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Background:Evaluations of cancer etiology and safety and effectiveness of cancer treatments are predicated on large numbers of patients with sufficient baseline and follow-up data. To assess feasibility of FDA’s Sentinel System’s... more
Background:Evaluations of cancer etiology and safety and effectiveness of cancer treatments are predicated on large numbers of patients with sufficient baseline and follow-up data. To assess feasibility of FDA’s Sentinel System’s electronic healthcare data for surveillance of malignancy onset and examination of product safety, this study examined patterns of enrollment surrounding new-onset cancers.Methods:Using a retrospective cohort of patients based on administrative claims, we identified incident events of 19 cancers among 292.5 million health plan members from January 2000 through February 2020 using International Classification of Diseases (ICD) diagnosis codes. Annual incident cases were stratified by sex, age, medical and drug coverage, and insurer type. Descriptive statistics were calculated for observable time prior to and following diagnosis.Results:We identified 10,697,573 incident cancer events among members with medical coverage. When drug coverage was additionally required, number of incident cancers was reduced by 41%. Medicare data contributed 61% of cases, with similar duration trends as other insurers. Mean duration of follow-up prior to diagnosis ranged from 4.0-4.6 years, while follow-up post diagnosis ranged from 1.1-3.3 years. Approximately a third (36.1%) had at least 2 years both prior to and following diagnosis.Conclusions:The FDA Sentinel System’s electronic healthcare data may be useful for characterizing relatively short latency cancer risk, examining cancer drug utilization and safety post diagnosis, and conducting surveillance for acute adverse events among patients with cancers.Impact:A national distributed system with electronic health data, the Sentinel system provides opportunity for rapid pharmacoepidemiologic assessments relevant in oncology.
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Context: Causes of kidney cancer are not fully understood. Incidence is highest in those ages 50 to 70, and almost twice as high in men as in women. Smokers are twice as likely as non-smokers to develop renal cell carcinoma and about four... more
Context: Causes of kidney cancer are not fully understood. Incidence is highest in those ages 50 to 70, and almost twice as high in men as in women. Smokers are twice as likely as non-smokers to develop renal cell carcinoma and about four times as likely to develop cancer of the renal pelvis. Insulin-like growth factor-I (IGF-I) has been shown to increase kidney microvascular growth and glomerular filtration rate, and its administration increases renal function in animal models of chronic renal failure, and has been proposed as a possible therapeutic agent (Hirschberg et al, 1998). However, the possible roles of IGF in the development of kidney cancer have not been well-studied. Objective: To examine the relation of serum levels of IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) to kidney cancer risk. Methods: We conducted a case-cohort study nested within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of 29,133 Finnish male smokers who were 50-69 years of age and not diagnosed with cancer at study entry. Serum concentrations of IGF-I, IGFBP-3 were measured in blood samples collected in 1985 to 1988. One hundred men were identified who had a diagnosis of kidney cancer >5 years after blood collection through the end of 1997. Self-reported information on lifestyle and medical history was collected and weight and height were measured at baseline. Multivariable logistic regression models were used to estimate the relative risk of kidney cancer associated with IGF levels. Results: A history of hypertension (known to be increased in those who are older, overweight, or heavier smokers) was more common among cases than among noncases. Men with IGF-I levels >108 ng/mL were 63% less likely to develop kidney cancer than men with IGF-I levels ≤108 ng/mL (OR=0.37; 95% CI=0.20-0.69). IGFBP-3 levels did not alter the association between IGF-I and kidney cancer risk. Further, no association was observed between IGFBP-3 levels and the development of kidney cancer. Conclusions: Low serum IGF-I levels in this cohort of older middle-aged male smokers are associated with increased kidney cancer risk, independent of IGFBP-3, age, anthropometry, lifestyle and medical history. Further research is needed to confirm the findings and examine the association in women and non-smokers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4830.
