Shabbir M.H. Alibhai

Impact of Androgen Deprivation Therapy on Cardiovascular Disease and Diabetes

PURPOSE Use of androgen deprivation therapy (ADT) may be associated with an increased risk of diabetes mellitus but the risk of both acute myocardial infarction (AMI) and cardiovascular mortality remain controversial because few outcomes and conflicting findings have been reported. We sought to clarify whether ADT is associated with these outcomes in a large, representative cohort. METHODS Using linked administrative databases in Ontario, Canada, men age 66 years or older with prostate cancer given continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 19,079) were matched with men with prostate cancer who had never received ADT. Treated and untreated groups were matched 1:1 (ie, hard-matched) on age, prior cancer treatment, and year of diagnosis and propensity-matched on comorbidities, medications, cardiovascular risk factors, prior fractures, and socioeconomic variables. Primary outcomes were development of AMI, sudden cardiac death, and diabetes. Fragility fracture was also examined. Results The cohort was observed for a mean of 6.47 years. In time-to-event analyses, ADT use was associated with an increased risk of diabetes (hazard ratio [HR], 1.16; 95% CI, 1.11 to 1.21) and fragility fracture (HR, 1.65; 95% CI, 1.53 to 1.77) but not with AMI (HR, 0.91; 95% CI, 0.84 to 1.00) or sudden cardiac death (HR, 0.96; 95% CI, 0.83 to 1.10). Increasing duration of ADT was associated with an excess risk of fragility fractures and diabetes but not cardiac outcomes. CONCLUSION Continuous ADT use for at least 6 months in older men is associated with an increased risk of diabetes and fragility fracture but not AMI or sudden cardiac death.

Medication Reconciliation at Hospital Discharge: Evaluating Discrepancies

Background: Hospital discharge is an interlace of care when patients are at a high risk of medication discrepancies as they transition from hospital to home. These discrepancies are important, as they may contribute to drug-related problems, medication errors, and adverse drug events. Objective: To Identify, characterize, and assess the clinical impact of unintentional medication discrepancies at hospital discharge. Methods: All consecutive general internal medicine patients admitted for at least 72 hours to a tertiary care teaching hospital were prospectively assessed. Patients were excluded if they were discharged with verbal prescriptions; died during hospitalization; or transferred from or to a nursing home, another institution, or another unit within the same hospital. The primary endpoint was to determine the number of patients with at least one unintended medication discrepancy on hospital discharge. Medication discrepancies were assessed through comparison of a best possible medication discharge list with the actual discharge prescriptions. Secondary objectives were to characterize and assess the potential clinical impact of the unintentional discrepancies. Results: From March 14,2006, to June 2,2006,430 patients were screened for eligibility; 150 patients were included in the study. Overall, 106 (70.7%) patients had at least one actual or potential unintentional discrepancy. Sixty-two patients (41.3%) had at least one actual unintentional medication discrepancy al hospital discharge and 83 patients (55.3%) had at least one potential unintentional discrepancy. The most common unintentional discrepancies were an incomplete prescription requiring clarification, which could result in a patient delay in obtaining medications (49.5%), and the omission of medications (22.9%). Of the 105 unintentional discrepancies, 31 (29.5%) had the potential to cause possible or probable patient discomfort and/or clinical deterioration. Conclusions: Medication discrepancies occur commonly on hospital discharge. Understanding the type and frequency of discrepancies can help clinicians better understand ways to prevent them. Structured medication reconciliation may help to prevent discharge medication discrepancies.

