Public preferences for policies promoting a healthy diet: a discrete choice experiment.

BACKGROUND: Worldwide obesity rates have nearly tripled over the past five decades. So far, policies to promote a healthier diet have been less intrusive than those to reduce tobacco and alcohol consumption. Not much is known about public support for policies that aim to promote a healthy diet. In this study, a discrete choice experiment (DCE) was used to elicit stated preferences for policies varying in intrusiveness among a representative sample of the public of The Netherlands. METHODS: The choice tasks presented respondents a hypothetical scenario of two policy packages, each comprising a mix of seven potential policies that differed in level of intrusiveness. We estimated mixed logit models (MXL) to estimate respondents' preferences for these policies and performed latent class analyses to identify heterogeneity in preferences. RESULTS: The MXL model showed that positive financial incentives like subsidies for vegetables and fruit yielded most utility. A tax of 50% on sugary drinks was associated with disutility while a tax of 20% was associated with positive utility compared to no tax at all. We identified three subgroups with distinct preferences for the seven policies to promote a healthy diet, which were characterized as being "against", "mixed" and "pro" policies to promote a healthy diet. CONCLUSION: Preferences for policies promoting a healthy diet vary considerably in the Dutch population, particularly in relation to more intrusive policies. This makes selection and implementation of a policy package that has wide public support challenging.

The Mental Health Quality of Life Questionnaire (MHQoL): development and first psychometric evaluation of a new measure to assess quality of life in people with mental health problems.

PURPOSE: The purpose of this study was to develop and psychometrically evaluate a new quality of life measure for use in people with mental health problems-the Mental Health Quality of Life questionnaire (MHQoL). METHODS: The MHQoL dimensions were based on prior research by Connell and colleagues, highlighting the seven most important quality of life dimensions in the context of mental health. Items were generated following a systematic review we performed and through inviting expert opinion. A focus group and an online qualitative study (N = 120) were carried out to assess the face and content validity of the MHQoL. The MHQoL was further tested for its internal consistency, convergent validity, known-group validity and test-retest reliability among mental healthcare service users (N = 479) and members of the general population (N = 110). RESULTS: The MHQoL consists of a descriptive system (MHQoL-7D), including s items covering seven dimensions (self-image, independence, mood, relationships, daily activities, physical health, future) and a visual analogue scale of general psychological well-being (MHQoL-VAS). Internal consistency was high (Cronbach's ∝ = 0.85) and correlations between MHQoL-7D scores and related measures (EQ-5D-5L, MANSA, ICECAP-A, and BSI) supported convergent validity. The intraclass correlation coefficient of the MHQoL-7D sum score for test-retest reliability was 0.85. Known-group validity was supported by the ability to detect significant differences in MHQoL-7D levels between service users and the general population, and between groups with different levels of psychological distress. CONCLUSION: The MHQoL demonstrated favourable psychometric properties and showed promise as a simple and effective measure to assess quality of life in people with mental health problems.

Instruments to assess quality of life in people with mental health problems: a systematic review and dimension analysis of generic, domain- and disease-specific instruments.

OBJECTIVES: The importance of economic evaluations of mental healthcare interventions is increasingly recognized. Despite the multitude of available quality of life instruments, concerns have been raised regarding the content validity of these instruments, and hence suitability for use in mental health. The aim of this paper, therefore, was to assess the content validity and the suitability of existing quality of life instruments for use in economic evaluations in mental health problems. METHODS: In order to identify available quality of life instruments used in people with mental health problems, a systematic review was performed using the Embase, Medline and PsycINFO databases (time period January 2012 to January 2018). Two reviewers independently assessed study eligibility and executed data extraction. The evaluation framework of Connell and colleagues was used to assess whether the identified quality of life instruments cover the dimensions valued highly by people with mental health problems. Two reviewers independently mapped the content of each identified instrument onto the evaluation framework and indicated the extent to which the instrument covered each of the dimensions of the evaluation framework. RESULTS: Searches of databases yielded a total of 5727 references. Following duplicate removal and double-independent screening, 949 studies were included in the qualitative synthesis. A total of 44 unique quality of life instruments were identified, of which 12 were adapted versions of original instruments. The best coverage of the dimensions of the evaluation framework of Connell and colleagues was by the WHOQOL-100, S-QoL, SQLS, EDQoL, QLI and the IMHQOL, but none fully covered all dimensions of the evaluation framework. CONCLUSIONS: The results of this study highlight the multitude of available quality of life instruments used in people with mental health problems and indicate that none of the available quality of life instruments fully cover the dimensions previously found to be important in people with mental health problems. Future research should explore the possibilities of refining or expanding existing instruments as well as the development and testing of new quality of life instruments to ensure that all relevant quality of life dimensions for people with mental health problems are covered in evaluations.

