By Gibram Ramos Ortiz, MD
Peer Reviewed
Last week, lawmakers in Congress continued the fight against the opioid epidemic with a bipartisan bill dubbed the SUPPORT for Patients and Communities Act. The bill, which passed in the House of Representatives 393 to 8, offers major policy changes that include the following: creating a grant program for Comprehensive Opioid Recovery Centers, lifting restrictions on medications for opioid addiction, expanding access for first responders to Naloxone, making changes to Medicaid and Medicare to limit the over prescription of opioid painkillers, increasing penalties for drug manufacturers, and improving coordination of federal agencies to stop drugs like fentanyl crossing the border [1]. The bill is expected to head to the Senate soon for a final vote.
Transcatheter Mitral Valve Repair in Patients with Heart Failure (NEJM) [2]
Mitral valve surgery is known to be curative in primary degenerative mitral regurgitation (MR), but offers no mortality benefit in MR secondary to heart failure (HF). Patients with the latter have few options besides medical therapy, as even transcatheter repair is only FDA approved for primary MR in non-surgical candidates. In this randomized clinical trial, researchers evaluated the safety and effectiveness of transcatheter mitral-leaflet approximation with MitraClip in patients with HF and secondary MR who remained symptomatic despite adequate medical therapy. 614 patients were assigned in a 1:1 ratio to transcatheter repair and medical therapy or to medical therapy alone (control). Eligible patients included those with a left ventricular ejection fraction of 20-50%, moderate-to-severe or severe mitral regurgitation, and those who were symptomatic despite medical therapy. Within 24 months of follow up, annual rates of hospitalizations secondary to HF were 35.8% in the device group and 67.9% in the control group (HR, 0.53; 95% CI, 0.40 to 0.70; P= <0.001). Similarly, death from any cause within 24 months occurred in 29.1% of patients in the device group compared to 46.1% in the control group (HR, 0.62; 95% CI, 0.46 to 0.82; P= <0.001). Additionally, quality of life (measured with the KCCQ questionnaire and NYHA functional class) was significantly better in the device group.
Bottom line: Among patients with HF and moderate-to-severe or severe secondary MR who are symptomatic despite maximal doses of guideline medical therapy, transcatheter mitral valve repair resulted in lower rates of hospitalization, lower mortality and better quality of life.
Successful Treatment of Pre-Diabetes in Clinical Practice using Physiological Assessment (Lancet Endocrinology) [3]
Approximately 33.9% of Americans aged 18 or older (84.1 million people) had prediabetes in 2015, with 1.5 million cases of diabetes newly diagnosed that same year [4]. In this retrospective observational study, researchers assessed whether targeted pharmacological treatment, in addition to lifestyle modification, would help prevent progression from prediabetes to diabetes in high-risk individuals. 422 patients from a community health clinic in California were stratified into high-risk or intermediate-risk of developing diabetes based on severity of insulin resistance, impaired β-cell function and glycemic response, all of this determined via oral glucose tolerance testing (which included measuring plasma glucose, insulin and C-peptide levels). The high-risk group received metformin, pioglitazone, a GLP-1 agonist and lifestyle modification therapy, the intermediate-risk group received metformin, pioglitazone and lifestyle modification therapy, and patients that refused pharmacological treatment received solely lifestyle modification therapy. Results showed only 28 patients progressed to develop DMII, 0 in the high-risk group, 7 in the intermediate-risk group, and 21 from the lifestyle only group. Compared to lifestyle therapy only, the adjusted hazard ratio for progression to DMII was 0.29 (95% CI 0.11-0.78, p=0.0009) for patients receiving metformin and pioglitazone, and only 0.12 (95% CI 0.02-0.94, p=0.04) for patients receiving metformin, pioglitazone and GLP-1 agonists.
Bottom line: Progression to DMII in high-risk patients with pre-diabetes can be markedly reduced with interventions designed to correct underlying pathological disturbances (insulin resistance, impaired insulin secretion).
Wearable Cardioverter-Defibrillator after Myocardial Infarction (NEJM) [5]
Although ultimately lifesaving, implantable cardiac defibrillators (ICDs) currently are not indicated in the acute period after a myocardial infarction (MI). This study was designed to see whether a wearable cardioverter-defibrillator would reduce the rate of sudden death during the early period after an MI; in the period prior to when an ICD would be indicated (40-90 days post-MI). 2302 patients that had an acute MI and reduced ejection fraction of 35% or less were assigned in a 2:1 ratio to either wearable defibrillator and guideline-directed therapy or guideline-directed therapy alone (control). Results showed that arrhythmic death occurred in 1.6% of patients in the device group and in 2.4% of the control group (RR, 0.67; 95% CI 0.37 to 1.21; P=0.18). Death from any cause occurred in 3.1% of patients in the device group and in 4.9% of the control group (RR, 0.64; 95% CI 0.43 to 0.98; uncorrected P= 0.04). Of the 48 patients in the device group that died, 12 did so while wearing the device. A total of 20 patients (1.3%) received an appropriate shock, while 9 (0.6%) received an inappropriate shock.
