scholarly journals Pharmacotherapy of Alzheimer Disease

2007 ◽  
Vol 52 (10) ◽  
pp. 620-629 ◽  
Author(s):  
Dennis Seow ◽  
Serge Gauthier
Keyword(s):  
Clinical Trials ◽  
Alzheimer Disease ◽  
English Language ◽  
Mini Mental State Examination ◽  
Randomized Clinical Trials ◽  
Primary Analysis ◽  
Aspartate Receptor ◽  
Asymptomatic Individuals ◽  
Post Hoc ◽  
State Examination

Objective: To systematically review published clinical trials of the pharmacotherapy of Alzheimer disease (AD). Method: We searched MEDLINE for published English-language medical literature, using Alzheimer disease and treatment as key words. No other search engine was used. Our review focused on randomized clinical trials (RCTs) and corresponding metaanalyses. Results: Although there are many RCTs for the treatment of mild cognitive impairment (MCI), none have been successful in their primary analysis. The cholinesterase inhibitors donepezil, rivastigmine, and galantamine have demonstrated efficacy in 3- to 12-month placebo-controlled RCTs assessing cognitive, functional, behavioural, and global outcomes in patients with mildly to moderately severe AD. Recent data from patients with severe stages of AD demonstrate the efficacy of donepezil on cognitive and functional measures but not on behaviour. The N-methyl-D-aspartate receptor antagonist memantine has been demonstrated to be effective in 6-month, placebo-controlled RCTs of 6 months duration assessing cognitive, functional, and global outcomes of inpatients with moderate-to-severe AD (defined as a Mini Mental State Examination score below 20). Post hoc analyses have demonstrated a benefit in regard to agitation and (or) aggression, but this needs to be confirmed in a prospective RCT across Canada. Disease-modifying treatments are being tested in mild stages of AD in 18-month RCTs with cognitive and global outcomes as primary efficacy outcomes, primarily with drugs reducing amyloid synthesis or aggregation. Successful treatment in mild stages of AD could lead to RCTs in MCI and, possibly, in genetically high-risk asymptomatic individuals. Conclusion: The significant advances in the symptomatic pharmacotherapy of AD may be followed by disease-modification treatments.

Effect of aerobic exercise on post-stroke cognitive function: a systematic review

2020 ◽  
Vol 27 (9) ◽  
pp. 1-15
Author(s):  
Muhammad Aliyu Abba ◽  
Olubukola Adebisi Olaleye ◽  
Talhatu Kolapo Hamzat
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Cognitive Function ◽  
Aerobic Exercise ◽  
Mini Mental State Examination ◽  
Cognitive Impairments ◽  
Inclusion Criteria ◽  
Post Stroke ◽  
Online Databases ◽  
State Examination

Background/Aims Literature suggests that aerobic exercise improves cognitive impairments post stroke. This systematic review was conducted to analyse evidence on the effectiveness of aerobic exercise in improving post-stroke cognitive impairments. Methods Online databases (PubMed, EMBASE and Web of Science) were systematically searched from inception until 13 July 2017 using the keywords stroke/exercise/cognition. Clinical trials that met the inclusion criteria were assessed for methodological quality using the PEDro scale. Extracted data were synthesised for evidence. Results A total of seven studies met the inclusion criteria. Participants in most of the studies were aged over 60 years and the majority had ischaemic stroke. The most commonly used measure for assessing cognition was the Mini Mental State Examination. The majority of studies included moderate to high intensity exercise (50–70% of VO2max) for 30–60 minutes three to five times per week. There is moderate evidence that aerobic exercise enhances global cognitive function, attention and working memory. Evidence that aerobic exercise improves memory, levels of brain-derived neurotrophic factor and executive function is conflicting and limited. Conclusions Aerobic exercise is moderately effective in improving post-stroke cognitive impairments. More clinical trials are needed in view of the methodological limitations and paucity of existing studies.

scholarly journals High-quality colon cleansing and multiple neoplasia detection with 1L NER1006 versus mid-volume options: Post hoc analysis of phase 3 clinical trials

2020 ◽  
Vol 08 (05) ◽  
pp. E628-E635
Author(s):  
Michael S. Epstein ◽  
Robert Benamouzig ◽  
Juha Halonen ◽  
Raf Bisschops
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Combined Treatment ◽  
Sulfate Solution ◽  
Lesion Detection ◽  
High Quality ◽  
Post Hoc Analysis ◽  
Colon Cleansing ◽  
Adenoma Detection ◽  
Post Hoc