Don't forget about the future: The impact of including future costs on the cost-effectiveness of adult pneumococcal conjugate vaccination with PCV13 in the Netherlands.

BACKGROUND: When vaccines increase longevity, vaccinated people may experience costs and benefits during added life-years. These future benefits and costs may include increased productivity as well as medical and non-medical costs. Such impacts should be considered in cost-effectiveness analyses (CEA) of vaccines but are often omitted. Here, we illustrate the impact of including future costs on the cost-effectiveness of vaccination against pneumococcus disease. We emphasize the relevance of differentiating cost estimates between risk groups. METHODS: We updated an existing Dutch CEA of vaccination against pneumococcus disease with the 13-valent pneumococcal conjugate vaccine (PCV13) to include all future medical and non-medical costs. We linked costs by age and risk with survival information and estimates of cases prevented per vaccination strategy based on the original study to calculate the impact of inclusion. Future medical costs were adjusted for relevant risk groups. RESULTS: For the base-case strategy, the original incremental cost-effectiveness ratio (ICER) of PVC13 was €9,157 per quality adjusted life-year (QALY). Including all future medical costs increased the ICER to €28,540 per QALY. Also including future non-medical costs resulted in an ICER of €45,691 per QALY. The impact of future medical costs varied considerably per risk group and generally increased with age. DISCUSSION AND CONCLUSION: This study showed a substantial effect of the inclusion of future costs on the ICER of vaccinating with PCV13. Especially when lives of people with underlying health conditions are extended, the impact of future medical costs is large. This inclusion may make vaccination a less attractive option, especially in relation to low thresholds as often applied for prevention. Although this raises important questions, ignoring these real future costs may lead to an inefficient use of healthcare resources. Our results may imply that prices for some vaccines need to be lowered to be cost-effective.

[Opinions about oral care: an online questionnaire among readers of NTvT]. / Meningen over mondzorg: een online-onderzoek onder NTVT-lezers.

By means of a brief online questionnaire with 12 statements about the organisation, quality and impact of oral care in the Netherlands, the readers of the Netherlands Journal of Dentistry (NTVT) were asked to express their opinions on a number of important subjects concerning oral care in the Netherlands with respect to health economic matters. A total of 237 readers (61% men, 39% women) completed the online questionnaire. 70% of them were working as dentists and had been active in a practice for between 31 and 40 years. According to the study, a shift from curing to prevention was considered to be necessary. Most of the respondents also thought inequality in oral health in the Netherlands is increasing and people avoid going to the dentist due to the associated costs. In conclusion, most oral care providers appear to be reasonably positive about Dutch oral care. Attention for prevention, appreciation of oral health and the reduction of inequality in oral care continue to be necessary.

[Health economics and oral care: an introductory anthology]. / Gezondheidseconomie en mondzorg: een inleidende bloemlezing.

Healthcare expenditures will continue to increase in the coming years, raising questions regarding the sustainability of the Dutch healthcare system and solidarity, but also about the optimal use of available resources. Given the issues in the oral care sector, attention for economic insights is appropriate there as well. Relevant issues in this regard are the design of the basic and supplementary health insurance schemes for oral care, the market structure and financing of oral care, questions regarding task shifting in oral care, as well as socio-economic inequalities in oral health. A closer cooperative relationship between oral care and the health economy can help in achieving an optimal and sustainable organisation of the Dutch oral care sector. In other words, an organisation contributing in an efficient and fair way to good oral care for all Dutch citizens.

The MMSE should not be the sole indicator of fitness to drive in mild Alzheimer's dementia.

