Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D.

SUMMARY: Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year. INTRODUCTION: Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized. METHODS: Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss. RESULTS: Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (-2.57 %, p = 0.006), with a trend towards greater declines at the total hip (p = 0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p < 0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p > 0.10) primarily in the first year. CONCLUSIONS: Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.

Rationale and protocol of the ENGAGE study: a double-blind randomized controlled preference trial using a comprehensive cohort design to measure the effect of a cognitive and leisure-based intervention in older adults with a memory complaint.

BACKGROUND: Leisure activities can be both enjoyable and cognitively stimulating, and participation in such activities has been associated with reduced age-related cognitive decline. Thus, integrating stimulating leisure activities in cognitive training programs may represent a powerful and innovative approach to promote cognition in older adults at risk of dementia. The ENGAGE study is a randomized controlled, double-blind preference trial with a comprehensive cohort design that will test the efficacy and long-term impact of an intervention that combines cognitive training and cognitively stimulating leisure activities. METHODS: One hundred and forty-four older adults with a memory complaint will be recruited in Montreal and Toronto. A particular effort will be made to reach persons with low cognitive reserve. Participants will be randomly assigned to one of two conditions: cognitive + leisure training (ENGAGE-MUSIC/SPANISH) or active control (ENGAGE-DISCOVERY). The ENGAGE-MUSIC/SPANISH training will include teaching of mnemonic and attentional control strategies, casual videogames selected to train attention, and classes in music or Spanish as a second language. The ENGAGE-DISCOVERY condition will comprise psychoeducation on cognition and the brain, low-stimulating casual videogames and documentary viewing with discussions. To retain the leisure aspect of the activities, participants will be allowed to exclude either music or Spanish at study entry if they strongly dislike one of these activities. Participants randomized to ENGAGE-MUSIC/SPANISH who did not exclude any activity will be assigned to music or Spanish based on a second random assignment. Training will be provided in 24 2-h sessions over 4 months. Outcomes will be measured at baseline, at 4-month follow-up, and at 24-month follow-up. The primary outcome will be cognitive performance on a composite measure of episodic memory (delayed recall scores for words and face-name associations) measured at baseline and at the 4-month follow-up. Secondary outcomes will include a composite measure of attention (speed of processing, inhibition, dual tasking, and shifting), psychological health, activities of daily living, and brain structure and function and long-term maintenance measured at the 24-month follow-up. Information on cognitive reserve proxies (education and lifestyle questionnaires), sex and genotype (apolipoprotein (Apo)E4, brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT)) will be collected and considered as moderators of training efficacy. DISCUSSION: This study will test whether a program combining cognitive training with stimulating leisure activities can increase cognition and reduce cognitive decline in persons at risk of dementia. TRIAL REGISTRATION: NCT03271190 . Registered on 5 September 2017.

An international study of the quality of national-level guidelines on driving with medical illness.

BACKGROUND: Medical illnesses are associated with a modest increase in crash risk, although many individuals with acute or chronic conditions may remain safe to drive, or pose only temporary risks. Despite the extensive use of national guidelines about driving with medical illness, the quality of these guidelines has not been formally appraised. AIM: To systematically evaluate the quality of selected national guidelines about driving with medical illness. DESIGN: A literature search of bibliographic databases and Internet resources was conducted to identify the guidelines, each of which was formally appraised. METHODS: Eighteen physicians or researchers from Canada, Australia, Ireland, USA and UK appraised nine national guidelines, applying the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS: Relative strengths were found in AGREE II scores for the domains of scope and purpose, stakeholder involvement and clarity of presentation. However, all guidelines were given low ratings on rigour of development, applicability and documentation of editorial independence. Overall quality ratings ranged from 2.25 to 5.00 out of 7.00, with modifications recommended for 7 of the guidelines. Intra-class coefficients demonstrated fair to excellent appraiser agreement (0.57-0.79). CONCLUSIONS: This study represents the first systematic evaluation of national-level guidelines for determining medical fitness to drive. There is substantive variability in the quality of these guidelines, and rigour of development was a relative weakness. There is a need for rigorous, empirically derived guidance for physicians and licensing authorities when assessing driving in the medically ill.

Construction of the Patient-Oriented Prostate Utility Scale (PORPUS): a multiattribute health state classification system for prostate cancer.