Abstract Background and study aims Multiple neoplasia increase the risk of colorectal cancer. High-quality cleansing may improve adenoma detection. We assessed whether a new bowel preparation can improve colon cleansing and multiple lesion detection. Patients and methods This post hoc analysis of two randomized clinical trials in Europe and the US assessed the per study and combined cleansing efficacy of overnight split dosing with (preparation + clear fluids) 1 + 1 L polyethylene glycol (PEG) NER1006 versus 2 + 1 L PEG + ascorbate (2LPEG) or 1 + 2 L oral sulfate solution (OSS) combined. Treatment-blinded central readers assessed cleansing quality using the Harefield Cleansing Scale (HCS). Patients with full segmental scoring were included. HCS segmental scores 0–4 (high-quality = HCS 3–4) were analyzed for NER1006 versus 2LPEG/OSS. Mean number of polyps or adenomas per patient (MPP/MAP) was calculated for treatments in patients with at least one polyp or adenoma. Results In 1037 patients, NER1006 attained a greater rate of HCS 3 scores (29 % vs. 20 %; P < 0.001) and HCS 4 scores (20 % vs. 17 %; P = 0.007) versus 2LPEG/OSS. More polyps (678 versus 585) and adenomas (397 versus 331) were detected with NER1006 (N = 517) versus 2LPEG/OSS (N = 520). In all neoplasia-positive patients, with increasing minimal per-patient neoplasia multiplicity from 1 to 10, NER1006 numerically improved MPP (difference ± SE: 0.48 ± 0.24 to 3.89 ± 3.37) and MAP (0.47 ± 0.26 to 7.50 ± 9.00) versus 2LPEG/OSS. Conclusions Low-volume NER1006 enhances high-quality cleansing versus medium-volume 2LPEG or OSS, individually and when combined. NER1006 may consequently facilitate the detection of multiple neoplasia in patients.

Statistical power of negative randomized clinical trials (RCTs) presented at the American Society of Clinical Oncology (ASCO) Annual Meetings

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6516-6516
Author(s):  
P. Bedard ◽  
M. K. Krzyzanowska ◽  
M. Pintilie ◽  
I. F. Tannock
Keyword(s):  
Clinical Trials ◽  
Sample Size ◽  
Annual Meeting ◽  
Primary Endpoint ◽  
Effect Size ◽  
Statistical Power ◽  
Randomized Clinical Trials ◽  
Medium Effect ◽  
Post Hoc ◽  
Adequate Sample Size

6516 Background: Underpowered randomized clinical trials (RCTs) may expose participants to risks and burdens of research without scientific merit. We investigated the prevalence of underpowered RCTs presented at ASCO annual meetings. Methods: We surveyed all two-arm parallel phase III RCTs presented at the ASCO annual meeting from 1995–2003 where differences for the primary endpoint were non-statistically significant. Post hoc calculations were performed using a power of 80% and a=0.05 (two-sided) to determine the sample size required to detect a small, medium, and large effect size between the two groups. For studies reporting a proportion or time to event as a primary endpoint, effect size was expressed as an odds ratio (OR) or hazard ratio (HR) respectively, with a small effect size defined as OR/HR=1.3, medium effect size OR/HR=1.5, and large effect OR/HR=2.0. Logistic regression was used to identify factors associated with lack of statistical power. Results: Of 423 negative RCTs for which post hoc sample size calculations could be performed, 45 (10.6%), 138 (32.6%), and 333 (78.7%) had adequate sample size to detect small, medium, and large effect sizes respectively. Only 35 negative RCTs (7.1%) reported a reason for inadequate sample size. In a multivariable model, studies presented at plenary or oral sessions (p<0.0001) and multicenter studies supported by a co-operative group were more likely to have adequate sample size (p<0.0001). Conclusion: Two-thirds of negative RCTs presented at the ASCO annual meeting do not have an adequate sample to detect a medium-sized treatment effect. Most underpowered negative RCTs do not report a sample size calculation or reasons for inadequate patient accrual. No significant financial relationships to disclose.

scholarly journals Impact of Potential Modifications to Alzheimer’s Disease Clinical Trials in Response to Disruption by COVID-19

2021 ◽  
Author(s):  
Lon S Schneider ◽  
Yuqi Qiu ◽  
Ronald G Thomas ◽  
Carol Evans ◽  
Diane M. Jacobs ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Alzheimer Disease ◽  
Statistical Power ◽  
Randomized Clinical Trials ◽  
Adaptive Methods ◽  
Disease Modification ◽  
Threats To Validity ◽  
Remote Assessment ◽  
Political Milieu ◽  
The Impact

