A randomized controlled trial of the effect of dietary soy and flaxseed muffins on quality of life and hot flashes during menopause.

OBJECTIVE: To compare the effects of daily ingestion of soy flour (S), ground flaxseed (F), or wheat flour (W) muffins, on quality of life and hot flash frequency and severity in postmenopausal women. DESIGN: This was a double-blind, randomized, controlled, intention-to-treat trial. Ninety-nine women, 1 to 8 years after menopause, ingested muffins with 25 g of flaxseed (50 mg of lignans), 25 g of soy (42 mg of isoflavones), or wheat (control) daily for 16 weeks. Subjects completed the Menopause-specific Quality of Life instrument monthly along with daily hot flash frequency and severity diaries. Compliance measures included a 3-day food diary and urinary isoflavone and lignan analyses at weeks 0 and 16 and returned muffin counts monthly. RESULTS: Eighty-seven women (28, ground flaxseed muffins; 31, soy flour muffins; and 28, wheat flour muffins) completed the trial. Multivariate analysis of variance of all quality-of-life domains yielded an insignificant treatment x time interaction (F46,122 = 0.92, P = 0.62) but a significant time main effect (P <.0001). Repeated-measures analyses of covariance controlling for body mass index showed no significant group x time interaction nor time nor group differences on all quality-of-life domains and hot flash measures except severity. Hot flashes were less severe with flaxseed (P = 0.001) compared to placebo; however, the group x by time interaction was not significant. Phytoestrogen excretion analysis showed treatment group exposure as allocated and no contamination. CONCLUSION: Neither dietary flaxseed nor soy flour significantly affected menopause-specific quality of life or hot flash symptoms in this study.

Physiotherapy coupled with dextroamphetamine for rehabilitation after hemiparetic stroke: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: Hemiparesis is the commonest disabling deficit caused by stroke. In animals, dextroamphetamine (AMPH) paired with training enhances motor recovery, but its clinical efficacy is uncertain. METHODS: In a randomized, double-blind, placebo-controlled trial, 71 stroke patients were stratified by hemiparesis severity and randomly assigned to 10 sessions of physiotherapy coupled with either 10 mg AMPH or placebo. Study treatments were administered by 1 physiotherapist, beginning 5 to 10 days after stroke and continuing twice per week for 5 weeks. Outcomes were assessed by 1 physiotherapist at baseline, after each treatment session, at 6 weeks, and at 3 months. The primary outcome was motor recovery (impairment level) on the Fugl-Meyer (FM) scale. Secondary outcomes assessed mobility, ambulation, arm/hand function, and independence in activities of daily living. RESULTS: Baseline hemiparesis was severe overall (mean FM score 27.7+/-20.0). Motor scores improved during treatment in both groups (mean change, baseline to 3 months 29.5+/-16.6). Repeated-measures ANOVA revealed no significant differences in recovery between the treatment groups for the entire cohort (n=67) or for subgroups with a severe hemiparesis (n=43), moderate hemiparesis (n=24), or cortically based stroke (n=26). In the moderate subgroup, there was a significant drug x time interaction for upper extremity motor recovery (F=5.14; P<0.001), although there was a significant baseline imbalance in motor scores in this subgroup. CONCLUSIONS: In stroke patients with a severe motor deficit, 10 mg AMPH coupled with physiotherapy twice per week for 5 weeks in the early poststroke period provided no additional benefit in motor or functional recovery compared with physiotherapy alone. Patients with moderate severity hemiparesis deserve further investigation. Increased intensity and longer duration drug/therapy dosing regimens should be explored, targeting the upper and lower limbs separately.

Mild cognitive impairment: an operational definition and its conversion rate to Alzheimer's disease.

OBJECTIVE: Because of discrepant findings regarding the accuracy of mild cognitive impairment (MCI) in predicting Alzheimer's disease (AD), further study of this construct and conversion rates is essential before use in clinical settings. We aimed to develop an operational definition of MCI consistent with criteria proposed by the Mayo Alzheimer's Disease Center, and to examine its conversion rate to AD. METHODS: Patients were identified from an inception cohort of patients with at least a 3-month history of memory problems, and referred to a 2-year university teaching hospital investigation by primary care physicians. We classified 161 nondemented patients at baseline using MCI criteria. Diagnostic workups were completed annually, and patients were classified as meeting criteria for AD or showing no evidence of dementia after 1 and 2 years. RESULTS: Of 161 patients, 35% met MCI criteria at baseline. Conversion rates to AD were 41% after 1 year, and 64% after 2 years. Logistic regression analyses to examine predictive accuracy of MCI after 1 and 2 years, with age and education as covariates, were significant (p < 0.0001). After 1 year, MCI showed an optimal sensitivity of 91% and specificity of 79%, and after 2 years, these values were 88 and 83%, respectively. CONCLUSIONS: MCI is an accurate predictor of AD over 1 and 2 years in patients referred by their primary care physicians. Discrepancies in conversion rates may be due to the manner in which patients are recruited to studies as well as the use of different measures to operationalize the construct.

