Patient-reported health outcomes in long-term lung transplantation survivors: A prospective cohort study.

During the last three decades lung transplantation (LTx) has become a proven modality for increasing both survival and health-related quality of life (HRQoL) in patients with various end-stage lung diseases. Most previous studies have reported improved HRQoL shortly after LTx. With regard to long-term effects on HRQoL, however, the evidence is less solid. This prospective cohort study was started with 828 patients who were on the waiting list for LTx. Then, in a longitudinal follow-up, 370 post-LTx patients were evaluated annually for up to 15 years. For all wait-listed and follow-up patients, the following four HRQoL instruments were administered: State-Trait Anxiety Inventory, Zung Self-rating Depression Scale, Nottingham Health Profile, and a visual analogue scale. Cross-sectional and generalized estimating equation (GEE) analysis for repeated measures were performed to assess changes in HRQoL during follow-up. After LTx, patients showed improvement in all HRQoL domains except pain, which remained steady throughout the long-term follow-up. The level of anxiety and depressive symptoms decreased significantly and remained constant. In conclusion, this study showed that HRQoL improves after LTx and tends to remain relatively constant for the entire life span.

Vaccine preferences and acceptance of older adults.

BACKGROUND: Expanding vaccination programs for the older population might be important as older adults are becoming a larger proportion of the general population. The aim of this study is to determine the relative importance of vaccine and disease specific characteristics and acceptance for Dutch older adults, including pneumococcal disease, herpes zoster, pertussis vaccination, and influenza vaccination. METHODS: A discrete choice experiment was conducted to generate choice data that was analyzed using a mixed multinomial logit statistical model. RESULTS: Important factors that were associated with vaccination acceptance in older adults are high mortality risk of the infectious disease, high susceptibility of getting the infectious disease, and high vaccine effectiveness. Age, influenza vaccination in 2013 and self-perceived health score were identified as personal factors that affect vaccine preference. Potential vaccination rates of older adults were estimated at 68.1% for pneumococcal vaccination, 58.1% for herpes zoster vaccination, 53.9% for pertussis vaccination and 54.3% for influenza vaccination. For persons aged 50-65, potential vaccination rates were estimated at 58.1% for pneumococcal vaccination, 49.5% for herpes zoster vaccination, 43.9% for pertussis vaccination and 42.2% for influenza vaccination. For persons aged 65 and older, these were respectively 76.2%, 67.5%, 57.5% and 65.5%. DISCUSSION: Our results suggest that older adults are most likely to accept pneumococcal vaccination of the four vaccines. Information provision accompanied with the implementation of a new vaccine has to be tailored for the individual and the vaccine it concerns. Special attention is needed to ensure high uptake among persons aged 50-65years.

Multi-criteria decision analysis (MCDA): testing a proposed MCDA framework for orphan drugs.

BACKGROUND: Since the introduction of the orphan drugs legislation in Europe, it has been suggested that the general method of assessing drugs for reimbursement is not necessarily suitable for orphan drugs. The National Institute for Health and Clinical Excellence indicated that several criteria other than cost and efficacy could be considered in reimbursement decisions for orphan drugs. This study sought to explore the multi-criteria decision analysis (MCDA) framework proposed by (Orphanet J Rare Dis 7:74, 2012) to a range of orphan drugs, with a view to comparing the aggregate scores to the average annual cost per patient for each product, and thus establishing the merit of MCDA as a tool for assessing the value of orphan drugs in relation to their pricings. METHODS: An MCDA framework was developed using the nine criteria proposed by (Orphanet J Rare Dis 7:74, 2012) for the evaluation of orphan drugs, using the suggested numerical scoring system on a scale of 1 to 3 for each criterion. Correlations between the average annual cost of the drugs and aggregate MCDA scores were tested and plotted graphically. Different weightings for each of the attributes were also tested. A further analysis was conducted to test the impact of including the drug cost as an attribute in the aggregate index scores. RESULTS: In the drugs studied, the R 2, that statistically measures how close the data are to the fitted regression line was 0.79 suggesting a strong correlation between the drug scores and the average annual cost per patient. CONCLUSION: Despite several limitations of the proposed model, this quantitative study provided insight into using MCDA and its relationship to the average annual costs of the products.

