Cognitive effects of adjuvant endocrine therapy in older women treated for early-stage breast cancer: a 1-year longitudinal study.

PURPOSE: Evidence suggests endocrine therapy (ET) for breast cancer (BC) has adverse cognitive effects, but its specific effects on older women are unknown. This is despite the fact that older women are at increased risk of both breast cancer (BC) and cognitive decline relative to younger women. This study prospectively examined the cognitive effects of ET in a cohort of older BC patients. Our primary outcome measure was change in verbal memory, the cognitive domain most consistently affected by estrogen deprivation. METHODS: Forty-two chemotherapy-naïve women age 60+, without dementia and recently diagnosed with hormone receptor-positive BC, completed neuropsychological tests at the time of ET initiation and after 1 year of treatment. Change in age-standardized verbal memory performance was examined using paired t tests. To assess a broader range of potential cognitive effects, we also examined changes in visual memory, processing speed, frontal executive function, and perceptual reasoning. RESULTS: Participants exhibited significant decline from baseline to 1 year in verbal memory (p = 0.01). This decline was small to moderate in effect size (d = - 0.40). Performance on other domains did not change significantly over the year (all p > 0.05). CONCLUSIONS: Our findings suggest potentially detrimental effects of ET on verbal memory in older women after just 1 year of treatment. Given that ET is prescribed for courses of 5 to 10 years, additional studies examining longer-term effects of treatment in older women are critical.

Cognitive sequelae of endocrine therapy in women treated for breast cancer: a meta-analysis.

PURPOSE: Evidence suggests anti-estrogen endocrine therapy (ET) is associated with adverse cognitive effects; however, findings are based on small samples and vary in the cognitive abilities affected. We conducted a meta-analysis to quantitatively synthesize the evidence. METHODS: Electronic databases were searched in November 2016. Fourteen studies totaling 911 BC patients on aromatase inhibitors (AIs) or tamoxifen (TAM) and 911 controls (i.e., non-cancer controls and BC controls not using ET) were included. Neuropsychological tests were categorized into six domains. Effect sizes were computed to compare (1) ET patients versus controls and (2) TAM patients versus AI patients. RESULTS: In cross-sectional comparisons, ET patients performed worse than control groups on verbal learning/memory, visual learning/memory, frontal executive function, and processing speed, but did not differ on psychomotor efficiency or visuospatial function. Subgroup analyses revealed that verbal learning/memory was the only domain where ET patients performed worse than both non-cancer and BC controls. In other domains, ET patients and BC controls performed equivalently. Regarding change from pre-treatment performance, ET patients did not differ from controls on any domain. TAM and AI patients did not from one another differ overall; however, subgroup analyses indicated that TAM patients performed better than non-steroidal AI patients on several domains, but showed few performance differences relative to steroidal AI patients. CONCLUSIONS: Verbal learning/memory was the only domain where ET patients performed worse than both non-cancer and BC controls, suggesting specific adverse effects on this domain. Additional studies assessing change from pre-treatment performance and differences between steroidal and non-steroidal AIs are warranted.

A population-based study of ethnicity and breast cancer stage at diagnosis in Ontario.

BACKGROUND: Breast cancer stage at diagnosis is an important predictor of survival. Our goal was to compare breast cancer stage at diagnosis (by American Joint Committee on Cancer criteria) in Chinese and South Asian women with stage at diagnosis in the remaining general population in Ontario. METHODS: We used the Ontario population-based cancer registry to identify all women diagnosed with breast cancer during 2005-2010, and we applied a validated surname algorithm to identify South Asian and Chinese women. We used logistic regression to compare, for Chinese or South Asian women and for the remaining general population, the frequency of diagnoses at stage ii compared with stage i and stages ii-iv compared with stage i. RESULTS: The registry search identified 1304 Chinese women, 705 South Asian women, and 39,287 women in the remaining general population. The Chinese and South Asian populations were younger than the remaining population (mean: 54, 57, and 61 years respectively). Adjusted for age, South Asian women were more often diagnosed with breast cancer at stage ii than at stage i [odds ratio (or): 1.28; 95% confidence interval (ci): 1.08 to 1.51] or at stages ii-iv than at stage i (or: 1.27; 95% ci: 1.08 to 1.48); Chinese women were less likely to be diagnosed at stage ii than at stage i (or: 0.82; 95% ci: 0.72 to 0.92) or at stages ii-iv than at stage i (or: 0.73; 95% ci: 0.65 to 0.82). CONCLUSIONS: Breast cancers were diagnosed at a later stage in South Asian women and at an earlier stage in Chinese women than in the remaining population. A more detailed analysis of ethnocultural factors influencing breast screening uptake, retention, and care-seeking behavior might be needed to help inform and evaluate tailored health promotion activities.

