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Thursday, October 19, 2006

Obesity Epidemic: US Temporal Trends

Although well known to most obesity researchers and epidemiologists, the public generally is not aware of the full magnitude of the obesity epidemic. Below is a classic report by the CDC of the emergence of the obesity epidemic in the United States from the early 1985 to 2004.



















And finally - 2004

(Note the different color scheme)

[Click to enlarge]


A flash animated version of these maps is available here.

These slides are also available for download in Powerpoint format from the Centers of Disease Control and Prevention.

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Thursday, October 05, 2006

Journal Impact Factors for 2005

Impact Factors for leading medical and science journals in 2005 are listed below.
(Source: ISI Journal Citation Reports impact factors tabulated from each journal's public website)

Also visit the online H-index Calculator of Scientist Impact and Influence, powered by Google Scholar.

Additional journal impact factors:

--> Impact Factors of Genetics journals

--> Impact Factors of Cancer journals

--> Impact Factors of Cardiovascular disease journals

--> Impact Factors of Diabetes journals

--> Impact Factors of Epidemiology and Public Health journals

--> Impact Factors of Nutrition and Obesity journals


Journal Impact Factors

(note: review journals are not included)

General (internal) medicine

  1. New England Journal of Medicine 44.0
  2. Nature Medicine 28.9
  3. The Lancet 23.4
  4. Journal of the American Medical Association (JAMA) 23.3
  5. Annals of Internal Medicine 13.3
  6. British Medical Journal (BMJ) 9.0
  7. Public Library of Science (PLOS) Medicine 8.4
  8. Archives of Internal Medicine 8.0
  9. Canadian Medical Association Journal (CMAJ) 7.4
  10. Medicine 5.0
  11. Am J Medicine 4.4
  12. J Internal Medicine 4.0

Basic Science and Biology

  1. Science 30.9
  2. Cell 29.4
  3. Nature 29.3
  4. Nature Immunology 27.0
  5. Nature Genetics 25.8
  6. Nature Cell Biology 19.7
  7. Nature Materials 15.9
  8. Immunity 15.2
  9. J Clinical Investigation 15.1
  10. Molecular Cell 15.0
  11. PLOS Biology 14.7
  12. Developmental Cell 14.6
  13. J Cell Biology 11.0
  14. Proceedings of the National Academy of Science (PNAS) 10.3

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Welcome to Epidemiologic Inquiry. Please subscribe below to our email list for regular updates on new content (average less than 1 email per week).

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    NIH Grant Success Rates and Change from 2004, by NIH institutes FY2005

    The figure below shows a summary of NIH research grant application awards and success rates by NIH institutes in 2005, as well as change in awards and success rates from 2004.

    Overall, results indicate that overall grant success rate dropping by 2.3%, or an absolute grant award decrease by 453 funded projects and -$171 million.

    [Click to image to enlarge]

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    Impact Factors of Genetics Journals

    Below are 2005 journal IMPACT FACTORS for genetics journals.

    Visit here for general science and general clinical journal impact factors.

    Genetics

    Nature Genetics 25.8
    Nature Rev Genetics 19.2
    Genes Dev 15.6
    Ann Rev Genetics 14.0
    Am J Human Genetics 12.6
    Trends Genetics 12.0
    Ann Rev Genomics Human Genetics 10.1
    Genome Res 10.1
    Genome Biology 9.7
    Curr Opin Genetics Dev 9.4
    Human Mutation 7.9
    Human Molecular Genetics 7.8
    Oncogene 6.9
    Molecular Biology Evol 6.2
    Pharmacogenetics 5.9
    Molecular Therapy 5.4
    Mutation Res 5.3
    Genetic Epidemiology 5.1
    DNA Repair 5.0
    Gene Therapy 4.8
    J Mol Medicine (JMM) 4.7
    BMC Evol Biology 4.4
    Human Genetics 4.3
    J Medical Genetics 4.3
    Genetics 4.3
    Am J Medical Genetics (Parts B and C) 4.3 and 3.5
    Evolution 4.2
    BMC Genomics 4.1
    Human Gene Therapy 4.1
    Pharmacogenomics J 4.0
    DNA Res 3.9
    Genes Immunity 3.8
    J Gene Medicine 3.7
    Human Heredity 3.6
    Genes Cells 3.4
    Clinical Genetics 3.3
    Eur J Hum Genetics 3.3
    Genetic in Medicine 3.1

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    Impact Factors of Nutrition and Obesity Journals

    Below are 2005 journal IMPACT FACTORS for nutrition and obesity journals.

    Visit here for general science and general clinical journal impact factors.

    Nutition/Obesity

    Ann Rev Nutrition 8.6
    Am J Clinical Nutrition 5.9
    Int J Obesity 4.5
    Obesity Research 4.0
    Crit Rev Food Science 3.9
    Obesity Surgery 3.8
    J Nutrition 3.7
    Curr Opin Clinical Nutrition 3.3
    British J Nutrition 3.0
    Proc Nutrition Soc 2.6
    Diabetes Obesity and Metabolism 2.5
    Nutrition Rev 2.5
    J Am Diet Assoc 2.4
    Nutrition and Cancer 2.4
    Clinical Nutrition 2.3
    Eur J Nutrition 2.3
    J Am Coll Nutrition 2.2
    Eur J Clinical Nutrition 2.2
    Nutrition 2.1
    Nutrition Res Review 2.1
    Public Health Nutrition 1.9

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    Impact Factors of Cancer Journals

    Below are 2005 journal IMPACT FACTORS for cancer-related journals.

    Visit here for general science and general clinical journal impact factors.

    Cancer

    Cancer Cell 18.7
    J National Cancer Institute 15.2
    J Clinical Oncology 11.8
    Lancet Oncology 7.9
    Cancer Research 7.6
    Carcinogenesis 5.1
    Cancer 4.8
    Int J Cancer 4.7
    Cancer Epidemiology Biomarkers and Prevention 4.5
    Cancer Causes and Control 3.2
    Biomedcentral (BMC) Cancer 2.0

    Review Journals:
    Ca-Cancer J Clin 49.8
    Nature Rev Cancer 31.7
    Cancer Metast Rev 8.0

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    Impact Factors of Diabetes Journals

    Below are journal IMPACT FACTORS for diabetes-related journals.

