Primecuts – This Week In The Journals

December 13, 2016

PrimeCuts 8 min read

energyBy Shriram Alapaty, MD

Peer Reviewed

This week, America’s president-elect Donald Trump continued to defy expectations by selecting Mr. Scott Pruitt, a close ally of the fossil fuel industry, to head the Environmental Protection Agency. In stark contrast, Google has targeted 2017 as the date by which to completely run on renewable energy. The environment has been a subject of global attention, with Paris opting to make all public transport free in the face of the worst air pollution in 10 years. While America continues to prepare itself for a transition in leadership, the medical community looks at its own process for transitions of care within the hospital.

JAMA: Association Between End-of-Rotation Resident Transition in Care and Mortality Among Hospitalized Patients

Over the past few years, residency programs across the country have been looking at safety around transitions of care in the context of the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour restrictions.. The iCOMPARE trial1 was designed to address this concern; however, most currently available work on transitions of care focus on shift-to-shift handoff. This week in JAMA, a group lead by our own former Chief Resident Joshua Denson published an association between end-of-rotation transitions in care and mortality in hospitalized patients2. This retrospective cohort study examined over 230,000 patient discharges from 10 university-affiliated United Stated Veterans Affairs hospitals from 2008-2014. Transitions were defined as the handoff of information, responsibility, and authority for patient care to another clinician. Patients were stratified into transition and control groups. The transition group included patients admitted any time prior to end-of-rotation transition who were discharged or deceased within 7 days following transition, with exclusion of patients having a length of stay greater than 33 days. The primary outcome was in-hospital mortality, with secondary outcomes of 30- and 90-day mortality and readmission rates. Moreover, difference-in-difference analysis was performed to look for a change in the difference between groups after ACGME duty hour regulations were instituted. For intern-only and intern+resident transitions, mortality was higher compared to control (OR 1.12; 95% CI 1.03-1.21 and OR 1.18; 95% CI 1.06-1.33, respectively). Interestingly, in resident-only transitions the difference was not significant (OR 1.07; 95% CI 0.99-1.16). The 2011 ACGME changes were also shown to have higher adjusted mortality for transition patients in intern-only and intern+resident groups (OR 1.11; 95% CI 1.02-1.21 and OR 1.17; 95% CI 1.02-1.34 respectively). Overall, this study shows rigorously that transitions, marked by incomplete information transfer and unfamiliarity with patients, may truly be harmful for our patients. The findings also demonstrate that ACGME duty hour regulations strengthened the association of intern-only and intern+resident transitions with hospitalized patient mortality. While results from iCOMPARE will be necessary to propose dramatic duty-hour redesign, this study does highlight the need for more rigorous transitions in the current paradigm.

NEJM: Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease

In patients with left main coronary artery disease, the debate regarding which patients should undergo percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) has been ongoing for years. U.S and European guidelines suggest CABG as the standard3,4. In subgroup analysis of the SYNTAX5 trial; however, mortality and major cardiovascular adverse events at 5 years were similar when comparing CABG to PCI with first-generation paclitaxel-eluting stents. This week in NEJM, a randomized controlled trial follows up on this finding to challenge the CABG status quo6. In this multi-center, multi-national study, 1,905 patients at 126 sites in 17 countries were included based on left main coronary artery disease with >70% stenosis visually or 50-70% stenosis with hemodynamic significance. Moreover, consensus from a team with an interventional cardiologist and a cardiac surgeon was necessary to assess eligibility for revascularization with either PCI or CABG. Finally, patients were required to have a low to intermediate complexity of coronary artery disease as defined by a SYNTAX score of less than 32. The authors excluded patients with highly complex coronary anatomy as the SYNTAX trial suggested a worse prognosis with PCI compared to CABG in this subgroup. In short, this trial assessed the low and intermediate score cohorts that were deemed equivalent in prognosis for PCI vs CABG. Patients had follow-ups at 1 month, 6 months, and annually for 5 years. The primary endpoint was measured as death, stroke or MI at 3 years. Although PCI outperformed CABG in the secondary endpoint of 30-day death, stroke, and MI (HR 0.61; 95% CI 0.48 to 0.88; p = 0.008 for superiority), the difference was not sustained over the 3 year follow-up (HR 1.00; P=0.02 with 95% CI 0.79 to 1.26). Balancing the higher early mortality in CABG with higher rates of ischemia-driven revascularization in the PCI group, this study group suggests that in patients with low-intermediate SYNTAX scores who are candidates for either procedure, PCI with everolimus-eluting stents is a reasonable alternative to CABG. Although this was suggested by SYNTAX, this RCT should prompt physicians to suggest PCI for low and intermediate SYNTAX cohorts with CABG reserved for patients with high SYNTAX scores.