Impact of socio-economic status on breast cancer screening in women with diabetes: a population-based study.

AIMS: There is evidence to suggest that mammography rates are decreased in women with diabetes and in women of lower socio-economic status. Given the strong association between low socio-economic status and diabetes, we explored the extent to which differences in socio-economic status explain lower mammography rates in women with diabetes. METHODS: A population-based retrospective cohort study in Ontario, Canada, of women aged 50 to 69 years with diabetes between 1999 and 2010 age matched 1:2 to women without diabetes. Main outcome measure is the likelihood of at least one screening mammogram in women with diabetes within a 36-month period, starting as of either 1 January 1999, their 50th birthday, or 2 years after diabetes diagnosis--whichever came last. Outcomes were compared with those in women without diabetes during the same period as their matched counterparts, adjusting for socio-economic status based on neighbourhood income and other demographic and clinical variables. RESULTS: Of 504,288 women studied (188,759 with diabetes, 315,529 with no diabetes), 63.8% had a screening mammogram. Women with diabetes were significantly less likely to have a mammogram after adjustment for socio-economic status and other factors (odds ratio 0.79, 95% CI 0.78-0.80). Diabetes was associated with lower mammogram use even in women from the highest socio-economic status quintile (odds ratio 0.79, 95% CI 0.75-0.83). CONCLUSIONS: The presence of diabetes was an independent barrier to breast cancer screening, which was not explained by differences in socio-economic status. Interventions that target patient, provider, and health system factors are needed to improve cancer screening in this population.

Maternal and newborn outcomes among women with schizophrenia: a retrospective population-based cohort study.

OBJECTIVE: More women with schizophrenia are becoming pregnant, such that contemporary data are needed about maternal and newborn outcomes in this potentially vulnerable group. We aimed to quantify maternal and newborn health outcomes among women with schizophrenia. DESIGN: Retrospective cohort study. SETTING: Population based in Ontario, Canada, from 2002 to 2011. POPULATION: Ontario women aged 15-49 years who gave birth to a liveborn or stillborn singleton infant. METHODS: Women with schizophrenia (n = 1391) were identified based on either an inpatient diagnosis or two or more outpatient physician service claims for schizophrenia within 5 years prior to conception. The reference group comprised 432 358 women without diagnosed mental illness within the 5 years preceding conception in the index pregnancy. MAIN OUTCOME MEASURES: The primary maternal outcomes were gestational diabetes mellitus, gestational hypertension, pre-eclampsia/eclampsia, and venous thromboembolism. The primary neonatal outcomes were preterm birth, and small and large birthweight for gestational age (SGA and LGA). Secondary outcomes included additional key perinatal health indicators. RESULTS: Schizophrenia was associated with a higher risk of pre-eclampsia (adjusted odds ratio, aOR 1.84; 95% confidence interval, 95% CI 1.28-2.66), venous thromboembolism (aOR 1.72, 95% CI 1.04-2.85), preterm birth (aOR 1.75, 95% CI 1.46-2.08), SGA (aOR 1.49, 95% CI 1.19-1.86), and LGA (aOR 1.53, 95% CI 1.17-1.99). Women with schizophrenia also required more intensive hospital resources, including operative delivery and admission to a maternal intensive care unit, paralleled by higher neonatal morbidity. CONCLUSIONS: Women with schizophrenia are at higher risk of multiple adverse pregnancy outcomes, paralleled by higher neonatal morbidity. Attention should focus on interventions to reduce the identified health disparities.

