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Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research.

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalizability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers.This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated web site (http://www.strobe-statement.org) should be helpful resources to improve reporting of observational research.

Large tumor burdens in advanced non-small-cell lung carcinoma (NSCLC) are thought to be immunosuppressive. To determine whether CD8-mediated immune responses could be elicited in stage IIIB/IV NSCLC patients, 14 subjects were immunized several times with allogeneic NSCLC cells transfected with CD80 (B7.1) and HLA-A1 or A2. Patients enrolled were matched or unmatched at the HLA A1 or A2 locus and their immune response compared. Immunization significantly increased the frequencies of interferon-gamma secreting CD8 T cells in all but one patient in response to ex vivo challenge with NSCLC cells. The CD8 response of matched and unmatched patients was not statistically different. NSCLC reactive CD8 cells did not react to K562. Clinically, five of 14 patients responded to immunization with stable disease or partial tumor regression. The study demonstrates that CD8 Ifn-gamma responses against nonimmunogenic or immunosuppressive tumors can be evoked by cellular vaccines even at advanced stages of disease. The positive clinical outcome suggests that nonimmunogenic tumors may be highly susceptible to immune effector cells generated by immunization.

Although past studies have shown that oral contraceptives with 50 microg or more of estrogen reduce the risk of ovarian cancer, it is not clear whether newer, lower-dose formulations do as well. We conducted a population-based, case-control study in the Delaware Valley to assess the impact of dose of oral contraception on risk of ovarian cancer. Cases aged 20-69 years with a diagnosis of epithelial ovarian cancer ascertained between May 1994 and July 1999 (n = 767) were compared with community controls (n = 1,367). Compared with never users, the adjusted risk of ovarian cancer was reduced by 40% for oral contraceptive users overall, with longer duration of use affording greater protection. The ovarian cancer risk reduction was similar for women who initiated oral contraception before 1972, when high-dose pills dominated the market; between 1972 and 1980; and after 1980, when newer, lower-dose pills dominated. Oral contraceptive estrogen and progestin content were compared for cases and controls after adjustment for current age, number of pregnancies, race, and family history of ovarian cancer. Use of low-estrogen/low-progestin pills afforded an estimated risk reduction (odds ratio = 0.5, 95% confidence interval: 0.3, 0.6) that was identical to that for high-estrogen/high-progestin pills (odds ratio = 0.5, 95% confidence interval: 0.3, 0.7).

Previous epidemiologic observations consistently suggest that suppression of ovulation, tubal ligation, and hysterectomy reduce the risk of ovarian cancer and that perineal talc use increases the risk. We examined these and other risk factors in the context of a new hypothesis: that inflammation may play a role in ovarian cancer risk. Ovulation entails ovarian epithelial inflammation; talc, endometriosis, cysts, and hyperthyroidism may be associated with inflammatory responses of the ovarian epithelium; gynecologic surgery may preclude irritants from reaching the ovaries via ascension from the lower genital tract. We evaluated these risk factors in a population-based case-control study. Cases 20-69 years of age with a recent diagnosis of epithelial ovarian cancer (767) were compared with community controls (1,367). We found that a number of reproductive and contraceptive factors that suppress ovulation, including gravidity, breast feeding, and oral contraception, reduced the risk of ovarian cancer. Environmental factors and medical conditions that increased risk included talc use, endometriosis, ovarian cysts, and hyperthyroidism. Gynecologic surgery including hysterectomy and tubal ligation were protective. Tubal ligation afforded a risk reduction even 20 or more years after the surgery. The spectrum of associations provides support for the hypothesis that inflammation may mediate ovarian cancer risk.

In case-control studies, exposure to a risk factor often occurs at several levels, so the attributable risk at each level is of interest. In this paper, estimation for the 2 X 2 table (case-control status versus dichotomous exposure) and the 2 X k table (case-control status versus exposure at several levels) are reviewed along with an example. A method for finding confidence intervals for attributable risk in the 2 X k table is proposed, and its application to estimates adjusted across strata (the 2 X k X s case) is indicated. The results of a Monte Carlo study of the procedure demonstrate that the nominal and actual coverage probabilities agree satisfactorily for practical applications.

Optimal allocation strategies for the comparison of proportions, p1 and p2, in two groups are discussed. Allocations which (i) maximize the precision in the estimation of the difference p1-p2, (ii) maximize the precision in the estimation of the ratio p1/p2, (iii) maximize the power to detect a group difference, and (iv) minimize the total cost of a study are compared. The recommended allocation varies markedly with the desired objective. Furthermore, there is a wide range of allocation schemes which are effectively optimal with regard to each criterion considered. A study of congenital malformations occurring in pregnancies of diabetic women is used to illustrate how these considerations apply to the planning of a study.