Adverse Effects of Androgen Deprivation Therapy and Strategies to Mitigate Them

CONTEXT Androgen-deprivation therapy (ADT) is a key component of treatment for aggressive and advanced prostate cancer, but it has also been associated with adverse effects on bone, metabolic, cardiovascular, sexual, and cognitive health as well as body composition. OBJECTIVE To review the current literature on the adverse effects of ADT and strategies for ameliorating harm from ADT. EVIDENCE ACQUISITION The Medline database (through PubMed) was searched from inception to August 1, 2013, for studies documenting the side effects of ADT and for randomized and prospective trials of interventions to mitigate those side effects. EVIDENCE SYNTHESIS Adverse effects of ADT include decreases in bone mineral density; metabolic changes such as weight gain, decreased muscle mass, and increased insulin resistance; decreased libido and sexual dysfunction; hot flashes; gynecomastia; reduced testicle size; anemia; and fatigue. Several observational studies suggest an increased risk of diabetes and cardiovascular events, although most published studies report that ADT is not linked to greater cardiovascular mortality. Randomized trials have found value in treatments for some adverse effects including bone loss (bisphosphonates, denosumab, selective estrogen receptor modulators), markers of metabolic syndrome (exercise, diet, metformin), gynecomastia (tamoxifen, prophylactic radiation), muscle loss (resistance and aerobic exercise), and hot flashes (venlafaxine, medroxyprogesterone, cyproterone acetate, gabapentin). CONCLUSIONS ADT is often a necessary component of the treatment of aggressive prostate cancer, yet it has known harms that can impair health and quality of life. Clinicians should be aware of interventions that can help mitigate these adverse effects. PATIENT SUMMARY Androgen deprivation therapy is a critical component of the management of aggressive and advanced prostate cancer, but it causes adverse effects including bone loss, metabolic changes, gynecomastia, muscle loss, hot flashes, and possibly increased cardiovascular events. Clinicians should be aware of interventions that can help mitigate these adverse effects.

Use of Geriatric Assessment for Older Adults in the Oncology Setting: A Systematic Review

Background Geriatric assessment is a multidisciplinary diagnostic process that evaluates the older adult’s medical, psychological, social, and functional capacity. No systematic review of the use of geriatric assessment in oncology has been conducted. The goals of this systematic review were: 1) to provide an overview of all geriatric assessment instruments used in the oncology setting; 2) to examine the feasibility and psychometric properties of those instruments; and 3) to systematically evaluate the effectiveness of geriatric assessment in predicting or modifying outcomes (including the impact on treatment decision making, toxicity of treatment, and mortality). Methods We searched Medline, Embase, Psychinfo, Cinahl, and the Cochrane Library for articles published in English, French, Dutch, or German between January 1, 1996, and November 16, 2010, reporting on cross-sectional, longitudinal, interventional, or observational studies that assessed the feasibility or effectiveness of geriatric assessment instruments. The quality of articles was evaluated using relevant quality assessment frameworks. Results We identified 83 articles that reported on 73 studies. The quality of most studies was poor to moderate. Eleven studies examined psychometric properties or diagnostic accuracy of the geriatric assessment instruments used. The assessment generally took 10–45min. Geriatric assessment was most often completed to describe a patient’s health and functional status. Specific domains of geriatric assessment were associated with treatment toxicity in 6 of 9 studies and with mortality in 8 of 16 studies. Of the four studies that examined the impact of geriatric assessment on the cancer treatment decision, two found that geriatric assessment impacted 40%–50% of treatment decisions. Conclusion Geriatric assessment in the oncology setting is feasible, and some domains are associated with adverse outcomes. However, there is limited evidence that geriatric assessment impacted treatment decision making. Further research examining the effectiveness of geriatric assessment on treatment decisions and outcomes is needed.

An approach to the management of unintentional weight loss in elderly people

UNINTENTIONAL WEIGHT LOSS, or the involuntary decline in total body weight over time, is common among elderly people who live at home. Weight loss in elderly people can have a deleterious effect on the ability to function and on quality of life and is associated with an increase in mortality over a 12-month period. A variety of physical, psychological and social conditions, along with age-related changes, can lead to weight loss, but there may be no identifiable cause in up to one-quarter of patients. We review the incidence and prevalence of weight loss in elderly patients, its impact on morbidity and mortality, the common causes of unintentional weight loss and a clinical approach to diagnosis. Screening tools to detect malnutrition are highlighted, and nonpharmacologic and pharmacologic strategies to minimize or reverse weight loss in older adults are discussed.

