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Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study.

CONTEXT: In anthroposophical medicine, total extracts of Viscum album (mistletoe) have been developed to treat cancer patients. The oldest such product is Iscador. Although Iscador is regarded as a complementary cancer therapy, it is the most commonly used oncological drug in Germany. OBJECTIVE: To determine whether Iscador treatment prolongs survival time of patients with carcinoma of the colon, rectum, or stomach; breast carcinoma with or without axillary or remote metastases; or small cell or non-small-cell bronchogenic carcinoma; and to explore synergies between Iscador treatment and psychosomatic self-regulation. DESIGN: Prospective nonrandomized and randomized matched-pair studies nested within a cohort study. SETTING: General community in Germany. PARTICIPANTS: 10,226 cancer patients involved in a prospective long-term epidemiological cohort study, including 1668 patients treated with Iscador and 8475 who had taken neither Iscador nor any other mistletoe product (control patients). INTERVENTION: Iscador. MAIN OUTCOME MEASURE: Survival time. RESULTS: In the nonrandomized matched-pair study, survival time of patients treated with Iscador was longer for all types of cancer studied. In the pool of 396 matched pairs, mean survival time in the Iscador groups (4.23 years) was roughly 40% longer than in the control groups (3.05 years; P < .001). Synergies between Iscador treatment and self-regulation manifested in a longer survival advantage for Iscador patients with good self-regulation (56% relative to control group; P = .03) than for patients with poor self-regulation. Results of the 2 randomized matched-pair studies largely confirmed the results of the non-randomized studies. CONCLUSION: Iscador treatment can achieve a clinically relevant prolongation of survival time of cancer patients and appears to stimulate self-regulation.

Antineoplastic Agents, Phytogenic↗

Outcome of pediatric traumatic brain injury at three years: a cohort study.

This cohort study examined the neurobehavioral, academic, and "real world" consequences of mild, moderate, and severe traumatic brain injury in children at 3 years following the resolution of posttraumatic amnesia. Seventy-two children, aged 6 to 15 years at time of injury, were individually matched with controls on the basis of age, gender, school grade, and the classroom teacher's assessment of premorbid academic achievement and behavior. Both groups were assessed using the same standardized neuropsychological test battery and parent and teacher report measures as were used initially and at 1-year follow-up covering 10 cognitive, behavioral, and functional domains. The performance of both moderately and severely injured children was worse than their controls on 40 out of 53 variables. The association of outcome variables with injury severity was validated using school achievement tests and grades. Analyses of the impact of preinjury variables and study dropouts on outcome showed no threat to the validity of study findings. These results provide strong validation for the persisting and comprehensive nature of neuropsychological deficits in children and adolescents with moderate and severe traumatic brain injury.

Adolescent↗

[Case-cohort studies: an effective design for the investigation of biomarkers as risk factors for chronic diseases--demonstrated by the example of the MONICA/KORA Augsburg Case-Cohort Study 1984-2002].

As it is often not possible to determine specific measures of exposure in all participants of a prospective cohort study due to financial or other restrictions, new study designs have been developed. The aim of these designs is to obtain valid results even though expensive measurements are restricted to a limited number of participants of the original cohort study. The case-cohort study is a design that has recently become interesting as an alternative to the well known nested case-control study. The following article describes the case-cohort design considering as an example data from the MONICA/KORA Augsburg cohort study 1984-2002 and the outcomes of type 2 diabetes mellitus and acute myocardial infarction. Furthermore, results obtained in the full cohort for selected exposures are compared with results obtained in the case-cohort study.

Adult↗

Cancer after pre-eclampsia: follow up of the Jerusalem perinatal study cohort.

