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

International development of a patient-centered core outcome set for assessing health-related quality of life in metastatic breast cancer patients

Purpose For patients living with metastatic breast cancer (MBC), achieving best possible health-related quality of life, along with maximizing survival, is vital. Yet, we have no systemic way to determine if we achieve these goals. A Core Outcome Set (COS) that allows standardized measurement of outcomes important to patients, but also promotes discussing these outcomes during clinical encounters, is long overdue. Methods An international expert group (EG) of patient advocates, researchers, medical specialists, nurse specialists, and pharmaceutical industry representatives (n = 17) reviewed a list of relevant outcomes retrieved from the literature. A broader group (n = 141: patients/patient advocates (n = 45), health care professionals/researchers (n = 64), pharmaceutical industry representatives (n = 28), and health authority representatives (n = 4)) participated in a modified Delphi procedure, scoring the relevance of outcomes in two survey rounds. The EG finalized the COS in a consensus meeting. Results The final MBC COS includes 101 variables about: (1) health-related quality of life (HRQoL, n = 26) and adverse events (n = 24); (2) baseline patient characteristics (n = 9); and (3) clinical variables (n = 42). Many outcome that cover aspects of HRQoL relevant to MBC patients are included, e.g. daily functioning (including ability to work), psychosocial/emotional functioning, sexual functioning, and relationship with the medical team. Conclusion The COS developed in this study contains important administrative data, clinical records, and clinician-reported measures that captures the impact of cancer. The COS is important for standardization of clinical research and implementation in daily practice and has received accreditation by the International Consortium for Health Outcomes Measurement (ICHOM)

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