Putative Gonadotropin-Releasing Hormone Agonist Therapy and Dementia: An Application of Medicare Hospitalization Claims Data.

BACKGROUND: Estrogen and hormone replacement therapies to reduce Alzheimer's disease (AD) have yielded conflicting results. However, this study proposes that the well-characterized increase in serum gonadotropins following menopause or andropause are accountable for the increased risk of developing AD among the elderly population. OBJECTIVE: To determine the role of gonadotropins in the development of AD and investigate gonadotropin-releasing hormone (GnRH) agonist therapy as a potential preventative and/or disease-modifying approach to AD management. METHODS: Male Medicare beneficiaries aged 67 to 75 and hospitalized with prostate cancer (n = 115,789) were compared to three control groups: men of the same demographics undergoing a cholecystectomy (n = 97,267), herniorrhaphy (n = 68,778), or transurethral prostatectomy (n = 267,691). A proportion of the patients hospitalized with prostate cancer were assumed to have low concentrations of serum gonadotropins and sex steroids as a result of GnRH agonist therapy, while those in the control groups were assumed to have elevated gonadotropin but lowered sex steroid levels that are associated with andropause in this age group. RESULTS: The rates of development of select diagnoses of dementia, including AD, over a twelve-year follow-up period following surgery. When compared to control patients, men hospitalized with prostate cancer have a protection against dementia after twelve years of follow-up, with relative risks ranging from 0.48 to 0.83. CONCLUSION: Patients with prostate cancer are treated with the GnRH analogue leuprolide acetate, our data suggest that leuprolide acetate may be therapeutic for AD via its downregulation of serum gonadotropins.

The impact of delayed chemotherapy on its completion and survival outcomes in stage II colon cancer patients.

BACKGROUND: Delayed chemotherapy is associated with inferior survival in stage III colon and stage II/III rectal cancer patients, but similar studies have not been performed in stage II colon cancer patients. We investigate the association between delayed and incomplete chemotherapy, and the association of delayed chemotherapy with survival in stage II colon cancer patients. PATIENTS AND METHODS: Patients (age ≥ 66) diagnosed as stage II colon cancer and received chemotherapy from 1992 to 2005 were identified from the linked SEER-Medicare database. The association between delayed and incomplete chemotherapy was assessed using unconditional and conditional logistic regressions. Survival outcomes were assessed using stratified Cox regression based on propensity score matched samples. RESULTS: 4,209 stage II colon cancer patients were included, of whom 73.0% had chemotherapy initiated timely (≤ 2 months after surgery), 14.7% had chemotherapy initiated with moderate delay (2-3 months), and 12.3% had delayed chemotherapy (≥ 3 months). Delayed chemotherapy was associated with not completing chemotherapy (adjusted odds ratio (OR): 1.33 (95% confidence interval: 1.11, 1.59) for moderately delayed group, adjusted OR: 2.60 (2.09, 3.24) for delayed group). Delayed chemotherapy was associated with worse survival outcomes (hazard ratio (HR): 1.75 (1.29, 2.37) for overall survival; HR: 4.23 (2.19, 8.20) for cancer-specific survival). CONCLUSION: Although the benefit of chemotherapy is unclear in stage II colon cancer patients, delay in initiation of chemotherapy is associated with an incomplete chemotherapy course and poorer survival, especially cancer-specific survival. Causal inference in the association between delayed initiation of chemotherapy and inferior survival requires further investigation.

Sero-prevalence of herpes simplex type 2 virus (HSV-2) and HIV infection in Kampala, Uganda.

