(Cost-)effectiveness of a personalized multidisciplinary eHealth intervention for knee arthroplasty patients to enhance return to activities of daily life, work and sports - rationale and protocol of the multicentre ACTIVE randomized controlled trial.

BACKGROUND: With the worldwide rising obesity epidemic and the aging population, it is essential to deliver (cost-)effective care that results in enhanced societal participation among knee arthroplasty patients. The purpose of this study is to describe the development, content, and protocol of our (cost-)effectiveness study that assesses a perioperative integrated care program, including a personalized eHealth app, for knee arthroplasty patients aimed to enhance societal participation post-surgery compared to care as usual. METHODS: The intervention will be tested in a multicentre randomized controlled trial with eleven participating Dutch medical centers (i.e., hospitals and clinics). Working patients on the waiting-list for a total- or unicompartmental knee arthroplasty with the intention to return to work after surgery will be included. After pre-stratification on medical centre with or without eHealth as usual care, operation procedure (total- or unicompartmental knee arthroplasty) and recovery expectations regarding return to work, randomization will take place at the patient-level. A minimum of 138 patients will be included in both the intervention and control group, 276 in total. The control group will receive usual care. On top of care as usual, patients in the intervention group will receive an intervention consisting of three components: 1) a personalized eHealth intervention called ikHerstel ('I Recover') including an activity tracker, 2) goal setting using goal attainment scaling to improve rehabilitation and 3) a referral to a case-manager. Our main outcome is quality of life, based on patient-reported physical functioning (using PROMIS-PF). (Cost-)effectiveness will be assessed from a healthcare and societal perspective. Data collection has been started in 2020 and is expected to finish in 2024. DISCUSSION: Improving societal participation for knee arthroplasty is relevant for patients, health care providers, employers and society. This multicentre randomized controlled trial will evaluate the (cost-)effectiveness of a personalized integrated care program for knee arthroplasty patients, consisting of effective intervention components based on previous studies, compared to care as usual. TRIAL REGISTRATION: Trialsearch.who.int; reference no. NL8525, reference date version 1: 14-04-2020.

The longitudinal relationships between pain severity and disability versus health-related quality of life and costs among chronic low back pain patients.

PURPOSE: Previous studies found higher levels of pain severity and disability to be associated with higher costs and lower health-related quality of life. However, these findings were based on cross-sectional data and little is known about the longitudinal relationships between pain severity and disability versus health-related quality of life and costs among chronic low back pain patients. This study aims to cover this knowledge gap by exploring these longitudinal relationships in a consecutive cohort. METHODS: Data of 6316 chronic low back pain patients were used. Measurements took place at 3, 6, 9, and 12 months. Pain severity (Numeric pain rating scale; range: 0-100), disability (Oswestry disability index; range: 0-100), health-related quality of life (EQ-5D-3L: range: 0-1), societal and healthcare costs (cost questionnaire) were measured. Using linear generalized estimating equation analyses, longitudinal relationships were explored between: (1) pain severity and health-related quality of life, (2) disability and health-related quality of life, (3) pain severity and societal costs, (4) disability and societal costs, (5) pain severity and healthcare costs, and (6) disability and healthcare costs. RESULTS: Higher pain and disability levels were statistically significantly related with poorer health-related quality of life (pain intensity: - 0.0041; 95% CI - 0.0043 to - 0.0039; disability: - 0.0096; 95% CI - 0.0099 to - 0.0093), higher societal costs (pain intensity: 7; 95% CI 5 to 8; disability: 23; 95% CI 20 to 27) and higher healthcare costs (pain intensity: 3; 95% CI 2 to 4; disability: 9; 95% CI 7 to 11). CONCLUSION: Pain and disability were longitudinally related to health-related quality of life, societal costs, and healthcare costs. Disability had a stronger association with all outcomes compared to pain.

Reduction of routine use of radiography in patients with ankle fractures leads to lower costs and has no impact on clinical outcome: an economic evaluation.

