Measuring quality of life of people with predementia and dementia and their caregivers: a systematic review protocol

Introduction Dementia is the fastest growing major cause of disability globally and may have a profound impact on the health-related quality of life (HRQoL) of both the patient with dementia and those who care for them. This review aims to systematically identify and synthesise the measurements of HRQoL for people with, and their caregivers across the full spectrum of, dementia from its preceding stage of predementia to end of life. Methods and analysis A systematic literature review was conducted in Medical Literature Analysis and Retrieval System Online , ExcerptaMedicadataBASE, Cochrane Database of Systematic Reviews , Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effect, National Health Service Economic Evaluation Database and PsycINFO between January 1990 and the end of April 2017. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed with the Effective Public Health Practice Project quality assessment tool. HRQoL measurements will be presented separately for people with dementia and caregivers by instrument used and, when possible, HRQoL will be reported by disease type and stage of the disease. Descriptive statistics of the results will be provided. A narrative synthesis of studies will also be provided discussing differences in HRQoL measurements by instrument used to estimate it, type of dementia and disease severity. Ethics and dissemination This systematic literature review is exempt from ethics approval because the work is carried out on published documents. The findings of the review will be disseminated in a related peer-reviewed journal and presented at conferences. They will also contribute to the work developed in the Real World Outcomes across the Alzheimer’s disease spectrum for better care: multimodal data access platform (ROADMAP)

Challenges for Optimizing Real-World Evidence in Alzheimer’s Disease: The ROADMAP Project

ROADMAP is a public-private advisory partnership to evaluate the usability of multiple data sources, including real-world evidence, in the decision-making process for new treatments in Alzheimer’s disease, and to advance key concepts in disease and pharmacoeconomic modeling. ROADMAP identified key disease and patient outcomes for stakeholders to make informed funding and treatment decisions, provided advice on data integration methods and standards, and developed conceptual cost-effectiveness and disease models designed in part to assess whether early treatment provides long-term benefit

Mining a Cathepsin Inhibitor Library for New Antiparasitic Drug Leads

The targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas' disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ∼2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases. Compounds active against parasite enzymes were subsequently screened against cultured Plasmodium falciparum, Trypanosoma brucei brucei and/or Trypanosoma cruzi parasites and evaluated for cytotoxicity to mammalian cells. The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts

Examination of hospital length of stay in Canada among patients with acute bacterial skin and skin structure infection caused by methicillin-resistant Staphylococcus aureus

Michele H Potashman,1 Michael Stokes,2 Jieruo Liu,2 Robin Lawrence,1 Linda Harris1 1Global Health Outcomes, Merck & Co, Inc., Kenilworth, NJ, USA; 2Evidera, Lexington, MA, USA Purpose: Skin infections, particularly those caused by resistant pathogens, represent a clinical burden. Hospitalization associated with acute bacterial skin and skin structure infections (ABSSSI) caused by methicillin-resistant Staphylococcus aureus (MRSA) is a major contributor to the economic burden of the disease. This study was conducted to provide current, real-world data on hospitalization patterns for patients with ABSSSI caused by MRSA across multiple geographic regions in Canada. Patients and methods: This retrospective cohort study evaluated length of stay (LOS) for hospitalized patients with ABSSSI due to MRSA diagnosis across four Canadian geographic regions using the Discharge Abstract Database. Patients with ICD-10-CA diagnosis consistent with ABSSSI caused by MRSA between January 2008 and December 2014 were selected and assigned a primary or secondary diagnosis based on a prespecified ICD-10-CA code algorithm. Results: Among 6,719 patients, 3,273 (48.7%) and 3,446 (51.3%) had a primary and secondary diagnosis, respectively. Among patients with a primary or secondary diagnosis, the cellulitis/erysipelas subtype was most common. The majority of patients presented with 0 or 1 comorbid condition; the most common comorbidity was diabetes. The mean LOS over the study period varied by geographic region and year; in 2014 (the most recent year analyzed), LOS ranged from 7.7 days in Ontario to 13.4 days in the Canadian Prairie for a primary diagnosis and from 18.2 days in Ontario to 25.2 days in Atlantic Canada for a secondary diagnosis. A secondary diagnosis was associated with higher rates of continuing care compared with a primary diagnosis (10.6%–24.2% vs 4.6%–12.1%). Conclusion: This study demonstrated that the mean LOS associated with ABSSSI due to MRSA in Canada was minimally 7 days. Clinical management strategies, including medication management, which might facilitate hospital discharge, have the potential to reduce hospital LOS and related economic burden associated with ABSSSI caused by MRSA. Keywords: ABSSSI, MRSA, Canadian provinces, LOS, hospital outcomes, time trend