Health status indexes, such as the EuroQol, consist of a health state classification system and a set of utility weights. Indexes measure quality of life using a 0-1 utility score. Utilities for outcomes in prostate cancer (PC) are of unique importance, but generic indexes do not represent PC outcomes (e.g., sexual, urinary, bowel dysfunction) well, and may not capture their full impact. As a step toward improved utility measurement, we constructed a classification system for PC. We generated items for each of six health domains and rated their importance using interviews with 10 clinical experts and 80 patients. Key concepts were selected for each domain using item importance weightings, and a set of predetermined criteria. Text was developed to express levels of severity within each domain. Experts and two additional groups of patients (n = 40, n = 96) evaluated textual clarity and endorsed the content validity of the instrument. The final system consists of 10 domains with 4-6 levels each. The content validity of the system was endorsed by patients and experts. In conjunction with a set of utility weights, it may be used to develop a health status index, to improve utility measurement in patients, and to serve as a short psychometric (nonutility) instrument.

A randomized trial of a decisional aid for mental capacity assessments.

The objective of this study was to evaluate the clinical utility of a decisional aid for mental capacity assessments which was developed using a group judgment methodology. This was carried out by a randomized, controlled trial. The subjects comprised 64 University of Toronto psychiatry residents in postgraduate years 1 through 4. Residents were randomized to carry out mental capacity assessments on simulated cases with, or without, the use of the decisional aid. The main outcome measure was the extent of agreement between the mental capacity determinations of residents and those of experts. There was no difference between the intervention and control groups with respect to the overall mean level of agreement with experts (0.87 vs 0.86, p = 0.88; 95% confidence interval for the difference between the study groups, -0.07 to +0.08). A logistic regression analysis, which adjusted for imbalances between the groups, also revealed no difference between the groups in their agreement with experts. The mean time per competency assessment was significantly longer in the intervention group (19.1 vs 10.8 min; p < 0.001). It was concluded that the decisional aid did not improve the ability of the psychiatry residents to make mental capacity assessments on simulated cases. Despite relatively limited formal training, the psychiatry residents had a high level of agreement with experts.

Age as a determinant of cardiopulmonary resuscitation outcome in the coronary care unit.

OBJECTIVE: To determine whether age is associated with the outcome of cardiopulmonary resuscitation (CPR) in the coronary care unit (CCU). DESIGN: Retrospective chart review. SETTING: The coronary care units of two Canadian tertiary care teaching hospitals. PATIENTS: Two hundred sixty-four coronary care unit patients undergoing cardiopulmonary resuscitation between January 1, 1985 and June 30, 1992. RESULTS: There was no significant difference in survival to discharge after CPR between patients less than 70 years of age (17.0%) and patients 70 years of age and older (17.2%) (odds ratio = 0.99; 95% confidence interval = 0.46, 1.80). Patients 70 years of age and older who survived to discharge after CPR had significantly greater lengths of stay (28.1 vs 19.3 days, P = .008). CONCLUSIONS: Age was not associated with a difference in survival to discharge after CPR in the CCU, although a clinically significant difference could not be excluded because of limited power.

Tuberculosis surveillance practices in long-term care institutions.

OBJECTIVES: To identify the tuberculosis (TB) skin-testing practices of long-term care facilities for the elderly in Toronto, Ontario. DESIGN: A telephone survey using a 25-item questionnaire. SETTING: Twenty-nine nursing homes (NHs) and 26 Homes for the Aged (HFAs) in metropolitan Toronto. RESULTS: Thirty-one percent of facilities (17 of 55) had no formal tuberculin skin-testing program, including 52% of NHs (15 of 29) versus 8% of HFAs (2 of 26; P = 0.001). Ninety-two percent of HFAs (24 of 26), compared with 45% of NHs (13 of 29), obtained preadmission or admission skin-test status of residents (P = 0.0005). Annual testing was performed at 46% of HFAs (12 of 26) and 27% of NHs (8 of 29; P = 0.28). Of facilities that carried out any skin testing, 64% of HFAs (16 of 25) versus 32% of NHs (6 of 19) measured induration to establish test positivity (P = 0.068). Fifty-two percent of HFAs (13 of 25), compared with 21% of NHs (4 of 19), recorded the actual size of induration in the patient record (P = 0.085). Only 28% of HFAs (7 of 25) and 21% of NHs (4 of 19) correctly defined a positive tuberculin skin test. CONCLUSIONS: TB surveillance practices in long-term care institutions in Toronto are inadequate and often yield results that do not predict the risk of infection and cannot be used to investigate outbreaks. Tuberculin skin-testing practices were better at HFAs, which are subject to provincial legislation regarding TB surveillance, than at NHs, which are not subject to this legislation. Staff at HFAs and NHs require education regarding tuberculin skin-testing policies and procedures.

Do geriatric programs decrease long-term use of acute care beds?