Since Alzheimer's disease may affect driving performance, patients with Alzheimer's disease are assessed on fitness to drive. On-road driving assessments are widely used, and attempts have also been made to develop strategies to assess fitness to drive in a clinical setting. Preferably, a first indication of fitness to drive is obtained quickly after diagnosis using a single test such as the Mini-Mental State Examination (MMSE). The aim of this study is to investigate whether the MMSE can be used to predict whether patients with Alzheimer's disease will pass or fail an on-road driving assessment. Patients with Alzheimer's disease (n = 81) participated in a comprehensive fitness-to-drive assessment which included the MMSE as well as an on-road driving assessment [PLoS One 11(2):e0149566, 2016]. MMSE cutoffs were applied as suggested by Versijpt and colleagues [Acta Neurol Belg 117(4):811-819, 2017]. All patients with Alzheimer's disease who scored below the lower cutoff (MMSE ≤ 19) failed the on-road driving assessment. However, a third of the patients with Alzheimer's disease who scored above the upper cutoff (MMSE ≥ 25) failed the on-road driving assessment as well. We conclude that the MMSE alone has insufficient predictive value to correctly identify fitness to drive in patients with very mild-to-mild Alzheimer's disease implicating the need for comprehensive assessments to determine fitness to drive in a clinical setting.

A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B.

BACKGROUND: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. AIMS: To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this effect. METHODS: STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation and secretion of interferon-gamma (IFN-γ) according to STAT4 genetic variation was examined. RESULTS: STAT4 rs7574865 genotype was independently associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele frequency of rs7574865 was significantly lower than that in healthy controls. rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in NK cells, while NK cells from patients with the risk genotype had impaired STAT4 phosphorylation following stimulation with IL-12/IL-18 and a reduction in secretion of IFN-γ. CONCLUSION: Genetic susceptibility to HBV persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-γ production likely contribute to these effects.

Looking back and moving forward: On the application of proportional shortfall in healthcare priority setting in the Netherlands.

The increasing demand for healthcare and the resulting pressure on available budgets render priority setting inevitable. If societies aim to improve health and distribute health(care) fairly, equity-efficiency trade-offs are necessary. In the Netherlands, proportional shortfall (PS) was introduced to quantify necessity of care, allowing a direct equity-efficiency trade-off. This study describes the history and application of PS in the Netherlands and examines the theoretical and empirical support for PS as well as its current role in healthcare decision making. We reviewed the international literature on PS from 2001 onwards, along with publicly accessible meeting reports from the Dutch appraisal committee, Adviescommissie Pakket (ACP), from 2013 to 2016. Our results indicate that there is support for the decision model in which necessity is quantified and incremental cost-effectiveness ratios are evaluated against associated monetary reference values. The model enables a uniform framework for priority setting across all healthcare sectors. Although consensus about the application of PS has not yet been reached and alternative ways to quantify necessity were found in ACP reports, PS has increasingly been applied in decision making since 2015. However, empirical support for PS is limited and it may insufficiently reflect societal preferences regarding age and reducing lifetime-health inequalities. Hence, further investigation into refining PS-or exploration of another approach-appears warranted for operationalising the equity-efficiency trade-off.

Indicators to facilitate the early identification of patients with major depressive disorder in need of highly specialized care: A concept mapping study.

BACKGROUND: Early identification of the subgroup of patients with major depressive disorder (MDD) in need of highly specialized care could enhance personalized intervention. This, in turn, may reduce the number of treatment steps needed to achieve and sustain an adequate treatment response. The aim of this study was to identify patient-related indicators that could facilitate the early identification of the subgroup of patients with MDD in need of highly specialized care. METHODS: Initial patient indicators were derived from a systematic review. Subsequently, a structured conceptualization methodology known as concept mapping was employed to complement the initial list of indicators by clinical expertise and develop a consensus-based conceptual framework. Subject-matter experts were invited to participate in the subsequent steps (brainstorming, sorting, and rating) of the concept mapping process. A final concept map solution was generated using nonmetric multidimensional scaling and agglomerative hierarchical cluster analyses. RESULTS: In total, 67 subject-matter experts participated in the concept mapping process. The final concept map revealed the following 10 major clusters of indicators: 1-depression severity, 2-onset and (treatment) course, 3-comorbid personality disorder, 4-comorbid substance use disorder, 5-other psychiatric comorbidity, 6-somatic comorbidity, 7-maladaptive coping, 8-childhood trauma, 9-social factors, and 10-psychosocial dysfunction. CONCLUSIONS: The study findings highlight the need for a comprehensive assessment of patient indicators in determining the need for highly specialized care, and suggest that the treatment allocation of patients with MDD to highly specialized mental healthcare settings should be guided by the assessment of clinical and nonclinical patient factors.

A (Latent) Class of Their Own: Response Patterns in Trading Off Quantity and Quality of Life in Time Trade-Off Exercises.

