Primecuts – This Week in the Journals

March 6, 2019

By Mirza Omari, 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.


Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis[1]

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the critically-ill population [2]. Although prior studies have shown that pharmacologic deep venous thrombosis (DVT) prophylaxis with unfractionated or low-molecular weight heparin can reduce the occurrence of VTE events by about half, a significant proportion of patients in the intensive care unit (ICU) setting will still develop deep vein thromboses [3]. Until now, there have been no studies to assess whether the addition of mechanical prophylaxis to pharmacologic agents further reduces the risk of venous thromboembolic events.

The Pneumatic Compression for Preventing Venous Thromboembolism (PREVENT) trial was an international, multi-center, randomized, controlled trial investigating whether the addition of pneumatic compression devices to pharmacologic prophylaxis could further reduce the incidence of VTE in the critically-ill population. The study included 2003 participants from the medical, surgical and trauma intensive care units (ICU). Patients were randomized to receive either intermittent pneumatic compression with pharmacologic VTE prophylaxis or pharmacologic prophylaxis alone – the experimental and control populations shared similar characteristics with regards to demographics and illness severity. Twice-weekly compression ultrasonography was done to assess for lower extremity DVT, whereas evaluation for pulmonary embolism or non-lower extremity DVT was done according to clinical judgment. The primary outcome, incident proximal lower-limb DVT, ensued in 3.9% in the cohort receiving adjunctive pneumatic compression as compared to 4.2% in the pharmacologic prophylaxis only group (RR 0.93; CI 95% 0.6 to 1.44; P=0.74), not achieving statistical significance. This study was limited by a reduction in trial power due to the over-estimation of VTE incidence in the control group, as well as the inability to blind both patients and ultrasonographers to treatment group [1].

While the use of mechanical prophylaxis alone has previously been shown to reduce the risk of VTE when compared to no thromboprophylaxis, these devices are not without their downsides – including increased costs, the potential for skin injury and limitations to patient mobility. Taking all of this into consideration, adjunctive treatment with compression devices may not contribute to a further reduction in the incidence of DVT among critically ill ICU patients, however further studies may be warranted exploring their utility in other patient populations, such as non-ambulatory stroke patients [4].

Association of fried food consumption with all cause, cardiovascular, and cancer mortality: prospective cohort[5]

Chronic diseases such as stroke, diabetes and cardiovascular disease comprise the leading causes of death worldwide [6] with diet and nutrition acting as significant modifiable risk factors for these conditions. Although there is increasing awareness on the impact of food choices on morbidity and mortality, a large proportion of Americans continue to consume fried foods on a daily basis [7].

A recent prospective cohort study aimed to identify an association between the consumption of fried foods and all cause mortality, as well as mortality due to both cardiovascular events and malignancy. The cohort was comprised of 106,966 postmenopausal women of ages 50-79 from the Women’s Health Initiative, a long-term national study involving women from 40 centers across the United States. Fried food consumption was assessed using a food frequency questionnaire describing portion size and type of fat intake. Results of the study demonstrated that once daily fried food consumption was associated with an increase in all cause mortality (multivariable adjusted HR 1.08, 1.01 to 1.16) when compared to those who did not consume fried foods. With regards to specific food intake, both fried chicken and fried fish/shellfish were associated with both increased all cause (HR 1.13 [1.07 to 1.19]; HR 1.07 [1.03 to 1.12], respectively) as well as cardiovascular mortality (HR 1.12 [1.02 to 1.23]; HR 1.13 [1.04 to 1.22], respectively). No association was found between total or specific fried foods and cancer-related deaths [5].

This study is an important initiative in exploring the effect that fried foods may contribute to health – a prevalent public health concern – but it has several limitations. Although the sample size is large, the study is limited to post-menopausal women, an overwhelming majority of whom are white (90.5%), thus limiting its generalizability [8]. Additionally, the results are based on self-reported dietary habits, and therefore prone to bias. The study also lacks detailed information regarding food preparation and may not accurately reflect eating habits of specific populations. Thus, although the study is a promising start, more controlled trials are needed to provide more insight into this complex

Antibiotic management of urinary tract infection in elderly patients in primary care and its association with bloodstream infections and all cause mortality: population based cohort study [9]

Urinary tract infections (UTI) are the most common bacterial infections in the elderly, and are thus responsible for billions of dollars in healthcare costs. This is further complicated by the challenge in accurately diagnosing UTIs in this vulnerable population due to often atypical clinical presentations [10]. In light of increasing antibiotic resistance, physicians are faced with a dilemma on the appropriate use of antibiotics for UTIs in the elderly – balancing the benefits of treating these infections with the potential risk for the development of resistant organisms.

