. Friedman Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc., K. Saunders Employee of: Corrona, LLC., A. Ganguli Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc.

Background Biologic agents are effective therapies for rheumatoid arthritis (RA). It has been suggested that biologic taper and discontinuation may be a viable option for a subset of RA patients whose disease activity is in control. Objectives The objective of this study was to describe the outcomes of biologic withdrawal in RA in the real world setting. Methods Data from the Corrona registry were used. RA patients who discontinued biologic therapies after ≥1 year of continuous use, and who had no additional biologic use for the subsequent 12 months were included. Disease activity were evaluated at baseline (time of biologic discontinuation), 3, 6 and 12 months post biologic discontinuation. The percentage of patients who had at least 1 flare (i.e. an increase in Clinical Disease Activity Index (CDAI) by ≥16.11, 2) off biologic therapy was assessed. Results Of the 120 included patients: 97 (80.8%) were female; age (mean ± SD) was 58.7±12.5 years, CDAI was 15.2±15.1, ESR was 48.7±34.3, CRP was 9.1±10.2 and HAQ 1.0±0.7, all at baseline. After biologic discontinuation, 8.3% of patients had at least 1 flare by 3 months, 30% by 6 months and 41.7% by 12 months. Conclusions In the current study using data from Corrona, biologic discontinuation in RA was associated with flares whose rates increase over time. References Yoshida et al. Annals of the rheumatic diseases (2013). Ranganath, et al. Annals of the rheumatic diseases (2007). Acknowledgements The Corrona, LLC. RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, Astra Zeneca, BMS, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. The design, study conduct, and financial support for the study was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. Disclosure of Interest D. Pappas Employee of: Corrona, LLC., Paid instructor for: Novartis, G. Reed Employee of: Corrona, LLC., Y. Bao Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc., S. Grant Employee of: Fred Hutchinson Cancer Center, V. Garg Shareholder of: AbbVie, Inc., Employee of: AbbVie, Inc.

Background A treat-to-target (T2T) approach to the care of patients with rheumatoid arthritis (RA) has been advocated, which involves regular assessment of disease activity using validated metrics, frequent follow-up visits for patients with moderate to high disease activity, and escalation of therapy when patients have inadequate therapeutic response as assessed by standard disease activity scores. Objectives The goal of this abstract is to examine whether cluster randomization will result in comparable patients for a behavioral intervention trial designed to assess the impact of implementing a structured T2T approach vs routine care. Methods This trial cluster-randomized 31 rheumatology practices based on practice size from the Corrona network of private and academic rheumatology sites to either the T2T intervention (n=16) or usual care (n=15) between July 29, 2011, and July 30, 2013. RA patients with moderate or high disease activity, defined as Clinical Disease Activity Index (CDAI) >10, and no contraindication to T2T were enrolled by the practices and followed for 12 months. In the T2T group, medications were to be accelerated based on disease activity levels with visits occurring as frequently as monthly in those with active disease. Treatment acceleration was defined as a new initiation or increase to the dose or frequency of a prescribed biologic or non-biologic DMARD, or changing route of methotrexate from oral to subcutaneous. In contrast, the usual care subjects were seen at least every 3 months with medication changes per the treating provider. The co-primary endpoints were achievement of low disease activity, defined as CDAI of ≤10, and an assessment of feasibility of implementing T2T in rheumatology practices (e.g., rates of treatment acceleration, frequency of visits, time to next visit conditional on disease activity, and probability of acceleration conditional on disease activity). Results There were 249 patients enrolled from the T2T practices and 289 from usual care practices. The two groups were similar in terms of mean age, gender, and race but not for ethnicity (Table). Patients were also similar in terms of education level, employment status, insurance type and clinical features (disease duration, rheumatoid factor seropositivity, tender joint count, swollen joint count, disease activity, and patient pain); however, functional status was different. Both groups had similar proportions of subjects receiving prednisone and methotrexate as well as similar dosing for those taking these medications. Study retention at 12 months (time window is 9 to 15 months after enrollment) was 83% of the usual care subjects and 79% of the T2T subjects. Conclusions This cluster-randomized approach to implementing a behavioral intervention successfully identified similar patients for the two treatment arms for a study of T2T. Acknowledgements The Corrona T2T study is sponsored by Corrona, LLC, with support from a development and subscription agreement/contract with Genentech and additional support from AbbVie. Disclosure of Interest L. Harrold Employee of: University of Massachusetts Medical School, G. Reed Employee of: Corrona, LLC, J. T. Harrington Shareholder of: AbbVie, Amgen, BMS, GlaxoSmithKline, Johnson & Johnson, Pfizer and Roche, Consultant for: AbbVie, Amgen, Antares, AstraZeneca, Celgene, Horizon, Iroko, Pfizer, Roche and UCB, Speakers bureau: AbbVie, Amgen, Pfizer, Roche and UCB, C. Barr Employee of: Corrona, LLC, K. Saunders Employee of: Corrona, LLC, A. Gibofsky: None declared, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Novartis and Pfizer, Employee of: Corrona, LLC, A. John Employee of: Genentech, Inc, J. Devenport Employee of: Genentech, Inc, J. Kremer Shareholder of: Corrona, LLC, Grant/research support from: Genentech, Inc, Consultant for: Genentech, Inc, Employee of: Corrona, LLC

