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.

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.

Reporting of age data in clinical trials of arthritis. Deficiencies and solutions.

OBJECTIVE: We studied recent nonsteroidal anti-inflammatory drug (NSAID) randomized control trials of arthritis to identify the age and number of older people (> or = 65 years) and to document the way information on age was presented. We hypothesized that older people, who are most likely to take NSAIDs are underrepresented and underreported. STUDY SELECTION AND DATA EXTRACTION: All NSAID articles (n = 1008) in MEDLINE between September 1987 and May 1990 were identified. Eighty-three trials employing NSAIDs in a randomized control trial of arthritis reported in 73 articles were identified and studied in detail for age-related information. RESULTS: A total of 9664 subjects with a female-to-male ratio of 2.3:1 were enrolled. Forty-four trials studied osteoarthritis (53.0%), 37 studied rheumatoid arthritis (44.6%), and two studied both conditions (2.4%). More than half of the studies reviewed included people 65 years of age or older, only 207 people in this older age group could be identified (2.1%). While there was inclusion of the 'young-old' (65 to 74 years of age), only 14 of the 9664 people studied were between 75 and 84 years of age, and no one 85 years or older could be identified. The inclusion of the young-old is documented by the weighted mean age that ranged from 59.6 to 64.9 years for patients with osteoarthritis (mean, 62.9; SD, 1.67) and from 47.4 to 53.0 years (mean, 49.9; SD, 2.16) for those with rheumatoid arthritis. CONCLUSION: We demonstrate that older people, who represent a high proportion of the population treated with NSAIDs in practice, are generally omitted from drug trials. Recommendations designed to improve the reporting of age information to make clinical trials more informative and applicable to older people are presented.

Atrial fibrillation and stroke prevention with warfarin in the long-term care setting.

BACKGROUND: While the benefits of warfarin sodium therapy for stroke prevention in patients with atrial fibrillation (AF) have been extensively documented, generalizing clinical trial results to the majority of elderly persons with AF, especially to those who reside in the long-term care setting, remains challenging. OBJECTIVES: To determine the prevalence of AF in the institutionalized elderly population and the proportion receiving anticoagulation therapy with warfarin: to identify the clinical and functional characteristics of institutionalized elderly persons with AF that are associated with the use of warfarin; and to assess the quality of prescribing and monitoring of warfarin therapy in institutionalized elderly persons with AF. METHODS: This study involved 30 long-term care facilities (total No. of beds, 6437) located in New England, Quebec, and Ontario. The proportion of patients with AF who were receiving treatment with warfarin was determined. The association between clinical and functional characteristics and the use of warfarin was examined with crude and multivariable-adjusted analyses. For study subjects with at least 2 weeks of warfarin therapy during the 12-month period preceding the date of medical record abstraction, we assessed the quality of warfarin prescribing based on all international normalized ratio or prothrombin time ratio values during this period. RESULTS: An electrocardiogram indicating AF was present in the records of 413 of 5500 long-term care residents (7.5%); 32% of such patients were being treated with warfarin. Only a history of stroke was found to be positively associated with the use of warfarin in this setting. Patients with a diagnosis of dementia and those in the oldest age group (> or = 85 years) were less likely to receive warfarin therapy. Warfarin was commonly prescribed to patients with a history of bleeding, substantial comorbidity and functional impairment, a history of falls, or concomitant potentiating drug therapy. Patients were maintained above or below the recommended therapeutic range 60% of the time. CONCLUSIONS: Atrial fibrillation is common in patients residing in long-term care facilities, but its management with warfarin is highly variable. A more systematic approach to decision making regarding the use of warfarin for stroke prevention in these patients is required. Among patients receiving warfarin, the quality of anticoagulation care warrants improvement.

A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis.