    Visit here for general science and general clinical journal impact factors.

    Diabetes

    Diabetes 8.0
    Diabetes Care 7.8
    Diabetologia 5.3
    Diabetic Medicine 2.7
    Diabetes Obesity Metab 2.5
    Diabetic Metab Research 2.5
    Nutrition Metab Cardiovascular Diseases 1.5

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    Impact Factors of Cardiovascular Journals

    Below are 2005 journal IMPACT FACTORS for cardiovascular disease-related journals.

    Visit here for general science and general clinical journal impact factors.

    Cardiovascular Diseases

    Circulation 11.6
    Blood 10.1
    Circulation Research 9.4
    J American College Cardiology 9.2
    European Heart J 7.3
    ATVB 7.1
    Hypertension 6.3
    Stroke 5.9
    Cardiovascular Research 5.3
    J Hypertension 5.2
    Atherosclerosis 3.8
    Am Heart J 3.5
    Am J Hypertension 3.5
    Thromb Haemost 3.1
    Am J Cardiology 3.0
    Eur J Cardiov Prev R 2.3

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    Impact Factors for leading medical and science journals in 2005

    Impact Factors for leading medical and science journals in 2005
    (Source: ISI Journal Citation Reports impact factors tabulated from each journal's public website)

    General (internal) medicine

    1. New England Journal of Medicine 44.0
    2. Nature Medicine 28.9
    3. The Lancet 23.4
    4. Journal of the American Medical Association (JAMA) 23.3
    5. Annals of Internal Medicine 13.3
    6. British Medical Journal (BMJ) 9.0
    7. Public Library of Science (PLOS) Medicine 8.4
    8. Archives of Internal Medicine 8.0
    9. Can Medical Assoc J 7.4
    10. Medicine 5.0
    11. Am J Medicine 4.4
    12. J Intern Medicine 4.0

    Basic Science and Biology

    1. Science 30.9
    2. Cell 29.4
    3. Nature 29.3
    4. Nature Immunology 27.0
    5. Nature Genetics 25.8
    6. Nature Cell Biology 19.7
    7. Nature Materials 15.9
    8. Immunity 15.2
    9. J Clinical Investigation 15.1
    10. Molecular Cell 15.0
    11. PLOS Biology 14.7
    12. Developmental Cell 14.6
    13. J Cell Biology 11.0
    14. PNAS 10.3

    (note: review journals are not included)


    Additional journal impact factors:

    --> Impact Factors of Genetics journals

    --> Impact Factors of Cancer journals

    --> Impact Factors of Cardiovascular disease journals

    --> Impact Factors of Diabetes journals

    --> Impact Factors of Epidemiology and Public Health journals

    --> Impact Factors of Nutrition and Obesity journals

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    The Impact of Pre-Publication Presentation of Results: Epi Inquiry Accolade 03/20/2006

    When is it a good idea, and when is it a bad idea to announce scientific results before formal publication? Does the medical community and the public quickly adopt pre-publication findings even though the results are not yet peer-reviewed? Such were the questions address by the recent article in JNCI by Giordano et al. and its accompanying editorial by Woloshin and Schwartz.

    Giordano et al. investigated whether a new taxane treatment for lymph-node positive breast cancer significantly increased after its efficacy results were reported at the May 1998 meeting of the American Society of Clinical Oncology. Even though the taxane was not yet FDA approved and the formal publication was not to appear until 5 years later, the authors found that use of the newly reported treatment significantly increased >400% overall after the conference report. Furthermore, even though the treatment was shown only efficacious in lymph-node positive breast cancers (use increased 800%), results also showed that its use in patients with lymph-node negative breast cancers also increased 300%, which is in fact quite clinically disturbing as the drug was not even shown efficacious for such a disease.

    The accompanying editorial by Woloshin and Schwartz summarized the risk and benefits of early adoption of pre-publication results, as well as noted examples in which early adoption has been clinically detrimental. Notably, the drug gefitinib (Iressa) had once been granted early FDA approval for increasing survival of patients with non-small-cell lung cancer who failed chemotherapy, even though the trial was unpublished, was a single uncontrolled trial, and subsequent issues were raised regarding adverse pneumonia deaths. Though over 200,000 people used the drug by 2004, a subsequent placebo-controlled trial shows no increased survival benefit. Such is an example in which adoption of pre-publication results did not benefit the public, and may have in fact caused more harm.

    Woloshin and Schwartz summarize the following set of guideline regarding when to potentially adopt any pre-publication results:
    1) large difference in all-cause mortality
    2) no adverse effects
    3) results are from a large randomized trial with long duration
    4) confirms prior trial results, or presents first randomized trial evidence
    5) no alternative treatments exist

    For highlighting such important issues, the editors select as the dual-Epidemiologic Inquiry Accolade: Investigation of the Week...

    Giordano SH, Duan Z, Kuo YF, Hortobagyi GN, Freeman J, Goodwin JS. Impact of a scientific presentation on community treatment patterns for primary breast cancer. J Natl Cancer Inst. 2006 Mar 15;98(6):382-8.

    Woloshin S, Schwartz LM. What's the rush? The dissemination and adoption of preliminary research results. J Natl Cancer Inst. 2006 Mar 15;98(6):372-3.

    ~The Editors

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    Trusting Early Results Before Publication? Transition from Meetings to Journals

    While doing a literature search, it is relatively common to find that either the results of a RCT presented at a scientific meeting were never published in a journal; or the results in the journal publication are discordant from those presented at the scientific meeting. Should we use the results from the scientific meeting, even if the results were never published later? Or should be just use the results from the peer-reviewed journal article, which might ensure completeness and proper interpretation of the data? This week's paper by Toma et al. in JAMA attempts to address these questions by examining the proportion of RCTs presented at American College of Cardiology (ACC) scientific meetings which were subsequently published as full-length journal articles; and the consistency between the data presented in the meeting abstract and the subsequent full-length publication.