BACKGROUND: To evaluate the cost-effectiveness of a reduction in the number of routine radiographs in the follow-up of patients with ankle fractures. METHODS: We performed an economic evaluation alongside the multicentre, randomised WARRIOR trial. Participants were randomised to a reduced imaging follow-up protocol (i.e. radiographs at week 6 and 12 follow-up obtained on clinical indication) or usual care (i.e. routine radiography at weeks 6 and 12). The Olerud & Molander Ankle Score (OMAS) was used to assess ankle function and the EQ-5D-3L was used to estimate Quality-Adjusted Life Years (QALYs). Costs and resource use were assessed using self-reported questionnaires and medical records, and analysed from a societal perspective. Multiple imputation was used for missing data, and data were analysed using seemingly unrelated regression analysis and bootstrapping. RESULTS: In total, 246 patients had data available for analysis (reduced imaging = 118; usual care = 128). Fewer radiographs were obtained in the reduced imaging group (median = 4) compared with the usual-care group (median = 5). Functional outcome was comparable in both groups. The difference in QALYs was - 0.008 (95% CI:-0.06 to 0.04) and the difference in OMAS was 0.73 (95% CI:-5.29 to 6.76). Imaging costs were lower in the reduced imaging group (-€48; 95% CI:- €72 to -€25). All other cost categories did not statistically differ between the groups. The probability of the reduced imaging protocol being cost-effectiveness was 0.45 at a wiliness-to-pay of €20,000 per QALY. CONCLUSIONS: Reducing the number of routine follow-up radiographs has a low probability of being cost-effective compared with usual care. Functional outcome, health-related quality of life and societal costs were comparable in both groups, whereas imaging costs were marginally lower in the reduced imaging group. Given this, adherence to a reduced imaging follow-up protocol for those with routine ankle fractures can be followed without sacrificing quality of care, and may result in reduced costs. TRIAL REGISTRATION: The trial was registered on 26-05-2014 in the Netherlands Trial Registry, with reference number NL4477 ( www.trialregister.nl/trial/4477 ).

Cost-effectiveness of laparoscopic ileocaecal resection versus infliximab treatment of terminal ileitis in Crohn's disease: the LIR!C Trial.

OBJECTIVE: Evaluate the cost-effectiveness of laparoscopic ileocaecal resection compared with infliximab in patients with ileocaecal Crohn's disease failing conventional therapy. DESIGN: A multicentre randomised controlled trial was performed in 29 centres in The Netherlands and the UK. Adult patients with Crohn's disease of the terminal ileum who failed >3 months of conventional immunomodulators or steroids without signs of critical strictures were randomised to laparoscopic ileocaecal resection or infliximab. Outcome measures included quality-adjusted life-years (QALYs) based on the EuroQol (EQ) 5D-3L Questionnaire and the Inflammatory Bowel Disease Questionnaire (IBDQ). Costs were measured from a societal perspective. Analyses were performed according to the intention-to-treat principle. Missing cost and effect data were imputed using multiple imputation. Cost-effectiveness planes and cost-effectiveness acceptability curves were estimated to show uncertainty. RESULTS: In total, 143 patients were randomised. Mean Crohn's disease total direct healthcare costs per patient at 1 year were lower in the resection group compared with the infliximab group (mean difference €-8931; 95% CI €-12 087 to €-5097). Total societal costs in the resection group were lower than in the infliximab group, however not statistically significant (mean difference €-5729, 95% CI €-10 606 to €172). The probability of resection being cost-effective compared with infliximab was 0.96 at a willingness to pay (WTP) of €0 per QALY gained and per point improvement in IBDQ Score. This probability increased to 0.98 at a WTP of €20 000/QALY gained and 0.99 at a WTP of €500/point of improvement in IBDQ Score. CONCLUSION: Laparoscopic ileocaecal resection is a cost-effective treatment option compared with infliximab. CLINICAL TRIAL REGISTRATION NUMBER: Dutch Trial Registry NTR1150; EudraCT number 2007-005042-20 (closed on 14 October 2015).

Do socio-demographic characteristics and/or health status explain the magnitude of differences between patient and general public utility values? A chronic low back pain patients case study.