OBJECTIVE: To compare the incidence of cancer among women with and without a history of pre-eclampsia. DESIGN: Cohort study. SETTING: Jerusalem perinatal study of women who delivered in three large hospitals in West Jerusalem during 1964-76. PARTICIPANTS: 37 033 women. MAIN OUTCOME MEASURES: Age adjusted and multivariable adjusted hazard ratios for cancer incidence for the entire cohort and for women who were primiparous at study entry. RESULTS: Cancer developed in 91 women who had pre-eclampsia and 2204 who did not (hazard ratio 1.27, 95% confidence interval 1.03 to 1.57). The risk of site specific cancers was increased, particularly of the stomach, ovary epithelium, breast, and lung or larynx. The incidence of cancer of the stomach, breast, ovary, kidney, and lung or larynx was increased in primiparous women at study entry who had a history pre-eclampsia. CONCLUSIONS: A history of pre-eclampsia is associated with increases in overall risk of cancer and incidence at several sites. This may be explained by environmental and genetic factors common to the development of pre-eclampsia and cancer in this population.

Epidemiologic Methods↗

Southern community cohort study: establishing a cohort to investigate health disparities.

OBJECTIVES: To demonstrate the methods of recruitment of a low-income, predominantly African-American study population for the Southern Community Cohort Study (SCCS), a prospective epidemiologic investigation of racial disparities in cancer risk. METHODS: Partnerships with community health centers (CHCs) were formed to reach underserved populations throughout the south. Recruitment of participants (aged 40-79) in CHCs began in March 2002. Participants complete a comprehensive baseline interview and provide a blood or buccal cell sample. Recruitment will expand to the general population of the south to achieve a broad cross-section of socioeconomic status, The final cohort size is expected to be approximately 100,000. RESULTS: A high level of cooperation and recruitment was achieved in the CHCs. From March 2002 to October 2004, 32,632 participants (80% black, 41% male, 62% with total household income < $15,000, 34% with < 12 years schooling) enrolled. Participants reported a high prevalence of medical conditions (21% diabetic, 44% obese) and adverse health behaviors (45% current smokers). CONCLUSIONS: Working in CHCs is successful for recruiting a population that has been difficult to reach in previous studies. The SCCS is a unique cohort that will provide a rich resource for evaluating disparities in cancer and other chronic disease risk as it is followed over time.

Adult↗

Validity of self-reported cancers in a prospective cohort study in comparison with data from state cancer registries.

The accuracy of self-reported cancer diagnoses in a prospective study was compared with population-based cancer registry data in four states. The study cohort included 65,582 men and women aged 39-96 years who were participants in the Cancer Prevention Study II Nutrition Survey, begun by the American Cancer Society in 1992. Estimates of sensitivity (the proportion of study participants with a registry-documented cancer who self-reported the cancer) ranged from 0.79 for an exact match of cancer site and year of diagnosis (+/- 1 year) to 0.93 for a match of any reported cancer. The sensitivity of exact matches varied considerably by cancer site and was highest for breast, prostate, and lung cancers (0.91, 0.90, and 0.90, respectively) and lowest for rectal cancer and melanoma (0.16 and 0.53, respectively). Sensitivity also varied slightly by the age, education, and smoking status of study participants. Estimates of sensitivity were virtually identical for each of the four states. The positive predictive value (the proportion of self-reported cancers that were confirmed by the registries) was 0.75 overall and also varied by cancer site. Unlike sensitivity, however, this proportion varied considerably by state. All self-reports of cancer that were not confirmed by the registries were further investigated by repeat questionnaires and acquisition of medical records. Low positive predictive values were due to underascertainment of true cancer cases by the registries, inaccurate reporting on the part of study participants, and problems with the algorithm used by the state to link the study population to the registry data. In conclusion, the ability of members of this cohort to report a past diagnosis of cancer accurately is quite high, especially for cancers of the breast, prostate, lung, and colon, or for the occurrence of any cancer.

Aged↗

An application of a weighting method to adjust for nonresponse in standardized incidence ratio analysis of cohort studies.

