How healthy participants value additional diagnostic testing with amyloid-PET in patients diagnosed with mild cognitive impairment - a bidding game experiment.

BACKGROUND: To estimate the perceived value of additional testing with amyloid-PET in Euros in healthy participants acting as analogue patients with mild cognitive impairment (MCI). METHODS: One thousand four hundred thirty-one healthy participants acting as analogue MCI patients (mean age 65 ± 8, 929 (75%) female) were recruited via the Dutch Brain Research Registry. Participants were asked to identify with a presented case (video vignette) of an MCI patient and asked whether they would prefer additional diagnostic testing with amyloid PET in this situation. If yes, respondents were asked how much they would be willing to pay for additional diagnostic testing. Monetary value was elicited via a bidding game in which participants were randomized over three conditions: (A) additional testing results in better patient management, (B) Same as condition A and a delay in institutionalization of 3 months, and (C) same as A and a delay in institutionalization of 6 months. Participants who were not willing to take a test were compared with participants who were willing to take a test using logit models. The highest monetary value per condition was analyzed using random-parameter mixed models. RESULTS: The vast majority of participants acting as analogue MCI patients (87% (n = 1238)) preferred additional testing with amyloid PET. Participants who were not interested were more often female (OR = 1.61 95% CI [1.09-2.40]) and expressed fewer worries to get AD (OR = 0.64 [0.47-0.87]). The median "a priori" (i.e., before randomization) monetary value of additional diagnostic testing was €1500 (IQR 500-1500). If an additional amyloid PET resulted in better patient management (not further specified; condition A), participants were willing to pay a median price of €2000 (IQR = 1000-3500). Participants were willing to pay significantly more than condition A (better patient management) if amyloid-PET testing additionally resulted in a delay in institutionalization of 3 months (€530 [255-805] on top of €2000, condition B) or 6 months (€596 [187-1005] on top of €2000, condition C). CONCLUSIONS: Members of the general population acting as MCI patients are willing to pay a substantial amount of money for amyloid-PET and this increases when diagnostic testing leads to better patient management and the prospect to live longer at home.

Cost-effectiveness of selective decontamination of the digestive tract to decrease infectious complications in colorectal cancer surgery: An analysis of the SELECT trial.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) is effective in reducing infectious complications in elective colorectal cancer (CRC) surgery. However, it is unclear whether SDD is cost-effective compared to standard antibiotic prophylaxis. MATERIAL & METHODS: Economic evaluation alongside multicenter randomized controlled trial, the SELECT-trial, from a healthcare perspective. Patients included underwent elective surgery for non-metastatic CRC. The intervention group received oral non-absorbable colistin, tobramycin and amphotericin B (SDD) next to standard antibiotic prophylaxis. Both groups received a single shot intravenous cefazolin and metronidazole preoperatively as standard prophylaxis. Occurrence of postoperative infectious complication in the first 30 postoperative days was extracted from medical records, Quality-Adjusted Life-Years (QALYs) based on the ED-5D-3L, and healthcare costs collected from the hospital's financial administration. RESULTS: Of the 455 patients, 228 were randomly assigned to intervention group and 227 patients to the control group. SDD significantly reduced the number of infectious complications compared to control (difference = -0.13, 95 % CI -0.05 to -0.20). No difference was found for QALYs (difference = 0.002, 95 % CI -0.002 to 0.005). Healthcare costs were statistically significantly lower in the intervention group (difference = -€1258, 95 % CI -2751 to -166). The ICER was -9872 €/infectious complication prevented and -820,380 €/QALY gained. For all willingness-to-pay thresholds, the probability that prophylactic SDD was cost-effective compared to standard prophylactic practice alone was 1.0. CONCLUSION: The addition of SDD to the standard preoperative intravenous antibiotic prophylaxis is cost-effective compared to standard prophylactic practice from a healthcare perspective and should be considered as the standard of care.

Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment.

INTRODUCTION: A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB. METHODS AND ANALYSIS: The SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study. ETHICS AND DISSEMINATION: This is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NL8347 (the Netherlands Trial Register).

Internet-delivered cognitive behavioural therapy for insomnia disorder in depressed patients treated at an outpatient clinic for mood disorders: protocol of a randomised controlled trial.