BACKGROUND: Utility values can be obtained from different respondent groups, including patients and members of the general public. Evidence suggests that patient values are typically higher than general public values. This study explores whether the magnitude of disagreement between both values can be explained by socio-demographic characteristics and/or health status. METHODS: Data of 5037 chronic low back pain patients were used. Self-reported EQ-VAS was employed as a proxy of patients' preference for their own health state. General public values for the patients' EQ-5D-3L health states were obtained using the Dutch VAS-based tariff. The difference between patient and general public values was assessed using a paired t-test. Subsequently, this difference was used as a dependent variable and regressed upon dummy variables of socio-demographic and health status characteristics. Coefficients represented age, gender, education level, social support, back pain intensity, leg pain intensity, functional status, comorbidities, catastrophizing, and treatment expectations. RESULTS: Patient values were higher than general public values (0.069; 95%CI:0.063-0.076). The magnitude of disagreement between both values was associated with age, gender, education level, social support, functional status, and comorbidities, but not with back pain intensity, leg pain intensity, catastrophizing, and treatment expectations. CONCLUSIONS: Patients were found to value their own health status higher than members of the general public. The magnitude of disagreement between both values was found to differ by various socio-demographic and/or health status characteristics. This suggest that patient characteristics account for a relevant fraction of the identified disagreements between patient and general public values, and that mechanisms thought to be responsible for these disagreements, such as adaptation and response shift, have a differential impact across patient sub-groups.

Patient versus general population health state valuations: a case study of non-specific low back pain.

PURPOSE: The purpose of this study was twofold: (1) to compare non-specific low back pain (LBP) patients' health state valuations with those of the general population, and (2) to explore how aspects of health-related quality of life as measured by the EQ-5D-3L impact non-specific LBP patient valuations. METHODS: Data were used of a randomized controlled trial, including 483 non-specific LBP patients. Outcomes included the EQ-VAS and the EQ-5D-3L. Patient valuations were derived from the EQ-VAS. Population valuations were derived from the EQ-5D-3L using a Dutch VAS-based tariff. The difference between patient and population valuations was assessed using t tests. An OLS linear regression model was constructed to explore how various aspects of health-related quality of life as measured by the ED-5D-3L impact non-specific LBP patient valuations. RESULTS: Non-specific LBP patients valued their health states 0.098 (95% CI 0.082-0.115) points higher than the general population. Only 22.2% of the variance in patient valuations was explained by the patients' EQ-5D-3L health states (R 2 = 0.222). Non-specific LBP patients gave the most weight to the anxiety/depression dimension. CONCLUSIONS: This study demonstrated that non-specific LBP patients value their health states higher than members of the general population and that the choice of valuation method could have important implications for cost-effectiveness analyses and thus for clinical practice.

Cost-effectiveness of a combined physical exercise and psychosocial training intervention for children with cancer: Results from the quality of life in motion study.

This study was performed to estimate the cost-effectiveness of a combined physical exercise and psychosocial intervention for children with cancer compared with usual care. Sixty-eight children, aged 8-18 years old, during or within the first year post-cancer treatment were randomised to the intervention (n = 30) and control group (n = 38). Health outcomes included fitness, muscle strength and quality adjusted life years; all administered at baseline, 4- and 12-month follow-up. Costs were gathered by 1 monthly cost questionnaires over 12 months, supplemented by medication data obtained from pharmacies. Results showed no significant differences in costs and effects between the intervention and control group at 12-month follow-up. On average, societal costs were €299 higher in the intervention group than in the control group, but this difference was not significant. Cost-effectiveness acceptability curves indicated that the intervention needs large societal investments to reach reasonable probabilities of cost-effectiveness for quality of life and lower body muscle strength. Based on the results of this study, the intervention is not cost-effective in comparison with usual care.

The cost-effectiveness and return-on-investment of a combined social and physical environmental intervention in office employees.

