Linda M. Rubenstein

Association of smoking, body mass, and physical activity with risk of prostate cancer in the Iowa 65+ Rural Health Study (United States)

Smoking, obesity, alcohol, and physical activity can modulate theendocrine system, and therefore have been hypothesized to play a role in theetiology of prostate cancer. At baseline in 1982, 80 percent (n = 3,673) ofthe noninstitutionalized persons age 65+ in two rural Iowa (United States)counties were enrolled into the Iowa 65+ Rural Health Study. Follow-up formortality was complete through 1993, and cancer experience was determined bylinkage to the State Health Registry of Iowa cancer database for the years1973-93. We analyzed data on 1,050 men aged 65 to 101 years (mean age 73.5)with a full interview in 1982 and with no documented cancer in the 10 yearsprior to baseline. Through 1993 (8,474 person-years of follow-up), there were71 incident cases of prostate cancer. In a multivariate model, age, cigarettesmoking (relative risk [RR] = 2.9 for currently smoking 20 or more cigarettesper day compared with never smoking; P trend = 0.009), greater body massindex (BMI) (wt/ht 2 ) (RR = 1.7 for BMI > 27.8 kg/m 2 compared with <23.6; P trend = 0.1), and greater level of physical activity (RR = 1.9 forhigh activity level cf inactive; P trend = 0.05) were independent predictorsof prostate cancer, and these associations were stronger for regional ordisseminated disease at diagnosis. Percent change in BMI from age 50 tobaseline was associated positively with risk (P trend = 0.01), and thisassociation appeared to be stronger in heavier men. There were no data ondiet. These findings suggest that smoking, overweight, and weight gain inlater life are risk factors for prostate cancer and support a hormonaletiology; the positive association for physical activity confirms someprevious reports, but remains without a credible biologicmechanism.

Evaluation of the Iowa Medicaid pharmaceutical case management program.

OBJECTIVE To test the effect of pharmaceutical case management (PCM) on medication safety and health care utilization. DESIGN Prospective cohort design with 9-month follow-up period (enrollment from October 1, 2000, through July 1, 2001, with follow-up through July 1, 2002). SETTING Iowa Medicaid program. PARTICIPANTS 2,211 noninstitutionalized, continuously eligible Iowa Medicaid patients taking four or more chronic medications including at least one agent commonly used in at least 1 of 12 specific diseases who were cared for by pharmacists in 117 pharmacies. INTERVENTIONS Reimbursement for PCM services (initial patient assessment, written recommendations to physician, follow-up assessments and communication of progress and new problems to physician). MAIN OUTCOME MEASURES Use of high-risk medications, Medication Appropriateness Index (MAI) score, health care utilization. RESULTS Pharmacists in 114 pharmacies had eligible patients during at least one quarter during the study period; 28 pharmacies were classified as high intensity based on the number of PCM patients they managed. A total of 524 of the eligible patients received 1,599 PCM services; 90% of claims were filed by pharmacists, and the remainder by physicians. Nearly one half (46.1%) of medications and 92.1% of patients had at least one medication problem before PCM. By closeout, the percentage of medications with problems decreased in 8 of 10 MAI domains for those who received PCM. Compared with baseline, mean MAI score improved significantly from 9.4 to 8.3 among PCM recipients (P < .001). Percentage of PCM recipients using high-risk medications decreased significantly compared with PCM eligibles who did not receive the service. In the 28 pharmacies that adopted the new service most intensely, patients had a significant decrease in high-risk medication use, compared with patients of low-intensity pharmacies (P < .001). No difference was observed between PCM recipients and PCM eligibles who did not receive PCM in health care utilization or charges, even after including reimbursements for PCM. CONCLUSION Medication safety problems were prevalent in this high-risk population. The PCM program improved medication safety during a 9-month follow-up period.

Complex Etiology Underlies Risk and Survival in Head and Neck Cancer Human Papillomavirus, Tobacco, and Alcohol: A Case for Multifactor Disease

Findings are inconsistent about whether tobacco, alcohol, and human papillomavirus (HPV) are two independent HNC risk factor groups that distinguish an infection-associated cancer from a tobacco/alcohol-associated HNC. We found that cancer in the oral cavity risk was greater in HPV-E6/E7 seropositive/heavy tobacco users (adjusted OR = 3.5) than in HPV-seronegative/heavy tobacco users (adjusted OR = 1.4); and HPV-seropositive/heavy alcohol users (adjusted OR = 9.8) had greater risk than HPV-seronegative/heavy alcohol users (adjusted OR = 3.1). In contrast, the risk of oropharyngeal cancer was greater in the HPV-seronegative/heavy tobacco (adjusted OR = 11.0) than in HPV-seropositive/heavy tobacco (adjusted OR = 4.7) users and greater in HPV-seronegative/heavy alcohol users (adjusted OR = 24.3) compared to HPV-seropositive/heavy alcohol users (adjusted OR = 8.5). Disease-specific and recurrence-free adjusted survival were significantly worse in oropharyngeal HPV-seronegative cases with no survival differences by HPV status seen in oral cavity cases. The association between tobacco/alcohol, HPV, and tumor site is complex. There appear to be distinct tumor site differences in the combined exposure risks, suggesting that different molecular pathways are involved.