    The authors selected all RCTs presented at the scientific meetings of ACC between 1999 and 2002 and then searched the literature to see if these were ever published as full-length journal articles till the time of literature search. A distinction was made between the late- breaking clinical trials and the trials presented at other sessions of the ACC (oral or poster sessions). Significant results included the findings that the late-breaking clinical trials were more likely to be published as a full-length journal article subsequently (92% vs 69%); it was more likely that a design paper had been published prior to presentation of results for the late-breaking clinical trials (31% vs 13%); the late-breaking trials were likely to be larger (Median n=725 vs n=196); and the late-breaking trials were less likely to report a favorable effect of the intervention (OR of 0.46; 95% CI = 0.24, 0.90). The late-breaking trials also had higher quality scores and were more likely to be published in a journal with higher impact factor as compared to the RCTs presented at other sessions.

    The authors believe that the differences between the late-breaking clinical trials and others can be explained to a certain extent by the process of selection of these RCTs. The application for presenting at the late-breaking session needs to be made at least 3 months in advance of the meeting and needs to be supported by details of the purpose, design, and methods of the trial. Also, since the results of these RCTs are not known at the time of application, it is more likely that they would report both favorable as well as negative results for the tested interventions.

    Most importantly though, 41% of the RCTs (both late-breaking trials as well as others) which were subsequently published had a different estimate of primary outcome in the journal article as compared to what was presented at the scientific meetings. This suggests that we should not be over-eager in embracing the results from scientific meetings into clinical practice or in meta-analyses and we should wait for a peer-reviewed publication first. As the authors say - "As Shakespeare may have said in the 21st century, there are many slips betwixt podium and page".

    ~The Editors

    Reference: Toma M, McAlister FA, Bialy L, Adams D, Vandermeer B, Armstrong PW. Transition From Meeting Abstract to Full-length Journal Article for Randomized Controlled Trials. JAMA 2006;295:1281-1287.

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    Sex Differences of Sex Hormones in Type 2 Diabetes: Implications for Sex-based Medicine

    Recently, the theme of sex/gender-based medicine has been emerging as an ever more prevalent theme in clinical medicine. Thus, this also forces researchers to also ponder and consider sex-based epidemiologic investigations more carefully.

    In last week's issue of JAMA, Ding et al. investigated sex differences of how plasma sex hormones affect risk of type 2 diabetes. From a systematic review of cross-sectional and prospective studies and randomized trials, it was consistently found that testosterone increased the risk of type 2 diabetes in women, but testosterone had opposite effects in men by decreasing the risk of type 2 diabetes. Additionally, the binding protein, sex hormone-binding globulin, was found to be strongly protective in women, but only marginally protective against type 2 diabetes in men.

    Given such innate sex differences in action of one the most fundamental sex hormones, there is now strong biologic plausibility of sex differences in a wide variety of other etiologic pathways for disease, not just related to diabetes and its associated morbidities. Thus, perhaps epidemiologists and other clinical investigators should more carefully examine future exposure-disease relationships stratifying on sex and assessing sex-specific associations, rather than just adjusting for sex and giving little notice to sex interactions.

    ~The Editors

    Reference: Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2006 Mar 15;295(11):1288-99.

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    Smokefree U.S. States: Still Progress to be Made

    In the ever waging war against tobacco, the concept of "smokefree" states has gained momentum in several U.S. states as well as certain international countries. Below is a tabulation of U.S. states with laws ensuring smokefree offices, restaurants, bars, and casinos. However, the list is still short, and much progress is yet to be made.

    [A more recent updated list of smokefree U.S. states is available here]

    Source: www.smokefree.net

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    "Reproducibility Should Be Minimum Standard for Epidemiologic Research" - press release of JHSPH

    (press release of Johns Hopkins Bloomberg School of Public Health)

    Epidemiologic findings, especially those on which public policies are based, are strengthened when they can be replicated by others. However, full replication by independent investigators is not always possible, due to time constraints or a lack of funding. A commentary by researchers from the Johns Hopkins Bloomberg School of Public Health suggests that analytic research data should be made available so that reproducibility of epidemiologic studies can be the new minimum standard for which investigators strive. The commentary will be published in the April 15, 2006, print edition of the American Journal of Epidemiology and can currently be viewed on the journal’s webpage.

    “All epidemiologic studies should be held to the standard of full replication. But in cases where this is not possible, study investigators should make it possible for others to reproduce their findings,” said Roger Peng, PhD, lead author of the commentary and an advocate for making research reproducible by others.

    Peng and colleagues said the first requirement in reproducibility is that the analytical data set must be made available for others to view and use. The availability of data sets enables other investigators to verify previously published findings, conduct alternative analyses of the same data, eliminate uninformed criticisms and expedite the exchange of information among scientists. In addition to providing the computer code, or instructions for data analysis, authors must also explain how the computer code is linked to the data and which code sections apply to which data.

    The Hopkins researchers acknowledged that making data available to others gives the original investigator little control over how the data will be used. They suggest a system by which partial rights are licensed to interested investigators according to how the data will be used.

    “Providing others with partial rights to the data benefits both the original investigator and those interested in the data. The recipients obtain access to the data and the donor meets data disclosure obligations and maintains some control over others’ use of the data,” said Peng.

    As an example of how epidemiologic studies can meet the reproducibility minimum, Peng and his coauthors applied the standard to a study on quantification of air pollution risk, called the National Morbidity, Mortality and Air Pollution Study (NMMAPS). They created the Internet Health and Air Pollution Surveillance System—at www.ihapss.jhsph.edu—to disseminate the entire database and software used for the study. Other scientists are now able to fully reproduce the study results, apply the study’s methodology to their own data or apply their methodology to the NMMAPS data.

    A handful of scholarly journals, such as Science and Nature, already require authors to place biologic data in public databases, and the National Institutes of Health requires grantees to have a data-sharing policy. Biologists have already made great strides toward integrating research databases, sharing software and making their analyses reproducible. “

    Reproducibility is feasible now. Journals can play an important role in ensuring that their published work is reproducible,” said Scott Zeger, PhD, professor and chair of the Bloomberg School’s Department of Biostatistics.

    The compendium, which is a full study linked with the data and code, for Peng and his colleagues’ commentary can be found at https://webmail.sph.harvard.edu/horde/services/go.php?url=http%3A%2F%2Fwww.biostat.jhsph.edu%2F%7Erpeng%2Freproducible%2F.“Reproducible Epidemiologic Research” was authored by Roger D. Peng, PhD, Francesca Dominici, PhD, and Scott L. Zeger, PhD, all with the Johns Hopkins Bloomberg School of Public Health.

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    Mendelian Randomization: A Perfect Causal Epidemiologic Approach to Simulate a Randomized Trial?

