Burden of disease study of overweight and obesity; the societal impact in terms of cost-of-illness and health-related quality of life

Background Little is known about the burden that overweight and obesity impose on Dutch society. The aim of this study is to examine this burden in terms of cost-of-illness and health-related quality of life. Method A bottom-up, prevalence-based burden of disease study from a societal perspective was performed. Cost-of-illness information including healthcare costs, patient and family costs, and other costs was obtained via the Treatment Inventory of Costs in Patients with psychiatric disorders (TiC-P) questionnaire. Health-related quality of life was assessed through the EuroQol (EQ-5D-5L) and the BODY-Q instruments. Non-parametric bootstrapping was applied to test for significant differences in costs. Subgroup analyses were performed on all outcomes. Results A total of 97 people with overweight and obesity completed the survey. Per respondent, mean healthcare costs were €2907, patient and family costs were €4037, and other costs were €4519, leading to a total societal cost of €11,463 per respondent per year. Total costs were significantly higher for respondents with obesity versus overweight and between low & intermediate versus highly educated respondents. The mean utility score of our population was 0.81. A significantly lower utility score was found for respondents with obesity in comparison with respondents with overweight. BODY-Q results show that respondents with obesity scored a significantly lower Rasch-score than did respondents with overweight in three scales. Respondents with a high education level and having paid work scored significantly higher Rasch-scores in two scales than did those with a low education level and without having paid work. The age group 19–29 have significantly higher Rasch-scores in three scales than respondents in the other two age categories. Conclusions Overweight and obesity have a considerable impact on the societal costs and on health-related quality of life. The results show that the impact of overweight and obesity go beyond the healthcare sector, as the other costs have the biggest share of the total costs. Another interesting finding of this study is that obesity leads to significant higher costs and lower health-related quality of life than overweight. These findings draw attention to policy making, as collective prevention and effective treatment are needed to reduce this burden.

Danish population health measured by the EQ-5D-5L

Aims: The aims of this study were to provide Danish population norms for the EQ-5D-5L and to assess the measurement properties of the instrument in a Danish population setting. Methods: We used data from the Danish 5L valuation study in which a representative sample of the Danish population completed the EQ-5D-5L and answered socio-demographic questions. We generated population norms for the five EQ-5D-5L dimensions, corresponding utility scores and the EQ-5D visual analogue scale (EQ VAS) according to age and sex. Measurement properties of ceiling effects, known-group construct validity and convergent validity were assessed. Results: The mean EQ-5D-5L utility score for the 1014 respondents completing the EQ-5D-5L was 0.90 (standard deviation ( SD)=0.16). No significant differences emerged across age groups (minimum mean utility score=0.88 ( SD=0.19); maximum mean utility score=0.93 ( SD=0.11)) or sex (mean utility score for women=0.89 ( SD=0.17); mean utility score for men=0.91 ( SD=0.15)). Statistical differences were found across educational level, occupational status, income and living situation. Similar patterns were observed for the EQ VAS. Generally, respondents most often reported problems with pain and discomfort, but young women most often reported problems with anxiety/depression. There was a significant strong correlation between EQ-5D-5L utility and the EQ VAS and a significant correlation between overall health and each of the five EQ-5D-5L dimensions. The overall ceiling effect for the EQ-5D-5L was 39% (compared to 56% for the EQ-5D-3L). Conclusions: Danish population norms for the EQ-5D-5L are now available. We found fewer ceiling effects for the EQ-5D-5L compared to the EQ-5D-3L, and we provide evidence for convergent and known-group validity of the EQ-5D-5L.

Perceptions of Hospice and Transfusion Access Among Patients with Advanced Blood Cancers: Results from a Best-Worst Scaling Survey

