A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. [Effectiveness of brief infusions with Ginkgo biloba Special Extract EGb 761 in dementia of the vascular and Alzheimer type]. Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial. Effectiveness of a group exercise program in a long-term care facility: a randomized pilot trial. Effects of a newly developed cognitive intervention in amnestic mild cognitive impairment and mild Alzheimer's disease: a pilot study. Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial. Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. Switching patients with asthma from chlorofluorocarbon (CFC) albuterol to hydrofluoroalkane-134a (HFA) albuterol. An outreach intervention to implement evidence based practice in residential care: a randomized controlled trial [ISRCTN67855475].
To determine the efficacy of acetyl-l-carnitine (ALCAR) on the rate of decline in early-onset AD patients.
                A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were 45 to 65 years old, with a diagnosis of probable AD according to National Institute of Neurological Communicative Disorders-Alzheimer's Disease and Related Disorders Association criteria and had a Mini-Mental State Examination (MMSE) score between 12 and 26. They were treated with ALCAR (1 g tid) or placebo. Primary outcome measures were the Alzheimer's Disease Assessment Scale-Cognitive Component and the Clinical Dementia Rating Scale. Secondary measures included the ADAS Non-Cognitive Subscale, the MMSE, an Activities of Daily Living Scale (ADL), and a Clinician-Based Impression of Change (CIBIC).
                Two-hundred twenty-nine patients were enrolled and randomized to drug treatment, with 117 taking placebo and 112 taking ALCAR. There were no significant differences between the two groups at baseline. For the primary outcome measures, there were no significant differences between the treatment groups on the change from baseline to endpoint in the intent-to-treat analysis. In the completer sample only, there was less deterioration in the MMSE for the ALCAR-treated subjects. There was no difference in rate of decline on the CIBIC and the ADL scale. There were no significant differences in the incidence of adverse events by treatment arm.
                Overall, in a prospectively performed study in young-onset AD patients, ALCAR failed to slow decline. Less decline was seen on the MMSE in the completer sample only, with the difference being mediated by reducing decline in attention. A combination of ALCAR and a cholinesterase inhibitor should be tested for additivity. In a placebo-controlled, randomized, double-blind clinical trial, 40 patients with a mean age of 68 (+/- 12.5) years suffering from moderate dementia (Alzheimer, vascular, or mixed type) according to DSM-III-R criteria were included. Severity of the disease had to correspond to stages 4 or 5 of Reisberg's Global Deterioration Scale. Infusions of either EGb 761 or placebo were administered 4 days per week for 4 weeks. Primary outcome measure was the activities of daily living as assessed by the Nürnberger-Alters-Beobachtungsskala (NAB). The Clinical Global Impressions of change (CGI, item 2) and the actual intelligence as assessed by the Kurztest für Allgemeine Intelligenz (KAI) were further target variables. No relevant group differences could be detected at baseline. After therapy, patients of the active substance group scored significantly better (p < 0.05) on each outcome measure than those who received placebo. Using a sequential testing procedure, a global significance level of p < 0.05 could be assured. Superiority of EGb 761 therapy was also found with respect to a self-rating scale for instrumental activities of daily living (Nürnberger-Alters-Alltagsaktivitätenskala), the improvement of the most prominent symptom of illness, and the decrease of depression. Thus clinical efficacy of EGb 761 could be shown on three planes of assessment: the behavioral, the psychopathologic and the psychometric plane. It could be confirmed that, in patients with moderate dementia, short-term intravenous infusion therapy with EGb 761 results in an improvement of psychopathology and cognitive performance, which is reflected in an increased ability to cope with the demands of daily living. Delirium is common and often goes undetected in older patients admitted to medical services. It is associated with poor outcomes. We conducted a randomized clinical trial to determine whether systematic detection and multidisciplinary care of delirium in older patients admitted to a general medical service could reduce time to improvement in cognitive status.
