Management of pregnancy in women with rheumatoid arthritis

Rheumatoid arthritis (RA) disease activity may improve during pregnancy but postpartum flares are common. Patients taking disease-modifying antirheumatic drugs should be counselled about effective contraception. Knowledge about drug safety in pregnancy is limited but the Therapeutic Goods Administration categories and online resources are a guide to the data currently available. Begin prepregnancy counselling as early as possible to allow for cessation of teratogenic medications and optimisation of RA disease control. For unplanned pregnancies, cease teratogenic medications immediately and refer to a genetic counsellor and maternal–fetal medicine specialist for risk assessment and advice

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes

Background The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. Methods In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. Results A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P=0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. Conclusions In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .)

Stress-strain characteristic of SFRC using recycled fibres

This paper presents work from a comprehensive study on the development of a flexural design framework for concrete reinforced with steel fibres that are recovered from used tyres. The experimental flexural behaviour of notched concrete prisms reinforced with these fibres is initially presented. For comparison purposes, prisms reinforced with industrially produced fibres are also considered. An attempt to adopt an existing RILEM design framework to derive appropriate tensile stress-strain blocks is made, but problems are identified with key parameters of the framework. The influence of crack propagation and location of neutral axis depth on the tensile stress distribution is examined. Following an analytical study, it is concluded that the uniaxial stress-strain model, proposed by RILEM overestimates the load-carrying capacity and should be modified by utilising more advanced analytical techniques. © RILEM 2006

Should nitrous oxide ever be used in oncology patients receiving methotrexate therapy?

Nitrous oxide (N2O) is frequently used for short anesthesia/analgesia in children undergoing painful or repetitive procedures. Children with acute lymphoblastic leukemia (ALL) require repeated lumbar punctures with direct instillation of intrathecal chemotherapy, usually the anti‐folate agent methotrexate, during their treatment. These procedures are frequently performed under anesthesia. Concerns have been intermittently raised about a drug interaction between methotrexate and N2O that may potentiate the undesirable side effects of methotrexate, including neurotoxicity. However, the clinical evidence consists mainly of isolated case reports leading to a lack of consensus among pediatric anesthetists about the relative risk benefits of using N2O in children with ALL. In this article, we review the biochemical basis and scientific observations that suggest a significant interaction between N2O and methotrexate due to their dual inhibition of the key enzyme methionine synthase. The possible role of this interaction in potentiating neurotoxicity in children with cancer is discussed, and arguments and counterarguments about the clinical significance of this largely theoretical relationship are explored. Following comprehensive review of all the available data, we make the case for the circumstantial evidence being sufficiently compelling to prompt a review of practice by pediatric anesthetists and call for a precautionary approach by avoiding the use of N2O in children receiving concurrent methotrexate

Population-Level Incidence and Monitoring of Adverse Drug Reactions with Long-term Amiodarone Therapy

Introduction: Amiodarone is associated with significant long-lasting adverse drug reactions (ADRs). Guidelines recommend laboratory monitoring during long-term use. However, data of compliance with laboratory monitoring are lacking. Aims: The aim of this study was to assess laboratory monitoring of liver and thyroid function during amiodarone prescribing from 1989 to 2011 in the Tayside, UK, population (approximately 400 000) in relation to National Guidelines recommending laboratory monitoring every 6 months. We also report the population-level incidence of abnormal liver and thyroid function in relation to total exposure of amiodarone. Methods: Utilizing well-established record-linkage database, a longitudinal retrospective analysis of 1413 patients on long-term amiodarone was carried out, analyzing prescribing, biochemical, and clinical data. Results: Forty-six percent (46%), 28%, and 21% of patients underwent liver, thyroid, and combined testing, respectively, in accordance with guideline recommendations. Thirteen percent and 17% of patients did not have any ALT or TSH testing, respectively. During follow-up, 117 (9.5%) patients had an ALT 3×ULN and 16% patients had an abnormal TSH, (n=125, &lt;0.4 mU/L and n=28, >10 mU/L). One hundred and forty patients (10%) required thyroxine replacement therapy, and 40 (3%) required on hyperthyroid medication. Total amiodarone exposure increased the likelihood of abnormal biochemical testing 2.5-fold after 4 years therapy for liver and thyroid function (P&lt;.0005). Conclusion: In this population-based study, adherence to laboratory monitoring guidelines was suboptimal. There was a positive correlation with total amiodarone exposure and biochemical abnormalities and development of thyroid disease compared to the general population, highlighting the need for improvement and continued amiodarone monitoring

