Migraine patients' experiences with and expectations from physiotherapy.

BACKGROUND: Neck pain is prevalent in migraine and a common reason to receive physiotherapy. There is no information as to the type of modalities patients receive and whether these are perceived as effective and matching expectations. METHODS: A survey was designed with closed and open-ended questions allowing for quantitative evaluation and qualitative insights into experiences and expectations. The survey was available online from June-November 2021 and was disseminated in the German migraine league (patient organization) and via social media. Open questions were summarized using qualitative content analysis. Differences between receiving and not receiving physiotherapy were analyzed through Chi2 or Fisher's Test. Categories within groups through Chi2-goodness-of-fit-test and multivariate logistic regression indicated perceived clinical improvement. RESULTS: 149 (123 received physiotherapy) patients completed the questionnaire. Patients receiving physiotherapy had higher pain intensity (p < 0.001) and migraine frequency (p = 0.017). Most participants received 6 sessions or less (38%) (past 12 months) of manual therapy (82%) and soft-tissue techniques (61%). 63% perceived benefits after manual therapy, and 50% after soft-tissue techniques. Logistic regression revealed that ictal and interictal neck pain (OR: 9.12 and 6.41, respectively) and receiving manual therapy (OR: 5.52) are associated with improvement. Mat exercises and higher migraine frequency increased the odds for no improvement or worsening (OR: 0.25 and 0.65, respectively). Expectations included individualized and targeted treatment from a specialized physiotherapist (39%), easier access, more and longer sessions (28%), manual therapy (78%), soft-tissue techniques (72%) and education (26%). CONCLUSION: sThis first study on migraine patients' views on physiotherapy can serve as insight for researchers for future studies and clinicians to improve future care.

Bilateral lysis of aortic saddle thrombus with early tissue plasminogen activator (BLASTT): a prospective, randomized, placebo-controlled study in feline acute aortic thromboembolism.

OBJECTIVES: The aim of this study was to investigate the impact of tissue plasminogen activator (TPA) on the treatment of feline aortic thromboembolism (FATE). METHODS: Cats diagnosed with FATE involving ⩾2 limbs were enrolled in a prospective, multicenter, double-blinded, randomized, placebo-controlled study within 6 h of an event. Diagnosis was made by clinical findings and one confirmatory criterion. Cats received placebo or TPA (1 mg/kg/h with the first 10% by bolus). All cats received pain control and thromboprophylaxis. The primary outcome was a change from baseline in a published limb score at 48 h. Secondary outcomes included 48 h survival, survival to discharge and complication proportions. Statistical analyses included pattern-mixture models, logistic regression and Fisher's exact, Student's t- and Mann-Whitney-Wilcoxon tests. RESULTS: Based on a power analysis, 40 cats were enrolled; however, only 20 survived to 48 h (TPA, n = 12; placebo, n = 8 [P = 0.34]). There was a statistically significant improvement in limb scores compared with baseline for both groups (P <0.001). Limb score at 48 h was 1 point lower (better) in the TPA group (P = 0.19). Thrombolysis had no statistically significant effect on 48 h survival (P = 0.22). Lower affected limb lactate was associated with better 48 h survival (odds ratio 1.53, 95% confidence interval 1.08-2.17; P = 0.02). The survival to discharge rates were 45% (TPA) and 30% (placebo; P = 0.51). Complications in the TPA and placebo groups included acute kidney injury (22% and 19%, respectively; P = 1.00) and/or reperfusion injuries (33% and 19%, respectively; P = 0.45). CONCLUSIONS AND RELEVANCE: Survival and complication rates of acute FATE were not different with or without thrombolysis. High in-hospital mortality decreased the statistical power to detect a statistically significant difference between treatments with regard to our primary outcome.

Periodically Disturbing the Spatial Structure of Biofilms Can Affect the Production of an Essential Virulence Factor in Pseudomonas aeruginosa.

