Effect of Levodopa-Carbidopa Intestinal Gel on Non-Motor Symptoms in Patients with Advanced Parkinson\u27s Disease

Background: Levodopa-carbidopa intestinal gel (LCIG; carbidopa-levodopa enteral suspension in the United States), delivered via percutaneous gastrojejunostomy (PEG-J) and titrated in the inpatient setting, is an established treatment option for advanced Parkinson\u27s disease (PD) patients with motor fluctuations. However, long-term prospective data on the efficacy of LCIG on non-motor symptoms and the safety of outpatient titration are limited. Methods: In this 60-week, open-label phase 3b study, LCIG titration was initiated in an outpatient setting following PEG-J placement in PD patients. The efficacy of LCIG on motor and non-motor symptoms, quality of life, and safety was assessed. Results: Thirty-nine patients were enrolled in the study and 28 patients completed the treatment. A majority of patients (54%) completed outpatient titration within the first week of LCIG infusion. LCIG led to significant reductions from baseline in Non-Motor Symptom Scale (NMSS) total score (least squares mean ± SE = −17.6 ± 3.6, P \u3c 0.001) and 6 of the NMSS domain scores (sleep/fatigue, attention/memory, gastrointestinal tract, urinary, sexual function, miscellaneous) at week 12. These reductions were maintained at week 60 with the exception of the urinary domain. “Off” time (−4.9 ± 0.5 hours/day, P \u3c 0.001) and “On” time without troublesome dyskinesia (−4.3 ± 0.6 hours/day, P \u3c 0.001) were improved at week 60. Adverse events (AEs) were reported in 37 (95%) patients. Conclusions: LCIG treatment led to reductions in non-motor symptom burden and motor fluctuations in advanced PD patients. The safety profile was consistent with previous studies that used inpatient titration and outpatient titration did not appear to pose additional risk

The Role of Health-Related Lifestyle Attitudes in Understanding Health Behaviors and Outcomes