Background: Patients with hematologic malignancies have low rates of hospice use, and when they do enroll, they often do so in the last three days of life. While lack of access to transfusions in hospice has been posited to be a key barrier to hospice use for this population, data are lacking regarding the perception of patients with blood cancers about the importance of transfusion access compared to traditional hospice services. We sought to characterize the utility of transfusions and hospice services from the perspective of patients with advanced blood cancers, who would potentially be eligible for hospice care. Methods: In October 2020, we began a web-based survey of patients with hematologic malignancies recruited from the clinics of two large cancer centers. Eligible patients were at least 18 years of age, had at least two outpatient visits to the cancer center, and had a physician-estimated prognosis of six months or less based on their hematologic oncologist answering "no" to a modified "surprise" question (Hudson KE, JPM 2018): "would you be surprised if this patient died within the next six months?" A physician-estimated prognosis of ≤ 6 months was used for study inclusion as this is an eligibility criterion for hospice. The survey was developed through literature review, a series of patient/caregiver focus groups (n=27) and cognitive debriefing with blood cancer patients (n=5). The survey included a best-worst scaling (BWS) section to assess patients' perceptions of the utility of various services routinely provided in hospice (visiting nurse, case manager, home health aide, chaplain, social worker, respite care) as well as non-routine services (transfusion access, transportation, peer support, telemedicine through videoconferencing). We asked patients to imagine a program developed to support quality of life for patients with blood cancers just like them. We then presented them with 10 questions with different combinations of the services in groups of 4 and participants were asked to select the service they considered "most important" and "least important" in deciding whether to sign up for the program. The BWS questions were constructed using a near balanced incomplete block design (Louviere JJ, Patient 2010). We conducted a hierarchical Bayesian analysis to ascertain a standardized utility score assigned to each service, a measure of the average propensity to choose a service as most important more often than least important. Analyses were conducted using Sawtooth (Sawtooth Software, Inc). Results: As of July 2021, 102 patients had completed the survey (response rate: 64.6%). The median age of respondents was 71 years (IQR 63, 77). The majority of respondents were male, white, and married/living with partner (Table). The most common diagnosis was acute leukemia (38.2%). Patients considered access to blood transfusions to have the highest importance (Figure) with a standardized utility score of 21.1, 95% confidence interval [CI] [19.6-22.6], followed by telemedicine (19.4, 95% CI [17.8-20.9]), transportation to/from medical appointments (13.4, 95% CI 11.7-15.1), and visiting nurses (10.8, 95% [9.5-12.2]. The three least important services perceived by respondents were access to respite care (4.7, 95% CI [3.9-5.6]), social workers (4.5, 95% CI [3.5-5.5]), and chaplains (2.3, 95% CI [1.3-3.3]). Conclusions: In this cohort of blood cancer patients who would potentially be eligible for hospice care, access to blood transfusions had the greatest level of importance relative to services routinely provided in hospice settings. The high value placed on transfusion access suggests that this factor plays a crucial role in hospice decision making. Accordingly, lack of transfusion access in many hospices likely reduces the propensity of patients with blood cancers to choose hospice. Innovative hospice delivery models that include access to palliative transfusions may have strong potential to increase hospice use and optimize end-of-life care for this patient population. Figure 1 Figure 1. Disclosures Huntington: Genentech: Consultancy; SeaGen: Consultancy; Thyme Inc: Consultancy; Servier: Consultancy; Novartis: Consultancy; Bayer: Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy; DTRM Biopharm: Research Funding; TG Therapeutics: Research Funding; Flatiron Health Inc.: Consultancy; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Research Funding.

Exploring the Impact of Diffuse Large B-Cell Lymphoma (International Prognostic Index [IPI] 2-5) on Clinical and Patient-Relevant Outcomes in the Context of a Clinical Trial