Understanding the environmental factors that affect the production of virulence factors has major implications in evolution and medicine. While spatial structure is important in virulence factor production, observations of this relationship have occurred in undisturbed or continuously disturbed environments. However, natural environments are subject to periodic fluctuations, including changes in physical forces, which could alter the spatial structure of bacterial populations and impact virulence factor production. Using Pseudomonas aeruginosa PA14, we periodically applied a physical force to biofilms and examined production of pyoverdine. Intermediate frequencies of disturbance reduced the amount of pyoverdine produced compared to undisturbed or frequently disturbed conditions. To explore the generality of this finding, we examined how an intermediate disturbance frequency affected pyoverdine production in 21 different strains of P. aeruginosa. Periodic disturbance increased, decreased, or did not change the amount of pyoverdine produced relative to undisturbed populations. Mathematical modeling predicts that interactions between pyoverdine synthesis rate and biofilm density determine the amount of pyoverdine synthesized. When the pyoverdine synthesis rates are high, depletion of the biofilm due to disturbance reduces the accumulation of pyoverdine. At intermediate synthesis rates, production of pyoverdine increases during disturbance as bacteria dispersed into the planktonic state enjoy increased growth and pyoverdine production rates. At low synthesis rates, disturbance does not alter the amount of pyoverdine produced since disturbance-driven access to nutrients does not augment pyoverdine synthesis. Our results suggest that environmental conditions shape robustness in the production of virulence factors and may lead to novel approaches to treat infections. IMPORTANCE Virulence factors are required to cause infections. Previous work has shown that the spatial organization of a population, such as a biofilm, can increase the production of some virulence factors, including pyoverdine, which is produced by Pseudomonas aeruginosa. Pyoverdine is essential for the infection process, and reducing its production can limit infections. We have discovered that periodically changing the spatial structure of a biofilm of P. aeruginosa strain PA14 using a physical force can reduce the production of pyoverdine. A mathematical model suggests that this is due to the disruption of spatial organization. Using additional strains of P. aeruginosa isolated from patients and the environment, we use experiments and modeling to show that this reduction in pyoverdine is due to interactions between biofilm density and the synthesis rate of pyoverdine. Our results identify conditions where pyoverdine production is reduced and may lead to novel ways to treat infections.

Pandemics, Protests, and Pronouns: The Changing Landscape of Biomedical Visualisation and Education.

Events in early 2020 changed the landscape of education for the foreseeable future, perhaps permanently. Three events had a significant impact; (1) the Coronavirus disease 2019 (COVID-19) pandemic, (2) the death of George Floyd, which resulted in the most recent Black Lives Matter (BLM) protests, and (3) the Twitter storm, the resultant societal fallout and freedom of speech campaigns, following comments made by author JK Rowling which many deemed transphobic. These events had a differential impact on biomedical sciences, when compared to other sectors. COVID-19 resulted in a global lockdown, with higher education institutions closing campuses and moving to online-only delivery. This rapid change required radical shifts in the use of technology, with mass delivery of teaching at short notice. The BLM protests further raised awareness of the inequalities within society, particularly those experienced by Black people and other oppressed groups. As a result, there have been calls for the decolonisation of the curriculum. The implications of these three key events have led institutions to rethink their policies, teaching delivery, assessment, curricula, and physical environments. This chapter considers (1) the implications of a swift change in the primary mode of curriculum delivery within Higher Education to online formats and (2) how recent adverse events have resulted in calls for much-needed changes in visual representations within biomedical sciences. Finally, we consider (3) the role of the hidden curriculum and the potential impact of visual representations in curricula on the delivery of healthcare and the fight against health inequalities, which are often as a result of implicit biases. The year 2020 has proven timely in presenting the opportunity for change, provided through the power of imagery.

Two Tales of Cardiomyopathy: Underscore for One Health Initiative.

Hypertrophic cardiomyopathy, a common cause of sudden cardiac death, results from mutations in the cardiac sarcomere. Although there has been much scientific exploration regarding this disease, there is still much to be elucidated. This E-challenge highlights two cases of cardiomyopathy and underscores the need for future multidisciplinary collaboration as outlined by the One Health Initiative.

The mechanisms and cell signaling pathways of programmed cell death in the bacterial world.

While programmed cell death was once thought to be exclusive to eukaryotic cells, there are now abundant examples of well regulated cell death mechanisms in bacteria. The mechanisms by which bacteria undergo programmed cell death are diverse, and range from the use of toxin-antitoxin systems, to prophage-driven cell lysis. Moreover, some bacteria have learned how to coopt programmed cell death systems in competing bacteria. Interestingly, many of the potential reasons as to why bacteria undergo programmed cell death may parallel those observed in eukaryotic cells, and may be altruistic in nature. These include protection against infection, recycling of nutrients, to ensure correct morphological development, and in response to stressors. In the following chapter, we discuss the molecular and signaling mechanisms by which bacteria undergo programmed cell death. We conclude by discussing the current open questions in this expanding field.

