Incidence of Parkinson disease in North America.

Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence estimates have varied, for unclear reasons. There is a need for improved estimates of PD incidence, not only for care delivery planning and future policy but also for increasing our understanding of disease risk. The objective of this study was thus to investigate the incidence of Parkinson disease across five epidemiological cohorts in North America in a common year, 2012. The cohorts contained data on 6.7 million person-years of adults ages 45 and older, and 9.3 million person-years of adults ages 65 and older. Our estimates of age-sex-adjusted incidence of PD ranged from 108 to 212 per 100,000 among persons ages 65 and older, and from 47 to 77 per 100,00 among persons ages 45 and older. PD incidence increased with age and was higher among males. We also found persistent spatial clustering of incident PD diagnoses in the U.S. PD incidence estimates varied across our data sources, in part due to case ascertainment and diagnosis methods, but also possibly due to the influence of population factors (prevalence of genetic risk factors or protective markers) and geographic location (exposure to environmental toxins). Understanding the source of these variations will be important for health care policy, research, and care planning.

Prevalence of Parkinson's disease across North America.

Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.

Blueberry muffin rash, hyperbilirubinemia, and hypoglycemia: a case of hemolytic disease of the fetus and newborn due to anti-Kp(a).

Hemolytic disease of the fetus and newborn occurs when maternal IgG antibodies cross the placenta and cause hemolysis of fetal red blood cells. Kp(a) is a low frequency red blood cell antigen that has rarely been implicated in hemolytic disease of the fetus and newborn. The few reported cases attributed to anti-Kp(a) have typically had minimal clinical consequences. We report a critically ill neonate who presented with purpura, respiratory failure, severe liver dysfunction, hyperbilirubinemia, hypoglycemia and anemia. This case report broadens the spectrum of neonatal disease associated with anti-Kp(a), addresses the evaluation of hemolysis with liver failure in a neonate, and emphasizes the importance of screening for antibodies to low frequency red blood cell antigens in suspected hemolytic disease of the fetus and newborn.

Allogeneic hematopoietic cell transplantation outcomes for children with B-precursor acute lymphoblastic leukemia and early or late BM relapse.

Large registry studies have shown superior disease-free survival (DFS) with matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT) over chemotherapy alone for patients with B-precursor acute lymphoblastic leukemia (ALL) and a late BM relapse. As most of these patients will not have an MSD, the decision to pursue an unrelated allo-HCT in second remission (CR2) or await a future relapse and perform HCT in third remission (CR3) continues to be debated. Between 1990 and 2006, 41 children with relapsed B-precursor ALL received a myeloablative allo-HCT at the University of Minnesota. Graft sources consisted of matched related donor (n=11), matched unrelated donor (n=9), and unrelated umbilical cord blood (n=21). Before allo-HCT, 15 patients had an early relapse (<36 months from diagnosis) and 26 had an initial late relapse (36 months from diagnosis). In all, 30 patients (73%) were in CR2 and 11 were in CR3 (27%) at time of allo-HCT. Five year OS/DFS were similar for patients with an early or late marrow relapse, but there was inferior DFS among late-relapse patients transplanted in CR3 compared with CR2 (30% vs 75%, P=0.04). These results suggest that allo-HCT should be pursued in children after a first marrow relapse, rather than waiting for subsequent recurrence.

Informing older adults about non-hazardous, hazardous, and harmful alcohol use.

Low levels of alcohol may be hazardous in the elderly, but available education focuses on younger, abusive, and dependent drinkers. A total of 209 older persons participated in various components of the development and evaluation of 'A Toast To Health In Later Life!' health promotion materials for the elderly. Patient focus groups, physicians, educators, and alcohol-use researchers contributed to all materials and measures. An education model for older adults guided the instructional format. Knowledge and self-efficacy scores increased significantly from pre- to post-test. Over 45% of persons in selected senior centers reviewed the materials without prompting by the study team. Older adults are willing to read extensively about the relationships among drinking, health, and medication use. Patient educators should include consumers in the design of health promotion materials and measures. Practitioners who rely on written educational materials for patient education and counseling should be provided with evidence of appropriateness, effectiveness, and feasibility.