Background The goal of treatment for patients with rheumatoid arthritis (RA) is to reduce and maintain disease activity to low disease activity (LDA) or remission. However, there is little information available regarding the likelihood of sustained response once LDA/remission has been achieved, as well as what effect rituximab retreatment has on sustained response. Objectives The objective of this analysis was to examine factors associated with sustained response in patients with RA who were treated with rituximab in the US Corrona registry. Methods Patients with RA who initiated rituximab while in moderate or high disease activity (Clinical Disease Activity Index [CDAI] >10) and who subsequently achieved LDA/remission (CDAI ≤10) within 12 months of their last rituximab infusion were identified from the Corrona registry and included in this analysis. Patients were followed until they experienced loss of response (defined as CDAI >10), initiated another biologic or small molecule or exited from the registry. Covariates identified at the index date (when LDA/remission was achieved) included demographic and clinical characteristics, prior medications and concomitant steroid and conventional synthetic disease modifying anti-rheumatic drug (csDMARD) use. Covariates ascertained at the time of rituximab initiation included functional status, baseline CDAI, patient-reported pain and time to achieve LDA/remission. Time-varying covariates of interest included the rate of rituximab retreatment, as well as number of prednisone dose increases and initiations of csDMARDs over time. Survival analyses and Cox proportional hazard regression models were performed to estimate the overall likelihood of sustained response following rituximab treatment and associations between covariates of interest and sustained response. The primary estimate of interest was the hazard ratio or loss of response for rituximab retreatment. Results Of the 1184 patients who initiated rituximab and had ≥1 follow-up appointment in Corrona, a total of 306 patients subsequently achieved CDAI LDA/remission within 12 months of the last infusion. Most patients were female (75.8%) with a median (IQR) age of 60 (52-68) years and received prior csDMARDs (median [IQR], 2 [1-3]); over 84% of patients had received ≥2 prior biologics. The median (IQR) time to achieve LDA/remission was 5 (3-10) months. Of the 306 patients included in the final study population, 104 patients received rituximab retreatments at a median (IQR) rate of 1.01 (0.71-1.36) retreatments per year. Twelve months following achievement of LDA/remission, 49.2% of patients maintained this response. In unadjusted and adjusted models (Table), rituximab retreatment was associated with a significantly reduced likelihood of loss of response (45% reduction), while prednisone dose increases ≥7.5 mg and prior non-anti–tumor necrosis factor agent use increased it. Conclusions Retreatment with rituximab was associated with a significantly greater sustained response in patients who have achieved LDA/remission on the medication, while low to moderate prednisone increases and prior non-anti–tumor necrosis factor agent use reduced it. Acknowledgements This study is sponsored by Corrona, LLC. Disclosure of Interest L. Harrold Grant/research support from: Corrona, LLC, A. John Employee of: Genentech, Inc, G. Reed Employee of: Corrona, LLC, C. Karki Employee of: Corrona, LLC, R. Magner Employee of: University of Massachusetts Medical School, J. Kremer Shareholder of: Corrona, LLC, Grant/research support from: Genentech, Inc, Consultant for: Genentech, Inc, Employee of: Corrona, LLC, A. Shewade Employee of: Genentech, Inc, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Novartis and Pfizer, Employee of: Corrona, LLC