    In epidemiology, we always seek to find the perfect approach to assess causation, with the aim to simulate the randomized controlled trial in observational research. One special example in which perfect randomization can be observed is the case of Mendelian randomization in genetic epidemiology.

    Recently, there have been great interest in Mendelian randomization approaches for estimating causal effects of gene products. Briefly, because genetic polymorphisms are randomly assorted at conception, all covariates between individuals should theorectically be perfectly balanced between those with different polymorphisms--thus theorectically eliminating all confounding for any association between the genetic polymorphism and disease. Furthermore, if one assumes that the measured genetic polymorphisms directly affects the gene product (e.g. a biologic hormone), then one can also estimate the unconfounded association between the gene product and disease by implementing a instrumental variable analysis approach. (for more info, see Greenland, IJE 2000;29:722-729).

    While such a method theorectically estimates an unconfounded Mendelian-randomized causal association between the gene product and disease, a recent article in AJE summarized the many limitations of such a method. Beside general problems in genetic studies such as population stratification and linkage disequilibrium, one subtle but important issue that Mendelian-randomization's analytic approach cannot account for is the problem of "canalization", or the post-genetic adaptation for the genetic effects by other uncontrolled factors. Examples of such a phenomenon include differential nutrient intakes to compensate for genetic deficiency, different lifestyle behaviors to adapt to obesity, or differential use of exogenous hormone agents to compensate for genetically-predisposed low levels of endogenous hormones. (FYI: causally, this can also be considered a type of time-dependent confounding for those familiar with structural DAGs).

    Thus, while Mendelian randomization appears to be the perfect epidemiologic approach to directly estimate causal effects, it still has limitations and assumptions in its application, just as there are limitations of all study designs including randomized controlled trials.

    For highlighting such important issues, the editors select as the Epidemiologic Inquiry Accolade: Investigation of the Month...

    Limits to Causal Inference based on Mendelian Randomization: A Comparison with Randomized Controlled Trials
    Nitsch et al.
    Am. J. Epidemiol. 2006 163: 397-403.

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    WHI Low-Fat Dietary Trial: What a Billion-Dollar Trial Showed that Epidemiology Already Knew

    As they say in baseball and criminal felonies- "3 strikes and you're out" - however, is this adage necessary true in medical research? In a recent blockbuster issue of JAMA, investigators from the decade-long Women's Health Initiative low-fat dietary trial simultaneously reported the results for breast cancer, colorectal cancer, and cardiovascular disease... in essense, results indicated no overall benefit of a low-fat dietary pattern.

    Over a decade ago, when scientists first began proposing and planning this low-fat trial, FAT was the hottest craze in medical science. Total fat, not giving regard to types of fat, was deemed the key culprit to chronic diseases. However, around the same time, the majority of large prospective cohort studies had consistently found that total fat was consistently NOT associated with breast cancer, colorectal cancer, nor cardiovascular disease.

    Nevertheless, the a low-fat trial was funding by the NIH via pushing and lobbying of Congress, despite mounting scientific evidence that it was not the total fat per se, but rather different types of fats that differentially influenced the risk of such diseases. Notably, trans-fat was already known in the early 1990s that it increased the risk of CVD, while other unsaturated fats were more beneficial for CVD. Differences in types of fat was also being recognized for cancer risks. Thus, 10 years late, the WHI trial ultimately confirmed what epidemiologists from long-running prospectives studies knew all along.

    As for the WHI low-fat trial itself- it had many limitations. First of all, its study protocol specified that women reduce their fat intake to less than 20 percent of total intake, grains greater than 6 servings/day and fruits and vegetables greater than 5 servings/day. Nevertheless, only a minority of women hit these targeted goals, and even fewer hit all 3 targets. Furthermore, examining biomarkers of fat intake: serum triglycerides and HDL cholesterol, results indicated that these marker were barely changed at all by the intervention-- these issues raise suspicions of whether the trial accomplished its scientific aims to substantially change fat intake in the first place. Finally, because total energy intake was also decreased by fat in the trial, rather than isocalorically substiting of fat calories by other macronutrient sources, this is considered a major flaw in nutritional research. Essentially, one cannot tease out whether any effects of the intervention is related to reduction of fat or actually due to decreased calorie per se.

    Overall, these issues open up lots of questions:
    -Was there any true gain in informative knowledge from the trial?
    -Were the limitations in study design and methods significant enough to warrant concern?
    -Was the trial worth the multi-million dollar investment?
    -Should this trial have been conducted in the first place?

    In the end, perhaps medicine and public health should utilize a middle ground for equally relying on high quality prospective epidemiologic studies and randomized trials, both of which mutually complements each other study design's strengths and limitations.

    Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial
    Prentice et al.
    JAMA. 2006; 295:629-642.

    Low-Fat Dietary Pattern and Risk of Colorectal Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial
    Beresford et al.
    JAMA. 2006; 295:643-654.

    Low-Fat Dietary Pattern and Risk of Cardiovascular Disease: The Women's Health Initiative Randomized Controlled Dietary Modification Trial
    Howard et al.
    JAMA. 2006; 295:655-666.

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    Sham versus Placebo: Implications for Interpreting Randomized Controlled Trials

    Clinical investigators have often naively touted any trial to be the absolute truth, giving the randomized controlled design precedence over observational studies. However, in a recent issue of the BMJ, it was discovered that the type of control method used can significantly impact the interpretation of a randomized trial result.

    By comparing a sham acupuncture procedure versus an inert placebo on physical function, the investigators discovered that the two "control" methods yielded different functional results and different rates of adverse effects. Obviously the psychosocial placebo effect is much different depending on the method of control. This has implications for interpreting other randomized trials which use different intervention for controls (such as: placebo, general advice, normal behavior, alternative diet, etc), which may elicit a different confluence of adaptive factors (also known as "canalization").

    Thus, are randomized trials truly interpretable as the absolute gold standard? What other limitations are there? (to be continued).

