Infection rates in patients from five rheumatoid arthritis (RA) registries: contextualising an RA clinical trial programme

OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population. METHODS: We used data from Consortium of Rheumatology Research of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (Sweden), Norfolk Arthritis Register (UK), CORRONA International (multiple countries) and Institute of Rheumatology Rheumatoid Arthritis (Japan) and an RA clinical trial programme (fostamatinib). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data. Infection definitions were harmonised across registries. Sensitivity analyses to address potential confounding explored subcohorts defined by disease activity, treatment change and/or prior comorbidities and restriction by calendar time or follow-up. Rates of infections were estimated and standardised to the trial population for age/sex and, in one sensitivity analysis also, for Health Assessment Questionnaire (HAQ) score. RESULTS: Overall, age/sex-standardised rates of hospitalised infection were quite consistent across registries (range 1.14-1.62 per 100 patient-years). Higher and more consistent rates across registries and with the trial programme overall were seen when adding standardisation for HAQ score (registry range 1.86-2.18, trials rate 2.92) or restricting to a treatment initiation subcohort followed for 18 months (registry range 0.99-2.84, trials rate 2.74). CONCLUSION: This prospective, coordinated analysis of RA registries provided incidence rate estimates for infection events to contextualise infection rates from an RA clinical trial programme and demonstrated relative comparability of hospitalised infection rates across registries

Feed grain imports and feed grain prices in importing countries

The effects of several variables on the feed grain sector of six importing countries were investigated in this study. The six countries were Greece, Israel, Japan, Portugal, Spain, and the United Kingdom. A simultaneous model with six equations was used to explain the domestic price of feed grains in the importing country and the quantity of feed grains imported by the country. Other endogeneous variables in the model were the price of livestock, the production of livestock products, the demand for livestock products, and the size of the livestock inventory in the importing country. The simultaneous model for each importing country allows the government of the importing country to control the domestic price of feed grains through the government’s manipulation of trade barriers for feed grains. Because of the existence of trade barriers, the domestic price of feed grains is allowed to differ from the cost of importing feed grains. The cost of importing feed grains incorporates ocean transportation costs and the exchange rate of the importing country

Inquiring into our past: when the doctor is a survivor of abuse

BACKGROUND: Health care professionals like other adults have a substantial exposure to childhood and adult victimization, but the prevalence of abuse experiences among practicing family physicians has not been examined. Also unclear is the impact of such personal experiences of abuse on physicians\u27 screening practices for childhood abuse among their patients and the personal and professional barriers to such screening. METHODS: We surveyed Massachusetts family physicians about their screening practices of adult patients for a history of childhood abuse and found that 33.6% had some experience of personal trauma, with 42.4% of women and 24.3% of men reporting some kind of lifetime personal abuse, including witnessing violence between their parents. These rates are comparable to or higher than those reported in prior studies of physicians\u27 histories of abuse. RESULTS: Physicians with a past history of trauma were more likely to feel confident in screening and less likely to perceive time as a barrier to screening. CONCLUSIONS: Given the high prevalence of prior childhood and victimization of both men and women physicians with the associated effects on their clinical work, we recommend that educational and training settings adopt specific competencies to provide safe and confidential environments where trainees can safely explore these issues and the potential impact on their clinical practice and well-being

Real-world Comparative Effectiveness of Tocilizumab Monotherapy vs. Tumor Necrosis Factor Inhibitors with Methotrexate in Patients with Rheumatoid Arthritis

INTRODUCTION: Controlled clinical studies have shown that the efficacy of tocilizumab (TCZ) monotherapy is superior to that of tumor necrosis factor inhibitor (TNFi) monotherapy and comparable to that of TCZ plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). This study compared the real-world effectiveness of TCZ monotherapy vs. TNFis plus MTX in US patients with RA. METHODS: TCZ-naive patients from the Corrona RA registry with prior exposure to \u3e /= 1 TNFi who initiated TCZ monotherapy or TNFi + MTX were included. Outcomes included mean change in Clinical Disease Activity Index (CDAI), achievement of low disease activity (LDA; CDAI \u3c /= 10), achievement of modified American College of Rheumatology (mACR) 20/50 responses, and mean change in modified Health Assessment Questionnaire (mHAQ) at 6 months. Patients initiating TNFi + MTX were grouped by MTX dose ( \u3c /= 10 mg; \u3e 10 to \u3c /= 15 mg; \u3e 15 to \u3c /= 20 mg; \u3e 20 mg); outcomes in each group were compared with TCZ monotherapy using trimmed populations (excluding patients outside the propensity score distribution overlap). RESULTS: Patients in all groups experienced improvement in CDAI at 6 months (mean change, - 6.9 to - 9.7), with no significant differences between the TCZ monotherapy and TNFi + MTX groups. Achievement of LDA and mACR responses at 6 months were comparable between the TCZ monotherapy and TNFi + MTX groups; overall, 26.8-38.0% of patients achieved LDA, 24.3-37.6% achieved mACR20 response and 13.2-20.8% achieved mACR50 response. The mean change in mHAQ at 6 months was - 0.1 in all groups. CONCLUSIONS: In this real-world population of US patients with RA who had prior TNFi exposure, there was no evidence of a difference in the effectiveness of TCZ monotherapy compared with that of TNFi + MTX, regardless of MTX dose, at 6 months for improving RA disease activity. FUNDING: Corrona, LLC. Plain language summary available for this article

Validation of a new measure of concept of a good death

BACKGROUND: 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. PURPOSE: 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. POPULATION: 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\u27s degree students in nursing; (3) graduate students from the life sciences; and (4) practicing hospice nurses. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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

Treatment of Rheumatoid Arthritis with Marine and Botanical Oils: Influence on Serum Lipids (poster)