What outcomes are important to patients with mild cognitive impairment or Alzheimer’s disease, their caregivers, and health-care professionals? A systematic review

Introduction: Clinical trials involving patients with Alzheimer’s disease (AD) continue to try to identify disease-modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. Methods: A systematic review sought research that elicited information from people with AD, their caregivers, and health-care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. Results: Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. Discussion: Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments.</br

Health-related quality of life in people with predementia Alzheimer's disease, mild cognitive impairment or dementia measured with preference-based instruments: a systematic literature review

Background Obtaining reliable estimates of the health-related quality of life (HR-QoL) of people with predementia Alzheimer’s disease [AD] (preclinical or prodromal AD), mild cognitive impairment (MCI) and dementia is essential for economic evaluations of related health interventions. Aims To provide an overview of which quality of life instruments are being used to assess HR-QoL in people with predementia AD, MCI or dementia; and, to summarise their reported HR-QoL levels at each stage of the disease and by type of respondent. Methods We systematically searched for and reviewed eligible studies published between January 1990 and the end of April 2017 which reported HR-QoL for people with predementia AD, MCI or dementia. We only included instruments which are preference-based, allowing index scores/utility values to be attached to each health state they describe based on preferences obtained from population surveys. Summary results were presented by respondent type (self or proxy), type of instrument, geographical location and, where possible, stage of disease. Health state utility values derived using the EuroQoL 5-Dimensions (EQ-5D) were meta-analysed by pooling reported results across all studies by disease severity (MCI, mild, mild to moderate, moderate, severe dementia, not specified) and by respondent (person with dementia, carer, general public, not specified), using a fixed-effects approach. Results We identified 61 studies which reported HR-QoL for people with MCI or dementia using preference-based instruments, of which 48 used the EQ-5D. Thirty-six studies reported HR-QoL for mild and/or moderate disease severities, and 12 studies reported utility values for MCI. We found systematic differences between self-rated and proxy-rated HR-QoL, with proxy-rated utility valued being significantly lower in more severe disease states. Conclusions A substantial literature now exists quantifying the impact of dementia on HR-QoL using preference-based measures, giving researchers and modellers a firmer basis on which to select appropriate utility values when estimating the effectiveness and cost-effectiveness of interventions in this area. Further research is required on HR-QoL of people with preclinical and prodromal AD and MCI, possible differences by type of dementia, the effects of comorbidities, study setting and the informal caregiver’s own HR-QoL, including any effect of that on their proxy-ratings

Health-related quality of life in people with predementia Alzheimer's disease, mild cognitive impairment or dementia measured with preference-based instruments:a systematic literature review

Background Obtaining reliable estimates of the health-related quality of life (HR-QoL) of people with predementia Alzheimer’s disease [AD] (preclinical or prodromal AD), mild cognitive impairment (MCI) and dementia is essential for economic evaluations of related health interventions. Aims To provide an overview of which quality of life instruments are being used to assess HR-QoL in people with predementia AD, MCI or dementia; and, to summarise their reported HR-QoL levels at each stage of the disease and by type of respondent. Methods We systematically searched for and reviewed eligible studies published between January 1990 and the end of April 2017 which reported HR-QoL for people with predementia AD, MCI or dementia. We only included instruments which are preference-based, allowing index scores/utility values to be attached to each health state they describe based on preferences obtained from population surveys. Summary results were presented by respondent type (self or proxy), type of instrument, geographical location and, where possible, stage of disease. Health state utility values derived using the EuroQoL 5-Dimensions (EQ-5D) were meta-analysed by pooling reported results across all studies by disease severity (MCI, mild, mild to moderate, moderate, severe dementia, not specified) and by respondent (person with dementia, carer, general public, not specified), using a fixed-effects approach. Results We identified 61 studies which reported HR-QoL for people with MCI or dementia using preference-based instruments, of which 48 used the EQ-5D. Thirty-six studies reported HR-QoL for mild and/or moderate disease severities, and 12 studies reported utility values for MCI. We found systematic differences between self-rated and proxy-rated HR-QoL, with proxy-rated utility valued being significantly lower in more severe disease states. Conclusions A substantial literature now exists quantifying the impact of dementia on HR-QoL using preference-based measures, giving researchers and modellers a firmer basis on which to select appropriate utility values when estimating the effectiveness and cost-effectiveness of interventions in this area. Further research is required on HR-QoL of people with preclinical and prodromal AD and MCI, possible differences by type of dementia, the effects of comorbidities, study setting and the informal caregiver’s own HR-QoL, including any effect of that on their proxy-ratings