Dying cells stimulate inflammation, and this response is thought to contribute to the pathogenesis of many diseases. Very little has been known, however, about how cell death triggers inflammation. We found here that the acute neutrophilic inflammatory response to cell injury requires the signaling protein myeloid differentiation primary response gene 88 (Myd88). Analysis of the contribution of Myd88-dependent receptors to this response revealed only a minor reduction in mice doubly deficient in Toll-like receptor 2 (Tlr2) and Tlr4 and normal responses in mice lacking Tlr1, Tlr3, Tlr6, Tlr7, Tlr9, Tlr11 or the interleukin-18 receptor (IL-18R). However, mice lacking IL-1R showed a markedly reduced neutrophilic inflammatory response to dead cells and tissue injury in vivo as well as greatly decreased collateral damage from inflammation. This inflammatory response required IL-1alpha, and IL-1R function was required on non-bone-marrow-derived cells. Notably, the acute monocyte response to cell death, which is thought to be important for tissue repair, was much less dependent on the IL-1R-Myd88 pathway. Also, this pathway was not required for the neutrophil response to a microbial stimulus. These findings suggest that inhibiting the IL-1R-Myd88 pathway in vivo could block the damage from acute inflammation that occurs in response to sterile cell death, and do so in a way that might not compromise tissue repair or host defense against pathogens.

Objective To examine cyclooxygenase 2 inhibitor (coxib) utilization by rheumatologists for patients receiving nonsteroidal antiinflammatory drugs (NSAIDs) prior to the coxib market withdrawals. Methods A prospective study of patients with rheumatoid arthritis enrolled in the Consortium of Rheumatology Researchers of North America registry was performed. Results Of 1,833 patients receiving prescription NSAIDs, 1,380 (75.3%) received gastroprotection, defined as either coxib monotherapy and/or gastroprotective agent (GPA) cotherapy, and 1,207 (65.8%) received coxibs. The distribution of gastroprotective strategies included 860 (46.9%) patients who were prescribed coxib monotherapy, 347 (18.9%) prescribed dual coxib plus GPA cotherapy, 173 (9.4%) prescribed a nonselective NSAID (NS-NSAID) plus GPA cotherapy, and 453 (24.7%) prescribed an NS-NSAID without GPA cotherapy. For patients with 0, 1, and ≥2 identifiable gastrointestinal (GI) risk factors, coxib prescribing rates as a proportion of NSAID agents were 64.1%, 66.4%, and 68.6%, respectively; among dual aspirin/NSAID users, coxib prescribing rates were 66.2%, 78.3%, and 68.5% of NSAID prescriptions, respectively. Conclusion The majority of NSAID users were prescribed a gastroprotective strategy, primarily attributable to coxib utilization. Coxib utilization rates were consistently high across all levels of GI risk, including patients without identifiable risk factors. These data indicate that rheumatologists broadly adopted the coxib class of NSAIDs in a nonselective manner with respect to underlying GI risk and concomitant aspirin use. As novel therapeutic classes are introduced, early evaluation of prescribing patterns using arthritis registries can determine the appropriateness of prescribing patterns and may improve patient outcomes.

Disclosure of medical errors is encouraged, but research on how patients respond to specific practices is limited.This study sought to determine whether full disclosure, an existing positive physician-patient relationship, an offer to waive associated costs, and the severity of the clinical outcome influenced patients' responses to medical errors.Four hundred and seven health plan members participated in a randomized experiment in which they viewed video depictions of medical error and disclosure.Subjects were randomly assigned to experimental condition. Conditions varied in type of medication error, level of disclosure, reference to a prior positive physician-patient relationship, an offer to waive costs, and clinical outcome.Self-reported likelihood of changing physicians and of seeking legal advice; satisfaction, trust, and emotional response.Nondisclosure increased the likelihood of changing physicians, and reduced satisfaction and trust in both error conditions. Nondisclosure increased the likelihood of seeking legal advice and was associated with a more negative emotional response in the missed allergy error condition, but did not have a statistically significant impact on seeking legal advice or emotional response in the monitoring error condition. Neither the existence of a positive relationship nor an offer to waive costs had a statistically significant impact.This study provides evidence that full disclosure is likely to have a positive effect or no effect on how patients respond to medical errors. The clinical outcome also influences patients' responses. The impact of an existing positive physician-patient relationship, or of waiving costs associated with the error remains uncertain.

