A Model to Assess the Outcomes Associated With Dementia With Lewy Bodies.

BACKGROUND: Research investigating outcomes associated with dementia with Lewy bodies (DLB) disease progression is scarce. Developing models of DLB disease progression will provide information on the burden of disease and facilitate the evaluation of treatments for DLB from a clinical and cost perspective. METHODS: Longitudinal, cognitive evaluation data were utilized in order to identify distinct health states for DLB and to estimate transition probabilities across the DLB disease continuum. These probabilities were applied to a health state transition model to evaluate disease progression and associated outcomes for a closed cohort over a fixed time horizon. The effect of a reduction in the risk of disease progression on outcomes was assessed. RESULTS: Estimated transition probabilities indicate that a patient >60 years of age with mild DLB has a 54%, 30%, 4%, and 12% chance of remaining mild, progressing to severe DLB, being institutionalized, and dying after 1 year, respectively. Reducing the annual risk of transitioning from mild to severe DLB by 40% decreased time institutionalized and increased time to death. CONCLUSIONS: This study used real-world longitudinal data to create a clinically relevant DLB disease progression model. Reducing the rate of disease progression resulted in meaningful benefits with potentially significant public health implications.

Direct Medical Costs of Dementia With Lewy Bodies by Disease Complexity.

OBJECTIVES: There is currently no accurate profile of the economic burden of dementia with Lewy bodies (DLB), particularly any examination of the direct medical costs of DLB by the number of affected clinical domains. Understanding how trends in the use of healthcare resources evolve as DLB progresses presents opportunities for the development of earlier and more appropriate interventions. DESIGN: Retrospective study using claims data extracted from the IBM MarketScan Commercial and Medicare Supplemental database. SETTING AND PARTICIPANTS: In total, 536 patients with DLB from the Commercial database and 5485 patients with DLB from the Medicare Supplemental database. METHODS: Patients were grouped into disease complexity categories based on core clinical features (ie, fluctuating cognition, motor symptoms, visual hallucinations, and rapid eye movement sleep behavior disorder in addition to dementia) observed during the study period: dementia with no core features observed, dementia plus 1, 2, or ≥3 core features, respectively. Outcome measures included healthcare resource utilization and healthcare costs. RESULTS: In both databases, total healthcare resource utilization and costs increased with number of core features. Compared with patients with no core features observed, patients in all other complexity categories had significantly higher mean medical visits and costs in both adjusted and unadjusted analyses. Fluctuating cognition was associated with the highest total costs, suggesting that this clinical feature in particular is associated with a considerable economic burden. CONCLUSIONS AND IMPLICATIONS: Analyzing direct medical costs of DLB by disease complexity using claims data showed that a higher cost impact was associated with increasing number of clinical domains affected and with specific clinical domains, suggesting the need for both targeted and comprehensive interventions to improve the overall economic burden of DLB.

The clinical and economic burden among caregivers of patients with Alzheimer's disease in Canada.

OBJECTIVE: To estimate the clinical and direct medical economic burden among Alzheimer disease (AD) caregivers using real-world, longitudinal patient-level data in Canada. METHODS/DESIGN: This retrospective observational study assessed the clinical and direct medical economic burden among individuals who cohabitate with AD patients ("AD caregiver cohort") compared with older adults who were cohabiting with another adult without dementia ("comparison cohort") using real-world data from the Southwestern Ontario database, a representative Canadian electronic health record (EHR) longitudinal EHR. RESULTS: The AD caregiver cohort (n = 2749; mild AD: n = 2254, moderate AD: n = 302, and severe AD, n = 193) had a similar or higher level of clinical and economic burden than the comparison cohort (n = 12 152). The overall AD cohort and caregivers of patients with mild AD had a similar clinical burden to the comparison cohort. Those caregiving for more severely affected AD patients had an increased risk of comorbidities and required more medication, physician attention, and hospital encounters compared with caregivers of less severe AD patients and the comparison cohort. Mean annual costs were higher among the AD caregiver cohort than the comparison cohort, and those caregiving for moderate and severe AD patients incurred the highest costs. Overall mortality was higher in the AD caregiver cohort compared with the comparison cohort. CONCLUSIONS: Caregivers of patients with mild AD had a similar clinical and direct economic burden to older adults who were not dementia caregivers, whereas the burden among caregivers of moderate and severe AD patients was much greater.