This study explored the cost-effectiveness and return-on-investment of a combined social and physical environmental worksite health promotion program compared with usual practice, and of both intervention conditions separately. Participants were randomized to the combined intervention (n = 92), social environmental intervention (n = 118), physical environmental intervention (n = 96), or control group (n = 106). The social environmental intervention consisted of group motivational interviewing and the physical environmental intervention of workplace modifications. Both interventions were aimed at improving physical activity and relaxation. Effects included need for recovery (NFR), general vitality and job satisfaction. Cost-effectiveness analyses were performed from the societal and employer's perspective, and return-on-investment analyses from the employer's perspective. Compared with usual practice, the combined intervention was significantly more effective in improving NFR (-8.4;95% CI:-14.6;-2.2) and significantly more expensive to the employer (3102; 95%CI:598;5969). All other between-group differences were non-significant. For NFR, the combined intervention became the preferred option at willingness-to-pays of ≥€170/point improvement (society) and ≥€300/point improvement (employer). For general vitality and job satisfaction, the interventions' maximum probabilities of cost-effective were low (≤0.55). All interventions had a negative return-on-investment. The combined intervention may be cost-effective for NFR depending on the decision-makers' willingness-to-pay. Both separate interventions are not cost-effective for NFR. All interventions were neither cost-effective for general vitality and job satisfaction, nor cost-saving to the employer.

Insights into the concept of vitality: associations with participation and societal costs.

BACKGROUND: In healthcare, the focus is currently shifting from someone's disabilities to someone's abilities, which is also evident from the increasing focus on vitality. Vitality (here defined as energy, motivation and resilience) is an often used concept, which also aims at someone's capabilities. However, little is known about vitality yet; in particular about its association with participation and societal costs. METHODS: Within a cross-sectional design, information regarding vitality, participation and societal costs was collected among 8015 Dutch adults aged 20 years and over. Vitality was measured using the validated Dutch Vitality Questionnaire (Vita-16). Information on economic (i.e. want/able to work, work absenteeism, work performance), societal (i.e. voluntary work, informal care giving) and social participation (i.e. quantity and quality of social contacts) and societal costs (i.e. healthcare and work-related costs) was collected using an internet survey. RESULTS: Significant associations were found between vitality and various economic (i.e.sustainable employability:want to work: ß = 1.21, 95% CI: 0.99-1.43,able to work:ß = 2.09, 95% CI: 1.79-2.38;work absenteeism: OR = 0.75, 95% CI: 0.71-0.79;work performance:ß = 0.49, 95% CI: 0.46-0.52), societal (i.e.voluntary work, informal care) and social (i.e.quantity and quality of social contacts) participation measures, as well as between vitality and societal costs (i.e.healthcare costs:ß = -213.73, 95% CI: €-311.13 to €-107.08),absenteeism costs: ß = -338.57, 95% CI: €-465.36 to €-214.14 and presenteeism costs:ß = -1293.31, 95% CI: €-1492.69 to €-1088.95). CONCLUSION: This study showed significant positive associations between vitality and economic, societal and social participation and negative associations between vitality and societal costs. This may stimulate research on interventions enhancing and maintaining vitality and thereby contributing to improved participation and reduced costs.

Cost-effectiveness of manual therapy versus physiotherapy in patients with sub-acute and chronic neck pain: a randomised controlled trial.

PURPOSE: To evaluate the cost-effectiveness of manual therapy according to the Utrecht School (MTU) in comparison with physiotherapy (PT) in sub-acute and chronic non-specific neck pain patients from a societal perspective. METHODS: An economic evaluation was conducted alongside a 52-week randomized controlled trial, in which 90 patients were randomized to the MTU group and 91 to the PT group. Clinical outcomes included perceived recovery (yes/no), functional status (continuous and yes/no), and quality-adjusted life-years (QALYs). Costs were measured from a societal perspective using self-reported questionnaires. Missing data were imputed using multiple imputation. To estimate statistical uncertainty, bootstrapping techniques were used. RESULTS: After 52 weeks, there were no significant between-group differences in clinical outcomes. During follow-up, intervention costs (ß:€-32; 95 %CI: -54 to -10) and healthcare costs (ß:€-126; 95 %CI: -235 to -32) were significantly lower in the MTU group than in the PT group, whereas unpaid productivity costs were significantly higher (ß:€186; 95 %CI:19-557). Societal costs did not significantly differ between groups (ß:€-96; 95 %CI:-1975-2022). For QALYs and functional status (yes/no), the maximum probability of MTU being cost-effective in comparison with PT was low (≤0.54). For perceived recovery (yes/no) and functional status (continuous), a large amount of money must be paid per additional unit of effect to reach a reasonable probability of cost-effectiveness. CONCLUSIONS: From a societal perspective, MTU was not cost-effective in comparison with PT in patients with sub-acute and chronic non-specific neck pain for perceived recovery, functional status, and QALYs. As no clear total societal cost and effect differences were found between MTU and PT, the decision about what intervention to administer, reimburse, and/or implement can be based on the preferences of the patient and the decision-maker at hand. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00713843.

