Are acceptance and mindfulness-based interventions 'value for money'? : evidence from a systematic literature review

Objectives: Acceptance and mindfulness‐based interventions (A/MBIs) are recommended for people with mental health conditions. Although there is a growing evidence base supporting the effectiveness of different A/MBIs for mental health conditions, the economic case for these interventions has not been fully explored. The aim of this systematic review was to identify and appraise all available economic evidence of A/MBIs for the management of mental health conditions. Methods: Eight electronic bibliographic databases (MEDLINE, MEDLINE In‐Process & Other Non‐Indexed Citations, EMBASE, Web of Science, NHS Economic Evaluation Database (EED), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) database, and EconLit) were searched for relevant economic evaluations published from each database's inception date until November 2017. Study selection, quality assessment, and data extraction were carried out according to published guidelines. Results: Ten relevant economic evaluations presented in 11 papers were identified. Seven of the included studies were full economic evaluations (i.e., costs and effects assessed), and three studies were partial economic evaluations (i.e., only costs were considered in the analysis). The A/MBIs that had been subjected to economic evaluation were acceptance and commitment therapy (ACT), dialectical behaviour therapy (DBT), mindfulness‐based cognitive therapy (MBCT), and mindfulness‐based stress reduction (MBSR). In terms of clinical presentations, the evaluation of cost‐effectiveness of A/MBIs has been more focused on depression and emotional unstable personality disorder with three and four economic evaluations, respectively. Three out of seven full economic evaluations observed that A/MBIs were cost‐effective for the management of mental health conditions. Nevertheless, the heterogeneity of included populations, interventions, and economic evaluation study types limits the extent to which firm conclusions can currently be made. Conclusion: This first substantive review of economic evaluations of A/MBIs indicates that more research is needed before firm conclusions can be reached on the cost‐effectiveness of A/MBIs for mental health conditions

Building solids inside nano-space: from confined amorphous through confined solvate to confined ‘metastable’ polymorph

The nanocrystallisation of complex molecules inside mesoporous hosts and control over the resulting structure is a significant challenge. To date the largest organic molecule crystallised inside the nano-pores is a known pharmaceutical intermediate – ROY (259.3 g mol1). In this work we demonstrate smart manipulation of the phase of a larger confined pharmaceutical – indomethacin (IMC, 357.8 g mol1), a substance with known conformational flexibility and complex polymorphic behaviour. We show the detailed structural analysis and the control of solid state transformations of encapsulated molecules inside the pores of mesoscopic cellular foam (MCF, pore size ca. 29 nm) and controlled pore glass (CPG, pore size ca. 55 nm). Starting from confined amorphous IMC we drive crystallisation into a confined methanol solvate, which upon vacuum drying leads to the stabilised rare form V of IMC inside the MCF host. In contrast to the pure form, encapsulated form V does not transform into a more stable polymorph upon heating. The size of the constraining pores and the drug concentration within the pores determine whether the amorphous state of the drug is stabilised or it recrystallises into confined nanocrystals. The work presents, in a critical manner, an application of complementary techniques (DSC, PXRD, solid-state NMR, N2 adsorption) to confirm unambiguously the phase transitions under confinement and offers a comprehensive strategy towards the formation and control of nano-crystalline encapsulated organic solids

Intrathecal drug delivery systems for the management of chronic non-cancer pain : a systematic review of economic evaluations

Background: Intrathecal drug delivery (ITDD) systems are one of a limited number of management options for chronic non-cancer pain, cancer pain and spasticity. Concerns over their effectiveness and high initial costs led NHS England to decommission ITDD for patients with chronic non-cancer pain. However, the extent to which this decision is in line with existing economic evidence is unclear. The aim of this systematic review is to identify and review the existing evidence on the cost-effectiveness of ITDD for chronic non-cancer pain. Methods: Full and partial economic evaluations on ITDD were identified through systematic searches in MEDLINE, EMBASE, Web of Science and the National Health Service Centre for Reviews and Dissemination databases. Database searches were complemented by hand searching of reference lists of relevant studies and searches of grey literature. Study selection was carried out by two assessors, independently. Study quality assessment was performed to inform critical appraisal of health economics studies. Data were extracted using a data extraction form developed for this study. Results: 4464 unique studies were identified, of which seven met the inclusion criteria. With the exception of one study, the studies found ITDD to be either cost-saving or cost-effective compared to conventional medical management. ITDD becomes cost-ineffective in one further study following price year adjustment to 2016. Conclusions: Study findings show ITDD as not cost-effective only in extremely conservative scenarios. There is limited evidence on the effectiveness of ITDD in non-cancer pain; however, the available economic evidence controverts arguments to refute the treatment on economic grounds

Radiographers supporting radiologists in the interpretation of screening mammography: a viable strategy to meet the shortage in the number of radiologists.