Incidence of diabetes among postmenopausal breast cancer survivors.

AIMS/HYPOTHESIS: Evidence is emerging of an association between breast cancer and diabetes; however, it is uncertain whether diabetes incidence is increased in postmenopausal breast cancer survivors compared with women without breast cancer. The objective of this study was to determine whether postmenopausal women who develop breast cancer have a higher incidence of diabetes than those who do not develop breast cancer. METHODS: We used population-based data from Ontario, Canada to compare the incidence of diabetes among women with breast cancer, aged 55 years or older, from 1996 to 2008, with that of age-matched women without breast cancer. We used Cox proportional hazard models to estimate the effect of breast cancer on the cause-specific hazard of developing diabetes overall and in the subgroup of women who received adjuvant chemotherapy. RESULTS: Of 24,976 breast cancer survivors and 124,880 controls, 9.7% developed diabetes over a mean follow-up of 5.8 years. The risk of diabetes among breast cancer survivors compared with women without breast cancer began to increase 2 years after diagnosis (HR 1.07 [95% CI, 1.02, 1.12]), and rose to an HR of 1.21 (95% CI, 1.09, 1.35) after 10 years. Among those who received adjuvant chemotherapy (n = 4,404), risk was highest in the first 2 years after diagnosis (HR 1.24 [95% CI 1.12, 1.38]) and then declined. CONCLUSIONS/INTERPRETATION: We found a modest increase in the incidence of diabetes among postmenopausal breast cancer survivors that varied over time. In most women the risk began to increase 2 years after cancer diagnosis but the highest risk was in the first 2 years in those who received adjuvant therapy. Our study suggests that greater diabetes screening and prevention strategies among breast cancer survivors may be warranted.

Care and outcomes in patients with ischemic stroke with and without preexisting dementia.

OBJECTIVE: To describe clinical characteristics and evaluate processes of care and outcomes at discharge in patients with ischemic stroke with and without preexisting dementia. METHODS: Retrospective cohort study using the Registry of the Canadian Stroke Network including patients presenting with an acute ischemic stroke between 2003 and 2008. Preexisting dementia was defined as any type of dementia that was present prior to the index stroke case. Palliative patients were excluded. Demographic information, clinical presentation, selected process measures (e.g., thrombolysis, admission to stroke unit, carotid imaging, stroke prevention), pneumonia, death, disability, and disposition at discharge were analyzed. RESULTS: Among 9,304 eligible patients with an acute ischemic stroke, 702 (9.1%) had a history of dementia. Patients with dementia were older (mean age 81 vs 70 years; p < 0.001), had more severe strokes (Canadian Neurological Scale score <4, 20.7% vs 10.5%; p < 0.001), and were more likely to have atrial fibrillation (22.8% vs 15.3%; p < 0.001) than those without dementia. Patients with dementia were slightly less likely to be admitted to a stroke unit (63% vs 67.6%; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70-0.96) or to receive thrombolysis (10.5% vs 15.7%; OR 0.63, 95% CI 0.49-0.81). There were no differences in other performance measures. Patients with preexisting dementia had higher disability at discharge (OR 3.20, 95% CI 2.64-3.87) and were less likely to be discharged to their prestroke place of residence (24% vs 45%; p < 0.001). CONCLUSIONS: In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system.

Published randomized controlled trials of drug therapy for dementia often lack complete data on harm.

OBJECTIVE: The objective of the study was to determine the extent to which published randomized controlled trials (RCTs) report data on harm. STUDY DESIGN AND SETTING: A systematic search strategy was used to identify RCTs published between 1996 and 2005 on the use of cholinesterase inhibitors or atypical antipsychotics in patients with dementia. A structured abstraction form was used to determine if data on mortality or serious adverse events were reported and if the articles followed Consolidated Standards of Reporting Trials format for reporting harm. RESULTS: Thirty-three RCTs were identified (27 on cholinesterase inhibitors and 6 on atypical antipsychotics). Nineteen trials (58%) had explicit data on mortality and only four (12%) reported regulatory-agency-defined serious adverse events. Most abstracts (31, 94%) stated that harm was studied but few studies (9, 27%) provided a clear definition of the measures of harm. CONCLUSIONS: Although most published RCTs state that they examine harm, many failed to provide data on mortality and most lacked clear definitions or detailed analyses of harm. Better reporting of harm would provide timely and important information that could help physicians and the public to make more informed decisions.