Do Older Men Benefit From Curative Therapy of Localized Prostate Cancer

PURPOSE Prior decision-analytic models are based on outdated or suboptimal efficacy, patient preference, and comorbidity data. We estimated life expectancy (LE) and quality-adjusted life expectancy (QALE) associated with available treatments for localized prostate cancer in men aged >/= 65 years, adjusting for Gleason score, patient preferences, and comorbidity. METHODS We evaluated three treatments, using a decision-analytic Markov model: radical prostatectomy (RP), external beam radiotherapy (EBRT), and watchful waiting (WW). Rates of treatment complications and pretreatment incontinence and impotence were derived from published studies. We estimated treatment efficacy using three data sources: cancer registry cohort data, pooled case series, and modern radiotherapy studies. Utilities were obtained from 141 prostate cancer patients and from published studies. RESULTS For men with well-differentiated tumors and few comorbidities, potentially curative therapy (RP or EBRT) prolonged LE up to age 75 years but did not improve QALE at any age. For moderately differentiated cancers, potentially curative therapy resulted in LE and QALE gains up to age 75 years. For poorly differentiated disease, potentially curative therapy resulted in LE and QALE gains up to age 80 years. Benefits of potentially curative therapy were restricted to men with no worse than mild comorbidity. When cohort and pooled case series data were used, RP was preferred over EBRT in all groups but was comparable to modern radiotherapy. CONCLUSION Potentially curative therapy results in significantly improved LE and QALE for older men with few comorbidities and moderately or poorly differentiated localized prostate cancer. Age should not be a barrier to treatment in this group.

Comparison of Health-Related Quality of Life 5 Years After SPIRIT: Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial

PURPOSE The American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial comparing radical prostatectomy (RP) and brachytherapy (BT) closed after 2 years due to poor accrual. We report health-related quality of life (HRQOL) at a mean of 5.3 years for 168 trial-eligible men who either chose or were randomly assigned to RP or BT following a multidisciplinary educational session. PATIENTS AND METHODS After initial lack of accrual, a multidisciplinary educational session was introduced for eligible patients. In all, 263 men attended 47 sessions. Of those, 34 consented to random assignment, 62 chose RP, and 94 chose BT. Five years later, these 190 men underwent HRQOL evaluation by using the cancer-specific 50-item Expanded Prostate Cancer Index Composite, the Short Form 12 Physical Component Score, and Short Form 12 Mental Component Score. Response rate was 88.4%. The Wilcoxon rank sum test was used to compare summary scores between the two interventions. RESULTS Of 168 survey responders, 60.7% had BT (9.5% randomly assigned) and 39.3% had RP (9.5% randomly assigned). Median age was 61.4 years for BT and 59.4 for RP (P = .05). Median follow-up was 5.2 years (range, 3.2 to 6.5 years). For BT versus RP, there was no difference in bowel or hormonal domains, but men treated with BT scored better in urinary (91.8 v 88.1; P = .02) and sexual (52.5 v 39.2; P = .001) domains, and in patient satisfaction (93.6 v 76.9; P < .001). CONCLUSION Although treatment allocation was random in only 19%, all patients received identical information in a multidisciplinary setting before selecting RP, BT, or random assignment. HRQOL evaluated 3.2 to 6.5 years after treatment showed an advantage for BT in urinary and sexual domains and in patient satisfaction.

The effect of English language proficiency on length of stay and in-hospital mortality

AbstractBACKGROUND: In ambulatory care settings, patients with limited English proficiency receive lower quality of care. Limited information is available describing outcomes for inpatients. OBJECTIVE: To investigate the effect of English proficiency on length of stay (LOS) and in-hospital mortality. DESIGN: Retrospective analysis of administrative data at 3 tertiary care teaching hospitals (University Health Network) in Toronto, Canada. PARTICIPANTS: Consecutive inpatient admissions from April 1993 to December 1999 were analyzed for LOS differences first by looking at 23 medical and surgical conditions (59,547 records) and then by a meta-analysis of 220 case mix groups (189,119 records). We performed a similar analysis for in-hospital mortality. MEASUREMENTS: LOS and odds of in-hospital death for limited English-proficient (LEP) patients relative to English-proficient (EP) patients. RESULTS: LEP patients stayed in hospital longer for 7 of 23 conditions (unstable coronary syndromes and chest pain, coronary artery bypass grafting, stroke, craniotomy procedures, diabetes mellitus, major intestinal and rectal procedures, and elective hip replacement), with LOS differences ranging from approximately 0.7 to 4.3 days. A meta-analysis using all admission data demonstrated that LEP patients stayed 6% (approximately 0.5 days) longer overall than EP patients (95% confidence interval, 0.04 to 0.07). LEP patients were not at increased risk of in-hospital death (relative odds, 1.0; 95% confidence interval, 0.9 to 1.1). CONCLUSIONS: Patients with limited English proficiency have longer hospital stays for some medical and surgical conditions. Limited English proficiency does not affect in-hospital mortality. The effect of communication barriers on outcomes of care in the inpatient setting requires further exploration, particularly for selected conditions in which length of stay is significantly prolonged.