OBJECTIVE: To determine whether the introduction of coordinated geriatric and discharge planning services at teaching and community hospitals in Toronto has changed the number of beds occupied by patients awaiting transfer to long-term care institutions. DESIGN: Retrospective review of social work records for the period 1985-1992. SETTING: Two tertiary and four primary acute care hospitals in Metropolitan Toronto. PARTICIPANTS: Hospitals were matched for location, acuity, and teaching affiliation. MAIN OUTCOME MEASURES: The numbers of beds occupied by patients awaiting transfer to nursing homes or chronic care hospitals were noted. RESULTS: In those teaching and community hospitals that had introduced coordinated geriatric and discharge planning services, there was a reduction in the percentage of beds occupied by patients awaiting long-term care placement (average-51%), whereas in hospitals without geriatric services, the percentage of beds occupied by patients awaiting long-term care placement increased (average + 25%) (P = .05 by Fisher's exact method, 95% confidence limit odds ratio 0, .9999). CONCLUSION: The introduction of coordinated geriatric and discharge planning services was associated with a decrease in the percentage of beds occupied by patients awaiting long-term care in both teaching and community hospitals.

Primer on medical decision analysis: Part 3--Estimating probabilities and utilities.

This paper describes how to estimate probabilities and outcome values for decision trees. Probabilities are usually derived from published studies, but occasionally are derived from existing databases, primary data collection, or expert judgment. Outcome values represent quantitative estimates of the desirability of the outcome states, and are often expressed as utility values between 0 and 1. Utility values for different health states can be derived from the published literature, from direct measurement in appropriate subjects, or from expert opinion. Methods for assigning utilities to complex outcome states are described, and the concept of quality-adjusted life years is introduced.

Primer on medical decision analysis: Part 5--Working with Markov processes.

Clinical decisions often have long-term implications. Analysis encounter difficulties when employing conventional decision-analytic methods to model these scenarios. This occurs because probability and utility variables often change with time and conventional decision trees do not easily capture this dynamic quality. A Markov analysis performed with current computer software programs provides a flexible and convenient means of modeling long-term scenarios. However, novices should be aware of several potential pitfalls when attempting to use these programs. When deciding how to model a given clinical problem, the analyst must weigh the simplicity and clarity of a conventional tree against the fidelity of a Markov analysis. In direct comparisons, both approaches gave the same qualitative answers.

Primer on medical decision analysis: Part 1--Getting started.

This paper is Part 1 of a five-part series covering practical issues in the performance of decision analysis. The intended audience is individuals who are learning how to perform decision analyses, not just read them. The series assumes familiarity with the basic concepts of decision analysis. It imparts many of the recommendations the authors have learned in teaching a one-semester course in decision analysis to graduate students. Part 1 introduces the topic and covers questions such as choosing an appropriate question, determining the tradeoff between accuracy and simplicity, and deciding on a time frame.

Primer on medical decision analysis: Part 2--Building a tree.

This part of a five-part series covering practical issues in the performance of decision analysis outlines the basic strategies for building decision trees. The authors offer six recommendations for building and programming decision trees. Following these six recommendations will facilitate performance of the sensitivity analyses required to achieve two goals. The first is to find modeling or programming errors, a process known as "debugging" the tree. The second is to determine the robustness of the qualitative conclusions drawn from the analysis.

Primer on medical decision analysis: Part 4--Analyzing the model and interpreting the results.

This paper is the fourth of a five-part series that describes the principles of construction and evaluation of valid decision models. In this review, the authors describe the key principles of detecting and eliminating structural and programming errors in decision trees (debugging). In addition, they offer guidelines to facilitate the interpretation of analytic results of decision models.

Guidelines for verbal presentations of medical decision analyses.

Individuals new to decision analysis often have difficulty with oral presentations of original research projects. This article provides general guidelines on how to present effectively. Points include: 1) articulating the research issue, 2) reviewing current beliefs, 3) portraying the study question, 4) listing the main assumptions, 5) presenting the base-case analysis, 6) showing sensitivity analyses, and 7) discussing the implications. The guidelines comment on what to exclude from presentation and how best to handle audience questions. The guidelines do not replace general instruction in public speaking (or rigorous training in decision analysis), but may help students present research projects effectively.

Erythrocyte protoporphyrin levels in patients with Friedreich's and other ataxias.