BackgroundAn alternative approach to the traditional model of radiologists interpreting screening mammography is necessary due to the shortage of radiologists to interpret screening mammograms in many countries.MethodsWe evaluated the performance of 15 Mexican radiographers, also known as radiologic technologists, in the interpretation of screening mammography after a 6 months training period in a screening setting. Fifteen radiographers received 6 months standardized training with radiologists in the interpretation of screening mammography using the Breast Imaging Reporting and Data System (BI-RADS) system. A challenging test set of 110 cases developed by the Breast Cancer Surveillance Consortium was used to evaluate their performance. We estimated sensitivity, specificity, false positive rates, likelihood ratio of a positive test (LR+) and the area under the subject-specific Receiver Operating Characteristic (ROC) curve (AUC) for diagnostic accuracy. A mathematical model simulating the consequences in costs and performance of two hypothetical scenarios compared to the status quo in which a radiologist reads all screening mammograms was also performed.ResultsRadiographer's sensitivity was comparable to the sensitivity scores achieved by U.S. radiologists who took the test but their false-positive rate was higher. Median sensitivity was 73.3 % (Interquartile range, IQR: 46.7-86.7 %) and the median false positive rate was 49.5 % (IQR: 34.7-57.9 %). The median LR+ was 1.4 (IQR: 1.3-1.7 %) and the median AUC was 0.6 (IQR: 0.6-0.7). A scenario in which a radiographer reads all mammograms first, and a radiologist reads only those that were difficult for the radiographer, was more cost-effective than a scenario in which either the radiographer or radiologist reads all mammograms.ConclusionsGiven the comparable sensitivity achieved by Mexican radiographers and U.S. radiologists on a test set, screening mammography interpretation by radiographers appears to be a possible adjunct to radiologists in countries with shortages of radiologists. Further studies are required to assess the effectiveness of different training programs in order to obtain acceptable screening accuracy, as well as the best approaches for the use of non-physician readers to interpret screening mammography

Validation of the Bluebelle Wound Healing questionnaire (WHQ) for assessment of surgical site infection in primary surgical wounds after hospital discharge

Background Accurate assessment of surgical‐site infection (SSI) is crucial for surveillance and research. Self‐reporting patient measures are needed because current SSI tools are limited for assessing patients after leaving hospital. The Bluebelle Wound Healing Questionnaire (WHQ) was developed for patient or observer completion; this study tested its acceptability, scale structure, reliability and validity in patients with closed primary wounds after abdominal surgery. Methods Patients completed the WHQ (self‐assessment) within 30 days after leaving hospital and returned it by post. Healthcare professionals completed the WHQ (observer assessment) by telephone or face‐to‐face. Questionnaire response rates and patient acceptability were assessed. Factor analysis and Cronbach's α examined scale structure and internal consistency. Test–retest and self‐ versus observer reliability assessments were performed. Sensitivity and specificity for SSI discrimination against a face‐to‐face reference diagnosis (using Centers for Disease Control and Prevention criteria) were examined. Results Some 561 of 792 self‐assessments (70·8 per cent) and 597 of 791 observer assessments (75·5 per cent) were completed, with few missing data or problems reported. Data supported a single‐scale structure with strong internal consistency (α greater than 0·8). Reliability between test–retest and self‐ versus observer assessments was good (κ 0·6 or above for the majority of items). Sensitivity and specificity for SSI discrimination was high (area under the receiver operating characteristic (ROC) curve 0·91). Conclusion The Bluebelle WHQ is acceptable, reliable and valid with a single‐scale structure for postdischarge patient or observer assessment of SSI in closed primary wounds

Clinical Outcomes and Survival Following Treatment of Metastatic Castrate-Refractory Prostate Cancer With Docetaxel Alone or With Strontium-89, Zoledronic Acid, or Both

