Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer.
Comprehensive ...audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age- and sex-matched controls.
Increasing cumulative cisplatin dose (median, 400 mg/m(2); range, 200 to 800 mg/m(2)) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to < .001): every 100 mg/m(2) increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P < .001). Cumulative cisplatin doses > 300 mg/m(2) were associated with greater American Speech-Language-Hearing Association-defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P < .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose-adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage.
Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing.
Cocoa flavanols may improve cardiometabolic health. Evidence from small short-term randomized clinical trials (RCTs) remains inconsistent, and large long-term RCTs testing the efficacy of cocoa ...flavanols are still lacking.
We performed a systematic review and meta-analysis of RCTs to quantify the effect of cocoa flavanol intake on cardiometabolic biomarkers.
We searched PubMed, Web of Science, and the Cochrane Library for RCTs that evaluated the effects of cocoa flavanols on biomarkers relevant to vascular disease pathways among adults. Data were extracted following a standardized protocol. We used DerSimonian and Laird random-effect models to compute the weighted mean differences (WMDs) and 95% CIs. We also examined potential modification by intervention duration, design, age, sex, comorbidities, and the form and amount of cocoa flavanol intake.
We included 19 RCTs that comprised 1131 participants, and the number of studies for a specific biomarker varied. The amount of cocoa flavanols ranged from 166 to 2110 mg/d, and intervention duration ranged from 2 to 52 wk. Cocoa flavanol intake significantly improved insulin sensitivity and lipid profile. The WMDs between treatment and placebo were -0.10 mmol/L (95% CI: -0.16, -0.04 mmol/L) for total triglycerides, 0.06 mmol/L (95% CI: 0.02, 0.09 mmol/L) for HDL cholesterol, -2.33 μIU/mL (95% CI: -3.47, -1.19 μIU/mL) for fasting insulin, -0.93 (95% CI: -1.31, -0.55) for the homeostatic model assessment of insulin resistance, 0.03 (95% CI: 0.01, 0.05) for the quantitative insulin sensitivity check index, 2.54 (95% CI: 0.63, 4.44) for the insulin sensitivity index, -0.83 mg/dL (95% CI: -0.88, -0.77 mg/dL) for C-reactive protein, and 85.6 ng/mL (95% CI: 16.0, 155 ng/mL) for vascular cell adhesion molecule 1. No significant associations were found for other biomarkers. None of the modifiers seemed to qualitatively modify the effects of cocoa flavanol intake.
Our study suggests that cocoa flavanol intake has favorable effects on select cardiometabolic biomarkers among adults. These findings support the need for large long-term RCTs to assess whether cocoa flavanol intake reduces the risk of diabetes and cardiovascular events.
Dietary supplements are widely used and offer the potential to improve health if appropriately targeted to those in need. Inadequate nutrition and micronutrient deficiencies are prevalent conditions ...that adversely affect global health. Although improvements in diet quality are essential to address these issues, dietary supplements and/or food fortification could help meet requirements for individuals at risk of deficiencies. For example, supplementation with vitamin A and iron in developing countries, where women of reproductive age, infants and children often have deficiencies; with folic acid among women of reproductive age and during pregnancy; with vitamin D among infants and children; and with calcium and vitamin D to ensure bone health among adults aged ≥65 years. Intense debate surrounds the benefits of individual high-dose micronutrient supplementation among well-nourished individuals because the alleged beneficial effects on chronic diseases are not consistently supported. Daily low-dose multivitamin supplementation has been linked to reductions in the incidence of cancer and cataracts, especially among men. Baseline nutrition is an important consideration in supplementation that is likely to modify its effects. Here, we provide a detailed summary of dietary supplements and health outcomes in both developing and developed countries to help guide decisions about dietary supplement recommendations.
PTEN is a tumor suppressor frequently deleted in prostate cancer that may be a useful prognostic biomarker. However, the association of PTEN loss with lethal disease has not been tested in a large, ...predominantly surgically treated cohort.
In the Health Professionals Follow-up Study and Physicians' Health Study, we followed 1044 incident prostate cancer cases diagnosed between 1986 and 2009 for cancer-specific and all-cause mortality. A genetically validated PTEN immunohistochemistry (IHC) assay was performed on tissue microarrays (TMAs). TMPRSS2:ERG status was previously assessed in a subset of cases by a genetically validated IHC assay for ERG. Cox proportional hazards models adjusting for age and body mass index at diagnosis, Gleason grade, and clinical or pathologic TNM stage were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association with lethal disease. All statistical tests were two-sided.