    Sham device v inert pill: randomised controlled trial of two placebo treatments.
    Kaptchuk TJ, Stason WB, Davis RB, Legedza AR, Schnyer RN, Kerr CE, Stone DA, Nam BH, Kirsch I, Goldman RH.
    BMJ. 2006 Feb 1; EPUB

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    Resolving Differences of Studies of Estrogen and Cardiovascular Disease

    One of the greatest controversies in the world of observational research and randomized trials has been the discrepant findings between epidemiologic results that indicate oral estrogen is beneficial for lowering risk of coronary heart disease (CHD) and the Women's Health Initiative trial results that indicate no effect on risk of CHD.


    However, upon closer inspection of the original results, there indeed may be a strong biologic explanation for the heterogeneity not due to residual confounding. This month in the Journal of Women's Health, the original estrogen investigators Grodstein et al. examined the estrogen-CHD association in a reanalysis of the Nurses' Health Study and reviewed the contrasting results between NHS and the WHI.


    Notably, they first highlighted that women in the WHI were significantly older (majority a full decade since menopause) than women in the NHS at initation of estrogen therapy (who were mostly perimenopausal and <5 year since menopause at baseline). Previous experimental evidence from primates indicated that oral estrogen has strongly divergent effects of being protective against CVD risk factors among younger primates, while not protectives in older primates.


    More importantly, the original NHS study found that the benefits of estrogen therapy diminished over time with longer duration of use (longer time since menopause). Indeed, the latest reanalysis confirm that among a subset of nurses of comparable age and years since menopause to WHI women, results were consistent in which there was no effect of estrogen on CHD risk; meanwhile among younger nurses of relatively few years since menopause, NHS women using oral estrogen did show decreased risk of CHD.


    To top it off, Grodstein et al.'s reanalysis of the WHI age-stratified results indeed also confirms such heterogeneity in which younger WHI women age 50-59 showed protective benefits of estrogen RR=0.56, while moderately older women age 60-69 and older women age 70-79 showed no benefit of estrogen therapy on CHD risk, RR=0.92 and RR=1.04 respectively (meta-regression p trend=0.036).


    In summary, multiple lines of evidence from primate experimental results, observational studies, and randomized trials all support the above effect modification of estrogen's effects on CHD risk. Thus, perhaps the worlds of observational epidemiology and randomized trials unite afterall.


    Hormone Therapy and Coronary Heart Disease: The Role of Time since Menopause and Age at Hormone Initiation.
    Grodstein F, Manson JE, Stampfer MJ.
    J Womens Health (Larchmt). 2006 January/February;15(1):35-44.


    [The Editors have no personal or professional conflict of interest in the above editorial]

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    Obesity versus Physical Activity In Predicting CHD and Mortality: Epi Inquiry Accolade 02/5/2006

    In the past few years, some researchers have suggested that adiposity is not an important risk factor of disease and mortality as long as individuals maintain high levels of physical activity (in other words," it is okay to be fat as long as you're active"). However, such assertion has been refuted by many other epidemiologists as highly inaccurate and woefully irresponsible for public health.

    Notably, in December 2004 in the New England Journal of Medicine, investigators from the Nurse's Health Study jointly stratified by levels of adiposity and physical activity. Results indicated that adiposity and physical activity were clearly independent risk factors for overall mortality (in fact, opposite of the refuted theory, those lean and inactive were at relatively lower risk compared to those obese and active).

    Moreover, a similar analysis was published this past week in the journal Circulation, to assess the independence of adiposity and physical activity for risk of coronary heart disease (CHD). As found in the mortality analysis, increasing adiposity and decreasing physical activity again independently predicted CHD risk. The authors noted that most studies in the literature supported such independent results, and the few dissensing studies were often conducted among those with very short follow-up, relatively fewer number of cases, and among those with pre-existing cardiovascular disease.

    Thus, for clearly highlighting such important issues, the editors select as the Epidemiologic Inquiry Accolade: Investigation of the Week...

    Obesity as compared with physical activity in predicting risk of coronary heart disease in women.
    Li TY, Rana JS, Manson JE, Willett WC, Stampfer MJ, Colditz GA, Rexrode KM, Hu FB.
    Circulation. 2006 Jan 31;113(4):499-506.

    and also recognize...
    Adiposity as compared with physical activity in predicting mortality among women.
    Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA, Manson JE.
    N Engl J Med. 2004 Dec 23;351(26):2694-703.

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    If not saturated fat, then eat what?: Epi Inquiry Accolade- RCT 01/2006

    Excess dietary intake of saturated fat has long been recognized an a major culprit in contributing to heart disease, and virtually all dietary recommendations urge people to reduce its intake. However, given that people have daily caloric energy requirements below any excesses, the key questions is -- if one reduces saturated fat intake, then one should replace such intake with what for optimal cardiovascular health? Carbohydrate? Protein? Unsaturated fat?

    This key question was the impetus behind the recent OMNIHEART randomized crossover trial by Appel et al. Based on the healthy DASH diet, the investigators isocalorically replaced saturated fat with calories from carbohydrates (mix of refined and whole grain), proteins (mix of vegetable and animal), and unsaturated fat (mix of mono- and polyunsaturated). Based on changes in a series cardiovascular risk factors (blood pressure, LDL, HDL, triglycerides), they determined all 3 replacements are indeed better than saturated fat in reducing Framingham risk factors, with particuarly protein and unsaturated fat being better than carbohydrate replacement. While future studies will attempt to further examine protein sources and types of dietary fat in a randomized setting-- this current trial significantly establishes current understanding in nutritional epidemiology of the more optimal macronutrient to substitute for saturated fat.

    Therefore, for these important contributions, the editors select as the Epidemiologic Inquiry Accolade: Randomized Trial of the Month ...

    Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial.
    Appel LJ, Sacks FM, Carey VJ, Obarzanek E, Swain JF, Miller ER 3rd, Conlin PR, Erlinger TP, Rosner BA, Laranjo NM, Charleston J, McCarron P, Bishop LM; OmniHeart Collaborative Research Group.
    JAMA. 2005 Nov 16;294(19):2455-64.

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    Wednesday, October 04, 2006

    Advancing sex-based medicine via meta-analysis

    An important role of epidemiology is to advance medicine and clinical practice. Typically, meta-analyses can be helpful in summarizing study results to guide clinical practice and disease prevention. However, meta-analyses can ascend beyond fulfilling that simple role, as the truly outstanding meta-analyses can also advance scientific thinking beyond simple exposure-outcome relationships.