Readers should systematically assess methods used to identify, measure and analyze confounding in observational cohort studies.

OBJECTIVE: To describe techniques used to address confounding in published observational studies. STUDY DESIGN AND SETTING: A systematic literature review identified studies using administrative or registry data to investigate health effects of drug therapies. Studies published from January 2001 to December 2005 came from BMJ, New England Journal of Medicine, Lancet, Annals of Internal Medicine, and JAMA. A structured abstraction form was used to collect information about confounding. RESULTS: The search identified 29 studies. Twenty-two studies (76%) had 10,000 or more subjects and 18 (62%) used a mortality outcome. None mentioned use of a literature search to identify confounders, however, 28 (97%) listed confounders included, and 26 (90%) listed confounders not included in the study. Eighteen (62.1%) discussed the validity of confounder data. Most (22, or 76%) studies included a table with the distribution of confounders but none used effect size to assess imbalance between comparison groups. Almost all studies used regression techniques (28, or 97%); fewer used stratification (16, or 55%) or matching (four, or 14%) to address confounding. Eleven (40%) studies discussed sensitivity analyses. CONCLUSION: Published cohort studies routinely include a list of potential confounders but there is room for improvement in confounder identification, measurement, and analysis.

Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort.

OBJECTIVE: To investigate predictors of survival in Parkinson disease (PD). METHODS: Vital status was determined in 800 subjects enrolled in a clinical trial of deprenyl (selegiline) and tocopherol 13 years earlier. RESULTS: Two hundred ninety-six deaths were recorded. There was no difference in the standardized mortality ratios across gender or age group. In univariate analyses, PD-specific variables associated with mortality were increased symmetry of parkinsonism, gait dysfunction as an initial symptom, severity of parkinsonism, and rate of worsening of parkinsonism prior to study enrollment. Cumulative exposure to deprenyl was not associated with mortality. In multivariable analysis, severity of parkinsonism and rate of worsening of parkinsonism remained associated with mortality. A poorer response to levodopa was associated with increased mortality independent of disease severity or dosage of levodopa. Results were unchanged when the analysis was restricted to 747 subjects maintaining a most likely diagnosis of PD throughout 6 years of active follow-up. CONCLUSIONS: Parkinson disease did not affect survival differently across gender or age groups in this selected group of otherwise healthy clinical trial participants. Severity and rate of worsening of parkinsonism and response to levodopa are strongly related to survival.

Increased risk of somnolence with the new dopamine agonists in patients with Parkinson's disease: a meta-analysis of randomised controlled trials.

BACKGROUND: Recent case reports and letters have alerted practitioners to the risk of sleep attacks, usually preceded by somnolence, in patients with Parkinson's disease treated with pramipexole and ropinirole. OBJECTIVE: To quantify the risk of somnolence with the new dopamine agonists pramipexole and ropinirole in patients with Parkinson's disease. METHODS: We searched MEDLINE, EMBASE, International Pharmaceutical Abstracts and Cochrane Library, contacted experts and pharmaceutical manufacturers, and manually reviewed all references retrieved to identify possible articles to include. Information on randomisation, blinding, type of treatment and reporting of somnolence were abstracted by 2 independent reviewers. Disagreements were resolved by a third author. ANALYSIS: We made 2 separate analyses. The first analysis compared the risk of somnolence in patients taking either pramipexole or ropinirole to that in patients taking placebo. The second analysis compared the risk of somnolence with these drugs (plus levodopa) versus that with levodopa alone. We calculated pooled relative risk estimates using the random effects model and when no heterogeneity was detected we used the fixed effects model. RESULTS: Four trials were included in the analysis of patients taking pramipexole or ropinirole compared with those taking placebo. The pooled relative risk of somnolence in this analysis was 4.98 [95% confidence interval (CI) 1.79 to 13.89]. Seven trials were included in the analysis of patients taking levodopa and pramipexole or ropinirole compared with those taking levodopa alone. The pooled relative risk was 2.06 (95% CI 1.47 to 2.88). CONCLUSION: Patients with Parkinson's disease using pramipexole or ropinirole are at higher risk of experiencing somnolence relative to patients taking placebo. Patients taking levodopa plus either one of these dopamine agonists are at higher risk than those taking levodopa alone. Clinicians should carefully weigh this risk against the benefit of these agents when prescribing these drugs.