Individual patient information to select patients for different radiation techniques.

BACKGROUND AND PURPOSE: Proton therapy is an emerging technique in radiotherapy which results in less dose to the normal tissues with similar target dose than photon therapy, the current standard. Patient-level simulation models support better decision making on which patients would benefit most. MATERIALS AND METHODS: A simulation model was developed tracking individual patients' status regarding the primary tumour and multiple complications. As a proof of principle, the model was populated based on information from a cohort of 1013 head and neck cancer patients. Dose-volume parameters for photon and proton radiation treatment plans were then fed into the model to compare outcomes in terms of length and quality of life and select patients that would benefit most. RESULTS: The illustrative model could adequately replicate the outcomes of photon therapy in the cohort. Improvements from proton therapy varied considerably between patients. The model projects medium-term outcomes for specific individuals and determines the benefits of applying proton rather than photon therapy. CONCLUSIONS: While the model needs to be fed with more and especially recent data before being fully ready for use in clinical practice, it could already distinguish between patients with high and low potential benefits from proton therapy. Benefits are highest for patients with both good prognosis and high expected damage to adjacent organs. The model allows for selecting such patients a priori based on patient relevant outcomes.

[Cost-effectiveness in Dutch mental health care: future because of ROM?]. / Doelmatigheid in de ggz: toekomst dankzij ROM?

BACKGROUND: The document reporting Dutch mental health care negotiations for 2014-2017 calls for a cost decrease based on cost-effectiveness. Thanks to ROM, the Dutch mental health care seems well prepared for cost-effectiveness research. AIM: Evaluate how valid cost-effectiveness research should be established in mental health care and the role of rom therein. METHOD: Evaluation of requirements of cost-effectiveness research, trends, and a translation to Dutch mental health care. RESULTS: Valid cost-effectiveness research in mental health care requires the application of a societal perspective, a long time-horizon and an adequate evaluation of quality of life of patients. Healthcare consumption, outcome of care and characterisation of the patient population should be measured systematically and continuously. Currently, rom-data are not suitable to serve as a basis for cost-effectiveness research, although a proper basis is present. Further development of rom could lead to a situation in which mental health care is purchased on the basis of cost-effectiveness. However, cost-effectiveness will only really be improved if quality of care is rewarded, rather than rewarding activities that are not always related to outcome of care. CONCLUSION: Cost-effectiveness research in mental health care should focus on societal costs and benefits, quality of life and a long time-horizon. If developed further, rom has the potential to be a basis for cost-effectiveness research in the future.

Validation of the Care-Related Quality of Life Instrument in different study settings: findings from The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS).

PURPOSE: Validity is a contextual aspect of a scale which may differ across sample populations and study protocols. The objective of our study was to validate the Care-Related Quality of Life Instrument (CarerQol) across two different study design features, sampling framework (general population vs. different care settings) and survey mode (interview vs. written questionnaire). METHODS: Data were extracted from The Older Persons and Informal Caregivers Minimum DataSet (TOPICS-MDS, www.topics-mds.eu ), a pooled public-access data set with information on >3,000 informal caregivers throughout the Netherlands. Meta-correlations and linear mixed models between the CarerQol's seven dimensions (CarerQol-7D) and caregiver's level of happiness (CarerQol-VAS) and self-rated burden (SRB) were performed. RESULTS: The CarerQol-7D dimensions were correlated to the CarerQol-VAS and SRB in the pooled data set and the subgroups. The strength of correlations between CarerQol-7D dimensions and SRB was weaker among caregivers who were interviewed versus those who completed a written questionnaire. The directionality of associations between the CarerQol-VAS, SRB and the CarerQol-7D dimensions in the multivariate model supported the construct validity of the CarerQol in the pooled population. Significant interaction terms were observed in several dimensions of the CarerQol-7D across sampling frame and survey mode, suggesting meaningful differences in reporting levels. CONCLUSIONS: Although good scientific practice emphasises the importance of re-evaluating instrument properties in individual research studies, our findings support the validity and applicability of the CarerQol instrument in a variety of settings. Due to minor differential reporting, pooling CarerQol data collected using mixed administration modes should be interpreted with caution; for TOPICS-MDS, meta-analytic techniques may be warranted.

