Brenda Cartmel

Randomized Exercise Trial of Aromatase Inhibitor-Induced Arthralgia in Breast Cancer Survivors

PURPOSE Arthralgia occurs in up to 50% of breast cancer survivors treated with aromatase inhibitors (AIs) and is the most common reason for poor AI adherence. We conducted, in 121 breast cancer survivors receiving an AI and reporting arthralgia, a yearlong randomized trial of the impact of exercise versus usual care on arthralgia severity. PATIENTS AND METHODS Eligibility criteria included receiving an AI for at least 6 months, reporting ≥ 3 of 10 for worst joint pain on the Brief Pain Inventory (BPI), and reporting < 90 minutes per week of aerobic exercise and no strength training. Participants were randomly assigned to exercise (150 minutes per week of aerobic exercise and supervised strength training twice per week) or usual care. The BPI, Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, and Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were completed at baseline and at 3, 6, 9, and 12 months. Intervention effects were evaluated using mixed-model repeated measures analysis, with change at 12 months as the primary end point. RESULTS Over 12 months, women randomly assigned to exercise (n = 61) attended 70% (± standard deviation [SD], 28%) of resistance training sessions and increased their exercise by 159 (± SD, 136) minutes per week. Worst joint pain scores decreased by 1.6 points (29%) at 12 months among women randomly assigned to exercise versus a 0.2-point increase (3%) among those receiving usual care (n = 60; P < .001). Pain severity and interference, as well as DASH and WOMAC pain scores, also decreased significantly at 12 months in women randomly assigned to exercise, compared with increases for those receiving usual care (all P < .001). CONCLUSION Exercise led to improvement in AI-induced arthralgia in previously inactive breast cancer survivors.

Alcohol and tobacco use prediagnosis and postdiagnosis, and survival in a cohort of patients with early stage cancers of the oral cavity, pharynx, and larynx.

As more people begin to survive first cancers, there is an increased need for science-based recommendations to improve survivorship. For survivors of head and neck cancer, use of tobacco and alcohol before diagnosis predicts poorer survival; however, the role of continuing these behaviors after diagnosis on mortality is less clear, especially for more moderate alcohol consumption. Patients (n = 264) who were recent survivors of early stage head and neck cancer were asked to retrospectively report their tobacco and alcohol histories (before diagnosis), with information prospectively updated annually thereafter. Patients were followed for an average of 4.2 years, with 62 deaths observed. Smoking history before diagnosis dose-dependently increased the risk of dying; risks reached 5.4 [95% confidence interval (95% CI), 0.7-40.1] among those with >60 pack-years of smoking. Likewise, alcohol history before diagnosis dose-dependently increased mortality risk; risks reached 4.9 (95% CI, 1.5-16.3) for persons who drank >5 drinks/d, an effect explained by beer and liquor consumption. After adjusting for prediagnosis exposures, continued drinking (average of 2.3 drinks/d) postdiagnosis significantly increased risk (relative risk for continued drinking versus no drinking, 2.7; 95% CI, 1.2-6.1), whereas continued smoking was associated with nonsignificantly higher risk (relative risk for continued smoking versus no smoking, 1.8; 95% CI, 0.9-3.9). Continued drinking of alcoholic beverages after an initial diagnosis of head and neck cancer adversely affects survival; cessation efforts should be incorporated into survivorship care of these patients. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3368–74)

Noninvasive assessment of dermal carotenoids as a biomarker of fruit and vegetable intake

BACKGROUND Resonance Raman spectroscopy (RRS) has been suggested as a feasible method for noninvasive carotenoid measurement of human skin. However, before RRS measures of dermal carotenoids can be used as a biomarker, data on intra- and intersubject variability and validity are needed. OBJECTIVE The purpose of this study was to evaluate the reproducibility and validity of RRS measures of dermal total carotenoids and lycopene in humans. DESIGN In study 1, 74 men and women with diverse skin pigmentation were recruited. RRS measures of the palm, inner arm, and outer arm were obtained at baseline, 1 wk, 2 wk, 1 mo, 3 mo, and 6 mo (to maximize seasonal variation). The RRS device used visible light at 488 nm to estimate total carotenoids and at 514 nm to estimate lycopene. Reproducibility was assessed by intraclass correlation coefficients (ICCs). In study 2, we recruited 28 subjects and assessed dietary carotenoid intake, obtained blood for HPLC analyses, performed RRS measures of dermal carotenoid status, and performed dermal biopsies (3-mm punch biopsy) with dermal carotenoids assessed by HPLC. RESULTS ICCs for total carotenoids across time were 0.97 (palm), 0.95 (inner arm), and 0.93 (outer arm). Total dermal carotenoids assessed by RRS were significantly correlated with total dermal carotenoids assessed by HPLC of dermal biopsies (r = 0.66, P = 0.0001). Similarly, lycopene assessed by RRS was significantly correlated with lycopene assessed by HPLC of dermal biopsies (r = 0.74, P < 0.0001). CONCLUSION RRS is a feasible and valid method for noninvasively assessing dermal carotenoids as a biomarker for studies of nutrition and health.

