Primecuts-This Week in the Journals

November 10, 2015

By: Loren Franco, MD

Russia has suspended all flights to Egypt amidst mounting reports and evidence that a terrorist bomb took down the Metrojet flight to St. Petersburg. Last week on October 31st, a Metrojet plane carrying 224 individuals exploded soon after taking off in a resort town in Egypt on its way to St. Petersburg, killing everyone on board. Soon after the news hit, ISIS affiliates began to take credit for the crash but never described how it was done, prompting authorities to question the validity of the claim. Regardless, both the Russian and British Government are not taking any chances. All British and Russian tourists still in the resort-town of Sharm el-Sheikh in Egypt will be traveling without their checked luggage, which will be transferred to cargo planes upon checking in at the airport. Many still remain stranded in Egypt. 1

Long working hours associated with increase risk of stroke

Beginning with a study that is particularly relevant to physicians, The Lancet has released a meta-analysis studying the risk of coronary heart disease (CHD) and stroke associated with long working hours.2 An extensive systematic review identified 5 published cohort studies that qualified for inclusion. These studies were further supplemented with unpublished data from 20 prospective cohort studies. The meta-analysis, adjusted for age, sex and socioeconomic status (SES), revealed that working long hours (> 55 hours per week) was associated with a modest increase in risk of incident coronary heart disease (non-fatal MI or death), yielding a relative risk (RR) of 1.13 (p=0.02), while a greater and statistically significant risk of incident stroke was found (RR 1.33, P=0.002). A dose-response relationship between the amount of hours worked and incident stroke was also found. Of note, while subgroup differences were generally small, those in lower SES were found to have an increased risk of coronary heart disease with long working hours when compared to those in higher SES, a finding which has been reported in prior studies.3 Factors that may contribute to the increased stroke risk with longer working hours include repetitive triggering of the stress response, physical inactivity (i.e. sitting for long periods), increased alcohol consumption, which has been previously associated with working long hours, and increased likelihood to ignore disease symptoms and delay visiting the physician.4-6 Therefore, physicians may need to pay more attention to prevention and management of stroke risk factors in their patients who work longer hours. Further research is needed to determine whether the risk varies with the amount of exposure to long work hours.

Modified valsalva maneuver more effective than valsalva alone in emergency treatment of supraventricular tachycardias  

The valsava maneuver, which increases parasympathetic tone via vagal stimulation and decreased venous return to the heart, is a universally accepted first-line treatment for supraventricular tachycardias (SVT) in the emergent setting. The REVERT trial, a randomized controlled trial published in The Lancet, assessed whether modifying the valsalva maneuver with the addition of leg elevation and supine positioning would improve its effectiveness.7 433 patients presenting to 10 different emergency departments with SVT (defined as a regular, narrow complex tachycardia on ECG) were randomly assigned to a standard valsalva maneuver (control) or modified valsava (intervention). In both groups, valsalva strain was performed in a semi-recumbent position at 45 degrees, standardized to a pressure of 40mmHg, and sustained for 15s by forced expiration. Patients in the modified group performed the standardized strain and then immediately laid flat with their legs raised to 45 degrees for 15 seconds, followed by an additional 45 seconds in the semi-recumbent position before re-assessment. The primary outcome measured was return to sinus rhythm within 1 minute, while secondary outcomes included the use of adenosine or any other emergency treatment, hospital admission, and adverse events. In the modified valsalva group, 43% of patients achieved sinus rhythm at 1 minute compared to only 17% of the control group (OR 3.7, 95% CI 2.3-5.8, P<0.001) with the absolute difference being 26.2%. Therefore, three patients needed to be treated with the modified valsalva maneuver in order to have one additional patient return to sinus rhythm. Adenosine or any other emergency anti-arrhythmic treatment was needed significantly less in the treatment group compared to the control, and no serious adverse events were reported. This study shows that a simple postural adjustment to the well-known valsalva maneuver is extremely effective in the treatment of SVT and further work should be done in order to implement this in routine clinical practice.

The under recognized burden of adverse events dietary supplements

Dietary supplements encompass a wide variety of substances that include herbals, micronutrients, and amino-acids. As neither safety data nor FDA approval is required before going to market, the only way a dietary supplement can be banned by the FDA is if it is found unsafe after it is used by consumers nation-wide. Since data on the frequency of adverse events related to dietary supplements is at best sparse, a study in the NEJM sought to estimate the amount of emergency department (ED) visits each year related to dietary supplements.8 Using data from 63 hospitals between 2004 and 2013, patients with problems explicitly attributed to the use of dietary supplements by the treating physician were identified. On the basis of 3,667 cases, the study reported a calculated average of 23,005 ED visits and 2,154 hospitalizations related to adverse events from dietary supplements. Over a quarter of these ED visits involved young adults (ages 20 to 34) and a fifth involved ingestion by unsupervised children. After excluding these children from the analysis, 65.9% of the ED visits were estimated to be from herbal or complementary nutritional products and 31.8% from micronutrients. Weight-loss or energy products were implicated in over 70% of adverse events involving palpitations, chest pain, or tachycardia. Over half of these adverse events were in individuals aged 20 to 34 years with the majority being female. Bodybuilding and sexual-enhancing products were also commonly associated with cardiac symptoms. Micronutrients were mostly associated with allergic reactions and swallowing problems (i.e. choking, pill-induced dysphagia or globus), which occurred mostly in the elderly population.