On average, men were followed 11.7 years, during which there were 81 lethal events. Sixteen percent of cases had complete PTEN loss in all TMA cores and 9% had heterogeneous PTEN loss across cores. After adjustment for clinical-pathologic variables, complete PTEN loss was associated with lethal progression (HR = 1.8, 95% CI = 1.2 to 2.9). The association of PTEN loss (complete or heterogeneous) with lethal progression was only among men with ERG-negative (HR = 3.1, 95% CI = 1.7 to 5.7) but not ERG-positive (HR = 1.2, 95% CI = 0.7 to 2.2) tumors.
PTEN loss is independently associated with increased risk of lethal progression, particularly in the ERG fusion-negative subgroup. These validated and inexpensive IHC assays may be useful for risk stratification in prostate cancer.
Vitamin D and calcium may affect the cardiovascular system independently and interactively.
To assess whether vitamin D and calcium supplements reduce the risk for cardiovascular events in adults.
...Studies published in English from 1966 to July 2009 in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials.
Two investigators independently selected 17 prospective studies and randomized trials that examined vitamin D supplementation, calcium supplementation, or both and subsequent cardiovascular events.
Three investigators extracted and checked data about study designs, participants, exposures or interventions, outcomes, and data quality.
Five prospective studies of patients receiving dialysis and 1 study involving a general population showed consistent reductions in cardiovascular disease (CVD) mortality among adults who received vitamin D supplements. Four prospective studies of initially healthy persons found no differences in incidence of CVD between calcium supplement recipients and nonrecipients. Results of secondary analyses in 8 randomized trials showed a slight but statistically nonsignificant reduction in CVD risk (pooled relative risk, 0.90 95% CI, 0.77 to 1.05) with vitamin D supplementation at moderate to high doses (approximately 1000 IU/d) but not with calcium supplementation (pooled relative risk, 1.14 CI, 0.92 to 1.41), or a combination of vitamin D and calcium supplementation (pooled relative risk, 1.04 CI, 0.92 to 1.18) compared with placebo.
Only articles published in English that reported cardiovascular event outcomes were included. The small number of studies, the lack of trials designed specifically to assess primary effects on cardiovascular outcomes, and important between-study heterogeneity preclude definitive conclusions.
Evidence from limited data suggests that vitamin D supplements at moderate to high doses may reduce CVD risk, whereas calcium supplements seem to have minimal cardiovascular effects. Further research is needed to elucidate the role of these supplements in CVD prevention.
The American Heart Association and the National Heart, Lung, and Blood Institute.
Elevated body mass index (BMI; weight in kilograms divided by height in meters squared) in the obese range (> or =30 kg/m(2)) is associated with an excess risk of heart failure (HF). However, the ...impact of overweight or preobese (BMI, 25 to 29.9 kg/m(2)) status and physical activity on HF risk is unclear.
In a prospective cohort of 21,094 men (mean age, 53 years) without known coronary heart disease at baseline in the Physicians' Health Study, we examined the individual and combined effects of BMI and vigorous physical activity (exercise to the point of breaking a sweat) on HF incidence from 1982 to 2007. We evaluated BMI as both a continuous (per 1-kg/m(2) increment) and a categorical (lean, <25 kg/m(2); overweight, 25 to 29.9 kg/m(2); and obese, > or =30 kg/m(2)) variable; we evaluated vigorous physical activity primarily as a dichotomous variable (inactive rarely/never versus active > or =1 to 3 times a month). During follow-up (mean, 20.5 years), 1109 participants developed new-onset HF. In multivariable analyses, every 1-kg/m(2) increase in BMI was associated with an 11% (95% confidence interval CI, 9 to 13) increase in HF risk. Compared with lean participants, overweight participants had a 49% (95% CI, 32 to 69) and obese participants had a 180% (95% CI, 124 to 250) increase in HF risk. Vigorous physical activity conferred an 18% (95% CI, 4 to 30) decrease in HF risk. No interaction was found between BMI and vigorous physical activity and HF risk (P=0.96). Lean active men had the lowest and obese inactive men had the highest risk of HF. Compared with lean active men, the hazard ratios were 1.19 (95% CI, 0.94 to 1.51), 1.49 (95% CI, 1.30 to 1.71), 1.78 (95% CI, 1.43 to 2.23), 2.68 (95% CI, 2.08 to 3.45), and 3.93 (95% CI, 2.60 to 5.96) in lean inactive, overweight active, overweight inactive, obese active, and obese inactive men, respectively.
In this cohort of men, elevated BMI, even in the preobese range, was associated with an increased risk of HF, and vigorous physical activity was associated with a decreased risk. Public health measures to curtail excess weight, to maintain optimal weight, and to promote physical activity may limit the scourge of HF.
Blueberries and anthocyanins, their key bioactive component, may improve eye health. However, few long-term studies have examined blueberries and anthocyanins with cataract and age-related macular ...degeneration (AMD).
To investigate the prospective association between blueberry and anthocyanin intake with incident cataract, total AMD, and visually significant AMD among middle-aged and older women.
