2 Minute Medicine Rewind September 25, 2017

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Lipid-lowering agents play a central role in the prevention of atherosclerosis progression. However, inflammation is also thought to contribute to the pathogenesis of atherosclerosis. In this randomized controlled trial, canakinumab, an anti-inflammatory monoclonal antibody that targets interleukin-1β, was investigated for its utility in preventing atherosclerosis-related adverse events. Specifically, 10,061 patients with a previous myocardial infarction and C-reactive protein level of 2 mg/L or above were enrolled and randomized to receive doses of 50 mg, 150 mg, or 300 mg of subcutaneous canakinumab every three months or placebo to evaluate whether canakinumab could prevent recurrent vascular events in patients with a persistent pro-inflammatory response. The primary end-points of this study were occurrence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Results showed that, at a median follow-up length of 3.7 years, the primary end point occurred 3.90 times per 100 person-years in the 300 mg group (HR 0.86, 95% CI 0.75 to 0.99, p=0.031, 3.86 times per 100 person-years in the 150 mg group (HR 0.85, 95% CI 0.74 to 0.98, p=0.021), and 4.11 times per 100 person-years in the 100 mg group (HR 0.93, 95% CI 0.80 to 1.07, p=0.3) However, when the multiplicity-adjusted threshold was applied, only the 150 mg dose of canakinumab was shown to result in significantly fewer events (p=0.02075). Investigators therefore concluded that this type of anti-inflammatory therapy, specifically 150 mg of subcutaneous canakinumab every three months, lowers the risk of cardiovascular events.

Effect of Post-Cesarean Delivery Oral Cephalexin and Metronidazole on Surgical Site Infection Among Obese Women: A Randomized Clinical Trial

Obesity is a risk factor for surgical site infection after caesarean delivery. Though pre-operative cephalosporin treatment is standard, the efficacy of post-operative antibiotic prophylaxis is unknown. In this randomized, double-blind trial, 403 women with a pre-pregnancy BMI greater than or equal to 30 were randomized to receive either 500 mg of oral cephalexin and 500 mg of oral metronidazole or placebo to investigate the effects of post-operative prophylactic cephalexin and metronidazole on surgical site infection. All treatments were given every 8 hours for a total of 48 hours after delivery and patients were monitored for a primary outcome of surgical site infection within 30 days. The group treated with antibiotics had an infection rate of 6.4% compared to 15.4% in the placebo group (RR 0.41, 95% CI 0.22 to 0.77, p=0.01). Investigators therefore concluded that post-operative antibiotic prophylaxis with metronidazole and cephalexin is effective in reducing the incidence of surgical site infection.

Weight and Metabolic Outcomes 12 Years after Gastric Bypass

While a number of studies have investigated clinical outcomes after bariatric surgery in obese patients with type 2 diabetes, the long-term effects of bariatric surgery are not well understood. In this prospective cohort study, researchers aimed to investigate Roux-en-Y gastric bypass for its effects on the development of type 2 diabetes, hypertension, and dyslipidemia, as well as the percentage of weight lost, over 12 years. Patients (n=1156) fell into one of three groups: 418 patients who underwent Roux-en-Y gastric bypass, 417 patients who desired surgery but were not able to undergo the procedure, and 321 patients who did not pursue surgery. These patients were all examined serially at 2, 6, and 12 years to monitor for incidence and remission of the aforementioned conditions. At 12 years of follow-up, the surgical group had a mean weight change of -35.0 kg (95% CI -38.4 to -31.7), as compared to -2.9 kg (95% CI -6.9 to -1.0) in the group that desired but did not receive surgery, and 0 kg (95% CI -3.5 to 3.5) in the group that did not seek surgery. Also at 12 years, compared to the group who desired but did not receive surgery, patients who underwent surgery were less likely to develop incident type 2 diabetes (OR 0.08, 95% CI 0.03 to 0.24, p<0.001), hypertension (OR 0.23, 95% CI 0.11 to 0.49, p<0.001), low HDL cholesterol (OR 0.12, 95% CI 0.03 to 0.46, p<0.001), high LDL cholesterol (OR 0.17, 95% CI 0.09 to 0.31, p<0.001), and high triglycerides (OR 0.15, 95% CI 0.02 to 0.97, p<0.05). Similar results were obtained when comparing the surgical group to the group that did not desire surgery, the results of which were all statistically significant, with exception of the incidence of high triglycerides. Compared to the group that desired but did not receive surgery, remission rates for type 2 diabetes (OR 8.9, 95% CI 2.0 to 40.0), hypertension (OR 5.1, 95% CI 1.7 to 15.6), low HDL (OR 3.8, 95% CI 1.6 to 9.3), high LDL (OR 7.1, 95% CI 1.6 to 31.7) and high triglycerides (OR 14.7, 95% CI 4.5 to 48.4) were also significantly higher in the surgical group, as compared to the. When compared to the group not interested in surgery, the remission rates were significantly higher for all of the diseases investigated other than high triglycerides. Investigators therefore concluded that Roux-en-Y gastric bypass results in long-term weight loss and prevention, as well as remission of type 2 diabetes, hypertension, and dyslipidemia.