Factors affecting the uptake of vaccination by the elderly in Western society.

OBJECTIVE: To present the results of a literature review on factors related to vaccine uptake by elderly persons. METHODS: A systematic literature search was performed using Medline, Embase, and SciSearch to collect all publications available on factors related to vaccine uptake from 1966 until October 2012 for West European and North American societies. In total, 1001 articles were identified and 60 were included in the review. RESULTS: We identified six main themes that influence the willingness to be vaccinated: 1) attitudes and beliefs regarding vaccination in general including positive and negative attitudes and beliefs; 2) perceived risk and severity including knowledge, perceived susceptibility and severity and personal experience; 3) vaccine characteristics including side-effects, effectiveness, content of the vaccine and knowledge; 4) advice and information including influence of the healthcare worker and relatives and the information source and format; 5) general health-related behavior including previous vaccinations, visiting GP or senior center and other preventive behaviors; and 6) accessibility and affordability including logistics, combinations of vaccines and costs. CONCLUSION: The most important factors related to vaccine uptake are people's attitudes and beliefs regarding vaccination (especially their negative attitudes), recommendations of healthcare workers, side effects and effectiveness of the vaccine, and perceived susceptibility.

Evaluating interventions to improve somatic health in severe mental illness: a systematic review.

OBJECTIVE: To present a systematic review of the evaluation of randomized interventions directed toward improving somatic health for patients with severe mental illness (SMI). METHOD: A systematic search in PubMed, Embase, Cinahl, and PsycInfo was performed. The scope of the search was prospective studies for patients aged 18-70, published from January 2000 till June 2011. Randomized interventions directed toward improving somatic health for patients with SMI were selected. We excluded studies on elderly, children, and studies performed before 2000. Information on population, type of intervention, follow-up, outcome measures, and on authors' conclusions were drawn from the original articles. RESULTS: Twenty-two original studies were included, presenting four types of interventions: health education (n = 9), exercise (n = 6), smoking cessation (n = 5), and changes in health care organization (n = 2). To evaluate the effect of these studies 93 different outcome measures were used in 16 categories. CONCLUSION: Many interventions directed toward improving somatic health for patients with SMI have been started. These studies did not apply similar evaluations, and did not use uniform outcome measures of the effect of their interventions. Valuable comparisons on effectiveness are therefore almost impossible.

Endocarditis: effects of routine echocardiography during Gram-positive bacteraemia.

BACKGROUND: Despite firm recommendations to perform echocardiography in high-risk patients with Gram-positive bacteraemia, routine echocardiography is not embedded in daily practice in many settings. The aim of this study was to evaluate whether a regime including routine echocardiography results in better outcome. METHODS: A total of 115 patients with Gram-positive bacteraemia and at least one risk factor for developing metastatic infection were prospectively included. Routine echocardiography was advocated and facilitated in these patients. Results were compared with a matched historical control group of 230 patients in whom echocardiography was performed at the discretion of the attending physician. Endocarditis was diagnosed according to the Duke criteria. RESULTS: Echocardiography was performed more often in the study group (82 vs 27%, p.

Quality of life one year post myocardial revascularization and aortic valve replacement in patients aged 70 year or older.

AIM: The aim of this study was to investigate changes of health-related quality of life (HRQOL) at one year post myocardial revascularization (CABG) and post aortic valve replacement (AVR) in patients aged 70 years or older. METHODS: Of 102 CABG patients and 69 AVR patients preoperative and follow-up data on QOL, were completed. For assessing HRQoL, the EuroQol instrument (EQ) was used. The EQ-5D index score was calculated, based on separate scores of 5 health domains, to express the global health status of the patient. The EQ visual analogue scale (VAS) was used to describe patients' subjective HRQoL. RESULTS AND CONCLUSION: At one year postoperative, the EQ-5D index of the CABG group shows a significant increase (P=0.038), while that of the AVR group does not (P=0.26). The EQ-VAS registration, however, shows a significant increase for both the CABG group (P=0.003) and the AVR group (P=0.021). Considering the 5 domains of the registered HRQOL, in the AVR group only the calculated mean of the item "pain and discomfort" shows a significantly better score postoperatively (P=0.006). In the CABG group, mobility (P=0.016), pain and discomfort (P=0.15) and anxiety (P=0.036) get significantly better scores postoperatively. In conclusion, in elderly patients HRQOL strongly increases after CABG and AVR. However the improvement of functional and social quality of life is less far-going in patients undergoing AVR than in CABG patients.