Background: Most patients (pts) with diffuse large B-cell lymphoma (DLBCL) receiving first-line (1L) rituximab plus CHOP (R-CHOP) have similar mortality to the general population (gen popn) if they are progression-free at 24 months (PFS24; Maurer et al. Ann Oncol 2018). Characterization of quality of life (QoL) and clinical outcomes may enable more patient-relevant treatment decisions. Using GOYA trial data (NCT01287741) comparing obinutuzumab (G) + CHOP (G-CHOP) with R-CHOP, we present an exploratory analysis of 1L DLBCL pts with IPI 2-5 and assess overall survival (OS) and QoL relative to the gen popn. GOYA was not included in the previous PFS24 analysis by Maurer et al. Methods: We used data from both GOYA treatment arms to identify pts with IPI 2-5 DLBCL (n=1132 pts, intent-to-treat popn). Post-progression survival (PPS) in DLBCL is independent of prior treatment (Coiffier et al. Blood 2010) and as PFS was similar between treatment arms in GOYA, we assumed similar mortality after PFS24. Clinical outcomes were PFS24 (progression-free ≥24 months [m] from treatment start); early relapse (disease progression [PD]<24m from treatment start); late relapse (PD after PFS24). Outcomes for study pts vs gen popn were evaluated using standardized mortality ratios (SMR; deaths in study pts relative to expected deaths in gen popn matched by age, sex, country, and calendar time-at-risk). Expected deaths were derived using the Human Mortality Database, which provides detailed mortality and population data by country and can be used to estimate the background mortality during the observation period. Post-relapse survival in pts with early vs late relapse was assessed using Kaplan-Meier (KM) estimates and Cox regression. QoL was assessed using EQ-5D-3L and UK-based tariffs (Dolan. Med Care 1997); association between QoL and clinical outcomes used a linear mixed-effects model. The proportion of pts with PFS24 reporting QoL problems at baseline and after 24m was compared with age- and country-matched values in the gen popn (Janssen et al. Springer 2014). Data cut-off was Jan 2018 (GOYA final data cut); overall median follow-up was 48m. Results: In the overall IPI 2-5 population, mean age at treatment initiation was 61 yrs. 711 pts reached PFS24, of whom 64 experienced a late relapse (Table 1). Early relapse was experienced by 261 pts, of whom 164 were <6 months from end of treatment (EOT). OS following PFS24 was 98.6% at 2 years (including patients who later relapsed). 2-year PPS was 35.7% for pts with early relapse vs 74.8% for patients with late relapse (Figure 1.) Mortality following PFS24 was 72% of the matched gen popn (SMR 0.72; not significant: 95% CI 0.44-1.11). Mortality following relapse in pts who experienced early relapse was over 33 times higher than expected in the matched gen popn (SMR 33.57, 95% CI 27.69-40.33). However, risk of death following late relapse was reduced by 78% compared with risk following early relapse (HR 0.22 95 CI% 0.12-0.40), and mortality following late relapse was significantly higher than in the matched gen popn (SMR 6.7, 95% CI 3.05-12.67). Mean QoL utility score at baseline was 0.69 for all pts. After pts reached PFS24, estimated mean utility score was 0.86 (95% CI 0.84-0.87) and worsened by -0.07 (95% CI -0.14 to -0.01) at time of subsequent relapse. For early-relapsing pts, the worsening in utility was -0.15 (95% CI -0.20 to -0.10) compared with those still progression-free (Table 2). Among all PFS24 pts at baseline, problems were reported with mobility (28.1%), self-care (12.6%), usual activities (41.8%), pain/discomfort (62.7%), and anxiety/depression (48.8%); these rates were 2.2-4.7 times higher than the gen popn based on age- and country-standardized values. Compared with the gen popn, after pts reached PFS24, pain/discomfort was 10% lower, whereas anxiety/depression was 34% higher and other QoL items were approximately 20% higher. Conclusions: Most of the clinical course of 1L DLBCL occurred ≤2 years after start of treatment. In DLBCL pts with IPI 2-5 achieving PFS24, mortality was similar to the gen popn, and with the exception of mental health metrics, QoL scores were also similar to the gen popn. Late relapse (≥2 yrs) was associated with better post-relapse survival than early relapse (<2 yrs); however, this was inferior to the gen popn. Health state utilities improved whilst patients were relapse-free but the decline in QoL after early relapse was worse than after late relapse. Figure 1 Figure 1. Disclosures Launonen: F. Hoffmann-La Roche Ltd: Current Employment. Ho: F. Hoffmann-La Roche Ltd: Current Employment. Knapp: F. Hoffmann-La Roche Ltd: Current Employment. Canales Ruiz: Clinical Project Manager in Clinica Universidad de Navarra: Current Employment. Simonella: F. Hoffmann-La Roche Ltd: Current Employment. Thuresson: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company.

The burden of colorectal cancer survivors in the Netherlands: costs, utilities, and associated patient characteristics

Purpose The aim of this study is to assess the societal burden of colorectal cancer (CRC) survivorship 2–10 years post-diagnosis in terms of (1) societal costs, and (2) quality of life/utilities, and to analyze associated patient characteristics. Methods This is a cross-sectional, bottom-up prevalence-based burden of disease study, conducted from a societal perspective in the Netherlands. In total, 155 CRC survivors were included. Utilities were measured by the EQ-5D-5L, using the Dutch tariffs. A cost questionnaire was developed to obtain cost information. Subgroup analyses were performed, based on patient characteristics and sensitivity analyses. Results Of all CRC survivors, 81(54%) reported no problems for mobility, 133(88%) for self-care, 98(65%) for daily activities, 59(39%) for pain/discomfort, and 112(74%) for anxiety/depression on the EQ-5D-5L. The average EQ-5D-5L utility score was 0.82 (SD = 0.2) on a scale from 0 (death) to 1 (perfect health). Significant differences in utility score were found for gender, tumor stage, number of comorbidities, and lifestyle score. The average societal costs per CRC survivor per 6 months were estimated at €971 (min = €0, max = €32,425). Significant differences in costs were found for the number of comorbidities. Conclusions This study shows a considerable burden of CRC survivors 2–10 years after diagnosis, in comparison with survivors sooner after diagnosis and with healthy individuals in the Netherlands. Implications for Cancer Survivors Long-term care of CRC survivors should focus on improving the societal burden by identifying modifiable factors, as summarized in the WCRF/AICR lifestyle score, including body composition, physical activity, and diet.

