Monthly Archives: October 2013

Does Vitamin C prevent pneumonia?

Hemila H, Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst Rev. 2013 Aug 8;8:CD005532. (Review) PMID: 23925826

BACKGROUND: Pneumonia is one of the most common serious infections, causing two million deaths annually among young children in low-income countries. In high-income countries, pneumonia is mostly a problem of the elderly.

OBJECTIVES: To assess the prophylactic and therapeutic effects of vitamin C on pneumonia.

SEARCH METHODS: We searched CENTRAL 2013, Issue 3, MEDLINE (1950 to March week 4, 2013), EMBASE (1974 to April 2013) and Web of Science (1955 to April 2013).

SELECTION CRITERIA: To assess the therapeutic effects of vitamin C, we selected placebo-controlled trials. To assess prophylactic effects, we selected controlled trials with or without a placebo.

DATA COLLECTION AND ANALYSIS: Two review authors independently read the trial reports and extracted data.

MAIN RESULTS: We identified three prophylactic trials which recorded 37 cases of community-acquired pneumonia in 2335 people. Only one was satisfactorily randomised, double-blinde, and placebo-controlled. Two trials examined military recruits and the third studied boys from “lower wage-earning classes” attending a boarding school in the UK during World War II. Each of these three trials found a statistically significant (80% or greater) reduction in pneumonia incidence in the vitamin C group. We identified two therapeutic trials involving 197 community-acquired pneumonia patients. Only one was satisfactorily randomised, double-blinded, and placebo-controlled. That trial studied elderly patients in the UK and found lower mortality and reduced severity in the vitamin C group; however, the benefit was restricted to the most ill patients. The other therapeutic trial studied adults with a wide age range in the former Soviet Union and found a dose-dependent reduction in the duration of pneumonia with two vitamin C doses. We identified one prophylactic trial recording 13 cases of hospital-acquired pneumonia in 37 severely burned patients; one-day administration of vitamin C had no effect on pneumonia incidence. The identified studies are clinically heterogeneous which limits their comparability. The included studies did not find adverse effects of vitamin C.

AUTHORS’ CONCLUSIONS: The prophylactic use of vitamin C to prevent pneumonia should be further investigated in populations who have a high incidence of pneumonia, especially if dietary vitamin C intake is low. Similarly, the therapeutic effects of vitamin C should be studied, especially in patients with low plasma vitamin C levels. The current evidence is too weak to advocate prophylactic use of vitamin C to prevent pneumonia in the general population. Nevertheless, therapeutic vitamin C supplementation may be reasonable for pneumonia patients who have low vitamin C plasma levels because its cost and risks are low.


General Practice(GP)/Family Practice(FP):  The tangible evidence of the potential effectiveness of Vitamin C in patients with pneumonia gives new life to a much used, but perhaps scientifically underrated, substance

General Internal Medicine-Primary Care(US): The consistency of the benefits across the various trials, and the dose response is enlightening. It suggests we should seriously consider vitamin c supplementation in older adults diagnosed with community-acquired pneumonia.

Do bed bugs transmit diseases to humans?

DynaMed Resident Focus

Insufficient Evidence that Bed Bugs are a Vector for Disease Transmission to Humans

Bed bugs (Cimex lectularius) are arthropods that feed on the blood of humans and/or domestic animals. Typically they are uncommon in developed countries, but a resurgence of outbreaks has increased medical interest. It has been postulated that bed bugs could transmit pathogens to humans. Over 40 pathogens have been considered candidates for transmission, but the evidence is very heterogeneous and sometimes incomplete concerning this issue. According to this clinical review article, evidence for disease transmission by bed bugs is lacking.

In this systematic review, authors reviewed and summarized 53 articles that met inclusion criteria. Information published from 1960 to 2008 was sought using computer-assisted literature searches in computer databases, including MEDLINE and EMBASE; manual searches were also used to identify pertinent articles in sources frequently not included in computer databases, such as newspapers and older journals. The search strategy was limited to English language papers and used the medical subject heading term “bed bugs” with publication types including clinical trials or randomized controlled trials. There were 16 studies found investigating potential disease transmission of Chagas disease, filariasis, HIV, or hepatitis B virus (HBV).

Vector competence refers to the ability to acquire, maintain, and transmit an infectious agent. Bed bugs were hepatitis B surface antigen positive in samples collected from South Africa, Senegal, Egypt, the Ivory Coast, and China, thus displaying pathogen acquisition. Regarding maintenance of infection, HBV DNA has been detected by polymerase chain reaction assays in bed bugs and their excrement up to 6 weeks after feeding on infected blood. However, no evidence of viral replication has been detected in bed bugs manually infected with HBV. In regards to transmission of disease, an experiment with chimpanzees failed to demonstrate infections or seroconversion in the primates 2 weeks after HBV-infected bed bugs took a blood meal from them. In another study, despite 100% reduction of bed bug numbers in a bed bug eradication project in Gambia, there was no effect on rates of HBV infection in children. The conclusion drawn from this study was that Hepatitis B was probably being spread through some route other than bed bugs.