Objective Although the relationship between religious practice and health is well established, the relationship between spirituality and health is not as well studied. The objective of this study was to ascertain whether participation in the mindfulness-based stress reduction (MBSR) program was associated with increases in mindfulness and spirituality, and to examine the associations between mindfulness, spirituality, and medical and psychological symptoms. Methods Forty-four participants in the University of Massachusetts Medical School's MBSR program were assessed preprogram and postprogram on trait (Mindful Attention and Awareness Scale) and state (Toronto Mindfulness Scale) mindfulness, spirituality (Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being Scale), psychological distress, and reported medical symptoms. Participants also kept a log of daily home mindfulness practice. Mean changes in scores were computed, and relationships between changes in variables were examined using mixed-model linear regression. Results There were significant improvements in spirituality, state and trait mindfulness, psychological distress, and reported medical symptoms. Increases in both state and trait mindfulness were associated with increases in spirituality. Increases in trait mindfulness and spirituality were associated with decreases in psychological distress and reported medical symptoms. Changes in both trait and state mindfulness were independently associated with changes in spirituality, but only changes in trait mindfulness and spirituality were associated with reductions in psychological distress and reported medical symptoms. No association was found between outcomes and home mindfulness practice. Conclusions Participation in the MBSR program appears to be associated with improvements in trait and state mindfulness, psychological distress, and medical symptoms. Improvements in trait mindfulness and spirituality appear, in turn, to be associated with improvements in psychological and medical symptoms.

Rheumatoid arthritis among elderly people is an increasingly important health concern. Despite several cross-sectional studies, it has not been clearly established whether there are important clinical differences between elderly-onset rheumatoid arthritis (EORA) and younger-onset rheumatoid arthritis (YORA). The aim of this study was to compare disease activity and treatment in EORA and YORA, using the Consortium of Rheumatology Researchers of North America (CORRONA) registry, a database generated by rheumatologist investigators across the USA. From the CORRONA registry database of 9381 patients with rheumatoid arthritis, 2101 patients with disease onset after the age of 60 years (EORA) were matched, on the basis of disease duration, with 2101 patients with disease onset between the ages of 40 and 60 years (YORA). The primary outcome measures were the proportion of patients on methotrexate, multiple disease-modifying antirheumatic drugs (DMARD) and biological agents (etanercept, infliximab, adalimumab and kineret) in each group. Disease activity and severity differed slightly between the EORA and YORA groups: Disability Index of the Health Assessment Questionnaire: 0.30 v 0.35; tender joint count: 3.7 v 4.7; swollen joint count: 5.3 v 5.2; Disease Activity Score 28: 3.8 v 3.6; patient global assessment: 29.1 v 30.9; physician global assessment: 24.9 v 26.3; patient pain assessment: 31.4 v 34.9. Regarding treatment, the use of methotrexate use was slightly more common among patients with EORA (63.9%) than among those with YORA (59.6%), although the mean methotrexate dose among the YORA group was higher than that in the EORA group. The percentage of patients with EORA who were on multiple DMARD treatment (30.9%) or on biological agents (25%) was considerably lower than that of patients with YORA (40.5% and 33.1%, respectively; p

Background . The aim of the present study was to evaluate the efficacy of a school nurse-delivered smoking cessation intervention to improve abstinence rates among adolescents interested in quitting. Methods . Seventy-one high schools in Massachusetts were randomized to either a four-session one-on-one school nurse-delivered smoking cessation intervention (37 schools, n = 571) or usual smoking cessation care control condition (34 schools, n = 577). Adolescents in grades 9–12 who smoked in the past 30 days completed surveys at baseline, 6 weeks and 3 months. The study was conducted during the 2002–2003 school year. Results . Thirty-day self-reported abstinence rates were significantly greater in students in the intervention compared to control condition at 6 weeks (18% vs. 2%, respectively) and 3 months (24% vs. 5%, respectively). After adjusting for school and potential confounders, students in the intervention schools had odds of quitting 8 times greater than students in the control schools at 6 weeks (OR = 8.4; 95% CI 3.7, 20.6) and 6 times greater at 3 months (OR = 6.4; 95% CI 3.4, 11.4). School nurses delivered intervention with a high degree of fidelity. Conclusions . A four-session smoking cessation intervention can feasibly be delivered by school nurses and increase self-reported short-term abstinence rates among students interested in quitting smoking.