A recent retrospective population-based cohort study conducted in the UK evaluated the association between antibiotic treatment of UTIs in patients 65 years and older with the occurrence of bloodstream infection and all cause mortality within 60 days of diagnosis, with a secondary endpoint of hospitalization rate. Participants presenting with urinary tract infections were divided into three cohorts: those who received antibiotics at the initial doctor’s visit, those who received antibiotics within 7 days of presentation and those who received no prescription. Results of this study showed that patients in the delayed or deferred antibiotic cohorts had an increased likelihood of developing bloodstream infections within 60 days of a UTI (7.12 adjusted OR, CI 6.22-8.14 and 8.08 adjusted OR, CI 7.12-9.16, respectively). Researchers also demonstrated that those without immediate antibiotics had significantly higher 60-day all cause mortality, and approximately double the rate of hospitalizations than those who received antibiotics at presentation [9].

This retrospective cohort study concludes that early initiation of antibiotics in the elderly population – more specifically in males, those over 85, and those from underserved areas – may reduce UTI-related sepsis, hospitalizations and all cause mortality. Although these findings may make physicians more comfortable prescribing antibiotics for UTIs, further research is needed on antibiotic choice and duration in the elderly population, and this decision must be weighed against the risk of antibiotic-related complications.

Pre-hospital advanced airway management for adults with out-of-hospital cardiac arrest: nationwide cohort study[11]

Out of hospital cardiac arrest (OHCA) has unfavorable survival outcomes, with only about 6-8% survival compared to 24% for in-hospital cardiac arrests (IHCA). Multiple factors affect survival in cardiac arrest, with worse outcomes occurring in the presence of co-morbid conditions, and better outcomes associated with high-quality CPR and the presence of a shockable rhythm. Airway management is an important contributor to successful resuscitation, but the impact of Advanced Airway Management (AAM) in survival during OHCA remains unclear [12].

This registry-based prospective cohort study by Izawa et al. examined survival associated with AAM in adults with OHCA. Adult patients with OHCA were divided into two subgroups: those with shockable rhythms (defined as V-fib or pulseless V-tach) and non-shockable rhythms (PEA/asystole). Survivors were followed up to one month and functional outcomes were assessed with the Cerebral Performance Category (CPC) scoring system. Results showed that, while a similar percentage of patients with shockable and non-shockable rhythms received an advanced airway, increased survival was only observed in those with non-shockable rhythms (adjusted RR 1.27, 1.2-1.35). Surprisingly, those who received AAM in the shockable rhythm group experienced worse neurologic outcomes (adjusted RR 0.87, 0.79-0.96), while there was no difference in functional status recorded in those with non-shockable rhythms.

According to the results of this trial, the association of AAM with increased survival in patients with OHCA was dependent on the initial rhythm, with increased survival seen in those with non-shockable rhythm. The study has the potential for significant impact in that it provides insight into different factors that may contribute to survival in OHCA – where good quality CPR and defibrillation are imperative in shockable rhythms, AAM may be beneficial in non-shockable rhythms.

Mini Cuts

Declining Mortality in patient with Acute Respiratory Distress Syndrome. An analysis of the Acute Respiratory Distress Syndrome Network Trials. [13]

This multicenter analysis of ARDS network randomized clinical trials investigates temporal trends and mortality in ARDS. Results showed improvement in ARDS-associated mortality attributed to lung protective ventilation and decreased daily fluid balance. Considering the complexity of ARDS patients in the ICU, this study offers improved understanding on appropriate approaches to management of these patients.

Methicillin resistant Staphylococcus Aureus and Colonization and Pre- and Post- hospital discharge infection risk[14]

This was a retrospective cohort study comparing the rates of MRSA infections of VA hospital inpatients in those with prior MRSA colonization with those who acquired MRSA during of after hospitalization. Results showed increased development of infection during hospitalized in those with prior MRSA colonization, therefore providing insight into the importance of MRSA control measures in colonized patients.

Low dose methotrexate for the prevention of atherosclerotic events. [15]

The CANTOS trial showed that use of a Canakinumab, a monoclonal antibody, reduced cardiovascular events, presumably due to reduction of inflammatory markers [16]. A recent double-blind, randomized clinical trial conducted by the CANTOS trial group hypothesized that low dose methotrexate may also reduce inflammation resulting in fewer cardiovascular events, however, they found no benefit to this effect among patients using low dose methotrexate compared to placebo.