The public and private benefit of an impure public good determines the sensitivity of bacteria to population collapse in a snowdrift game.

When cooperation is critical for survival, cheating can lead to population collapse. One mechanism of cooperation that permits the coexistence of cooperators and cheaters is an impure public good, whose public benefits are shared, but with a private benefit retained by the cooperator. It has yet to be determined how the contributions of the public and private benefit affect population survival. Using simulations and experiments with ß-lactamase-expressing bacteria, we found that for a given amount of public and private benefit, the population was most sensitive to collapse when initiated from an intermediate fraction of cooperators due to the near-concurrent collapse of the cooperator and cheater populations. We found that increasing the ratio of public to private benefit increased sensitivity to collapse. A low ratio allowed cooperators to survive on their private benefit after the public benefit could not rescue the cheaters. A high ratio allowed the cheaters to survive to high concentrations of ampicillin due to the high public benefit. However, small increases in ampicillin caused a rapid decline in the entire population as the private benefit was insufficient to allow self-rescue of the cooperators. Our findings have implications in the persistence of populations that rely on cooperation for survival.

Doxycycline improves clinical outcomes during cystic fibrosis exacerbations.

Matrix metalloprotease-9 (MMP-9) plays a role in progression of cystic fibrosis, and doxycycline can reduce MMP-9 in vitro Here, we explore the effect of doxycycline during cystic fibrosis exacerbation treatment on MMP-9 related readouts and clinical end-points.This randomised, double-blind, placebo-controlled study enrolled hospitalised patients with cystic fibrosis undergoing exacerbation. In total, 20 participants were given doxycycline and 19 participants were given placebo over an 8-day period during hospitalisation. Biospecimens were collected at the beginning and the end of the study period. Primary end-points were total MMP-9 levels in the sputum and safety/tolerability. Secondary end-points included change in lung function, time to next exacerbation, and markers of MMP-9-related protease activity (active MMP-9 and TIMP-1). Nonparametric testing was used for within-group and between-group analyses.Doxycycline was well tolerated, with no treatment discontinuations or serious adverse events. Doxycycline reduced total sputum MMP-9 levels by 63.2% (p<0.05), and was also associated with a 56.5% reduction in active MMP-9 levels (p<0.05), a 1.6-fold increase in sputum TIMP-1 (p<0.05), improvement in forced expiratory volume in 1 s (p<0.05), and an increase in time to next exacerbation (p<0.01).Adjunctive use of doxycycline improved dysregulated MMP-9 levels in sputum, along with biomarkers consistent with a reduced proteolytic pulmonary environment. Improvement in clinical outcome measures suggests an important therapeutic benefit of doxycycline for individuals with cystic fibrosis.

Evaluation of red blood cell distribution width as a prognostic indicator in cats with acquired heart disease, with and without congestive heart failure.

Objectives Congestive heart failure secondary to cardiomyopathy is a common manifestation of cardiac disease in cats, carrying a variable prognosis. The objective of this retrospective study was to evaluate the relationship between red blood cell distribution width (RDW) and survival time in feline patients with acquired heart disease with and without congestive heart failure (CHF). Methods Three hundred and forty-nine client-owned cats with echocardiograms and complete blood count, including RDW measurement, performed between March 2006 and December 2011, were included in the study. Patient characteristics, including signalment, hematocrit, RDW, echocardiographic parameters and survival, were recorded. Comparisons between RDW in cats with asymptomatic acquired heart disease and those with CHF were made. Survival was documented and compared at 30 days and 6 months. Results CHF was present in 80 cats and absent in 269 cats. Cats with CHF had an increase in mortality compared with cats without CHF at 30 days and 6 months ( P = 0.007 and P = 0.04, respectively). RDW was not significantly associated with survival in cats with or without CHF at 30 days or 6 months. A significant difference was found between median RDW values in cats with CHF vs cats without CHF (16.3% vs 15.8%; P = 0.02). The median RDW value was significantly higher in cats with unclassified cardiomyopathy compared with cats with other types of cardiomyopathy (16.3% vs 15.8%; P = 0.03). Conclusions and relevance Single RDW values did not predict mortality in cats with acquired heart disease but may be useful in determining if cats have decompensated heart disease and CHF. Human studies indicate that incremental increases in serial RDW measurements are associated with decreased survival; serial RDW measurements in cats may be an area of future study.

