Primecuts – This Week in the Journals

October 11, 2019


By Kirsten Salline, MD

Peer Reviewed

With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature. This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose.

Evidence Relating Health Care Provider Burnout and Quality of Care: A Systematic Review and Meta-analysis [1]

Healthcare provider burnout has become a popular research topic as of late; however, burnout assessment and analysis are not standardized, leaving results prone to several types of bias. This systematic review and meta-analysis aimed to produce an overall estimation of the relationship between healthcare provider burnout and quality of care, while also analyzing sources of bias.

Researchers included 123 publications on 142 study populations in their final analysis. These studies encompassed a total of 241,533 healthcare providers – physicians, nurses, and other providers, across both adult and pediatric, inpatient and outpatient settings.

Quality-of-care outcomes were grouped by category and compared to measures of burnout. Of the 114 burnout-quality combinations, 51% showed an inverse relationship between burnout and quality of care, 5% showed a positive relationship between burnout and quality of care, and 44% showed no relationship.

The authors also found that there is a disproportionately larger number of studies published with significant results than would be expected by chance (73% observed versus 62% predicted; P=0.011), indicating that the current literature may be affected by reporting bias.

In the end, the lack of standardization for measuring and reporting burnout and quality of care makes it difficult to determine the true relationship. Further studies with pre-specified primary outcomes and analysis plans are required to better elucidate the relationship and reduce the risk of bias.

Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure [2]

Older ICU patients with underlying cardiac and pulmonary disease are at risk of failing extubation. High-flow nasal cannula (HFNC) has been shown to be noninferior to non-invasive ventilation (NIV) in preventing reintubation in patients, but HFNC combined with NIV, compared to NFNC alone, had not been previously studied.

This multicenter, randomized controlled trial did the above comparison among patients at high risk of extubation failure, defined as age over 65 or chronic cardiac or pulmonary disease. Other inclusion criteria were intubation for more than 24 hours in an ICU and successful completion of a spontaneous breathing trial (SBT). Patients in the NIV + HFNC group received at least 4 hours of NIV immediately after extubation and for a minimum of 12 hours per day in the first 48 hours after extubation. The rest of the time was spent with HFNC. The primary outcome was reintubation rate at day 7.

648 patients were randomized and 641 were included in analysis. Randomization was stratified by PaCO2 at the end of the SBT. The 7-day reintubation rate was 11.8% with NIV + HFNC and 18.2% in NFNC alone, for a difference of -6.4% (95% CI, -12.0% to -0.9%; P=0.02).

This study may have been influenced by the open nature of its design: Physicians were aware of group allocation, which may have altered the decision to reintubate despite having standardized reintubation criteria. It does show, however, that among patients at high risk of reintubation, a combination of NIV and HFNC can be effective.

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm [3]

The effectiveness of hypothermia after cardiac arrest from a nonshockable rhythm (asystole or pulseless electrical activity) to improve neurologic outcomes has mixed evidence.

This study was an open-label, multi-center, randomized controlled trial with blinded outcome assessment conducted in 25 ICUs in France. Adults over the age of 18 who were resuscitated after a cardiac arrest from a nonshockable rhythm from any cause, and with a post-resuscitation Glasgow Coma Scale score of 8 or less, were included.

Patients were randomized 1:1 to moderate hypothermia (33°C) or normothermia (37°C). The primary outcome was a favorable 90-day neurologic outcome, defined as a Cerebral Performance Category (CPC) scale score of 1 or 2. CPC is a scale from 1 to 5, with a score of 1 indicating full recovery or mild disability and a score of 5 indicating brain death.

A total of 584 patients were randomized and 581 were included in the analysis. In both groups, most cardiac arrests were out-of-hospital and had non-cardiac causes. At the end of 90 days, 29 patients in the hypothermia group (10.2%) compared to 17 patients in the normothermia group (5.7%) had a favorable neurologic outcome with a CPC score of 1 or 2 (difference 4.5%; 95% CI, 0.1-8.9%; P=0.04). 90-day mortality did not differ between the two groups.

A 4.5% increase in neurologic recovery, while borderline statistically significant, offers a potentially clinically significant increase in chances of neurologic recovery, without worsening mortality or adverse events. In a patient group with an overall poor prognosis, moderate hypothermia appears to offer a somewhat improved chance of neurologic recovery.

Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock: The SEPSIS-ACT Randomized Clinical Trial [4]

The first-line vasopressor for adults with septic shock is norepinephrine. However, norepinephrine is associated with many side effects, including peripheral tissue ischemia. Selepressin is a selective vasopressin V1a receptor agonist that may be useful in treating septic shock, and with fewer side effects than norepinephrine or vasopressin, a nonselective vasopressin receptor agonist.

This study was a blinded, randomized, placebo-controlled, phase 2b/3 clinical trial which aimed to first determine the efficacy of multiple selepressin dosing regimens (phase 2b) and then confirm the efficacy of that dose in a 1:1 comparison of optimal dose to placebo (phase 3). Included patients were adults older than 18 years with septic shock requiring more than 5ug/min of norepinephrine for more than 1 hour despite 1L of fluid resuscitation. The primary endpoint was the number of ventilator- and vasopressor-free days counted at day 30 from initiation of the study drug.

