William B. Goggins

Evidence for an Association Between Air Pollution and Daily Stroke Admissions in Kaohsiung, Taiwan

Background and Purpose— Many studies have reported increases in daily cardiovascular mortality and hospital admissions associated with increases in levels of air pollutants. However, little is known about the relationship between hospital admissions for stroke and air pollution. This study was undertaken to determine whether there is an association between air pollution and hospital admissions for stroke in Kaohsiung, Taiwan. Methods— Data on a total of 23 179 stroke admissions were obtained for the period 1997 through 2000. The relative risk of hospital admissions was estimated with a case-crossover approach. Results— In the single-pollutant models, on warm days (≥20°C), significant positive associations were found between levels of PM10, NO2, SO2, CO, and O3 and both primary intracerebral hemorrhage and ischemic stroke admissions. On cool days (<20°C), only CO levels and ischemic stroke admissions were significantly associated. For the 2-pollutant models, PM10 and NO2 remained consistently and significantly associated with admissions for both types of stroke on warm days. We observed estimated relative risks of 1.54 (95% confidence interval [95%], 1.31 to 1.81) and 1.56 (95% CI, 1.32 to 1.84) for primary intracerebral hemorrhage for each interquartile range increase in PM10 and NO2. The values for ischemic stroke were 1.46 (95% CI, 1.32 to 1.61) and 1.55 (95% CI, 1.40 to 1.71), respectively. The effects of CO, SO2, and O3 were mostly nonsignificant when either NO2 or PM10 was controlled for. Conclusions— This study provides an association between exposure to air pollution and hospital admissions for stroke.

Social Determinants of Frailty

Background: Frailty represents a body-wide set of a linked deterioration that occurs with ageing, but is susceptible to active intervention and is reversible. The concept of frailty should include broader environmental factors. A quantitative measure of frailty, the frailty index (FI), developed for elderly Canadians and shown to be valid for an elderly Chinese population, was examined for its association with socioeconomic, lifestyle, and social support network factors in an elderly Chinese cohort. Objective: 2,032 people aged 70 years and over recruited by stratified random sampling of the population were surveyed in 1990–1991, and information obtained regarding physical and functional health, psychological factors, lifestyle, socioeconomic and social support factors. The FI was constructed from 62 variables covering cognitive, psychological and physical health, and tested for association with socioeconomic, lifestyle and social support factors using ANOVA and t test. Results: The mean FI for women was higher than for men (0.16 ± 0.08, n = 1,033 vs. 0.13 ± 0.08, n = 999, p < 0.001, t test). For men, increasing frailty was observed with non-white collar occupations, inadequate expenses, no or little exercise, abstinence from alcohol, few relatives or neighbours and no or infrequent participation in helping others. For women, little contact with relatives (rather than number of relatives), and absence of participation in community/religious activities were additional factors. Conclusion: FI is influenced by social and environmental factors in keeping with the concept of frailty being multi-dimensional. Such a quantitative measure may be a useful indicator of the health of elderly populations as well as for public health measures to combat frailty.

A population-based analysis of risk factors for a second primary cutaneous melanoma among melanoma survivors

The results of several studies have provided evidence that patients diagnosed with cutaneous melanoma (CM) are at a higher risk of developing a second primary CM than the general population. In this study, the authors examined how the risk of a second primary tumor varied with time from diagnosis of CM and examined the patient‐specific factors that modify a CM patients risk of developing a second primary tumor.

Evidence for an association between cutaneous melanoma and non-Hodgkin lymphoma

Over the past 2 decades both cutaneous melanoma (CM) and non‐Hodgkin lymphoma (NHL) incidence rates have increased substantially. One approach to better understanding the etiologic basis for these increases is to examine the risk of NHL in CM survivors and the risk of CM in NHL survivors.