BACKGROUND: Major depression is a highly prevalent disorder causing severe personal distress, and high societal costs. Patients with depression often have comorbid insomnia disorder (ID) leading to even worse personal distress and worse treatment outcomes. Recent results from a non-randomised pilot study with internet-delivered Cognitive Behavioural Therapy (CBTi) for Insomnia (I-Sleep) added to regular depression care were promising regarding feasibility and initial effects on insomnia complaints and depression. However, no randomised controlled trial (RCT) has been performed yet to access the (cost-) effectiveness of I-Sleep for depression. Therefore, this protocol article presents the design of an RCT aimed to assess the (cost-) effectiveness of I-Sleep in addition to usual care for depression compared to usual care alone in depressed patients with a comorbid Insomnia Disorder (ID) treated at outpatient clinics for mood disorders.  METHODS /DESIGN: This is a multi-centre RCT with measurements at baseline and at 3, 6, 9, and 12 months of follow-up. Patients with depression and an ID are randomised to either I-Sleep treatment followed by regular depression care or to regular depression care alone. Our aim is to recruit one hundred and seventy-five patients from multiple outpatient clinics for mood disorders. The primary outcome is the change in depressive symptoms over 12 months of follow-up measured with the Patient Health Questionnaire (PHQ-9). Secondary outcomes are recovery from depression (PHQ-9), insomnia severity (Insomnia Severity Index, ISI), daily functioning (Work and Social Adjustment Scale, WSAS), general quality of life (EuroQol 5-level version, EQ-5D-5L), and societal costs (Adapted versions of the iMTA Productivity Cost Questionnaire, iPCQ and iMTA Medical Cost Questionnaire, iMCQ). DISCUSSION: We hypothesize that the addition of I-Sleep to usual care will result in a significant improvement in depression treatment outcomes and quality of life as well as a decrease in healthcare and societal costs compared to usual care alone. This study is the first pragmatic RCT evaluating the effectiveness and cost-effectiveness of adding CBTi to usual care for depression. TRIAL REGISTRATION: Netherlands Trial Register (NL8955). Registered on October 6th2020. https://trialsearch.who.int/Trial2.aspx?TrialID=NL8955.

The MOMANT study, a caregiver support programme with activities at home for people with dementia: a study protocol of a randomised controlled trial.

BACKGROUND: Because of the expected increase in the number of people with dementia, and the associated social and economic costs, there is an urgent need to develop effective and cost-effective care for people with dementia and their caregivers. The intervention proposed here combines two approaches to caregiver support that have shown to be effective in empowering caregivers, i.e., multiple components for caregiver support and actively engaging caregivers to involve the person with dementia in activities at home. The aim is to investigate whether the intervention is effective in improving quality of life in the caregiver and the person with dementia. A further aim will be to investigate whether this intervention can improve caregivers' feeling of competence, experience of caregiving, and mood. METHODS: The study design is a pragmatic, cluster randomised controlled trial with cost-effectiveness analysis. The study participants are informal caregivers and home-living persons with dementia for whom they care, recruited in various regions in the Netherlands. The trial will compare outcomes in two groups of participants: 85 dyads who receive the intervention, and 85 dyads who receive care as usual. The intervention is a caregiver support training that is manual based and consists of 6 group sessions over 2 months. Training takes place in small groups of caregivers led by a health care professional presented at dementia day care centres. Randomisation occurs at the level of the day care centre. Participants are assessed on the outcome measures at baseline, prior to the intervention, and at 3 and 6 months after baseline. DISCUSSION: The study will provide insight into effectiveness and cost-effectiveness of an intervention that has not previously been evaluated or implemented in the Netherlands. The intervention potentially adds to the effective support options for informal caregivers of people with dementia without greatly increasing the workload for health- or social care professionals. TRIAL REGISTRATION: The trial is registered at the Dutch Trial Register at NTR6643 ; August 22nd, 2017.

Inadequate awareness of adherence to ARRIVE guidelines, regarding reporting quality of hernia models repaired with meshes: a systematic review.