A total of 36,653 and 35,402 women initially free of AMD and cataract, respectively, aged ≥45 y from the Women’s Health Study provided semiquantitative food frequency questionnaire data on blueberry intake categorized as none, 1–3 servings/mo, 1 serving/wk, or ≥2 servings/wk, plus a combined category of ≥1 serving/wk. Total anthocyanin intake and major subclasses were energy-adjusted and categorized into quintiles. Self-reported risk factors of eye disease were adjusted in multivariable hazard ratios (HRs) (95% confidence intervals CIs) of confirmed cataract, AMD, and visually significant AMD with mean follow-up of 11 y.
Among the participants, 10.5% consumed ≥1 serving/wk of blueberries, with mean total anthocyanin intake of 11.2 mg/d. Compared to no blueberry intake, women consuming 1–3 servings/mo, 1 serving/wk, and ≥2 servings/wk had corresponding multivariable HRs of total AMD of 0.90 (95% CI: 0.73, 1.11), 0.71 (95% CI: 0.50, 1.00), and 0.36 (95% CI: 0.14, 0.93) (Ptrend = 0.011); those consuming ≥1 servings/wk had an HR of 0.68 (95% CI: 0.47, 0.98). A similar magnitude of HRs were found for visually significant AMD (Ptrend = 0.012) but not for cataract. There were no significant associations between increasing total anthocyanin quintiles and total and visually significant AMD, but there was a modest inverse association with cataract (Ptrend = 0.022), driven by a 10% reduction in cataract in the upper 2 quintiles.
Greater blueberry intake significantly reduced total AMD, but not visually significant AMD or cataract. However, the magnitude of effect for visually significant AMD was similar to total AMD. There was a modest but significant inverse association between dietary anthocyanin intake with cataract but not AMD.
Lipid biomarkers, such as HDL-cholesterol concentrations, have been shown to have positive, inverse, and null associations with total, breast, and colorectal cancer risks. Studies of novel lipid ...biomarkers, such as apolipoprotein A-I (apo A-I) and apolipoprotein B-100 (apo B-100), and cancer risk have been sparse, to our knowledge.
We evaluated the prospective association of total, breast, colorectal, and lung cancers and cancer mortality with circulating lipid biomarkers in 15,602 female health professionals in the Women's Health Study (aged ≥45 y, free of cardiovascular disease and cancer, and without hormone replacement therapy or lipid-lowering medications at baseline).
Cox regression models estimated HRs of cancer endpoints (19 y median follow-up) across quartiles 1 (reference) to 4 of each lipid biomarker after adjustment for cancer risk factors.
Confirmed cases included 2163 incident cancer cases (864 breast, 198 colorectal, and 190 lung cancers) and 647 cancer deaths. Total cancer risk was significantly lower in the highest quartile of apo A-I (adjusted HR: 0.79; 95% CI: 0.70, 0.90; P-trend = 0.0008) and HDL cholesterol (HR: 0.85; 95% CI: 0.75, 0.97; P-trend = 0.01). For site-specific cancers, significant associations included colorectal cancer risk with HDL cholesterol (HR: 0.63; 95% CI; 0.41, 0.98; P-trend = 0.03), triglycerides (HR: 1.86; 95% CI: 1.17, 2.97; P-trend = 0.02), and apo B-100 (HR: 1.60; 95% CI: 1.03, 2.49; P-trend = 0.006) and lung cancer risk with HDL cholesterol (HR: 0.59; 95% CI: 0.38, 0.93; P-trend = 0.01). LDL cholesterol was not significantly associated with risk of total cancer or any site-specific cancers. In time-dependent models that were adjusted for the use of a lipid-lowering medication after baseline, these associations remained.
Lipids were associated with total, lung, and colorectal cancer risks in women. Lifestyle interventions for heart-disease prevention, which reduce apo B-100 or raise HDL cholesterol, may be associated with reduced cancer risk. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479.
A Prospective Study of Cigarette Smoking and Risk of Incident Hypertension in Women Thomas S. Bowman, J. Michael Gaziano, Julie E. Buring, Howard D. Sesso Few prospective studies have examined the ...relationship between smoking and hypertension. In a prospective cohort study among 28,236 women in the Women’s Health Study, there were 8,571 (30.4%) cases of incident hypertension during a median follow-up of 9.8 years. The multivariable-adjusted hazard ratios of developing hypertension among never, former, and current smokers of 1 to 14 and ≥15 cigarettes per day were 1.00 (reference), 1.03 (95% confidence interval CI 0.98 to 1.08), 1.02 (95% CI 0.92 to 1.13), and 1.11 (95% CI 1.03 to 1.21), respectively. In conclusion, cigarette smoking was modestly associated with an increased risk of developing hypertension, with an effect that was strongest among women smoking at least 15 cigarettes per day.
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