The burden of treatment-resistant depression: A systematic review of the economic and quality of life literature.

BACKGROUND: Major depressive disorder (MDD) is a global public health concern. In particular, treatment-resistant depression (TRD) represents a key unmet need in the management of MDD. A systematic review of the epidemiological and economic literature on the burden associated with an increasing number of treatment steps due to TRD/non-response within an MDD episode was performed to quantify the burden of TRD. METHODS: Studies were identified in the PubMed/Medline databases through April 27th, 2017. Articles were limited to full-length peer-reviewed journal publications with no date restrictions. Economic and patient health-related quality of life (HRQoL) data on non-response by the number of treatment steps were quantified and, where appropriate, compared across studies; otherwise, comparative data within studies were reported. RESULTS: The 12 studies on economic burden found an association between increasing levels of TRD/non-response and elevations in direct and indirect costs. Likewise, the 19 studies studying HRQoL burden found that increasing levels of TRD/non-response correlated with reduced patient HRQoL and health status. LIMITATIONS: TRD is defined inconsistently, which results in notable heterogeneity between published studies and poses methodological challenges for between-study comparisons. It is unknown if the increased economic and patient HRQoL burden are due to factors associated with TRD/non-response in addition to those due to depression persistence or severity. CONCLUSIONS: A consistent trend was observed such that medical costs increased and patient HRQoL and health status decreased by increasing level of TRD/non-response within an MDD episode. These findings highlight the need for improved therapies for TRD to help reduce disease burden.

Estimating Alzheimer's Disease Progression Rates from Normal Cognition Through Mild Cognitive Impairment and Stages of Dementia.

BACKGROUND: Alzheimer's Disease (AD) can be conceptualized as a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Prior research has measured transition probabilities among later stages of AD, but not for the complete spectrum. OBJECTIVE: To estimate annual progression rates across the AD continuum and evaluate the impact of a delay in MCI due to AD on the trajectory of AD dementia and clinical outcomes. METHODS: Patient-level longitudinal data from the National Alzheimer's Coordinating Center for n=18,103 patients with multiple visits over the age of 65 were used to estimate annual, age-specific transitional probabilities between normal cognition, MCI due to AD, and AD severity states (defined by Clinical Dementia Rating score). Multivariate models predicted the likelihood of death and institutionalization for each health state, conditional on age and time from the previous evaluation. These probabilities were used to populate a transition matrix describing the likelihood of progressing to a particular disease state or death for any given current state and age. Finally, a health state model was developed to estimate the expected effect of a reduction in the risk of transitioning from normal cognition to MCI due to AD on disease progression rates for a cohort of 65-year-old patients over a 35-year time horizon. RESULTS: Annual transition probabilities to more severe states were 8%, 22%, 25%, 36%, and 16% for normal cognition, MCI due to AD, and mild/moderate/severe AD, respectively, at age 65, and increased as a function of age. Progression rates from normal cognition to MCI due to AD ranged from 4% to 10% annually. Severity of cognitive impairment and age both increased the likelihood of institutionalization and death. For a cohort of 100 patients with normal cognition at age 65, a 20% reduction in the annual progression rate to MCI due to AD avoided 5.7 and 5.6 cases of MCI due to AD and AD, respectively. This reduction led to less time spent in severe AD dementia health states and institutionalized, and increased life expectancy. CONCLUSION: Transition probabilities from normal cognition through AD severity states are important for understanding patient progression across the AD spectrum. These estimates can be used to evaluate the clinical benefits of reducing progression from normal cognition to MCI due to AD on lifetime health outcomes.

Assessing the Relationship between Performance on the University of California Performance Skills Assessment (UPSA) and Outcomes in Schizophrenia: A Systematic Review and Evidence Synthesis.