Verbal fluency patterns in two subgroups of patients with Alzheimer's disease.

Previous research has identified two subgroups of patients with Alzheimer's disease (AD) based on performance discrepancies on semantic and visual-constructional measures: Left AD (LAD) and Right AD (RAD). In this study, verbal fluency performances (Animal Fluency [AF] and Letter Fluency [FAS]) of these two subgroups were examined. It was hypothesized that LAD patients would perform worse on AF compared to FAS, due to an underlying breakdown of left-hemisphere semantic networks. On the other hand, the RAD group, which theoretically has a relatively preserved semantic system, yet difficulties retrieving overlearned information, was not expected to differ on the two fluency tasks. These predictions were based on the notion that the AF task requires intact retrieval and semantic processes, whereas the FAS task is reliant on retrieval processes alone. Patients were classified into subgroups on the basis of performance discrepancies on the Boston Naming Test (BNT) and Copy tasks: LAD (BNT < Copy); RAD (BNT > Copy). A split-plot ANOVA using demographically corrected standard T-scores revealed a significant main effect for fluency task, and a significant subgroup x fluency task interaction. LAD patients performed poorer on AF compared to FAS; there was no fluency task difference for the RAD group. Analysis of within-subcategory response clustering on AF revealed more instances of serial subclass exemplar responses by RAD members. These results support the loss theory in explaining the semantic deficit of LAD, and suggest that retrieval difficulties underlie the fluency problems of RAD.

Medical illness and the risk of suicide in the elderly.

BACKGROUND: Suicide is a leading cause of death, and rates are especially high among the elderly. Medical illnesses may predispose to suicide, but few controlled studies have examined the association between specific diseases and suicide. We explored the relationship between treatment for several illnesses and the risk of suicide in elderly patients using a population-based approach. METHODS: All Ontario residents 66 years or older who committed suicide between January 1, 1992, and December 31, 2000, were identified from provincial coroners' records. Their prescription records during the preceding 6 months were compared with those of living matched controls (1:4) to determine the presence or absence of 17 illnesses potentially associated with suicide. RESULTS: During the 9-year study period, we identified 1354 elderly patients who died of suicide. The most common mechanisms involved firearms (28%), hanging (24%), and self-poisoning (21%). Specific illnesses associated with suicide included congestive heart failure (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.33-2.24), chronic obstructive lung disease (OR, 1.62; 95% CI, 1.37-1.92), seizure disorder (OR, 2.95; 95% CI, 1.89-4.61), urinary incontinence (OR, 2.02; 95% CI, 1.29-3.17), anxiety disorders (OR, 4.65; 95% CI, 4.07-5.32), depression (OR, 6.44; 95% CI, 5.45-7.61), psychotic disorders (OR, 5.09; 95% CI, 3.94-6.59), bipolar disorder (OR, 9.20, 95% CI, 4.38-19.33), moderate pain (OR, 1.91; 95% CI, 1.66-2.20), and severe pain (OR, 7.52; 95% CI, 4.93-11.46). Treatment for multiple illnesses was strongly related to a higher risk of suicide. Almost half the patients who committed suicide had visited a physician in the preceding week. CONCLUSIONS: Many common illnesses are independently associated with an increased risk of suicide in the elderly. The risk is greatly increased among patients with multiple illnesses. These data may help clinicians to identify elderly patients at risk of suicide and open avenues for prevention.

The Toronto outcome measure for craniofacial prosthetics: a condition-specific quality-of-life instrument.

PURPOSE: The objective was to develop a patient-based outcome measure of condition-specific quality of life that would minimize measurement error related to the instrument when used with patients requiring extraoral craniofacial prostheses. MATERIALS AND METHODS: An item pool of potential questionnaire items covered 10 clinical/technical and social/psychologic domains. They sought how frequently the issue in the item affected patients and how important the problem in the item was. The 139 items were administered to 94 treated patients in 5 centers in the United States, Canada, and the United Kingdom. Items were eliminated using relevance (frequency x importance), frequency of answer endorsement, Cronbach's alpha (internal consistency), and correlation of items on the same subject. International cultural agreement was tested using analysis of variance and Tukey comparisons within each domain. Scoring was transformed to a scale (0 to 100). RESULTS: The final instrument contained 52 items yielding a mean quality of-life score of 72.5% and a standard deviation of 17.9. Very high internal consistency was demonstrated with a final Cronbach's alpha of 0.967. No international cultural disagreement was found in 9 of the 10 domains. DISCUSSION: The relative weight of each of the domains is (partially) based on the relevance to the patients. Of the 52 items, 29 were identified that do not mention a prosthesis. This subscale has a Cronbach's alpha of 0.976. These items may therefore be useful where within-patient change is of interest. CONCLUSION: A patient-based outcome measure of condition-specific quality of life has been developed with control of bias and demonstrated performance characteristics.