There is still a possibility that certain illnesses may spread through bed bug bites. In 1 study of Chagas disease, white mice were infected with Trypanosoma cruzi (the causative agent) 15 days after being bitten by infected bed bugs. No human studies have been done to see if Chagas disease can be spread to humans through bed bugs.

Support for bed bugs as vectors for transmission of human disease in general is lacking. No study has been performed showing that an infection is passed to humans through bed bugs and one study did not find that bed bug eradication changed HBV infection rates. Even in animal studies the evidence is very limited. Further analysis of cohort studies in endemic areas might help support evidence against vector competency of bed bugs for reassurance of the general public who are exposed to bed bugs.

Reference: Jerome G, deShazo R. Bed Bugs (Cimicidae lectularius) and Clinical Consequence of Their Bites. JAMA. 2009;301(13):1358-1366

For more information, see Bed bug bites in DynaMed.

Does adenotonsillectomy improve outcomes in children with obstructive sleep apnea?

Bottom Line

Early adenotonsillectomy and watchful waiting both options for children with sleep apnea.  Early surgery provides some symptomatic benefit and greater normalization of polysomnographic findings (a disease-oriented outcome) than watchful waiting for children with obstructive sleep apnea (OSA). However, many of the children in the watchful-waiting group improved during the study period, and there were no cognitive or behavioral consequences to watchful waiting. Thus, either approach is a reasonable option. (LOE = 1b)


Marcus CL, Moore RH, Rosen CL, et al, for the Childhood Adenotonsillectomy Trial (CHAT). A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med 2013;368(25):2366-2376.

  • Study Design: Randomized controlled trial (single-blinded)
  • Funding: Government
  • Setting: Outpatient (specialty)
  • Allocation: Concealed


More than half a million children in the United States still get their tonsils and adenoids removed each year, with the most common indication being OSA. This multicenter trial included children, aged 5 years to 9 years, with an apnea-hypopnea index (AHI) score of 2 or more events per hour or an obstructive apnea index (OAI) score of at least 1 event per hour. The authors excluded children who had severe OSA, characterized by an AHI score greater than 30 per hour, an OAI score greater than 20 per hour, or an O2 saturation of less than 90% for 2% or more of sleep time. Children with significant obesity (the top 0.13% of body mass index for age), those taking medications for attention-deficit/hyperactivity disorder (ADHD), and those with recurrent tonsillitis were also excluded. The authors recruited a total of 464 children — who were randomized to receive adenotonsillectomy within 4 weeks (early surgery group) or watchful waiting — and followed them up for 7 months. Sixteen children in each group did not receive the assigned treatment. There were 30 patients lost to follow-up or who withdrew from the early surgery group; 23 in the watchful waiting group. Groups were similar at the beginning of the study: approximately half the children were girls, slightly less than half were obese or overweight, and slightly more than half were black. The outcomes were mixed. The primary outcome of measures of attention and executive function by masked outcome assessors showed no significant difference between groups. Unmasked assessment of behavior by parents using the Connors’ scale for ADHD found greater improvement in the early surgery group, as did the parental assessment of executive function and behavior. Unmasked assessment of symptoms and quality of life showed slightly greater improvement in the early surgery group. Polysomnographic abnormalities improved more in the early surgery group (from 4.8 to 1.3 per hour in the early surgery group and from 4.5 to 2.9 in the watchful-waiting group). However, it’s important to note that these differences were small and did not meet the usual cutoff for a clinically important difference. In general, a “clinically important difference” requires a change of at least 10% to 15% on a rating scale, and the above improvements were closer to a 5% difference between groups on the scale.

Low Diagnostic Yield of Elective Coronary Angiography

Reference: Patel MR, Peterson ED, Dai D. New England Journal of Medicine 2010 Mar 11;362:886-895.


Background Guidelines for triaging patients for cardiac catheterization recommend a risk assessment and noninvasive testing. We determined patterns of noninvasive testing and the diagnostic yield of catheterization among patients with suspected coronary artery disease in a contemporary national sample.

Methods From January 2004 through April 2008, at 663 hospitals in the American College of Cardiology National CardiovascularData Registry, we identified patients without known coronary artery disease who were undergoing elective catheterization.The patients’ demographic characteristics, risk factors, and symptoms and the results of noninvasive testing were correlated with the presence of obstructive coronary artery disease, which was defined as stenosis of 50% or more of the diameter of the left main coronary artery or stenosis of 70% or more of the diameter of a major epicardial vessel.