Health systems throughout the world increasingly recognize health-related quality of life (HRQoL) as a key patient-centered health outcome. HRQoL is particularly important in conditions which impair daily living (e.g. Parkinson’s Disease) and in those that are largely subjective in nature (e.g. pain). HRQoL, when assessed using a preference-based measure, is an essential component in the calculation of quality adjusted life years (QALYs). QALYs gained form the denominator in an incremental cost-effectiveness ratio (ICER), which is the most common result derived in a cost-utility analysis and is used to inform patient and system-level decisions and incorporated into pricing and reimbursement decisions. HRQoL can be viewed as an individual’s perception of his/her own health. An individual’s perception is often influenced by attitudes and beliefs, which in turn also influence health behaviors and overall health. This dissertation examines the role of health and life-style related attitudes (HLA) in understanding health behaviors and outcomes through three separate studies. The studies evaluated the validity of measures of HRQoL and HLA in a community population and examined the relationship between HLA and health behaviors, self-assessment of health and life-satisfaction. The first chapter introduces key study concepts including HLA, self-assessment and life-satisfaction along with a conceptual framework that facilitates the understanding of the relationship between HLA, health behaviors and outcomes (including self-assessment of health and life satisfaction). The introductory chapter highlights the gaps in the evidence, research objectives and hypotheses that were examined in subsequent chapters, and explains the significance of the research. All the studies are based on secondary analyses from a large scale community health study conducted in Kirklees, United Kingdom, in 2012. The second chapter examines the properties of the recently developed EQ-5D-5L as a measure of population health in a large community-based survey. The assessment of the construct validity of the EQ-5D-5L in a community sample helps to facilitate in the use of EQ-5D-5L in general population health studies. A secondary aim of the study was to compare EQ-5D-5L summary scores based on an English value set (5L-ENG), crosswalk scores based on 3L values (XW), and scores based on equal weighting (5L-EWS). Properties of the EQ-5D-5L that were examined included discriminative ability, strength of correlations with related measures of health, and statistical efficiency, as assessed with relative efficiency (RE) ratios between summary scores from known group comparisons, using the XW as the referent. Correlations between EQ-5D dimensions and other measures of health ranged from r =0.56-0.73. Compared to the XW, the RE of the 5L-ENG and 5L-EWS were similar or higher (Age:RE5L-ENG=0.96,RE5L-EWS=1.36; BMI:RE5L-ENG=1.00,RE5L-EWS=1.0; Number of prescription medications:RE5L-ENG=1.00,RE5L-EWS=1.18; Number of Chronic conditions:RE5L-ENG=1.00,RE5L-EWS=1.61; General Health:RE5L-ENG=1.13,RE5L-EWS=1.20). The results provided evidence to support the validity of EQ-5D-5L in large community based surveys. If statistical efficiency of a summary score is a desirable property, the EWS should be considered for non-QALY purposes. The third chapter describes the second study which sought to determine the extent to which health and lifestyle related attitudes (HLA) explained health behaviors and outcomes. If certain HLAs are associated with specific health behaviors, it raises the possibility of using HLA based segmentation to improve the uptake of health interventions designed, for instance, to reduce drug abuse. Individuals were characterized based on HLA using two different approaches: (1) as five discrete segments; and (2) as 3 single-item scales (“importance of health”, “involvement in health” and “control of health”). The association between each HLA approach and several potentially modifiable behaviors/conditions was assessed using logistic regression. When respondents were categorized according to HLA segments, 30.8% were health conscious realists, 15.0% balanced compensators, 17.7% life-for-todays, 10.0% hedonistic immortals and 26.4% unconfident fatalists. Correlational analysis between HLA segments and trait scales produced low scores and moderate negative correlations between specific HLA traits and segments, which indicated the approaches were complementary. The model fit between HLA and health behaviors/conditions was weak and except for mental health problems, was similar across the approaches. Both approaches demonstrated convergent and divergent validity, e.g. unconfident fatalists and those with low levels of the trait “involvement in health” were significantly more likely to report poor diet [OR=2.27 (95%CI: 2.02, 2.55), OR=1.59 (95%CI: 1.45, 1.74), respectively. The HLA segmentation approach performed better as a predictor of certain behaviors (e.g. tobacco use) than others (e.g. exercise). Both the segment and the trait methods had comparable performance in explaining health behaviors and outcomes. Thus, both provided viable approaches to identify sub-groups of the population who are more likely to engage in certain negative health behaviors that could be targeted for tailored healthcare interventions. The fourth chapter describes the third study, which examined the relationship between HLA and self-assessment of health and life-satisfaction. Evaluation of the relationship between HLA and health behaviors and self-assessment of HRQoL and life satisfaction may help to identify groups which systematically differ in their valuation of health, despite of being in similar health state. In this study, individuals were characterized based on HLA segments [Health Conscious Realists(HCR), Balanced Compensators(BC), Live for Todays(LFT), Hedonistic Immortals(HI), and Unconfident Fatalists(UF)] using an algorithm for the 19-item Healthy Foundations Lifestyle Segmentation questionnaire. Associations between HLA and outcomes of interest [(i) self-assessment of health (EQ-VAS), (ii) differences between personal (i.e. EQ-VAS) and societal valuation of health (Dev), and (iii) life-satisfaction] were examined by multivariate regression analyses, adjusting for current health and relevant individual characteristics. The societal valuation was based on the preference-based algorithm for the EQ-5D-5L. Dev was examined to evaluate if HLA segments differ systematically between personal valuation of health and societal valuation of the health state. In the analytical sample (n=9,130), compared to HCR respondents (reference): (i) mean VAS scores for UF, LFT and BC respondents were 9.02 (p<0.001) and 1.96 points lower (p=0.002) and 1.15 points higher (p<0.01) respectively; (ii) Dev score in UF respondents was 0.027 lower (p<0.001), and (iii) BC respondents were less likely (OR:0.8,95%CI:0.6, 0.9), while UF were more likely (OR:3.5, 95%CI: 2.9, 4.2) to report low lifesatisfaction. Thus, HLA were associated with systematic differences in self-assessment of health and life-satisfaction, most notably UF, who rated their health much more negatively and had much lower life satisfaction, even after adjusting for characteristics such as age and gender. Results suggest that unconfident fatalists, who compromised 30% of survey respondents, are an important subgroup in the community who may need to be separately targeted for health care interventions, particularly behavioral. Importantly from a health services research perspective, the assessment of self reported HRQoL in this subgroup using measures of health and well-being may need to be separately considered in analysis and interpretation. Further research on this topic is warranted given the increasing use of patient-reported outcomes in health systems, particularly in conditions in which UF are disproportionately represented. The fifth chapter provides an overall conclusion to the dissertation. The characterization of individuals based on HLA's implications for health promotion and self assessment of health is discussed, and future research directions are proposed

The long-term direct and indirect economic burden among Parkinson's disease caregivers in the United States.