BACKGROUND: To study the relation between reported drug performance in published trials and support of the trials by the manufacturer of the drug under evaluation, we studied a sample of trials of nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of arthritis. METHODS: All randomized control trials of NSAIDs published between September 1987 and May 1990 identified by MEDLINE were reviewed. If an article met the following criteria (n = 61), it was selected: trials involving adult patients with osteoarthritis or rheumatoid arthritis (n = 180), use of nonsalicylate NSAIDs marketed in the United States (n = 101), randomized control trial (n = 81), duration of the trial 4 or more days (n = 78), and use of an efficacy outcome measure (n = 61). Reviewers, "blinded" to manufacturer status, evaluated the narrative interpretation of results and extracted numeric data on efficacy and toxicity. Manufacturer-associated trials were defined as those that acknowledged an association with a pharmaceutical manufacturer. Because of the scarcity of non-manufacturer-associated trials (n = 9), we report only on the manufacturer-associated articles. RESULTS: Fifty-two publications (85.2%) representing 56 trials were associated with a manufacturer. The manufacturer-associated drug was reported as comparable with (71.4%) or superior to (28.6%) the comparison drug in all 56 trials. These narrative claims of superiority were usually justified with trial data. Of the trials identifying one drug as less toxic (n = 22), the manufacturer-associated drug's safety was reported as superior to the comparison drug in 86.4% of cases. Justification for the narrative interpretation of the trial findings regarding less toxicity was provided in only 12 (54.5%) of 22 trials. CONCLUSION: The manufacturer-associated NSAID is almost always reported as being equal or superior in efficacy and toxicity to the comparison drug. These claims of superiority, especially in regard to side effect profiles, are often not supported by trial data. These data raise concerns about selective publication or biased interpretation of results in manufacturer-associated trials.

Are randomized control trial outcomes influenced by the inclusion of a placebo group?: a systematic review of nonsteroidal antiinflammatory drug trials for arthritis treatment.

Placebo groups are often included in randomized control trials evaluating drug therapy, yet we know little about the placebo effect. The purpose of our study was to evaluate how the presence of a placebo group in a randomized control trial (RCT) influences the patients' ratings of the efficacy of an active drug therapy and their reporting of its adverse effects. We identified studies published between 1966 and 1994 using MEDLINE. Randomized control trials evaluating acetylsalicylic acid, diclofenac, or indomethacin for the treatment of osteo or rheumatoid arthritis were included in our sample. Two investigators independently extracted data. Fifty-eight treatment arms met our inclusion criteria and were available for analysis. Twenty-five treatment arms evaluated a nonsteroidal antiinflammatory drug (NSAID) in placebo control trials and 33 in comparative trials. Using a logistic regression model to adjust for the differences between the evaluated drugs and between the types of arthritis, we found that patients receiving an NSAID in a placebo control trial were more likely to withdraw due to inefficacy (OR=1.3; 95% CI, 1.0 to 1.6; P=0.04). Using a similar model, withdrawals due to adverse effects were found to be more common when the NSAID was given in trials that did not include a placebo group (OR=1.5; 95% CI, 1.1 to 1.9; P=0.002) as were reports of cutaneous (OR=4.2; 95% CI, 1.7 to 9.9), gastrointestinal (OR=1.6; 95% CI, 1.3 to 2.0), and other types (OR=5.3; 95% CI, 3.8 to 7.4) of adverse effects. Although reports of central nervous system adverse effects were more frequent in the comparative trials, this difference was not significant. Including a placebo group in a RCT changes how patients rate the efficacy and adverse effects of their therapy. Our results highlight the need to consider the placebo effect in the design and analyses of clinical trials.

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.

Physician attitudes concerning warfarin for stroke prevention in atrial fibrillation: results of a survey of long-term care practitioners.

