TNF-α inhibitor treatment and the risk of cardiovascular events in patients newly diagnosed with rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that is mainly treated with various non-biologic and biologic disease modifying anti-rheumatic drugs (DMARDs). RA patients experience cardiovascular diseases (CVD) at a higher rate compared to the general population. Biologic DMARDs that inhibit the effects of the pro-inflammatory cytokine, tumor necrosis factor (TNF)-α which is implicated in various atherosclerotic processes, may reduce the risk of CVD. Very little evidence exists evaluating the association between TNF-inhibitors (TNF-Is) and CVD in early RA patients. Using data from Truven's MarketScan claims database for the period of 2007-2010, we first examined the factors influencing treatment with biologics in RA patients in a retrospective cohort study. We observed that treatment initiation with biologics in RA patients is associated with patient age, RA severity, RA type, pre-index non-biologic DMARD and steroid use, health insurance type, and drug benefit generosity. Neither the presence of cardiovascular risk factors, hypertension, hyperlipidemia or diabetes nor the history of CVD, including acute myocardial infarction, chronic heart failure, stroke or other CVD, were found to be associated with the initiation of biologic treatments. We then evaluated the impact of treatment with TNF-Is on the risk of incident CVD events in patients newly diagnosed with RA using a nested case-control design with incidence density sampling. We observed that the risk of an incident CVD event was reduced by current treatment with TNF-Is and non-biologic DMARDs compared to no treatment with DMARDs. Further, we observed that this protective effect was found to be associated with the duration of TNF-I and non-biologic DMARD use in a linear manner. Finally, we examined the independent effects of infliximab, adalimumab and etanercept on the risk of CVD in the same cohort. We observed that treatment with adalimumab, but not with infliximab and etanercept, was found to be associated with a reduced risk of incident CVD events compared to no treatment with DMARDs. In conclusion, we observed that early TNF-I or non-biologic DMARD treatment may play a vital role in reducing the increased CVD burden in RA patients, potentially by producing favorable changes in traditional cardiovascular risk factors and RA risk factors.Doctor of Philosoph

EgoTV: Egocentric Task Verification from Natural Language Task Descriptions

To enable progress towards egocentric agents capable of understanding everyday tasks specified in natural language, we propose a benchmark and a synthetic dataset called Egocentric Task Verification (EgoTV). EgoTV contains multi-step tasks with multiple sub-task decompositions, state changes, object interactions, and sub-task ordering constraints, in addition to abstracted task descriptions that contain only partial details about ways to accomplish a task. We also propose a novel Neuro-Symbolic Grounding (NSG) approach to enable the causal, temporal, and compositional reasoning of such tasks. We demonstrate NSG's capability towards task tracking and verification on our EgoTV dataset and a real-world dataset derived from CrossTask (CTV). Our contributions include the release of the EgoTV and CTV datasets, and the NSG model for future research on egocentric assistive agents

Utilizing video on myocardial infarction as a health educational intervention in patient waiting areas of the developing world: A study at the emergency department of a major tertiary care hospital in India

<p>Abstract</p> <p>Objective</p> <p>To study the effect of health educational video instruction on increasing patients' knowledge in a hospital waiting area of a developing country.</p> <p>Methods</p> <p>An educational video on signs, symptoms, and risk factors of myocardial infarction (MI) was played in an Emergency Department (ED) patient waiting area of an urban tertiary care hospital in India. Participants (n = 217) were randomly assigned to two groups: an intervention group that viewed the MI video (n = 111) and a control group that did not view the video (n = 106). Each group took a standard survey of thirty-seven questions to assess baseline knowledge pertaining to MI (pretest). The intervention group then viewed the video and the initial survey was re-administered to each group (posttest).</p> <p>Results</p> <p>At baseline (pretest) there was no statistically significant difference between the intervention and control group in the mean number of correct (18.1 vs. 19.0, p = 0.19), incorrect (9.4 vs. 8.6, p = 0.27) and unsure (9.6 vs. 9.3, p = 0.78) responses per participant. After viewing the video on MI, the intervention group had a statistically significant improvement in the mean number of correct responses (27.0 vs. 20.0, p < 0.001), and a significant decline in the mean number of unsure responses (1.8 vs. 9.4, p < 0.001) compared to the posttest responses of the control group. There was no significant change in the number of incorrect responses on the posttest between the intervention and control groups, (8.3 vs. 7.7, p = 0.35), respectively.</p> <p>Conclusion</p> <p>A health educational video can serve as an effective tool for increasing patients' short-term knowledge and awareness of health conditions in a hospital waiting area of a developing country.</p> <p>Practice Implications</p> <p>Health educational videos serve as a public health low cost intervention that demonstrates clear short term benefits. Health care workers in developing countries can help educate individuals presenting to hospitals by displaying these videos in hospital waiting areas.</p

The “Dry-Run” Analysis: A Method for Evaluating Risk Scores for Confounding Control