PURPOSE: Research papers involving animal studies often display poor reporting standards, leading to lower study reproducibility. We aim to determine the difference in reporting animal studies regarding abdominal wall hernia repair with mesh placement, before and after the publication of ARRIVE-2010 (Animal Research: Reporting of In Vivo Experiments) guidelines. Furthermore, we aim to present the most up-to-date reporting quality using the updated ARRIVE-2020 as criteria. METHODS: All animal studies concerning hernia repair with meshes were systematically searched. Articles published in the 5 years leading up to the ARRIVE-2010 (pre-ARRIVE) and articles within the last 5 years until the updated ARRIVE 2.0 (post-ARRIVE) were compared for overall species and specific species separately. Articles published last year were evaluated for presenting fully reported (sub)items. RESULTS: The number of fully reported (sub)items per article was on average significantly higher for pre-ARRIVE than post-ARRIVE for overall species (mean (SD) = 14.0 (2.8) vs. 12.6 (2.5), P < 0.001). The same applies to rabbit (mean (SD) = 14.8 (2.6) vs. 12.6 (2.6), P = 0.001) and pig studies (mean (SD) = 14.5 (2.7) vs. 11.6 (2.6), P = 0.004), with no significance in rat studies (mean (SD) = 13.6 (2.9) vs. 12.9 (2.3), P = 0.076). Significance was found in several (sub)items between pre-ARRIVE and post-ARRIVE (n = 7, 3, 8, and 3 for overall species, rat, rabbit, and pig studies, respectively). CONCLUSION: General reporting quality of animal experiments has been improved markedly by ARRIVE guidelines. However, more improvements are required considering the arrival of ARRIVE 2.0 guidelines.

Cost-effectiveness of custom-made insoles versus usual care in patients with plantar heel pain in primary care: cost-effectiveness analysis of a randomised controlled trial.

OBJECTIVES: To evaluate the cost-effectiveness of custom-made insoles compared with general practitioner (GP)-led usual care after 26 weeks of follow-up in individuals with plantar heel pain (PHP) from a societal perspective. DESIGN: Cost-effectiveness analysis of a double-blinded randomised controlled trial. SETTING: General practice in the Netherlands. PARTICIPANTS: 116 participants with PHP for at least 2 weeks, aged 18-65 years and presenting to the GP. INTERVENTIONS: Participants were randomised to GP-led usual care (n=46) or referral to a podiatrist for treatment with a custom-made insole (n=70). Participant randomised to a sham insole (n=69) were excluded from this analysis. PRIMARY AND SECONDARY OUTCOMES: Outcomes comprised pain during rest and activity, and quality of life. Costs included healthcare and lost productivity costs. Statistical uncertainty was estimated using bootstrapping and presented using cost-effectiveness acceptability curves. RESULTS: Participants in the custom-made insole group experienced statistically significant more pain during activity at 26 weeks than participants in the usual care group (overall effect 1.06; 95% CI 0.36 to 1.75). There were no significant differences between groups in other outcomes. Total societal costs in the custom-made insole group were non-significantly higher than in the usual care group (mean difference €376; 95% CI -€1775 to €2038). The intervention with custom-made insoles was dominated by usual care by the GP (ie, more expensive and less effective) for pain during activity and quality of life outcomes. For the outcome pain at rest, the intervention was more expensive and more effective than usual care. However, the maximum probability of cost-effectiveness was only 0.59 at very high ceiling ratios. CONCLUSIONS: These findings show that that custom-made insoles are not cost-effective in comparison with GP-led usual care. Clinicians should be reserved in prescribing custom-made insoles for PHP as a primary intervention. TRIAL REGISTRATION NUMBER: NTR5346.

'Implementing a broad quality of life tool for determining care wishes and needs of older adults living at home.

The aim was to investigate the views of stakeholders on the practical relevance of a broad quality of life (QoL) outcome tool for care in older adults: the Extended Quality of Life Tool (EQLT). We conducted individual interviews and focus groups with a variety of stakeholders involved in the care for older adults which were analyzed using a framework analysis. Stakeholders considered relevant: focus on the client perspective; perspective on QoL broader than health; the possibility to take diversity into account; and the possibility to determine a minimum level of QoL. Three facilitators for implementation of the tool were mentioned as well as four barriers. The EQLT can support conversations with clients about their needs and wishes, thus enabling decisions about care services based on a broad set of domains of QoL. Implementation of the tool should take into account the facilitators and barriers identified in the current study.