OBJECTIVE: To perform a systematic review of the published literature to evaluate how functional capacity, as measured by the University of California at San Diego (UCSD) Performance-based Skills Assessment (UPSA), relates to other functional measures and real-world outcomes among individuals with schizophrenia. METHODS: The MEDLINE® and Embase® databases were searched to identify joint evaluations with UPSA and key functional outcomes (functional scale measures; generic or disease-specific, health-related quality of life [HRQoL]; or real-world outcomes [residential status; employment status]) in patients with schizophrenia. Pearson correlations were estimated between UPSA scores, HRQoL, other functional scale measures, and real-world outcomes, for outcomes described in at least six studies. RESULTS: The synthesis included 76 studies that provided 73 unique data sets. Quantitative assessment between the Specific Level of Function (SLOF) (n=18) scores and UPSA scores demonstrated a moderate borderline-significant correlation (0.45, p=0.06). Quantitative analysis of the relationship between the Global Assessment of Functioning (GAF) (n=11) and the Multidimensional Scale of Independent Functioning (MSIF) (n=6) scales revealed moderate and small nonsignificant Pearson correlations of -0.34 (p=0.31) and 0.12 (p=0.83), respectively. There was a small borderline-significant correlation between UPSA score and residential status (n=36; 0.31; p=0.08), while no correlation was found between UPSA score and employment status (n=19; 0.04; p=0.88). CONCLUSION: The SLOF was the most often used functional measure and had the strongest observed correlation with the UPSA. Although knowledge gaps remain, evidence from this review indicates that there is a quantitative relationship between functional capacity and real-world outcomes in individuals with schizophrenia.

Liver-specific case fatality due to chronic hepatitis C virus infection: a systematic review.

Despite reports that mortality is increasing, overall case fatality due to hepatitis C virus (HCV) is thought to be low. Given the variability in published rates, we aimed to synthesize estimates of liver-specific case fatality and all-cause mortality in chronic HCV according to follow-up duration, sustained viral response (SVR) to treatment, and liver disease severity. A systematic review was conducted of studies published in English from 2003 to 2013, reporting liver-specific case fatality estimates from HCV-infected samples. Thirty-five eligible articles were identified; 26 also presented estimates of all-cause mortality. Among community-based samples, liver-specific case fatality ranged from 0.3% over 5.7 years to 9.2% over 8.2 years of follow-up; and of all-cause mortality, from 4.0% over 5.7 years, to 23.0% over 8.2 years of follow-up. Estimates were higher among clinic-based samples and those with more severe liver disease. Among treated patients achieving SVR, liver-specific case fatality was low: up to 1.4% over 11.5 years of follow-up among samples with any severity of liver disease. Estimates were higher among those without SVR: up to 14.0% over 10 years of followup among samples with any severity of liver disease, and higher still among samples with more severe liver disease. The proportion of deaths attributable to liver-specific causes ranged from 55 to 85% among those with severe liver disease. Published estimates of fatality are high among certain populations of chronic HCV patients, with liver-specific causes being an important contributor. Understanding current HCV mortality rates is important for quantifying the total burden of HCV disease.

Impact of JIA on parents' work absences.

OBJECTIVE: Children with JIA have long-term morbidity and require extensive parental assistance. This study aimed to evaluate the impact of having a child with JIA on parents' missed work time, which can lead to decreased work productivity. METHODS: The Truven Health MarketScan Commercial Database (2000-9) was accessed to identify a cohort of parents having a child with newly diagnosed JIA. For comparison, a cohort of parents having no children with JIA was identified and matched with the preceding cohort. Parents' work absences were analysed using descriptive statistics and multivariable regression. Estimates were weighted to be generalizable to the US employer-sponsored insurance population. RESULTS: The study identified 108 parents having a child with newly diagnosed JIA (mean age 42.5 years), representing an estimated 3335 (weighted) parents nationally. Most of them were from the South (45%), male (71%) and employed in the transportation and utilities industry (58%). The demographic characteristics of the control cohort of parents were generally similar. Children with JIA (mean age 10.6 years) represented an estimated 3528 cases nationally. The mean number of reported missed work-time hours was 281.81 (s.e. 40.50) in a 9 year period for parents having a child with JIA compared with other parents 183.36 (28.55). Work-time loss was significantly related to having a child with JIA, sex and geographical region of residence. Parents having a child with JIA were 2.78 times more likely to report work-time loss [odds ratio (OR) 2.78 (95% CI 1.47, 5.26)] than those having no children with JIA. CONCLUSION: Parents having a child with JIA report significant work-time loss compared with parents with no children having JIA, particularly during the year following the child's diagnosis.