Although limited by the inability to calculate rates of ED visits for specific supplement ingredients or type, this study should still make physicians more aware of the dangers associated with supplements, particularly the cardiac effects. As dietary supplements are not required to identify adverse effects on their packaging, physicians should be encouraged to not only ask patients what supplements they are using but to advise them of associated risks. Additionally, elderly patients should be warned against taking supplements in a pill larger than 22 mm (which is the FDA regulation on pharmaceutical tablets) and should be encouraged to use other vehicles such as liquids or gels. Parents should also be warned to keep their supplements in safe places, as the packaging is generally not childproof in non-iron containing supplements.

Temporal mortality trends in the US

An important part of preventative medicine is the ability to examine long-term mortality trends and identify potential modifiable contributory factors. An investigation sought to update a previous analysis of temporal mortality trends to include more recent years (2002 through 2013) and the results were published in JAMA.9,10 “Cause of death” data was taken from the US national vital statistics from 1969 through 2013 and age-standardized death rates were calculated for all causes combined and the 6 leading causes of death (heart disease, stroke, cancer, injuries, COPD and diabetes). Investigators found that the death rate for all causes combined decreased by 42.9 % with an average annual decrease of 1.3% between the years 1969 and 2013. However in more recent years (between 2010 and 2013), the rate of decline has slowed for stroke and leveled off for heart disease and diabetes. Of the 6 leading causes of death, only COPD death rates were shown to increase (and double) during the last 44 years, but have slowed down in men since 1999. No major differences were found between men and women.

The overall decline in death rates, which can be mostly attributed to a decrease in cancer, stroke, and heart disease, likely reflects better management and treatment of cardiac risk factors and cancer screening.11,12 Smoking cessation has played a critical role in mitigating cancer, heart disease and stroke risk, however the persistent increase in COPD-related deaths (particularly in women) reflects the delayed effects of earlier smoking prevalence. Although all-cause death rates continue to decline in more recent years, the recent slowing of the decline for heart disease, diabetes, and stroke, all of which are obesity-related diseases, may reflect a delayed impact of increasing obesity rates in the United States since the 1980s.


A retrospective cohort study determined that J waves and QRS slurs do not predict an increased risk for cardiovascular death in a long-term follow-up. 13

A multi-center case-control study showed that prenatal exposure to maternal cancer did not impact cognitive, cardiac or general development of children in early childhood, regardless of whether or not the mother received treatment. 14

A study surveying over 37,000 adults showed an overall increase in prescription drug use and polypharmacy from 1999 to 2012, particularly in drug classes that include antihyperlipidemic agents, prescription proton-pump inhibitors, antidepressants, and muscle relaxers. 15

A meta-analysis in JAMA revealed that patients with acute ischemic stroke have better functional outcomes and higher rates of angiographic revascularization when undergoing endovascular mechanical thrombectomy compared to tPA, but no difference was found in all cause mortality at 90 days. 16


  1. Starr B, Jethro Mullen, Steve Almasy, and Tim Hume. “U.S. Official: ‘99.9% Certain’ Bomb on Metrojet Flight –” CNN. Cable News Network, 8 Nov. 2015. Web. 08 Nov. 2015.
  2. Kivimaki M, Jokela M, Nyberg ST, et al. Long working hours and risk of coronary heart disease and stroke: a systematic review and meta-analysis of published and unpublished data for 603 838 individuals. Lancet 2015.
  3. O’Reilly D, Rosato M. Worked to death? A census-based longitudinal study of the relationship between the numbers of hours spent working and mortality risk. International journal of epidemiology 2013;42:1820-30.
  4. Kumar A, Prasad M, Kathuria P. Sitting occupations are an independent risk factor for Ischemic stroke in North Indian population. The International journal of neuroscience 2014;124:748-54.
  5. Mazzaglia G, Britton AR, Altmann DR, Chenet L. Exploring the relationship between alcohol consumption and non-fatal or fatal stroke: a systematic review. Addiction 2001;96:1743-56.
  6. Steptoe A, Kivimaki M. Stress and cardiovascular disease: an update on current knowledge. Annual review of public health 2013;34:337-54.
  7. Appelboam A, Reuben A, Mann C, et al. Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial. Lancet 2015.
  8. Geller AI, Shehab N, Weidle NJ, et al. Emergency Department Visits for Adverse Events Related to Dietary Supplements. The New England journal of medicine 2015;373:1531-40.
  9. Jemal A, Ward E, Hao Y, Thun M. Trends in the leading causes of death in the United States, 1970-2002. Jama 2005;294:1255-9.
  10. Ma J, Ward EM, Siegel RL, Jemal A. Temporal Trends in Mortality in the United States, 1969-2013. Jama 2015;314:1731-9.
  11. Edwards BK, Noone AM, Mariotto AB, et al. Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer 2014;120:1290-314.
  12. Young F, Capewell S, Ford ES, Critchley JA. Coronary mortality declines in the U.S. between 1980 and 2000 quantifying the contributions from primary and secondary prevention. American journal of preventive medicine 2010;39:228-34.
  13. Pargaonkar VS, Perez MV, Jindal A, Mathur MB, Myers J, Froelicher VF. Long-Term Prognosis of Early Repolarization With J-Wave and QRS Slur Patterns on the Resting Electrocardiogram: A Cohort Study. Annals of internal medicine 2015.
  14. Amant F, Vandenbroucke T, Verheecke M, et al. Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy. The New England journal of medicine 2015;373:1824-34.
  15. Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in Prescription Drug Use Among Adults in the United States From 1999-2012. Jama 2015;314:1818-30.
  16. Badhiwala JH, Nassiri F, Alhazzani W, et al. Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis. Jama 2015;314:1832-43.

Loren Franco, MD is a first year resident at NYU Langone Medical Center.

Peer Reviewed by Ian Henderson, MD, Contributing Editor, Clinical Correlations