BACKGROUND: Conflicting results regarding associations of time trade-off (TTO) valuations with respondent characteristics have been reported, mostly on the basis of regression analyses. Alternative approaches, such as the latent class analysis (LCA), may add to the further understanding of variations in TTO responses. OBJECTIVES: To identify whether subgroups of respondents can be identified on the basis of their responses to TTO exercises and to investigate which respondent characteristics are associated with membership of the identified subgroups. METHODS: Members of the Dutch general public, aged 18 to 65 years, completed a Web-based questionnaire concerning sociodemographic characteristics, three TTO exercises valuing health states described using the domains of the EuroQol five-dimensional questionnaire, and preference for quality versus quantity of life. LCA was used to identify patterns in the responses. Predictive variables were included in the final LCA model to identify the particular respondent characteristics that predict subgroup membership. RESULTS: The sample consisted of 1067 respondents. Four latent classes were identified in the responses to TTO exercises. Two were high traders, focusing on quality of life and trading off a relatively high number of years. The other two were low traders, focusing on length of life. Predictive analyses revealed significant differences between subgroups in terms of age, sex, subjective life expectancy, and preference for quantity over quality of life. CONCLUSIONS: We showed that distinct classes of respondents can be discerned in TTO responses from the general public, distinguishing subgroups of low and high traders. More research in this area should confirm our findings and investigate their implications for health state valuation exercises.

The search for relevant outcome measures for cost-utility analysis of systemic family interventions in adolescents with substance use disorder and delinquent behavior: a systematic literature review.

PURPOSE: Systemic family interventions have shown to be effective in adolescents with substance use disorder and delinquent behavior. The interventions target interactions between the adolescent and involved systems (i.e. youth, family, peers, neighbors, school, work, and society). Next to effectiveness considerations, economic aspects have gained attention. However, conventional generic quality of life measures used in health economic evaluations may not be able to capture the broad effects of systemic interventions. This study aims to identify existing outcome measures, which capture the broad effects of systemic family interventions, and allow use in a health economic framework. METHODS: We based our systematic review on clinical studies in the field. Our goal was to identify effectiveness studies of psychosocial interventions for adolescents with substance use disorder and delinquent behavior and to distill the instruments used in these studies to measure effects. Searched databases were PubMed, Education Resource Information Center (ERIC), Cochrane and Psychnet (PsycBOOKSc, PsycCRITIQUES, print). Identified instruments were ranked according to the number of systems covered (comprehensiveness). In addition, their use for health economic analyses was evaluated according to suitability characteristics such as brevity, accessibility, psychometric properties, etc. RESULTS: One thousand three hundred seventy-eight articles were found and screened for eligibility. Eighty articles were selected, 8 instruments were identified covering 5 or more systems. CONCLUSIONS: The systematic review identified instruments from the clinical field suitable to evaluate systemic family interventions in a health economic framework. None of them had preference-weights available. Hence, a next step could be to attach preference-weights to one of the identified instruments to allow health economic evaluations of systemic family interventions.

Prediction of long-term clinical outcome in a diverse chronic hepatitis B population: Role of the PAGE-B score.

An abundance of noninvasive scores have been associated with fibrosis and hepatocellular carcinoma (HCC) development. We aimed to compare the prognostic ability of these scores in relation to liver histology in chronic hepatitis B (CHB) patients. Liver biopsies from treatment-naïve CHB patients at one tertiary care centre were scored by a single hepato-pathologist. Laboratory values at liver biopsy were used to calculate the PAGE-B, REACH-B, GAG-HCC, CU-HCC and FIB-4 scores. Any clinical event was defined as HCC development, liver failure, transplantation and mortality. HCC and mortality data were obtained from national database registries. Of 557 patients, 40 developed a clinical event within a median follow-up of 10.1 (IQR 5.7-15.9) years. The PAGE-B score predicted any clinical event (C-statistic.86, 95% CI: 0.80-0.92), HCC development (C-statistic .91) and reduced transplant-free survival (C-statistic .83) with good accuracy, also when stratified by ethnicity, antiviral therapy after biopsy or advanced fibrosis. The C-statistics (95% CI) of the REACH-B, GAG-HCC, CU-HCC and FIB-4 scores for any event were .70 (0.59-0.81), .82 (0.75-0.89), .73 (0.63-0.84) and.79 (0.69-0.89), respectively. The PAGE-B event risk assessment improved modestly when combined with the Ishak fibrosis stage (C-statistic .87, 95% CI: 0.82-0.93). The PAGE-B score showed the best performance in assessing the likelihood of developing a clinical event among a diverse CHB population over 15 years of follow-up. Additional liver histological characteristics did not appear to provide a clinically significant improvement.