                Consecutive patients aged 65 or more who were newly admitted to 5 general medical units between Mar. 15, 1996, and Jan. 31, 1999, were screened with the Confusion Assessment Method within 24 hours after admission to detect prevalent delirium and rescreened within a week to detect incident cases. Patients with delirium were randomly allocated to receive the intervention or usual care. Subjects in the intervention group were seen by a geriatric specialist consultant and followed in hospital for up to 8 weeks by an intervention nurse who liaised with the consultant, attending physicians, family and the primary care nurses. Subjects in the usual care group received standard hospital services but could consult geriatric specialists as needed. A research assistant, blinded as to treatment allocation, administered within 24 hours after enrolment the MiniMental Status Exam (MMSE), Delirium Index (measuring the severity of the delirium) and Barthel Index (measuring independence of personal care). Improvement was defined as an increase in the MMSE score of 2 or more points, with no decrease below baseline plus 2 points, or no decrease below a baseline MMSE score of 27. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly was completed to identify patients with possible dementia. Subjects were assessed 3 times during the first week and weekly thereafter for up to 8 weeks in hospital or until discharge. Data on clinical severity of illness, length of stay and living arrangements after discharge were also collected. The primary outcome measure was time to improvement in MMSE score.
                Of the 1925 patients who met the inclusion criteria and were screened, 227 had prevalent or incident delirium and consented to participate (113 in intervention group and 114 in usual care group). There were no clinically significant differences between the intervention and usual care groups except for sex (female 58.4% v. 50.0%) and marital status (married 34.8% v. 41.2%). Overall, 48% of the patients in the intervention group and 45% of those in the usual care group met the predetermined criteria for improvement. The Cox proportional hazards ratio (HR) for a shorter time to improvement with the intervention versus usual care, adjusted for age, sex and marital status, was 1.10 (95% confidence interval [CI] 0.74-1.63). There were no significant differences within 8 weeks after enrolment between the 2 groups in time to and rate of improvement of the Delirium Index, the Barthel Index, length of stay, rate of discharge to the community, living arrangements after discharge or survival. Outcomes between the 2 groups did not differ statistically significantly for patients without dementia (HR 1.54, 95% CI 0.80-2.97), for those who had less co-morbidity (HR 1.36, 95% CI 0.75-2.46) or for those with prevalent delirium (HR 1.15, 95% CI 0.48-2.79).
                Systematic detection and multidisciplinary care of delirium does not appear to be more beneficial than usual care for older patients admitted to medical services. The purpose of this pilot was to determine whether a strength and flexibility program in frail long-term care facility (LTC) residents would result in improved function.
                A prospective, randomized, controlled, semicrossover trial was designed with participants assigned either to group exercise (EX) or recreational therapy (C). In the EX group, the intervention continued for 1 year. In the C group, recreation continued for 6 months; these controls were then crossed over to the same exercise intervention as the EX group and followed for an additional 6 months. Functional outcomes were measured at baseline and 3, 6, 9, and 12 months for both groups.
                A LTC facility, which included both assisted living (AL) and nursing home (NH) residents.
                Twenty frail residents (5 from NH, 15 from AL) aged 75 to 99 years at one LTC facility.
                After random group assignment, the EX group met 1 hour three times per week. An exercise physiologist and LTC staff conducted sessions which included seated range of motion (ROM) exercises and strength training using simple equipment such as elastic resistance bands (therabands) and soft weights. The C group met three times per week and participated in activities such as painting during the first 6 months, before crossing over to exercise.
                Objective measures of physical and cognitive function were obtained at baseline and 3, 6, 9, and 12 months using the timed get-up-and-go test (TUG), Berg balance scale, physical performance test (PPT), and mini-mental status exam (MMSE). Because we were interested in the impact of exercise on multiple endpoints and to protect the type I error rate, a global hypothesis test was used.
                There was a significant overall impact across the four measures of the exercise intervention (P = 0.013). Exercise benefit as indicated by the difference between exercise and control conditions showed exercise decreased TUG by 18 seconds, which represents an effect size (in standard deviation units) of 0.50, increased PPT scores by 1.3, with effect size = 0.40, increased Berg scores by 4.8, with effect size of 0.32, and increased MMSE by 3.1, with effect size = 0.54. Except for the Berg, 90% confidence intervals on these exercise effects excluded 0.
