Friday, July 31, 2015

Genetic variants are associated with severe cutaneous reactions to phenytoin

A number of SNPs were identified in this study:

Design, Setting, and Participants Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia.

Main Outcomes and Measures Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions.

Results The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10−17). The statistically significant association between CYP2C9*3 and phenytoin-related severe cutaneous adverse reactions was observed in additional samples from Taiwan, Japan, and Malaysia. A meta-analysis using the data from the 3 populations showed an overall odds ratio of 11 (95% CI, 6.2-18; z=8.58; P less than .00001) for CYP2C9*3 association with phenytoin-related severe cutaneous adverse reactions. Delayed clearance of plasma phenytoin was detected in patients with severe cutaneous adverse reactions, especially CYP2C9*3 carriers, providing a functional link of the associated variants to the disease.

Thursday, July 30, 2015

Fruit and vegetable servings and mortality

From a recent BMJ meta-analysis:

Results Sixteen prospective cohort studies were eligible in this meta-analysis. During follow-up periods ranging from 4.6 to 26 years there were 56 423 deaths (11 512 from cardiovascular disease and 16 817 from cancer) among 833 234 participants. Higher consumption of fruit and vegetables was significantly associated with a lower risk of all cause mortality. Pooled hazard ratios of all cause mortality were 0.95 (95% confidence interval 0.92 to 0.98) for an increment of one serving a day of fruit and vegetables (P=0.001), 0.94 (0.90 to 0.98) for fruit (P=0.002), and 0.95 (0.92 to 0.99) for vegetables (P=0.006). There was a threshold around five servings of fruit and vegetables a day, after which the risk of all cause mortality did not reduce further. A significant inverse association was observed for cardiovascular mortality (hazard ratio for each additional serving a day of fruit and vegetables 0.96, 95% confidence interval 0.92 to 0.99), while higher consumption of fruit and vegetables was not appreciably associated with risk of cancer mortality.

It looks like the five serving rule still holds!

Wednesday, July 29, 2015

Volume controlled versus pressure controlled ventilation in ARDS

Given that treatment needs to be individualized, there is insufficient evidence to tell whether one is better than the other across the board according to a Cochrane review.

Tuesday, July 28, 2015

Relationships between exercise, hunger and energy balance

Interesting article in the American Journal of Lifestyle Medicine:

High-intensity exercise causes a short-term suppression of hunger of approximately 15 to 60 minutes. Although there is evidence for compensatory food consumption, it usually does not make up for the energy deficit created by exercise. The exception occurs when individuals consume or reward themselves with energy-dense foods or drink. Because people tend to eat the same volume of food each day, on days when they exercise, they will remain in an energy deficit. However, on sedentary days, a positive energy balance is likely if caloric restriction is not imposed, which could result in weight gain. Caloric restriction alone leads to loss of lean body mass, while the inclusion of exercise with an energy deficit helps conserve lean tissue.

Monday, July 27, 2015

What’s new in the management of acute severe asthma?

From a recently published update:

Recent findings: β2-agonist heliox-driven nebulization significantly increased by 17% [95% confidence interval (CI) 5.2–29.4] peak expiratory flow, and decreased the rate of hospital admissions (risk ratio 0.77, 95% CI 0.62–0.98), compared with oxygen-driven nebulization. Other findings indicate that there is no robust evidence to support the use of intravenous or nebulized magnesium sulphate in adults with severe acute asthma, and that levalbuterol was not superior to albuterol regarding efficacy and safety in individuals with acute asthma. Finally, hyperlactatemia developed during the first hours of acute asthma treatment has a high prevalence, is related with the use of β2-agonists and had no clinical consequences.

Sunday, July 26, 2015

Exercise to improve cognitive function

This review focuses on the cognitive impairment associated with heart failure. Neurophysiologic mechanisms are discussed.

Saturday, July 25, 2015

When hypersensitivity pneumonitis enters the fibrotic stage

---it can mimic many other diffuse ILDs as outlined in this review.