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Recent restrictions in access to and availability of dextromethorphan (DXM) cough and cold medications may correlate with changes in abuse exposures. To extend and update existing knowledge about DXM abuse, we describe recent trends and... more
Recent restrictions in access to and availability of dextromethorphan (DXM) cough and cold medications may correlate with changes in abuse exposures. To extend and update existing knowledge about DXM abuse, we describe recent trends and patterns of calls to poison control centers involving DXM abuse, by demographics, geography, common brands, and medical outcomes. We utilized data from the National Poison Data System (NPDS) maintained by the American Association of Poison Control Centers (AAPCC), which captures data on calls to U.S. poison centers on a near real-time basis. We analyzed demographic, geographic, brand and medical outcome data for single-substance DXM cough and cold product intentional abuse exposure calls in multiple age groups reported to NPDS from 2000 to 2015. The annual rate of single-substance DXM intentional abuse calls tripled from 2000 to 2006 and subsequently plateaued from 2006 to 2015. The highest abuse call rate was observed among adolescents 14-17 years old, where the mean annual number of calls was 1761 per year, corresponding to an annual rate of 103.6 calls per million population. From 2006 to 2015, the rate for single-substance DXM abuse calls among adolescents 14-17 years decreased by 56.3%, from 143.8 to 80.9 calls per million population. DXM intentional abuse exposure call rates have declined among adolescents 14-17 years, since their peak in 2006. The observed decline in DXM abuse call rates corresponds to a period of growing public health efforts to curtail the abuse of over-the-counter (OTC) DXM containing products, particularly among adolescents. Further evaluation of state-level sales and abuse trends among adolescents would be valuable to better understand how restricted availability of OTC DXM cough and cold products and other efforts may affect abuse rates.
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PurposeTo evaluate the impact of increased federal restrictions on hydrocodone combination product (HCP) utilization, misuse, abuse, and overdose death.MethodsWe assessed utilization, misuse, abuse, and overdose death trends involving... more
PurposeTo evaluate the impact of increased federal restrictions on hydrocodone combination product (HCP) utilization, misuse, abuse, and overdose death.MethodsWe assessed utilization, misuse, abuse, and overdose death trends involving hydrocodone versus select opioid analgesics (OAs) and heroin using descriptive and interrupted time‐series (ITS) analyses during the nine quarters before and after the October 2014 rescheduling of HCPs from a less restrictive (CIII) to more restrictive (CII) category.ResultsHydrocodone dispensing declined >30% over the study period, and declines accelerated after rescheduling. ITS analyses showed that immediately postrescheduling, quarterly hydrocodone dispensing decreased by 177M dosage units while codeine, oxycodone, and morphine dispensing increased by 49M, 62M, and 4M dosage units, respectively. Postrescheduling, hydrocodone‐involved misuse/abuse poison center (PC) case rates had a statistically significant immediate drop but a deceleration of preperiod declines. There were small level increases in codeine‐involved PC misuse/abuse and overdose death rates immediately after HCP's rescheduling, but these were smaller than level decreases in rates for hydrocodone. Heroin‐involved PC case rates and overdose death rates increased across the study period, with exponential increases in PC case rates beginning 2015.ConclusionsHCP rescheduling was associated with accelerated declines in hydrocodone dispensing, only partially offset by smaller increases in codeine, oxycodone, and morphine dispensing. The net impact on hydrocodone and other OA‐involved misuse/abuse and fatal overdose was unclear. We did not detect an immediate impact on heroin abuse or overdose death rates; however, the dynamic nature of the crisis and data limitations present challenges to causal inference.