Herbal-drug therapy interactions: a focus on dementia.

Older people with dementia are often prescribed numerous medications. Use of herbal therapies in addition to these conventional drug therapies may lead to interactions that result in an adverse drug event. We have conducted a systematic review to identify all studies that examined interactions between herbal and conventional drug therapies (i.e. prescription or over-the-counter). Using a MEDLINE search of English-language studies published between 1980 and 2000, we limited our search to those herbal therapies most likely to be used for the treatment of dementia (memory loss and decreased concentration) and related symptoms. We identified 28 articles that describe interactions between these herbal (i.e. St. John's wort, ginkgo biloba, kava, valerian, and ginseng) and conventional drug therapies. Of these articles, 11 examined St. John's wort, four examined ginkgo biloba, five examined kava, one examined valerian, and seven examined ginseng. We identified a series of potential interactions between herbal and conventional drug therapy that place older people at risk for an adverse drug event. Health care professionals need to be aware of these potential interactions.

Rate of heart failure and 1-year survival for older people receiving low-dose beta-blocker therapy after myocardial infarction.

BACKGROUND: Many older people do not receive beta-blocker therapy after myocardial infarction or receive doses lower than those tested in trials, perhaps because physicians fear that beta-blockers may precipitate heart failure. We examined the relation between use of beta-blockers, the dose used, and hospital admission for heart failure and 1-year survival in a cohort of all older patients surviving myocardial infarction in Ontario, Canada. METHODS: We collected data on a cohort of 13,623 patients aged 66 years or older who were discharged from hospital after a myocardial infarction and who did not receive beta-blocker therapy or received low, standard, or high doses. We used Cox's proportional-hazards models to study the association of dose with admission for heart failure and survival with adjustment for factors including age, sex, and comorbidity. FINDINGS: Among 8232 patients with no previous history of heart failure, dispensing of beta-blocker therapy was associated with a 43% reduction in subsequent admission for heart failure (adjusted risk ratio 0.57 [95% CI 0.48-0.69]) compared with patients not dispensed this therapy. Among the 4681 patients prescribed beta-blockers, the risk of admission was greater in the high-dose than in the low-dose group (1.53 [1.01-2.31]). Among all 13,623 patients in the cohort, 2326 (17.1%) died by 1 year. Compared with those not dispensed beta-blocker therapy, the adjusted risk ratio for mortality was lower for all three doses (low 0.40 [0.34-0.47], standard 0.36 [0.31-0.42], high 0.43 [0.33-0.56]). INTERPRETATION: Compared with high-dose beta-blocker therapy, low-dose treatment is associated with a lower rate of hospital admission for heart failure and has a similar 1-year survival benefit. Our findings support the need for a randomised controlled trial comparing doses of beta-blocker therapy in elderly patients.

Subcutaneous fluid infusion in a long-term care setting.