Prevention program at construction worksites aimed at improving health and work ability is cost-saving to the employer: results from an RCT.

BACKGROUND: To prolong sustainable healthy working lives of construction workers, a prevention program was developed which aimed to improve the health and work ability of construction workers. The objective of this study was to analyze the cost-effectiveness and financial return from the employers' perspective of this program. METHODS: A total of 293 workers in 15 departments were randomized to the intervention (n = 8 departments) or control group (n = 7). Data on work ability and health were collected using questionnaires. Sick leave data were obtained from the companies. Both the cost-effectiveness analyses and return on investment analyses were performed. RESULTS: After 12 months, the absenteeism costs were significantly lower in the intervention group than in the control group. At 12-month follow-up, no significant differences were found with respect to the primary outcomes (work ability, mental and physical health status) and secondary outcomes (musculoskeletal symptoms), meaning that the intervention was not cost-effective in comparison with the control group. The net-benefit was €641 per worker, and the intervention generated a positive financial return to the employer. CONCLUSION: The intervention in the present study was cost-saving to the employer due to reduced sickness absenteeism costs in the intervention group compared with the control group. However, the intervention cannot be regarded as cost-effective as no significant effects were found for work ability and health.

The cost-effectiveness of an indicated blended care intervention in primary care compared to usual care in patients with moderate persistent somatic symptoms.

INTRODUCTION: Appropriate treatment for people with an increased risk for developing chronic Persistent Somatic Symptoms (PSS) is of great importance at an early stage to improve quality of life and prevent high costs for society. OBJECTIVE: To evaluate the cost-effectiveness of an integrated blended care intervention compared to usual care for QALYs, subjective symptom impact and physical and mental health status in patients with moderate PSS. METHODS: This economic evaluation was conducted alongside a 12-month prospective, multicenter cluster randomized controlled trial in Dutch primary care. 80 participants received the intervention and 80 participants received usual care. Seemingly unrelated regression analyzes were performed to estimate cost and effect differences. Missing data were imputed using multiple imputation. Bootstrapping techniques were used to estimate uncertainty. RESULTS: We found no significant difference in total societal costs. Intervention, primary and secondary healthcare and absenteeism costs were higher for the intervention group. The ICER for QALYs demonstrated the intervention was on average less costly and less effective compared to usual care. For the subjective symptom impact and physical health, the ICER indicated that the intervention group was on average less costly and more effective. For mental health, the intervention was on average more costly and less effective. CONCLUSION: We didn't find an integrated blended primary care intervention to be cost-effective compared to usual care. However, when looking on relevant, but specific outcome measures (subjective symptom impact and physical health) for this population, average costs are found to be lower and the effectiveness found to be higher.

The (cost-)effectiveness of combined lifestyle interventions for people with persistent low-back pain who are overweight or obese: A systematic review.

INTRODUCTION: Lifestyle factors are expected to contribute to the persistence and burden of low-back pain (LBP). However, there are no systematic reviews on the (cost-)effectiveness of combined lifestyle interventions for overweight or obese people with LBP. AIM: To assess whether combined lifestyle interventions are (cost-)effective for people with persistent LBP who are overweight or obese, based on a systematic review. DESIGN: Systematic review METHOD: PubMed, Cochrane, Embase, CINAHL, PsycINFO and the Wiley/Cochrane Library were searched from database inception till January 6th 2023. Two independent reviewers performed study selection, data-extraction and risk of bias scoring using the Cochrane RoB tool 2 and/or the Consensus Health Economic Criteria list. GRADE was used to assess the level of certainty of the evidence. RESULTS: In total 2510 records were screened, and 4 studies on 3 original RCTs with 216 participants were included. Low certainty evidence (1 study) showed that combined lifestyle interventions were not superior to usual care for physical functioning, pain and lifestyle outcomes. Compared to usual care, moderate certainty evidence showed that healthcare (-$292, 95%CI: 872; -33), medication (-$30, 95% CI -65; -4) and absenteeism costs (-$1000, 95%CI: 3573; -210) were lower for the combined lifestyle interventions. CONCLUSION: There is low certainty evidence from 3 studies with predominantly small sample sizes, short follow-up and low intervention adherence that combined lifestyle interventions are not superior to physical functioning, pain and lifestyle outcomes compared to usual care, but are likely to be cost-effective.