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Research Interests: Emergency Medicine, Adolescent, Medicine, Population, Humans, and 14 moreChild, Hospitalization, United States, Female, Male, Young Adult, Adult, Public health systems and services research, Acetaminophen, Emergency Department, Pharmacoepidemiology and drug safety, Child preschool, Adverse effect, and Pharmacology and pharmaceutical sciences
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Research Interests: Genetics, Epidemiology, Genetic Epidemiology, Biology, Medicine, and 15 moreLinear models, Humans, Female, Male, Heritability, Phenotype, Aged, Middle Aged, Adult, Single Nucleotide Polymorphism, Public health systems and services research, Genetic Architecture, Genetic Association, Case Control Studies, and Polygenic score
Genome-wide association studies have found an association between pancreatic cancer and the TERT or telomerase gene. Smoking and diabetes, consistent risk factors for pancreatic cancer, are also factors that influence telomere length... more
Genome-wide association studies have found an association between pancreatic cancer and the TERT or telomerase gene. Smoking and diabetes, consistent risk factors for pancreatic cancer, are also factors that influence telomere length maintenance. To test whether blood leukocyte telomere length is associated with pancreatic cancer risk, we conducted a nested case-control study in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50-69 years at baseline. Between 1992 and 2004, 193 incident cases of pancreatic adenocarcinoma occurred (mean follow-up from blood draw: 6.3 years) among participants with whole blood samples available for telomere length assays. For these cases and 660 controls, we calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, adjusting for age, number of years smoked regularly, and history of diabetes mellitus. Telomere length was categorized into quartiles (shortest to longest) and analyzed as both a categorical and a continuous normal variable (reported per 0.2 unit increase in telomere length). All statistical tests were two-sided. Longer telomere length was significantly associated with increased pancreatic cancer risk (continuous OR=1.26 95% CI=1.09-1.46; highest quartile compared to lowest, OR=1.57, 95% CI=1.01-2.43, p-trend=0.007). This effect remained for subjects diagnosed within the first five years of blood draw (continuous OR=1.46, 95% CI=1.19-1.79 highest quartile OR=2.92, 95%CI=1.47-5.77, p-trend=0.002), but not subjects diagnosed greater than five years from blood draw (continuous OR=1.03, 95%CI=0.85-1.22; highest quartile OR=1.04, 95%CI=0.60-1.79). This is the first study to suggest an association between longer blood leukocyte telomere length and increased pancreatic cancer risk. Citation Format: Shannon M. Lynch, Jacqueline M. Major, Richard Cawthon, Stephanie J. Weinstein, Jarmo Virtamo, Qing Lan, Nathaniel Rothman, Demetrius Albanes, Rachael Z. Stolzenberg-Solomon. Telomere length and pancreatic cancer in the alpha-tocopherol beta-carotene cancer prevention (ATBC) study. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 13.
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Research Interests: Breast Cancer, Fluorescence Microscopy, Biology, Histochemistry, Immunohistochemistry, and 14 moreMedicine, Estrogen Receptor, Humans, Female, Estrogen, Fluorescent Antibody Technique, Progesterone receptor expression, Protein Expression, Reproducibility of Results, Digital Image, Image Acquisition, Autofluorescence, Breast Neoplasms, and Medical and Health Sciences
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Research Interests: Health Communication, Medicine, Stroke, Humans, COPD, and 15 moreUnited States, Female, Male, Two Stroke Engine, Aged, Middle Aged, Adult, Combination drug therapy, Database, United States Food and Drug Administration, Tiotropium bromide, Interrupted Time Series Analysis, Drug prescriptions, Bronchodilator agents, and Pulmonary Disease Chronic Obstructive
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Background: Stemming from the US Cancer Moonshot initiative and 21st Century Cures Act, efforts to harness information technology to evaluate safety and effectiveness of cancer treatment are of high public health interest.... more
Background: Stemming from the US Cancer Moonshot initiative and 21st Century Cures Act, efforts to harness information technology to evaluate safety and effectiveness of cancer treatment are of high public health interest. Pharmacoepidemiologic cancer etiology and safety evaluations of cancer treatment are predicated upon sufficient number of patients and adequate follow-up time. Objective: To investigate whether Sentinel System’s electronic healthcare data is useful for these purposes, we assessed observable enrollment surrounding a member’s new-onset cancer diagnosis. Methods: Using administrative claims paid by Medicare and 16 other insurers, we identified incident cases of 19 cancer types among 292.5 million members between January 2000 and August 2017. International Classification of Diseases (ICD) diagnosis codes were used to define the cancers, after confirming diagnostic code mappings across the 2015 switch from ICD-9 to ICD-10 era. Study inclusion required 1 year of enrollment without claims for each respective diagnostic code. For each cancer, we summed annual incident cases by sex, age group, medical and drug coverage type, and Medicare or other insurer. Prior to and following diagnosis, we examined median observable time and duration (≥1 yr, ≥2, ≥3, ≥4 yrs). End of observable time was defined by member disenrollment, death, or end of insurer data. Results: We identified 7,926,450 members with medical coverage and an incident cancer diagnosis. Medicare data constituted 49.7% of the identified cases, with similar enrollment duration trends as the 16 commercial insurers. Across cancer types, median duration of observable time prior to and following diagnosis ranged from 2.5-3.8 and 0.5-2.5 years, respectively; 1,701,600 (21% of the cases) had at least 4 years of observable time following cancer diagnosis. Observable time following diagnosis varied greatest by cancer type, as expected. Observable time ended most frequently because insurer data ended; death was the least common reason. When drug coverage was additionally required, the number of incident cancers reduced to 4,705,968 (41% decrease). Range in median observable time did not change markedly (0.5-2.3 years post-diagnosis), albeit the sex differential increased after requiring drug coverage (with 54% women and 46% men having ≥4 years post-diagnosis). Conclusion: A distributed system with routinely updated data and standardized analysis tools provides opportunities for Sentinel System to contribute rapid and large-scale assessments of cancer incidence. Results suggest observable time following cancer diagnosis may provide sufficient duration of follow-up for drug-related adverse events of relatively short latency. Consideration of study-specific eligibility criteria and utilization of specific drug products is warranted prior to performing in-depth pharmacoepidemiologic studies. Citation Format: Nicole R. Haug, Anita K. Wagner, Katherine A. McGlynn, Charles E. Leonard, Michael D. Nguyen, Jacqueline M. Major. New-onset cancer cases in FDA’s Sentinel System: A large distributed system of US electronic healthcare data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-156.