External cephalic version beginning at 34 weeks' gestation versus 37 weeks' gestation: a randomized multicenter trial.

OBJECTIVE: In about 3% to 4% of all pregnancies at term, the fetal presentation will be noncephalic. External cephalic version (ECV) at term has been shown to decrease the rate of noncephalic presentation at birth and to decrease the rate of cesarean section associated with breech presentation. However, success rates for ECV are low. We did a randomized trial to compare a policy of beginning ECV early, at between 34 and 36 weeks' gestation, and beginning ECV at 37 to 38 weeks' gestation. STUDY DESIGN: At 25 centers in seven countries, 233 women with a singleton breech fetus were randomly assigned to having an ECV procedure done early (at between 34 weeks 0 days and 36 weeks 0 days), or delayed (at between 37 weeks 0 days and 38 weeks 0 days). An experienced practitioner undertook the ECV procedure, and repeat ECV procedures were allowed. Tocolytics and use of epidural analgesia were included as part of the protocol. The primary outcome was the rate of noncephalic presentation at birth. An intention-to-treat analysis was used. RESULTS: Data were received for 232 women, with 116 women in each of the early and delayed ECV groups. Of these, 86.2% in the early ECV group and 67.2% in the delayed ECV group had at least one ECV performed. The rate of noncephalic presentation at birth in the early ECV group was 66 of 116 (56.9%) and 77 of 116 (66.4%) in the delayed ECV group (relative risk [RR] [95% CI] 0.86 [0.70-1.05], P =.09). The rate of serious fetal complications and the rate of preterm birth at <37 weeks were not significantly increased in the early ECV group compared with the delayed ECV group (6.9% vs 7.8%, RR [95% CI] 0.89 [0.36-2.22], P =.69 and 8.6% vs 6.1%, RR [95% CI] 1.42 [0.56-3.59], P =.31, respectively). The rate of cesarean section in the early ECV group was 75 of 116 (64.7%) and 83 of 116 (71.6%) in the delayed ECV group (RR [95% CI] 0.90 [0.76-1.08], P =.32). Neonatal outcomes were comparable in the two groups. The rate of reversion to noncephalic was low in both groups. The majority of women in both groups indicated that they would consider having an ECV in another pregnancy. CONCLUSION: Early ECV performed at 34 to 36 weeks compared with 37 to 38 weeks may reduce the risk of noncephalic presentation at delivery. A large pragmatic trial of early ECV is now required to assess this approach further in terms of cesarean section rates and neonatal outcomes before changes in clinical practice.

Contribution of informant and patient ratings to the accuracy of the mini-mental state examination in predicting probable Alzheimer's disease.

OBJECTIVES: To determine whether the accuracy of the Mini-Mental State Examination (MMSE) in predicting future Alzheimer's disease (AD) could be improved by the addition of patient and informant ratings of cognitive difficulties. DESIGN: An inception cohort of nondemented patients followed longitudinally for 2 years. SETTING: Patients referred to a university teaching hospital research investigation by their family physicians because of concerns about memory impairment. PARTICIPANTS: One hundred sixty-five community-residing patients were included who did not have dementia or any identifiable cause for memory impairment. After 2 years, 29 met criteria for AD, and 95 were not demented. MEASUREMENTS: Baseline assessments included MMSE, an Informant Rating Scale, and a Patient Rating Scale of cognitive difficulties. After 2 years, patients were diagnosed following the reference standard for probable AD. Diagnosticians were blind to baseline scores. RESULTS: Age and education were included in all analyses as covariates. The best logistic regression model included the Informant Rating Scale and the MMSE (sensitivity = 83%, specificity = 79%). An empirically reduced six-item model that included two items each from the MMSE, the Patient Rating Scale, and the Informant Rating Scale produced a significantly better model than the one with the full test scores (sensitivity = 90%, specificity = 94%). CONCLUSION: Results indicate that inclusion of informant ratings with the MMSE significantly improved its accuracy in the prediction of probable AD. Replication in a new prospective cohort of nondemented patients is necessary to confirm these findings.