Emotional and physical demands on caregivers in home care to the elderly in Switzerland and their relationship to nursing home admission.

BACKGROUND: Planning the home care of growing numbers of old, dependent people must include the caregivers' burden. METHODS: A convenience sample of 129 caregivers of elderly patients with multiple diagnoses was interviewed about the caregiving context, burden, caregivers' tolerance of patients' troublesome behaviours and physical symptoms, mutuality and feelings of closeness between caregiver and patient. Continued maintenance of home care was assessed by a follow-up telephone call. RESULTS: Caregivers were mainly spouses (67%) and female (73%), and the mean duration of care was 5.5 years. In five activities of daily living (ADL) 50-69% of the patients needed full help. Caregivers reported predominantly negative effects of caregiving on their physical and mental health, rest and sleep, leisure time and social life, problems with patients' symptoms and behaviours and little or no conversing (51%) or exchanging feelings with patients (71%). PREDICTIVE MODELS: Contributors to variance were for burden (35%), impact of care on caregivers' mental health, social relations and leisure time, patients' gender, accumulation of patients' symptoms and behaviours; for caregivers' tolerance toward patients' symptoms and behaviours (17%) caregivers' physical health, patients' level of confusion, feelings of mutuality; for mutuality (22%) and for closeness (19%) caregivers' mental health, patients' accumulation of symptoms and behaviours. Within 23 months 19% of the patients had been institutionalized. Factors giving a higher likelihood of institutionalization were: being male, caregiver was not a partner, and less closeness between caregiver and patient. CONCLUSION: Caregiving of older persons has bio-psychosocial ramifications for caregivers. Closeness between caregiver and patient seems to be a key factor in determination of the long-term outcome.

[Test-retest reliability of a German language multidimensional assessment instrument in elderly probands]. / Test-Retest-Reliabilität eines deutschsprachigen multidimensionalen Assessmentinstruments bei älteren Personen.

Most geriatric assessment instruments have been developed in the English language. Translated versions might differ in their psychometric properties. We analyzed the test-retest reliability and internal consistency of a German instrument for multidimensional geriatric assessment that was based on a newly developed English version. A group of 100 over 75-year-old community-dwelling persons (mean age 83.0 years, 81% women) in Hamburg (n = 26) and Ulm (n = 51), Germany, and Berne (n = 23), Switzerland was interviewed twice by the same trained interviewers with a one week interval. We administered questions on general health, chronic disorders, basic and instrumental activities of daily living, urinary incontinence, nutrition, falls, pain, the social support/network and preventive care measures. In addition, the Functional Status Questionnaire, the Physical Activity Scale for the Elderly, the Geriatric Oral Health Assessment Index, the Visual Function Questionnaire, the Hearing Handicap Inventory for the Elderly and the Geriatric Depression Scale were administered. Cohen's kappa was good to excellent (0.64 < or = kappa < or = 0.89) with only three exceptions (pain questions, kappa = 0.53; questions on preventive care services, kappa = 0.51; and one of the questions on recent falls, kappa = 0.44). Cronbach alpha (internal consistency) was good to excellent for all domains (0.76 < or = alpha < or = 0.95). The study results confirm good test-retest reliability of the German version of this multidimensional geriatric assessment instrument. Adapted versions of this instrument can be used for different purposes, e.g., preventive home visits, outpatient geriatric assessments or epidemiological studies in older persons.

An in vivo/in vitro comparison with a leuprolide osmotic implant for the treatment of prostate cancer.

An osmotically driven implantable system was designed and characterized for the delivery of leuprolide over a year-long duration. Leuprolide has been used in the treatment of prostate cancer since the 1980s. The DUROS implant consists of a titanium alloy cylinder, measures 4 mm in diameter by 45 mm in length and holds approximately 150 microl of formulation. Stability studies indicated that leuprolide was stable, as a solution formulation in DMSO, for several years at 37 degrees C. In vitro release rate testing, at weekly intervals, showed zero-order delivery for 1 year. DUROS implants demonstrated release rates that were reproducible and similar to one another after storage at 25 degrees C for 18 months prior to testing. In vivo studies, with implants placed subcutaneously, revealed delivery rates comparable to those observed under in vitro conditions. Leuprolide stability was also comparable between in vivo and in vitro conditions. Steady leuprolide serum levels produced by the implant resulted in the desired pharmacodynamic efficacy endpoint of testosterone suppression, both in canines and in humans. The good agreement between in vivo/in vitro delivery rates was as expected for a delivery system based on the principles of osmosis.

