Primecuts – This Week In The Journals

February 10, 2014

By Luke O’Donnell, MD

Peer Reviewed

I guess being single in New York should make me dread Valentine’s Day. But I don’t. Maybe it is my years of studying a language that has words to distinguish love in all its manifestations: the once-in-a-lifetime stuff (amour) versus the form with the same amount of intimacy but less commitment (amant). Anyway, enjoy the first article; it is about an emerging communicable disease. Kisses everyone.

If the ever-looming scare of H5N1 was not enough, the New England Journal of Medicine (NEJM) published an epidemiological study concerning a novel avian influenza (H7N9) that is emerging in eastern China. Following the international scare of severe acute respiratory syndrome (SARS), the Chinese government instituted national surveillance of pneumonia of unknown origin. In February 2013, the database showed an increase in rapidly progressing severe pneumonia. H7N9 was later found to be the cause. There were 139 confirmed cases between February and December 2013, which by the researcher’s models correlates with 27,000 (95% CI, 9350-65000) symptomatic cases [1].

Of these patients, most were older (interquartile range 46-73 years), men (71%), urban dwellers (73%), who had some unspecified underlying medical condition (73%), with a history of animal exposure (82%). Interestingly only 9% of these confirmed cases were in poultry workers. The vast majority of patients were exposed to livestock at urban animal markets where chickens were the primary culprit in 82% of cases [1].

In affected patients, the disease course proved to be severe. The incubation period lasted an average of 6 days, after which symptoms became so overwhelming that 99% of patient needed hospitalization. Ninety percent of these patients were deemed to have pneumonia in lower respiratory track or respiratory failure. Sixty-three percent of patients required intensive care unit (ICU) monitoring. Of the confirmed cases, there was a 34% case fatality, usually from acute respiratory distress syndrome (ARDS) or multi-organ failure [1].

More concerning was the possible human-to-human viral spread in four identified “family clusters.” Studies of these families showed likely spread from the index patient who usually had some history of livestock exposure to a family member who had no contact with animals in any way. While these secondary patients usually had very close/intimate contact with the index patient, there is a fear that viral mutations could make human-to-human transmission easier [1].

While the researchers noted that cases petered out after May 2013, an editor’s note states that there has been an additional 60 confirmed cases since the end of the study period (December 1, 2013). This resurgence possibly correlates with the northern flu season [1].

And if you are inclined to chuck dizziness with the likes of “total body pain,” the Mayo Clinic publish a study that makes this otherwise eye-rolling complaint a whole lot scarier.

Harvard researchers investigated the relationship between dizziness and acute stroke in non-straight forward cases. Citing a 1989 Annual of Emergency Medicine article in this study, dizziness (in all its descriptive nuances that included vertigo, lightheadedness, gait instability) is secondary to a serious cause in 30% of cases. Strokes in the posterior fossa are particularly associated with this complaint and dizziness can be the sole presenting symptom in 10% of cases [2].

In this study, researchers imaged all patients with self-reported complaints of dizziness with unclear etiology. Patients with a straightforward reason for their dizziness were excluded, such as those with focal neurological deficit (clear evidence of a stroke), acute ST-segment elevation, active hemorrhage, hypotension, orthostatic vital signs, diarrheal illness, and hypoglycemia among others. The remaining patients were then imaged either by computer tomography (CT) or magnetic resonance imaging (MRI) and read by the neurology department [2].

Of the 473 patients imaged, 14 (3%) were found to have acute stroke. Unsurprising, these 14 patients were more likely to be older,have hyperlipidemia, hypertension, and coronary artery disease. Interestingly, abnormal tandem gait test was associated with stroke (OR, 3.13; 95% Cl, 1.10-8.89). The rest of the physical exam did not hold up as well: nystagmus, Dix-Hallpike, dysmetria, ataxia, Romberg all had no association with or against acute stroke. In this study, ED clinicians—attendings and emergency medicine residents—were also told to judge the likelihood of stroke as low, moderate, high in these patients before seeing any imaging. As painful as it might be to hear, their gestalt proved the best predictor of strokes in this study (OR, 18.8; 95% CI 4.17-74.5) [2]. This study reflects the benefits of clinical judgment and the ability to synthesize the different aspects of the patient’s history and presentation, over just sole isolated findings.

This next article is for those who share a bed. If they don’t snore now, they probably will…and you have options.

Obstructive sleep apnea (OSA) causes considerable health risks: excessive sleepiness, insulin resistance, vascular disease, and increased risk of death among others. Continuous positive airway pressure is the usual go-to treatment option, but has low patient compliance. A newer possible therapy is hypoglossal nerve stimulation (HGNS). The onset of apnea is accompanied by reduced stimulation of the upper airway muscles leading to decreased patency. With HGNS, an implanted electrode simulates the hypoglossal nerve causing genioglossus contraction and tongue protrusion leading to upper airway patency. This device works by placing a pulsatile electrode on the hypoglossal nerve. The electrode is linked with a ventilator sensory device that is embedded in the fourth intercostal region. Patients activate the device before going to bed. While sleeping, the hypoglossal nerve is stimulated to open up the airway with inspiration [3].