Cost-effectiveness of recommended nurse staffing levels for short-stay skilled nursing facility patients

BACKGROUND: Among patients in skilled nursing facilities for post-acute care, increased registered nurse, total licensed staff, and nurse assistant staffing is associated with a decreased rate of hospital transfer for selected diagnoses. However, the cost-effectiveness of increasing staffing to recommended levels is unknown. METHODS: Using a Markov cohort simulation, we estimated the incremental cost-effectiveness of recommended staffing versus median staffing in patients admitted to skilled nursing facilities for post-acute care. The outcomes of interest were life expectancy, quality-adjusted life expectancy, and incremental cost-effectiveness. RESULTS: The incremental cost-effectiveness of recommended staffing versus median staffing was $321,000 per discounted quality-adjusted life year gained. One-way sensitivity analyses demonstrated that the cost-effectiveness ratio was most sensitive to the likelihood of acute hospitalization from the nursing home. The cost-effectiveness ratio was also sensitive to the rapidity with which patients in the recommended staffing scenario recovered health-related quality of life as compared to the median staffing scenario. The cost-effectiveness ratio was not sensitive to other parameters. CONCLUSION: Adopting recommended nurse staffing for short-stay nursing home patients cannot be justified on the basis of decreased hospital transfer rates alone, except in facilities with high baseline hospital transfer rates. Increasing nurse staffing would be justified if health-related quality of life of nursing home patients improved substantially from greater nurse and nurse assistant presence

Labour induction near term for women aged 35 or over: an economic evaluation

Objective Induction of labour at 39 weeks for nulliparous women aged 35 years and over may prevent stillbirths and does not increase caesarean births, so it may be popular. But the overall costs and benefits of such a policy have not been compared. Design A cost–utility analysis alongside a randomised controlled trial (the 35/39 trial). Setting Obstetric departments of 38 UK National Health Service hospitals and one UK primary-care trust. Population Nulliparous women aged 35 years or over on their expected due date, with a singleton live fetus in a cephalic presentation. Methods Costs were estimated from the National Health Service and Personal Social Services perspective and quality-adjusted life-years (QALYs) were calculated based on patient responses to the EQ-5D at baseline and 4 weeks. Main outcome measures Data on antenatal care, mode of delivery, analgesia in labour, method of induction, EQ-5D (baseline and 4 weeks postnatal) and participant-administered postnatal health resource use data were collected. Results The intervention was associated with a mean cost saving of £263 and a small additional gain in QALYs (though this was not statistically significant), even without considering any possible QALY gains from stillbirth prevention. Conclusion A policy of induction of labour at 39 weeks for women of advanced maternal age would save money

Access to shops: The views of low-income shoppers

Concern is mounting as the retail stranglehold upon access to food grows. Research on the implications of restructuring retailing and health inequality has failed to involve low-income consumers in this debate. This paper reports on an exercise conducted for the UK Government's, Social Exclusion Unit's Policy Action Team on Access to Shops. The survey provides a useful baseline of the views of low-income groups in England. The choices that people on low income can make were found to be dominated by certain factors such as income and, most importantly, transport. Consumers reported varying levels of satisfaction with retail provision. The findings suggest gaps between what people have, what they want and what the planning process does and does not offer them. Better policy and processes are needed to include and represent the interests of low-income groups

Prediction of photoperiodic regulators from quantitative gene circuit models

Photoperiod sensors allow physiological adaptation to the changing seasons. The external coincidence hypothesis postulates that a light-responsive regulator is modulated by a circadian rhythm. Sufficient data are available to test this quantitatively in plants, though not yet in animals. In Arabidopsis, the clock-regulated genes CONSTANS (CO) and FLAVIN, KELCH, F-BOX (FKF1) and their lightsensitive proteins are thought to form an external coincidence sensor. We use 40 timeseries of molecular data to model the integration of light and timing information by CO, its target gene FLOWERING LOCUS T (FT), and the circadian clock. Among other predictions, the models show that FKF1 activates FT. We demonstrate experimentally that this effect is independent of the known activation of CO by FKF1, thus we locate a major, novel controller of photoperiodism. External coincidence is part of a complex photoperiod sensor: modelling makes this complexity explicit and may thus contribute to crop improvement