Results A total of 398,978 patients were included in the study.The median age was 61 years; 52.7% of the patients were men,26.0% had diabetes, and 69.6% had hypertension. Noninvasive testing was performed in 83.9% of the patients. At catheterization,149,739 patients (37.6%) had obstructive coronary artery disease.No coronary artery disease (defined as <20% stenosis in all vessels) was reported in 39.2% of the patients. [Non-obstructive coronary artery disease was reported in 23.2% of the patients. A total of 60.8% of the patients had coronary artery disease with >20% stenosis in one or more vessels.—M Crouch comment] Independent predictors of obstructive coronary artery disease included male sex (odds ratio, 2.70; 95% confidence interval [CI], 2.64 to2.76), older age (odds ratio per 5-year increment, 1.29; 95%CI, 1.28 to 1.30), presence of insulin-dependent diabetes (odds ratio, 2.14; 95% CI, 2.07 to 2.21), and presence of dyslipidemia (odds ratio, 1.62; 95% CI, 1.57 to 1.67). Patients with a positive result on a noninvasive test were moderately more likely to have obstructive coronary artery disease than those who didnot undergo any testing (41.0% vs. 35.0%; P<0.001; adjusted odds ratio, 1.28; 95% CI, 1.19 to 1.37).

Conclusions In this study, slightly more than one third of patients without known disease who underwent elective cardiac catheterization had obstructive coronary artery disease. [Almost two-thirds of the patients had significant coronary artery disease with >20% stenosis in one or more coronary artery segments.—MC comment] Better strategies for risk stratification are needed to inform decisions and to increase the diagnostic yield of cardiac catheterization in routine clinical practice. [dubious conclusion—MC comment]

Source Information: From the Duke Clinical Research Institute, Duke University, Durham, NC (M.R.P., E.D.P., D.D., J.M.B., P.S.D.); University of California at San Francisco, San Francisco (R.F.R., R.G.B.); and the University of Texas Health Science Center, Houston (H.V.A.). Address reprint requests to Dr. Patel at the Duke Clinical Research Institute, DukeUniversityMedicalCenter, P.O. Box 17969, Durham, NC27715

The problem with Patel et al’s interpretation of the elective coronary angiography data in the March NEJM article, is that it ignores the 23.2% of patients found to have non-obstructive CAD (20-49% left main or 20-69% other coronary stenosis). These patients are also at high risk for myocardial infarction (and stroke, since they are likely to have concomitant carotid artery disease). Aggressive medical management of their reversible risk factors is advisable to reduce their cardiovascular event risk. If they are like my patients, many of them are reluctant to take statins unless they think they “have to.” Finding out that they have clinically significant coronary artery disease breaks through their denial of their high-risk status. Knowing that they have coronary artery disease makes many of them more receptive to starting and continuing statin therapy.

So detecting those with sub-critical CAD can prevent some heart attacks and save some lives. If the non-obstructive CAD cases are added to the obstructive CAD, that makes the diagnostic yield 60.8%. Patel et al’s “glass half empty” conclusion is that a little over one-third of the patients had obstructive coronary disease. My “glass half full” conclusion is that almost two-thirds of the patients had clinically significant coronary artery disease. It seems to me that 60.8% is a very acceptable diagnostic yield for a condition that is still the leading cause of death each year in the U.S. (see above).

My opinion is that Patel et al’s conclusion that “Better strategies for risk stratification are needed to inform decisions and to increase the diagnostic yield of cardiac catheterization in routine clinical practice” is not a valid conclusion.

Michael Crouch, MD, MSPH   5/28/10

Routine stress testing after negative Troponin tests seldom helpful

Clinical question: What is the diagnostic yield of performing routine stress testing in patients who have tested negative for acute coronary artery syndrome?

Bottom Line:  Fewer than 1% of patients who present to the ER with acute chest pain and then undergo routine provocative cardiac testing after 2 sets of negative serum troponin results are likely to benefit from angioplasty (American Heart Association [AHA] class I or IIa). False-positive results will be common.(True positive rate 51.2%) (LOE = 2b)


Hermann LK, Newman DH, Pleasant WA, et al. Yield of routine cardiac testing among patients in an emergency department-based chest pain unit. JAMA Intern Med 2013; 173(12):1128-1133.

Study Design: Cohort (retrospective)

Funding: Self-funded or unfunded

Setting: Emergency department

Allocation: Unknown

Synopsis: The AHA recommends provocative testing (eg, stress testing) in patients with acute chest pain who have negative biomarker results, with the idea that it will identify patients who may benefit from revascularization. The researchers conducting this study identified all patients (N = 4181) without previously identified coronary artery disease who presented to an emergency department over a 6-year period. All included patients had been ruled out for acute coronary syndrome and then had exercise stress testing (n = 512) or myocardial perfusion imaging (n = 3669) while still in the emergency department. Of these patients, 470 (11.2%) had inducible myocardial ischemia. Most were managed medically, but 26.2% of them were deemed to require coronary angiography to determine whether they had obstructive disease that would benefit from revascularization. Of this group, a total of 63 had obstructive disease, but only 28 patients had disease that would benefit from revascularization (AHA class I or IIa). As a result, the true positive rate was only 51.2% for patients undergoing provocative testing and subsequent angiography. Only 0.7% of patients who underwent provocative testing would have benefited from intervention, and an equal percentage had obstructive disease that would have been harmed by catheterization (eg, AHA class III).

Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Tufts University
Boston, MA