Primecuts – This Week In The Journals

February 29, 2016

Primecuts 2.29.16By Monil Shah, MD

Peer Reviewed

Last week Virgin Galactic, a spaceflight company that aims to bring space tourism to reality, unveiled a new spaceship at the Mojave Air and Space Port in California. The new spaceship has been named Virgin Spaceship (VSS) Unity by Professor Stephen Hawking [1]. VSS Unity is still undergoing preliminary test flights. A seat with VSS Unity will cost around US $250,000. On an interesting note, the world’s first space tourist was an American business man and former NASA engineer Dennis Tito who paid nearly $20 million USD for a trip to the International Space Station in April 2001 [2].

This week in medicine:

Third International Consensus Definitions for Sepsis and Septic shock

Sepsis is a syndrome of physiological, pathologic, and biochemical abnormalities induced by infection that results in significant morbidity and mortality in addition to accounting for nearly $20 billion in total US hospital costs [3]. The definitions of sepsis and septic shock were last revised in 2001 [4]. However, according to a recent study about 1 in 8 patients admitted to critical care units with infection and new organ failure failed to meet the requisite minimum number of 2 SIRS criteria to fulfill the definition of sepsis [5]. New consensus definitions published this week in JAMA now define sepsis as life threatening organ dysfunction caused by a host’s dysregulated response to infection. Furthermore, septic shock is defined as a subset of sepsis with underlying circulatory and cellular/metabolic abnormalities associated with substantial mortality [6]. Organ dysfunction can be identified by an increasing Sequential Organ Failure Assessment [SOFA] score, which includes the PaO2/FiO2 ratio, platelet count, bilirubin, mean arterial pressure or use of vasopressor, GCS scale, urine output, and creatinine. A SOFA score of 2 or more reflects an in-hospital mortality risk of greater than 10%. Patients with septic shock can be identified by a vasopressor requirement to maintain MAP > 65 or serum lactate > 2 mmol/L in the absence of hypovolemia. The presence of these two criteria is associated with in-hospital mortality rates > 40%. Finally, a new bedside clinical score termed quickSOFA (qSOFA) can be used to rapidly identify patients with suspected infection who are likely to have poor outcomes (prolonged ICU course, death). The qSOFA criteria include respiratory rate, altered mental status, and systolic blood pressure <100mmHg. This set of definitions will allow for immediate recognition of critically ill patients requiring prompt medical management to lower in-hospital mortality.

Can Proton Pump Inhibitors Cause Dementia?

Proton pump inhibitors [PPI] are among the most frequently prescribed class of drugs. Observational studies have shown that the majority of PPI prescriptions are considered inappropriate without adequate documentation of gastrointestinal disease [7, 8, 9]. As benign as these medications may seem, they do have significant side effects. The use of PPI has been indirectly associated with cognitive decline. There has been a significant association between the use of PPI and vitamin B12 deficiency [10], and vitamin B12 deficiency has been associated with cognitive decline in elderly [11]. However, the direct association between PPI use and dementia remains uncertain. Recently, a prospective cohort study was conducted using observational data from 2004 to 2011 derived from the largest German statutory health insurer to examine the association between the use of PPI and the risk of dementia in the elderly [12]. In the study 73,679 participants over the age of 75 who were free of dementia at baseline were analyzed based on their coding for insurance. Patients receiving PPI (n = 2950) had a significantly increased risk of dementia compared to patients not receiving PPI (hazard ratio 1.44; 95% CI, 1.36-1.52; P < 0.001). The mechanism by which PPI might influence development of dementia is yet to be determined.

Pioglitazone Use in Reducing TIA or Ischemic Stroke

Patients who have an ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events [13, 14]. Insulin resistance is present in more than 50% of patients without diabetes who have an ischemic stroke or TIA [15]. As such, treatment of insulin resistance represents a potential new strategy for secondary prevention after ischemic stroke or TIA. In a multicenter, double-blind placebo-controlled trial, 3876 patients who had insulin resistance without diabetes were assigned to either pioglitazone or placebo after a recent ischemic stroke or TIA [16]. The primary outcome of the study was first fatal or nonfatal stroke or myocardial infarction (MI). During a median follow-up of 4.8 years, the primary outcome of stroke or MI occurred in 9% of patients in the pioglitazone group compared to 11.8% of patients in the placebo group (hazard ratio 0.76; 95% CI, 0.62 to 0.93; P = 0.007). However, pioglitazone was associated with increased weight gain (52% vs. 33.7% P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1 vs. 3.2%, P=0.003) when compared to placebo.

