Evaluating Response to High-Dose 13.3 mg/24 h Rivastigmine Patch in Patients with Severe Alzheimer's Disease

AIMS: To identify factors predicting improvement/stabilization on the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) and investigate whether early treatment responses can predict long-term outcomes, during a trial of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch in patients with severe Alzheimer's disease (AD). METHODS: Logistic regression was used to relate Week 24 ADCS-CGIC score to potential baseline predictors. Additional analyses based on receiver-operating characteristic curves were performed using Week 8/16 ADCS-CGIC scores to predict response (13.3 mg/24 h patch) at Week 24. ADCS-CGIC score of (1) 1-3 = "improvement," (2) 1-4 = "improvement or no change". RESULTS: "Treatment" (13.3 mg/24 h patch) and increased age were significant predictors of "improvement" (P = 0.01 and P = 0.003, respectively), and "treatment" (P = 0.001), increased age (P = 0.002), and prior AD treatment (P = 0.03) for "improvement or no change". At Week 8 and 16, ADCS-CGIC scores of 4 and 5 were optimal thresholds in predicting "improvement," and "improvement or no change," respectively, at Week 24. CONCLUSIONS: A significant therapeutic effect of high-dose rivastigmine patch on ADCS-CGIC response was observed. The 13.3 mg/24 h patch was identified as a predictor of "improvement" or "improvement or no change". Patients with minimal worsening/improvement/no change after treatment initiation may be more likely to respond following long-term therapy

Evaluating High-Dose Rivastigmine Patch in Severe Alzheimer’s Disease: Analyses with Concomitant Memantine Usage as a Factor

Background: ACTION, a 24-week, prospective, randomized, parallel-group, double-blind study in patients with severe Alzheimer’s disease (AD), demonstrated significant efficacy of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch on the Severe Impairment Battery (SIB) and Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale–Severe Impairment Version (ADCS-ADL-SIV). Overall, 61% of the study population received at least 1 dose of concomitant memantine, regardless of dose or duration. This retrospective analysis investigated the effects of concomitant memantine on the efficacy, safety and tolerability of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch. Methods: Patients were stratified according to whether or not they received at least one dose of concomitant memantine during the double-blind phase. Changes from baseline on the SIB and ADCS-ADL-SIV were compared using analysis of covariance (ANCOVA) with treatment, pooled center, memantine usage and treatment-by-memantine as factors, and baseline as a covariate. Safety and tolerability were assessed. Results: Memantine-treated patients were younger than those not receiving memantine (mean 75.9 and 78.8 years, respectively), with a lower screening Mini-Mental State Examination (8.6 and 9.2, respectively). ANCOVA confirmed there was no significant interaction (p>0.1) between study treatment and memantine use on the SIB or ADCS-ADL-SIV. The incidence of adverse events was: 71.4%, 13.3 mg/24 h patch with memantine; 79.7%, 13.3 mg/24 h patch alone; 74.7%, 4.6 mg/24 h patch with memantine; and 71.1%, 4.6 mg/24 h patch alone. Conclusion: These data suggest benefit of 13.3 mg/24 h versus 4.6 mg/24 h rivastigmine patch, regardless of concomitant memantine use. The incidence of adverse events with highdose patch was similar in memantine-treated patients and those not receiving memantine

A Practical Algorithm for Managing Alzheimer\u27s Disease: What, When, and Why?