Bottom line: In patients with an acute MI and an ejection fraction of 35% or less, the use of a wearable cardioverter-defibrillator in the early post-MI period did not result in a lower rate of arrhythmic death when compared to guideline-directed medical therapy alone.
Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia (JAMA) [6]
Despite staphylococci being the most common pathogen encountered in hospital-acquired and community-acquired bloodstream infections, the optimal length of treatment is currently unknown, with expert consensus guiding current treatment guidelines. Due to this, patients with uncomplicated staphylococci infections are exposed to prolonged courses of antibiotic therapy and their associated side-effects, while patient’s with complicated infections at times receive shortened courses that increase their risk for relapse, morbidity and mortality. In this randomized trial, 509 adults with staphylococcal bacteremia were divided in two groups, one treated via an algorithm (detailing antibiotic selection and length of use), while in the second group the choice and length of antibiotic use was determined by the treating physician. Results showed that 82% of the patients in the algorithm-based therapy group had clinical success (clearance of infection) when compared to 81.5% of patient’s in the usual practice group (difference 0.5%; 1-sided 97.5% CI, -6.2% to ∞). Adverse events were reported in 32.5% of patients in the algorithm group, while only in 28.3% of the usual practice patients (difference 4.2%; 95% CI -3.8% to 12.2%). Among patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days in the algorithm group vs 6.2 days in the usual practice group (difference -1.8 days; 95% CI -3.1 to -0.6).
Bottom line: Among patients with staphylococcal bacteremia, the use of an algorithm to guide treatment resulted in a non-inferior rate of clinical success when compared to usual therapy. Adverse events were not significantly different, but interpretation is limited due to wide confidence intervals.
Mini-Cuts:
Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Chord Injury (NEJM) [7]
A brief report showed that 4 patients with motor complete spinal cord injury were able to achieve trunk stability and independent standing after intense locomotor treadmill training with simultaneous spinal cord epidural stimulation. Two of them achieved over-ground walking (not on treadmill).
Phase 2b Controlled Trial of M72/AS01E Vaccine to Prevent Tuberculosis (NEJM) [8]
A vaccine provided 54% protection for M.tuberculosis-infected adults against active pulmonary tuberculosis disease, without any evident safety concerns.
Five-Year Follow-Up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial (JAMA) [9]
Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, recurrence within 5 years was 39.1%. Now with long-term follow up data, the feasibility of only using antibiotics for acute appendicitis as an alternative for surgery should be considered.
Dr. Gibram Ramos Ortiz is a 1st year resident at NYU Langone Health
Peer reviewed by Dana Zalkin, MD, Chief Resident, Internal Medicine, NYU Langone Health
Image courtesy of Wikimedia Commons
References:
- Lopez, G. “The House just passed a bipartisan bill to confront the opioid epidemic”. Vox. Accessed September 29, 2018. https://www.vox.com/policy-and-politics/2018/9/28/17913938/congress-opioid-epidemic-support-bill-law
- Stone GW, et al. Transcatheter Mitral Valve Repair in Patients with Heart Failure. NEJM. 2018; [e-pub]. (https://doi.org/10.1056/NEJMoa1806640).
- Armato JP, et al. Successful Treatment of Pre-Diabetes in Clinical Practice using Physiological Assessment. The Lancet Diabetes and Endocrinology. 2018; 6(10):781-789. doi: https://doi.org/10.1016/S2213-8587(18)30234-1.
- Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2017. Estimates of Diabetes and its Burden in the United States. February 24, 2018. https://www.cdc.gov/diabetes/data/statistics/statistics-report.html (accessed September 30, 2018).
- Olgin JE, et al. Wearable Cardioverter-Defibrillator after Myocardial Infarction. NEJM. 2018; 379:1205-1215. doi: 10.1056/NEJMoa1800781
- Holland TL, Raad I, Boucher HW, et al. Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia A Randomized Clinical Trial. JAMA.2018; 320(12):1249–1258. doi:10.1001/jama.2018.13155.
- Angeli CA, et al. Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Chord Injury. NEJM. 2018; 379(13):1244-1250. doi:10.1056/NEJMoa1803588.
- Van Der Meeren O, Hatherill M, Nduba V, et al. Phase 2b placebo-controlled trial of M72/AS01Ecandidate vaccine to prevent active tuberculosis in adults. NEJM. September 2018:10.1056/NEJMoa1803484. doi:10.1056/NEJMoa1803484.
- Salminen P, Tuominen R, Paajanen H, et al. Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial. JAMA.2018;320(12):1259–1265. doi:10.1001/jama.2018.13201.