Long-term global quality of life in patients treated for colorectal liver metastases.

BACKGROUND: Surgical treatment of colorectal liver metastases has become increasingly aggressive. The influence of this more active surgical approach on patients' health-related quality of life (HRQoL) has hardly been evaluated. This study investigated the impact of surgical and systemic treatment on HRQoL in patients undergoing hepatic resection for colorectal metastases. METHODS: A total of 145 patients with colorectal liver metastases were entered prospectively into the study. Based on HRQoL values derived from the EuroQol-5D, health summary measures were calculated to express the overall impact on four distinct clinical states. The HRQoL instrument was used at baseline, 3 and 6 weeks after surgery, and every 3 months thereafter for up to 3 years. RESULTS: Patients showed a clear deterioration in HRQoL in the first weeks after surgery, followed by a recovery to baseline levels at 3 months after potentially curative surgery. In contrast, a sustained decline was noted when initial surgery for colorectal liver metastases was considered futile and palliative chemotherapy was started immediately. Three years after initial surgery, there were distinct differences in HRQoL between patients with or without recurrence. The latter group still had HRQoL scores at baseline levels, whereas patients with tumour recurrence showed a significant deterioration in HRQoL. Remarkably, there was no decline in HRQoL in patients with recurrent disease who could be treated by secondary surgical intervention. CONCLUSION: Superior overall HRQoL in the first 3 years after initial successful surgical intervention merits an aggressive surgical approach and intensive follow-up to detect recurrence early.

Comparison of two region of interest definition methods for metabolic response evaluation with [18F]FDG-PET.

AIM: In therapy response monitoring by [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), different tumor delineations are used, resulting in different values for change in glucose metabolic rate (DMRglu). We propose a technique to compare metabolic rates in a region of interest (ROI) based on fixed volumes rather than on fixed thresholds. This method involves change in lesion size. METHODS: In 49 patients with colorectal carcinoma (CRC) and 50 patients with non-small cell lung carcinoma (NSCLC) scheduled for chemotherapy, FDG-PET was performed at baseline and during chemotherapy. A ROIfixed thresholds was determined by using a 50% threshold on both baseline and follow-up FDG-PET. A ROIfixed volumes was determined by using a 50% threshold, determined on the series with the largest tumor volume. This ROIfixed volumes is used on consecutive scans. Predictive effects of both methods were investigated by survival analysis for overall and progression free survival. RESULTS: In CRC, only ROIfixed volumes based DMRglu showed significant predictive ability. In NSCLC, both techniques showed significant predictive ability. During multivariate analysis, ROIfixed volumes determined DMRglu was an independent predictor for both overall and progression free survival in NSCLC whereas ROIfixed thresholds determined MRglu was not. After dichotomization at the median DMRglu, median survival ratio was higher in ROIfixed volumes than ROIfixed thresholds for CRC (overall survival: 1.78 vs 1.25, progression free survival: 1.57 vs 1.21) and NSCLC (overall survival: 2.01 vs 2.01, progression free survival: 2.93 vs 2.13). CONCLUSION: ROIfixed volumes based DMRglu shows better correlation with survival than DMRglu determined from a ROIfixed thresholds.

Comparison of two region of interest definition methods for metabolic response evaluation with [¹8F]FDG-PET.