Retrospective evaluation of the incidence and prognostic significance of spontaneous echocardiographic contrast in relation to cardiac disease and congestive heart failure in cats: 725 cases (2006-2011).

OBJECTIVE: To determine whether the presence of spontaneous echocardiographic contrast (SEC) in cats with cardiomyopathy is associated with increased mortality. To establish whether specific types of cardiomyopathy are more often associated with SEC in an attempt to provide a risk-stratification scheme for cats with increased risk of thromboembolic events. DESIGN: Retrospective study 2006-2011. SETTING: Tertiary referral and teaching hospital. ANIMALS: Seven hundred twenty-five client-owned cats undergoing echocardiographic evaluation. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, including age, breed, clinical signs, type of cardiovascular disease, presence of SEC, and survival time were recorded. Thyroxine, HCT, and blood pressure were recorded when available. Among cats diagnosed with cardiac abnormalities based on echocardiographic findings, those with SEC were at significantly increased risk of death as compared to those without SEC. Cats with dilated cardiomyopathy, unclassified cardiomyopathy, and hypertrophic cardiomyopathy were significantly more likely to have SEC compared to cats with other types of cardiac disease. CONCLUSIONS: Cats with cardiomyopathy and SEC have an increased risk of death compared to cats without SEC, although other previously identified factors such as the presence of congestive heart failure and increased left atrium to aorta ratio remain important determinants of mortality. Cats with hypertrophic cardiomyopathy, unclassified cardiomyopathy, and dilated cardiomyopathy may benefit from anticoagulant therapy due to the increased risk of SEC in these subpopulations.

Biomarkers for differentiation of causes of respiratory distress in dogs and cats: Part 1--Cardiac diseases and pulmonary hypertension.

OBJECTIVE: To review the current veterinary and relevant human literature regarding biomarkers of cardiac disease leading to respiratory compromise. DATA SOURCES: Veterinary and human medical literature: original research articles, scientific reviews, consensus statements, and recent textbooks. HUMAN DATA SYNTHESIS: Cardiac troponins (cTn) and natriuretic peptides are routinely used in human medicine. VETERINARY DATA SYNTHESIS: Although biomarkers should not be accepted in lieu of gold standard diagnostics, they may be useful in directing care in the stabilization process. Biomarkers of congestive heart failure (CHF) include natriuretic peptides, cTn, and endothelin. cTnI is useful in differentiating causes of pericardial effusion, but is unlikely to be useful in differentiating CHF from other causes of respiratory distress. The most extensively studied and promising cardiac biomarker is amino-terminal probrain natriuretic peptide, although a bedside test is not currently available. Other natriuretic peptides have also proven useful, but have lower availability. Endothelin is unlikely to be clinically useful. Although critically evaluated for their use in cardiac diseases, many of the biomarkers are affected by more than one type of respiratory or systemic disease. Several cardiac biomarkers are increased in cases of pulmonary hypertension (PH), but discerning CHF alone from PH or a combination of heart disease and PH is challenging when evaluating biomarkers alone. CONCLUSION: At this time, there are no point-of-care tests for biomarkers that can reliably differentiate among causes of dyspnea of cardiac origin in dogs and cats, although there are reference laboratory tests that show promise and future development of point-of-care tests that may be useful in certain situations.

Biomarkers for differentiation of causes of respiratory distress in dogs and cats: Part 2--Lower airway, thromboembolic, and inflammatory diseases.