Current analysis of the Tarasoff duty: an evolution towards the limitation of the duty to protect.

In 1976, the Tarasoff case established a new legal duty to protect third parties from a psychiatric patient's foreseeable violence. After the Tarasoff case, courts expanded the scope and role of a clinician's duty to protect, sometimes in novel ways. Later interpretations of Tarasoff began to limit significantly the situations in which a duty to protect would attach. Recent Tarasoff-type cases in which courts have rejected the clinician's duty to warn suggest that Tarasoff is declining in significance. The advent of state statutes that codify the establishment and discharge of Tarasoff duty have contributed to a further limitation of the duty to protect. Lastly, when faced with the management of dangerous patients, we advocate for a thorough, well documented assessment of risk of violence as the best means for addressing concern about potential legal liability.

Collection of genomic DNA from adults in epidemiological studies by buccal cytobrush and mouthwash.

Blood samples are an excellent source of large amounts of genomic DNA. However, alternative sources are often needed in epidemiological studies because of difficulties in obtaining blood samples. This report evaluates the buccal cytobrush and alcohol-containing mouthwash protocols for collecting DNA by mail. Several DNA extraction techniques are also evaluated. The study was conducted in two phases. In phase 1, we compared cytobrush and mouthwash samples collected by mail in two different epidemiological studies: (a) cytobrush samples (n = 120) from a United States case-control study of breast cancer; and (b) mouthwash samples (n = 40) from a prospective cohort of male United States farmers. Findings from phase 1 were confirmed in phase 2, where we randomized cytobrush (n = 28) and mouthwash (n = 25) samples among participants in the breast cancer study to directly compare both collection methods. The median human DNA yield determined by hybridization with a human DNA probe from phenol-chloroform extracts was 1.0 and 1.6 microg/2 brushes for phases 1 and 2, respectively, and 27.5 and 16.6 microg/mouthwash sample for phases 1 and 2, respectively. Most (94-100%) mouthwash extracts contained high molecular weight DNA (>23 kb), in contrast to 55-61% of the brush extracts. PCR success rates for amplification of beta-globin gene fragments (268, 536, and 989 bp) were similar for cytobrush and mouthwash phenol-chloroform extracts (range, 94.4-100%). Also, we obtained high success rates in determining the number of CAG repeats in the androgen receptor gene, characterizing tetranucleotide microsatellites in six gene loci, and screening for mutations in the BRCA1/2 genes in a subset of phenol-chloroform DNA extracts. Relative to DNA extracted by phenol-chloroform from cytobrush samples, DNA extracted by NaOH had lower molecular weight, decreased PCR success rates for most assays performed, and unreliably high spectrophotometer readings for DNA yields. In conclusion, although DNA isolated from either mouthwash or cytobrush samples collected by mail from adults is adequate for a wide range of PCR-based assays, a single mouthwash sample provides substantially larger amounts and higher molecular weight DNA than two cytobrush samples.

Are older hazardous and harmful drinkers less likely to participate in health-related behaviors and practices as compared with nonhazardous drinkers?