Cost-effectiveness of a stepped care program to prevent depression among primary care patients with diabetes mellitus type 2 and/or coronary heart disease and subthreshold depression in comparison with usual care.

BACKGROUND: Patients with diabetes mellitus type 2 (DM2) and/or coronary heart disease (CHD) are at high risk to develop major depression. Preventing incident major depression may be an important tool in reducing the personal and societal burden of depression. The aim of the current study was to assess the cost-effectiveness of a stepped care program to prevent major depression (Step-Dep) in diabetes mellitus type 2 and/or coronary heart disease patients with subthreshold depression in comparison with usual care. METHODS: An economic evaluation with 12 months follow-up was conducted alongside a pragmatic cluster-randomized controlled trial from a societal perspective. Participants received care as usual (n = 140) or Step-Dep (n = 96) which consisted of four sequential treatment steps: watchful waiting, guided self-help, problem solving treatment and referral to a general practitioner. Primary outcomes were quality-adjusted life years (QALYs) and cumulative incidence of major depression. Costs were measured every 3 months. Missing data was imputed using multiple imputation. Uncertainty around cost-effectiveness outcomes was estimated using bootstrapping and presented in cost-effectiveness planes and acceptability curves. RESULTS: There were no significant differences in QALYs or depression incidence between treatment groups. Secondary care costs (mean difference €1644, 95% CI €344; €3370) and informal care costs (mean difference €1930, 95% CI €528; €4089) were significantly higher in the Step-Dep group than in the usual care group. The difference in total societal costs (€1001, 95% CI €-3975; €6409) was not statistically significant. The probability of the Step-Dep intervention being cost-effective was low, with a maximum of 0.41 at a ceiling ratio of €30,000 per QALY gained and 0.32 at a ceiling ratio of €0 per prevented case of major depression. CONCLUSIONS: The Step-Dep intervention is not cost-effective compared to usual care in a population of patients with DM2/CHD and subthreshold depression. Therefore, widespread implementation cannot be recommended. TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register ( NTR3715 ).

Implementing preoperative Botulinum toxin A and progressive pneumoperitoneum through the use of an algorithm in giant ventral hernia repair.

BACKGROUND: Repair of large ventral hernias with loss of domain can be facilitated by preoperative Botulinum toxin A (BTA) injections and preoperative progressive pneumoperitoneum (PPP). The aim of this study is to evaluate the outcomes of ventral hernioplasty using a standardized algorithm, including component separation techniques, preoperative BTA and PPP. METHODS: All patients between June 2014 and August 2018 with giant hernias (either primary or incisional) of more than 12 cm width were treated according to a previously developed standardized algorithm. Retrospective data analysis from a prospectively collected dataset was performed. The primary outcome was closure of the anterior fascia. Secondary outcomes included complications related to the preoperative treatment, postoperative complications, and recurrences. RESULTS: Twenty-three patients were included. Median age was 65 years (range 28-77) and median BMI was 31.4 (range 22.7-38.0 kg/m2). The median loss of domain was 29% (range 12-226%). For the primary and secondary endpoints, 22 patients were analyzed. Primary closure of the anterior fascia was possible in 82% of all patients. After a median follow-up of 19.5 months (range 10-60 months), 3 patients (14%) developed a hernia recurrence and 16 patients (73%) developed 23 surgical site occurrences, most of which were surgical site infections (54.5%). CONCLUSION: Our algorithm using both anterior or posterior component separation, together with preoperative BTA injections and PPP, achieved an acceptable fascial closure rate. Further studies are needed to explore the individual potential of BTA injections and PPP, and to research whether these methods can prevent the need for component separation, as postoperative wound morbidity remains high in our study.

A systematic review of seroma formation following drain-free mastectomy.