Acceptable health and priority weighting: Discussing a reference-level approach using sufficientarian reasoning.

Health care systems are challenged in allocating scarce health care resources, which are typically insufficient to fulfil all health care wants and needs. One criterion for priority setting may be the 'acceptable health' approach, which suggests that society may want to assign higher priority to health benefits in people with "unacceptable" than in people with "acceptable" health. A level of acceptable health then serves as a reference point for priority setting. Empirical research has indicated that people may be able and willing to define health states as "unacceptable" or "acceptable", but little attention has been given to the normative implications of evaluating health benefits in relation to a reference level of acceptable health. The current paper aims to address this gap by relating insights from the distributive justice literature, i.e. the sufficientarian literature, to the acceptable health approach, as we argue that these approaches are related. We specifically focus on the implications of an 'acceptability' approach for priority weighting of health benefits, derived from sufficientarian reasoning and debates, and assess the moral implications of such weighting.

Health or Happiness? A Note on Trading Off Health and Happiness in Rationing Decisions.

BACKGROUND: Economic evaluations typically value the effects of an intervention in terms of quality-adjusted life-years, which combine length and health-related quality of life. It has been suggested that economic evaluations should incorporate broader outcomes than health-related quality of life. Broader well-being, for instance measured as happiness, could be a better measure of the overall welfare effects in patients because of treatment. An underexplored question is whether and how people trade off information on health and broader outcomes from treatment in rationing decisions. OBJECTIVES: This article presents the results of a first experiment aimed at exploring such trade-offs between health and happiness. METHODS: We used a Web-based questionnaire in a representative sample of the public from the Netherlands (N = 1015). People made choices between two groups of patients differing in terms of their health and happiness levels before treatment and gains from treatment. RESULTS: The results showed that about half the respondents were willing to discriminate between patient groups on the basis of their health and happiness levels before and after treatment. In the trader group, health gains were considered somewhat more important than happiness gains. CONCLUSIONS: Our findings suggest that both health and happiness levels of patients may play a role in priority setting.

Prevalence and risk factors for viral blipping in chronic hepatitis B patients treated with nucleos (t) ide analogues.

The clinical relevance of viral blipping during nucleos (t) ide analogue (NA) treatment is unclear in chronic hepatitis B (CHB). We investigated the prevalence, risk factors and clinical outcomes for those with viral blipping during NA treatment. A retrospective cohort study investigated consecutively treated CHB patients from May 2008 to February 2015 on the NAs such as entecavir (ETV), tenofovir (TDF) and lamivudine (LAM). Included patients were previously treatment naive. Viral blipping was defined as serum HBV DNA >20 IU/mL on one occasion, and not >200 IU/mL, with subsequent measurement returning to undetectable levels, that is <20 IU/mL. A total of 242 treatment-compliant CHB patients were included with 44 (18.2%) experiencing viral blipping. In multivariable Cox regression, Asian race (HR=7.40, 95% CI 1.01-54.29, P<.049), LAM therapy (vs ETV/TDF, HR=2.53, 95% CI 1.29-4.95, P<.007), higher creatinine (per SD, HR=1.47, 95% CI 1.21-1.79, P<.001), HBeAg positivity (HR=2.68, 95% CI 1.39-5.03, P<.003) and longer time to achieve undetectable HBV DNA (per month, HR=1.05, 95% CI 1.02-1.08, P=.001) were associated with an increased risk of viral blipping. Viral blipping did not show any significant association with viral breakthrough, HBsAg loss, ALT flares or disease progression. Viral blipping is a frequent event during NA therapy; however, it did not lead to any clinically significant outcomes. Thus, it may not require more frequent blood work and patient visits in clinical practice.

Patient and general public preferences for health states: A call to reconsider current guidelines.

In economic evaluations of health care interventions, benefits are often expressed in terms of Quality-Adjusted Life-Years (QALYs). The QALY comprises length and quality of life into one measure which allows cross-disease comparability. The quality adjustment of the QALY is based on preferences for health states. An important normative choice is the question whose preferences for states of health we wish to capture. The answer to this question is directly related to the normative question regarding the appropriate maximand in health care decisions. Currently, preferences are commonly derived from the general public, rather than from actual patients. This choice, which can have large consequences on final outcomes of economic evaluations, has always been a topic of debate. This paper clarifies and furthers the discussion regarding the appropriate source of preferences for health state valuations, acknowledges the plurality of different perspectives, and argues that health economic guidelines could require analysis of benefit in terms of QALYs based on both patient and general public preferences.

