Michael A. Cunningham

Complex Antioxidant Blend Improves Memory in Community-Dwelling Seniors

One hundred thirteen community dwelling subjects between the ages of 50 and 75 without dementia were recruited. A blind administrator randomly assigned 54 subjects to placebo and 59 to active treatment groups. The active treatment consisted of four months treatment with a complex antioxidant blend. Placebo treatment was an identical gel and bottle administered for four months. Forty-eight active subjects and 38 placebo subjects completed the study. Memory testing with a 50 part paired association test and a 20-word immediate recall test were significantly improved, p=0.015 and p=0.005 respectively. A secondary study of serum homocysteine was completed in 25 active treatment subjects and 17 placebo subjects. Significant reduction in serum homocysteine levels was seen in the active treatment subjects (p=0.005). A complex antioxidant blend taken over four months improves performance on two difficult memory tests in community dwelling elderly subjects. Furthermore, the antioxidant significantly reduced the serum homocysteine level in treatment group.

Long-term health experience of jet engine manufacturing workers: II. Total and cause-specific mortality excluding central nervous system neoplasms.

Objective: As part of an exploratory investigation of an unusual occurrence of glioblastoma at one jet engine manufacturing facility located in North Haven, Connecticut (CT), we examined total and cause-specific (excluding central nervous system neoplasms) mortality rates at eight of the company’s CT facilities. Methods: Subjects were 223,894 workers ever employed in one or more of the manufacturing facilities from 1952 to 2001. Vital status was determined through 2004 for 99% of subjects and cause of death for 95% of 68,701 deaths. We computed standardized mortality ratios (SMRs) based on US and CT state rates and modeled internal cohort rates. Results: We observed overall deficits in deaths based on national and state comparisons from all causes, all cancers and most of the cause of death categories examined. State comparisons revealed statistically significant excesses in deaths greater than 25% for kidney cancer (68 deaths, SMR = 1.30, CI = 1.01–1.65) and “other non-malignant respiratory disease” (291 deaths, SMR = 1.27, CI = 1.13–1.42) among subjects employed only at North Haven, and for bronchitis (713 deaths, SMR = 1.28, CI = 1.18–1.37) among all hourly workers. These excesses occurred mainly among short-term workers and hourly workers. Conclusions: We found no evidence of elevated mortality risks for all causes combined, all cancers combined and most of the causes of death categories examined. The pattern of findings for kidney cancer, bronchitis and other non-malignant respiratory disease, based on currently available data, suggests these excesses may be due to non-occupational risk factors or to external occupational factors. We will investigate these excesses further when detailed work history and exposure data from the companion exposure assessment project become available.

An Ecological Study of Cancer Mortality Rates in High Altitude Counties of the United States

To test the hypothesis that sustained, increased hemoglobin levels as measured by residence in high altitudes lead to an increase of malignant cancer deaths, we performed an assessment of U.S. cancer mortality rates for people residing in high altitude counties compared with those in counties with altitudes close to sea level. This included a graphical analysis of mortality rates for all cancers, female breast cancer, respiratory system cancer (RSC) and non-Hodgkin lymphoma (NHL), computation of standardized mortality ratios (SMRs) and Poisson regression modeling. Overall, our ecological evaluation showed statistically significantly reduced SMRs and rate ratios (RRs) for high altitude residents compared to sea level residents. For the causes of death categories examined, we found no evidence that persons residing in high altitude counties are at an elevated risk of cancer mortality compared with persons living close to sea level. Our results corroborate previous altitude studies of cancer mortality.

Long-term health experience of jet engine manufacturing workers: I. Mortality from central nervous system neoplasms

Objective: In response to an unusual occurrence of glioblastoma at one jet engine manufacturing facility located in North Haven (NH), Connecticut (CT), we examined mortality rates from central nervous system (CNS) neoplasms at NH and seven other company facilities. Methods: Subjects were 223,894 workers ever employed in one or more of the company’s eight CT manufacturing facilities from 1952 to 2001. Vital status was determined through 2004 for 99% of subjects and cause of death for 95% of 68,701 deaths. We computed standardized mortality ratios (SMRs) based on US and CT state rates and modeled internal relative risks (RRs). Results: State comparisons revealed overall deficits in deaths from all CNS neoplasms (606 deaths, SMR = 0.84, confidence interval [CI] = 0.78 to 0.91), including all malignant (462 deaths, SMR = 0.87, CI = 0.79 to 0.95), all benign (23 deaths, SMR = 0.65, CI = 0.41 to 0.98), and all unspecified (121 deaths, SMR = 0.79, CI = 0.65 to 0.94). Not statistically significant excesses in deaths from all malignant brain neoplasms were found among subjects who worked only at NH (49 deaths, SMR = 1.11, CI = 0.82 to 1.47) or partly at NH (24 deaths, SMR = 1.04, CI = 0.67 to 1.55) compared with deficits in non-NH plant groups. In the combined NH plant groups, we found not statistically significant higher risks of malignant brain neoplasms for salaried workers, older hires and the most recent time period, but no association with duration of employment or time since first employment. Conclusions: Total cohort mortality rates for malignant, benign or unspecified CNS neoplasms were not elevated relative to the US and CT general populations. The malignant brain neoplasm excesses in certain subgroups of workers from NH may reflect external occupational factors, nonoccupational factors or workplace factors unique to NH that were not measured in the current study. We will explore reasons for the NH excesses and examine specific types of brain neoplasms (eg, glioblastoma) in our companion cancer incidence, case–control and exposure assessment studies.