    Such was the unique contribution of the sex-specific meta-analysis of diabetes and risk of CHD mortality by Huxley et al., demonstrating that sex is an important factor in determining the etiologic relationship between these two conditions. While the diabetes-heart disease relationship has long been recognized and sex differences have been suggested, this study was the first to formally document this important sex difference, as it ever more emphasizes the need for sex-based medicine and studying epidemiology in diverse populations.

    Therfore, for making this important contribution, the editors select as the Epidemiologic Inquiry Accolade: Meta-Analysis of the Month 01/2006...

    Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies
    BMJ 2006;332:73-78
    Rachel Huxley, Federica Barzi, Mark Woodward

    Click here to learn more information about the Epidemiologic Inquiry award series

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    Scientific Integrity of Publications? Epi Inquiry Accolade 01/29/2006

    Given the recent rash of scientific scandals regarding fabricated stem cell research, concealment of adverse events in the rofecoxib VIGOR trial, and other incidents this past month alone... studies examining the quality of scientific publications and review process are becoming ever more important. This week, two interesting studies (one in JAMA, one in BMJ) explored such issues.

    The article by Biondi-Zoccai et al. in the BMJ studied the degree of scientific agreement between the findings and conclusions of overlapping meta-analyses of the same clinical topic. Interestingly, they found that the the same meta-analysis topic-- longer manuscripts and articles published by those with non-profit funding scored higher in quality. This attests to potential biases due to funding, and potential adverse consequences of tight word lengths of scientific journals (this is most ironic for the BMJ, as the BMJ has the reputation to be the most restrictive in word length of articles).

    Meanwhile, BMJ investigators also published in JAMA that for the peer review process, the practice of requesting author-suggested reviewers and/or having open-reviews (revealing the reviewer's identity) led to more favorable reviews. Though this is an intuitive bias of human-nature, journal editors fortunately were not swayed by differences in such peer review practices, which is reassuring for scientific integrity.

    Therefore, for these important contributions to investigate the integrity of the scientific process, the editors this week select as the Epidemiologic Inquiry Accolade: Investigation of the Week (co-winners)...

    Compliance with QUOROM and quality of reporting of overlapping meta-analyses on the role of acetylcysteine in the prevention of contrast associated nephropathy: case study
    Biondi-Zoccai GG, Lotrionte M, Abbate A, Testa L, Remigi E, Burzotta F, Valgimigli M, Romagnoli E, Crea F, Agostoni P.
    BMJ. 2006 Jan 28;332(7535):202-9.

    Differences in review quality and recommendations for publication between peer reviewers suggested by authors or by editors.
    Schroter S, Tite L, Hutchings A, Black N. (of the BMJ Editorial Office)
    JAMA. 2006 Jan 18;295(3):314-7.

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    Epidemiologists Lead Among Top Scientists in Clinical Medicine

    Thomson Scientific recently released the list of the top cited scientists in Clinical Medicine. Among the Top 10- epidemiologists garner 5/10, and lead with the top 3. Truly, nobody can still doubt the value and intermarriage of epidemiology and medicine anymore...

    Most-Cited Scientists in Clinical Medicine
    (Ranked by total citations, based on papers published and cited in Thomson-indexed journals between January 1995 and August 2005)
    Rank -- Name -- Field -- Citations

    1 Meir J. Stampfer -- Epidemiology, Citations: 34,872
    2 Walter C. Willett -- Epidemiology, Citations: 33,724
    3 Charles H. Hennekens -- Epidemiology, Citations: 27,629
    6 Graham A. Colditz -- Epidemiology, Citations: 25,702
    10 JoAnn E. Manson -- Epidemiology, Citations: 19,141


    Source: Thomson Scientific, of The Thomson Corporation. The Thomson Corporation (http://www.thomson.com), with 2004 revenues of US$8.10 billion, is a global leader in providing integrated information solutions to business and professional customers. Thomson provides value-added information, software tools and applications to more than 20 million users in the fields of law, tax, accounting, financial services, higher education, reference information, corporate e-learning and assessment, scientific research and healthcare. With operational headquarters in Stamford, Conn., Thomson has approximately 38,000 employees and provides services in approximately 130 countries. The Corporation's common shares are listed on the New York and Toronto stock exchanges (NYSE: TOC; TSX: TOC). Web site: http://www.scientific.thomson.com

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    Relevant causal question - Epi Inquiry Accolade 01/22/2006: Kurth et al.

    In epidemiology, we often launch an investigation to examine the simple causal association between exposure and disease outcome. However, too often, we can lose sight of the more important purpose- to determine "the relevant causal question"...

    This week in AJE, Kurth et al. investigates the comparative results between multivariable adjustment of confounders via various methods of propensity score adjustment and propensity score weighting (inverse probability weighting standardization, aka marginal structural model), in the observational setting studying the use of a pharmacologic agent and risk of death.They found the overall results varied dramatically between the method of adjustment, ranging from RR=1 (conventional propensity adjustment) to RR=10 (IPW) for the same disease association. However, they discovered that IPW did report consistent RR=1 among those with propensity greater than 5% probability of treatment...

    This article demonstrates the importance of the "relevant causal question" in epidemiology and clinical medicine, as those contraindicated with probability of drug treament less than 5% would not likely receive treatment in a realistic population. Thus, forcing every individual to take the drug in an entire population, regardless of clinical contraindications, would not be the relevant causal question in epidemiology, nor relevant to clinical practice. (That said, there are also important advantages of IPW standardization for time-dependent confounding, not discussed here.)

    Thus, for clearly highlighting such key methodologic issues in epidemiologic research, the editors select as the Epidemiologic Inquiry Accolade: Investigation of the Month...

    Results of Multivariable Logistic Regression, Propensity Matching, Propensity Adjustment, and Propensity-based Weighting under Conditions of Nonuniform Effect
    Tobias Kurth, Alexander M. Walker, Robert J. Glynn, K. Arnold Chan, J. Michael Gaziano, Klaus Berger, and James M. Robins
    American Journal of Epidemiology 2006 163(3):262-270

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    Sex-Specific Investigations into Etiology

    Recently, epidemiology and medicine have begun to focus more and more on sex-specific etiologies for disease. Men and women may not necessarily be as far apart as Mars and Venus... however, it is becoming more and more clear that not all drugs act the same in men and women, and not all conditions lead to other diseases with the same rate in both sexes.

