2 Minute Medicine Rewind April 25, 2016

Patient Outcomes When Housestaff Exceed Eight Hours per Week

Over a decade ago, the Accreditation Council for Graduate Medical Education began restricting resident hours. However, the restrictions and their consequences in terms of patient care have not been studied to a sufficient degree. This retrospective cohort study investigates the patient care effects of housestaff working more than 80 hours per week. Over a calendar year, 4,767 admissions into a housestaff-run general medicine service at a large academic institution were monitored and categorized by whether or not the admitting residents had worked 80 or more hours during the patient’s hospitalization. Using the electronic health record, the investigators were able to audit the housestaff hours, as well as look at outcomes, such as ICU transfers, in-hospital mortality, length of stay, and 30-day readmission rate. 40.9% of the admissions were handled by housestaff that had worked more than 80 hours during that week. There was not a statistically significant difference in the rate of in-hospital mortality, with rates of 3.18% for those admitted by housestaff exceeding 80 hours vs. 2.42% for those who were not (p = 0.115), or a significant difference in the rate of 30-day readmission (13.7% vs. 12.8%, p = 0.395) between the two categories of patients. However, the study led to the conclusion that there was a higher length of stay (5.12 vs. 4.66 days, p = 0.048) as well as a higher rate of ICU transfers (3.18% vs. 2.38% , p = 0.029) in patients managed by residents working more than 80 hours in that week,. Looking at the outcomes as a composite, there was a significant increase in the rate of these events, 19.2% vs. 16.7% (p=0.031), for the patients admitted by the residents who had worked more.

One-Year Risk of Stroke After Transient Ischemic Attack or Minor Stroke

Though there were studies as recently as 2003 on the risk of future stroke or acute coronary syndrome following a transient ischemic attack (TIA) or minor stroke, since then, management of TIA has changed drastically. This study aimed to re-examine the profiles of these patients, the etiology of their attack, their 1- and 5-year outcomes, as well as improve the risk-assessment process. From 61 sites that had a specified system for managing TIA patients, including the use of a stroke specialist, this study enrolled 4,789 participants who, within seven days of admission, had a TIA or a minor stroke that scored 0 or 1 on the modified Rankin scale. It was observed that the average age of these patients was 66.1 years, 60% of them were male, and 70% had hypertension as part of their medical history. Other common historical aspects were dyslipidemia (69.9%) and smoking, either presently or in the past (46.5%). Of the 78.4% of patients observed by a stroke specialist within 24 hours of symptom onset, 33.4% were observed to have acute brain infarction, 23.2% had one extra or intracranial stenosis with occlusion of greater than 50% of the vessel, and 10.4% were found to have atrial fibrillation. The one-year event rate was shown to be 6.2% (95% CI, 5.5 to 7.0) for a major cardiovascular event and a 12% 1-year event rate was shown for future TIA or stroke. Multiple factors were associated with a more than doubled risk of future stroke, including atherosclerosis in large arteries, multiple brain infarctions, and a score of 6 or 7 on the ABCD scale. This analysis showed lower risks of cardiovascular events than previous studies and confirmed that the ABCD risk stratification was accurate in evaluating risk, but should not be used to preclude those with an ABCD score of less than 4 from urgent evaluation.

Association of Pembrolizumab with Tumor Response and Survival Among Patients with Advanced Melanoma

Programmed cell death protein 1 (PD-1) is an immune checkpoint inhibitor that diminishes the effects of T-cells on chronic inflammation. This study examined the safety and efficacy of pembrolizumab, a monoclonal IgG antibody against PD-1 that was administered with doses of 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks, in 655 patients with advanced melanoma. The main result being examined was objective response rate, using the Response Evaluation Criteria in Solid Tumors, but other end points were observed including length of response, toxicity, progression-free survival, and overall survival. The objective response rate was shown to be 35% (95% CI, 30 to 37%) and 44% of those who responded did so for at least one year with 74% having an ongoing response at the time of data collection concluding. Additionally, 35% (95% CI, 31 to 39%) of all participants in the study and 52%  (95% CI, 43 to 60%) of participants who had never had treatment had a year of progression-free survival, with the overall survival shown to be 23 months (95% CI, 20 to 29 months) for the study as a whole and 31 months (95% CI, 24 to not reached) for the group that hadn’t been treated previously. 4% of patients, however, had to discontinue treatment and 14% had at least one grade 3 or 4 adverse event. Overall, this article broadly exemplifies the effects of pembrolizumab on advanced melanoma patients.

Efficacy and Tolerability of Evolocumab vs. Ezetimibe in Patients with Muscle-related Statin Intolerance

Statins, or HMG-CoA reductase inhibitors, are a common pharmacological therapy used to reduce low-density lipoprotein cholesterol (LDL-C) and, in turn, limit atherosclerosis. Muscle-related adverse events occur in a significant proportion of those prescribed statins, though, and result in these patients being unable to take the recommended doses. This two-stage randomized study aimed to examine the efficacy of two nonstatin drugs, evolocumab and ezetimibe, in 511 patients with uncontrolled LDL-C who had reported intolerance to at least two statins. First, the patients were randomized to atorvastatin or a placebo for 24 weeks and then, after a two week wash-out period, participants who had muscle-related symptoms while on the atorvastatin were randomized to ezetimibe or evolocumab arms for the subsequent 24 weeks, evaluating for the mean percentage change in LDL-C in these patients from baseline to the mean of the values at weeks 22 and 24. 42.6% percent of participants were seen to have the adverse muscle events while on atorvastatin in the first phase of the trial and, with a mean LDL-C level of 219.9 mg/dL (SD, 72), these participants went on to the second phase. When comparing baseline to the mean of weeks 22 and 24, ezetimibe had a mean percent LDL-C change of -16.7% (95% CI, -20.5% to -12.9%) and a mean absolute change of -21 mg/dL while evolocumab yielded a mean percent change of -54.5% (95% CI, -57.2 to -51.8%) and a mean absolute change of -106.8 mg/dL. This resulted in a difference of -37.8% change for evolocumab relative to ezetimibe, as well as an absolute difference of -75.8 mg/dL. However, 28.8% of ezetimibe patients reported muscle symptoms, as did 20.7% of evolocumab patients. In conclusion, evolocumab resulted in a more significant reduction of LDL-C levels as compared to ezetimibe after 24 weeks in patients with intolerance to statins. Further research for long-term effects is still needed.

Image: PD

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