BACKGROUND: The prevalence of atrial fibrillation (AF) increases dramatically with advancing patient age, and, as a result, this condition is common in persons residing in the long-term care setting. OBJECTIVES: To assess the knowledge and attitudes of physicians regarding the use of warfarin for stroke prevention in patients with atrial fibrillation in long-term care facilities. METHODS: We surveyed physicians actively providing primary care to older patients in 30 long-term care facilities located in New England, Quebec, and Ontario. Physicians were requested to complete a structured questionnaire about use of warfarin therapy for stroke prevention in patients with AF residing in long-term care facilities. The questionnaire included two clinical scenarios designed to provide substantial contrasts in patient characteristics including underlying comorbidity, functional status, bleeding risk, and stroke risk. RESULTS: A total of 269 physicians were asked to participate in the survey, and 182 (67.7%) completed the questionnaire between February 1, 1995, and July 31, 1995. Only 47% of respondents indicated that the benefits of warfarin therapy "greatly outweigh the risks" in this setting; the remainder of physicians indicated that benefits only "slightly outweigh the risks" (34%) or that risks "outweigh benefits" (19%). The most frequently cited contraindications to warfarin use were: excessive risk of falls (71%), history of gastrointestinal bleeding (71%), history of other non-central nervous system bleeding (36%), and history of cerebrovascular hemorrhage (25%). Among the 164 physicians who reported using the international normalized ratio to monitor warfarin therapy, 27% indicated a target range with a lower limit less than 2, 71% indicated a target range between 2 and 3, and 2% indicated an upper limit greater than 3. Among respondents who answered questions about the two clinical scenarios, estimates of the risk of a stroke without warfarin therapy and the risk of an intracranial hemorrhage with therapy varied widely. CONCLUSIONS: Our findings suggest that many uncertainties surround the decision to prescribe warfarin to patients with AF in the long-term care setting, as well as questions about the appropriate intensity of this treatment when it is prescribed. Concerns about the risks of bleeding appear to prevail over stroke prevention when physicians make such prescribing decisions.

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.

A systematic review of the evidence for hypodermoclysis to treat dehydration in older people.

BACKGROUND: The purpose of the study was to evaluate the evidence supporting the use of hypodermoclysis (i.e., subcutaneous infusion of fluids) to treat dehydrated elderly patients, and to discuss clinical applications of this mode of therapy in the long-term care setting. METHOD: Articles reporting the use of hypodermoclysis were identified using a systematic MEDLINE search between January 1966 and May 1996. Articles were included in our sample if they contained original patient data that evaluated either the efficacy or adverse effects associated with the use of subcutaneous infusions to treat dehydration in adults, whether hyaluronidase was required to facilitate the absorption of subcutaneous fluid, or if potassium could be added to the solution. RESULTS: Eighteen articles met the inclusion criteria. Since we hypothesized that adverse effects associated with hypodermoclysis may have been related largely to the use of nonelectrolyte or hypertonic solutions, the studies were evaluated according to the type of fluid administered. Six hundred and eighty-five patients were described in 13 studies evaluating the efficacy and toxicity of subcutaneously administered fluid. Four studies evaluated hypodermoclysis using electrolyte-containing solutions in 25 patients. Two of these were randomized control trials (RCT) that compared hypodermoclysis to intravenous therapy. Both reported similar absorption of fluids. In the single RCT that evaluated adverse effects, 4 of 17 patients receiving hypodermoclysis reported minor side effects similar to those reported with intravenous therapy. Adverse effects were more severe when electrolyte-free or hypertonic solutions were evaluated. Of the 639 patients who may have received electrolyte-free solutions, 16 patients (2.5%) reported adverse effects, 8 of which were severe. Both patients reported to have received hypertonic solutions noted adverse effects, one of which was severe. The use of hyaluronidase to facilitate absorption was evaluated in 74 patients. These studies suggest that hyaluronidase improves the speed of fluid absorption but may not change the patient's comfort level. A single case report of 350 subcutaneous infusions in 67 patients investigated the administration of up to 34 mmol/L of potassium chloride (KCl) by hypodermoclysis. The only adverse reaction observed was discomfort at the infusion site. CONCLUSIONS: Hypodermoclysis can be used to most safely provide fluids when electrolyte-containing fluids are administered. Hypodermoclysis may have fallen into disuse because of reports of severe adverse reactions related to infusions of electrolyte-free or hypertonic solutions that would likely be considered inappropriate today. Whether or not hyaluronidase is required to promote subcutaneous fluid absorption remains unresolved. Limited evidence suggests that potassium chloride may, with caution, be safely added to subcutaneous infusions. The majority of the available studies evaluating hypodermoclysis are of poor quality. Because of the tremendous potential benefits of administering fluid subcutaneously, there is a need for good quality studies to evaluate the efficacy of hypodermoclysis.

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.

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.

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.