Text-message Based Smoking Cessation Intervention

Many modalities are available to assist patients with smoking cessation. However, traditional approaches may fall short when it comes to the younger generation. Given the increase in the number of messaging apps on the market, it may be of value to utilize these resources to reach out to young people. Recently, a single-blind randomized clinical trial was conducted to determine the effectiveness of a text-message based smoking cessation intervention in this age demographic [17]. The authors of the study invited college and university students who smoke to participate in a text-messaging based motivational approach to smoking cessation. A total of 1590 participants were enrolled. The primary outcome of the study was complete smoking cessation at 4 weeks and prolonged abstinence at 8 weeks defined as not having smoked more than cigarettes over the past 8 weeks. The treatment arm received 157 text messages over the course of 12 weeks following a set date for cessation which included effective smoking cessation interventions. In comparison, the control group received 1 text every 2 weeks thanking them for their participation in the study. At conclusion of the study, 4-week complete cessation was reported in 20.6% of participants in the intervention group vs. 14.2% of participants in the control group (P = 0.001). Additionally, 8-week prolonged abstinence was reported in 25.9% vs. 14.6% (P< 0.001) of participants. Thus, a text message service may play in unique role in assisting the younger patient population with smoking cessation.

Also in Journals this week:

  • In the Carotid Revascularization Endarterectomy versus Stenting Trial, 10-year follow-up showed no significant difference between patients who underwent stenting and those who underwent endarterectomy with respect to the risk of peri-procedural stroke, myocardial infection, subsequent ipsilateral stroke, or death [18].
  • Among patients undergoing coronary artery surgery, the administration of preoperative aspirin was not related to lower thrombotic risk or higher bleeding risk compared to placebo [19].

Dr. Monil Shah is an Internal Medicine resident at NYU Langone Medical Center

Peer reviewed by  Jennifer Mulliken, MD, Internal Medicine, NYU Langone Medical Center


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  4. Abraham, E. New Definitions for Sepsis and Septic Shock: Continuing Evolution but With Much Still to Be Done. JAMA. 2016 Feb 23;315(8):757-59.
  5. Kaukonen, KM, et al. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015 April 23;372(17):1629-38.
  6. Singer, M., et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10.
  7. Mazer-Amirshahi M, et al. Rising rates of proton pump inhibitor prescribing in US emergency departments. Am J Emerg Med. 2014 June;32(6):618-22.
  8. Lazarus B, et al. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med. 2016 Feb;176(2):238-46.
  9. Cai S., et al. Uncomplicated peptic ulcer in the UK: trends from 1997 to 2005. Aliment Pharmacol Ther. 2009 Aug 26;30(10):1039-48.
  10. Lam JR, et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013 Dec 11;310(22):2435-42.
  11. Vogiatzoglou A, et al. Cognitive Function in an Elderly Population: Interaction Between Vitamin B12 Status, Depression, and Apolipoprotein E4: The Hordaland Homocysteine Study. Psychosom Med. 2013 Jan;75(1):20-29.
  12. Gomm W, et al. Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA Neurol. 2016 Feb 15. doi: 10.1001/jamaneurol.2015.4791. [Epub ahead of print]
  13. Dhamoon MS, et al. Recurrent stroke and cardiac risks after first ischemic stroke The Northern Manhattan Study. Neurology. 2006 Mar;66(5):641-46.
  14. Johnston, SC. Clinical practice. Transient ischemic attack. N Engl Jour Med. 2002 Nov 21; 347(21):1687-92.
  15. Kernan WN, et al. Impaired insulin sensitivity among nondiabetic patients with a recent TIA or ischemic stroke. Neurology. 2003 May 13;60(9):1447-51.
  16. Kernan, WN, et al. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl Jour Med. 2016 Feb 17. [Epub ahead of print]
  17. Müssener U, et al. Effectiveness of Short Message Service Text-Based Smoking Cessation Intervention Among University Students: A Randomized Clinical Trial. JAMA Intern Med. 2016 Feb 22. doi: 10.1001/jamainternmed.2015.8260. [Epub ahead of print]
  18. Brott TG, et al. Long-term results of stenting versus endarterectomy for carotid-artery stenosis. N Engl Jour Med. 2016 Feb 18. [Epub ahead of print]
  19. Myles PS, et al. Stopping vs. Continuing Aspirin before Coronary Artery Surgery. N Engl Jour Med. 2016 Feb 25;374:728-37.