2 Minute Medicine Rewind March 11, 2019
Chronic metabolic acidosis is often seen in patients with chronic kidney disease (CKD), and results from an inability to excrete metabolically produced acid. This, in turn, is associated with bone resorption, muscle catabolism, and progression of kidney disease. Veverimer is a non-absorbable medication that removes hydrochloric acid from the gut lumen in order to combat acidosis. In this multicenter, randomized controlled trial, 217 patients age 18 to 85 years with non-dialysis dependent CKD (estimated glomerular filtration rate between 20 and 40 mL/minute per 1.73 m2) with metabolic acidosis (serum bicarbonate between 12 and 20 mmol/L) were randomly assigned to receive either veverimer or placebo for 12 weeks while adhering to their regular diet to assess the efficacy and safety of veverimer as a treatment for metabolic acidosis in this patient population. Patients were followed up for the composite primary end point, which was the difference in the proportion of patients achieving either a 4 mmol/L increase in serum bicarbonate concentration from baseline or a serum bicarbonate level in the normal range of 22-29 mmol/L. Researchers found that there was a significant increase in the proportion of patients achieving the composite primary endpoint in the veverimer group, as compared to placebo (59% vs. 22%, difference 37%, 95% CI 23% to 49%, p<0.0001). The most common treatment-related adverse events observed in the interventional group were gastrointestinal, including diarrhea, flatulence, nausea, and constipation; these events were typically mild to moderate in severity. This study therefore shows that veverimer is a safe and effective therapy for metabolic acidosis in patients with CKD. Further studies are needed in investigating the long-term effect and safety of this medication.
Association of Atopic Dermatitis with Sleep Quality in Children
Atopic dermatitis, a common disorder in the pediatric population, is associated with pruritus that is often worse at night and, thus, can interfere with sleep. This longitudinal cohort study aimed to assess whether active atopic dermatitis impacts sleep duration and quality, and to examine the association between severity of disease and these symptoms. Between 1990 and 2008, children (n=13,988) between the ages of 2 and 16 years, with and without active atopic dermatitis, were followed up for self-reported atopic dermatitis severity and self-reported sleep duration and disturbances, such as difficulty falling asleep, early morning awakening, nighttime awakening, and nightmares. Researchers found that there was no clinically significant difference in sleep duration between children with and without active atopic dermatitis, as the average decrease in sleep over all ages for children with active disease was only 2 minutes (95% CI 0 to 4 minutes). However, active atopic dermatitis was associated with an increased risk of sleep disturbance (OR 1.48, 95% CI 1.33 to 1.66). This increased risk of sleep disturbance was more profound among children with more severe atopic dermatitis, rated as “quite bad” or “very bad” (OR 1.68, 95% CI 1.42 to 1.98). A significantly increased risk of sleep disturbance was also found among children with comorbid asthma or allergic rhinitis (OR 1.79, 95% CI 1.54 to 2.09). Investigators therefore concluded that atopic dermatitis is associated with sleep disturbances in childhood, with more severe disease, comorbid asthma and allergic rhinitis contributing to more severe sleep impairment.
Universal decontamination in the intensive care unit (ICU) has led to success in reducing bloodstream infections and infections with multi-drug resistant organisms. In this cluster-randomized trial of 53 hospitals, a similar protocol of universal decontamination using daily chlorhexidine bathing, as well as the administration of muciprocin for known methicillin-resistant staph aureus (MRSA) carriers, was investigated for its effects on infection due to multi-drug resistant organisms in non-critical-care units, as compared to routine bathing. Hospitals were randomized to deliver routine care or daily chlorhexidine bathing for all patients plus mupirocin for known MRSA carriers. The 194 non-critical-care units in 53 hospitals in the study, patients (n=156,889) were followed for infection rates, specifically for MRSA and vancomycin-resistant enterococcus (VRE). Researchers found that the chlorhexidine and muciprocin intervention led to a significant decrease in multi-drug resistant organism infections, as compared to the baseline period before the intervention (HR 0.79, 95% CI 0.73 to 0.87). However, the routine care group also saw a significant decrease in these infections, as compared to the baseline period (HR 0.87, 95% CI 0.79 to 0.95). No significant difference in effect was found between the two interventions (p=0.17). Investigators therefore concluded that daily chlorhexidine bathing, along with muciprocin for MRSA carriers, was not associated with lower multi-drug resistant organism infection rates, as compared to usual bathing.
State Gun Laws, Gun Ownership, and Mass Shootings in the US: Cross-Sectional Time Series
In the United States, there are limited national gun laws, with significant variability between individual states. Previously studies have documented an association between permissive statewide laws and higher levels of gun homicide and suicide. However, there has not been significant research into the varying state gun laws on mass shootings. In this cross-sectional time series using from 1998 to 2015, researchers examined annual ratings of states in terms of the permissiveness of their gun laws (scale: 0 to 100), taken from a reference guide for gun owners, as well as gun ownership in the state, and the incidence of mass shootings, defined as an event where four or more people were killed with a firearm. A regression analysis showed that, for a 10-unit increase in state gun law permissiveness, there was a significantly higher rate of mass shootings (11.5%, 95% CI 4.2% to 19.3%, p=0.002). Additionally, significantly higher rates of mass shootings were found with a 10% increase in gun ownership (35.1%, 95% CI 12.7 to 62.7%, p=0.001). This study therefore shows that more permissive gun laws and increased gun ownership are associated with an increase in mass shooting incidence.
Gastroesophageal reflux disease (GERD) is a common disorder associated with reflux of gastric contents through the gastroesophageal junction. There are a wide variety of treatment options, including laparoscopic surgical intervention. Laparoscopic anti-reflux surgery has been reported to be superior to proton pump inhibitors (PPIs) in terms of subjective and objective efficacy. However, potential mechanical side effects after surgical intervention, including dysphagia and bloating can be significant and limit the utility of surgery as a therapeutic option. The most commonly performed laparoscopic anti-reflux surgery procedure is total fundoplication (TF); however, alternate surgical strategies are often commonly employed, including partial wrap fundoplication (PF). Which surgical strategy is superior, is an issue of debate; while it has been argued that PF is associated with fewer mechanical adverse effects, TF may be superior to PF in terms of gastroesophageal reflux control, durability of wrap function, number of re-herniations, and the recurrence rate of GERD. In this randomized clinical trial, 456 patients were randomized to receive either a posterior partial fundoplication (PF) surgical technique, previously reported to have less mechanical side effects, or a Nissen total fundoplication (TF) surgical technique to determine whether PF or TF is superior in laparoscopic anti-reflux surgery. The primary end point was therapeutic efficacy, as measured by esophageal acid exposure 3 years after surgery. Researchers found that both techniques significantly reduced esophageal acid exposure, as PF reduced levels from 14.6% pre-operatively to 1.8% at 3 years post-operatively, and TF reduced levels from 16.0% to 2.5%. No significant difference between the two groups was noted (p=0.31). However, significantly lower rates of liquid dysphagia at 6 weeks (p=0.01), solid dysphagia at 12 months (p<0.001), and solid dysphagia at 24 months (p=0.001) were found in the PF group, as compared to TF. Investigators therefore concluded that both PF and TF are effective and not significantly different with respect to their efficacy in the treatment of GERD, however, PF is associated with less dysphagia in the post-operative period. This has important implications in the minimization of mechanical side effects following laparoscopic anti-reflux surgery.
Image: PD
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