Direct discharge of patients with simple stable musculoskeletal injuries as an alternative to routine follow-up: a systematic review of the current literature.

PURPOSE: There is growing evidence that patients with certain simple stable musculoskeletal injuries can be discharged directly from the Emergency Department (ED), without compromising patient outcome and experience. This study aims to review the literature on the effects of direct discharge (DD) of simple stable musculoskeletal injuries, regarding healthcare utilization, costs, patient outcome and experience. METHODS: A systematic review was performed in Medline, Embase, CINAHL, Cochrane Library and Web of Science using PRISMA guidelines. Comparative and non-comparative studies on DD of simple stable musculoskeletal injuries from the ED in an adult/paediatric/mixed population were included if reporting ≥ 1 of: (1) logistic outcomes: DD rate (proportion of patients discharged directly); number of follow-up appointments; DD return rate; (2) costs; (3) patient outcomes/experiences: functional outcome; treatment satisfaction; adverse outcomes; other. RESULTS: Twenty-six studies were included (92% conducted in the UK). Seven studies (27%) assessed functional outcome, nine (35%) treatment satisfaction, and ten (38%) adverse outcomes. A large proportion of studies defined DD eligibility criteria as injuries being minor/simple/stable, without further detail. ED DD rate was 26.7-59.5%. Mean number of follow-up appointments was 1.00-2.08 pre-DD, vs. 0.00-0.33 post-DD. Return rate was 0.0-19.4%. Costs per patient were reduced by €69-€210 (ranging from - 38.0 to - 96.6%) post-DD. Functional outcome and treatment satisfaction levels were 'equal' or 'better' (comparative studies), and 'high' (non-comparative studies), post-DD. Adverse outcomes were low and comparable. CONCLUSIONS: This systematic review supports the idea that DD of simple stable musculoskeletal injuries from the ED provides an opportunity to reduce healthcare utilization and costs without compromising patient outcomes/experiences. To improve comparability and facilitate implementation/external validation of DD, future studies should provide detailed DD eligibility criteria, and use a standard set of outcomes. Systematic review registration number: 120779, date of first registration: 12/02/2019.

Effectiveness and cost-effectiveness of surgery versus casting for elderly patients with Displaced intra-Articular type C distal Radius fractures: protocol of a randomised controlled Trial with economic evaluation (the DART study).

INTRODUCTION: Current literature is inconclusive about the optimal treatment of elderly patients with displaced intra-articular distal radius fractures. Cast treatment is less invasive and less expensive than surgical treatment. Nevertheless, surgery is often the preferred treatment for this common type of distal radius fracture. Patients with a non-acceptable position after closed reduction are more likely to benefit from surgery than patients with an acceptable position after closed reduction. Therefore, this study aims to assess non-inferiority of functional outcomes after casting versus surgery in elderly patients with a non-acceptable position following a distal radius fracture. METHODS AND ANALYSIS: This study is a multicentre randomised controlled trial (RCT) with a non-inferiority design and an economic evaluation alongside. The population consists of patients aged 65 years and older with a displaced intra-articular distal radius fracture with non-acceptable radiological characteristics following either inadequate reduction or redisplacement after adequate reduction. Patients will be randomised between surgical treatment (open reduction and internal fixation) and non-operative treatment (closed reduction followed by cast treatment). We will use two age strata (65-75 and >75 years of age) and a web-based mixed block randomisation. A total of 154 patients will be enrolled and evaluated with the patient-rated wrist evaluation as the primary outcome at 1-year follow-up. Secondary outcomes include the Disabilities of the Arm, Shoulder and Hand questionnaire, quality of life (measured by the EQ-5D), wrist range of motion, grip strength and adverse events. In addition, we will perform a cost-effectiveness and cost-utility analysis from a societal and healthcare perspective. Incremental cost-effectiveness ratios, cost-effectiveness planes and cost-effectiveness acceptability curves will be presented. ETHICS AND DISSEMINATION: The Research and Ethics Committee approved this RCT (NL56858.100.16). The results of this study will be reported in a peer-reviewed journal. We will present the results of this study at (inter)national conferences and disseminate the results through guideline committees. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov (NCT03009890). Dutch Trial Registry (NTR6365).