Background: Over the past 30 years substantial progress has been made in the medical and surgical management of patients with rheumatoid arthritis (RA). Despite this progress, there is an increasing gap in mortality between patients with RA (1.5-3.0 fold risk) and the general population. This disparity is mainly attributable to cardiovascular disease (CVD) as the CVD risk is comparable in RA patients as to patients with diabetes mellitus. Although the reasons for this gap are not entirely clear, the traditional risk of abnormalities in lipid profiles appears to be enhanced by a chronic increase in inflammatory cytokines, resulting in accelerated atherosclerosis. Study Objective: The object of this study was to determine the effect of marine (fish oil) and botanical oils (borage oil) on lipids (TC, HDL, LDL, TG), a risk factor for cardiovascular disease in patients with RA. The main outcome (to be presented elsewhere) was to determine whether a combination of borage seed oil rich in gammalinolenic acid (GLA) and fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is superior to either oil alone for the treatment of RA. Population and Setting: The study was an 18 month randomized, double-masked comparison of borage seed oil, fish oil, and the combination of both oils in RA patients with active synovitis. Intervention: Patients received 3.5 gm omega-3 fatty acids daily in a 2.1gm EPA/1.4 gm DHA ratio (7 fish oil and 6 sunflower oil capsules daily); or 1.8 gm /d GLA (6 borage oil and 7 sunflower oil capsules /d); or 7 fish oil and 6 borage oil capsules daily (combination therapy). Discussion: Rheumatoid Arthritis (RA) is a chronic systemic inflammatory disease. Mediators of inflammation and prothrombotic factors contribute to endothelial dysfunction and development of cardiovascular disease in RA patients. Marine and botanical oils represent an excellent primary or secondary therapy for improvement of the cardiovascular risk management in RA. Patients taking these oils exhibit significant additional reductions in total and LDL-cholesterol, triglycerides, the TC/HDL ratio, and in the atherogenic index, and experience a significant increase in HDL-cholesterol. All of these improvements in the lipid profile were seen after 9 months of therapy, and increased after 18 months of oils administration. The overall dropout rate was 51%, and was similar across groups: 25 in the borage oil group, 28 in the fish oil group, and 22 in the combination group. Reasons for dropout were mainly gastrointestinal distress (belching, bloating, diarrhea, nausea, cramping), or an inability to swallow the large number of rather sizable capsules. This can be ameliorated by freezing the capsules and reducing their size. Among those evaluated for this study, compliance was 100%, assessed by pill counts. Learning Outcome: All treatments were safe, thus treatment of RA patients with one or a combination of these or similar oils should prove useful for reduction of cardiovascular risk in RA patients

Design characteristics of the CORRONA CERTAIN study: a comparative effectiveness study of biologic agents for rheumatoid arthritis patients

BACKGROUND: Comparative effectiveness research has recently attracted considerable attention. The Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) is an ongoing prospective cohort study of adult patients with Rheumatoid Arthritis (RA). METHODS/DESIGN: CERTAIN uses the existing Consortium of Rheumatology Researchers of North America (CORRONA) network of participating private and academic sites in order to recruit patients fulfilling the 1987 ACR criteria that have at least moderate disease activity. Patients starting or switching biologic agents either anti-TNF therapy or a non anti-TNF biologic are eligible for enrollment, depending on the treatment selected by their physician. Enrollment is expected to be completed by March of 2014, and 2711 patients will participate in the study. As of October 7th 2013, 2234 patients have been enrolled. Patient visits and laboratory blood work are mandated every three months for one year. Safety data is collected through one year and beyond. The primary comparative effectiveness endpoint is attainment of low RA disease activity at one year among patients who have been exposed to at least one prior TNF-alpha inhibitor agent prior to enrollment. Multiple secondary effectiveness and safety endpoints will be addressed by investigating the entire population enrolled (naive and biologic experienced). DISCUSSION: The unique design features of CERTAIN will inform comparative effectiveness and safety questions for choosing biologic agents for the management of RA

Detecting attitudinal changes about death and dying as a result of end-of-life care curricula for medical undergraduates

BACKGROUND: There is heightened emphasis on teaching end-of-life (EOL) care in the medical school curriculum, but a relative paucity of tools focused on assessing key attitudinal changes due to curricula. OBJECTIVE: We sought to evaluate the responsiveness of two validated measures of relevant attitudes to changes caused by two EOL curricula: a year-long Elective and a day-long Inter-Clerkship for medical undergraduates. DESIGN: A case control design (n = 100) and a one group pretest-posttest design (n = 98) were used to ask: (1) Are these two attitudinal measures responsive to changes induced by two undergraduate EOL curricula? (2) Do these two curricula have an additive effect (i.e., taking both yields a stronger attitudinal change than taking only one)? (3) Are there attitudinal and sociodemographic differences between students who took the year-long elective EOL course and those who did not? SUBJECTS: Undergraduate medical students. MEASUREMENTS: Two self-report measures: Concept of a Good Death and Concerns about Dying. RESULTS: Compared to nonelective participants, Elective participants reported less concern about working with dying patients at the end of the course and increased their valuation of clinical criteria in thinking about a good death. There were trends suggesting decreased general concern about dying and increased valuation of closure, and an interaction suggesting a larger impact on those with higher precourse concern scores. There were no differences between elective and nonelective participants at baseline. The Interclerkship increased students\u27 valuation of personal control aspects of death, and there was a trend in reducing concerns about working with dying patients. We did not find an additive effect of taking both curricula. CONCLUSIONS: We conclude that both measures were responsive to the relatively large effects this study would have been able to detect, and may be useful in future research to substantiate the effectiveness of EOL curricula in influencing attitudes and level of comfort with death and dying