BACKGROUND: Seroma is a common complication after mastectomy. The aim of this review is to elucidate whether closed suction drainage can safely be omitted in patients undergoing mastectomy when assessing seroma formation and its complications. The second aim is to assess the influence of flap fixation on seroma related complications, as there is existing evidence showing that combining mastectomy with flap fixation may make the use of drainage systems obsolete. SEARCH & SELECTION: A review of the literature was performed and articles that compared mastectomy with drainage and mastectomy without drainage were selected. Due to the small number of eligible studies, no selection based on whether flap fixation was performed was possible. If outcome was described in terms of seroma formation or seroma related complications, papers were eligible for inclusion. Studies older than 20 years, animal studies, studies not written in English and studies with male patients were excluded. RESULTS: A total of eight articles were eligible for inclusion. Four prospective studies and four retrospective studies were included. In four studies, flap fixation was performed. Frequency of seroma formation as well as seroma that required intervention was reported. The included studies demonstrated that omitting closed suction drainage does not lead to a higher incidence of seroma formation in patients undergoing mastectomy. CONCLUSION: Despite substantial heterogeneity, there is evidence that drainage can safely be omitted without exacerbating seroma formation and its complications. A well-powered, randomized controlled trial evaluating the effect of drainage omission on seroma formation, with or without flap fixation, is needed.

SOMA-trial: surgery or medication for women with an endometrioma? Study protocol for a randomised controlled trial and cohort study.

STUDY QUESTIONS: The objective of this study is to evaluate the effectiveness and cost-effectiveness of surgical treatment of women suffering from pain due to an ovarian endometrioma when compared to treatment with medication (analgesia and/or hormones). The primary outcome is defined as successful pain reduction (-30% reduction of pain) measured by the numeric rating scale (NRS) after 6 months. Secondary outcomes include successful pain reduction after 12 and 18 months, quality of life, affective symptoms, cost-effectiveness, recurrence rate, need of adjuvant medication after surgery, ovarian reserve, adjuvant surgery and budget impact. WHAT IS KNOWN ALREADY: Evidence suggests that both medication and surgical treatment of an ovarian endometrioma are effective in reducing pain and improving quality of life. However, there are no randomised studies that compare surgery to treatment with medication. STUDY DESIGN SIZE DURATION: This study will be performed in a research network of university and teaching hospitals in the Netherlands. A multicentre randomised controlled trial and parallel prospective cohort study in patients with an ovarian endometrioma, with the exclusion of patients with deep endometriosis, will be conducted. After obtaining informed consent, eligible patients will be randomly allocated to either treatment arm (medication or surgery) by using web-based block randomisation stratified per centre. A successful pain reduction is set at a 30% decrease on the NRS at 6 months after randomisation. Based on a power of 80% and an alpha of 5% and using a continuity correction, a sample size of 69 patients in each treatment arm is needed. Accounting for a drop-out rate of 25% (i.e. loss to follow up), we need to include 92 patients in each treatment arm, i.e. 184 in total. Simultaneously, a cohort study will be performed for eligible patients who are not willing to be randomised because of a distinct preference for one of the two treatment arms. We intend to include 100 women in each treatment arm to enable standardization by inverse probability weighting, which means 200 patients in total. The expected inclusion period is 24 months with a follow-up of 18 months. PARTICIPANTS/MATERIALS SETTING METHODS: Premenopausal women (age ≥ 18 years) with pain (dysmenorrhoea, pelvic pain or dyspareunia) and an ovarian endometrioma (cyst diameter ≥ 3 cm) who visit the outpatient clinic will make up the study population. Patients with signs of deep endometriosis will be excluded. The primary outcome is successful pain reduction, which is defined as a 30% decrease of pain on the NRS at 6 months after randomisation. Secondary outcomes include successful pain reduction after 12 and 18 months, quality of life and affective symptoms, cost-effectiveness (from a healthcare and societal perspective), number of participants needing additional surgery, need of adjuvant medication after surgery, ovarian reserve and recurrence rate of endometriomas. Measurements will be performed at baseline, 6 weeks and 6, 12 and 18 months after randomisation. STUDY FUNDING/COMPETING INTERESTS: This study is funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-85200-98-91041. The Department of Reproductive Medicine of the Amsterdam UMC location VUmc has received several research and educational grants from Guerbet, Merck KGaA and Ferring not related to the submitted work. B.W.J. Mol is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for ObsEva, Merck KGaA and Guerbet. V. Mijatovic reports grants from Guerbet, grants from Merck and grants from Ferring outside the submitted work. All authors declare that they have no competing interests concerning this publication. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NTR 7447, http://www.trialregister.nl). TRIAL REGISTRATION DATE: 2 January 2019. DATE OF FIRST PATIENT'S ENROLMENT: First inclusion in randomised controlled trial October 4, 2019. First inclusion in cohort May 22, 2019.

