Background Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system that results in progressive and irreversible disability. Fatigue is one of the most common MS-related symptoms and is characterized by a persistent lack of energy that impairs daily functioning. The burden of MS-related fatigue is complex and multidimensional, and to our knowledge, no systematic literature review has been conducted on this subject. The purpose of this study was to conduct a systematic literature review on the epidemiology and burden of fatigue in people with multiple sclerosis (pwMS). Methods Systematic searches were conducted in MEDLINE, Embase, and Evidence-Based Medicine Reviews to identify relevant studies of fatigue in pwMS. English-language records published from 2010 to January 2020 that met predefined eligibility criteria were included. We initially selected studies that reported quality of life (QoL) and economic outcomes according to categories of fatigue (e.g., fatigued vs non-fatigued). Studies assessing associations between economic outcomes and fatigue as a continuous measure were later included to supplement the available data. Results The search identified 8147 unique records, 54 of which met the inclusion criteria. Of these, 39 reported epidemiological outcomes, 11 reported QoL, and 9 reported economic outcomes. The supplementary screen for economic studies with fatigue as a continuous measure included an additional 20 records. Fatigue prevalence in pwMS ranged from 36.5 to 78.0%. MS-related fatigue was consistently associated with significantly lower QoL. Results on the economic impact of fatigue were heterogeneous, but most studies reported a significant association between presence or severity of fatigue and employment status, capacity to work, and sick leave. There was a gap in evidence regarding the direct costs of MS-related fatigue and the burden experienced by caregivers of pwMS. Conclusion Fatigue is a prevalent symptom in pwMS and is associated with considerable QoL and economic burden. There are gaps in the evidence related to the direct costs of MS-related fatigue and the burden of fatigue on caregivers. Addressing fatigue over the clinical course of the disease may improve health and economic outcomes for patients with MS.

Introduction Understanding patients’ preferences for long-acting injectable (LAI) or oral antipsychotics (pills) could help reduce potential barriers to LAI use in schizophrenia. Methods Post hoc analyses were conducted from a double-blind, randomized, non-inferiority study (NCT01515423) of 3-monthly vs 1-monthly paliperidone palmitate in patients with schizophrenia. Data from the Medication Preference Questionnaire, administered on day 1 (baseline; open-label stabilization phase), were analyzed. The questionnaire includes four sets of items: 1) reasons for general treatment preference based on goals/outcomes and preference for LAI vs pills based on 2) personal experience, 3) injection-site (deltoid vs gluteal), 4) dosing frequency (3-monthly vs 1-monthly). A logistic regression analysis was performed to assess the effect of baseline variables on preference (LAIs or pills). Results Data from 1402 patients were available for analysis. Patients who preferred LAIs recognized these outcomes as important: “I feel more healthy” (57%), “I can get back to my favorite activities” (56%), “I don’t have to think about taking my medicines” (54%). Most common reasons for medication preference (LAI vs pills) were: “LAIs/pills are easier for me” (67% vs 18%), “more in control/don’t have to think about taking medicine” (64% vs 14%), “less pain/sudden symptoms” (38% vs 18%) and “less embarrassed” (0% vs 46%). Majority of patients (59%) preferred deltoid over gluteal injections (reasons: faster administration [63%], easier [51%], less embarrassing [44%]). In total, 50% of patients preferred 3-monthly over 1-monthly (38%) or every day (3%) dosing citing reasons: fewer injections [96%], fewer injections are less painful [84%], and fewer doctor visits [80%]. From logistic regression analysis, 77% of patients preferred LAI over pills; culture and race appeared to play a role in this preference. Conclusion Patients who preferred LAI antipsychotics prioritized self-empowerment and quality-of-life-related goals. When given the option, patients preferred less-frequent, quarterly injections over monthly injections and daily oral medications.