868 patients were enrolled, with 585 assigned to one of three selepressin dosing regimens, and 283 to placebo; 828 were included in the analysis. The trial was stopped for futility. The primary endpoint of ventilator- and vasopressor-free days did not differ between the selepressin and placebo groups (mean, 15.0 versus 14.5 days; 95% CI, -1.3 to 2.4; P=0.30). The secondary endpoints, including 90-day mortality, also did not differ.

Selepressin, a promising new vasopressor, needs to undergo further testing to elucidate whether it will have a role in the treatment of septic shock.

Minicuts

Differences in COPD Exacerbation Risk Between Women and Men: Analysis from the UK Clinical Practice Research Datalink Data [5]

In a retrospective cohort study of 22,429 UK patients newly diagnosed with COPD, women, especially those aged 40-65, were at higher risk of moderate or severe COPD exacerbation and had a shorter median time to first COPD exacerbation when compared to men. This study highlights the importance of diagnosing and adequately treating younger women with COPD.

Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults [6]

In a matched cohort study of European patients with NAFLD or NASH, patients with NAFLD or NASH had a moderately higher risk of MI compared to matched controls (HR 1.17; 95% CI, 1.05-1.30), but this association went away after adjusting for cardiovascular risk factors including diabetes, hypertension, hyperlipidemia, and statin use. A similar trend was observed for stroke risk. This study suggests that NAFLD or NASH is not an independent predictor of cardiovascular risk.

Ticagrelor in Patients with Stable Coronary Disease and Diabetes [7]

In a randomized, double-blinded, placebo-controlled trial of patients with stable coronary artery disease and type 2 diabetes, patients randomized to receive aspirin and ticagrelor had a lower incidence of cardiovascular death, MI or stroke, but they had a higher incidence of major bleeding compared to patients on aspirin and placebo. In this population, ticagrelor appears to be protective against MI and stroke, but the 0.8% absolute risk reduction, while statistically significant, may not be worth the added bleeding risk.

Efficacy and Safety of Early vs Elective Colonoscopy for Acute Lower Gastrointestinal Bleeding [8]

In an open-label, randomized controlled trial of 170 patients presenting to hospitals with acute lower GI bleeding in Japan, early colonoscopy (within 24 hours of presentation) did not increase the identification of signs of recent bleeding and was associated with a higher, though not statistically significant, rate of rebleeding within 30 days compared to late colonoscopy (24-96 hours after presentation). Delaying colonoscopy beyond the first 24 hours after presentation does not appear to decrease the rate of bleeding source identification.

Dr. Kirsten Salline is a first-year resident physician at NYU Langone Health

Peer reviewed by Christian Torres, MD, chief resident, internal medicine, NYU School of Medicine

Image courtesy of Wikimedia Commons

References

[1] Tawfik DS, Scheid A, Profit J, et al. Evidence Relating Health Care Provider Burnout and Quality of Care: A Systematic Review and Meta-analysis. Ann Intern Med. Published online October 08, 2019. doi: 10.7326/M19-1152 https://annals.org/aim/article-abstract/2752698/evidence-relating-health-care-provider-burnout-quality-care-systematic-review

[2] Thille AW, Muller G, Gacouin A, et al. Effect of Postextubation High-Flow Nasal Oxygen With Noninvasive Ventilation vs High-Flow Nasal Oxygen Alone on Reintubation Among Patients at High Risk of Extubation Failure: A Randomized Clinical Trial. JAMA. Published online October 02, 2019. doi:10.1001/jama.2019.14901 https://jamanetwork.com/journals/jama/article-abstract/2752582

[3] Lascarrou, J-B, Merdji, H, Le Gouge, A, et al. Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm. N Eng J Med. Published online October 02, 2019. doi: 0.1056/NEJMoa1906661 https://www.nejm.org/doi/full/10.1056/NEJMoa1906661

[4] Laterre P, Berry SM, Blemings A, et al. Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock: The SEPSIS-ACT Randomized Clinical Trial. JAMA. Published online October 02, 2019. doi:10.1001/jama.2019.14607 https://jamanetwork.com/journals/jama/article-abstract/2752580

[5] Stolz, D, Kostikas, K, Loefroth, E, et al. Differences in COPD Exacerbation Risk Between Women and Men: Analysis From the UK Clinical Practice Research Datalink Data. Chest. 2019; 156(4), 674-684. doi:10.1016/j.chest.2019.04.107. https://journal.chestnet.org/article/S0012-3692(19)31055-4/fulltext

[6] Alexander, M, Loomis, AK, van der Lei, J, et al. Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults. BMJ. 2019; 367 :l5367. doi: 10.1136/bmj.l5367 https://www.bmj.com/content/367/bmj.l5367

[7] Steg, PG, Bhatt, DL, Simon, T, et al., Ticagrelor in Patients with Stable Coronary Disease and Diabetes. N Engl J Med. 2019; 381(14): 1309-1320. doi: 10.1056/NEJMoa1908077 https://www.nejm.org/doi/full/10.1056/NEJMoa1908077

[8] Niikura, R, Nagata, N, Yamada, A, et al., Efficacy and Safety of Early vs Elective Colonoscopy for Acute Lower Gastrointestinal Bleeding. Gastroenterology. Published online September 26, 2019. doi:10.1053/j.gastro.2019.09.010 https://www.gastrojournal.org/article/S0016-5085(19)41343-7/fulltext

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