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Background: Current important regulatory resources and methods to identify cardiac implantable electronic devices (CIED) lead failure include post-approval studies, which may be limited in scope, participant numbers, and by attrition;... more
Background: Current important regulatory resources and methods to identify cardiac implantable electronic devices (CIED) lead failure include post-approval studies, which may be limited in scope, participant numbers, and by attrition; studies relying on administrative codes, which lack specificity in multi-chamber systems; and voluntary adverse event reporting, which cannot determine incidence or attribution to the lead. We determined whether adjudicated remote monitoring (RM) data can help to address these limitations and augment lead safety evaluation. Methods: We evaluated 48,148 patients from the Veterans Affairs National Cardiac Device Surveillance Program (VANCDSP), 4/1/19-4/1/21. We identified RM transmissions signifying incident lead abnormalities (possible lead failure, failure to capture, impedance out of range). We queried VA electronic health record (EHR) and Medicare fee-for-service claims data to determine if patients had administrative codes for lead failure. We verif...
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Research Interests: Demography, Primary Care, Epidemiology, Prostate Cancer, Preventive medicine, and 15 moreHealth Equity, Medicine, Prospective studies, Humans, Male, African Americans, Aged, Middle Aged, Neoplasms, Community Health and Preventive Medicine, European Continental Ancestry Group, Proportional Hazards Models, Delivery of Health Care, Prostatic neoplasms, and hazard ratio
Research Interests: Demography, Mortality, Cardiovascular disease, Medicine, Multidisciplinary, and 15 moreMultivariate Analysis, Humans, Female, Male, Health Status, Aged, Middle Aged, Longitudinal Studies, Neoplasms, Community Health and Preventive Medicine, Educational Status, Cardiovascular Diseases, Confidence Interval, Nutrition assessment, and hazard ratio
Research Interests: Primary Care, Epidemiology, Environmental Health, Diet, Preventive medicine, and 15 morePublic Health, Medicine, Prospective studies, Humans, Female, Animals, Meat, Male, Risk factors, Middle Aged, Community Health and Preventive Medicine, Risk Factors, Proportional Hazards Models, Cohort Studies, and Socioeconomic Factors
Research Interests: Nutrition and Dietetics, Nutrition, Biology, Prostate Cancer, Medicine, and 15 moreAnimal Production, Humans, Internal Medicine, Male, Risk factors, Aged, Middle Aged, European Continental Ancestry Group, Food Sciences, Genetic variation, Risk Factors, Case Control Studies, Prostatic neoplasms, mass Screening, and Genetic predisposition to disease
Background: In an effort to understand the molecular mechanism behind the association between circulating vitamin D and prostate cancer, we measured relative telomere length and 25(OH)D levels in a cohort of older Finnish men. Methods:... more
Background: In an effort to understand the molecular mechanism behind the association between circulating vitamin D and prostate cancer, we measured relative telomere length and 25(OH)D levels in a cohort of older Finnish men. Methods: Using a nested study design, we examined quantitative PCR measured telomere length, season-adjusted serum 25-hydroxyvitamin D [25(OH)D], and subsequent prostate cancer risk in 1000 men (n=500 cases, 500 matched controls) participating in the extension study of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Trial. Conditional regression models were used to explore mediation and effect modification of telomere length on the relation between serum 25(OH)D and prostate cancer risk. Results: An increased risk of prostate cancer was observed among men with longer (>median) relative telomere length (OR = 1.41, 95% CI: 1.06 to 1.90; continuous: OR = 2.36, 95%CI: 0.96 to 5.83) as well as men with higher 25(OH)D concentrations (OR = 1.67, 95% CI: 1.08 to 2.57 for highest vs. lowest quintile, P-trend = 0.03). No significant association between 25(OH)D levels and telomere length was observed. A suggested joint effect of 25(OH)D and telomere length on prostate cancer risk was observed. Conclusion: Serum 25(OH)D and relative telomere length are independent predictors of prostate cancer risk in this sample of older male Finnish smokers. No evidence of mediation between circulating vitamin D concentrations and telomere length was observed. Future studies are needed to further clarify the underlying biologic mechanisms of the 25(OH)D-prostate cancer association. Citation Format: Jacqueline M. Major, Barry I. Graubard, Stephanie J. Weinstein, Jeeyun Kim, Immaculata De Vivo, Jarmo Virtamo, Sharon A. Savage, Demetrius Albanes. Understanding the mechanism underlying vitamin D and prostate cancer: Exploring telomere length [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-172.