AIM: In therapy response monitoring by [¹8F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), different tumor delineations are used, resulting in different values for change in glucose metabolic rate (ΔMR(glu)). We propose a technique to compare metabolic rates in a region of interest (ROI) based on fixed volumes rather than on fixed thresholds. This method involves change in lesion size. METHODS: In 49 patients with colorectal carcinoma (CRC) and 50 patients with non-small cell lung carcinoma (NSCLC) scheduled for chemotherapy, FDG-PET was performed at baseline and during chemotherapy. A ROI(fixed thresholds) was determined by using a 50% threshold on both baseline and follow-up FDG-PET. A ROI(fixed volumes) was determined by using a 50% threshold, determined on the series with the largest tumor volume. This ROI(fixed volumes) is used on consecutive scans. Predictive effects of both methods were investigated by survival analysis for overall and progression free survival. RESULTS: In CRC, only ROI(fixed volumes) based ΔMR(glu) showed significant predictive ability. In NSCLC, both techniques showed significant predictive ability. During multivariate analysis, ROI(fixed volumes) determined ΔMR(glu) was an independent predictor for both overall and progression free survival in NSCLC whereas ROI(fixed thresholds) determined MRglu was not. After dichotomization at the median ΔMR(glu), median survival ratio was higher in ROI(fixed volumes) than ROI(fixed thresholds) for CRC (overall survival: 1.78 vs 1.25, progression free survival: 1.57 vs 1.21) and NSCLC (overall survival: 2.01 vs 2.01, progression free survival: 2.93 vs 2.13). CONCLUSION: ROI(fixed volumes) based ΔMR(glu) shows better correlation with survival than ΔMR(glu) determined from a ROI(fixed thresholds).

Cost-effectiveness of post-diagnosis treatment in dementia coordinated by Multidisciplinary Memory Clinics in comparison to treatment coordinated by general practitioners: an example of a pragmatic trial.

BACKGROUND: With the rising number of dementia patients with associated costs and the recognition that there is room for improvement in the provision of dementia care, the question arises on how to efficiently provide high quality dementia care. OBJECTIVE: To describe the design of a study to determine multidisciplinary memory clinics' (MMC) effectiveness and cost-effectiveness in post-diagnosis treatment and care-coordination of dementia patients and their caregivers compared to the post-diagnosis treatment and care-coordination by general practitioners (GP). Next, this article provides the theoretical background of pragmatic trials, often needed in complex interventions, with the AD- Euro study as an example of such a pragmatic approach in a clinical trial. METHOD: The study is a pragmatic multicentre, randomised clinical trial with an economic evaluation alongside, which aims to recruit 220 independently living patients with a new dementia diagnosis and their informal caregivers. After baseline measurements, patient and caregiver are allocated to the treatment arm MMC or GP and are visited for follow up measurements at 6 and 12 months. Primary outcome measures are Health Related Quality of Life of the patient as rated by the caregiver using the Quality of Life in Alzheimer's Disease instrument (Qol-AD) and self-perceived caregiving burden of the informal caregiver measured using the Sense of Competence Questionnaire (SCQ). To establish cost-effectiveness a cost-utility analysis using utilities generated by the EuroQol instrument (EQ-5D) will be conducted from a societal perspective. Analyses will be done in an intention-to-treat fashion. RESULTS: The inclusion period started in January 2008 and will commence until at least December 2008. After finalising follow up the results of the study are expected to be available halfway through 2010. DISCUSSION: The study will provide an answer to whether follow-up of dementia patients can best be done in specialised outpatient memory clinics or in primary care settings with regard to quality and costs. It will enable decision making on how to provide good and efficient health care services in dementia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00554047.

Efficacy of follow-up after surgical treatment of colorectal liver metastases.

PURPOSE: There is an increasing tendency for an aggressive approach to colorectal liver metastases (CLM), even as second stage procedures after initial hepatic resection. This study assesses the efficacy of intensive follow-up after resection of CLM. PATIENTS AND METHODS: Hundred and three patients, operated on for CLM, were followed for disease recurrence. Outcome measures were time and imaging modality that revealed recurrence, performed treatment for recurrence, and overall survival. RESULTS: After hepatic resection, 1- and 3-year overall survival (OS) rates were 91% and 50%, the disease-free survival rates 63% and 45%. Seventy-four patients developed recurrent disease during follow-up. Resection of recurrence was performed in 25 patients. OS of this group was 51 months. Patients with recurrence treated by chemotherapy had an OS of 34 months. In case of recurrence, 70% was observed within 12 months, 92% within 24 months. CT appeared to be far a very useful surveillance modality, directing surgical treatment in 19 asymptomatic patients. DISCUSSION: Follow-up of patients after surgical treatment of CLM proves worthwhile, resulting in meaningful re-operations in a quarter of all patients that underwent hepatic resection for CLM.

