Primecuts – This Week in the Journals

April 24, 2018

By Jennifer Whealdon, MD

Peer Reviewed 

Prior to her passing, former First Lady Barbara Bush announced her decision to forego further aggressive interventions for her chronic medical issues and instead elected for “comfort care”, to spend the final days of her life at home with her loved ones(1).  Her courageous decision revitalized discussion about how we approach end of life care in the United States. Particularly, by publicizing her decision to forego further invasive treatment, she exemplified a thoughtful and intentional consideration for what constitutes quality of life for any given patient and their loved ones.

Continued below is further review of notable publications from the recent medical literature.

Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD; the IMPACT rial 

The recommended treatment per the Global Initiative for Chronic Obstructive Lung Disease for patients with significant symptoms despite dual therapy is triple therapy, which currently requiring the use of multiple inhalers per day. In this industry-sponsored randomized double-blind trial, patients were randomized to daily dual-therapy vs. triple therapy inhaler with the primary outcome being the rate of moderate or severe COPD exacerbations (2). The rate of moderate or severe exacerbations among patients assigned to triple therapy was 0.91 per year, compared to 1.07 and 1.21 per year amongst the dual therapy groups. This difference was statistically significant (p < 0.001). It is worth noting that given the option in the dual therapy group for either LABA-LAMA or inhaled glucocorticoid-LABA, there was a statistically significant reduction in exacerbations in the inhaled glucocorticoid-LAMA group compared to the LAMA-LABA group. This is in contrast to the 2016 FLAME trial (3). This contrast was attributed to variation in patient population and study methods.

The Bottom Line: Triple therapy reduced the rate of moderate of severe COPD exacerbations when compared to dual therapy with LAMA-LABA or inhaled glucocorticoid-LABA. Secondary outcomes were in contrast to the 2016 FLAME trial, showing superiority of inhaled-glucocorticoid-LABA therapy over LABA-LAMA.

Lung Ultrasound Prior to Spontaneous Breathing Trial Is Not Helpful in Weaning the Decision Making Process

Ultrasound is becoming an increasingly integral diagnostic tool in the critical care setting, particularly as a low-cost method for evaluating lung physiology in the mechanically intubated patient. In this prospective observational study, patients in a medical-surgical ICU who were endotracheally intubated underwent lung ultrasound prior to a spontaneous breathing trial(SBT) (4). Patients with a tracheostomy were excluded from the trial. Lung ultrasound was performed to identify B-lines or B-pattern, deemed to be an indicator of interstitial edema. The primary study outcome was SBT failure, characterized by an inability to tolerate T-piece trial for greater than 30 minutes. Ultimately, the presence of B-pattern on ultrasound was found to be a very weak predictor for SBT outcome with a 47% sensitivity and 64% specificity, 25% PPV and 82% NPV. This study is consistent with prior literature demonstrating the poor utility of bedside imaging modalities for predicting success of SBTs. Previous attempts to use ultrasound following diaphragmatic excursion during SBT showed similarly weak predictability for extubation success (5).

The Bottom Line: B-lines or B-pattern detected on bedside ultrasound is not an effective predictive tool for SBT success and should not preclude patients from an SBT trial.

Association between after-hours admission to the intensive care unit, strained capacity, and mortality: a retrospective cohort study

Strained or fixed resources is a palpable stress encountered in the critical care setting, where the discrepancy between available ICU resources and demand for admission and high quality intensive care creates a barrier to effective care of critically ill patients. In this multi-center retrospective observational study, data was analyzed from 9 adult ICUs to investigate the association between strain, defined as available beds <1 or occupancy > 95%, and patient outcomes (6). Using a two-step path analysis model, it was demonstrated that lower bed availability was associated with a higher APACHE-II score, but bed availability and increased occupancy showed no direct effect on ICU mortality. However, the authors found that bed availability and increased occupancy had an indirect effect on ICU mortality mediated by increased illness acuity. This study effectively demonstrated that there are small, but measurable consequences on patient care when ICUs are strained. These results demonstrate a need for strategy development to respond to and manage strain in the ICU setting.

The limitations of this study include its retrospective design, creating susceptibility for confounding bias. More importantly however was the particular and limited definition of strain, which did not include other factors such as patterns of admission, bedside workload and staffing patterns.

The Bottom Line: ICU strain, defined as limited bed availability, has small, but measurable indirect impact on patient outcomes and creates potential for development of new critical care unit design to respond to and adapt to strain.

Relationship between Clinic and Ambulatory Blood-Pressure Measurements and Mortality

Ambulatory blood pressure monitoring has been validated in relatively small populated-based studies as a better predictor of health outcomes than one-time blood pressure readings taken in a clinic setting (7). Following patients in the Spanish Ambulatory Blood Pressure Registry, this observational study aimed to report the prognostic value of clinic and ambulatory blood pressures on total and cardiovascular mortality (8). With a median follow up of 4.7 years, it was demonstrated that ambulatory systolic blood pressure was a stronger predictor of all-cause and cardiovascular mortality than clinic systolic pressure. This result was consistent when accounting for subgroup characteristics including age, sex, obesity, diabetes, other cardiovascular disease, and antihypertensive treatment. This study was one of the first to demonstrate consistently greater mortality associated with masked hypertension than with sustained hypertension, thought to be attributed to delayed detection of elevated blood pressure in the clinical setting alone.