BACKGROUND: Prevalence of herpes simplex type 2 virus (HSV-2) is high worldwide. Previous studies in Uganda were rural or in women. We estimated age and sex-specific sero-prevalence of HSV-2 in Kampala, Uganda. METHODS: Using two-stage random sampling stratified on population density, a survey of persons 15-65 years was conducted. Type-specific serological tests for HSV-2, HSV-1(HerpeSelect2 and 1 ELISA), HIV (Rapid tests and ELISA), syphilis (RPR and TPHA) were done. Additional prevalence analysis included post-stratification weighting on the Uganda 2002 Census gender distribution. RESULTS: Among 1124 persons, HSV-2 prevalence was 58% (95% CI: 55, 60), HSV-1; 98% (95% CI: 97.6, 99.1), HIV; 17.7% (95% CI: 14.8, 19.2) and syphilis; 1.7% (95% CI: 1.4, 1.9). Weighted HSV-2 prevalence was 53.8% (Women; 63.8%, men; 43.2%), similar to unweighted data. Weighted HIV prevalence was 20.7% in women, 8.6% in men. Of 165 HIV infected persons, 85.4% had HSV-2. Risk factors for HSV-2 were being a woman (OR 2.0; 95% CI: 1.42, 2.78), age (OR 3.3; 95% CI: 2.43, 4.53), education (OR 1.70; 95% CI: 1.34, 2.34) and HIV (OR 4.5; 95% CI: 2.70, 7.50). CONCLUSION: Prevalence of HSV-2 and HIV was high especially in women. Syphilis was rare. Awareness of herpes was low. Interventions in young people are needed.

Comparison of adiposity measures as risk factors in postmenopausal women.

CONTEXT: There is a continuing debate about which adiposity measure is the best risk factor. OBJECTIVES: This study compared the associations of 14 health outcomes with combinations of four adiposity measures: body mass index (BMI), waist to hip ratio (WHR), waist, and waist to height ratio. DESIGN: Data were from the Women's Health Initiative, a prospective study of women enrolled from 1993-1998 with a median follow-up time of 8 yr. Regression models were used to test the association of adiposity measures with outcome after adjusting for a number of variables related to demographic characteristics and health behavior. SETTING: The women were recruited from 40 clinical centers throughout the United States. PARTICIPANTS: The sample analyzed included 141,652 postmenopausal women age 50-79 yr who met the criteria for the Women's Health Initiative randomized control trials. MAIN OUTCOME MEASURES: Outcomes included death and eight medical conditions. RESULTS: Adiposity measures were most strongly associated with diabetes, hypertension, joint replacement, and gallbladder disease; moderately associated with myocardial infarction, endometrial cancer, and death; and least strongly associated with colon cancer, stroke, and breast cancer. Associations were nearly identical for waist and waist to height ratio. For most outcomes, waist was a stronger individual risk factor than BMI or WHR. However, BMI and WHR were the most useful combination of adiposity measures for stratifying participants according to risk of hypertension or diabetes. CONCLUSIONS: The adiposity measure most useful for stratifying persons on the basis of risk depends on the outcome of interest. When the outcome is diabetes or hypertension in postmenopausal women, the best indication of risk is a combination BMI and WHR.

A meta-analysis of the impact of IVF and ICSI on major malformations after adjusting for the effect of subfertility.

OBJECTIVE: To estimate the effect of assisted reproductive technology (ART) on major malformation (MM) rate in ART offspring independent of the effect of subfertility on MM. DESIGN: Meta-analysis. METHODS: This meta-analysis is based on our previously published meta-analysis of observational studies evaluating the relationship between ART treatment and MM rates, as well as recent research by Zhu et al. to estimate the impact of subfertility alone on MM in subfertile couples conceiving spontaneously. RESULTS: The overall odds ratio for MM in our original meta-analysis, in which all studies used apparently inappropriate control groups of "normal" populations, was 1.29 (95% CI 1.01-1.67). Here we attempted to estimate the risk of subfertility and used this estimate to perform an adjusted meta-analysis. Zhu et al. found that about 40% of the odds of MM was due to subfertility. When we took Zhu's finding into account, the adjusted odds ratio in the meta-analysis was 1.01 (95% CI 0.82-1.23). CONCLUSIONS: Our study suggests ART does not increase the risk of MM as much as previously reported. More research is needed to quantify the underlying risk of subfertility and separate it from the risk associated with ART. Physicians who counsel subfertile couples should recognize that previous studies of MM rates in ART patients probably overestimated the risk.

The association between mucin balls and corneal infiltrative events during extended contact lens wear.