Levels of antibody in serum after infection with Haemophilus influenza type b or challenge with polysaccharide vaccine are highly variable. Convalescent-phase serum antibody to the capsular polysaccharide of H. influenzae type b was measured in two groups of patients with pathophysiologically distinct diseases, meningitis and acute epiglottitis. Antibody response after H. influenzae meningitis was subnormal. Mean levels of antibody, the distribution of antibody levels by age, and erythrocyte and genetic marker lymphocyte antigens were studied; all results suggested that these two groups of patients were genetically and immunologically different from each other. Evidence suggested that the magnitude of the important host immunologic response was under host genetic control.

Covalent binding to immunogenic proteins increases the immunogenicity of the capsular polysaccharides of Haemophilus influenzae type b (Hib) and pneumococcus type 6A (Pn6A). Conjugates composed of Hib, Pn6A, or the cross-reacting Escherichia coli K100 covalently bound to tetanus toxoid (TT) were injected into young adult volunteers. Local reactions were common and were probably due to Arthus reactivity mediated by the preexisting antibodies reacting with the TT component of the conjugates. Fever occurred in about 10% of the volunteers after the first injection; no volunteers had fever after the second injection. Similar levels of Hib or Pn6A antibodies were elicited by either 50- or 100-micrograms doses or by concurrent injection of two different conjugates (Hib-TT and Pn6A-TT or Hib-TT and K100-TT). The Hib-TT elicited about a 180-fold increase in Hib antibodies, and the Pn6A-TT conjugate elicited about an 8-fold increase in Pn6A antibodies after one injection. Booster reactions were not elicited in adults; similar levels of antibodies in the five experimental groups suggested that the responses elicited by the conjugates were maximal. A one-way cross-reaction was noted as Pn6A conjugates elicited rises of Hib antibodies in 13 of 20 volunteers; only 4 of 59 volunteers immunized with Hib-TT had increases in Pn6A antibodies. The preimmunization Hib antibodies were composed of immunoglobulin M (IgM), IgA, and IgG. The postimmunization sera showed an increase in all three isotypes; the elevation of the IgG was the highest of the three isotypes. Conjugate-induced antibodies to both the polysaccharide and TT exerted biological activities that have been correlated with immunity. Adsorption of the Hib-TT onto aluminium hydroxide resulted in higher levels and an earlier Hib antibody response in infant rhesus. These results encourage the evaluation of Hib and Pn6A conjugates in human children and infants.

Approximately 16,000 children, from two months to five years of age, were vaccinated with the capsular polysaccharide of either Haemophilus influenzae type b or group C Neisseria meningitidis. Immunizations were carried out in a double-masked, randomized manner; the doses of immunogens used were 10 microgram of H. influenzae type b polysaccharide and 25 micron g of the group CN. meningitidis polysaccharide. Immunogenicity of the two vaccines was measured in single, random specimens of blood taken from vaccinees of all ages at various intervals after immunization. A positive effect on formation of serum antibody was observed in children of all ages vaccinated with N. meningitidis polysaccharide, but increased levels of serum antibody to H. influenzae type b were observed only in recipients of that vaccine who were three years of age or older. No untoward reactions to either vaccine were noted, and both vaccines retained their original molecular size after storage for three years. Too few cases of disease have been studied for a definitive assessment of vaccine efficacy; however, a slightly protective effect against meningitis was observed for the H. influenzae type b vaccine in infants up to one year of age.

Data concerning ethinylestradiol (EE) blood levels among 93 healthy women using oral contraceptives are presented. Seventy-two per cent of the observed variation in EE blood levels was unexplainable on the basis of time since ingestion of the last oral contraceptive, day of menstrual cycle, race, age, weight, height, blood pressure, cigarette consumption, alcohol consumption, diurnal variation, or lifetime use of oral contraceptives.

Follow-up studies of certain diseases such as cervical dysplasia and carcinoma in situ may employ repeated screening to determine disease incidence in selected cohorts. Where errors of diagnosis occur, the true cohort experience will be distorted by an amount dependent upon the frequency of screening and the magnitude of the probabilities of incorrect diagnoses. These effects are investigated through a simple model of follow-up which employs three basic assumptions: that the probability of false positive and false negative diagnoses are constant; that individuals diagnosed as positive are treated and removed from the study, irrespective of whether or not they actually have the disease; and that fixed intervals occur between follow-up exams. The analysis permits one to assess the amount of bias introduced, and numerical examples are provided.