By Mirza Omari, MD, 1st year resident, Neurology Preliminary, NYU Langone-Brooklyn Campus

Peer reviewed by Neil Shapiro, Editor-In-Chief, Clinical Correlations


1.Arabi YM, Al-Hameed F, Burns K, Mehta S et al. Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis. NEJM. 2019. Published 2019 Feb 18. DOI: 10.1056/NEJMoa1816150

2.Cook D, Crowther M, Meade M, Rabbat C, Griffith L, Schiff D, Geerts W, Guyatt G. Deep Venous Thrombosis in medical-surgical critically ill patients: Prevalence, incidence and risk factors. Crit Care. 2005: 33(7):1565-71. Published 2005 July. doi: 10.1097/01.CCM.0000171207.95319.B2.

3.Minet C, Potton L, Bonadona A, et al. Venous thromboembolism in the ICU: main characteristics, diagnosis and thromboprophylaxis. Crit Care. 2015;19(1):287. Published 2015 Aug 18. doi:10.1186/s13054-015-1003-9

4.Khan MT, Ikram A, Saeed O, et al. Deep Vein Thrombosis in Acute Stroke – A Systemic Review of the Literature. Cureus. 2017;9(12):e1982. Published 2017 Dec 23. doi:10.7759/cureus.1982

5.Sun Y, Liu B, Snetselaar LG, Robinson JG, Wallace RB, Peterson LL, Bao W.  Association of fried food consumption with all cause, cardiovascular, and cancer mortality: prospective cohort study. BMJ 2019;364:5420

6.Global Health Estimates 2016: Deaths by Cause, Age, Sex, by Country and by Region, 2000-2016. Geneva, World Health Organization; 2018.

7.Vikraman S, Fryar CD, Ogden CL. Caloric intake from fast food among children and adolescents in the United States, 2011–2012. NCHS data brief, no 213. Hyattsville, MD: National Center for Health Statistics. 2015.

8.Catalyst, Quick Take: Women of Color in the United States (November 7, 2018).

9.Gharbi M, Drysdale JH, Lishman H, Goudie R, Molokhia M, Johnson AP, Holmes AH, Aylin P. Antibiotic management of urinary tract infection in elderly patients in primary care and its association with bloodstream infections and all cause mortality: population based cohort study. BMJ 2019;364:l525

10.Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol. 2015;13(5):269-84.

11.Izawa J, Komukai S, Gibo K, Okubo M, Kiyohara K, Nishiyama C, Kiguchi T, Matsuyama T, Kawamura T, Iwami T, Callaway CW, Kitamura T. Pre-hospital advanced airway management for adults with out-of-hospital cardiac arrest: nationwide cohort study.BMJ. 2019; 364. Published 2019 Feb 28. doi:

12.Daya MR, Schmicker RH, Zive DM, et al. Out-of-hospital cardiac arrest survival improving over time: Results from the Resuscitation Outcomes Consortium (ROC). Resuscitation. 2015;91:108-15.

13.Zhang Z, Spieth P, Chiumello, D, Goyal H, Torres A, Laffey J.G, Hong Y. Declining Mortality in patient with Acute Respiratory Distress Syndrome. An analysis of the Acute Respiratory Distress Syndrome Network Trials. Crit Care. 2019;47(3):315-23. Published 2019 Mar. doi: 10.1097/CCM.0000000000003499

14.Nelson RE, Evans ME, Simbartl L, Jones M, Samore MH, Kralovic SM, Rosell GM, Rubin MA. Methicillin-resistant Staphylococcus aureus Colonization and Pre- and Post-hospital Discharge Infection Risk, Clinical Infectious Diseases. 2019: 68(4) 545-53.Published 2019 Feb 1.

15.Ridker PMEverett BMPradhan AMacFadyen JGSolomon DHZaharris EMam VHasan ARosenberg YIturriaga EGupta MTsigoulis MVerma SClearfield MLibby PGoldhaber SZSeagle ROfori CSaklayen MButman SSingh NLe May MBertrand OJohnston JPaynter NPGlynn RJCIRT Investigators. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019;380(8):752-762. Published 2019 Feb 21.doi: 10.1056/NEJMoa1809798

16. RIdker PM, Everett BM, Thuren T, MacFadyen JG. Antiinflammatory therapy with Canakinumab for Atherosclerotic Disease. NEJM 2017; 377: 1119-31. Published 2017 Sep 21. DOI: 10.1056/NEJMoa1707914