                Frail elderly in a LTC facility were able to participate and benefit from a strength training program. The program was delivered with low-cost equipment by an exercise physiologist and LTC staff. The advantage of such a program is that it provides recreational and therapeutic benefits. Recent studies have shown that patients with Alzheimer's disease (AD) and its possible prodromal stage mild cognitive impairment benefit from cognitive interventions. Few studies so far have used an active control condition and determined effects in different stages of disease. We evaluated a newly developed 6-month group-based multicomponent cognitive intervention in a randomized controlled pilot study on subjects with amnestic mild cognitive impairment (aMCI) and mild AD patients. Forty-three subjects with aMCI and mild AD were recruited. Primary outcome measures were change in global cognitive function as determined by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Mini Mental Status Examination (MMSE). Secondary outcomes were specific cognitive and psychopathological ratings. Thirty-nine patients were randomized to intervention groups (IGs: 12 aMCI, 8 AD) and active control groups (CGs: 12 aMCI, 7 AD). At the end of the study, we found significant improvements in the IG(MCI) compared to the CG(MCI) in the ADAS-cog (p = 0.02) and for the secondary endpoint Montgomery Asberg Depression Rating Scale (MADRS) (p < 0.01) Effects on the MMSE score showed a non-significant trend (p = 0.07). In AD patients, we found no significant effect of intervention on the primary outcome measures. In conclusion, these results suggest that participation in a 6-month cognitive intervention can improve cognitive and non-cognitive functions in aMCI subjects. In contrast, AD patients showed no significant benefit from intervention. The findings in this small sample support the use of the intervention in larger scales studies with an extended follow-up period to determine long-term effects. A recent Cochrane review of reality orientation therapy identified the need for large, well-designed, multi-centre trials.
                To test the hypothesis that cognitive stimulation therapy (CST) for older people with dementia would benefit cognition and quality of life.
                A single-blind, multi-centre, randomised controlled trial recruited 201 older people with dementia. The main outcome measures were change in cognitive function and quality of life. An intention-to-treat analysis used analysis of covariance to control for potential variability in baseline measures.
                One hundred and fifteen people were randomised within centres to the intervention group and 86 to the control group. At follow-up the intervention group had significantly improved relative to the control group on the Mini-Mental State Examination (P=0.044), the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) (P=0.014) and Quality of Life - Alzheimer's Disease scales (P=0.028). Using criteria of 4 points or more improvement on the ADAS-Cog the number needed to treat was 6 for the intervention group.
                The results compare favourably with trials of drugs for dementia. CST groups may have worthwhile benefits for many people with dementia. To investigate if ethyl-eicosapentaenoic acid (E-EPA) augmentation improves antipsychotic efficacy and tolerability in first-episode psychosis (FEP).
                We performed a 12-week, randomized, double-blind, placebo-controlled trial of 2-g E-EPA augmentation in 80 FEP patients. Sixty-nine patients were eligible for analysis; a post hoc analysis was computed for a subgroup of nonaffective FEP patients (N = 53). The first participant was included in November 2000 and the last participant completed the trial in August 2003. Primary outcome measures were symptom change scores and time to first response, while tolerability measures and cumulative antipsychotic dose were secondary outcome measures.
                Analysis of covariance controlling for baseline symptoms found no significant mean difference between E-EPA and placebo at week 12 for symptom change scores. Cox regression analysis revealed a significant treatment by diagnosis interaction (p = .024) for time to first response favoring E-EPA in nonaffective psychosis. Post hoc analysis for cumulative response rates further confirmed a higher response rate at week 6 (42.9% [15/35] vs. 17.6% [6/34] for all participants, p = .036; 54.2% [13/24] vs. 17.2% [5/29] for the nonaffective psychosis subset, p = .008); however, the difference at week 12 was no longer significant. Analysis of secondary outcome measures revealed that E-EPA-augmented participants needed 20% less antipsychotic medication between weeks 4 through 6 (p = .03), had less extrapyramidal side effects in the initial 9 weeks (p < .05 for all participants and for all timepoints), and reported less constipation (p = .011) and fewer sexual side effects (p = .016) than those treated with antipsychotic medication alone.
                The findings suggest that E-EPA may accelerate treatment response and improve the tolerability of antipsychotic medications. However, it was not possible to demonstrate a sustained symptomatic benefit of E-EPA in early psychosis, possibly due to a ceiling effect, since a high proportion of first-episode patients already achieve symptomatic remission with antipsychotic medication alone. Further controlled trials in nonaffective early psychosis seem warranted.