Lancet: Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière’s disease: a randomised, double-blind, comparative effectiveness trial

Prospere Meniere was the first to characterize a fluid filled inner ear manifesting as vertigo and tinnitus. The current standard of treatment for Meniere’s disease with frequent severe vertigo attacks utilizes intratympanic gentamicin’s vestibular neurotoxic effect to eliminate vertigo while attempting to preserve hearing. In this week’s Lancet, Patel et al compare intratympanic methylprednisone vs gentamicin in patients with unilateral Meniere’s disease7. They performed a randomized, double-blind trial that enrolled 60 patients of ages 18-70 at two hospitals in the UK. Injections were administered 2 weeks apart with follow-up performed for 2 years. The primary outcome was comprised of vertigo frequency 18-24 months after injection as compared to the participant’s baseline frequency for the 6 months prior to injections. In intention-to-treat analysis, the primary outcome was decreased from 19.9 to 2.5 in gentamicin group and from 16.4 to 1.6 in the methylprednisolone group, suggesting no significant difference between groups (p = 0.27). Notably, there were two patients who crossed over from methylprednisolone to gentamicin; however, both were classified as treatment failures and per-protocol analysis demonstrated no significant difference compared to intention-to-treat analysis. Interestingly, mean hearing level and hearing change from baseline were also not significantly different amongst the two groups (p=0.96 and p=0.07, respectively), despite conventional teaching of the effects of aminoglycosides. Post-hoc analysis suggested severe vertigo and vomiting 3-7 days after injection was more frequent with gentamicin (OR 10.5; 95% CI 1.2-90.7; p=0.01). Overall, the authors found no significant difference in terms of treating vertigo between the two groups. Notably, most of the reduction in vertigo frequency occurred at approximately 2 months after injections. The authors conclude that for patients who are apprehensive of severe vertigo and vomiting after injection or who depend on hearing professionally, methylprednisolone seems an appropriate alternative to gentamicin treatment for severe vertigo secondary to Meniere’s disease.

JAMA IM: Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: Randomized Clinical Trial 

Delirium remains a common but challenging illness in hospital medicine. Traditionally, supportive care and redirection are employed as the first line approach, with pharmacologic intervention utilized if necessary for safety. Dopamine and cholinergic imbalance has been implicated in delirium, thereby prompting the use of antipsychotics as first line therapy8. However, the safety or efficacy of this approach is not well established and randomized control trial data for the condition is limited. Delirium is exceedingly common in palliative care, with 4 in 10 patients having delirium on admission to palliative care9. This week in JAMA Internal Medicine, Agar et al report a randomized trial evaluating the efficacy of oral risperidone, haloperidol, and placebo for delirium in patients receiving palliative care10. In this study, 247 patients from 11 Australian hospice or palliative care services were enrolled in a double-blind dose-titrated study. Medication was administered every 12 hours for 72 hours titrated to symptoms of delirium. The mainstays of delirium therapy including supportive and individualized environmental care were continued. The primary outcome was measured as the average of final two delirium scores on day 3 as compared to baseline score before the first dose. Despite the physiologic rationale regarding antipsychotic use in delirium, patients in the risperidone and haloperidol groups had higher delirium scores compared to the placebo group (0.48 higher; 95% CI 0.09-0.86; p=0.02 and 0.24 higher; 95% CI 0.06-0.42; p=0.009 respectively). Less surprisingly, patients in the risperidone and haloperidol groups had higher extrapyramidal effects (0.73; 95% CI 0.09-1.37; p=0.03 and 0.79; 95% CI 0.17-1.41; p=0.01 respectively). Overall survival also favored the placebo group when compared to haloperidol but not risperidone (HR 1.73; 95% CI 1.2-2.5; p=0.003). In conclusion this study suggests that in patients who are in palliative care, delirium is best managed with supportive care focused on removing or undoing instigators of delirium as opposed to pharmacologic intervention with risperidone and haloperidol. Midazolam was used as needed for all groups, but was used the least in the placebo group. This study suggests that rigorous trials are plausible to study delirium and that patients in other delirium prone settings, such as the ICU, may benefit from additional research using this study’s design.