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Background: Given the large racial differences in prostate cancer risk, further investigation of socioeconomic (SES) indicators at the individual and community level is warranted among high-risk groups. The purpose of this study was to... more
Background: Given the large racial differences in prostate cancer risk, further investigation of socioeconomic (SES) indicators at the individual and community level is warranted among high-risk groups. The purpose of this study was to examine the association between neighborhood deprivation, healthcare facilities, and prostate cancer risk among African-American men. Methods: In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995–1996) data from African-American participants, ages 50–71 years. Incident prostate cancer cases (n=1,089) were identified through December 2006. Life-style and health risk information was ascertained by questionnaires administered at baseline. Area-level socioeconomic indicators were ascertained by linkage to the US Census and the Area Resource File. Multilevel survival models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among African-American men, no associations were observed between area-level factors and development of nonadvanced prostate cancer. Compared to African-American men living in counties with the highest density of radiologists, those in the middle tertile had the highest risks of advanced prostate cancer (HR=2.88, 95% CI=1.61-5.18), however, no significant trend was found (Ptrend=0.08). Certain socioeconomic (SES) indicators were positively associated with prostate cancer risk among African-American men. Further studies are needed to replicate these findings. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A79.
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Research Interests: Cancer, Diet, Prostate Cancer, Medicine, Prospective studies, and 15 moreHumans, Cooking, Animals, Meat, Male, Prostate, African Americans, Middle Aged, Questionnaires, Public health systems and services research, Mutagens, Heterocyclic compounds, Prospective Cohort Study, Prostatic neoplasms, and hazard ratio
Research Interests: Complementary and Alternative Medicine, Clinical Trial, Cancer, Radiation Therapy, Treatment Outcome, and 15 moreProstate Cancer, Medicine, Humans, Male, Patient Compliance, Aged, Middle Aged, Dietary Assessment, Food habits, Disease Progression, Medical Records, Asymptomatic, Prostate Specific Antigen, Doubling Time, and Prostatic neoplasms
A rising level of prostate-specific antigen (PSA), after primary surgery or radiation therapy, is the hallmark of recurrent prostate cancer and is often the earliest sign of extraprostatic spread in patients who are otherwise... more
A rising level of prostate-specific antigen (PSA), after primary surgery or radiation therapy, is the hallmark of recurrent prostate cancer and is often the earliest sign of extraprostatic spread in patients who are otherwise asymptomatic. While hormonal therapy may slightly extend survival in a minority of patients, it is not curative and produces side effects including hot flashes, decreased libido, and loss of bone mass. Alternatively, dietary modification may offer an important tool for clinical management. Epidemiologic studies have associated the Western diet not only with prostate cancer incidence but also with a greater risk of disease progression after treatment. Conversely, many elements of plant-based diets have been associated with reduced risk of progression. However, dietary modification can be stressful and difficult to implement. We therefore conducted a 6-month pilot clinical trial to investigate whether adoption of a plant-based diet, reinforced by stress management training, could attenuate the rate of further PSA rise. Urologists at the University of California, San Diego, and San Diego Veterans Affairs Medical Centers recruited 14 patients with recurrent prostate cancer. A pre-post design was employed in which each patient served as his own control. Rates of PSA rise were ascertained for each patient for the following periods: from the time of posttreatment recurrence up to the start of the study (prestudy) and from the time immediately preceding the intervention (baseline) to the end of the intervention (0-6 months). There was a significant decrease in the rate of PSA rise from prestudy to 0 to 6 months ( P < .01). Four of 10 evaluable patients experienced an absolute reduction in their PSA levels over the entire 6-month study. Nine of 10 had a reduction in their rates of PSA rise and an improvement of their PSA doubling times. Median PSA doubling time increased from 11.9 months (prestudy) to 112.3 months (intervention). These results provide preliminary evidence that adoption of a plant-based diet, in combination with stress reduction, may attenuate disease progression and have therapeutic potential for clinical management of recurrent prostate cancer.