PURPOSE: To determine the association between mucin ball formation and corneal infiltrative events (CIEs) during continuous wear with lotrafilcon A silicone hydrogel contact lenses. METHODS: Subjects (n = 205) in the Longitudinal Analysis of Silicone Hydrogel Contact Lens Study wore lotrafilcon A contact lenses for 12 months of continuous wear. The primary outcome was a CIE. Kaplan-Meier methods were used to estimate the unadjusted cumulative incidence of remaining CIE free stratified by mucin ball presence. Cox proportional hazards regression was used to model the hazard of developing a CIE as a function of mucin ball formation and other covariates. RESULTS: Over half (54.2%) of the subjects displayed some presence of mucin balls during at least 1 visit and about one third (32.8%) displayed repeated episodes. Mucin ball scores were correlated between the 2 eyes and weakly correlated with corneal curvature (P ≤ 0.005). Univariate analyses revealed that the relative hazard for a CIE was 0.35 [95% confidence interval (CI), 0.19-0.68] if a single episode of mucin balls was detected and 0.17 (95% CI, 0.06-0.43) if repeated episodes were detected. Upon multivariate analysis, repeated presence of mucin balls was associated with an 84% decreased hazard of experiencing a CIE (hazard ratio: 0.16; 95% CI, 0.06-0.44). CONCLUSIONS: The presence of mucin balls is significantly associated with a decreased incidence of CIEs, and the effect is greatest when they are repeatedly present over time. We hypothesize that the mucin ball presence represents a more concentrated or viscous mucus layer, which prevents upregulation of the immune response against bacterial ligands.

Risk factors for corneal infiltrative events during continuous wear of silicone hydrogel contact lenses.

PURPOSE: This study determined which microbiologic, clinical, demographic, and behavioral factors are associated with corneal infiltrative events (CIEs) during continuous wear of silicone hydrogel (SH) contact lenses. METHODS: Subjects (n = 205) were fitted with lotrafilcon A lenses for continuous wear and observed for 1 year. The main exposures of interest were corneal staining and bacterial lens contamination. Kaplan-Meier (KM) plots were used to estimate the cumulative unadjusted probability of remaining CIE free, and Cox proportional hazards regression was used to model the hazard of having a CIE, as a function of key predictor variables. RESULTS: The KM-unadjusted cumulative probability of remaining CIE free was 73.3%. Approximately 53% of subjects had repeated episodes of corneal staining (mild or greater), and 11.3% had repeated episodes of moderate or greater corneal staining. Corneal staining was not associated with the development of a CIE. The frequency of substantial bacterial bioburden on worn lenses at the time of a CIE was 64.7%, compared with only 12.2% during uncomplicated wear. The presence of substantial lens bacterial bioburden was associated with the development of a CIE (adjusted hazards ratio [HR], 8.66; 95% confidence interval [CI], 2.88-26.01). Smoking was also associated with a CIE (adjusted HR, 4.13; 95% CI, 1.27-13.45). CONCLUSIONS: Corneal staining is common during continuous wear of SH lenses, but it is not associated with the development of a CIE. Smoking and substantial lens bacterial bioburden pose prominent risks of a CIE. In this study, more than 70% of the total risk of CIE in those with substantial lens bioburden is attributable to this exposure. (ClinicalTrials.gov number, NCT00727402).

Post-acute care services received by older adults following a cardiac event: a population-based analysis.

BACKGROUND: Post-acute care (PAC) is available for older adults who need additional services after hospitalization for acute cardiac events. With the aging population and an increase in the prevalence of cardiac disease, it is important to determine current PAC use for cardiac patients to assist health care workers to meet the needs of older cardiac patients. The purpose of this study was to determine the current PAC use and factors associated with PAC use for older adults following hospitalization for a cardiac event that includes coronary artery bypass graft and valve surgeries, myocardial infarction (MI), percutaneous coronary intervention (PCI), and heart failure (HF). METHODS AND RESULTS: A cross-sectional design and the 2003 Medicare part A database were used for this study. The sample (n = 1493521) consisted of patients 65 years and older discharged after their first cardiac event. Multinomial logistic regression was used to examine factors associated with PAC use. Overall, PAC use was 55% for cardiac valve surgery, 50% for MI, 45% for HF, 44% for coronary artery bypass graft, and 5% for PCI. Medical patients use more skilled nursing facility care, and surgical patients use more home health care. Only 0.1% to 3.4% of the cardiac patients use intermediate rehabilitation facilities. Compared with those who do not use PAC, those who use home health care and skilled nursing facility care are older and female, have a longer hospital length of stay, and have more comorbidity. Asians, Hispanics, and Native Americans were less likely to use PAC after hospitalization for an MI or HF. CONCLUSIONS: The current rate of PAC use indicates that almost half of nondisabled Medicare patients discharged from the hospital following a cardiac event use one of these services. Health care professionals can increase PAC use for Asians, Hispanics, and Native Americans by including culturally targeted communication. Optimizing recovery for cardiac patients who use PAC may require focused cardiac rehabilitation strategies.