                Australian Clinical Trials Registry identifier 12605000267651 (http://actr.org.au). Chlorofluorocarbon (CFC) propellants deplete stratospheric ozone. Production and use of CFCs, except for certain critical exemptions, has been prohibited by the Montreal Protocol. Use of CFCs as propellants in metered-dose inhalers (MDIs) is still allowed, but the U.S. Food and Drug Administration is planning the transition to alternative propellants for use in MDIs. Hydrofluoroalkane-134a (HFA), a non-ozone-depleting propellant, has been used to reformulate albuterol (HFA albuterol). This study evaluates whether comparable safety and efficacy continues for 12 weeks after patients with asthma are switched from CFC albuterol to HFA albuterol. Patients with asthma stabilized on CFC albuterol during a 12-week safety and efficacy trial were randomized to either continue receiving CFC albuterol or to be switched to receive HFA albuterol in a yearlong safety and efficacy trial. Safety and efficacy were compared over the first 12 weeks of the yearlong trial between patients who had remained on CFC albuterol and those who had been switched to HFA albuterol. Bronchodilator efficacy was evaluated by serial spirometry for 6 hr after the patients self-administered the study drug in the clinic. Safety was assessed by measuring changes in pulse rate, blood pressure, and electrocardiogram (ECG) intervals after dosing with study drug, monitoring adverse events, and performing prestudy and poststudy laboratory testing and physical examinations. No significant differences in bronchodilator efficacy between the patients continuing to receive CFC albuterol and those switched to HFA albuterol were found in the 12 weeks after the switch. No differences between the two products were found for changes in pulse rate, blood pressure, and ECG intervals. Adverse event profiles were similar for the two products, except the patients remaining on CFC albuterol reported increased asthma symptoms and rhinitis significantly more often than the patients switched to HFA albuterol. No clinically meaningful changes in laboratory tests or physical examinations were found in either treatment group. Patients with asthma switched from CFC albuterol to HFA albuterol receive comparable bronchodilation with a similar safety profile as those continuing to receive CFC albuterol. The aim of this project was to assess whether outreach visits would improve the implementation of evidence based clinical practice in the area of falls reduction and stroke prevention in a residential care setting.
                Twenty facilities took part in a randomized controlled trial with a seven month follow-up period. Two outreach visits were delivered by a pharmacist. At the first a summary of the relevant evidence was provided and at the second detailed audit information was provided about fall rates, psychotropic drug prescribing and stroke risk reduction practices (BP monitoring, aspirin and warfarin use) for the facility relevant to the physician. The effect of the interventions was determined via pre- and post-intervention case note audit. Outcomes included change in percentage patients at risk of falling who fell in a three month period prior to follow-up and changes in use of psychotropic medications. Chi-square tests, independent samples t-test, and logistic regression were used in the analysis.
                Data were available from case notes at baseline (n = 897) and seven months follow-up (n = 902), 452 residential care staff were surveyed and 121 physicians were involved with 61 receiving outreach visits. Pre-and post-intervention data were available for 715 participants. There were no differences between the intervention and control groups for the three month fall rate. We were unable to detect statistically significant differences between groups for the psychotropic drug use of the patients before or after the intervention. The exception was significantly greater use of "as required" antipsychotics in the intervention group compared with the control group after the pharmacy intervention (RR = 4.95; 95%CI 1.69-14.50). There was no statistically significant difference between groups for the numbers of patients "at risk of stroke" on aspirin at follow-up.
                While the strategy was well received by the physicians involved, there was no change in prescribing patterns. Patient care in residential settings is complex and involves contributions from the patient's physician, family and residential care staff. The project highlights challenges of delivering evidence based care in a setting in which there is a paucity of well controlled trial evidence but where significant health outcomes can be attained.
There is evidence for benefit of ALC on clinical global impression as a categorical measure and on MMSE at 24 weeks, but there is no evidence using objective assessments in any other area of outcome. Given the large number of comparisons made, the statistically significant results may be due to chance. At present there is no evidence to recommend its routine use in clinical practice. Many of the trials used rather vague descriptions of dementia and trials using more strictly defined groups may be informative. Individual patient data may add to the findings, as would trials including other outcomes (e.g. mood and caregiver quality of life). However, the evidence does not suggest that ALC is likely to prove an important therapeutic agent. More work on the pharmacokinetics of ALC in humans is also required.