Safety of allopurinol compared with other urate-lowering drugs in patients with gout: a systematic review and meta-analysis

Allopurinol is the most widely used urate-lowering drug (ULD). Together with efficacy and cost, safety is an aspect that helps taking clinical decisions. This systematic review analyzes allopurinol safety. The literature search was performed in MEDLINE, EMBASE, and the Cochrane Library (January 2014). Selection criteria: (a) patients >18, (b) gout by the ACR criteria or evidence of urate crystal in synovial fluid, (c) comparator (placebo or other ULD), and (d) RCTs, cohorts, or meta-analysis. Primary outcomes: rate of adverse events and death. The quality was assessed with the Jadad’s scale. A meta-analysis with fixed effects was performed. From 544 studies, seven met the eligibility criteria and were included. All RCT presented a low power for safety. All RCTs included a mixed population of patients with gout and hyperuricemia. Allopurinol (300 mg) was compared to febuxostat (40–240 mg) in five RCTs, to benzbromarone and probenecid in two RCTs, and to placebo in one. In the RCTs comparing allopurinol with benzbromarone and probenecid, the highest discontinuation rate was with probenecid (26 %), followed by allopurinol (11 %) and benzbromarone (4 %). The incidence of adverse events was similar between allopurinol (range 38.6–85) and febuxostat (range 41.8–80). Six patients on febuxostat and three on allopurinol died during the studies; no deaths were judged related to drug. The combined risk of adverse events was RR = 1.04 (95 % CI 0.98, 1.11). Allopurinol is a safe option, slightly better than other ULDs. The grade of evidence is high, but further research is needed to evaluate higher doses and long-term safety.     

On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier

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Prevention of catheter-related bloodstream infection in critically ill patients using a disinfectable, needle-free connector: a randomized controlled trial

OBJECTIVE: The aim of this study was to assess the efficacy of a disinfectable, needle-free connector in the prophylaxis of catheter-related bloodstream infection. METHODS: A randomized controlled trial was performed in a polyvalent intensive care unit. Patients who needed multilumen central venous catheters were randomly assigned to a study or a control group. All catheters were inserted and manipulated according to the Centers for Disease Control and Prevention (CDC) recommendations. Study group patients were equipped with catheters with disinfectable, needle-free connectors whereas control group patients were equipped with catheters with 3-way stopcocks. Two peripheral blood cultures and a semiquantitative culture of the catheter tip were performed on removal of the catheter. RESULTS: The study included 243 patients, with a total of 278 central venous catheters. The catheters' mean insertion duration was 9.9 days. Both groups were comparable regarding patient and catheter characteristics. Incidence rate of catheter-related bloodstream infection was 0.7 per 1000 days of catheter use in the study group, compared with 5.0 per 1000 days of catheter use in the control group (P=.03). CONCLUSIONS: To add a disinfectable, needle-free connector to the CDC recommendations reduces the incidence of catheter-related bloodstream infection in critically ill patients with central venous catheters.     

Cardiovascular Events in Systemic Lupus Erythematosus: A Nationwide Study in Spain From the RELESSER Registry

This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis.RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis.From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2–66.1], and SLE duration of 212.0 months [120.8–289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02–1.04]), hypertension (1.71 [1.20–2.44]), smoking (1.48 [1.06–2.07]), diabetes (2.2 [1.32–3.74]), dyslipidemia (2.18 [1.54–3.09]), neurolupus (2.42 [1.56–3.75]), valvulopathy (2.44 [1.34–4.26]), serositis (1.54 [1.09–2.18]), antiphospholipid antibodies (1.57 [1.13–2.17]), low complement (1.81 [1.12–2.93]), and azathioprine (1.47 [1.04–2.07]) as risk factors for CV events.We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows—for the first time—an association between diabetes and CV events in SLE patients.     

Prevalence of exposure to occupational risks during pregnancy in Spain

Objectives

We describe reported exposures to main categories of occupational agents and conditions in Spanish pregnant workers.

Methods

Women were recruited at 12th week of pregnancy from main public gynaecological consults to be included in the INMA Spanish cohorts study (n?=?2,058). Through personal interviews with structured questionnaires, information on working situation and working conditions during pregnancy was obtained.

Results

Fifty percent of the women reported frequent exposure to physical load (standing, heavy lifting) and 45?% reported exposure to three or more indicators of job strain. Exposure to at least one physical agent (noise, vibrations, etc.) affected 25?% of the women. Exposure to chemicals was reported by 20?% of the women, mostly including solvents and cleaning products. Eight percent of the women worked at night shifts. Job strain was more prevalent in office workers and industrial operators. Industrial workers showed the highest prevalence of exposure to chemical and physical pollutants.

Conclusions

Our data suggest that working conditions of pregnant women may need increased control in Spain.     

Immunophenotypical changes of T lymphocytes in the elderly

BACKGROUND: Substantial changes in both representation and function of T lymphocyte subsets have been reported with advancing age. However, till now, no systematic studies focused on age-dependent changes in the expression intensity of the major T lymphocyte surface receptors. OBJECTIVE: The present study was undertaken in order to establish age-related differences in lymphocyte subpopulations by simultaneously measuring three surface antigens in young and elderly people. METHOD: Peripheral blood T cell subsets from 20 healthy elderly individuals and 15 healthy young adult donors were examined by means of a quantitative three-color flow cytometry method. RESULTS: Activated (HLA-DR+) and memory (CD45RO+) T cells, CD3+CD7- T lymphocytes, and cells expressing natural killer (NK) markers (CD3-CD56+ NK cells and CD3+CD56+ T lymphocytes) were expanded, whereas T lymphocytes expressing the adhesion molecule CD62L were lower in elderly compared with young donors. In addition to alterations in the percentages of T cell subsets during senescence, several changes in the intensity expression of T cell antigens were also detected. CD3 antigen expression was downregulated on total T lymphocytes as well as on the memory T cell subset, while CD56+ T cells exhibited increased CD3 levels. Moreover, CD2 expression, unchanged on NK cells, was upregulated on T lymphocytes from elderly subjects. CD3+CD7- T cells exhibited increased expression of CD8 antigen, while the intensity expression of HLA-DR on activated T cells and CD7 on both T and NK lymphocytes was decreased. T cells from elderly subjects also exhibited higher expression of CD50 and CD62L adhesion molecules as compared with young ones. CONCLUSION: These T cell antigen expression modulations during senescence, in addition to the alteration in the frequency of the various T lymphocyte subsets, could contribute to the complex remodeling of the immune function characteristic of the elderly.