Risk factors for contact lens bacterial contamination during continuous wear.

PURPOSE: Microbial contamination of contact lenses is associated with corneal infection and inflammation. This study determined the microbiological, clinical, and demographic factors that are associated with bacterial contamination of a silicone hydrogel contact lens when worn for continuous wear (CW). METHODS: Two hundred five healthy subjects were enrolled in the Longitudinal Analysis of Silicone Hydrogel Contact Lens Study and were fitted with lotrafilcon A lenses for monthly CW and followed for 1 year. Lenses were aseptically removed after 1 week and 4 months of wear and cultured using an agar sandwich technique. Lids and conjunctiva were routinely cultured at baseline and after 1 week and 4 months of CW. Lenses and ocular sites were considered to have substantial microbial bioburden when they harbored pathogenic organisms or high levels of commensal organisms. Univariate and multivariate logistic regression analyses were conducted to examine whether substantial conjunctival or lid bioburden, subject demographics, lens-wearing history, symptoms, and biomicroscopic signs were associated with lens bioburden. RESULTS: About one third (32.4%) of subjects had substantial bacterial bioburden in either eye across multiple visits. Over half (53.2%) and about one tenth (11.7%) of subjects had substantial lid and conjunctival bioburden, respectively, and 11.2% discontinued because of discomfort. The adjusted odds ratios (and 95% confidence intervals) for presence of substantial lens bioburden were 2.49 (1.17-5.30), 4.24 (1.45-12.40), and 4.11 (1.17-14.46) for substantial lid bioburden, substantial conjunctival bioburden, and lens discomfort, respectively. CONCLUSIONS: Bacterial contamination of silicone hydrogel contact lenses is common during CW. Substantial lens bioburden is associated with discomfort precluding successful CW. The presence of substantial lid and conjunctival bioburden is associated with a 2.5-fold and more than fourfold greater risk of substantial lens bioburden and is likely the major route of contamination.

Radiotherapy and survival in prostate cancer patients: a population-based study.

PURPOSE: To investigate the association of overall and disease-specific survival with the five standard treatment modalities for prostate cancer (CaP): radical prostatectomy (RP), brachytherapy (BT), external beam radiotherapy, androgen deprivation therapy, and no treatment (NT) within 6 months after CaP diagnosis. METHODS AND MATERIALS: The study population included 10,179 men aged 65 years and older with incident CaP diagnosed between 1999 and 2001. Using the linked Ohio Cancer Incidence Surveillance System, Medicare, and death certificate files, overall and disease-specific survival through 2005 among the five clinically accepted therapies were analyzed. RESULTS: Disease-specific survival rates were 92.3% and 23.9% for patients with localized vs. distant disease at 7 years, respectively. Controlling for age, race, comorbidities, stage, and Gleason score, results from the Cox multiple regression models indicated that the risk of CaP-specific death was significantly reduced in patients receiving RP or BT, compared with NT. For localized disease, compared with NT, in the monotherapy cohort, RP and BT were associated with reduced hazard ratios (HR) of 0.25 and 0.45 (95% confidence intervals 0.13-0.48 and 0.23-0.87, respectively), whereas in the combination therapy cohort, HR were 0.40 (0.17-0.94) and 0.46 (0.27-0.80), respectively. CONCLUSIONS: The present population-based study indicates that RP and BT are associated with improved survival outcomes. Further studies are warranted to improve clinical determinates in the selection of appropriate management of CaP and to improve predictive modeling for which patient subsets may benefit most from definitive therapy vs. conservative management and/or observation.