Association between female breast cancer and cutaneous melanoma

Epidemiologic studies have provided suggestive evidence of a link between cutaneous melanoma (CM) and breast cancer (BC). Moreover, carriers of mutations in the breast cancer predisposition gene, BRCA2, have an increased risk of melanoma while carriers of mutations in the melanoma susceptibility gene, CDKN2A, exhibit a higher than expected risk of breast cancer. These findings raise the possibility that pathways involved in the development of CM and BC overlap and that survivors of one cancer may be prone to develop the other. To this end, we set out to determine if survivors of female BC in the Surveillance, Epidemiology and End Result (SEER) database are at increased risk for CM and vice versa. We followed female BC patients registered in the 1973—1999 SEER database for development of a second CM and female CM patients for the development of a second BC. The expected number of cases was then compared to the observed number of cases using standardized incidence ratios. Overall, we found a modest but statistically significant increased risk of CM among female BC survivors and vice versa. Among young BC patients, we observed a 46% elevated risk of a second CM. Women who underwent radiation therapy exhibited a 42% increased risk for CM. The risks of BC among female CM survivors and CM among BC survivors were also elevated, albeit to a much lesser degree (overall, 11% and 16%, respectively). We found a mutual association between female BC and CM. The elevated risk for CM, especially among younger BC patients, suggests that the genetic observations from high‐risk groups may also be operative at a much lower level in the general BC population.

A Markov Chain Monte Carlo EM Algorithm for Analyzing Interval-Censored Data Under the Cox Proportional Hazards Model

This paper proposes a Monte Carlo EM (MCEM) algorithm for fitting the proportional hazards model for interval-censored failure-time data. The algorithm generates orderings of the failures from their probability distribution under the model. We maximize the average of the log-likelihoods from these completed data sets to obtain updated parameter estimates. As with the standard Cox model, this algorithm does not require the estimation of the baseline hazard function. The performance of the algorithm is evaluated using simulations, and the method is applied to data from AIDS and cancer studies. Our results indicate that our method produced more precise and unbiased estimates than methods of right and midpoint imputation.

Relationship between air pollution and daily mortality in a tropical city: Kaohsiung, Taiwan.

Air pollution has been associated with daily mortality in numerous studies over the past decade. However, most of these studies were conducted in the United States and Europe, with relatively few done in Asia. In this study, the association between ambient air pollution and daily mortality in Kaohsiung, Taiwan, a large industrial city with a tropical climate, was investigated for the period 1994-2000 using a case-crossover analysis. This design is an alternative to Poisson time-series regression for studying the short-term adverse health effects of air pollution. The air pollutants examined included particulate matter (PM 10 ), sulfur dioxide (SO 2 ), ozone (O 3 ), nitrogen dioxide (NO 2 ), and carbon monoxide (CO). No significant effects were found between PM 10 and SO 2 exposure levels and respiratory-related mortality. The well-established link between air pollution levels and daily mortality may not be as strong in cities in tropical areas, although other factors such as differences in pollutant mixtures or underlying health of the population may explain the lack of a strong association in this study. Further studies of this type in cities with varying climates and cultures are needed.

Thymosin beta-15 predicts for distant failure in patients with clinically localized prostate cancer—results from a pilot study