The limitations of this study include its observational design, which limits the inferences that can be made about the treatment value of ambulatory blood pressure monitoring. Additionally, the population studied was primarily white, which limits its applicability to patients of other races.

The Bottom Line: Ambulatory blood pressure monitoring is a stronger predictor of all-cause and cardiovascular mortality than clinic blood pressure readings and may serve as a more effective means of diagnosis.


  1. A recent randomized clinical trial in the Annals of Internal Medicine demonstrated that using a digital interface model that allows patients to self-order testing can increase compliance with routine colorectal screening (9).
  2. A systematic review in Annals demonstrated no convincing evidence that the severe sepsis and septic shock early management bundle, the sepsis performance measure used by Medicare and Medicaid Services, improves survival in patients with sepsis (10).
  3. A recent article in the Journal of Cardiology demonstrated that thiazide diuretic use was associated with higher rates of hospital acquired hyponatremia and mortality when compared to loop diuretics (11).

Dr. Jennifer Whealdon is a 1st year resident at NYU Langone Health

Peer reviewed by Ian Henderson, MD, editor, Clinical Correlations and chief resident in internal medicine, NYU Langone Health.

Image courtesy of Wikimedia Commons


(1) Baker, Peter.  “Barbara Bush, Gravely Ill, Opts to Halt Treatment.” New York Times 15 April 2018. A2. Web. 20 April 2018.

(2) Lipson, D. A., Barnhart, F., Brealey, N., Brooks, J., Criner, G. J., Day, N. C., Pascoe, S. J. (2018). Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. New England Journal of Medicine. doi:10.1056/nejmoa1713901

(3) Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol–glycopyrronium versus salmeterol–fluticasone for COPD. N Engl J Med 2016;374:2222-2234.

(4) Antonio, A. C., Knorst, M. M., & Teixeira, C. (2018). Lung Ultrasound Prior to Spontaneous Breathing Trial Is Not Helpful in Weaning the Decision Making Process. Respiratory Care. doi:10.4187/respcare.05817

(5) Palkar, A., Mayo, P., Singh, K., Koenig, S., Narasimhan, M., Singh, A., Gottesman, E. (2018). Serial Diaphragm Ultrasonography to Predict Successful Discontinuation of Mechanical Ventilation. Lung. doi:10.1007/s00408-018-0106-x

(6)Hall, A. M., Stelfox, H. T., Wang, X., Chen, G., Zuege, D. J., Dodek, P., Bagshaw, S. M. (2018). Association between afterhours admission to the intensive care unit, strained capacity, and mortality: A retrospective cohort study. Critical Care, 22(1). doi:10.1186/s13054-018-2027-8

(7) Sega, R. (2005). Prognostic Value of Ambulatory and Home Blood Pressures Compared With Office Blood Pressure in the General Population: Follow-Up Results From the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) Study. Circulation, 111(14), 1777-1783. doi:10.1161/01.cir.0000160923.04524.5b

(8) Banegas, J. R., Ruilope, L. M., Sierra, A. D., Vinyoles, E., Gorostidi, M., Cruz, J. J., Williams, B. (2018). Relationship between Clinic and Ambulatory Blood-Pressure Measurements and Mortality. New England Journal of Medicine, 378(16), 1509-1520. doi:10.1056/nejmoa1712231

(9) Miller, D. P., Denizard-Thompson, N., Weaver, K. E., Case, L. D., Troyer, J. L., Spangler, J. G., Pignone, M. P. (2018). Effect of a Digital Health Intervention on Receipt of Colorectal Cancer Screening in Vulnerable Patients. Annals of Internal Medicine, 168(8), 550. doi:10.7326/m17-2315

(10) Pepper, D. J., Natanson, C., & Eichacker, P. Q. (2018). Evidence Underpinning the Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock Management Bundle (SEP-1). Annals of Internal Medicine, 168(8), 610. doi:10.7326/l18-0140

(11) Yamazoe, M., Mizuno, A., Kohsaka, S., Shiraishi, Y., Kohno, T., Goda, A., Yoshikawa, T. (2018). Incidence of hospital-acquired hyponatremia by the dose and type of diuretics among patients with acute heart failure and its association with long-term outcomes. Journal of Cardiology, 71(6), 550-556. doi:10.1016/j.jjcc.2017.09.015

(11) Yeh, D. D., Johnson, E., Harrison, T., Kaafarani, H. M., Lee, J., Fagenholz, P.,  Velmahos, G. (2018). Serum Levels of Albumin and Prealbumin Do Not Correlate With Nutrient Delivery in Surgical Intensive Care Unit Patients. Nutrition in Clinical Practice. doi:10.1002/ncp.10087