Research Interests: Complementary and Alternative Medicine, Clinical Trial, Cancer, Prostate Cancer, Medicine, and 15 moreHumans, Disease, Male, Prostate, Alternative Medicine, Aged, Middle Aged, Disease Progression, Hormone Therapy, Asymptomatic, Pilot Projects, Epidemiologic Studies, Combined Modality Therapy, Bone mass, and Doubling Time
Research Interests: Geography, Demography, Medicine, Colorectal cancer, Humans, and 15 moreMathematical Sciences, Female, Male, American, Aged, Middle Aged, Community Health and Preventive Medicine, Bayes Theorem, Consumer Organizations, Investigative Techniques, Cohort Studies, Colorectal Neoplasms, Cause of death, Medical and Health Sciences, and hazard ratio
Objective: Given the large racial differences in prostate cancer risk, further investigation of diet and prostate cancer is warranted among high-risk groups. The purpose of this study was to examine the association between type of meat... more
Objective: Given the large racial differences in prostate cancer risk, further investigation of diet and prostate cancer is warranted among high-risk groups. The purpose of this study was to examine the association between type of meat intake and prostate cancer risk among African-American men. Methods: In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995–1996) data from African-American participants, ages 50–71 years. Incident prostate cancer cases (n=1,089) were identified through 2006. Dietary and risk factor data were ascertained by questionnaires administered at baseline. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) within intake quantiles. Results: Neither white nor processed meat intake was associated with prostate cancer, regardless of meat cooking method. Red meats cooked at high temperatures were associated with an increased risk of prostate cancer (HR=1.18, 95%CI=1.00-1.38 and HR=1.22, 95%CI=1.03-1.44, for the upper two intake tertiles). Intake of the heterocyclic amine (HCA), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (DiMeIQx) was positively associated with prostate cancer (HR=1.30; 95% CI=1.05-1.61, P=0.02). No associations were observed for intake of other HCAs. Conclusion: Red meats cooked at high temperatures were positively associated with prostate cancer risk among African-American men. Further studies are needed to replicate these findings. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B53.
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Research Interests: Demography, Primary Care, Incidence Geometry, Cancer, Preventive medicine, and 15 moreMedicine, Colorectal cancer, Humans, Female, Male, Incidence, Aged, Middle Aged, Neoplasms, Community Health and Preventive Medicine, Educational Status, Adenocarcinoma, Colorectal Neoplasms, Residence Characteristics, and Rectum
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Background: An increased risk of prostate cancer was observed in Parkinson’s disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial. Objective: To investigate a potential association between... more
Background: An increased risk of prostate cancer was observed in Parkinson’s disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial. Objective: To investigate a potential association between entacapone use and prostate cancer in an ambulatory setting. Methods: Using data from the Department of Veterans Affairs (VA) healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014. Patients were followed on-treatment for occurrence of prostate cancer, identified via VA cancer registry linkage. Cox proportional hazards regression with time-dependent exposure was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Confounding was controlled by using inverse probability treatment weighting calculated from propensity scores. Results: Mean follow-up time was 3.1 and 4.0 years in the entacapone and control cohort, respectively. There were 17,666 subjects meeting study criteria (mean age, 74 (SD 8.6) years); the group treated with entacapone comprised 5,257 subjects. Twenty-three prostate cancers occurred in the entacapone cohort and 97 in the control cohort. The overall incidence of prostate cancer was 1.8 per 1000 person-years of risk. There was no difference in risk of prostate cancer between the cohorts for increased duration of entacapone intake (adjusted HR: 1.08; 95% confidence interval: 0.46-2.51 for cumulative exposure of ≥2 years). Time since starting drug therapy and cumulative dose (mg) were also examined. Conclusion: In this cohort of PD patients, extended duration of entacapone use was not associated with an increased incidence of prostate cancer. Note: This abstract was not presented at the meeting. Citation Format: Jacqueline M. Major, Francesca Cunningham, Diane Dong, Kunthel By, Kwan Hur, David C. Shih, Simone P. Pinheiro, Gerald D. Podskalny, David J. Graham. Entacapone and prostate cancer in patients with Parkinson’s disease: A large Veterans Health Administration study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2303. doi:10.1158/1538-7445.AM2017-2303