Purpose: Relapse and treatment adherence to paliperidone palmitate once-monthly (PP1M) and three-monthly (PP3M) formulations in patients with schizophrenia were evaluated and compared using health claims data. Patients and Methods: Data (June 2015─June 2018) obtained from the MarketScan ® Multi-State Medicaid Database were retrospectively analyzed. Patients aged ≥18 years with ≥1 claim for schizophrenia diagnosis prior to and/or at index date (i.e., date of first PP3M prescription record for PP3M patients and same month/year as the matched PP3M patients for PP1M patients) and continuous enrollment in the insurance plan for ≥12 months prior to index date (baseline) were included. PP1M cohort included patients who received ≥4 PP1M doses. PP3M patients were matched with PP1M patients (1:3) using propensity score matching and prevalent new user design. Outcome measures were relapse rate, time to relapse, proportion of days covered (PDC), and level of treatment adherence defined by PDC in five levels. Time to relapse was compared by Kaplan-Meier survival curves and log-rank test with the hazard ratio calculated using Cox proportion hazards model; PDC by t-test, and relapse rate and PDC categories by chi-square test. Results: A total of 1564 patients (428 PP3M and 1136 PP1M) were included. Relapse rate was lower in PP3M cohort (10.5%) compared with PP1M cohort (15.7%). Incidence rate of relapse was 8.98/100 person-years (PY) in PP3M cohort and 13.81/100 PY in PP1M cohort. After a mean (SD) follow-up of 456.1 (240.28) days in PP3M cohort and 465.4 (237.95) days in PP1M cohort, PP3M patients had a significantly lower relapse risk (hazard ratio: 0.65, 95% CI: 0.47, 0.90) than PP1M patients. Treatment adherence was significantly (p<0.0001) higher in PP3M versus PP1M cohort. Conclusion: Risk of relapse was significantly lower, and treatment adherence was significantly higher in PP3M cohort compared with PP1M cohort. Higher treatment adherence was associated with lower relapse rate.

The therapeutic paradigm in Alzheimer's disease (AD) is shifting from symptoms management towards prevention goals. Secondary prevention requires the identification of individuals without clinical symptoms of AD, yet "at-risk" of developing Alzheimer's dementia in the future, and thus, the use of predictive modeling. The objective of this study was to review the ethical concerns and social implications generated by this new approach. We conducted a systematic literature review in Medline, Embase, PsycInfo, and Scopus, and complemented it with a gray literature search between March and July 2018. Then we analyzed data qualitatively using a thematic analysis technique. We identified thirty-one ethical issues and social concerns corresponding to eight ethical principles: (i) Respect for autonomy, (ii) Beneficence, (iii) Non-maleficence, (iv) Equality, Justice and diversity, (v) Identity and stigma, (vi) Privacy, (vii) Accountability, transparency and professionalism, and (viii) Uncertainty avoidance. Much of the literature sees the discovery of disease-modifying treatment as a necessary and sufficient condition to justify AD risk assessment, overlooking future challenges in providing equitable access to it, establishing long-term treatment outcomes and social consequences of this approach, e.g. medicalization. The ethical/social issues associated specifically with predictive models, such as the adequate predictive power and reliability, infrastructural requirements, data privacy, potential for personalized medicine in AD and limiting access to future AD treatment based on risk stratification, were covered scarcely. Therefore, the ethical discussion needs to advance to reflect recent scientific developments and guide clinical practice now and in the future, so that necessary safeguards are implemented for large-scale AD secondary prevention.

Background: Dementia has been described as the greatest global health challenge in the 21st Century on account of longevity gains increasing its incidence, escalating health and social care pressures. These pressures highlight ethical, social, and political challenges about healthcare resource allocation, what health improvements matter to patients, and how they are measured. This study highlights the complexity of the ethical landscape, relating particularly to the balances that need to be struck when allocating resources; when measuring and prioritizing outcomes; and when individual preferences are sought. Objective: Health outcome prioritization is the ranking in order of desirability or importance of a set of disease-related objectives and their associated cost or risk. We analyze the complex ethical landscape in which this takes place in the most common dementia, Alzheimer’s disease. Methods: Narrative review of literature published since 2007, incorporating snowball sampling where necessary. We identified, thematized, and discussed key issues of ethical salience. Results: Eight areas of ethical salience for outcome prioritization emerged: 1) Public health and distributive justice, 2) Scarcity of resources, 3) Heterogeneity and changing circumstances, 4) Knowledge of treatment, 5) Values and circumstances, 6) Conflicting priorities, 7) Communication, autonomy and caregiver issues, and 8) Disclosure of risk. Conclusion: These areas highlight the difficult balance to be struck when allocating resources, when measuring and prioritizing outcomes, and when individual preferences are sought. We conclude by reflecting on how tools in social sciences and ethics can help address challenges posed by resource allocation, measuring and prioritizing outcomes, and eliciting stakeholder preferences.