META Score: An International Consensus Scoring System on Mesh-Tissue Adhesions.

BACKGROUND: Currently, the lack of consensus on postoperative mesh-tissue adhesion scoring leads to incomparable scientific results. The aim of this study was to develop an adhesion score recognized by experts in the field of hernia surgery. METHODS: Authors of three or more previously published articles on both mesh-tissue adhesion scores and postoperative adhesions were marked as experts. They were queried on seven items using a modified Delphi method. The items concerned the utility of adhesion scoring models, the appropriateness of macroscopic and microscopic variables, the range and use of composite scores or subscores, adhesion-related complications and follow-up length. This study comprised two questionnaire-based rounds and one consensus meeting. RESULTS: The first round was completed by 23 experts (82%), the second round by 18 experts (64%). Of those 18 experts, ten were able to participate in the final consensus meeting and all approved the final proposal. From a total of 158 items, consensus was reached on 90 items. The amount of mesh surface covered with adhesions, tenacity and thickness of adhesions and organ involvement was concluded to be a minimal set of variables to be communicated separately in each future study on mesh adhesions. CONCLUSION: The MEsh Tissue Adhesion scoring system is the first consensus-based scoring system with a wide backing of renowned experts and can be used to assess mesh-related adhesions. By including this minimal set of variables in future research interstudy comparability and objectivity can be increased and eventually linked to clinically relevant outcomes.

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.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Cost-effectiveness of home-based vs. in-hospital treatment of paediatric tuberculous meningitis.

SETTING: Cape Town, South Africa, 2014. OBJECTIVE: To assess the societal costs and cost-effectiveness of home-based vs. in-hospital treatment of paediatric tuberculous meningitis. DESIGN: This was an economic evaluation from a societal perspective using probabilistic analysis. Health care, informal care, lost productivity costs and costs in other sectors, health-related quality of life (HRQoL) and family impact were assessed during interviews with care givers, children, medical staff and management. RESULTS: Societal costs for home-based treatment were USD3857, and USD28 043 for in-hospital treatment. Home-based vs. in-hospital treatment HRQoL scores were 90.9% vs. 84.5%, while family impact scores were 94.8% vs. 73.1%. The point estimate of the incremental cost-effectiveness ratio indicated that improving HRQoL and family impact by 1% was associated with a saving of respectively USD3726 and USD1140 for home-based vs. in-hospital treatment. The probability that home-based treatment was less expensive and more effective than in-hospital treatment was 96.3% for HRQoL and 100% for family impact. CONCLUSION: Societal costs of home-based treatment were lower than for in-hospital treatment. Children treated at home had a better HRQoL and family impact scores. Home-based treatment was a cost-effective alternative to in-hospital treatment of drug-susceptible tuberculous meningitis.

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.

Functional Compromise Cohort Study (FCCS): Sarcopenia is a Strong Predictor of Mortality in the Intensive Care Unit.