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Research Interests: Complementary and Alternative Medicine, Cytokines, Prostate Cancer, Medicine, Humans, and 15 moreInternal Medicine, Body Composition, Male, Follow-up studies, Aged, Sex Steroids, Middle Aged, Waist to Hip Ratio, Disease Progression, Medical Records, Asymptomatic, Pilot Projects, Prostate Specific Antigen, Prostatic neoplasms, and Waist Hip Ratio
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Post-market evaluation is important to ensure the ongoing safety and effectiveness of cardiovascular implantable electronic device (CIED) leads. The Twenty-First Century Cures Act and subsequent Food and Drug Administrative (FDA) Guidance... more
Post-market evaluation is important to ensure the ongoing safety and effectiveness of cardiovascular implantable electronic device (CIED) leads. The Twenty-First Century Cures Act and subsequent Food and Drug Administrative (FDA) Guidance provide an opportunity to leverage real-world data sources for this purpose. The past 4 years have seen the development of EP PASSION: a multi-stakeholder, collaborative effort between the FDA, CIED manufacturers, Heart Rhythm Society, and academics. Using real-world data, EP PASSION enables longitudinal evaluation of the long-term safety of CIED leads, addressing limitations of current approaches to generate evidence that informs regulatory, clinical, and manufacturer decision-making. This state of the art article describes the impetus for and launch of EP PASSION, the lessons learned, its current state, the current analytic approach, and the strengths and limitations of leveraging extant data sources for post-market lead evaluation. We also compare EP PASSION to traditional post-approval studies and describe possible future directions.
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Estimating hazard ratios (HR) presents challenges for propensity score (PS)-based analyses of cohorts with differential depletion of susceptibles. When the treatment effect is not null, cohorts that were balanced at baseline tend to... more
Estimating hazard ratios (HR) presents challenges for propensity score (PS)-based analyses of cohorts with differential depletion of susceptibles. When the treatment effect is not null, cohorts that were balanced at baseline tend to become unbalanced on baseline characteristics over time as “susceptible” individuals drop out of the population at risk differentially across treatment groups due to having outcome events. This imbalance in baseline covariates causes marginal (population-averaged) HRs to diverge from conditional (covariate-adjusted) HRs over time and systematically move toward the null. Methods that condition on a baseline PS yield HR estimates that fall between the marginal and conditional HRs when these diverge. Unconditional methods that match on the PS or weight by a function of the PS can estimate the marginal HR consistently but are prone to misinterpretation when the marginal HR diverges toward the null. Here, we present results from a series of simulations to hel...
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Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide... more
Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10(-17)) and rs10882272 (P =6.04× 10(-12)). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10(-5)), but found no ass...
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Background: Observed associations between vitamin E status and certain cancers (e.g., lung, prostate, colorectal, cervical and ovarian) suggest a protective relation may exist, with many studies focusing on the antioxidant and... more
Background: Observed associations between vitamin E status and certain cancers (e.g., lung, prostate, colorectal, cervical and ovarian) suggest a protective relation may exist, with many studies focusing on the antioxidant and antiproliferative properties of alpha-tocopherol. Recent findings suggest that gamma-tocopherol may play a similar role that is independent of alpha-tocopherol. The purpose of this study was to identify genetic variants associated with circulating levels of alpha- and gamma-tocopherol. This is the first genome-wide association study (GWAS) to examine these two nutritional phenotypes. Methods: Prior to analysis, tocopherol levels were log-transformed to normalize the distributions. General linear models were used to relate the log-transformed outcomes to a SNP by assuming an additive mode of inheritance. Analyses were adjusted for the effects of age, cancer status, body mass index, and cholesterol (because it is well established that vitamin E levels are affect...