Parkinson's disease is a progressive, disabling neurodegenerative disorder associated with significant economic burden for patients and caregivers. The objective of this study was to compare the direct and indirect economic burden of Parkinson's patients' caregivers with demographically matched controls in the United States, in the 5 years after first diagnosis of Parkinson's disease. Policyholders (18-64 years old) linked to a Parkinson's disease patient (≥2 diagnoses of Parkinson's disease; first diagnosis is the index date) from January 1, 1998 to March 31, 2014, were selected from a private-insurer claims database and categorized as Parkinson's caregivers. Eligible Parkinson's caregivers were matched 1:5 to policyholders with a non-Parkinson's dependent (controls). Multivariable regression adjusted for baseline characteristics estimated direct costs (all-cause insurer cost [medical and prescription] and comorbidity-related medical costs; patient out-of-pocket costs) and indirect costs (disability and medically related absenteeism costs). Income progression was also compared between cohorts. A total of 1211 eligible Parkinson's caregivers (mean age, 56 years; 54% female) were matched to 6055 controls. In adjusted analyses, Parkinson's caregivers incurred significantly higher year 1 total all-cause insurer costs ($8999 vs$7117) and medical costs ($7081 vs$5568) (both P < 0.01) and higher prescription costs (range for years 1-5, $2506-2573 vs$1405-$1687) and total out-of-pocket costs ($1259-1585 vs $902-$1192) in years 1-5 (all P < 0.01). Parkinson's caregivers had significantly higher adjusted indirect costs in years 1-3 (range for years 1-3, $2054-$2464 vs $1681-$1857; all P < 0.05) and higher cumulative income loss over 5 years ($5967 vs$2634 by year 5; P for interaction = 0.03). Parkinson's caregivers exhibited higher direct and indirect costs and greater income loss compared with matched controls. © 2018 International Parkinson and Movement Disorder Society © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.This study and manuscript were funded by AbbVie. The design, study conduct, and financial support for the study were provided by AbbVie. AbbVie participated in the study design, research, interpretation of data, writ- ing, reviewing, and approving the manuscript.S

Economic Evaluations of Clinical Pharmacy Services: 2006–2010

Studies have consistently evidenced the positive clinical, economic, and humanistic benefits of pharmacist-directed patient care in a variety of settings. Given the vast differences in clinical outcomes associated with evaluated clinical pharmacy services (CPS), more detail as to the nature of the CPS is needed to better understand observed differences in economic outcomes. With the growing trend of outpatient pharmacy services, these economic evaluations serve as viable decision-making tools in choosing the most effective and cost-effective pharmacy programs. We previously conducted three systematic reviews to evaluate the economic impact of CPS from 1988 to 2005. In this systematic review, our objectives were to describe and evaluate the quality of economic evaluations of CPS published between 2006 and 2010, with the goal of informing administrators and practitioners as to their cost-effectiveness. We searched the scientific literature by using the Medline, International Pharmaceutical Abstracts, Embase, and Cumulative Index to Nursing and Allied Health Literature databases to identify studies describing CPS published from 2006 to 2010. Studies meeting our inclusion criteria (original research articles that evaluated CPS and described economic and clinical outcomes) were reviewed by two investigators. Methodology used, economic evaluation type, CPS setting and type, and clinical and economic outcome results were extracted. Results were informally compared with previous systematic reviews. Of 3587 potential studies identified, 25 met inclusion criteria. Common CPS settings were hospital (36%), community (32%), and clinic or hospital-based ambulatory practices (28%). CPS types were disease state management (48%), general pharmacotherapeutic monitoring (24%), target drug programs (8%), and patient education (4%). Two studies (8%) listed CPS as medication therapy management. Costs were evaluated in 24 studies (96%) and sufficiently described in 13 (52%). Clinical or humanistic outcomes were evaluated in 20 studies (80%) and were sufficiently described in 18 (72%). Control groups were included in 16 (70%) of 23 studies not involving modeling. Study assumptions and limitations were stated and justified in eight studies (32%). Conclusions and recommendations were considered justified and based on results in 24 studies (96%). Eighteen studies (72%) involved full economic evaluation. The mean ± SD study quality score for full economic evaluations (18 studies) was 60.4 ± 22.3 of a possible 100 points. Benefit-cost ratios from three studies ranged from 1.05:1 to 25.95:1, and incremental cost-effectiveness ratios of five studies were calculated and reported. Fewer studies documented the economic impact of CPS from 2006-2010 than from 2001-2005, although a higher proportion involved controlled designs and were full economic evaluations. Evaluations of ambulatory practices were increasingly common. CPS were generally considered cost-effective or provided a good benefit-cost ratio

Abdominal compartment syndrome in trauma patients: New insights for predicting outcomes