Long-Term Health Experience of Jet Engine Manufacturing Workers: III. Incidence of Malignant Central Nervous System Neoplasms

Objective: To explore a perceived unusual occurrence of glioblastoma at one jet engine manufacturing facility located in North Haven (NH), Connecticut (CT). Methods: Subjects were 212,513 workers ever employed in 1 of 8 manufacturing facilities from 1952 to 2001 and at risk from 1976 to 2004. We identified 722 cases of CNS neoplasms mainly by tracing through 19 state cancer registries. We computed standardized incidence ratios (SIRs) based on CT state and national rates and modeled internal relative risks (RRs). Results: We found overall deficits in cases for glioblastoma (275 cases, SIR = 0.77, CI = 0.68–0.87) and most other histology categories examined. NH workers had a not statistically significant overall 8% excess in glioblastoma (43 cases, SIR = 1.08, CI = 0.78–1.46). Salaried NH workers had a statistically significant twofold risk of glioblastoma compared with hourly workers (17 cases, RR = 2.04, CI = 1.15–3.57). Other subgroups of NH workers revealed elevated but not statistically significant glioblastoma risks but little evidence of an association with duration of employment or time since first employment. Conclusions: Incidence rates for glioblastoma and other malignant CNS neoplasm histologies were not elevated in the total cohort. The glioblastoma excesses observed among NH workers may reflect external occupational factors, non-occupational factors or workplace factors unique to NH unmeasured in the current study.

Long-Term Health Experience of Jet Engine Manufacturing Workers: IV. A Comparison of Central Nervous System Cancer Ascertainment Using Mortality and Incidence Data

PURPOSE To compare ascertainment of central nervous system (CNS) neoplasms with the use of mortality and incidence data as part of an occupational epidemiology study. METHODS Deaths were identified by matching the cohort of 223,894 jet engine manufacturing employees to the U.S. Social Security Administration death files and the National Death Index. Incident cancer cases were identified by matching the cohort to 19 state cancer registries. RESULTS We identified 718 cases overall: 59% by the use of both mortality and cancer incidence tracing; 24% by the use of only mortality tracing, and 17% by the use of only cancer incidence tracing. Compared with state cancer registries, death certificates missed 38% of the malignant, more than six times the benign and nearly 1.5 times the unspecified CNS cases. The positive predictive value of death certificates, with cancer registry as gold standard, was 6% for unspecified, 35% for benign, and 86% for malignant histologies. CONCLUSIONS Death certificates seriously underascertained benign and unspecified CNS tumors; analyses determined with mortality data would not accurately capture the true extent of disease among the cohort. Most state cancer registries have only collected nonmalignant CNS tumor information since 2004, which currently limits the usefulness of state cancer registries as a source of nonmalignant CNS tumor identification. Underascertainment of CNS deaths could seriously affect interpretation of results, more so if examining nonmalignant CNS.

Pharmaceutical production workers and the risks of mortality from respiratory system cancer and lymphatic and hematopoietic tissue cancers.

Objectives: To evaluate further elevated mortality risks from respiratory system cancer (RSC) and lymphatic and hematopoietic tissue cancers (LHTC) in a cohort of 1466 male workers employed full-time in pharmaceutical production. Methods: We computed standardized mortality ratios, and in nested case-control studies of RSC and LHTC, evaluated mortality risks by plant exposures with adjustment for potential confounding factors. Results: Subjects with potential plant exposure had no elevated RSC risk and a statistically significant LHTC excess. The case-control study found many RSC risks reduced with adjustment for smoking, and LHTC risks increased with increasing levels of average exposure to dimethyl-formamide. Conclusions: RSC mortality risks decreased, and we found limited evidence that positive confounding by smoking may explain some remaining excess risks. For LHTC, increased mortality risks and exposure-response patterns in the case-control study may indicate a possible workplace association.