Long-term effectiveness and cost-effectiveness of high versus low-to-moderate intensity resistance and endurance exercise interventions among cancer survivors.

PURPOSE: This study aimed to evaluate the long-term effectiveness and cost-effectiveness of high intensity (HI) versus low-to-moderate intensity (LMI) exercise on physical fitness, fatigue, and health-related quality of life (HRQoL) in cancer survivors. METHODS: Two hundred seventy-seven cancer survivors participated in the Resistance and Endurance exercise After ChemoTherapy (REACT) study and were randomized to 12 weeks of HI (n = 139) or LMI exercise (n = 138) that had similar exercise types, durations, and frequencies, but different intensities. Measurements were performed at baseline (4-6 weeks after primary treatment), and 12 (i.e., short term) and 64 (i.e., longer term) weeks later. Outcomes included cardiorespiratory fitness, muscle strength, self-reported fatigue, HRQoL, quality-adjusted life years (QALYs) and societal costs. Linear mixed models were conducted to study (a) differences in effects between HI and LMI exercise at longer term, (b) within-group changes from short term to longer term, and (c) the cost-effectiveness from a societal perspective. RESULTS: At longer term, intervention effects on role (ß = 5.9, 95% CI = 0.5; 11.3) and social functioning (ß = 5.7, 95%CI = 1.7; 9.6) were larger for HI compared to those for LMI exercise. No significant between-group differences were found for physical fitness and fatigue. Intervention-induced improvements in cardiorespiratory fitness and HRQoL were maintained between weeks 12 and 64, but not for fatigue. From a societal perspective, the probability that HI was cost-effective compared to LMI exercise was 0.91 at 20,000€/QALY and 0.95 at 52,000€/QALY gained, mostly due to significant lower healthcare costs in HI exrcise. CONCLUSIONS: At longer term, we found larger intervention effects on role and social functioning for HI than for LMI exercise. Furthermore, HI exercise was cost-effective with regard to QALYs compared to LMI exercise. TRIAL REGISTRATION: This study is registered at the Netherlands Trial Register [NTR2153 [ http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2153 ]] on the 5th of January 2010. IMPLICATIONS FOR CANCER SURVIVORS: Exercise is recommended to be part of standard cancer care, and HI may be preferred over LMI exercise.

The Role of Vitality in the Relationship Between a Healthy Lifestyle and Societal Costs of Health Care and Lost Productivity: A Mediation Analysis.

PURPOSE: To examine the mediating effect of vitality in the relationship between healthy lifestyle characteristics and health-care and productivity-related costs. DESIGN: Observational prospective cohort study with 2 measurements. Online questionnaires were filled out in 2013 (T0) and 2014 (T1). SETTING: A random sample of a Dutch online interview panel was obtained. SUBJECTS: Data of 4231 Dutch adults who had complete data at T0 and T1 were used in the present study. Participants were representative for the Dutch adult population in terms of age, gender, and having chronic disease(s). MEASURES: Healthy Lifestyle Index (HLI), vitality, and health-care and productivity-related costs. The HLI consisted of the sum of 6 healthy lifestyle characteristics, including a healthy BMI (yes/no), meeting physical activity, fruit, vegetable, and alcohol consumption guidelines (yes/no), and smoking status (yes: non or former smoker/no: current smoker). Health-care and productivity-related costs were measured using a utilization questionnaire. ANALYSIS: Linear regression analysis. RESULTS: The HLI was related to vitality. In addition, vitality was related to health-care costs and productivity-related costs. Furthermore, vitality was found to transmit 28.4% of the effect of HLI on health-care costs and 39.4% of the effect of HLI on productivity-related costs. CONCLUSION: Lifestyle was related to vitality and vitality to health-care and productivity-related costs. Vitality mediated the relationship between lifestyle and health-care and productivity-related costs. Therefore, we recommend to sustain and improve both vitality and lifestyle.