Hepatitis B core-related antigen levels are associated with response to entecavir and peginterferon add-on therapy in hepatitis B e antigen-positive chronic hepatitis B patients.

Hepatitis B core-related antigen (HBcrAg), a new serum marker, may be useful in monitoring chronic hepatitis B infection. HBcrAg was measured in 175 hepatitis B e antigen-positive patients treated with entecavir (ETV) with or without peginterferon (PEG-IFN) add-on therapy. Decline in HBcrAg was stronger in patients with vs. without combined response (ETV: -3.22 vs. -1.71 log U/mL, p <0.001; PEG-IFN add-on: -3.16 vs. -1.83 IU/mL, p <0.001) and in patients with vs. without hepatitis B surface antigen (HBsAg) response (ETV: -2.60 vs. -1.74 log U/mL, p <0.001; PEG-IFN add-on: -2.38 vs. -2.15 log U/mL, p = 0.31). HBcrAg was associated with combined response (adjusted odds ratio 0.3, 95% confidence interval 0.2-0.5, p <0.001), but was not superior to quantitative HBsAg (qHBsAg).

"Back to the future": Influence of beliefs regarding the future on TTO answers.

BACKGROUND: A common approach to obtain health state valuations is the time-tradeoff (TTO) method. Much remains unknown regarding the influence of responder characteristics on TTO answers. The objective of this study is to increase understanding of the influence that beliefs regarding future health and death, as well as desires to witness certain life events, have on respondents' health state valuations. METHODS: An online survey was designed, including three TTO questions using a 10 year timeframe. Moreover, respondents completed demographic questions, the Health-Risk Attitude Scale (HRAS), the Expectations Regarding Aging (ERA) questionnaire, questions about beliefs regarding future health (i.e. life expectancy) and death (i.e. fear of death, belief in life after death and opinion about euthanasia), and about important life events taking place within the TTO timeframe. Regression analyses were performed in order to assess the influence of these different variables. RESULTS: One thousand sixty-seven respondents were included in the analyses. The following variables were significantly associated with years traded off: ERA mental health (decrease), ERA physical health (increase), HRAS (increase), support for euthanasia (increase), fear of death (decrease) and consideration of an important life event (decrease). The explained variance of the final model was low (0.08). CONCLUSION: TTO responses may be influenced by considerations of future health, including life events and attitudes regarding health risks and death. Further investigation of TTO responses remains warranted.

Peginterferon add-on results in more HBsAg decline compared to monotherapy in HBeAg-positive chronic hepatitis B patients.

It is unknown whether peginterferon (PEG-IFN) add-on to entecavir (ETV) leads to more HBsAg decline compared to PEG-IFN monotherapy or combination therapy, and whether ETV therapy may prevent HBsAg increase after PEG-IFN cessation. We performed a post hoc analysis of 396 HBeAg-positive patients treated for 72 weeks with ETV + 24 weeks PEG-IFN add-on from week 24 to 48 (add-on, n = 85), 72 weeks with ETV monotherapy (n = 90), 52 weeks with PEG-IFN monotherapy (n = 111) and 52 weeks PEG-IFN + lamivudine (combination, n = 110) within 2 randomized trials. HBsAg decline was assessed at the end of PEG-IFN (EOP) and 6 months after PEG-IFN (EOF) discontinuation. Differences in baseline characteristics were accounted for using inversed probability of treatment weights. At EOP, a HBsAg reduction of ≥1log10 IU/mL was more frequently achieved for patients in the add-on or combination therapy arms (both 36%), compared to PEG-IFN mono (20%) or ETV (8%) (add-on vs PEG-IFN mono P = 0.050). At EOF, the HBsAg reduction ≥1log10 IU/mL was only sustained in patients treated with ETV consolidation (add-on vs combination and PEG-IFN mono: 40% vs 23% and 18%, P = 0.029 and P = 0.003, respectively). For add-on, combination, PEG-IFN mono and ETV, the mean HBsAg-level change at EOF was -0.84, -0.81, -0.68 and -0.33 log10 IU/mL, respectively (P > 0.05 for PEG-IFN arms). HBeAg loss at EOF was 36%, 31%, 33% and 20%, respectively (P > 0.05). PEG-IFN add-on for 24 weeks results in more on-treatment HBsAg decline than does 52 weeks of PEG-IFN monotherapy. ETV therapy may maintain the HBsAg reduction achieved with PEG-IFN.