PURPOSE: Cohort studies often conduct periodic follow-up interviews (or waves) to determine disease incidence since the previous follow-up and to update measures of exposure and confounders. The common practice of excluding nonrespondents from standardized incidence ratio (SIR) analyses of these cohorts can bias the estimates of interest if nonrespondents and respondents differ on important characteristics related to outcomes of interest. We propose an analytic approach to reduce the impact of nonresponse in the analyses of SIRs. METHODS: Logistic regression models controlling baseline information are used to estimate the propensity, or the probability of response; the reciprocals of these propensities are used as weights in the analysis of risk. This is illustrated in the analysis of 15 years of follow-up of a cohort of US radiologic technologists after an initial interview to assess the risk at several cancer sites from occupational radiation exposure. We use information from the baseline survey and certification records to compute the propensity of responding to the second survey. SIRs are computed using Surveillance, Epidemiology, and End Results (SEER) cancer incidence rates. Variances of the SIRs are estimated by a jackknife method that accounts for additional variability resulting from estimation of the weights. RESULTS: We find that, in this application, weighting alters point estimates and confidence limits only to a small degree, thus providing reassurance that the results are robust to nonresponse. This indicates that results from the analyses excluding the missing data may be slightly biased and weighting helps in reducing the nonresponse bias. CONCLUSION: This method is flexible, practical, easy to use with existing software, and is applicable to missing data from cohorts with baseline information on all subjects.

Bias↗

Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study.

A cohort of 98 HIV-infected initially AIDS-free homosexual men from the Multicenter AIDS Cohort Study (MACS) was followed for 6 years to investigate whether CD8+ cell subsets have prognostic value for progression to AIDS. In the present study, four subsets of CD8+ T cells that previously have been shown to be selectively elevated in HIV-infected asymptomatic persons, specifically the CD8+ T cell subsets that were CD38+, HLA-DR+, CD57+ and L-selectin negative (Leu8-), were measured. Forty-nine of the 98 developed AIDS. Prognostic value of these CD8+ cell subsets was evaluated using the proportional hazards model. Levels of both CD38+ CD8+ and Leu8- CD8+ cells individually had prognostic value for progression to AIDS. In contrast, CD57+ CD8+ and HLA-DR+ CD8+ cell subsets levels did not have prognostic value. After adjustment for level of CD4+ T cells, however, only the elevation in the CD38+ CD8+ cell subset had additional prognostic value. These results suggest that the level of CD38+ CD8+ cells could be used together with the CD4+ T cell level to more accurately predict progression to AIDS among HIV-infected men. These results provide further support for the observation that dramatic and progressive activation of CD8+ T cells in HIV infection occurs. The power of elevated levels of the CD38+ CD8+ subset to predict poor prognosis in this cohort suggests these CD8+ T cells reflect an immune stimulation that is ultimately unable to control disease progression.

ADP-ribosyl Cyclase↗

The safety of field tubal sterilization: a cohort study.

A cohort study on female sterilization has been carried out to compare the safety of field-based procedures with hospital-based procedures. A total of 217 women were recruited, consisting of 103 field-based and 114 hospital-based acceptors. Married and healthy women 20-45 years of age, having at least two living children, not obese, no history of major abdominal surgery, no signs of acute pelvic inflammatory disease, and no contraindication to ketamin were included in the study. Women with severe pelvic adhesions encountered during surgery were excluded from the study. The ambulatory procedure was used for all acceptors except those who were sterilized in hospital immediately after delivery. They were asked to come to th Sarjito Hospital (hospital-based) or Puskesmas (primary health care center or field-based), after fasting the night before. Ketamin, 50-100 mg, was used intravenously for general anesthesia. Minilaparotomy followed by the Pomeroy method was used for standard female tubal sterilization. Tetracycline, 3 x 500 mg was given for five days prophylactically. Follow-up was carried out one and six weeks after the day of operation. Data were processed with an IBM-compatible PC, using version 3.0 SPSS program. Students t-test, chi-square test and relative risk (95% confidence limit (CL)) were used for statistical analysis. Both groups were comparable in terms of age, parity, body weight, and body height. The duration of operation in the field was somewhat longer than that in the hospital, i.e. 24.58 vs 21.14 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cigarette smoking and the risk of invasive epithelial ovarian cancer in a prospective cohort study.