    Simultaneously this week, two large meta-analyses clearly demonstrate that the above is likely true. Notably, the study by Berger et al. showed that aspirin has different effects on the primary prevention of stroke and myocardial infarction between the sexes. Additionally, the study by Huxley showed that diabetes is more adverse in women than men for CHD mortality-- diabetes may be considered a "CHD equivalent", but likely more so in women. Additionally, another study in AJE this week shows that fetal sex differentially influences maternal asthma.

    These studies highlight the need for sex-based medicine. These studies also show that epidemiologic research likely always requires a synthesis of knowledge from a variety of populations-- one study cannot prove a disease pattern, and one diesease pattern cannot be generalized to all populations.


    Aspirin for the Primary Prevention of Cardiovascular Events in Women and Men: A Sex-Specific Meta-analysis of Randomized Controlled Trials
    JAMA. 2006;295:306-313
    Jeffrey S. Berger; Maria C. Roncaglioni; Fausto Avanzini; Ierta Pangrazzi; Gianni Tognoni; David L. Brown

    Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies
    BMJ 2006;332:73-78
    Rachel Huxley, Federica Barzi, Mark Woodward

    Effect of Fetal Sex on Airway Lability in Pregnant Women with Asthma
    American Journal of Epidemiology 2006 163(3):217-221
    Helen L. Kwon, Kathleen Belanger, Theodore R. Holford and Michael B. Bracken

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    Better Drug Combo Treatment for HIV

    Always in search of a better treatment... it has been a long since new drug combination has proven itself to be more effective and safer above and beyond the current standard treatment regimen for HIV..

    "Tenofovir DF and emtricitabine plus efavirenz"
    --> proves superior in terms of virologic suppression, CD4 response, and adverse events

    Tenofovir DF, Emtricitabine, and Efavirenz vs. Zidovudine, Lamivudine, and Efavirenz for HIV
    NEJM Volume 354:251-260
    Joel E. Gallant, M.D., M.P.H., Edwin DeJesus, M.D., José R. Arribas, M.D., Anton L. Pozniak, M.D., Brian Gazzard, M.D., Rafael E. Campo, M.D., Biao Lu, Ph.D., Damian McColl, Ph.D., Steven Chuck, M.D., Jeffrey Enejosa, M.D., John J. Toole, M.D., Ph.D., Andrew K. Cheng, M.D., Ph.D., for the Study 934 Group

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    International geosentinal surveillance... Epi Inquiry Accolade 01/15/2006: Freedman et al.

    [Epidemiologic Inquiry 2006, 1: 4]

    For the inaugural Epi Inquiry award, it is fitting to recognize an outstanding investigation that simultaneously pays homage to the historical foundations of epidemiology...

    From a large international surveillance network data on 17,353 patients , this analysis is an eminent example of geosentinel surveillance applied in classic epidemiology, to predict the probability of travelers contracting a region-specific disease. In addition to being poorly understood previously, it also has important clinical impact on helping guide diagnosis and treatment for diseases suffered by returning international travelers. This study also reminds epidemiology of the important historical roots of the field in studying the distribution of disease. In addition, this study again emphasizes that population disease transmission, today, truly occurs on a global scale.

    Therefore, the editors select...
    Freedman et al. NEJM Volume 354:119-130 Number 2
    Spectrum of Disease and Relation to Place of Exposure among Ill Returned Travelers

    for Epidemiologic Inquiry Accolade: Investigation of the Week.


    Click here to learn more information about the Epidemiologic Inquiry award series

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    EPIDEMIOLOGIC INQUIRY AWARD Series

    Beginning January 2006, The Journal will regularly announce a series of "Epidemiologic Inquiry Awards" for best original investigations in epidemiology and clinical medicine from among new published papers in each award period. The award categories are:

    "Epidemiologic Inquiry Accolade: Original Investigation of the Month"
    Eligible papers are original epidemiologic studies of observational design, excluding reviews.

    "Epidemiologic Inquiry Accolade: Meta-Analysis of the Month"
    Eligible papers are original systematic reviews with a meta-analytic component. A systematic search of at least one major biomedical database is required. Meta-analyses of either randomized or observational studies are eligible. Pooling projects are not eligible.

    "Epidemiologic Inquiry Accolade: Randomized Trial of the Month"
    Eligible papers are original investigations of randomized interventions. Trials must be of sufficient size and duration to have significant impact on clinical medicine and public health.

    top-awards:
    "Epidemiologic Inquiry Award: Best Original Investigation" (annual)
    Eligible papers are original investigations of any study design. The winning paper may be selected from among previous weekly/monthly winning papers or from any new paper published during the eligible semi-annual time period (January-June).

    "Epidemiologic Inquiry Award: Best Methodologic Innovation" (annual)
    Eligible papers must contribute a novel method or an innovative approach to epidemiologic investigation.

    Papers are judged overall based on the following criteria:
    1) quality of study design and analysis
    2) clinical and public health significance
    3) innovation in understanding disease etiology

    4) innovation and novel approaches in analysis

    The body of journals from which articles are selected is comprised of leading epidemiology journals, leading general medicine journals (e.g. NEJM, JAMA, BMJ, etc), as well as leading journals in substantive fields (e.g. J Nat'l Cancer Institute, Diabetes / Diabetes Care, Circulation, Am J Clinical Nutr, etc).

    No monetary prizes are bestowed. Each winning paper will be featured in the newest issue of the Journal. Press releases for the paper named "Best Methodologic Innovation" will be distributed to schools of public health and the journal in which the article appears. Press releases for the paper named "Best Original Investigation" will be distributed to media outlets, schools of public health, and the journal in which the article appears.

    With exception of "Epidemiologic Inquiry Prize" top-awards, decisions are made by the editorial board of the Journal. The Prizes for top investigation are decided after peer consultation with editors of leading epidemiology and clinical journals and experts in epidemiology methods and biostatistics, for respective prizes.

    Nominations. Nominations from readers are considered, though self-nomination of an article on which one is a co-author is prohibited. However, official press releases sent from institutions' communications offices are acceptable. All nominations must be accompanied by the nominator's name, contact informations, URL to the nominated article's webpage, and a brief letter (or press release) describing the significance of the article's contribution to epidemiology and/or medicine.
    Nominations may be emailed to epidemiologic@gmail.com.