In a NEJM-published prospective cohort study, 126 patients with moderate-to-severe obstructive sleep apnea with poor CPAP compliance were implanted with the device. Patients were then followed for level of sleepiness, apnea-hypopnea index (AHI), and the oxygen desaturation index (ODI). AHI is the number of apnea or hypopnea events per hour. ODI is the number of times per hour that saturation drops more than 4 percentage points below baseline. Patients were followed with polysomnographic study before device activation then at 2, 6, 12 months afterwards. Sleepiness was judged on the Epworth scale and the Functional Outcomes of Sleep Questionnaire (FOSQ) [3].

Results were promising. At 12 months, the AHI decreased by 68%, from 29.3 pre-intervention to 9.0 post intervention. ODI score decreased by 70%, from 25.4 to 7.4. Symptoms of sleepiness also significantly improved. FOSQ increased by 2.9 points (95% CI 2.4-3.5), which was greater than the usually 2-point increase typically consistent with clinical meaningful improvement. The Epworth Sleepiness Scale score at 12 months was consistent with normalization—meaning the score was less than 10, which is consistent with the general public [3].

To further verify these results, researchers blindly withdraw therapy in 46 patients. After 1 week, the mean AHI increased from 7.6 to 25.8 (P<0.001) [3].

So basically if your amour/amant snores (no judgment), there might be other options besides sleeping next to Darth Vader.

Other studies circulating in this week’s literature include:

1. In a retrospective study, active tuberculosis (TB) was found to be an independent risk factor for venous thromboembolism. Using ICD-9-CM codes, researchers searched a database of 30 million for patient with codes for both TB and pulmonary embolism (PE) and/or deep vein thrombosis (DVT). Active TB was found to confer a greater risk of VTE compared to those without TB (odds ratio, 1.55 [95% CI, 1.23-1.97]) [4].

2. In a study in mice, neutralization of IL-1 and IL-18 with anakinra (a IL-1 receptor antagonist) and anti-IL-10 antibodies conferred complete protection from endotoxin-induced lethality associated with sepsis. The importance of this study is that previous focus was on the upstream activators CAPS1 and CAPS11 [5].

3. The Xpert MTB/RIF assay is an automatic nucleic-acid amplification test that can detect both mycobacterium tuberculosis (MTB) complex DNA and rifampicin (RIF) resistance in 2 hours. The targeted audience is developing countries where it could aid with both TB and resistance pattern diagnosis in the primary care setting. The Lancet published a study showing that Xpert MXRT/RIF could be administered successfully by nurses leading to decreased time to treatment commencement. However TB-related morbidity did not decrease. Researchers felt that it was likely secondary to high-levels of empiric treatment in smear-negative or smear-pending patients [6].

4. Young and middle-aged patients with fibromyalgia have poorer quality of life and worst symptoms than older patient with this diagnosis. These patients were also found to have both reduced mental and physical health compared to women of their same age group who did not have fibromyalgia [7].

Coming out this V-day is a less-than-Oscar-worthy movie about nurses in Manhattan…their schedules are just murder (and I stole that line). If you are otherwise too occupied to catch this slasher film Friday night, I posted the trailer here your convenience:

Dr. Luke O’Donnell is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Arnab Ghosh, MD, Contributing Editor, Clinical Correlations

Image courtesy of Wikimedia Commons.


1, Li Q, Zhou L, Zhou M et al. Epidemiology of Human Infectious with Avian Influenza A(H7N9) Virus in China. New England Journal of Medicine. 370(6), 520-532, 2014.

2, Chase M, Goldstein JN, Selim MH et al. A Prospective Pilot Study of Predictors of Acute Stroke in Emergency Department Patients With Dizziness. The Mayo Clinic Proceedings. 89(2), 173-180. 2014.!/ContentPlayerCtrl/doPlayContent/1-s2.0-S0025619613009786

3, Strollo PJ, Soose RJ, Maurer JT et al. Upper-Airway Stimulation for Obstructive Sleep Apnea. The New England Journal of Medicine. 370(2). 139-148. 2014.

4, Dentan C, Epaulard O, Saynaeve D et al. Active Tuberculosis and Venous Thromboembolism: Association According to International Classification of Diseases, Ninth Revision Hospital Discharge Diagnosis Codes. Clinical Infectious Diseases 58(4), 495-501. 2014.

5, Van Den Berghe A, Demon D, Bogart P et al. Simultaneous Targeting of IL-1 and IL-18 is Required for Protection against Inflammatory and Septic Shock. American Journal of Respiratory and Critical Care Medicine 189(3), 282-291. 2014.

6, Theron G, Zijenah L, Chanda D et al. Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicenter, randomized, controlled trail. The Lancet. 383, 424-435. 2014.

7, Jiao J, Vincent A, Cha SS et al. Relation of Age With Symptom Severity and Quality of Life in Patients with Fibromyalgia. The Mayo Clinic Proceedings. 89(2), 199-206. 2014.!/ContentPlayerCtrl/doPlayContent/1-s2.0-S0025619613009816



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