Abstract BackgroundThe COVID-19 pandemic disrupted Alzheimer disease randomized clinical trials (RCTs)forcing investigators to make changes in the conduct of such trials while endeavoring to maintain their validity. Changing ongoing RCTs carries risks for biases and threats to validity. To understand the impact of exigent modifications due to COVID-19 we examined several scenarios in symptomatic and disease modification trials that could be made.MethodsWe identified both symptomatic and disease modification Alzheimer disease RCTs as exemplars of those that would be affected by the pandemic and considered the types of changes that sponsors could make to each. We modeled three scenarios for each of the types of trialsusing existing datasets, adjusting enrollment, follow-ups, and dropouts to examine the potential effects COVID-19-related changes.Simulations were performed that accounted for completion and dropout patterns using linear mixed effects models, modeling time as continuous and categorical. The statistical power of the scenarios was determined.ResultsTruncating both symptomatic and disease modification trials, led to underpowered trials.By contrast, adapting the trials byextending the treatment period, temporarily stopping treatment, delaying outcomes assessments, and performing remote assessment allowed for increased statistical power nearly to the level originally planned.DiscussionThese analyses support the idea that disrupted trials under common scenarios are better continued and extended even in the face of dropouts, treatment disruptions, missing outcomes, and other exigencies, and that adaptations can be made that maintain the trials validity. We suggest some adaptive methods to do this noting that some changes become under-powered to detect theoriginal effect sizes and expected outcomes. These analyses provide insight to better plan trials that are resilient to unexpected changes to the medical, social, and political milieu.

scholarly journals Comparing The Efficacy of Anti-Infectious Drugs For The Treatment of Mild To Severe COVID-19 Patients: A Protocol For A Systematic Review And Network Meta-Analysis of Randomized Clinical Trials.

2021 ◽  
Author(s):  
Dejene Tolossa Debela ◽  
Kidist Digamo Heraro ◽  
Abebaw Fekadu ◽  
Merga Belina ◽  
Tsegahun Manyazewal
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
English Language ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Antiviral Drug ◽  
Standard Of Care ◽  
Randomized Controlled ◽  
Primary Endpoints ◽  
Independent Review

Abstract Background: COVID-19 is a viral infection spreading at a great speed and has quickly caused an extensive burden to individuals, families, countries, and the world. No intervention has yet been proven highly effective for the treatment of COVID-19. Different drugs were being evaluated and reported through randomized clinical trials, and more are currently under trial. This review aimed to compare the efficacy of anti-infectious drugs with a comparator of the standard of care or placebo in patients with COVID-19.Methods: Two independent review authors will extract data and assess a risk of bias using RoB2. Randomized controlled trials (RCT) that evaluate single and/or combined antiviral drugs recommended by WHO latest guideline for the treatment of COVID-19 will be included. We will search for Pub Med, the Cochrane Center for Clinical Trial database (CENTRAL), clinicaltrials.gov, etc. databases for articles published in the English language between December 2019 to April 2021. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) involving Network Meta-analysis guidelines to design and report of the results. The primary endpoints will be time to clinical recovery and time to RNA negativity. The certainty of evidence will be evaluated using the GRADE extension of NMA. Data analysis will be performed using the frequentist NMA approach with the netmeta package implemented in R.Discussion: This review will reveal the best antiviral drug treatment for covid-19 and show the hierarchy of those drugs.Systematic review registration: The protocol was registered on PROSPERO with ID number CRD42021230919

scholarly journals Predictive Factors of Rapid Cognitive Decline in Patients with Alzheimer Disease

2016 ◽  
Vol 6 (3) ◽  
pp. 549-558 ◽  
Author(s):  
Coralie Barbe ◽  
Isabella Morrone ◽  
J.L. Novella ◽  
Moustapha Dramé ◽  
Aurore Wolak-Thierry ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Caregiver Burden ◽  
Predictive Factors ◽  
Mini Mental State Examination ◽  
Care Plan ◽  
Factors Associated ◽  
Medical Needs ◽  
Rapid Cognitive Decline ◽  
State Examination

Aim: To determine predictive factors associated with rapid cognitive decline (RCD) in elderly patients suffering from Alzheimer disease (AD). Methods: Patients suffering from mild to moderate AD were included. RCD was defined as the loss of at least 3 points on the Mini-Mental State Examination (MMSE) over 12 months. Factors associated with RCD were identified by logistic regression. Results: Among 123 patients included, 61 were followed up until 12 months. RCD occurred in 46% of patients (n = 28). Polymedication (p < 0.0001), the fact that the caregiver was the child or spouse of the patient (p < 0.0001) and autonomy for washing (p < 0.0001) were protective factors against RCD, while the presence of caregiver burden (p < 0.0001) was shown to be a risk factor for RCD. Conclusion: Early detection of the RCD risk in AD patients could make it possible to anticipate the patient’s medical needs and adjust the care plan for caregiver burden.

Sign in / Sign up

Export Citation Format

Share Document