Alzheimer\u27s disease (AD) is the most common form of dementia and its prevalence is increasing. Recent developments in AD management provide improved ways of supporting patients and their caregivers throughout the disease continuum. Managing cardiovascular risk factors, maintaining an active lifestyle (with regular physical, mental and social activity) and following a Mediterranean diet appear to reduce AD risk and may slow cognitive decline. Pharmacologic therapy for AD should be initiated upon diagnosis. All of the currently available cholinesterase inhibitors (ChEIs; donepezil, galantamine, and rivastigmine) are indicated for mild-to-moderate AD. Donepezil (10 and 23 mg/day) and rivastigmine transdermal patch (13.3 mg/24 h) are indicated for moderate-to-severe AD. Memantine, an N-methyl-d-aspartate receptor antagonist, is approved for moderate-to-severe AD. ChEIs have been shown to improve cognitive function, global clinical status and patients\u27 ability to perform activities of daily living. There is also evidence for reduction in emergence of behavioral symptoms with ChEI therapy. Treatment choice (e.g., oral vs. transdermal) should be based on patient or caregiver preference, ease of use, tolerability, and cost. Treatment should be individualized; patients can be switched from one ChEI to another if the initial agent is poorly tolerated or ineffective. Memantine may be introduced in moderate-to-severe disease stages. Clinicians will regularly monitor symptoms and behaviors, manage comorbidities, assess function, educate and help caregivers access information and support, evaluate patients\u27 fitness to drive or own firearms, and provide advice about the need for legal and financial planning. Review of caregiver well-being and prompt referral for support is vital

A 24-Week, Open-Label Extension Study to Investigate the Long-term Safety, Tolerability, and Efficacy of 13.3 mg/24 h Rivastigmine Patch in Patients With Severe Alzheimer Disease

The long-term safety, tolerability, and efficacy of high-dose 13.3 mg/24 h rivastigmine patch in severe Alzheimer disease was evaluated in a 24-week, open-label extension to the double-blind ACTION study. Safety and tolerability, and efficacy on the Alzheimer’s Disease Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV), Severe Impairment Battery (SIB), and ADCS-Clinical Global Impression of Change (ADCS-CGIC) were assessed. Overall, 197 patients continued on 13.3 mg/24 h patch; 199 uptitrated from 4.6 mg/24 h to 13.3 mg/24 h patch. The incidence of adverse events (AEs), serious AEs and discontinuations due to AEs was similar in patients who continued on, and patients who uptitrated to, 13.3 mg/24 h patch (AEs: 57.9% and 59.8%; serious AEs: 16.2% and 16.1%; discontinuations: 11.2% and 12.1%, respectively). Larger mean changes from double-blind baseline were observed in patients uptitrated on the ADCS-ADL-SIV (−4.6; SD=8.7) and SIB (−7.0; SD=16.6), than those who continued on 13.3 mg/24 h patch (−3.9; SD=8.0 and −4.7; SD=16.8, respectively). ADCS-CGIC scores were comparable. There were no clinically relevant between-group differences in safety and tolerability. Greater decline was observed in patients with delayed uptitration to high-dose 13.3 mg/24 h patch than patients who continued on high-dose patch

Reliability of self-report of health in juvenile offenders

The aim of the present study was to investigate the accuracy of self-reports of juvenile offenders on physical factors (e.g., sleep difficulties, weight related behaviors and weight perceptions), health risk behaviors (e.g., alcohol use), trauma history (e.g., physical and sexual abuse) and psychological factors (e.g., anxiety, suicidal and self-harm behaviors). Self-reports obtained via a Health Questionnaire from 242 incarcerated juvenile offenders were compared with standardized measures (Body Mass Index, Adolescent Psychopathology Scale and Child Trauma Questionnaire) to investigate the reliability (via construct validity) and veracity of their self-report. Using kappa estimates and receiver operating characteristic curves, results generally showed high agreement across measures, suggesting that self-report questions from the health survey could all be used reliably. The degree of accuracy indicated that young offenders are as reliable as clinical and community samples of adolescents in their self-report. These findings have implications for routine assessments and practice evaluations that rely on self-report as the method of data collection and as the basis for clinical formulation and treatment planning