Minicuts:

  1. A study in the American Journal of Medicine11 found that depression alone and depression with comorbid psychological stress was associated with higher mortality when present after cardiac rehabilitation.
  2. An RCT in the Annals of Internal Medicine12 demonstrated that eight weeks of electro-acupuncture improved mean weekly complete spontaneous bowel movements in patients with chronic severe functional constipation.
  3. A case-control study in The Lancet Infectious Disease13 of the microcephaly epidemic in Brazil suggested an OR of 55.5 for neonates with microcephaly in patients with laboratory-confirmed Zika virus infection.

Dr.  Shriram Alapaty is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Kerrilynn Carney, MD, NYU Internal Medicine Residency Program

Image courtesy of Wikimedia Commons

References

  1. Individualized Comparative Effectiveness of Models Optimizing Patient Safety and Resident Education. (iCOMPARE). Individualized Comparative Effectiveness of Models Optimizing Patient Safety and Resident Education. – Full Text View – ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02274818. Accessed December 11, 2016.
  2. Denson JL, Jensen A, Saag HS, Wang B, Fang Y, Horwitz LI, Evans L, Sherman SE. Association Between End-of-Rotation Resident Transition in Care and Mortality Among Hospitalized Patients. JAMA. 2016;316(21):2204-2213. doi:10.1001/jama.2016.17424
  3. Fihn SD, Blankenship JC, Alexander KP, et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2014;64:1929-1949
  4. Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014;35:2541-2619
  5. Morice MC, Serruys PW, Kappetein AP, et al. Five-year outcomes in patients with left main disease treated with either percutaneous coronary intervention or coronary artery bypass grafting in the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery trial. Circulation 2014;129:2388-2394
  6. Stone GW, Sabik JF, Serruys PW, et al. Everolimus-eluting stents or bypass surgery for left main coronary artery disease. N Engl J Med 2016;375:2223-2235 http://www.nejm.org/doi/full/10.1056/NEJMoa1610227
  7. Patel, Mitesh et al. Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière’s disease: a randomised, double-blind, comparative effectiveness trial. The Lancet , Volume 388 , Issue 10061 , 2753 – 2762 http://thelancet.com/journals/lancet/article/PIIS0140-6736(16)31461-1/fulltext
  8. Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21(12):1190-1222. https://www.researchgate.net/publication/258425906_Neuropathogenesis_of_Delirium_Review_of_Current_Etiologic_Theories_and_Common_Pathways
  9. Hosie A, Davidson PM, Agar M, Sanderson CR, Phillips J. Delirium prevalence, incidence, and implications for screening in specialist palliative care inpatient settings: a systematic review. Palliat Med. 2013;27(6):486-498.
  10. Agar MR, Lawlor PG, Quinn S, Draper B, Caplan GA, Rowett D, Sanderson C, Hardy J, Le B, Eckermann S, McCaffrey N, Devilee L, Fazekas B, Hill M, Currow DC. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative CareA Randomized Clinical Trial. JAMA Intern Med. Published online December 05, 2016. doi:10.1001/jamainternmed.2016.7491.
  11. Kachur, Sergey et al. Significance of Comorbid Psychological Stress and Depression on Outcomes After Cardiac Rehabilitation. The American Journal of Medicine , Volume 129 , Issue 12 , 1316 – 1321. https://www.ncbi.nlm.nih.gov/pubmed/27480388
  12. Liu Z, Yan S, Wu J, He L, Li N, Dong G, et al. Acupuncture for Chronic Severe Functional Constipation: A Randomized Trial. Ann Intern Med. 2016;165:761-769. doi: 10.7326/M15-3118 https://www.ncbi.nlm.nih.gov/pubmed/27618593
  13. de Araújo, Thalia Velho Barreto et al. Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study. The Lancet Infectious Diseases , Volume 16 , Issue 12 , 1356 – 1363. http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(16)30318-8/abstract