Decision for reconstructive interventions of the upper limb in individuals with tetraplegia: the effect of treatment characteristics.

STUDY DESIGN: Survey. OBJECTIVE: To determine the effect of treatment characteristics on the decision for reconstructive interventions for the upper extremities (UE) in subjects with tetraplegia. SETTING: Seven specialized spinal cord injury centres in the Netherlands. METHOD: Treatment characteristics for UE reconstructive interventions were determined. Conjoint analysis (CA) was used to determine the contribution and the relative importance of the treatment characteristics on the decision for therapy. Therefore, a number of different treatment scenarios using these characteristics were established. Different pairs of scenarios were presented to subjects who were asked to choose the preferred scenario of each set. RESULTS: Forty-nine subjects with tetraplegia with a stable C5, C6 or C7 lesion were selected. All treatment characteristics significantly influenced the choice for treatment. Relative importance of treatment characteristics were intervention type (surgery or surgery with functional electrical stimulation implant) 13%, number of operations 15%, in-patient rehabilitation period 22%, ambulant rehabilitation period 9%, complication rate 15%, improvement of elbow function 10%, improvement of hand function 15%. In deciding for therapy, 40% of the subjects focused on one characteristic. CONCLUSION: CA is applicable in Spinal Cord Injury medicine to study the effect of health outcomes and non-health outcomes on the decision for treatment. Non-health outcomes, which relate to the intensity of treatment, are equally important or even more important than functional outcome in the decision for reconstructive UE surgery in subjects with tetraplegia.

Chemotherapy response evaluation with FDG-PET in patients with colorectal cancer.

BACKGROUND: The aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) for early assessment of chemotherapy response in patients with advanced colorectal cancer. METHODS: Dynamic FDG-PET was carried out before and at 2 (n = 50) and 6 months (n = 19) after the start of treatment. Quantitative Patlak analysis [metabolic rate of glucose (MRGlu)] and a simplified method to measure glucose metabolism [standardized uptake value (SUV)] were evaluated. The predictive value of changes in glucose metabolism was assessed with Cox proportional regression analysis. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates. RESULTS: There was an increase in the rates of death (P = 0.049 for DeltaMRGlu PET1-2; P = 0.017 for DeltaSUV PET1-2; P = 0.032 for DeltaMRGlu PET1-3; P = 0.048 for DeltaSUV PET1-3) and progression (P = 0.026 for DeltaMRGlu PET1-2; P = 0.035 for DeltaSUV PET1-2; P = 0.041 for DeltaMRGlu PET1-3; P = 0.081 for DeltaSUV PET1-3) associated with worse response as assessed by PET on Cox proportional regression analysis. The OS and PFS analysis showed a significant predictive value at broad ranges of DeltaMRGlu and DeltaSUV cut-off levels. CONCLUSION: The degree of chemotherapy-induced changes in tumor glucose metabolism is highly predictive for patient outcome. The use of FDG-PET for therapy monitoring seems clinically feasible since simplified methods (SUV) are sufficiently reliable.

Computer-based decision making in medicine: A model for surgery of colorectal liver metastases.

AIMS: Seeking the best available treatment for patients with colorectal liver metastases may be complex due to the interpretation of many variables. In this study conjoint analysis is used to develop a decision model to help clinicians selecting patients eligible for surgery of liver metastases. METHODS: Patient and tumor characteristics decisive for surgery of colorectal liver metastases were selected from literature. A factorial design was used to construct virtual patient cases by balanced combinations of these characteristics. Surgeons experienced in liver surgery (n=25) were asked to give their advised treatment (resection and/or local ablation, or chemotherapy). Different tumor and patient variables were weighted in the analysis for their contribution to treatment choices. RESULTS: Patient's age, the involvement of lobes and location of metastases in relation to large vessels were most important for treatment decisions. The number of metastases, size of the lesions, presence of resectable extrahepatic disease and time interval from primary tumor to metastases proved of less importance. Based on the analysis a computer-based decision model was designed. CONCLUSION: Conjoint analysis can be a valuable tool in clinical decision making. The computer-based decision model can assist clinicians in defining which patient should be referred for liver surgery.