OBJECTIVES: To describe the (1) prevalence of at-risk drinking and participation in health-related behaviors and practices and (2) associations of at-risk drinking with other health-related behaviors and practices among older persons completing a health-risk appraisal for the elderly (HRA-E). DESIGN: Cross-sectional study using data from a self-administered, mailed survey sample. SETTINGS: Persons from three organizations were surveyed: (1) the American Association of Retired Persons; and (2) a large medical group and (3) a community-based senior health center in southern California. PARTICIPANTS: 1,889 persons age 55 years and older. MEASUREMENTS: The HRA-E included items on health characteristics, drinking behaviors (including amount of alcohol use and two alcoholism screening measures: the CAGE (Cut down, Annoyed, Guilty, Eye opener) and Short Michigan Alcoholism Screening Test-Geriatric version (SMAST-G), and participation in selected health-related behaviors and practices. Social drinkers were defined as those who drank fewer than 14 drinks weekly and screened negative on the CAGE (defined as two or more "no" responses) and SMAST-G. Hazardous drinkers drank fewer than 14 drinks weekly and screened negative. Harmful drinkers drank fewer than 14 drinks weekly and screened positive. Possible at-risk drinkers drank 14 or more drinks weekly and screened positive. Least squares regression models were used to assess the effects of hazardous, harmful, and possible at-risk drinking on each of the health-related practices and behaviors. We also conducted these analyses using three other definitions of social, possible at-risk, hazardous, and harmful drinking. RESULTS: Of all respondents, 40% were social drinkers, 3% were harmful drinkers, 2% were hazardous drinkers, and 11% were possible at-risk drinkers. Hazardous, harmful, and possible at-risk drinkers commonly reported driving after drinking or being driven by someone who had been drinking (67%, 76%, and 64% respectively). Harmful and possible at-risk drinkers were more likely than social drinkers to smoke and were less likely to use seatbelts regularly. These findings were observed regardless of how the drinking groups were defined. CONCLUSION: All groups of at-risk drinkers more commonly engaged in selected adverse health-related behaviors and practices than did social drinkers.

Using data to enhance the expert panel process. Rating indications of alcohol-related problems in older adults.

OBJECTIVE: To enhance the validity of a well-known expert panel process, we used data from patient surveys to identify and correct rating errors. METHODS: We used the two-round RAND/UCLA panel method to rate indications of harmful (presence of problems), hazardous (at risk for problems), and nonhazardous (no known risks) drinking in older adults. Results from the panel provided guidelines for classifying older individuals as harmful, hazardous, or nonhazardous drinkers, using a survey. The classifications yielded unexpectedly high numbers of harmful and hazardous drinkers. We hypothesized possible misclassifications of drinking risks and used the survey data to identify indications that may have led to invalid ratings. We modified problematic indications and asked three clinician panelists to evaluate the clinical usefulness of the modifications in a third panel round. We revised the indications based on panelist response and reexamined drinking classifications. RESULTS: Using the original indications, 48% of drinkers in the sample were classified as harmful, 31% as hazardous, and 21% as nonhazardous. A review of the indications revealed framing bias in the original rating task and vague definitions of certain symptoms and conditions. The modified indications resulted in classifications of 22% harmful, 47% hazardous, and 31% nonhazardous drinkers. CONCLUSIONS: Analysis of survey data led to identification and correction of specific errors occurring during the panel-rating process. The validity of the RAND/UCLA method can be enhanced using data-driven modifications.

Feasibility of using an alcohol-screening and health education system with older primary care patients.

BACKGROUND: This study evaluated the feasibility of a combined alcohol-screening and health education system for elderly patients METHODS: The Computerized Alcohol-Related Problems Survey (CARPS) was evaluated in primary care practices among 106 current drinkers, 60 years and older. The CARPS contains (1) a self-administered screening survey; (2) software to scan or hand-enter survey responses; (3) software to process data and electronically generate reports of patients' drinking risks; (4) health education; and (5) a database useful for clinical and quality improvement purposes. RESULTS: Nearly all study participants were able to complete the CARPS while waiting for a prescheduled appointment with their physician. There were 44% of patients who were hazardous and 9% who were harmful drinkers. About 20% of men and 26% of women were binge drinkers. Most (85%) patients agreed that alcohol is an important topic, 67% reported learning new information, 78% had never discussed drinking with a physician, and 31% intended to do so. After reviewing CARPS data, physicians concluded that alcohol use in the elderly is an important quality improvement topic. CONCLUSIONS: Combined screening and health education systems appear feasible for use in practice if they deal with pertinent health problems such as alcohol use. Their data can encourage discussions between physicians and patients and might be used for quality improvement activities.

Chronic (60-week) toxicity study of DUROS leuprolide implants in dogs.