Health economic evidence gaps and methodological constraints in low back pain and neck pain: Results of the Research Agenda for Health Economic Evaluation (RAHEE) project.

Despite the increased interest in economic evaluations, there are difficulties in applying the results of such studies in practice. Therefore, the "Research Agenda for Health Economic Evaluation" (RAHEE) project was initiated, which aimed to improve the use of health economic evidence in practice for the 10 highest burden conditions in the European Union (including low back pain [LBP] and neck pain [NP]). This was done by undertaking literature mapping and convening an Expert Panel meeting, during which the literature mapping results were discussed and evidence gaps and methodological constraints were identified. The current paper is a part of the RAHEE project and aimed to identify economic evidence gaps and methodological constraints in the LBP and NP literature, in particular. The literature mapping revealed that economic evidence was unavailable for various commonly used LBP and NP treatments (e.g., injections, traction, and discography). Even if economic evidence was available, many treatments were only evaluated in a single study or studies for the same intervention were highly heterogeneous in terms of their patient population, control condition, follow-up duration, setting, and/or economic perspective. Up until now, this has prevented economic evaluation results from being statistically pooled in the LBP and NP literature, and strong conclusions about the cost-effectiveness of LBP and NP treatments can therefore not be made. The Expert Panel identified the need for further high-quality economic evaluations, especially on surgery versus conservative care and competing treatment options for chronic LBP. Handling of uncertainty and reporting quality were considered the most important methodological challenges.

Immunocytochemical localization of lysosomal acid phosphatase in normal and "I-cell" fibroblasts.

This study represents the first example of immunological localization of lysosomal acid phosphatase. The intracellular localization of lysosomal acid phosphatase was investigated with immunocytochemical methods at the light and electron microscopical level in cultured fibroblasts obtained from normal subjects and from a patient with I-cell disease. Double-labeling studies using fluorescence microscopy showed that acid phosphatase is present in the same organelles as other hydrolases. At the electron microscopic level in control fibroblasts acid phosphatase was found in the rough endoplasmic reticulum, lysosomes, at the plasma membrane, in vesicles just below the plasma membrane and in multivesicular bodies. This localization was comparable with that of other lysosomal enzymes tested (acid alpha-glucosidase, N-acetyl-beta-hexosaminidase, beta-galactosidase). Acid phosphatase labeling was mainly found in association with the lysosomal membrane and with membranous material present within the lysosome. In I-cell fibroblasts the label was present in the same subcellular organelles but always associated with membranous structures. We suggest that the association of acid phosphatase with membranes might explain the normal enzyme activity found in I-cell fibroblasts.

Immunoelectron microscopical localization of lysosomal beta-galactosidase and its precursor forms in normal and mutant human fibroblasts.

Immunoelectron microscopy was performed to study the biosynthesis of lysosomal beta-galactosidase (beta-gal) in normal and mutant human fibroblasts. Using polyclonal and monoclonal antibodies we show in normal cells precursor forms of beta-gal in the rough endoplasmic reticulum (RER) and in the Golgi apparatus throughout the stack of cisternae. In the lysosomes virtually all beta-gal exists as a high molecular weight multimer of mature enzyme. In the autosomal recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in galactosialidosis, associated with a combined deficiency of lysosomal neuraminidase and beta-gal, precursor forms of the latter enzyme are found in RER, Golgi and some labeling is present at the cell surface. The lysosomes remain unlabeled, indicative for the absence of enzyme molecules in this organelle. In galactosialidosis fibroblasts also no mature beta-gal is found in the lysosomes but in these cells the presence of the monomeric form can be increased by leupeptin (inhibition of proteolysis) whereas addition of a partly purified 32 kDa "protective protein" results in the restoration of high molecular weight beta-gal multimers in the lysosomes.