Human papillomavirus seropositivity and risks of head and neck cancer

We examined antibody response to VLP HPV‐16, HPV‐16 E6 and E7 antibodies as potential seromarkers of HPV‐related head and neck cancer (HNC). The study included 204 HNC cases and 326 controls evaluated for HPV presence in sera using ELISAs for anti‐HPV VLP antibodies and HPV‐16 E6 and/or E7 antibodies, and in tumor tissue using PCR and DNA sequencing. Anti‐HPV‐16 VLP was detected in 33.8% of cases and 22.4% of controls, anti‐E6 in 20.6% of cases and 0.9% of controls and anti‐E7 in 18.6% of cases and 0.6% of controls. HPV‐16 DNA was detected in 26.1% of tumors. The adjusted risk of HNC was elevated among those seropositive for HPV‐16 VLP (odds ratio (OR) = 1.7, 1.1–2.5), E6 (OR = 32.8, 9.7–110.8) or E7 (OR = 37.5, 8.7–161.2). Compared to HPV DNA‐negative/seronegative cases, tumor HPV‐16 cases had increased risk of detection with anti‐VLP antibodies (OR = 6.8, 3.1–14.9). The odds were more pronounced among cases seropositive for E6 (OR = 69.0, 19.3–247) or E7 (OR = 50.1, 14.7–171). Antibodies against E6 or E7 were associated with risk of cancer in the oral cavity (OR = 5.1, 1.2–22.4) and oropharynx (OR = 72.8, 16.0–330), and with disease characteristics: stage, grade and nodal status. Anti‐E6 and/or E7 antibodies were found in 74% of tumor HPV‐16 positive cases but in only 5% of tumor HPV‐negative cases (K =0.7, 0.6–0.8) suggesting good correlation between the serologic marker and HPV tumor status. Antibodies to HPV‐16 E6 and/or E7 represent a more specific biomarker than anti‐HPV‐16 VLP of an HPV‐related HNC. Because of the survival advantage of HPV‐related HNC, HPV‐16 E6/E7 detection may be useful in therapy targeted for HPV‐related tumors.

Demographic and risk factors in patients with head and neck tumors

The association between human papillomavirus (HPV) infection and the development of head and neck cancer has been documented recently. In this study on 86 head and neck cancer patients and 124 controls, data regarding demographics, behavioral risk factors, and risks related to HPV exposure were collected. HPV detection was carried out using polymerase chain reaction in the tumors and in oral exfoliated cells, and HPV typing by a reverse line blot assay specific for 37 HPV types. Sera were tested by an enzyme‐linked immunosorbent assay specific for HPV proteins. Head and neck cancer cases report significantly more oral‐anal contact (P = 0.02) and tobacco and alcohol use than controls (P = 0.001; P = 0.02, respectively). High‐risk HPV DNA was detected in 43% of oral washings of cases and 4% of controls (P < 0.0001). The association between the presence of high‐risk HPV DNA in oral exfoliated cells and in tumor tissues was statistically significant (adjusted P < 0.0001). The prevalence of HPV‐specific antibodies was significantly higher in cases than in controls (adjusted P < 0.0001). These results provide epidemiological and immunological evidence for HR HPV as a strong risk factor (OR = 44.3, P < 0.0001) for head and neck cancer, even after controlling for age, tobacco and alcohol use. The detection of high‐risk HPV DNA in oral exfoliated cells and HPV‐specific antibodies in serum can be considered as clinically relevant surrogate markers for the presence of a HPV‐associated head and neck cancer, with a high sensitivity (83%) and specificity (88%). J. Med. Virol. 81:878–887, 2009.

The impact of Parkinson's disease on health status, health expenditures, and productivity. Estimates from the National Medical Expenditure Survey.