Few cohort studies have examined the association between cigarette smoking and ovarian cancer risk, either overall, or by histological subtype. In relation to the latter, it has been suggested that mucinous ovarian tumours may be aetiologically unrelated to the other types of epithelial tumours and that their respective associations with cigarette smoking may differ. We examined the association between smoking and ovarian cancer risk using data from participants in a randomised controlled trial of screening for breast cancer involving 89,835 women aged 40-59 years at recruitment. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (CI). During an average of 16.5 years of follow-up, we observed 454 incident cases of ovarian cancer (184 serous, 67 endometrioid, 32 mucinous, 171 other or unknown). We found that women who had smoked for several decades had an approximately two-fold increased risk of epithelial ovarian cancer. Relative to never-smokers, women who had smoked for 40 years or more were at the highest risk (RR=2.50, 95% CI=1.37-4.56). The association with non-mucinous tumours was similar to that observed overall. For mucinous tumours, a two-fold increased risk was observed with smoking of shorter duration, although the number of mucinous tumours in our data-set was small. Long-term cigarette smoking may be associated with an increased risk of epithelial ovarian tumours.

Adenocarcinoma, Mucinous↗

Effects of job stress on occurrence of major depression in Japanese industry: a case-control study nested in a cohort study.

To examine the relationship between psychosocial job stress and major depression, a prospective cohort study was conducted of 3066 male workers in two factories of an electrical company in Japan. The workers were observed for 3 years; 15 workers newly developed major depression. The effects of six job stress variables, depressive symptoms, and other possible confounders were assessed by means of self-administered questionnaires once a year. Five workers without apparent psychiatric disorder were matched for each patient by gender (all male), age (within 5 years), marital status, factory, and occupation; the 15 cases and the 75 controls were compared. Proportions of perceived stress due to unsuitable jobs and human relations were significantly higher in the cases than in the controls. Results of the conditional multiple logistic regression analysis indicated that stress due to unsuitable jobs was significantly associated with occurrence of major depression after depressive symptoms were controlled for. It is suggested that stress due to unsuitable jobs is a possible risk factor for major depression in industry.

Adult↗

Obtaining a Diagnostic Yield via Scan findings prior to the introduction of SEquencing retrospectivelY (ODYSSEY): a cohort study.

OBJECTIVE: To determine the retrospective yield of prenatal exome sequencing (PES) by establishing the proportion of children with a postnatal monogenic diagnosis that could have been diagnosed prenatally if PES had been available. METHODS: The study cohort comprised a sample of children in Northern Ireland, born between January 2010 and January 2018 (predating routine availability of PES), who received a monogenic diagnosis postnatally via next generation sequencing as part of either of two UK-wide studies (the 100&#x2009;000 Genomes Project (2015-2018) or the Deciphering Developmental Disorders study (2011-2015)). Clinical data were collected retrospectively and correlated with the current UK National Health Service PES protocol, including the phenotypic eligibility criteria for PES and the associated fetal anomalies gene panel. Cases were considered retrospective diagnoses if the fetal phenotype would have been eligible for PES and the diagnostic gene was included on the test panel, meaning prenatal diagnosis in this current era could have been feasible. RESULTS: Of 101 children, 17.8% (95%&#x2009;CI, 10.3-25.3%) had both an eligible fetal structural anomaly (FSA) (i.e. high-risk FSA) and a diagnostic gene on the associated test panel, meaning that they could have been diagnosed prenatally in the current clinical landscape. The median length of the diagnostic odyssey for this subgroup of children was 3.7&#x2009;years (1354&#x2009;(range, 822-2450)&#x2009;days). Moreover, 58.4% (n&#x2009;=&#x2009;59) of cases had no anomalies detected prenatally and 19.8% (n&#x2009;=&#x2009;20) had a FSA that would not meet the eligibility criteria for PES (low-risk FSA). Although these cases would have been ineligible for PES under the current clinical pathway, 89.9% (n&#x2009;=&#x2009;71/79) were affected by severe or profound syndromes. Postnatally, the most common functional anomalies were neurodevelopmental delay/intellectual disability and/or behavioral abnormality, which were observed in 80.2% (n&#x2009;=&#x2009;81) of the included children. However, 80.2% (n&#x2009;=&#x2009;65/81) of these affected children did not present with fetal anomalies eligible for PES. CONCLUSIONS: Almost one-fifth of children with a monogenic condition included in this study could have received a diagnosis via modern PES, avoiding a diagnostic odyssey lasting almost 4&#x2009;years. However, despite having a monogenic condition, over half of the children did not present with any structural anomalies in utero. This demonstrates the degree to which fetal imaging is limited in its ability to reassure parents of the absence of a fetal genetic syndrome. &#xa9; 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Humans↗