How patients respond to medical errors may influence how physicians approach disclosure of medical errors, but information on patients' responses is limited. Research is needed on how the circumstances that surround a medical error affect how patients respond.To investigate whether patients' tendency to forgive a physician following a medical error varied under different circumstances.Cross-sectional survey.We mailed a questionnaire to 1500 randomly selected health plan members; the response rate was 66%. Questionnaire items assessed the likelihood of forgiveness following a medical error under 12 circumstances drawn from a review of the literature.Respondents were most likely to forgive a physician if the patient failed to provide complete information (93% would or might forgive) and least likely to forgive if the error was due to efforts to keep costs down (11% would or might forgive). Most respondents would not forgive a physician when the physician was tired or distracted (68%), was incomplete in data collection (76%), lacked knowledge (78%), or failed to follow up (85%). Men were more likely to forgive than women; the most educated respondents were most likely to forgive.Our findings suggest that patients are not likely to forgive a physician in circumstances in which they suspect incompetence, inattention, or a lack of caring on the part of the physician involved. A more comprehensive understanding of forgiveness and the effect of forgiveness on the physician-patient relationship following a medical error is needed.

Quality of life (QOL) is a central outcome measure in caring for seriously ill patients. The Missoula-VITAS Quality of Life Index (MVQOLI) is a 25-item patient-centered index that weights each of five QOL dimensions (symptoms, function, interpersonal, wellbeing, transcendence) by its importance to the respondent. The measure has been used to assess QOL for hospice patients, and has been found to be somewhat complex to use and analyze.This study aimed to simplify the measure, and evaluate the reliability and validity of a revised version as either a research or clinical tool (i.e., "psychometric" versus "clinimetric").Two data collection efforts are described. The psychometric study collected QOL data from 175 patients at baseline, 3-5 days, and 21 days later. The implementation study evaluated the feasibility and utility of the MVQOLI-R during over six weeks of use.End-stage renal patients on dialysis, hospice, or long-term care patients participated in the psychometric study. The implementation study was done in hospice, home health, and palliative care settings.The MVQOLI-R and the Memorial Symptom Assessment Scale.The psychometric and implementation studies suggest that the MVQOLI-R performs well as a clinical tool but is not powerful as an outcome research instrument. The MVQOLI-R has the heterogeneous structure of clinimetric tools, and demonstrated both relevance and responsiveness. Additionally, in a clinical setting the MVQOLI-R was useful therapeutically for stimulating communication about the psychosocial and spiritual issues important to the tasks of life completion and life closure.The MVQOLI-R has clinical utility as a patient QOL assessment tool and may have therapeutic utility as a tool for fostering discussion among patients and their clinicians, as well as for helping patients identify sources of suffering and opportunities during this time in their lives.

BACKGROUND: The objective of this study was to determine the effects of a brief primary care provider-delivered counseling intervention on the reduction of alcohol consumption by high-risk drinkers. The intervention was implemented as part of routine primary care medical practice.

Background Dengue hemorrhagic fever, the most severe form of dengue illness, is associated with secondary dengue virus (DV) infection. Preexisting nonneutralizing antibodies to DV that enhance the infection of Fc gamma receptor-bearing cells have been implicated in DV pathogenesis. Methods We conducted a prospective cohort study in Thai schoolchildren. Enhancing activity (EA) was measured as the percentage of DV-infected K562 cells, and viral titer (infected K562 cell supernatants) was measured in preillness plasma samples from children who subsequently had secondary DV2 or DV3 infection. Results Plaque-reduction neutralizing titers to the child's own DV2 or DV3 isolate were detected in 23 of 32 and 8 of 27 of the preillness plasma samples, and EA was detected to a low-passage Thai DV2 or DV3 in 31 of 32 and 26 of 27, respectively, of the samples. EA in undiluted preillness plasma did not correlate with subsequent disease severity or peak viremia levels in either secondary DV2 or DV3 infections. Conclusions Preillness plasma enhances DV infection of K562 cells even in the presence of detectable neutralizing antibodies in LLC-MK2 cells. However, levels of preillness plasma EA of DV infection in K562 cells did not correlate with the clinical severity or viral burden of secondary DV infection.