OBJECTIVE: To study the use of hypodermoclysis in a long-term care setting for chronic fluid supplementation and to compare it to intravenous (IV) fluid in the treatment of acute mild to moderate dehydration. DESIGN: A prospective observational study. PARTICIPANTS: Fifty-five residents of a long-term care facility treated with fluid therapy during a 5-week period. MAIN OUTCOME MEASURES: Efficacy of hydration and adverse effects were obtained from detailed chart review, interviews with healthcare providers, and investigators' observations. RESULTS: The study subjects were frail older people. Hypodermoclysis was used for maintenance fluid needs in 24 residents; none of these residents required any additional fluid therapy for dehydration. In addition, 37 residents received fluids for acute dehydration. In these residents, hypodermoclysis was associated with clinical improvement in 57% and no clinical change in 25%. Recipients of IV fluids improved 81% of the time and the remainder were unchanged. Hypodermoclysis was associated with fewer fluid therapy-related complications relative to IV therapy (P = .04). CONCLUSIONS: Hypodermoclysis is an effective procedure for providing fluids for both chronic maintenance needs and acute situations associated with mild to moderate dehydration in a long-term care setting. Hypodermoclysis appears safer and can avoid transfers to hospital for rehydration.

The prevalence of low back pain in the elderly. A systematic review of the literature.

STUDY DESIGN: The prevalence of low back pain in the older population (> = or 65 years) was reviewed in an analysis of the literature from 1966 to the present. OBJECTIVE: To determine the prevalence of low back pain in the geriatric population. SUMMARY OF BACKGROUND DATA: Back pain is one of the most frequently reported conditions affecting the adult population. However, the prevalence of low back pain in the older age population is not accurately known. METHODS: A methodologic search of five computerized bibliographic databases was performed to identify citations on the prevalence of low back pain in the elderly. Data were summarized, and prevalence studies were critically appraised in detail for their quality. RESULTS: There is wide variability in the reported prevalence of back pain. Many factors have been proposed to explain these findings including sample source, study design, definitions of back pain, and use of patient-reported data. Comorbidity among older patients also contributes to the variability in the reporting of prevalence of back pain. CONCLUSION: There is an under-representation of the older population in the back pain literature. The data in the current study suggest that the prevalence of low back pain in this population is not known with certainty and is not comparable with that in the younger population. The authors stress the need for future studies to improve the reporting of age information to make prevalence studies more informative and applicable.

Age- and gender-related use of low-dose drug therapy: the need to manufacture low-dose therapy and evaluate the minimum effective dose.

OBJECTIVES: Low-dose drug therapy is promoted as a way to maximize benefit and minimize adverse drug effects when prescribing for older adults. This population-based study evaluates the age and sex-related use of two common therapies: thiazide diuretics, where evidence supports the use of low-dose therapy, and beta-blockers, where trials have not evaluated the minimum effective dose. DESIGN: Using linked administrative databases we identified all of the 120,613 persons dispensed a thiazide diuretic therapy and 12,908 myocardial infarction survivors dispensed beta-blocker therapy in Canada's largest province. We used logistic regression models to study the association of age and sex with dispensing of low-dose thiazide diuretic and beta-blocker therapy at doses lower than evaluated in trials. RESULTS: Of 120,613 older people dispensed a thiazide diuretic, 32,372 (26.8%) were dispensed a low dose. Patients 85 years of age or older, relative to the youngest group, were 30% more likely to be dispensed low-dose therapy (OR=1.31; 95% CI, 1.27 to 1.36; P < .001). Women were 8% more likely than men to be dispensed a low-dose thiazide diuretic (OR=1.08; 95% CI, 1.05 to 1.11; P < .001). Of 10,991 myocardial infarction survivors dispensed atenolol, metoprolol, propranolol, or timolol, 9458 (86.1%) were dispensed a lower-than-evaluated dose. Patients 85 years of age or older, relative to those in the youngest group, were more than twice as likely to be dispensed a lower-than-evaluated beta-blocker therapy dose (OR=2.28; 95% CI, 1.74 to 3.04; P < .001). No difference was noted in the use of beta-blocker therapy dose by sex (OR=1.0; 95% CI, .89 to 1.15; P = .95). CONCLUSIONS: Low-dose thiazide diuretic therapy prescribed widely to older people, particularly those of advanced age and women. The vast majority of myocardial infarction survivors were dispensed beta-blocker therapy at lower-than-evaluated doses. These findings highlight the need to manufacture low-dose thiazide diuretic therapy and to evaluate the minimum effective dose of beta-blocker therapy.