The toxicity and pharmacodynamics of leuprolide acetate delivered from subcutaneously implanted DUROS leuprolide implants were examined in sexually mature male beagle dogs. The DUROS leuprolide implant is a sterile, nonpyrogenic, nonerodible, single-use, implantable, osmotically driven, drug delivery system for the palliative treatment of advanced prostate cancer. It contains 65 mg of leuprolide and is designed to deliver leuprolide continuously at a nominal rate of 120 microg per day for at least 12 months. Serum drug and testosterone concentrations were compared to values from dogs receiving monthly intramuscular injections of Lupron Depot 3.75 mg or no treatment (sham-operated). The local tissue response induced by subcutaneously implanted DUROS leuprolide implants was also evaluated. Beagles were implanted with a DUROS leuprolide implant for 52 weeks followed by removal and implantation of a new DUROS leuprolide implant for an additional 8 weeks. No mortality or morbidity occurred in this study. No treatment-related changes occurred in mean body weights, blood chemistry, or hematology during the study. Treatment-related atrophy of the testes, epididymides, and prostate gland, consistent with the known pharmacological effects of the drug, was observed in all dogs receiving the DUROS leuprolide implant or the Lupron Depot. Histological examination of these organs showed no distinguishable difference between dogs treated with the DUROS leuprolide implant or Lupron Depot. Weekly serum samples from dogs with DUROS leuprolide implants indicated continuous leuprolide delivery over 60 weeks, while some samples from the Lupron Depot group fell below measurable concentrations. Analysis of serum samples collected every 28 days just before Lupron Depot injection showed that 80% of these samples had leuprolide concentrations below the limit of quantitation (0.1 ng/ml). Serum testosterone concentrations were below castrate levels (<50 ng/dl) by 4 weeks after implantation of DUROS leuprolide implant and remained so for the duration of the study. Lupron Depot 3.75 mg also effectively lowered serum testosterone concentrations, but required reinjection every 28 days. All local tissue reactions to the DUROS leuprolide implant at implant sites were classified as mild following macroscopic examination. Microscopic site scores were mild to moderate. The DUROS leuprolide implant was shown to be safe, to provide continuous leuprolide delivery, and to effectively lower serum testosterone concentrations below castrate levels.

The Geriatric Pain Measure: validity, reliability and factor analysis.

BACKGROUND: Pain is a multidimensional experience that should be evaluated beyond an estimate of intensity. A multidimensional pain measure has not been developed for older persons undergoing comprehensive geriatric assessment. OBJECTIVE: To develop and evaluate validity and reliability of a multidimensional pain assessment instrument for older persons. RESEARCH DESIGN: A series of steps in instrument development and evaluation. SUBJECTS: A total of 176 subjects (mean age 84 +/- 6.0 years) in ambulatory geriatric clinics; 64% were women, and 73% had a history of chronic pain. MEASUREMENTS: Measurements included the Geriatric Pain Measure (GPM), the McGill Pain Questionnaire, Yesavage GDS, Katz ADLs, Lawton IADLs, Tinetti Gait and Balance, Folstein MMSE, and other demographic and clinical characteristics from interview and chart review. RESULTS: The GPM demonstrated a standardized alpha = 0.9445, homogeneity ratio =0.457, and average inter-item correlation =0.415. A subgroup of 50 subjects demonstrated concurrent validity of the GPM in comparison with the McGill Pain Questionnaire (Pearson's r correlation 0.6269 (P < .0000). Test-retest reliability was demonstrated in another subgroup of 50 subjects who repeated the GPM within 48 to 72 hours (Pearson's r = 0.9018; P < .0000). Factor analysis revealed five clusters of components: Pain Intensity, Disengagement, Pain with Ambulation, Pain with Strenuous Activities, and Pain with Other Activities. CONCLUSIONS: The GPM is a 24-item questionnaire that is easy to administer and has significant validity and reliability in older persons with multiple medical problems. The GPM may be a useful addition to the multidimensional geriatric assessment process.

Health services utilization of elderly Swiss: evidence from panel data.

The demand for health care services by the elderly is a topic of growing importance because of changes in the demographic structure in many countries. This paper provides estimates of the determinants of the demand for physician visits by the elderly, including the impact of a disability prevention intervention. We control for unobserved heterogeneity across individuals and the count data structure of the data by estimating random effects negative binomial models for all primary physician and specialist visits.