Mammography utilization rates among young white and black women in the USA.

OBJECTIVE: To determine mammography utilization rates for randomly selected white and black women in the USA. STUDY DESIGN: This was an observational study using data from 1988 to 2000. Data were extracted from the Behavioral Risk Factor Surveillance System, an annual self-report telephone survey conducted nationally by the Centers for Disease Control and Prevention. METHODS: The main outcome measure was the mammography utilization rates of women ages 18-40 years responding to 'Have you ever had a mammogram?'. In total, 354097 women were included in this study [310336 (87.6%) white women and 43761 (12.4%) black women]. RESULTS: In women ages 18-33, black women showed consistently higher mammography utilization rates than white women. Utilization rates among women ages 18-23 years were 20.0% and 11.0% for black and white women, respectively. Among women ages 24-29 years, rates were 22.2% and 11.5% for black and white women, respectively. For women ages 30-33 years, rates were 25.7% and 18.1% for black and white women, respectively. Utilization rates were similar in black and white women over 33 years of age. CONCLUSIONS: This study found that young black women were receiving more mammography screening than young white women between 1988-2000. This may be due to the increased risk of fibroid masses in young black women.

Gender differences in emergency department patients with chronic obstructive pulmonary disease exacerbation.

OBJECTIVES: Although more men are diagnosed as having chronic obstructive pulmonary disease (COPD), its prevalence is increasing among women. Little is known about gender differences in exacerbations of COPD. The objective of this study was to determine if acute presentation, management, and outcomes differ among men and women seeking care in the emergency department (ED) for exacerbation of COPD. METHODS: This was a secondary analysis of a prospective cohort study of ED patients aged 55 years or older who presented with an exacerbation of COPD. Subjects underwent structured interviews in the ED and two weeks later. RESULTS: The cohort consisted of 397 subjects with COPD, of whom 52% were women. Self-report of COPD only tended to be more common among men (61% of men vs. 52% of women), while mixed COPD/asthma tended to be more common among women (39% vs. 48%; p = 0.10). Despite reporting similar chronic symptom severity, women were less likely than men to use anticholinergic agents before their ED visit (59% vs. 69%; p = 0.04). During the exacerbation, women initiated less home therapy and were less likely to seek emergency care within the first 24 hours of symptom onset (25% vs. 36%; p = 0.01). Although ED care and disposition were similar, post-ED outcomes differed. At two-week follow-up, men were more likely to report an ongoing exacerbation (42% vs. 31%; p = 0.03). CONCLUSIONS: Men and women who present to the ED for treatment of an exacerbation of COPD have substantial differences in long-term medication use, self-treatment during exacerbation, delay in emergency care, and post-ED outcomes. Further studies are warranted to confirm and explain these gender-related differences.

Geographic and patient variation in receipt of surveillance procedures after local excision of cutaneous melanoma.

Little is known about variation in surveillance practices following the diagnosis of invasive melanoma. The objective of this study was to characterize geographic, patient, and tumor variation in the use of follow-up surveillance testing in patients with local or regional stage melanoma. A cohort of Medicare beneficiaries > or =65 y diagnosed with invasive melanoma during 1992 to 1996 living in a Surveillance, Epidemiology, and End Results registry area was studied. Outpatient and inpatient Medicare claims 3 mo following diagnosis were examined for up to 2 y for surveillance procedures of interest. Use of chest X-ray, chest computed tomography scan, abdominal and/or pelvic computed tomography scan, abdominal ultrasound, head computed tomography scan, head magnetic resonance imaging, laboratory testing, and skin examinations were compared between patient groups and geographic regions. A total of 3389 patients were identified for the analysis. Surveillance testing was relatively common, ranging from 13% for abdominal ultrasound to 80% for laboratory testing. Follow-up skin examinations were performed in 70% to 90% of patients. The use of most surveillance procedures was associated (p<0.01) with younger age, male gender, regional stage tumors, and geographical area, with up to 2-fold differences observed. In contrast, there was much less variability in the receipt of skin examinations. Further studies are needed to determine the etiology and impact of such disparities, and the influence of surveillance procedures on morbidity and mortality.