Indoor tanning and risk of early-onset basal cell carcinoma

BACKGROUND Despite an increase in incidence of basal cell carcinoma (BCC) among young people and the ubiquity of indoor tanning in this population, few epidemiologic studies have investigated this exposure-disease relationship. OBJECTIVE We sought to evaluate the association between indoor tanning and early-onset BCC. METHODS Patients with BCC (n = 376) and control subjects with minor benign skin conditions (n = 390) who were younger than 40 years of age were identified through Yale Dermatopathology. Participants provided information on ever indoor tanning, age of initiation, frequency, duration, burns while tanning, and type of tanning device during an in-person interview. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariate logistic regression with never indoor tanners as the referent group. RESULTS Ever indoor tanning was associated with a 69% increased risk of early-onset BCC (95% CI 1.15-2.48). This association was stronger among females (OR 2.14, 95% CI 1.31-3.47), for multiple BCCs (OR 2.16, 95% CI 1.26-3.70), and for BCCs on the trunk and extremities (OR 2.81, 95% CI 1.57-5.02). Risk increased dose dependently with years using regular indoor tanning devices (P trend = .003), number of overall burns (P trend < .001), and burns to biopsy site (P trend < .001) from indoor tanning. Approximately one quarter (27%) of early-onset BCCs (or 43% among women) could be prevented if individuals never tanned indoors. LIMITATIONS Potential recall bias of indoor tanning by patients and generalizability of the control population suggest replication in other studies is warranted. CONCLUSIONS Indoor tanning was a strong risk factor for early-onset BCC, particularly among females. Indoor tanning should continue to be targeted by both policy-based and behavioral interventions, as the impact on BCC-associated morbidity may be substantial.

Prevalence of polycythemia vera and essential thrombocythemia

Polycythemia vera (PV) and essential thrombocythemia (ET) are common types of myeloproliferative disorders (MPD), the prevalence of which has not been well documented in the United States. Recent breakthroughs in the molecular etiology of these disorders and the accelerated development of targeted pharmacotherapeutics to treat them underscore the need to define the affected population. In this study, we obtained health claims data from major commercial insurance payers in Connecticut and the Center for Medicare and Medicaid Services to estimate the prevalence of PV and ET. Specifically, logistic regression was utilized to develop algorithms to predict the probability that an individual with claims suggestive of MPD truly has PV or ET, and the algorithms were then applied to health claims to estimate the number of PV and ET patients in Connecticut. As of 2003, the age‐standardized prevalence was 22 per 100,000 and 24 per 100,000 for PV and ET, respectively, in Connecticut. Applying the age‐specific prevalence of PV and ET to the entire US population resulted in an estimated total of 65,243 patients with PV and 71,078 patients with ET in the United States in 2003. This study is the first to assess the prevalence of PV and ET in a large US population. Given the large number of individuals afflicted with these diseases and the fact that demographic changes alone will further increase the burden of these diseases in the foreseeable future, it is imperative to conduct more systematic research into the etiology and treatment of PV and ET. Am. J. Hematol., 2008.

Retinoids in prevention of skin cancer.

Two chemoprevention randomized clinical trials were begun in 1984 to evaluate retinoids in the prevention of skin cancers. Moderate risk subjects with a history of at least 10 actinic keratoses and at most two prior skin cancers were enrolled in the SKICAP-AK trial and randomized to 25,000 IU retinol or placebo daily for 5 years. High risk subjects with a history of at least four prior skin cancers were enrolled in the SKICAP-S/B trial and randomized to receive 25,000 IU retinol, 5-10 mg isotretinoin or placebo daily for 3 years. Data from the SKICAP-AK trial indicate that retinol reduces incidence of first new squamous cell skin cancers but had no effect on the incidence of first new basal cell skin cancer. The effect of retinoids had no significant benefit on squamous or basal cell skin cancers in the high risk subjects on the SKICAP-S/B trial, although intervention duration was less than planned. Daily retinol was effective in preventing squamous cell cancers in moderate risk subjects.

Skin carotenoid status measured by resonance Raman spectroscopy as a biomarker of fruit and vegetable intake in preschool children

Background/objective:Dietary assessment in children is difficult, suggesting a need to develop more objective biomarkers of intake. Resonance Raman spectroscopy (RRS) is a non-invasive, validated method of measuring carotenoid status in skin as a biomarker of fruit/vegetable intake. The purpose of this study was to examine the feasibility of using RRS in preschool children, to describe inter-individual variability in skin carotenoid status and to identify factors associated with the biomarker in this population.Subjects/methods:We conducted a cross-sectional study of 381 economically disadvantaged preschoolers in urban centers in Connecticut (USA). In all, 85.5% were black non-Hispanic or Hispanic/Latino, and 14.1% were obese and 16.9% were overweight by age- and sex-specific body mass index (BMI) percentiles. Children had their skin carotenoid status assessed by RRS in the palm of the hand. Fruit/vegetable consumption was assessed by a brief parent/guardian-completed food frequency screener and a liking survey.Results:We observed inter-individual variation in RRS values that was nearly normally distributed. In multiple regression analysis, higher carotenoid status, measured by RRS, was positively associated with fruit/vegetable consumption (P=0.02) and fruit/vegetable preference (P<0.01). Lower carotenoid status was observed among younger children, those participating in the US Supplemental Nutrition Assistance Program, and those with greater adiposity (P<0.05 for all).Conclusions:We observed wide variability in skin carotenoid status in a population of young children, as assessed by RRS. Parent-reported fruit/vegetable intake and several demographic factors were significantly associated with RRS-measured skin carotenoid status. We recommend further development of this biomarker in children, including evaluating response to controlled interventions.