Of 13 patients with Friedreich's ataxia (Type Ia) and 17 with type IIa recessive ataxias, all were found to have levels of "free erythrocyte protoporphyrin" (FEP) above the normal range. The rise in FEP in Friedreich's ataxia correlated well with the age of the individual and thus appears to be related to the course of the disease. Subjects with olivo-ponto-cerebellar atrophy, Charlevoix syndrome, Duchenne muscular dystrophy, and Parkinson's disease were also found to have significantly elevated FEP, although the distribution overlapped with the normal range. The finding of elevated FEP may indicate a relative heme deficiency in ataxia due to inhibition of ferrochelatase leading to a state of ineffective, persistent erythropoiesis. The possibility of a prostaglandin abnormality being related to this defect and to the pathogenesis of ataxia is considered.

The use of medications for cognitive enhancement.

OBJECTIVE: To provide Canadian physicians and allied health care professionals with the evidence they need to help them make treatment decisions in the management of patients with Alzheimer's disease or other dementias. OPTIONS: The full range and quality of diagnostic and therapeutic modalities available to Canadian physicians for the management of dementia. OUTCOMES: Improvement in the treatment of dementias, leading to reduced suffering, increased functional capacity and decreased economic burden. EVIDENCE AND VALUES: The creation of these evidence-based consensus statements involved literature reviews of the subject by the authors; comparison of alternative clinical pathways and description of the methods whereby published data were analyzed; definition of the level of evidence for data in each case; evaluation and revision in a conference setting (involving primary care physicians, neurologists, psychiatrists, geriatricians, psychologists, consumers and other interested parties); insertion of tables showing key variables and data from various studies and tables of data with recommendations; and reassessment by all authors. BENEFITS, HARMS, AND COSTS: A rational plan for the therapy of dementias is likely to lead to substantial benefits in both human and economic terms. RECOMMENDATIONS: Treatment decisions should be made taking into account the severity or stage of the disease, the availability of caregivers, the presence of disease affecting other bodily systems and the ability of the subject to pay the cost of the medications. Donepezil is considered to have positive effects upon certain tests of neuropsychological function and may produce some improvement in Alzheimer's disease of mild to moderate severity as measured by rating scales. Its ability to improve quality of life remains uncertain. No other drug treatments (apart from symptomatic therapies) are at present approved for the treatment of Alzheimer's disease*. VALIDATION: These recommendations were created by a writing committee, evaluated and revised at a consensus conference and further reviewed and revised by the writing committee prior to publication.

Cluster deaths in long-term care institutions: an investigation of excess deaths in two Ontario institutions.

OBJECTIVE: To review clusters of deaths in two Ontario long-term care institutions and to establish whether common etiologic factors could be identified. METHOD: Retrospective review of the health care records of all residents who died to assess the events leading to death and the actions of the institutions and local coroners in response to the deaths. RESULTS: A respiratory infectious outbreak appeared to lead to many of the deaths in both institutions. Several deficiencies were identified with respect to charting practices, coroners' case investigations and institutional responses to the infectious outbreaks. No formal mechanisms were in place to assist in the early detection of cluster deaths in these institutions. CONCLUSIONS: Infectious outbreaks may be an important cause of cluster deaths in long-term care institutions. Standards should be developed for patient charting, coroners' investigations and for the prevention, identification and management of infectious outbreaks in such settings.

Roles of Education and IQ in Cognitive Reserve in Parkinson's Disease-Mild Cognitive Impairment.

BACKGROUND/AIMS: The role of cognitive reserve in Parkinson's disease (PD)-mild cognitive impairment (MCI) is incompletely understood. METHODS: The relationships between PD-MCI, years of education, and estimated premorbid IQ were examined in 119 consecutive non-demented PD patients using logistic regression models. RESULTS: Higher education and IQ were associated with reduced odds of PD-MCI in univariate analysis. In multivariable analysis, a higher IQ was associated with a significantly decreased odds of PD-MCI, but education was not. CONCLUSION: The association of higher IQ and decreased odds of PD-MCI supports a role for cognitive reserve in PD, but further studies are needed to clarify the interaction of IQ and education and the impact of other contributors such as employment and hobbies.

Levels of sex hormones have limited effect on cognition in older men with or without prostate cancer.

Androgen deprivation therapy is commonly used to treat prostate cancer, but by lowering testosterone levels it may affect cognitive function. However, the relationship between testosterone and cognition remains unclear. We examined the relationship between sex hormones (total testosterone, bioavailable testosterone, and estradiol) and cognition in a cross-sectional study of 198 older men (mean age 69.2 years, median education 16 years) with and without prostate cancer, none of who had started androgen deprivation therapy. We found relationships between total testosterone and two of four measures of working memory. Similar relationships were found in regression analyses adjusted for age and education with both total testosterone and estradiol. Neither hormone was related to other cognitive domains, nor was bioavailable testosterone level. Although cognitive function was not generally related to sex hormone levels in older men, there may be a weak association with working memory. These results may help guide future studies.