Steroids with and Without Antivirals in the Treatment of Bell’s Palsy: Does It Make any Difference in Recovery? A Study at a Tertiary Care Center, Karachi, Pakistan

Objectives: To compare the pharmacological effects of steroids in comparison to steroids with antiviral drugs for the treatment of Bell’s Palsy. Methods: A total 60 patients were enrolled and segregated equally into two groups, where patients on prednisolone were labeled as group A (Control group), whereas patients on prednisolone + acyclovir were labeled as group B (study group). All patients had House Brackmann score. The control group started oral prednisolone 1 mg/kg for 10 days, whereas the study group started acyclovir 400 mg 4 times a day for 10 days along with prednisolone tablets. Patients were regularly observed till the study was completed. Primary outcome measure was facial nerve recovery. Health-related quality of life and facial appearance were considered secondary outcomes. Results: The primary outcomes assessed as complete recovery from Bell’s Palsy by Brackmann score at week 4 were found in 17/30 (57%) patients and 23/30 (77%) patients at week 8 in the control group. Complete recovery from Bell’s Palsy was also shown in the experimental group (Prednisolone + acyclovir) where 25/30 (83%) patients completed recovery at week 4, while 27/30 (90%) patients at week 8. Comparison of the two groups showed a significant improvement in the study group (prednisolone + acyclovir) (P = 0.047) at week 4 and (P = 0.02) at week 8. The secondary outcomes were assessed as improvement in the quality of life and facial appearance from Bell’s Palsy. Health utility score was 0.84 ± 0.01 in the control group (On prednisolone) with facial appearance score of (Derriford appearance scale 59) 61 ± 28. At week 4, the study group (on prednisolone+ acyclovir) showed 0.88 ± 0.12 score on Health utility index scale-3 and 46 ± 26 score on Derriford appearance scale. Comparison of the quality of life (Health quality index scale-3) and facial appearance among both control and study groups showed a significant improvement in the study group (P = 0.001 and P = 0.005, respectively). Moreover, when health utility score and Derriford appearance were compared among both groups, it showed a significant improvement in the study group (P = 0.001 and 0.016, respectively). Conclusions: The combination of prednisolone with acyclovir is found superior to prednisolone alone, and this combination treatment results in improvement in both recovery and quality of life.

Association of dialysis-related amyloidosis with lower quality of life in patients undergoing hemodialysis for more than 10 years: The Kyushu Dialysis-Related Amyloidosis Study

Background Dialysis-related amyloidosis (DRA) commonly develops in patients undergoing long-term dialysis and can lead to a decline in activities of daily living and quality of life (QOL), mainly owing to orthopedic complications. Methods First, we determined utility scores of the EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire in 1,323 patients with DRA who had undergone dialysis for more than 10 years and compared the score between those with and without DRA. Second, a 2-year follow-up was also performed, in which patients were divided into three groups: those complicated by DRA from the beginning, those with newly developed DRA within the 2-year period, and those not complicated by DRA throughout the survey period; changes in the EQ-5D-3L utility score were compared. In the group already complicated by DRA at the survey baseline, changes in the EQ-5D-3L utility score were compared according to the dialysis treatment method. Results A total of 1,314 and 931 patients were included in the first and second studies, respectively. EQ-5D-3L utility scores among patients diagnosed with DRA were significantly lower than scores in those not diagnosed with DRA. The reduction in the EQ-5D-3L utility score over the 2-year follow-up was significantly greater in patients newly complicated by DRA during the follow-up period after enrollment but not in those complicated by DRA from the beginning, as compared with patients not complicated by DRA throughout the survey period. The reduction in utility score tended to be lower in patients routinely treated with a β2-microglobulin adsorption column than in untreated patients with DRA. Conclusion Complication by DRA in patients undergoing long-term hemodialysis was significantly associated with a decline in QOL.