Impact of antidepressant side effects on adolescent quality of life.

OBJECTIVE: This study examines the relative impact of antidepressant side effects on adolescents with a history of major depression. METHODS: We used Q-sort methodology to capture the opinions of adolescents with a history of depression (n = 22), adults with a history of depression (n = 20), healthy adolescents (n = 20), and clinicians (n = 18) on the impact of 40 common antidepressant side effects. We asked subjects to force rank the side effects, judging each side effect on its relative impact on their daily lives. We also examined the impact of these side effects on health status and medication compliance. Primary analyses compared adolescents with depression with the other groups on their mean rankings for each of the 40 side effects. Secondary analyses included paired comparisons for ratings on health status and compliance. RESULTS: Although all groups ranked syncope and vomiting among the worst 5 side effects, significant differences were found between the groups on other side effects, such as anxiety, sleepiness, and hair loss. Based on the side effect with the most negative impact, adolescents with depression judged their own compliance (mean = 22%) to be higher than predicted by clinicians (mean = 11%). There were no significant differences between the groups on the mean rating of health status. CONCLUSIONS: Adolescents with depression, adults with depression, healthy adolescents, and clinicians agreed on the negative impact of 2 side effects: vomiting and syncope. Q-sort methodology provides valuable insight into the similarities and differences in opinion regarding the potential impact of side effects in patient groups.

Discrepant advice from poison centres and their medical directors.

OBJECTIVE: To characterize the recommendations of the medical directors of North American poison information centres for gastrointestinal decontamination of a hypothetical poisoned patient, and to examine the extent to which those recommendations agree with the advice previously issued by their poison information centres for the same scenario. METHODS: The medical directors of 72 poison centres in the United States and Canada were contacted and invited to participate in a survey. Each participant was asked to provide specific advice for gastrointestinal decontamination of a hypothetical patient presenting 1 h after a potentially life-threatening ingestion (32.5 g) of enteric-coated acetylsalicylic acid. The directors were then presented with the recommendation their poison centres had previously issued for the same overdose scenario. The main outcome measures were perceived agreement with their own centre's recommendation and director-centre concordance for each method of gastrointestinal decontamination. RESULTS: Sixty-seven of 72 (93%) medical directors participated in the survey. They issued 30 different management suggestions for our hypothetical patient, and were in full agreement with their own centres 27% of the time. Concordance was moderate for recommendations on syrup of ipecac (k=0.468, P<0.001), and fair for whole bowel irrigation (k=0.348, P=0.005) and the use of sorbitol with activated charcoal (k=0.305, P=0.005). Concordance was poorest for advice on gastric lavage (k=0.093, P=0.445) and multidose charcoal (k=0.039, P=0.745). CONCLUSIONS: The medical directors of North American poison centres offer widely varying advice on gastrointestinal decontamination for a hypothetical patient who is acutely poisoned with enteric-coated acetylsalicylic acid. Their advice was often different from that previously issued by their respective centres.

Minimising blood loss and transfusion requirements in hepatic resection.

BACKGROUND: Substantial blood loss and the requirement for blood transfusion remain major considerations for hepatic surgeons. We analysed the impact of a systematic protocol aimed at reducing intraoperative blood loss and homologous blood (HB) transfusion associated with hepatic resection. METHODS: Prospective clinical data were collected from 151 elective liver resections performed during the period between 1980 and 1999. Further data directly related to blood loss and anaesthesia were retrospectively collected from the anaesthetic intra-operative record. Strategies implemented in 1991 included preoperative autologous blood donation, low central venous pressure anaesthesia, aprotinin administration, ultrasonic dissection, hepatic vascular inflow occlusion and a Cell Saver. Blood loss and transfusion requirements were studied before and after the implementation of these strategies. RESULTS: There was no difference in the patient demographics, indications for operation or the scope of resections in the two time periods evaluated. Blood-saving strategies resulted in decreased estimated blood loss (4500 mL vs. 1000 mL p<0.001). In addition, the number of patients requiring transfusion decreased (91.8% vs. 25.5% respectively, p<0.001) and the mean number of units of HB transfusion was lower (I 3.7 vs. 2.3, p<0.001). Morbidity and mortality were also decreased (57.1% vs. 25.5%, p<0.001 and 10.2% and 4.9% p<0.001, respectively). No complications directly referrable to low CVP anesthesia were identified. CONCLUSION: Systematic implementation of strategies designed to control blood loss are effective and may reduce morbidity and mortality associated with hepatic resections.