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SummaryBackgroundGastro‐oesophageal reflux disease (GERD) patients on proton pump inhibitors before breakfast or dinner have acid recovery at night. Bedtime immediate‐release omeprazole (IR‐OME) demonstrated better control of nocturnal pH... more
SummaryBackgroundGastro‐oesophageal reflux disease (GERD) patients on proton pump inhibitors before breakfast or dinner have acid recovery at night. Bedtime immediate‐release omeprazole (IR‐OME) demonstrated better control of nocturnal pH than pantoprazole before dinner.AimTo compare repeated once daily bedtime dosing of IR‐OME, lansoprazole and esomeprazole on nocturnal gastric acidity.MethodsOpen‐label, randomized, crossover study enrolling 54 patients with nocturnal GERD symptoms comparing IR‐OME, lansoprazole and esomeprazole at steady state for nocturnal acid breakthrough (NAB), percentage of time with gastric pH > 4 and median gastric pH.ResultsOnset of nocturnal acid control with IR‐OME was rapid. During the first half of the night, percentage of time with gastric pH > 4 and median gastric pH were significantly higher after IR‐OME compared to esomeprazole or lansoprazole (P < 0.001, both comparisons). Over the 8‐h night‐time period, acid control with IR‐OME was signi...
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Objectives. We examined whether the risk of premature mortality associated with living in socioeconomically deprived neighborhoods varies according to the health status of individuals.Methods. Community-dwelling adults (n = 566 402;... more
Objectives. We examined whether the risk of premature mortality associated with living in socioeconomically deprived neighborhoods varies according to the health status of individuals.Methods. Community-dwelling adults (n = 566 402; age = 50–71 years) in 6 US states and 2 metropolitan areas participated in the ongoing prospective National Institutes of Health–AARP Diet and Health Study, which began in 1995. We used baseline data for 565 679 participants on health behaviors, self-rated health status, and medical history, collected by mailed questionnaires. Participants were linked to 2000 census data for an index of census tract socioeconomic deprivation. The main outcome was all-cause mortality ascertained through 2006.Results. In adjusted survival analyses of persons in good-to-excellent health at baseline, risk of mortality increased with increasing levels of census tract socioeconomic deprivation. Neighborhood socioeconomic mortality disparities among persons in fair-to-poor health were not statistically significant after adjustment for demographic characteristics, educational achievement, lifestyle, and medical conditions.Conclusions. Neighborhood socioeconomic inequalities lead to large disparities in risk of premature mortality among healthy US adults but not among those in poor health.
Research Interests: Demography, Health Behavior, Gerontology, Environmental Health, Life Style, and 15 morePreventive medicine, Health Equity, Medicine, Humans, Chronic Disease, Female, Male, Census, Health Status, Aged, Middle Aged, Community Health and Preventive Medicine, Health surveys, Cohort Studies, and Medical and Health Sciences
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Background: Evaluations of cancer etiology and safety and effectiveness of cancer treatments are predicated on large numbers of patients with sufficient baseline and follow-up data. To assess feasibility of FDA's Sentinel System's... more
Background: Evaluations of cancer etiology and safety and effectiveness of cancer treatments are predicated on large numbers of patients with sufficient baseline and follow-up data. To assess feasibility of FDA's Sentinel System's electronic healthcare data for surveillance of malignancy onset and examination of product safety, this study examined patterns of enrollment surrounding new-onset cancers. Methods: Using a retrospective cohort of patients based on administrative claims, we identified incident events of 19 cancers among 292.5 million health plan members from January 2000 to February 2020 using International Classification of Diseases (ICD) diagnosis codes. Annual incident cases were stratified by sex, age, medical and drug coverage, and insurer type. Descriptive statistics were calculated for observable time prior to and following diagnosis. Results: We identified 10,697,573 incident cancer events among members with medical coverage. When drug coverage was addition...
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An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S.... more
An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S. ambulatory setting. To investigate whether entacapone is associated with prostate cancer and to assess whether the associations are correlated with advanced disease at the time of cancer diagnosis. Using data from the Department of Veterans Affairs healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014. Patients were followed on-treatment for occurrence of prostate cancer, identified via linkage to the VA cancer registry. Mean follow-up time was 3.1 and 4.0 years in the entacapone and control cohort, respectively. There were 17,666 subjects meeting study criteria (mean age, 74 (SD 8.6) years); the entacapone-treated group c...