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On The Pulse - February 2017

On The Pulse

Tertius Lydgate

Friday, 24 February 2017

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E-cigarettes
Several studies have been published this month on e-cigarettes, making Dr Lydgate ponder the known and unknown risks versus benefits of these devices. While a long-term cross sectional study of 181 participants, published in the Annals of Internal Medicine, found that former smokers who completely replaced standard cigarettes with e-cigarettes substantially reduced their intake of cancer-causing chemicals compared to those who continued to smoke cigarettes, another cross-sectional case-control study of 42 participants, published in JAMA Cardiology, found that habitual e-cigarette users were more likely than the non-smoking control participants to have increased cardiac sympathetic activity and oxidative stress, which are known mechanisms associated with increased cardiovascular risk. Meanwhile, the results of a one-year follow-up of a national sample of 12th grade students in the US suggest that vaping is a “one-way bridge” to cigarette smoking among youth, prompting the researchers of this small observational study in Tobacco Control to call for youth access to e-cigarettes to be restricted.

Bariatric surgery for type 2 diabetes
Five-year outcome data published in the New England Journal of Medicine have shown that, among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing, or in some cases resolving, hyperglycaemia. The researchers randomly assigned 150 eligible patients to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. At five years, changes from baseline observed in the gastric-bypass and sleeve-gastrectomy groups were superior to the changes seen in the medical-therapy group with respect to body weight (−23%, −19%, and −5% in the gastric-bypass, sleeve-gastrectomy, and medical-therapy groups, respectively), triglyceride level (−40%, −29%, and −8%), high-density lipoprotein cholesterol level (32%, 30%, and 7%), use of insulin (−35%, −34%, and −13%), and quality-of-life measures.

Antiandrogen therapy plus radiation
The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. These are the findings from a double-blind, placebo-controlled trial published in the New England Journal of Medicine, which included 760 eligible patients. The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% CI, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005).

Lipid-lowering treatment
A large proportion of UK individuals with atherosclerotic cardiovascular disease (ASCVD) and high-risk non-ASCVD received statin treatment (79% and 62%, respectively) when NICE provided, in 2014, updated recommendations on lipid-modifying therapy. After assessing clinical practice contemporaneous to the release of these guidelines in a UK general practice setting for secondary and high-risk primary-prevention populations, researchers, writing in The BMJ Open, extrapolated the findings to UK nation level, based on 183,565 patients who met the inclusion criteria. They concluded that up to 94% of patients with ASCVD and 85% of high-risk non-ASCVD individuals, representing ∼3 million individuals in each group, would require statin uptitration or initiation to achieve full concordance with the updated guidelines.

Gestational diabetes
Gestational diabetes (GDM) is associated with a moderately increased risk of adverse perinatal outcomes, which is higher in insulin-treated GDM than in non-insulin-treated GDM for most outcomes. These are the conclusions from a large study published in Diabetologia, where researchers looked at all the deliveries taking place after 22 weeks in France in 2012. The cohort of 796,346 deliveries involved 57,629 mothers with GDM. Mother–infant linkage was obtained for 705,198 deliveries. After limiting the analysis to deliveries after 28 weeks to reduce immortal time bias, the risks of the following outcomes were increased in women with GDM compared with the non-diabetic population: preterm birth (30%), caesarean section (40%), pre-eclampsia/eclampsia (70%), macrosomia (80%), respiratory distress (10%), birth trauma (30%), and cardiac malformations (30%). By restricting analysis to deliveries after 37 weeks and excluding cases of undiagnosed pregestational diabetes, the researchers also identified a moderate increase in perinatal mortality in non-insulin-treated women with GDM. Authors pointed that their research helps illuminate the controversy about timing of delivery in GDM pregnancy.

Faecal microbiota transplantation
Microbiota transplantation is a novel form of therapeutic microbial manipulation and researchers set out to determine its efficacy in ulcerative colitis. They randomly allocated patients with active ulcerative colitis in a 1:1 ratio, using a pre-established randomisation list, to either faecal microbiota transplantation (n=41) or placebo colonoscopic infusion (n=40), followed by enemas five days per week for eight weeks. Faecal microbiota transplantation enemas were each derived from between three and seven unrelated donors. 27% of patients allocated faecal microbiota transplantation had steroid-free clinical remission with endoscopic remission or response at week eight, versus 8% of those who were assigned placebo. Microbial diversity increased with and persisted after faecal microbiota transplantation. The findings, published in the Lancet, therefore suggest that intensive-dosing, multidonor, faecal microbiota transplantation is a promising new therapeutic option for ulcerative colitis.

Vitamin D supplementation to prevent acute RTIs
Findings from a systematic review and meta-analysis of 10 933 individual participant data from 25 randomised controlled trials have shown that vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants. Protective effects were seen in those receiving daily or weekly vitamin D without additional bolus but not in those receiving one or more bolus doses. Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L. While the authors writing in the BMJ concluded their study reported the prevention of acute respiratory tract infection as a major new indication for vitamin D supplementation, authors of a linked editorial pointed to several methodological issues with the study, warning that the results were heterogeneous and not sufficiently applicable to the general population, and adding that they should be viewed as hypothesis generating only, requiring confirmation in well-designed adequately powered randomised controlled trials.

Antimicrobial stewardship
An updated systematic review of 221 studies, published in The Cochrane Library, has evaluated the impact of interventions to improve antibiotic prescribing to hospital inpatients. The results suggest there is high-certainty evidence that interventions lead to more hospital inpatients receiving the appropriate treatment for their condition according to antibiotic prescribing policies. Moderate-certainty evidence was found that interventions reduce the length of hospital stay (by 1.12 days) without increasing patient deaths. While both restriction and enabling techniques appeared to be successful in achieving effectiveness of the intervention, the authors suggested more research was required to understand the unintended consequences of the use of restrictive methods. However, they believe the study’s findings could have considerable health service and policy impact.

Author's Image

Tertius Lydgate

Originally from Northumberland, Tertius Lydgate studied medicine in Edinburgh, London and Paris. There he developed a special interest in communicable diseases and hoped to make great advances in treating and preventing them. But, after a promising start in a provincial centre of excellence in middle England, he was forced by circumstances (please, don't inquire) to abandon his high ideals. He now scrapes a living by pouring cold water on the over-enthusiastic at his private cryohydrotherapy clinic. Dreaming of the contributions he once hoped to make himself, he finds consolation in the latest medical journals and is happy to share his discoveries with his readers. He thinks that his creator, George Eliot, would have approved.
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