Context: Abdominal compartment syndrome (ACS) is associated with high morbidity and mortality among trauma patients. Several clinical and laboratory findings have been suggested as markers for ACS, and these may point to different types of ACS and complications. Aims: This study aims to identify the strength of association of clinical and laboratory variables with specific adverse outcomes in trauma patients with ACS. Settings and Design: A 5-year retrospective chart review was conducted at three Level I Trauma Centers in the City of Chicago, IL, USA. Subjects and Methods:A complete set of demographic, pre-, intra- and post-operative variables were collected from 28 patient charts. Statistical Analysis:Pearson's correlation coefficient was used to determine the strength of association between 29 studied variables and eight end outcomes. Results: Thirty-day mortality was associated strongly with the finding of an initial intra-abdominal pressure >20 mmHg and moderately with blunt injury mechanism. A lactic acid >5 mmol/L on admission was moderately associated with increased blood transfusion requirements and with acute renal failure during the hospitalization. Developing ACS within 48 h of admission was moderately associated with increased length of stay in the Intensive Care Unit (ICU), more ventilator days, and longer hospital stay. Initial operative intervention lasting more than 2 h was moderately associated with risk of developing multi-organ failure. Hemoglobin level 7 days were moderately associated with a disposition to long-term support facility. Conclusions: Clinical and lab variables can predict specific adverse outcomes in trauma patients with ACS. These findings may be used to guide patient management, improve resource utilization, and build capacity within trauma centers

The Seven Pillars Response to Patient Safety Incidents: Effects on Medical Liability Processes and Outcomes.

OBJECTIVE: To determine whether a communication and resolution approach to patient harm is associated with changes in medical liability processes and outcomes. DATA SOURCES/STUDY SETTING: Administrative, safety, and risk management data from the University of Illinois Hospital and Health Sciences System, from 2002 to 2014. STUDY DESIGN: Single health system, interrupted time series design. Using Mann–Whitney U tests and segmented regression models, we compared means and trends in incident reports, claims, event analyses, patient communication consults, legal fees, costs per claim, settlements, and self‐insurance expenses before and after the implementation of the “Seven Pillars” communication and resolution intervention. DATA COLLECTION METHODS: Queried databases maintained by Department of Safety and Risk Management and the Department of Administrative Services at UIH. Extracted data from risk module of the Midas incident reporting system. PRINCIPAL FINDINGS: The intervention nearly doubled the number of incident reports, halved the number of claims, and reduced legal fees and costs as well as total costs per claim, settlement amounts, and self‐insurance costs. CONCLUSIONS: A communication and optimal resolution (CANDOR) approach to adverse events was associated with long‐lasting, clinically and financially significant changes in a large set of core medical liability process and outcome measures

The Long-Term Impact of Levodopa/Carbidopa Intestinal Gel on ‘Off’-time in Patients with Advanced Parkinson’s Disease : A Systematic Review

Introduction: Levodopa/carbidopa intestinal gel (LCIG; carbidopa/levodopa enteral suspension) has been widely used and studied for the treatment of motor fluctuations in levodopa-responsive patients with advanced Parkinson’s disease (PD) when other treatments have not given satisfactory results. Reduction in ‘off’-time is a common primary endpoint in studies of LCIG, and it is important to assess the durability of this response. This systematic literature review was conducted to qualitatively summarise the data on the long-term effects of LCIG therapy on ‘off’-time. Methods: Studies were identified by searching PubMed, EMBASE and Ovid on 30 September 2019. Studies were included if they reported on patients with PD, had a sample size of ≥ 10, LCIG was an active intervention and ‘off’-time was reported for ≥ 12 months after initiation of LCIG treatment. Randomised clinical trials, retrospective and prospective observational studies, and other interventional studies were included for selection. Data were collected on: ‘off’-time (at pre-specified time periods and the end of follow-up), study characteristics, Unified Parkinson’s Disease Rating Scale (UPDRS) II, III and IV total scores, dyskinesia duration, quality of life scores, non-motor symptoms and safety outcomes. Results: Twenty-seven studies were included in this review. The improvement in ‘off’-time observed shortly after initiating LCIG was maintained and was statistically significant at the end of follow-up in 24 of 27 studies. ‘Off’-time was reduced from baseline to end of follow-up by 38–84% and was accompanied by a clinically meaningful improvement in quality of life. Stratified analysis of ‘off’-time demonstrated mean relative reductions of 47–82% at 3–6 months and up to 83% reduction at 3–5 years of follow-up. Most studies reported significant improvements in activities of daily living and motor complications. Most frequent adverse events were related to the procedure or the device. Conclusion: In one of the largest qualitative syntheses of published LCIG studies, LCIG treatment was observed to provide a durable effect in reducing ‘off’-time. Infographic: [Figure not available: see fulltext.] [MediaObject not available: see fulltext.