Many substances used in daily life, such as coffee, alcohol, and pharmaceutical treatment for hypertension, have been accused of "menace" in causing cancer or other major diseases. Although some of the accusations have subsequently been refuted or withdrawn, they have usually been based on statistical associations in epidemiologic studies that could not be done with the customary experimental methods of science. With these epidemiologic methods, however, the fundamental scientific standards used to specify hypotheses and groups, get high-quality data, analyze attributable actions, and avoid detection bias may also be omitted. Despite peer-review approval, the current methods need substantial improvement to produce trustworthy scientific evidence.

https://science.sciencemag.org/content/sci/242/4883/1257.full.pdf

Scientific standards in epidemiologic studies of the menace of daily life.

Diesel exhaust has been suspected to be a lung carcinogen. The assessment of this lung cancer risk has been limited by lack of studies of exposed workers followed for many years. In this study, we assessed lung cancer mortality in 54,973 U.S. railroad workers between 1959 and 1996 (38 years). By 1959, the U.S. railroad industry had largely converted from coal-fired to diesel-powered locomotives. We obtained work histories from the U.S. Railroad Retirement Board, and ascertained mortality using Railroad Retirement Board, Social Security, and Health Care Financing Administration records. Cause of death was obtained from the National Death Index and death certificates. There were 43,593 total deaths including 4,351 lung cancer deaths. Adjusting for a healthy worker survivor effect and age, railroad workers in jobs associated with operating trains had a relative risk of lung cancer mortality of 1.40 (95% confidence interval, 1.30-1.51). Lung cancer mortality did not increase with increasing years of work in these jobs. Lung cancer mortality was elevated in jobs associated with work on trains powered by diesel locomotives. Although a contribution from exposure to coal combustion products before 1959 cannot be excluded, these results suggest that exposure to diesel exhaust contributed to lung cancer mortality in this cohort. Key words: diesel exhaust, lung cancer, occupational exposure.

http://dash.harvard.edu/bitstream/handle/1/4457603/1247618.pdf?sequence=1

Lung cancer in railroad workers exposed to diesel exhaust.

Misdiagnosis at a university hospital in 4 medical eras : report on 400 cases

Outbreak investigations, an important and challenging component of epidemiology and public health, can help identify the source of ongoing outbreaks and prevent additional cases. Even when an outbreak is over, a thorough epidemiologic and environmental investigation often can increase our knowledge of a given disease and prevent future outbreaks. Finally, outbreak investigations provide epidemiologic training and foster cooperation between the clinical and public health communities.

/pdf/outbreak-investigations-a-perspective-3ymq2hxbwe.pdf

Outbreak investigations--a perspective.

Context.—Autopsy often reveals new diagnoses of malignant neoplasms, but as technological
advances to improve diagnosis during life have improved, autopsy rates have
declined dramatically.Objective.—To determine if there is still a high discordance rate between clinical
and autopsy diagnoses of malignant neoplasms despite increasing technological
advances in diagnostic methods.Design and Setting.—A 10-year retrospective study (1986-1995) of all autopsies performed
at the Medical Center of Louisiana at New Orleans.Participants.—All patients autopsied, excluding preterm fetuses, at the Medical Center
of Louisiana at New Orleans, by both Tulane and Louisiana State University
Schools of Medicine in which consent was obtained or authorization given from
the Orleans Parish Coroner's Office.Main Outcome Measures.—Discordance between clinical and autopsy diagnoses of malignant neoplasms.Results.—A total of 1625 cases were reviewed of which 520 preterm fetuses were
excluded. Of the remaining 1105 cases, 654 were male and 451 were female.
The mean age was 48.3 years (range, 1-98 years). A total of 433 neoplasms
were diagnosed, 250 of which were malignant. One hundred eleven malignant
neoplasms in 100 patients had been either undiagnosed or misdiagnosed, and
in 57 patients, the immediate cause of death could be attributed to the malignant
neoplasm. The discordance between clinical and autopsy diagnoses of malignant
neoplasms in this study is 44%, which is similar to previously reported studies.Conclusion.—The discordance rate between clinical and autopsy diagnoses of malignant
neoplasms is large and confirms the importance of the postmortem examination.

https://jamanetwork.com/journals/jama/articlepdf/188050/joc81255.pdf

Autopsy diagnoses of malignant neoplasms: how often are clinical diagnoses incorrect?