An historical cohort study of cardiac catheterization during childhood and the risk of cancer.

This study aimed to determine whether cancer risk was elevated among patients exposed to radiation from diagnostic cardiac catheterization during childhood. The study cohort included 3915 children who underwent at least one cardiac catheterization at a major children's hospital in Toronto, Canada, between 1950 and 1965, were < or = 18 years at the time of the procedure, and were residents of Ontario. Follow-up of the cohort was done by linkage to the Ontario Cancer Registry up to 1986. A total of seven cancer deaths were observed (O), compared with 5.7 expected (E) based on provincial cancer rates (mortality ratio [O/E] = 1.2; 90% confidence interval [CI] : 0.6-2.3). In the analysis of cancer incidence, 13 cancers were detected, compared with 17.3 expected (O/E = 0.75; 90% CI : 0.4-1.2). These mortality and incidence ratios were not statistically significantly elevated. Detailed analyses were conducted according to age at exposure, age at diagnosis, sex, number of procedures, year of first catheterization, and latent period. Detected deviations in risk were confined to an early period of exposure, indicating that later practices of cardiac catheterization were not associated with increased risk. In general, there was no statistically significant excess risk of cancer among the cohort.

Adolescent↗

A cohort study of employees of a manufacturing plant using trichlorethylene.

A prospective study was conducted of 2,646 employees who worked three months or more during the period January, 1957, through July, 1983, in a manufacturing plant that used trichlorethylene as a degreasing agent throughout the study period. Ninety-eight percent of the study cohort were traced; they accounted for 16,388 person-years of employment and 38,052 person-years of follow-up. Mortality experience was found to be generally more favorable than that of the comparable segment of the U.S. population over the same period of time. For the white male cohort there were fewer deaths than expected from heart disease, cancer, and trauma (standard mortality rate for all causes = 0.79, p less than .01). Reports by current and former employees of health problems requiring medical treatment showed that there were only one third as many persons with heart disease or hypertension as were reported in a comparable reference population studied over the past five years.

Adult↗

Association of socioeconomic status and receipt of colorectal cancer investigations: a population-based retrospective cohort study.

BACKGROUND: Although the Canadian health care system was designed to ensure equal access, inequities persist. It is not known if inequities exist for receipt of investigations used to screen for colorectal cancer (CRC). We examined the association between socioeconomic status and receipt of colorectal investigation in Ontario. METHODS: People aged 50 to 70 years living in Ontario on Jan. 1, 1997, who did not have a history of CRC, inflammatory bowel disease or colorectal investigation within the previous 5 years were followed until death or Dec. 31, 2001. Receipt of any colorectal investigation between 1997 and 2001 inclusive was determined by means of linked administrative databases. Income was imputed as the mean household income of the person's census enumeration area. Multivariate analysis was performed to evaluate the relationship between the receipt of any colorectal investigation and income. RESULTS: Of the study cohort of 1,664,188 people, 21.2% received a colorectal investigation in 1997-2001. Multivariate analysis demonstrated a significant association between receipt of any colorectal investigation and income (p < 0.001); people in the highest-income quintile had higher odds of receiving any colorectal investigation (adjusted odds ratio [OR] 1.38; 95% confidence interval [CI] 1.36-1.40) and of receiving colonoscopy (adjusted OR 1.50; 95% CI 1.48-1.53). INTERPRETATION: Socioeconomic status is associated with receipt of colorectal investigations in Ontario. Only one-fifth of people in the screening-eligible age group received any colorectal investigation. Further work is needed to determine the reason for this low rate and to explore whether it affects CRC mortality.