An update on a systematic review of the use of geriatric assessment for older adults in oncology

BACKGROUND Our previous systematic review of geriatric assessment (GA) in oncology included a literature search up to November 2010. However, the quickly evolving field warranted an update. Aims of this review: (i) provide an overview of all GA instruments developed and/or in use in the oncology setting; (ii) evaluate effectiveness of GA in predicting/modifying outcomes (e.g. treatment decision impact, treatment toxicity, mortality, use of care). MATERIALS AND METHODS Systematic review of literature published between November 2010 and 10 August 2012. English, Dutch, French and German-language articles reporting cross-sectional or longitudinal, intervention or observational studies of GA instruments were included. DATA SOURCES MEDLINE, EMBASE, PsycINFO, CINAHL and Cochrane Library. Two researchers independently reviewed abstracts, abstracted data and assessed the quality using standardized forms. A meta-analysis method of combining proportions was used for the outcome impact of GA on treatment modification with studies included in this update combined with those included in our previous systematic review on the use of GA. RESULTS Thirty-five manuscripts reporting 34 studies were identified. Quality of most studies was moderate to good. Eighteen studies were prospective, 11 cross-sectional and 5 retrospective. Three studies examined treatment decision-making impact and found decisions changed for fewer than half of assessed patients (weighted percent modification is 23.2% with 95% confidence interval (20.3% to 26.1%). Seven studies reported conflicting findings regarding predictive ability of GA for treatment toxicity/complications. Eleven studies examined GA predictions of mortality, and reported that instrumental activities of daily living, poor performance status and more numerous GA deficits were associated with increased mortality risk. Other outcomes could not be meta-analyzed. CONCLUSION Consistent with our previous review, several domains of GA are associated with adverse outcomes. However, further research examining effectiveness of GA on treatment decisions and oncologic outcomes is needed.

Impact of Androgen-Deprivation Therapy on Physical Function and Quality of Life in Men With Nonmetastatic Prostate Cancer

PURPOSE This prospective longitudinal study evaluated the effect of androgen deprivation therapy (ADT) on objective and self-reported physical function. PATIENTS AND METHODS Men with nonmetastatic prostate cancer (PC) starting continuous ADT were enrolled in this matched cohort study. Physical function was assessed with the 6-minute walk test (6MWT), grip strength, and the timed-up-and-go (TUG) test, representing endurance and upper and lower extremity strength, respectively. Quality of life (QOL) was measured with the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire. Subjects were assessed at baseline, 3, 6, and 12 months. Two control groups (PC without ADT; no PC), matched on age, education, and baseline function were enrolled. Mixed effects regression models were fitted, adjusting for baseline covariates. RESULTS We enrolled 87 patients on ADT, 86 PC controls, and 86 healthy controls; groups were similar in age (mean, 69.1 years; range, 50 to 87) and physical function. The 6MWT distance remained stable in the ADT group (P = .96) but improved in both control groups (P < .05). Grip strength declined in the ADT group (P = .04), remained stable in PC controls (P = .31), and improved in healthy controls (P = .008). TUG scores remained stable over time and across groups (P > .10). The SF-36 physical function summary score declined in the ADT group (P < .001), but increased in both control groups (P < .001). Negative effects on outcomes were observed within 3 months of starting ADT and were generally independent of age. CONCLUSION Endurance, upper extremity strength, and physical components of QOL are affected within 3 months of starting ADT. Up-front exercise interventions to counteract these losses are warranted.