An association between stress and health has been hypothesized. However, the association pathways are unclear. In this article, the authors examined the associations between stress, social support, and cortisol and the mediating effect of several psychosocial variables. Adult men and women (n = 146) completed psychosocial surveys and provided saliva samples for cortisol assessments, quarterly, for 1 year Cross-sectional analysis results showed an inverse relationship between basal cortisol and stress (Model 1: coefficient = -.068, SE = .024, p = .006). After controlling for stress, the authors also found an inverse relationship between basal cortisol and social support among individuals with high social support (upper tertile compared with 1st and 2nd tertiles) (Model 2: coefficient = -.440, SE = .155, p = .005). Longitudinal models showed similar findings for both associations. These findings do not support the general hypothesis of a negative effect of chronic intermittent stress on health through Hypothalamic Pituitary Adrenal (HPA) axis activation, but do support a positive effect of social support on the HPA axis. Both findings deserve further investigation.

Many studies assessing the role of sex hormones, like testosterone, on stress and hostility factors have been primarily conducted in selected atypical populations such as violent criminals as well as androgen users and abusers. Therefore, the main aim of the current study was to investigate the association between testosterone levels and two psychosocial variables: stress and hostility in a cohort of healthy individuals who were members of a health maintenance organization (HMO).At five quarterly visits, psychosocial scales and blood draws were collected. Psychological stress was measured by using several scales that assessed different types of stress, including daily hassles, major life events and perceived stress. Similarly, different aspects of hostility were measured, among them cynicism, hostile affect and aggressive responding. Plasma collected from each visit was used for testosterone level determinations.Testosterone levels were significantly associated with stress in both males and females. However, whereas this association exhibited a "threshold effect" in males, it demonstrated a direct and continuous linear relationship between these variables in females. Hostility was not correlated with testosterone levels in neither males nor females.These results suggest that testosterone levels in normal males and females may be more reflective of an intricate balance between physiological responding and emotional coping to stressors than the hostility profile of the individual.

The objective of this study was to determine which factors that are present at the time of intrauterine repair of spina bifida could predict the need for ventriculoperitoneal shunt for hydrocephalus during the first year of life.One hundred seventy-eight fetuses have undergone intrauterine repair of spina bifida at Vanderbilt University Medical Center since 1997. Among these, 116 fetuses had a postnatal follow-up period of at least 12 months. The primary outcome of the study was the need for a ventriculoperitoneal shunt for hydrocephalus during the first year of life. The following variables were analyzed: maternal demographics (age, race, gravidity, and parity), gestational age at the time of surgery, ventricular size, degree of hindbrain herniation (determined by magnetic resonance imaging in 33 cases), type of defect (myelomeningocele vs myeloschisis), upper level of the lesion, presence of talipes, and intraoperative use of a lumbar drain. Statistical analysis was performed with logistic regression (to test the association of fetal and maternal factors and the need for ventriculoperitoneal shunting), 2-sample t-tests for comparison of means, and receiver operating curves with the use of the probabilities that were generated by the logistic regression for both continuous and categoric versions of the factors.Sixty-one of 116 of the fetuses (54%) who underwent operation in utero required the placement of a ventriculoperitoneal shunt before the age of 1 year. The upper level of the lesion was the strongest predictor of shunt requirement (adjusted odds ratio per 1 level increase with the use of continuous variables [S1 through T10], 1.73 [95% CI, 1.22- 2.44]; adjusted odds ratio with the use of upper lesion levelor=L3 vsL3 as a categorized variable, 5.7 [95% CI, 2.18- 14.7]), followed by gestational age at the time of surgery (adjusted odds ratio per 1 week increase with the use of continuous variables, 1.37 [95% CI, 1.06-1.77]; adjusted odds ratio with the use of gestational ageor=25 weeks vs25 weeks as a categorized variable, 3.3 [95% CI, 1.28-8.24]), and preoperative ventricular size (adjusted odds ratio per 1 unit increase with the use of continuous variables, 1.17 [95% CI, 1.01-1.36]; adjusted odds ratio with the use of ventricular sizeor=14 mm vs14 mm as a categorized variable, 3.5 [95% CI, 1.08-11.16]). Receiver operating curves with the use of the probabilities that were generated by the logistic regression analyses for both the continuous and categoric versions of the factors were compared. The area under the curve was approximately 0.81 for both methods. Thirty-eight of 48 of the fetuses (79%) with an upper level of the lesionor=L3 required placement of a ventriculoperitoneal shunt, although 25 of 68 of the fetuses (37%) with lesionsor=L4 did not (P.0001). Eighty-four percent of the fetuses with a preoperative ventricular sizeor=14 mm (27/32 fetuses) needed a shunt compared with 41% of the fetuses (34/81 fetuses) with smaller ventricles (P=.03). Seventy-one percent of the fetuses who underwent operation at25 weeks of gestation also required shunt placement (37/52 fetuses); 39% of the fetuses (24/61 fetuses) who were treatedor=25 weeks of gestation did not (P=.01). Thirty-five fetuses had a lesion levelor=L4 and a ventricular size14 mm and underwent operation ator=25 weeks of gestation. Among these, 8 fetuses (23%) required a ventriculoperitoneal shunt during the first year of life.This study suggests that, among fetuses who underwent operation in utero for spina bifida, fetuses with a ventricular size of14 mm at the time of surgery, fetuses who had surgery ator=25 weeks of gestation, and fetuses with defects that were located ator=L4 were less likely to require ventriculoperitoneal shunting for hydrocephalus during the first year of life.