OBJECTIVESnTo report the results of a pilot study on the prognostic value of a newly identified actin-binding protein, thymosin beta-15 (Tbeta15), in predicting prostate-specific antigen (PSA) and bone failure in patients with Gleason 6/10 clinically localized prostate cancer.nnnMETHODSnThirty-two patients (median age 70 years) with clinically localized, moderately differentiated (Gleason 6/10) prostate cancer treated by external beam radiotherapy alone (68.4 Gy) with available paraffin blocks at the Massachusetts General Hospital were evaluated for this pilot study. All patients had clinical Stage M0 disease at initial presentation, which was documented by bone scan (T1c-4,NX). Their corresponding biopsy specimens were stained immunohistochemically for Tbeta15, which was then correlated with the clinical outcome in a blinded manner. The median follow-up was 6 years (range 1 to 19) for all of the patients.nnnRESULTSnThe outcomes of the 32 patients can be grouped into three categories: patients with no evidence of disease (n = 11), patients with PSA failure without documented bone failure (n = 11), and patients with PSA failure and documented bone failure (n = 10). Tbeta15 staining intensity strongly correlated with clinical outcome. Of those patients whose specimens stained 3+ (strongest staining), 62% developed bone failure compared with 13% of those patients whose specimens stained 1+ (weakest staining) (P = 0.01). The 5-year freedom from PSA failure was only 25% for those patients with 3+ staining compared with 83% for those with 1+ staining (P = 0.02).nnnCONCLUSIONSnThe results of this pilot study have demonstrated that Tbeta15 staining intensity may be a potentially important marker to identify high-risk patients with moderately differentiated, clinically localized prostate cancer.

MELPREDICT: a logistic regression model to estimate CDKN2A carrier probability

Background: Heritable alterations in CDKN2A account for a subset of familial melanoma cases although no robust method exists to identify those at risk of being a mutation carrier. Methods: We set out to construct a model for estimating CDKN2A mutation carrier probability using a cohort of 116 consecutive familial cutaneous melanoma patients evaluated at Massachusetts General Hospital Pigmented Lesion Center between April 2001 and September 2004. Germline CDKN2A and CDK4 status on the familial melanoma cases and clinical features associated with mutational status were then used to build a multiple logistic regression model to predict carrier probability and performance of model on external validation. Results: From the 116 kindreds prone to melanoma in the Boston area, 13 CDKN2A mutation carriers were identified and 12 were subsequently used in the modeling. Proband age at diagnosis, number of proband primaries, and number of additional family primaries were most closely associated with germline mutations. The estimated probability of the proband being a mutation carrier based on the logistic regression model (MELPREDICT) is given by where Lu200a=u200a1.99+[0.92×(no. of proband primaries)]+[0.74×(no. of additional family primaries)]−[2.11×ln(age)]. The mean estimated probabilities for subjects in the Boston dataset were 55.4% and 5.1% for the mutation carriers and non-carriers respectively. In a receiver operator characteristic analysis, the area under the curve was 0.881 (95% confidence interval 0.739 to 1.000) for the Boston model set (nu200a=u200a116) and 0.803 (0.729 to 0.877) for an external Toronto hereditary melanoma cohort (nu200a=u200a143). Conclusions: These results represent the first-iteration logistic regression model to approximate CDKN2A carrier probability. Validation of this model with an external dataset revealed relatively robust performance.

Elevation of thyroid cancer risk among cutaneous melanoma survivors

Recent molecular studies have identified recurrent BRAF mutations in both cutaneous melanoma and thyroid malignancies. This relatively selective shared genetic vulnerability raises the possibility that these 2 tumors are connected through a common undisclosed pathogenic mechanism. To assess for possible associations between these 2 genetically related tumors at the population level, we calculated standardized incidence ratios (SIRs) for thyroid cancer (TC) among cutaneous melanoma (CM) survivors and CM among TC survivors using the National Cancer Institutes Surveillance, Epidemiology and End Result (SEER) database. Between 1973 and 2000, there were 73,274 and 27,138 cases of CM and TC cases, respectively. Overall, we found a 2.17‐fold increase (p < 0.0000001) in the risk of TC after a diagnosis of CM. This augmented risk of TC is somewhat higher for males, for those diagnosed more recently and for the first 3 years after the CM diagnosis. We also detected a considerably smaller and borderline significant increased risk of CM (25%, p = 0.063) among the post‐TC survivors. Of note, TC patients who received radiation therapy had a 57% increased risk of a subsequent CM (p = 0.034). Our study documents a strong unilateral risk of TC after CM. More studies are clearly needed to better delineate this mechanism.