OBJECTIVES: To review the current veterinary and relevant human literature regarding biomarkers of respiratory diseases leading to dyspnea and to summarize the availability, feasibility, and practicality of using respiratory biomarkers in the veterinary setting. DATA SOURCES: Veterinary and human medical literature: original research articles, scientific reviews, consensus statements, and recent textbooks. HUMAN DATA SYNTHESIS: Numerous biomarkers have been evaluated in people for discriminating respiratory disease processes with varying degrees of success. VETERINARY DATA SYNTHESIS: Although biomarkers should not dictate clinical decisions in lieu of gold standard diagnostics, their use may be useful in directing care in the stabilization process. Serum immunoglobulins have shown promise as an indicator of asthma in cats. A group of biomarkers has also been evaluated in exhaled breath. Of these, hydrogen peroxide has shown the most potential as a marker of inflammation in asthma and potentially aspiration pneumonia, but methods for measurement are not standardized. D-dimers may be useful in screening for thromboembolic disease in dogs. There are a variety of markers of inflammation and oxidative stress, which are being evaluated for their ability to assess the severity and type of underlying disease process. Of these, amino terminal pro-C-type natriuretic peptide may be the most useful in determining if antibiotic therapy is warranted. Although critically evaluated for their use in respiratory disorders, many of the biomarkers which have been evaluated have been found to be affected by more than one type of respiratory or systemic disease. CONCLUSION: At this time, there are point-of-care biomarkers that have been shown to reliably differentiate between causes of dyspnea in dogs and cats. Future clinical research is warranted to understand of how various diseases affect the biomarkers and more bedside tests for their utilization.

Higher-dose oxytocin and hemorrhage after vaginal delivery: a randomized controlled trial.

OBJECTIVE: Higher-dose oxytocin is more effective than lower-dose regimens to prevent postpartum hemorrhage after cesarean delivery. We compared two higher-dose regimens (80 units and 40 units) to our routine regimen (10 units) among women who delivered vaginally. METHODS: In a double-masked randomized trial, oxytocin (80 units, 40 units, or 10 units) was administered in 500 mL over 1 hour after placental delivery. The primary outcome was a composite of any treatment of uterine atony or hemorrhage. Prespecified secondary outcomes included outcomes in the primary composite and a decline of 6% or more in hematocrit. A sample size of 600 per group (N=1,800) was planned to compare each of the 80-unit and 40-unit groups to the 10-unit group. At planned interim review (n=1,201), enrollment in the 40-unit group was stopped for futility and enrollment continued in the other groups. RESULTS: Of 2,869 women, 1,798 were randomized as follows: 658 to 80 units; 481 to 40 units; and 659 to 10 units. Most characteristics were similar across groups. The risk of the primary outcome in the 80-unit group (6%; relative risk [RR] 0.93, 95% confidence interval [CI] 0.62-1.40) or the 40-unit group (6%; RR 0.94, 95% CI 0.61-1.47) was not different compared with the 10-unit group (7%). Treatment with additional oxytocin after the first hour was less frequent with 80 units compared with 10 units (RR 0.41, 95% CI 0.19-0.88), as was a 6% or more decline in hematocrit (RR 0.83, 95% CI 0.69-0.99); both outcomes declined with increasing oxytocin dose. Outcomes were similar between the 40-unit and 10-unit groups. CONCLUSION: Compared with 10 units, 80 units or 40 units of prophylactic oxytocin did not reduce overall postpartum hemorrhage treatment when administered in 500 mL over 1 hour for vaginal delivery. Eighty units decreased the need for additional oxytocin and the risk of a decline in hematocrit of 6% or more. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00790062. LEVEL OF EVIDENCE: I.

Training inpatient mental health staff how to enhance patient engagement with medications: Medication Alliance training and dissemination outcomes in a large US mental health hospital.

RATIONALE, AIMS AND OBJECTIVES: The Medication Alliance training programme has previously been shown to be effective in enhancing clinician knowledge, attitudes and skills in regard to non-adherent individuals in a community-based psychiatric setting. The current study attempts to replicate these findings in an inpatient setting and assess the feasibility of dissemination using a train-the-trainer model. METHOD: One hundred and thirteen staff from four wards at an inpatient psychiatric facility attended Medication Alliance training workshops over 3 days. Two wards comprised an expert trained group (n = 67); and the remaining two wards made up a novice trained group (n = 46). The novice trained group attended training 6 months after the expert group, and were trained by selected trainees from the expert group. Participants completed a package of questionnaires both before and after their training to determine if Medication Alliance resulted in any changes in knowledge, attitudes and skills. RESULTS: Paired t-tests showed significant improvements across both groups for knowledge, attitudes and one skill domain following training in Medication Alliance. There were no differences at baseline between groups and analysis of post-test scores yielded no significant difference between the groups in terms of training effect for knowledge, attitudes or skills. CONCLUSIONS: Medication Alliance can be successfully implemented in an inpatient setting, enhancing knowledge, attitudes and at least some skill domains of staff in dealing with non-adherent patients. The equivalence of results between the expert and novice trained training groups suggests that Medication Alliance may be more broadly disseminated using a cost-effective train-the-trainer model.