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    FAQ

    Frequently Asked Questions (FAQ)


    -- Is Epidemiologic Inquiry a journal or a weblog?
    As of September 2006, Epidemiologic Inquiry re-premiered on http://www.Epidemiologic.org as a weblog and epidemiology resource center. However, it is important to highlight that in this day and age, weblogs are no longer informal journals, as reputable weblogs are now eligible for the famed Pulitzer Prize. Furthermore, we still uphold the professionalism expected in science.


    -- Who are the editors, and why the anonymity?
    We expect readers to notice the obvious enigma. We would first like to say that our editorial board indeed consists of epidemiologists with doctoral-qualifications and degrees in epidemiology and public health. Additionally, our editors have experience publishing in leading journals, including several first-author publications in major research journals, as well as serving as directors and principal investigators on federal research grants.

    After very careful consideration, the editors believe is it prudent to remain anonymous to avoid jeopardizing their academic careers, and more importantly to allow editors to remain objective and humble in their daily personal lives. Meanwhile, in context of the philosophy of protective anonymity in epidemiology -- it is of note that is the policy of the American Epidemiology Society (AES) to similarly not officially divulge the membership list of the society, nor publish any online site describing the nature of the organization. That said, we are not members of AES.

    Therefore, given the currently accepted nature of anonymity in certain epidemiology organizations, and for our unique personal reasons discussed, we feel it is prudent to not disclose the identity of our editors, who selflessly volunteer our own personal time and efforts and remain objective to the purposes of Epidemiologic.org. The founders of Epidemiologic.org believe in the power of the internet in providing a voice and forum for epidemiologists to debate and collaborate, and we hope readers see this ultimate altruistic objective.


    -- Do the editors have any conflicts of interest?
    Unless explicitly stated under unusual circumstances, the editors do not have any conflicts of interest regarding substantive content written on Epidemiologic.org. However, we declare that the editors do receive nominal revenue from contextual text-based Google ads and Amazon sales comissions to defray the costs of software upgrades, domain registration, and website server hosting (which totals to more than $100 per year, with costs expected to increase with increasing traffic). We emphasize that Epidemiologic.org is not for profit, but for open-science.


    -- Will subscription emails ever be distributed to third parties?
    No. We assure our readership that we will never distribute emails of Epidemiologic.org subscribers to third parties for any commercial reason. The only time Epidemiologic.org may allow an external group to borrow our email listserv is if it is for strictly a non-profit epidemiologic research project. Even then, we will not distribute our actually email list to the third party, but rather they may only send emails via our editors as proxy.


    [Others to be added as they arise]

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    About the Journal

    --UPDATE: On November 26, 2006, Epidemiologic Inquiry officially launched the premiere of the Epidemiology Forum: A community for fostering questions, debates, and collaborations in epidemiology. We believe building an online support community and a cadre of online collaborating epidemiologists can not only have the potential to improve research, but also advance the field of epidemiology. We strongly encourage and appreciate your contributions to the forum, which will go a long way towards fostering and nuturing an online epidemiology community.

    --UPDATE: As of September 2006, Epidemiologic Inquiry has been revamped as an online weblog for epidemiology, rather than a formal online journal. After feedback from readers, the editors have decided to adopt a weblog format to better serve interested readers. However, we still uphold our founding principles to not only bring news, but also insightful analyses in epidemiology. The founders of Epidemiologic.org inherently believe in the power of the internet in providing a voice and forum for epidemiologists to debate and collaborate.

    Thank you for your continued readership.

    Editor@epidemiologic.org

    Please also
    read the FAQ to understand more about Epidemiology Inquiry and the founding editors.


    =====FOUNDING MISSION STATEMENT=====

    In a world with ever increasing pace of scientific investigations, important research findings are often disseminated too slowly through the general scientific community-- slowly as in weeks or months, instead of hours and days. Furthermore, methodologic controversies are usually discussed via word of mouth soon after the publication, and written responses to journals often appear months after publication -- too slow to engage readers, too long of a lag to maintain relevance, and too long a period of time for potentially flawed study results to propagate uninhibited. Finally, outstanding investigations are too often under- or unrecognized in epidemiology and medicine...


    PURPOSE: The Journal is a fresh and innovative online weblog exploring the most outstanding, fascinating, and controversial. The Journal highlights and examines important epidemiologic contributions to medicine and public health - the latest controversies in contemporary epidemiology and medicine - as well as critiques of the occassional flawed study. The Journal also seek to discuss the need for new methods and analytic approaches in epidemiology whenever appropriate.

    Another innovative approach of the Journal is in highlighting the most important latest research in epidemiology and medicine at breaking-news speed of traditional mass-media-- all while maintaining depth of content and not sacrificing the sine-qua-non essense of a scientific publication.

    The Journal publishes brief commentaries and editorials, from both readers and editors, on the latest in epidemiology and clinical medicine by editors and submitting authors. The Journal also sponsors a series of prizes titled the "Epidemiologic Inquiry Awards" to recognize outstanding scientific investigations. The editorial board consists of a group of researchers who recognize the importance of highlighting important contemporary advances and critical achievements in epidemiology and medicine.

    SUBMISSIONS: Readers to highly encouraget to contribute your thoughts and insights to the Journal. To contribute your brief letter/commentary (less than 300 words) or carefully composed editorial review (less than 1200 words), please submit your article and figures in email format (no PDF) to editor@epidemiologic.org, along with your contact information. Any references should be listed in AMA format. All submissions are reviewed by the editorial board, although commentaries are frequently accepted to open forum for discussion.

    Rapid Response submissions: Rapid responses to online articles may be freely posted via the 'comment' box under each posting. All responses must be professional and courteous, slander is prohibited.

    OPEN ACCESS: All published material become open-access without charge to the public. However, the Journal and the original author(s) retain copyright of original content materials, unless otherwise declared. Distribution and reproduction of the Journal's content for commercial purposes without expressed permission is prohibited. The Journal remains independent to avoid all article processing and access charges, and is supported by time donated by the editors and by text-based Google ads to defray the costs of domain registration and website server hosting. Support for Epidemiologic.org via word of mouth, referral to peers and colleagues, and publicity on your website are welcome and appreciated. Advertisers of relevant job postings are welcome to contact the Journal.

    Please also read the FAQ to understand more about the Journal.

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