An Explainable Machine Learning Model for Early Prediction of Sepsis Using ICU Data

Early identification of individuals with sepsis is very useful in assisting clinical triage and decision-making, resulting in early intervention and improved outcomes. This study aims to develop an explainable machine learning model with the clinical interpretability to predict sepsis onset before 6 hours and validate with improved prediction risk power for every time interval since admission to the ICU. The retrospective observational cohort study is carried out using PhysioNet Challenge 2019 ICU data from three distinct hospital systems, viz. A, B, and C. Data from A and B were shared publicly for training and validation while sequestered data from all three cohorts were used for scoring. However, this study is limited only to publicly available training data. Training data contains 15,52,210 patient records of 40,336 ICU patients with up to 40 clinical variables (sourced for each hour of their ICU stay) divided into two datasets, based on hospital systems A and B. The clinical feature exploration and interpretation for early prediction of sepsis is achieved using the proposed framework, viz. the explainable Machine Learning model for Early Prediction of Sepsis (xMLEPS). A total of 85 features comprising the given 40 clinical variables augmented with 10 derived physiological features and 35 time-lag difference features are fed to xMLEPS for the said prediction task of sepsis onset. A ten-fold cross-validation scheme is employed wherein an optimal prediction risk threshold is searched for each of the 10 LightGBM models. These optimum threshold values are later used by the corresponding models to refine the predictive power in terms of utility score for the prediction of labels in each fold. The entire framework is designed via Bayesian optimization and trained with the resultant feature set of 85 features, yielding an average normalized utility score of 0.4214 and area under receiver operating characteristic curve of 0.8591 on publicly available training data. This study establish a practical and explainable sepsis onset prediction model for ICU data using applied ML approach, mainly gradient boosting. The study highlights the clinical significance of physiological inter-relations among the given and proposed clinical signs via feature importance and SHapley Additive exPlanations (SHAP) plots for visualized interpretation.

Health-related quality of life in amyotrophic lateral sclerosis using EQ-5D-5L

Background The study aimed to appraise the health-related quality of life (HRQoL) measured by the five-level EuroQol-5 dimensions (EQ-5D-5L) in amyotrophic lateral sclerosis (ALS), and to explore the associations between non-motor symptoms (mood changes, cognitive disturbances and sleep disturbances). Methods EQ-5D-5L descriptive scores were converted into a single aggregated “health utility” score. A calibrated visual analog scale (EQ-VAS) was used for self-rating of current health status. Multiple logistic regression analysis was used to explore the factors associated with HRQoL. Results Among the 547 enrolled ALS patients who were assessed using EQ-5D-5L, the highest frequency of reported problems was with usual activities (76.7%), followed by self-care (68.8%) and anxiety/depression (62.0%). The median health utility score was 0.78 and the median EQ-VAS score was 70. Clinical factors corresponding to differences in the EQ-5D-5L health utility score included age of onset, onset region, the ALS Functional Rating Scale-Revised (ALSFRS-R) score, and King’s College stages. Patients with depression, anxiety, and poor sleep had lower health utility scores. Patients with excessive daytime sleepiness and rapid eye movement sleep behavior disorder had lower EQ-VAS scores. Multivariate logistic analysis indicated that ALSFRS-R scores, depression, and anxiety were associated with health utility scores. After adjusting other parameters, ALSFRS-R score, stages, and depression were significantly associated with EQ-VAS scores (P < 0.05). Conclusion This study examined HRQoL in ALS patients using the Chinese version of the EQ-5D-5L scale across different stages of the disease. We found that HRQoL is related to disease severity and to mood disturbances. Management of non-motor symptoms may help improve HRQoL in ALS patients.

Health related quality of life among postmenopausal woman with hormone responsive HER2− breast cancer in Indonesia

Objectives Breast cancer (BC) in women could decrease health-related quality of life (HRQoL). HRQoL becomes important to be assessed to design a relevant treatment that could improve patient outcomes. Furthermore, assessing HRQoL by measuring health state utilities becomes pivotal for health economic evaluation. This study aimed to describe the HRQoL of postmenopausal women with hormone responsive (HR+) HER2− BC using the EQ5D5L instrument in Indonesia. Methods A cross-sectional study was conducted among 126 patients in Dr. Sardjito Hospital in Indonesia. The HRQoL was assessed by interviewing BC patients using the EQ5D5L questionnaire, and the utility index was calculated using the Indonesian value set. Information regarding clinical characteristic and socio-demographic were gained from patient medical records. One-way ANOVA and post-hoc Scheffe’s test was performed to compare the utility score within the health state. Results Of the 126 patients, a mean ± SD for the age of 59.2 ± 6.1 years. The major problems of patients were pain/discomfort (75.4%) followed by anxiety/depression (54.8%). The mean (SD) of EQ5D VAS was 76.64 (14.91). Mean (SD) of utility score was 0.87 (0.10), 0.77 (0.19) and 0.58 (0.44) for free metastasis (FM), locoregional metastasis (LM) and distant metastasis (DM), respectively. Poor QoL was observed at DM health state (p<0.05). Conclusions HRQoL of postmenopausal women with HR+ HER2− BC was low. The major reported problems were pain/discomfort and anxiety/depression.