Preliminary reliability of an observer rating scale for assessing medication adherence on psychiatric wards.

OBJECTIVES: Medication non-adherence is a major contributor to poor outcomes following discharge from psychiatric hospitals. It is therefore imperative that staff are able to accurately assess the extent to which patients have engaged with treatment. This study presents data on a new observer rating instrument of patient medication adherence. METHODS: Staff participating in a medication adherence training programme ('Medication Alliance') were given a brief overview of the Observer Rating of Medication Taking (ORMT) scale. Participants then watched six video vignettes of patient adherence behaviour and provided a rating on their scale for each vignette. Participant ratings were then compared with 'expert' ratings. RESULTS: Percentage agreement between 'experts' and participants ranged from a low of 68% through to 98% agreement. Only one vignette was rated significantly differently [Mdiff = 0.33, t(49) = 2.08, P = 0.007], with 32% of people falling outside the expert rating range (all of those ratings being higher). This difference was attributed to between group differences, [F(2,47) = 3.49, P < 0.05] and post hoc assessment suggested that the differences between expert and trainee ratings for the vignette may be explained by trainee characteristics, as distinct from inherent characteristics of the rating scale. CONCLUSION: The ORMT can help mental health professionals identify particular non-adherent behaviours thus facilitating identification and treatment of likely non-adherence before discharge. The scale appears to be accessible to a variety of professions with a range of experience and requires minimum training in order to be used reliably.

Vitamin E for Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Vitamin E is a dietary compound that functions as an antioxidant scavenging toxic free radicals. Evidence that free radicals may contribute to the pathological processes of cognitive impairment including Alzheimer's disease (AD) has led to interest in the use of Vitamin E in the treatment of Alzheimer's disease and Mild Cognitivie Impairment (MCI). OBJECTIVES: To assess the efficacy of Vitamin E in the treatment of Alzheimer's disease and prevention of progression of Mild Cognitive Impairment to Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement's Specialized Register was searched on 8 January 2007 using the following terms: "Vitamin E", vitamin-E, alpha-tocopherol. The CDCIG Registers contains records from major health care databases and ongoing trial databases and is updated regularly. SELECTION CRITERIA: All unconfounded, double blind, randomized trials in which treatment with Vitamin E at any dose was compared with placebo for patients with Alzheimer's disease or Mild Cognitive Impairment. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the selection criteria and assessed study quality and extracted and analysed the data. For each outcome measure data were sought on every patient randomized. Where such data were not available an analysis of patients who completed treatment was conducted. MAIN RESULTS: Only 2 studies met the inclusion criteria. The primary outcome used in the AD study was survival time to the first of 4 endpoints: death, institutionalisation, loss of 2 out of 3 basic activities of daily living and severe dementia (defined as a global Clinical Dementia Rating of 3). The investigators reported the total numbers in each group who reached the primary endpoint within two years for participants completing the study ("completers"). There appeared to be some benefit from Vitamin E with fewer participants reaching endpoint - 58% (45/77) of completers compared with 74% (58/78) - a Peto odds ratio of 0.49, 95% confidence interval 0.25 to 0.96.However, more participants taking Vitamin E suffered a fall (12/77 compared with 4/78; odds ratio 3.07, 95% CI 1.09 to 8.62). It was not possible to interpret the reported results for specific endpoints or for secondary outcomes of cognition, dependence, behavioural disturbance and activities of daily living.The primary outcome used in the MCI study which had 769 participants (257 in the Vitamin E group and 259 in the placebo group; a third Donepezil group of 253 was not included in this review) was the time to progression from MCI to possible or probable AD. A total of 214 of the 769 participants had progression to dementia, with 212 being classified as having possible or probable AD. There was no significant difference in the probability of progression from MCI to AD between the Vitamin E group and the placebo group. There was no significant difference between the placebo group and the Vitamin E group in adverse events. Five subjects died in each group and 72 discontinued treatment in the Vitamin E group and 66 in the placebo group. AUTHORS' CONCLUSIONS: There is no evidence of efficacy of Vitamin E in the prevention or treatment of people with AD or MCI. More research is needed to identify the role of Vitamin E, if any, in the management of cognitive impairment.