At the Boston City Hospital between 1955 and 1965 one fourth of all autopsies involved cancer patients Forty percent of these 2,734 patients had serious clinical errors for diagnosing cancer, and 63% of patients with these errors died from cancer Twenty-six percent of all patients reviewed had clinically undiagnosed cancer, and 45% of these neoplasms were fatal Nonmalignant diseases caused death in 24% of all cancer patients reviewed Generally, errors in clinical diagnoses of cancer were most common with the most common cancers Cancer patients were almost a decade older than control patients without cancer

An autopsy study of cancer patients. I. Accuracy of the clinical diagnoses (1955 to 1965) Boston City Hospital.

A cluster of five false-positive cerebrospinal fluid (CSF) Gram stains led to an investigation of possible causes of specimen or smear contamination. Specimen tubes supplied in commercial lumbar puncture trays from the lot being used in the involved hospital were shown to contain nonviable bacteria. When filled with a test solution and processed in a manner similar to that used for processing CSF specimens, 10 of 12 tubes evaluated yielded Gram stains containing either Gram-negative rods, diplococci, or coccobacilli. Before this problem was recognized, the patient from whom the first false-positive smear was obtained was treated for bacterial meningitis. It is important to realize that microbial contamination of commercial CSF specimen tubes can result in findings simulating those of early bacterial meningitis. (JAMA233:878-879, 1975)

Factitious meningitis. Diagnostic error due to nonviable bacteria in commercial lumbar puncture trays

We reported previously that 41% of all cancers in a large autopsy series were incorrectly diagnosed before death. We have now detected a direct association between accurate clinical diagnoses of cancer and increasing length and number of hospital admissions. The prevalence of incorrectly diagnosed cancer progressively decreased from a high of 53% to a low of 30% when both the number and length of hospitalizations increased. However, these relationships were limited to the first five hospital admissions and the first 20 hospital days. Beyond these limits, no further improvement in diagnostic accuracy was noted. Undiagnosed cancer caused 11% of the deaths of patients with more than 40 days of hospitalization as well as the deaths of those with more than one hospital admission. Accurate clinical diagnoses of diseases such as cancer can be associated with an optimum length and number of hospitalizations, beyond which little or no improvement in diagnostic accuracy occurs.

An Autopsy Study of Cancer Patients: II. Hospitalizations and Accuracy of Diagnoses (1955 to 1965) Boston City Hospital

The modern era of pathology generally is thought to have begun more than a century ago when Rudolph Virchow first proposed the cellular theory of disease, an achievement made possible chiefly by prior developments in what until then had been separate sciences—anatomy, in which the cellular structure of tissues had been established, and optical physics which had contributed greatly to refining the light microscope. Now, in our more modern epoch, the physicists' development of the electron microscope has led anatomists to confirm the presence of some existing cellular structures as the Golgi apparatus, and to discover the existence of new ones. Out of all this recent molecular hustle and activity a new term, "pathobiology," has been proposed to recognize that for teaching and research purposes fruitful interrelationships can be established among the various sciences. Hence, the title of this series. In his preface to this first volume the editor describes

Pathobiology Annual, 1971

In Reply.— We thank Dr Branson for relating her experience with another potential source of erroneous microbiologic results. The false-positive findings that we investigated derived from direct stains of cerebrospinal fluid (that had been contaminated by nonviable organisms in the specimen tubes of a commercial lumbar puncture tray); thus, we did not have to contend with the possibility of contaminated broth. There are, however, many well-recognized, though not always widely appreciated, laboratorybased sources of false-positive stain (and culture) results, including—in addition to contaminated media—contamination in other laboratory-prepared or commercial products such as stains and immersion oils. 1 Furthermore, methodologic problems may lead to cross-contamination of specimens or slides within the laboratory. 2 The problem cited by Dr Branson may especially confuse workers processing blood cultures since positive Gram stains of such cultures could not be readily called into question by visual inspection of the broth and would not usually have

Frederick W. Bauer

Papers

An autopsy study of cancer patients. I. Accuracy of the clinical diagnoses (1955 to 1965) Boston City Hospital.

Factitious meningitis. Diagnostic error due to nonviable bacteria in commercial lumbar puncture trays

An Autopsy Study of Cancer Patients: II. Hospitalizations and Accuracy of Diagnoses (1955 to 1965) Boston City Hospital

Pathobiology Annual, 1971

Factitial Meningitis-Reply