SummaryParkinson’s disease (PD) is a common disorder that leads to severe disability, despite pharmacological and surgical interventions. As PD progresses, patients and their families experience substantial health and economic burdens. Little research has been conducted into the economic consequences of PD or the impairment of health dimensions, such as social function and mental health, that may accompany the deterioration in economic resources and physical function.may accompany the deterioration in economic resources and physical function. In the current study, the US National Medical Expenditure Survey (NMES) was examined as a source of population-based information about health-resource use, medical expenditures and health status. 43 patients with PD were identified, and each was matched with 3 individuals without PD to estimate the costs attributable to PD.Data from the NMES demonstrate the serious health and economic burdens of PD. The patients with PD were clearly shown to have decreased health status, increased health expenditures and lost productivity relative to controls. However, these estimates of the magnitude of disease burden must be used with caution. The small sample size appears to have inadequately represented patients in the earliest and the most advanced stages of PD. There was also considerable variability in case-control groups, resulting in wide confidence intervals for the estimates.

Evidence for Vertical Transmission of HPV from Mothers to Infants

Few large studies have evaluated concordance based on a broad spectrum of human papillomavirus (HPV) types in oral and genital specimens of mothers and their recently born infants. This information is important in determining whether HPV vaccines administered prior to pregnancy may be useful for preventing vertical transmission. HPV DNA was positive in 30% of mothers and 1.5% of newborns. Maternal/newborn concordance (HPV+/+ or HPV-/-) was 71%. Among HPV DNA+ mothers, only 3% of their infants were DNA+ and only 1 pair had the same HPV type. Among HPV- women, 0.8% of infants were HPV+. HPV DNA detected in hospitalized newborns reflects current infection transmitted to infants during pregnancy or delivery. None of the mother/baby HPV DNA+ concordance pairs detected viral types found in HPV vaccines suggesting that vaccination prior to pregnancy is unlikely to be efficacious in preventing vertical transmission.

The Usefulness of the Functional Status Questionnaire and Medical Outcomes Study Short Form in Parkinson's Disease Research

Parkinsons disease (PD) has no cure and is a progressive neurological disorder with treatment aimed at the maintenance of function and limitation of the symptoms. No extensive studies of the diseases impact on health-related quality of life (HRQoL) have been conducted. The purpose of this study was to assess the potential usefulness of the Medical Outcomes Study Short Form (SP-36) and the Functional Status Questionnaire (FSQ) in Parkinsons disease research. This cross-sectional study of 193 PD patients who visited two hospital-based neurology clinics used self-administered in-clinic and take-home questionnaires to ascertain the demographic and environmental characteristics of the subjects and to gain health profile measures from the SF-36 and the FSQ. The two health profiles provide important HRQoL information supplementary to the traditional signs and symptoms evaluated by the Unified Parkinsons Disease Rating Scale (UPDRS). Many of the HRQoL measures discriminate progressive stages of disease in this study group and distinguish those with complications of therapy from subjects without complications.

Human papillomavirus, p16 and p53 expression associated with survival of head and neck cancer

BackgroundP16 and p53 protein expression, and high-risk human papillomavirus (HPV-HR) types have been associated with survival in head and neck cancer (HNC). Evidence suggests that multiple molecular pathways need to be targeted to improve the poor prognosis of HNC. This study examined the individual and joint effects of tumor markers for differences in predicting HNC survival. P16 and p53 expression were detected from formalin-fixed, paraffin-embedded tissues by immunohistochemical staining. HPV DNA was detected by PCR and DNA sequencing in 237 histologically confirmed HNC patients.ResultsOverexpression of p16 (p16+) and p53 (p53+) occurred in 38% and 48% of HNC tumors, respectively. HPV-HR was detected in 28% of tumors. Worse prognosis was found in tumors that were p53+ (disease-specific mortality: adjusted hazard ratios, HR = 1.9, 95% CI: 1.04-3.4) or HPV- (overall survival: adj. HR = 2.1, 1.1-4.3) but no association in survival was found by p16 status. Compared to the molecular marker group with the best prognosis (p16+/p53-/HPV-HR: referent), the p16-/p53+/HPV- group had the lowest overall survival (84% vs. 60%, p < 0.01; HR = 4.1, 1.7-9.9) and disease-specific survival (86% vs. 66%, p < 0.01; HR = 4.0, 1.5-10.7). Compared to the referent, the HRs of the other six joint biomarker groups ranged from 1.6-3.4 for overall mortality and 0.9-3.9 for disease-specific mortality.ConclusionThe p16/p53/HPV joint groups showed greater distinction in clinical outcomes compared to results based on the individual biomarkers alone. This finding suggests that assessing multiple molecular markers in HNC patients will better predict the diverse outcomes and potentially the type of treatment targeted to those markers.

Risk Factors for Adverse Drug Events in Older Adults with Mobility Limitations in the Community Setting

OBJECTIVES: To investigate risk factors for self‐reported adverse drug events (ADEs) in a cohort of annually surveyed Iowa Medicare beneficiaries with mobility limitations.