Media Roles in Suicide Prevention: A Systematic Review

The aim of the current systematic review was to monitor and provide an overview of the research performed about the roles of media in suicide prevention in order to find out possible effects media reporting on suicidal behaviours might have on actual suicidality (completed suicides, attempted suicides, suicidal ideation). The systematic review was performed following the principles of the PRISMA statement and includes 56 articles. Most of the studies support the idea that media reporting and suicidality are associated. However, there is a risk of reporting bias. More research is available about how irresponsible media reports can provoke suicidal behaviours (the ‘Werther effect’) and less about protective effect media can have (the ‘Papageno effect’). Strong modelling effect of media coverage on suicide is based on age and gender. Media reports are not representative of official suicide data and tend to exaggerate sensational suicides, for example dramatic and highly lethal suicide methods, which are rare in real life. Future studies have to encounter the challenges the global medium Internet will offer in terms of research methods, as it is difficult to define the circulation of news in the Internet either spatially or in time. However, online media can provide valuable innovative qualitative research material

Mind your words: Oncologists' communication that potentially harms patients with advanced cancer: A survey on patient perspectives

Background: Many complaints in medicine and in advanced illnesses are about communication. Little is known about which specific communications harm. This study explored the perspectives of patients with advanced cancer about potentially harmful communication behaviors by oncologists and helpful alternatives. Methods: An online survey design was used that was based on literature scoping and patient/clinician/researcher input. Patients with advanced cancer (n = 74) reflected on the potential harmfulness of 19 communication situations. They were asked whether they perceived the situation as one in which communication could be harmful (yes/no). If they answered “yes,” they were asked whether they perceived the examples as harmful (yes/no) or helpful (yes/no) and to provide open comments. Results were analyzed quantitatively and qualitatively (content analysis). Results: Communication regarding information provision, prognosis discussion, decision-making, and empathy could be unnecessarily potentially harmful, and this occurred in various ways, such as making vague promises instead of concrete ones (92%), being too directive in decision-making (qualitative), and not listening to the patient (88%). Not all patients considered other situations potentially harmful (eg, introducing the option of refraining from anticancer therapy [49%] and giving too much [prognostic] information [60%]). Exploring each individual patients' needs/preferences seemed to be a precondition for helpful communication. Conclusions: This article provides patient perspectives on oncologists' unnecessarily potentially harmful communication behaviors and offers practical tools to improve communication in advanced cancer care. Both preventable pitfalls and delicate challenges requiring an individualized approach, where exploration might help, are described. Although providing difficult and unwelcome news is a core task for clinicians, this study might help them to do so while preventing potentially unnecessary harm

Trends in Suicidology: Personality as an Endophenotype for Molecular Genetic Investigations

In studying the genetics of suicide, should personality be used as an endophenotype (an intermediate trait lying somewhere on the developmental pathway from genes to phenotype)

The big five personality traits, perfectionism and their association with mental health among UK students on professional degree programmes

Background In view of heightened rates of suicide and evidence of poor mental health among healthcare occupational groups, such as veterinarians, doctors, pharmacists and dentists, there has been increasing focus on the students aiming for careers in these fields. It is often proposed that a high proportion of these students may possess personality traits which render them vulnerable to mental ill-health. Aim To explore the relationship between the big five personality traits, perfectionism and mental health in UK students undertaking undergraduate degrees in veterinary medicine, medicine, pharmacy, dentistry and law. Methods A total of 1744 students studying veterinary medicine, medicine, dentistry, pharmacy and law in the UK completed an online questionnaire, which collected data on the big five personality traits (NEO-FFI), perfectionism (Frost Multidimensional Perfectionism Scale), wellbeing (Warwick-Edinburgh Mental Well-being Scale), psychological distress (General Health Questionnaire-12), depression (Beck Depression Inventory-II) and suicidal ideation and attempts. Results Veterinary, medical and dentistry students were significantly more agreeable than law students, while veterinary students had the lowest perfectionism scores of the five groups studied. High levels of neuroticism and low conscientiousness were predictive of increased mental ill-health in each of the student populations. Conclusions The study highlights that the prevailing anecdotal view of professional students possessing maladaptive personality traits that negatively impact on their mental health may be misplaced