A propensity score (PS) model's ability to control confounding can be assessed by evaluating covariate balance across exposure groups after PS adjustment. The optimal strategy for evaluating a disease risk score (DRS) model's ability to control confounding is less clear. DRS models cannot be evaluated through balance checks within the full population, and they are usually assessed through prediction diagnostics and goodness-of-fit tests. A proposed alternative is the "dry-run" analysis, which divides the unexposed population into "pseudo-exposed" and "pseudo-unexposed" groups so that differences on observed covariates resemble differences between the actual exposed and unexposed populations. With no exposure effect separating the pseudo-exposed and pseudo-unexposed groups, a DRS model is evaluated by its ability to retrieve an unconfounded null estimate after adjustment in this pseudo-population. We used simulations and an empirical example to compare traditional DRS performance metrics with the dry-run validation. In simulations, the dry run often improved assessment of confounding control, compared with the C statistic and goodness-of-fit tests. In the empirical example, PS and DRS matching gave similar results and showed good performance in terms of covariate balance (PS matching) and controlling confounding in the dry-run analysis (DRS matching). The dry-run analysis may prove useful in evaluating confounding control through DRS models

11-Hydroxy-7-Methoxy-2,8-Dimethyltetracene-5,12-Dione

We thank David Cordes and Aidan McKay (University of St Andrews) for collecting the single-crystal X-ray data. We thank Emmanuel T. Oluwabusola and Russell Gray for their continued support.Peer reviewe

Comparative Cardiovascular Risk of Abatacept and Tumor Necrosis Factor Inhibitors in Patients With Rheumatoid Arthritis With and Without Diabetes Mellitus: A Multidatabase Cohort Study

Background: We examined the cardiovascular risk of abatacept compared with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis with and without diabetes mellitus (DM). Methods and Results: We conducted a cohort study of patients with rheumatoid arthritis who newly started abatacept or TNF inhibitors using claims data from Medicare and MarketScan. The primary outcome was a composite cardiovascular end point of myocardial infarction (MI), stroke/transient ischemic attack, and coronary revascularization. To account for >60 baseline characteristics, abatacept initiators were 1:1 propensity score (PS) matched to TNF initiators in each database. Cox proportional hazards models estimated hazard ratio (HR) and 95% confidence interval (CI) in the PS‐matched cohort per database. A fixed‐effects meta‐analysis pooled database‐specific HRs. We included a total of 13 039 PS‐matched pairs of abatacept and TNF inhibitor initiators (6103 pairs in Medicare and 6936 pairs in MarketScan). A total of 34.7% in Medicare and 19.8% in MarketScan had baseline DM. The HR (95% CI) for the primary outcome associated with abatacept use versus TNF inhibitor was 0.81 (0.66–0.99) in Medicare and 0.95 (0.74–1.23) in MarketScan, with a pooled HR of 0.86 (95% CI, 0.73–1.01; P=0.3 for heterogeneity). The risk of the primary outcome was lower in abatacept initiators versus TNF inhibitors in the DM subgroup, with a pooled HR of 0.74 (95% CI, 0.57–0.96; P=0.7 for heterogeneity), but not in the non‐DM subgroup, with a pooled HR of 0.94 (95% CI, 0.77–1.14; P=0.4 for heterogeneity). Conclusions: In this large population‐based cohort of patients with rheumatoid arthritis, abatacept use appeared to be associated with a modestly reduced cardiovascular risk when compared with TNF inhibitor use, particularly in patients with DM

Association between inflammation and systolic blood pressure in RA compared to patients without RA

Background: The relationship between inflammation and blood pressure (BP) has been studied mainly in the general population. In this study, we examined the association between inflammation and BP across a broader range of inflammation observed in rheumatoid arthritis (RA) and non-RA outpatients. Methods: We studied subjects from a tertiary care outpatient population with C-reactive protein (CRP) and BP measured on the same date in 2009–2010; RA outpatients were identified using a validated algorithm. General population data were obtained from the National Health and Nutrition Examination Survey (NHANES) as comparison. To study the cross-sectional association between CRP and BP in the three groups, we constructed a generalized additive model. Longitudinal association between CRP and BP was examined using a repeated-measures linear mixed-effects model in RA outpatients with significant change in inflammation at two consecutive time points. Results: We studied 24,325 subjects from the outpatient population, of whom 1811 had RA, and 5561 were from NHANES. In RA outpatients, we observed a positive relationship between CRP and systolic BP (SBP) at CRP < 6 mg/L and an inverse association at CRP ≥ 6 mg/L. A similar inverse U-shaped relationship was observed in non-RA outpatients. In NHANES, we observed a positive relationship between CRP and SBP as demonstrated by previous studies. Longitudinal analysis in RA showed that every 10 mg/L increase in CRP was associated with a 0.38 mmHg reduction in SBP. Conclusions: Across a broad range of CRP observed in RA and non-RA outpatients, we found an inverse U-shaped relationship between CRP and SBP, highlighting a relationship not previously observed when studying the general population. Electronic supplementary material The online version of this article (10.1186/s13075-018-1597-9) contains supplementary material, which is available to authorized users

Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study

Objective: To provide absolute and relative risk estimates of neonatal abstinence syndrome (NAS) based on duration and timing of prescription opioid use during pregnancy in the presence or absence of additional NAS risk factors of history of opioid misuse or dependence, misuse of other substances, non-opioid psychotropic drug use, and smoking. Design: Observational cohort study. Setting: Medicaid data from 46 US states. Participants: Pregnant women filling at least one prescription for an opioid analgesic at any time during pregnancy for whom opioid exposure characteristics including duration of therapy: short term (<30 days) or long term (≥30 days); timing of use: early use (only in the first two trimesters) or late use (extending into the third trimester); and cumulative dose (in morphine equivalent milligrams) were assessed. Main outcome measure Diagnosis of NAS in liveborn infants. Results: 1705 cases of NAS were identified among 290 605 pregnant women filling opioid prescriptions, corresponding to an absolute risk of 5.9 per 1000 deliveries (95% confidence interval 5.6 to 6.2). Long term opioid use during pregnancy resulted in higher absolute risk of NAS per 1000 deliveries in the presence of additional risk factors of known opioid misuse (220.2 (200.8 to 241.0)), alcohol or other drug misuse (30.8 (26.1 to 36.0)), exposure to other psychotropic medications (13.1 (10.6 to 16.1)), and smoking (6.6 (4.3 to 9.6)) than in the absence of any of these risk factors (4.2 (3.3 to 5.4)). The corresponding risk estimates for short term use were 192.0 (175.8 to 209.3), 7.0 (6.0 to 8.2), 2.0 (1.5 to 2.6), 1.5 (1.0 to 2.0), and 0.7 (0.6 to 0.8) per 1000 deliveries, respectively. In propensity score matched analyses, long term prescription opioid use compared with short term use and late use compared with early use in pregnancy demonstrated greater risk of NAS (risk ratios 2.05 (95% confidence interval 1.81 to 2.33) and 1.24 (1.12 to 1.38), respectively). Conclusions: Use of prescription opioids during pregnancy is associated with a low absolute risk of NAS in the absence of additional risk factors. Long term use compared with short term use and late use compared with early use of prescription opioids are associated with increased NAS risk independent of additional risk factors

City Know-How

Human health and planetary health are influenced by city lifestyles, city leadership, and city development. For both, worrying trends are leading to increasing concern and it is imperative that human health and environmental impacts become core foci in urban policy. Changing trajectory will require concerted action; the journal Cities & Health is dedicated to supporting the flow of knowledge, in all directions, to help make this happen. We wish to foster communication between researchers, practitioners, policy-makers, communities, and decision-makers in cities. This is the purpose of the City Know-how section of the journal. ‘Research for city practice’ disseminates lessons from research by explaining key messages for city leaders, communities, and the professions involved in city policy and practice. ‘City shorts’ provide glimpses of what is being attempted or achieved ‘on the ground’ and ’case studies’ are where you will find evaluations of interventions. Last, ‘Commentary and debate’ extends conversations we are having to develop and mobilize much needed new thinking. Join in these conversations. In order to strengthen the community of interest, we would like to include many and varied voices, including those from younger practitioners and researchers who are supporting health and health equity in everyday urban lives

The Analysis of Teaching of Medical Schools (AToMS) survey: an analysis of 47,258 timetabled teaching events in 25 UK medical schools relating to timing, duration, teaching formats, teaching content, and problem-based learning.

BACKGROUND: What subjects UK medical schools teach, what ways they teach subjects, and how much they teach those subjects is unclear. Whether teaching differences matter is a separate, important question. This study provides a detailed picture of timetabled undergraduate teaching activity at 25 UK medical schools, particularly in relation to problem-based learning (PBL). METHOD: The Analysis of Teaching of Medical Schools (AToMS) survey used detailed timetables provided by 25 schools with standard 5-year courses. Timetabled teaching events were coded in terms of course year, duration, teaching format, and teaching content. Ten schools used PBL. Teaching times from timetables were validated against two other studies that had assessed GP teaching and lecture, seminar, and tutorial times. RESULTS: A total of 47,258 timetabled teaching events in the academic year 2014/2015 were analysed, including SSCs (student-selected components) and elective studies. A typical UK medical student receives 3960 timetabled hours of teaching during their 5-year course. There was a clear difference between the initial 2 years which mostly contained basic medical science content and the later 3 years which mostly consisted of clinical teaching, although some clinical teaching occurs in the first 2 years. Medical schools differed in duration, format, and content of teaching. Two main factors underlay most of the variation between schools, Traditional vs PBL teaching and Structured vs Unstructured teaching. A curriculum map comparing medical schools was constructed using those factors. PBL schools differed on a number of measures, having more PBL teaching time, fewer lectures, more GP teaching, less surgery, less formal teaching of basic science, and more sessions with unspecified content. DISCUSSION: UK medical schools differ in both format and content of teaching. PBL and non-PBL schools clearly differ, albeit with substantial variation within groups, and overlap in the middle. The important question of whether differences in teaching matter in terms of outcomes is analysed in a companion study (MedDifs) which examines how teaching differences relate to university infrastructure, entry requirements, student perceptions, and outcomes in Foundation Programme and postgraduate training