Understanding the dynamics of patient treatment preferences can be important for end-of life are research, and has particular salience not only to guide a process of advance care planning (ACP) but also as an outcome measure. Ascertaining the reliability and responsiveness of preferences for life-sustaining treatments within and between patients is a necessary foundation for utilizing patient-agent congruence as an outcome for ACP interventions. This study validated a modified version of the Emanuel and Emanuel Medical Directive for use in both research and clinical applications. Seriously ill patients (n = 168) were asked at baseline and 21 days to consider four common end-of-life health state scenarios, to indicate their goals for treatment, and to state their preferences for six specific treatments. We investigated the reliability and validity of this tool. We found that preferences for life-sustaining treatments were highly intercorrelated, and internally consistent across treatments by scenario and across scenarios by treatment. Preferences for pain medications were, however, distinct from preferences for other treatments. Preference scores exhibited stability over follow-up, and demonstrated both concurrent and discriminant validity. We detected a small effect size for change in preferences as a function of health state change, suggesting that re-prioritization response shifts do occur but are small in magnitude in these patient samples over this time frame. We conclude that this measure is reliable and valid for use in clinical settings and for evaluating interventions designed to improve patient-agent congruence about patient preferences for life-sustaining treatments. Clinical applications of the tool are discussed.

OBJECTIVE : To evaluate recall bias in the thentest and to explore response shifts in chronically ill patients over time. METHODS : In a five-year study of 93 multiple sclerosis patients, kappa statistics examined recall bias in thentest scores. The thentest examined changes in internal standards. Longitudinal factor analysis investigated changes in conceptualization in evaluating quality of life (QOL). RESULTS : Standard analyses revealed deteriorating physical role performance but stability in other QOL indicators over time. Agreement between baseline indicators and thentest scores was lower for fatigue than for ambulation ( p

The concept of a good death is central to end-of-life care research. Despite its importance and the high interest in the topic, there are few measures currently available for use in clinical research.The present work describes the development and testing of a set of items intended to measure the importance of several components posited to be critical to the concept of a good death. It is intended for use with health care providers and lay people in the context of end-of-life care research and education.Four cohorts (n = 596) were recruited to participate, representing two helping profession disciplines, nonhelping professionals, and a range of ages, specifically: (1) undergraduate medical students; (2) master's degree students in nursing; (3) graduate students from the life sciences; and (4) practicing hospice nurses.Participants completed self-report questionnaires at baseline and retest. Psychometric analyses included item frequency distributions, factor analysis, alpha reliability, intraclass correlation, and measures of association.The new Concept of a Good Death measure demonstrated good item frequency distributions, acceptable internal consistency reliability, and test-retest stability. Its factor structure revealed that three distinct domains are measured, reflecting the psychosocial/spiritual, physical, and clinical aspects of a good death. An examination of patterns of correlations showed differential associations with death anxiety, spiritual beliefs and practices, anxious mood, and sociodemographic characteristics.The new Concept of a Good Death instrument appears to measure three distinct factors which people consider important to a Good Death. Ratings of the importance of these factors are reliable and valid. The instrument has the advantage of being a brief, self-report index for use in end-of-life care research.