Lifetime history of indoor tanning in young people: a retrospective assessment of initiation, persistence, and correlates

BackgroundDespite educational and public health campaigns to convey the risks of indoor tanning, many individuals around the world continue to engage in this behavior. Few descriptive studies of indoor tanning have collected information pertaining to the lifetime history of indoor tanning, thereby limiting our ability to understand indoor tanning patterns and potentially target interventions for individuals who not only initiate, but continue to persistently engage in indoor tanning.MethodsIn-person interviews elicited detailed retrospective information on lifetime history of indoor tanning among white individuals (n = 401) under age 40 seen by a dermatologist for a minor benign skin condition. These individuals were controls in a case-control study of early-onset basal cell carcinoma. Outcomes of interest included ever indoor tanning in both males and females, as well as persistent indoor tanning in females - defined as females over age 31 who tanned indoors at least once in the last three or all four of four specified age periods (ages 11-15, 16-20, 21-30 and 31 or older). Multivariate logistic regression was used to identify sociodemographic and lifestyle correlates of ever and persistent indoor tanning in females.ResultsApproximately three-quarters (73.3%) of females and 38.3% of males ever tanned indoors, with a median age of initiation of 17.0 and 21.5, respectively. Among indoor tanners, 39.3% of females and 21.7% of males reported being burned while indoor tanning. Female ever indoor tanners were younger, had darker color eyes, and sunbathed more frequently than females who never tanned indoors. Using unique lifetime exposure data, 24.7% of female indoor tanners 31 and older persistently tanned indoors starting as teenagers. Female persistent indoor tanners drank significantly more alcohol, were less educated, had skin that tanned with prolonged sun exposure, and sunbathed outdoors more frequently than non-persistent tanners.ConclusionsIndoor tanning was strikingly common in this population, especially among females. Persistent indoor tanners had other high-risk behaviors (alcohol, sunbathing), suggesting that multi-faceted behavioral interventions aimed at health promotion/disease prevention may be needed in this population.

Resonance Raman spectroscopic evaluation of skin carotenoids as a biomarker of carotenoid status for human studies

Resonance Raman spectroscopy (RRS) is a non-invasive method that has been developed to assess carotenoid status in human tissues including human skin in vivo. Skin carotenoid status has been suggested as a promising biomarker for human studies. This manuscript describes research done relevant to the development of this biomarker, including its reproducibility, validity, feasibility for use in field settings, and factors that affect the biomarker such as diet, smoking, and adiposity. Recent studies have evaluated the response of the biomarker to controlled carotenoid interventions, both supplement-based and dietary [e.g., provision of a high-carotenoid fruit and vegetable (F/V)-enriched diet], demonstrating consistent response to intervention. The totality of evidence supports the use of skin carotenoid status as an objective biomarker of F/V intake, although in the cross-sectional setting, diet explains only some of the variation in this biomarker. However, this limitation is also a strength in that skin carotenoids may effectively serve as an integrated biomarker of health, with higher status reflecting greater F/V intake, lack of smoking, and lack of adiposity. Thus, this biomarker holds promise as both a health biomarker and an objective indicator of F/V intake, supporting its further development and utilization for medical and public health purposes.

Significant correlations of dermal total carotenoids and dermal lycopene with their respective plasma levels in healthy adults

Carotenoids in skin have been known to play a role in photoprotection against UV radiation. We performed dermal biopsies of healthy humans (N=27) and collected blood samples for pair-wise correlation analyses of total and individual carotenoid content by high performance liquid chromatography (HPLC). The hydrocarbon carotenoids (lycopene and beta-carotene) made up the majority of carotenoids in both skin and plasma, and skin was somewhat enriched in these carotenoids relative to plasma. Beta-cryptoxanthin, a monohydroxycarotenoid, was found in similar proportions in skin as in plasma. In contrast, the dihydroxycarotenoids, lutein and zeaxanthin, were relatively lacking in human skin in absolute and relative levels as compared to plasma. Total carotenoids were significantly correlated in skin and plasma (r=0.53, p<0.01). Our findings suggest that human skin is relatively enriched in lycopene and beta-carotene, compared to lutein and zeaxanthin, possibly reflecting a specific function of hydrocarbon carotenoids in human skin photoprotection.