BACKGROUND: Functional compromise in elderly patients is considered to be a significant contributing factor in increased postoperative morbidity and mortality. It is described as a state of reduced physiologic reserves including, e.g., sarcopenia, cachexia, malnutrition and frailty with increased susceptibility to adverse health outcomes. Aim of this study was to investigate the association of sarcopenia with mortality in ICU patients. METHODS: A retrospective analysis of a total of 687 patients admitted to the ICU from January 2013 until December 2014 was performed. Indirect measurements of functional compromise in these patients were conducted. Sarcopenia was assessed using the L3 muscle index by using Osirix© on computed tomography scans. Groningen Frailty Indicator (GFI) and Short Nutritional Assessment Questionnaire (SNAQ) scores were extracted from the digital patient filing system and were used to assess frailty and nutritional status. These factors were analyzed using logistic regression analysis as predictor for in-hospital mortality and 6-month mortality, which was the primary endpoint along with other secondary outcome measures. RESULTS: Age was an independent predictor of in-hospital mortality, OR 1.043 (95% CI 1.030-1.057, p < 0.001). Analysis of sarcopenia showed OR 2.361 (95% CI 1.138-4.895, p = 0.021), for GFI OR 1.012 (95% CI 0.919-1.113, p = 0.811) and for SNAQ OR 1.262 (95% CI 1.091-1.460, p = 0.002). CONCLUSION: This study shows a promising role for the sarcopenia score as a predictor of mortality on the ICU, based upon CT imaging at L3 level and SNAQ score. Further research is necessary to test this in larger cohorts and to develop a possible instrument to predict mortality in the intensive care unit.

Quality of life in a broader perspective: Does ASCOT reflect the capability approach?

PURPOSE: Economic evaluation of services and interventions in care services tends to focus on quality of life(QoL) based on health-related measures such as EQ5D, with a major focus on health and functioning. The Capability Approach (CA) provides an alternative framework for measuring QoL and challenges some of the conventional issues in the current practice of measurement of QoL. The Adult Social Care Outcomes Toolkit (ASCOT) aims to measure social care-related QoL in a broad sense. This article investigates whether and, if so, how the ASCOT addresses issues put on the agenda by the CA. METHODS: Literature analysis concerning theoretical assumptions and arguments of CA and ASCOT. RESULTS: The Capability Approach (CA) puts three issues on the agenda regarding QoL. First, the focus of evaluation should not be on functioning, but on freedom of choice. Second, evaluation should be critical about adaptive preferences, which entail that people lower expectations in situations of limited possibilities. Third, evaluation should not only address health, but also other domains of life. Our analysis shows that freedom of choice is reflected in the response option 'as I want' in the ASCOT questionnaire. The problem of adaptive preferences is countered in the ASCOT by developing a standard based on preferences of the general population. Third, the ASCOT contains several domains of life. CONCLUSIONS: We conclude that the CA and the ASCOT contribute to the discussion on QoL, and that the ASCOT operationalizes core assumptions of the CA, translating the issues raised by the CA in a practical way.

Cost-effectiveness of the psycho-educational blended (group and online) intervention HypoAware compared with usual care for people with Type 1 and insulin-treated Type 2 diabetes with problematic hypoglycaemia: analyses of a cluster-randomized controlled trial.

AIMS: To evaluate the cost-effectiveness of HypoAware, a blended (group and online) psycho-educational intervention based on the evidence-based Blood Glucose Awareness Training, in comparison with usual care in people with Type 1 and Type 2 diabetes with a high risk of severe hypoglycaemia. METHODS: We performed an economic evaluation, from a societal and healthcare perspective, that used data from a 6-month, multicentre, cluster-randomized controlled trial (n = 137). RESULTS: The proportion of people with at least one severe hypoglycaemic event per 6 months was 0.22 lower (95% CI -0.39 to -0.06) and the proportion of people with impaired hypoglycaemia awareness was 0.16 lower (95% CI -0.34 to 0.02) in the HypoAware group. There was no difference in quality-adjusted life-years (-0.0; 95% CI -0.05 to 0.05). The mean total societal costs in the HypoAware group were EUR708 higher than in the usual care group (95% CI -951 to 2298). The mean incremental cost per severe hypoglycaemic event prevented was EUR2,233. At a willingness-to-pay threshold of EUR20,000 per event prevented, the probability that HypoAware was cost-effective in comparison with usual care was 54% from a societal perspective and 55% from a healthcare perspective. For quality-adjusted life-years the incremental cost-effectiveness ratio was EUR119,360/quality-adjusted life-year gained and the probability of cost-effectiveness was low at all ceiling ratios. CONCLUSIONS: Based on the present study, we conclude that HypoAware is not cost-effective compared to usual care. Further research in less well-resourced settings and more severely affected patients is warranted. (Clinical Trials Registry no: Dutch Trial Register NTR4538.).