Aged↗

Does diffuse esophageal spasm progress to achalasia? A prospective cohort study.

Diffuse esophageal spasm (DES) and achalasia share both clinical and manometric characteristics. Some reports support the notion of progression of DES to achalasia. However, there are currently no prospective data in support of this theory. To assess prospectively the rate of manometric progression of DES to achalasia. Manometry tracings of DES patients diagnosed between 1992 and 2003 were independently reviewed blindly and agreed on by two esophageal experts. Patients with DES who agreed to undergo repeat esophageal manometry constituted the study cohort. Follow-up manometry tracings were evaluated blindly and independently by the same two interpreters to determine the rate of manometric progression to achalasia. Predictors of manometric progression were assessed. A total of 32 patients were diagnosed with DES between 1992-2003. Twelve patients (9M/3F; median age 62 years) agreed to participate and underwent second manometry (mean +/- SD follow-up of 4.8 +/- 3.4 years). Achalasia was diagnosed on follow-up manometry in one patient (8%), seven (58%) patients continued to have DES, three (25%) had normal motility, and one (8%) had nutcracker esophagus. There were no predictors of progression to achalasia based on the initial manometry parameters. A subgroup of DES patients with initial low esophageal body amplitude developed increase in esophageal simultaneous contractions on follow-up similar to the patient who evolved to achalasia. Following were the results. 1) Progression from DES to achalasia is uncommon. 2) DES patients with low esophageal body amplitude may develop increased simultaneous contractions over time. 3) DES remains an elusive diagnosis clinically and manometrically.

Aged↗

Social capital, the miniaturisation of community, traditionalism and first time acute myocardial infarction: a prospective cohort study in southern Sweden.

This longitudinal study investigates the impact of social participation, trust and the combinations of social participation and trust on the incidence of first time acute myocardial infarction (AMI) in the population of Scania, southern Sweden. It is based on the cross-sectional 2000 public-health survey in Scania with a 59% participation rate and 13,604 participants, and prospective morbidity/mortality data collected for three years (January 2000-December 2002). The study cohort was followed prospectively to examine first ever AMI. Hazard rate ratios (HRR) for first time AMI in the social participation, trust and social participation/trust combinations were calculated in a Cox regression model with adjustments for age, sex, education, economic stress, daily smoking, leisure time physical activity, body mass index (BMI), and self-reported health. The prevalence of low social participation was 32.8% among men and 31.5% among women. The prevalence of low trust was 40.0% among men and 44.2% among women. The three-year first time AMI rate was significantly higher among people with higher age, low education, daily smoking, poor self-reported health (among men), low social participation, and the combinations of low social participation/high trust and low social participation/low trust. The results show that low social participation but not trust was significantly associated with first time AMI after adjustment for age and sex. The positive association between low social participation and myocardial infarction remained significant after further adjustments for education, economic stress, daily smoking, physical activity and BMI, and became not significant only after additional adjustment for self-reported health, HRR 1.3 (0.9-2.0). High trust in combination with low social participation as well as low social capital (low trust/low social participation) were significantly associated with AMI, but after multiple adjustments only the low social participation/high trust category remained significant, HRR 1.6 (1.0-2.6).

Acute Disease↗