The Effect of Physical Activity on Mortality and Cardiovascular Disease in 130,000 people from 17 high-income, middle-income, and low-income countries: the PURE study

It has been well established that recreational physical activity helps in reducing cardiovascular disease and mortality, particularly in high-income countries. This prospective cohort study, however, aimed to investigate the effects of different types of physical activity in areas with different income levels on these same outcomes. Patients from 17 countries without pre-existing cardiovascular disease were enrolled, assessed for their physical activity using the International Physical Activity Questionnaire (IPQA), and followed for a mean of 6.9 years for end points of major cardiovascular disease (CVD), including heart failure, stroke, myocardial infarction, and CVD mortality, and mortality. It was found that moderate physical activity, defined as 600-3000 metabolic equivalents or 150-750 minutes per week of moderate intensity exercise, resulted in significantly decreased mortality (HR 0.80, 95% CI 0.74 to 0.87, p<0.001) and significantly decreased CVD (HR 0.86, 95% CI 0.78 to 0.93, p=0.0004) when compared with low physical activity. Additionally, high physical activity, defined as >3000 metabolic equivalents or >750 minutes per week of moderate intensity exercise, also resulted in significantly lower mortality (HR 0.73, 95% CI 0.68 to 0.77, p<0.0001) and major CVD (HR 0.75, 95% CI 0.69 to 0.82, p<0.0001). These improvements were significant in high-income, upper-middle income, lower-middle income, and low-income countries, and were significant for both recreational and non-recreational physical activity. Investigators concluded that physical activity reduces mortality and CVD, irrespective of income and type of physical activity.

Corticosteroids for Treatment of Sore Throat: Systematic Review and Meta-Analysis of Randomised Trials

Sore throat is an extremely common chief complaint for emergency and outpatient visits. While corticosteroids are able to provide some symptomatic relief for this complaint, the benefits and risks have not been well-characterized in this setting. This systematic review and meta-analysis of randomized controlled trials aimed to investigate the risks and benefits of using corticosteroids as part of the treatment for sore throats. The 10 trials extracted through this review studied patients age 5 years or older (n=1426), that had either the clinical syndrome of sore throat or signs of acute tonsillitis or pharyngitis. Researchers found that a single low dose of corticosteroids (i.e. oral dexamethasone), patients were more likely to experience pain relief after 24 hours (RR 2.2, 95% CI 1.2 to 4.3) and that the amount of pain relief, as measured by the visual analogue scale was also significantly greater (mean difference 1.3, 95% CI 0.7 to 1.9). Treatment also resulted in more patients being pain-free at 48 hours (RR 1.5, 95% CI 1.3 to 1.8). The adverse effect profile was also tolerable, with six studies reporting no adverse events, three studies reporting few adverse events that were similar between treatment and non-treatment groups, and 1 group not recording adverse events. Investigators concluded that low dose corticosteroids can add to symptom relief in those with sore throat and risks of treatment are acceptable.

Image: PD

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