Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy.

OBJECTIVES: Nicaraguan sugarcane workers, particularly cane cutters, have an elevated prevalence of chronic kidney disease of unknown origin, also referred to as Mesoamerican nephropathy (MeN). The pathogenesis of MeN may include recurrent heat stress, crystalluria, and muscle injury with subsequent kidney injury. Yet, studies examining the frequency of such events in long-term, longitudinal studies are limited. METHODS: Using employment and medical data for male workers at a Nicaraguan sugarcane company, we classified months of active work as either work as a cane cutter or other sugarcane job and determined occurrence of dysuria, heat events and muscle events. Work months and events occurred January 1997 to June 2010. Associations between cane cutting and each outcome were analyzed using logistic regression based on generalized estimating equations for repeated events, controlling for age. RESULTS: Among 242 workers with 7257 active work months, 19.5% of person-months were as a cane cutter. There were 160, 21, and 16 episodes of dysuria, heat events, and muscle events, respectively. Compared with work months in other jobs, cane cutting was associated with an elevated odds of dysuria [odds ratio 2.40 (95% confidence interval 1.56-3.68)]. The number of heat and muscle events by cane cutter and other job were limited. CONCLUSIONS: Working as a cane cutter compared with other jobs in the sugarcane industry was associated with increased dysuria, supporting the hypothesis that cane cutters are at increased risk of events suspected of inducing or presaging clinically evident kidney injury.

Relations of Metabolically Healthy and Unhealthy Obesity to Digital Vascular Function in Three Community-Based Cohorts: A Meta-Analysis.

BACKGROUND: Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. METHODS AND RESULTS: We meta-analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19-90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal-weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP-III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal-weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all P<0.0001). Metabolically unhealthy obese individuals had more impaired vascular function than metabolically healthy obese individuals (baseline pulse amplitude 6.28±0.01 versus 6.12±0.02; PAT ratio 0.49±0.01 versus 0.58±0.01, all P<0.0001). CONCLUSIONS: Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status.

Methotrexate dosage as a source of bias in biological trials in rheumatoid arthritis: a systematic review.

OBJECTIVES: To evaluate if optimal dose of either oral or injectable regimens of methotrexate (MTX) of 25 mg/week was used in the comparator arms of studies comparing biologic drugs with MTX in rheumatoid arthritis (RA). METHODS: A systematic literature search was carried out in MEDLINE, EMBASE and the Cochrane Library databases for randomised controlled trials comparing biologics with MTX in RA. A systematic review was performed among studies that met predefined criteria focusing on assessment of dose of MTX used in the comparator arm. Study authors were contacted when necessary. Study quality was assessed. RESULTS: A total of 3276 references were identified and 13 trials were included. We obtained maximal dose and regimen for all. The maximal dose of MTX used in the comparator arm of the trials was no more than 20 mg/week in any trial and for all but one trial, MTX was given orally and not by injection. The trial that used an injectable form reached a maximum of 15 mg/week. CONCLUSIONS: A suboptimal dose of MTX was used in biological clinical trials performed in RA, particularly regarding route of administration. This may have biased findings in favour of biological agents.