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      Visualizing Clinical Evidence: Citation Networks for the Incubation Periods of Respiratory Viral Infections


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          Simply by repetition, medical facts can become enshrined as truth even when there is little empirical evidence supporting them. We present an intuitive and clear visual design for tracking the citation history of a particular scientific fact over time. We apply this method to data from a previously published literature review on the incubation period of nine respiratory viral infections. The resulting citation networks reveal that the conventional wisdom about the incubation period for these diseases was based on a small fraction of available data and in one case, on no retrievable empirical evidence. Overall, 50% of all incubation period statements did not provide a source for their estimate and 65% of original sources for incubation period data were not incorporated into subsequent publications. More standardized and widely available methods for visualizing these histories of medical evidence are needed to ensure that conventional wisdom cannot stray too far from empirically supported knowledge.

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          Most cited references6

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          An outbreak of influenza aboard a commercial airliner.

          A jet airliner with 54 persons aboard was delayed on the ground for three hours because of engine failure during a takeoff attempt. Most passengers stayed on the airplane during the delay. Within 72 hours, 72 per cent of the passengers became ill with symptoms of cough, fever, fatigue, headache, sore throat and myalgia. One passenger, the apparent index case, was ill on the airplane, and the clinical attack rate among the others varied with the amount of time spent aboard. Virus antigenically similar to A/Texas/1/77(H3N2) was isolated from 8 of 31 passengers cultured, and 20 of 22 ill persons tested had serologic evidence of infection with this virus. The airplane ventilation system was inoperative during the delay and this may account for the high attack rate.
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            "Drink at least eight glasses of water a day." Really? Is there scientific evidence for "8 x 8"?

            H Valtin (2002)
            Despite the seemingly ubiquitous admonition to "drink at least eight 8-oz glasses of water a day" (with an accompanying reminder that beverages containing caffeine and alcohol do not count), rigorous proof for this counsel appears to be lacking. This review sought to find the origin of this advice (called "8 x 8" for short) and to examine the scientific evidence, if any, that might support it. The search included not only electronic modes but also a cursory examination of the older literature that is not covered in electronic databases and, most importantly and fruitfully, extensive consultation with several nutritionists who specialize in the field of thirst and drinking fluids. No scientific studies were found in support of 8 x 8. Rather, surveys of food and fluid intake on thousands of adults of both genders, analyses of which have been published in peer-reviewed journals, strongly suggest that such large amounts are not needed because the surveyed persons were presumably healthy and certainly not overtly ill. This conclusion is supported by published studies showing that caffeinated drinks (and, to a lesser extent, mild alcoholic beverages like beer in moderation) may indeed be counted toward the daily total, as well as by the large body of published experiments that attest to the precision and effectiveness of the osmoregulatory system for maintaining water balance. It is to be emphasized that the conclusion is limited to healthy adults in a temperate climate leading a largely sedentary existence, precisely the population and conditions that the "at least" in 8 x 8 refers to. Equally to be emphasized, lest the message of this review be misconstrued, is the fact (based on published evidence) that large intakes of fluid, equal to and greater than 8 x 8, are advisable for the treatment or prevention of some diseases and certainly are called for under special circumstances, such as vigorous work and exercise, especially in hot climates. Since it is difficult or impossible to prove a negative-in this instance, the absence of scientific literature supporting the 8 x 8 recommendation-the author invites communications from readers who are aware of pertinent publications.
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              Determination of the appropriate quarantine period following smallpox exposure: an objective approach using the incubation period distribution.

              Determination of the most appropriate quarantine period for those exposed to smallpox is crucial to the construction of an effective preparedness program against a potential bioterrorist attack. This study reanalyzed data on the incubation period distribution of smallpox to allow the optimal quarantine period to be objectively calculated. In total, 131 cases of smallpox were examined; incubation periods were extracted from four different sets of historical data and only cases arising from exposure for a single day were considered. The mean (median and standard deviation (SD)) incubation period was 12.5 (12.0, 2.2) days. Assuming lognormal and gamma distributions for the incubation period, maximum likelihood estimates (and corresponding 95% confidence interval (CI)) of the 95th percentile were 16.4 (95% CI: 15.6, 17.9) and 16.2 (95% CI: 15.5, 17.4) days, respectively. Using a non-parametric method, the 95th percentile point was estimated as 16 (95% CI: 15, 17) days. The upper 95% CIs of the incubation periods at the 90th, 95th and 99th percentiles were shorter than 17, 18 and 23 days, respectively, using both parametric and non-parametric methods. These results suggest that quarantine measures can ensure non-infection among those exposed to smallpox with probabilities higher than 95-99%, if the exposed individuals are quarantined for 18-23 days after the date of contact tracing.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                29 April 2011
                : 6
                : 4
                : e19496
                [1 ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [2 ]Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                University of Hong Kong, Hong Kong
                Author notes

                Conceived and designed the experiments: JL NGR DATC. Analyzed the data: NGR. Wrote the paper: JL NGR TMP DATC. Designed and created the citation network graphics: JL.

                Reich et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                : 2 November 2010
                : 8 April 2011
                Page count
                Pages: 6
                Research Article
                Clinical Epidemiology
                Disease Informatics
                Infectious Disease Epidemiology
                Infectious Diseases
                Viral Diseases
                Common Cold
                Human Metapneumovirus Infection
                Human Parainfluenza Virus Infection
                Rhinovirus Infection
                Science Policy
                Research Assessment
                Research Validity
                Research Errors
                Publication Practices



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