Importance Bony metastatic castrate-refractory prostate cancer (CRPC) has a poor prognosis and high morbidity. Zoledronic acid (ZA) is commonly combined with docetaxel in practice but lacks evidence that combining is effective, and strontium-89 (Sr89) is generally used palliatively in patients unfit for chemotherapy. Phase 2 analysis of the TRAPEZE trial confirmed combining the agents was safe and feasible, and the objectives of phase 3 include assessment of the treatments on survival. Objective To determine clinical effectiveness and cost-effectiveness of combining docetaxel, ZA, and Sr89, all having palliative benefits and used in bony metastatic CRPC to control bone symptoms and, for docetaxel, to prolong survival. Design, Setting, and Participants The TRAPEZE trial is a 2 × 2 factorial trial comparing docetaxel alone or with ZA, Sr89, or both. A cohort of 757 participants were recruited between February 2005 and February 2012 from hospitals in the United Kingdom. Overall, 169 participants (45%) had received palliative radiotherapy, and the median (IQR) prostate-specific antigen level was 146 (51-354). Follow-ups were performed for at least 12 months. Interventions Up to 10 cycles of docetaxel alone; docetaxel with ZA; docetaxel with a single Sr89 dose after 6 cycles; or docetaxel with both ZA and Sr89. Main Outcomes and Measures Primary outcomes included clinical progression-free survival (CPFS) (pain progression, skeletal-related events [SREs], or death) and cost-effectiveness. Secondary outcomes included SRE-free interval, pain progression–free interval, total SREs, and overall survival (OS). Results Overall, of 757 participants, 349 (46%) completed docetaxel treatment. Median (IQR) age was 68 (63-73) years. Clinical progression-free survival did not reach statistical significance for either Sr89 or ZA. Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (hazard ratio [HR], 0.85; 95% CI, 0.73-0.99; P = .03) and confirmed no effect of ZA (HR, 0.98; 95% CI, 0.85-1.14; P = .81); ZA had a significant effect on SRE-free interval (HR, 0.78; 95% CI, 0.65-0.95; P = .01). For OS, there was no effect of either Sr89 (HR, 0.92; 95% CI, 0.79-1.08; P = 0.34) or ZA (HR, 0.99; 95% CI, 0.84-1.16; P = 0.91). Conclusions and Relevance Strontium-89 combined with docetaxel improved CPFS but did not improve OS, SRE-free interval, or total SREs; ZA did not improve CPFS or OS but did significantly improve median SRE-free interval and reduced total SREs by around one-third, suggesting a role as postchemotherapy maintenance therapy

Study protocol of cost-effectiveness and cost-utility of a biopsychosocial multidisciplinary intervention in the evolution of non-specific sub-acute low back pain in the working population: cluster randomised trial.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain (LBP), with high incidence and prevalence rate, is one of the most common reasons to consult the health system and is responsible for a significant amount of sick leave, leading to high health and social costs. The objective of the study is to assess the cost-effectiveness and cost-utility analysis of a multidisciplinary biopsychosocial educational group intervention (MBEGI) of non-specific sub-acute LBP in comparison with the usual care in the working population recruited in primary healthcare centres. Methods/design: The study design is a cost-effectiveness and cost-utility analysis of a MBEGI in comparison with the usual care of non-specific sub-acute LBP.Measures on effectiveness and costs of both interventions will be obtained from a cluster randomised controlled clinical trial carried out in 38 Catalan primary health care centres, enrolling 932 patients between 18 and 65 years old with a diagnosis of non-specific sub-acute LBP. Effectiveness measures are: pharmaceutical treatments, work sick leave (% and duration in days), Roland Morris disability, McGill pain intensity, Fear Avoidance Beliefs (FAB) and Golberg Questionnaires. Utility measures will be calculated from the SF-12. The analysis will be performed from a social perspective. The temporal horizon is at 3 months (change to chronic LBP) and 12 months (evaluate the outcomes at long term. Assessment of outcomes will be blinded and will follow the intention-to-treat principle. Discussion: We hope to demonstrate the cost-effectiveness and cost-utility of MBEGI, see an improvement in the patients' quality of life, achieve a reduction in the duration of episodes and the chronicity of non-specific low back pain, and be able to report a decrease in the social costs. If the intervention is cost-effectiveness and cost-utility, it could be applied to Primary Health Care Centres. Trial registration: ISRCTN: ISRCTN5871969

Using simulation to interpret a discrete time survival model in a complex biological system: fertility and lameness in dairy cows

The ever-growing volume of data routinely collected and stored in everyday life presents researchers with a number of opportunities to gain insight and make predictions. This study aimed to demonstrate the usefulness in a specific clinical context of a simulation-based technique called probabilistic sensitivity analysis (PSA) in interpreting the results of a discrete time survival model based on a large dataset of routinely collected dairy herd management data. Data from 12,515 dairy cows (from 39 herds) were used to construct a multilevel discrete time survival model in which the outcome was the probability of a cow becoming pregnant during a given two day period of risk, and presence or absence of a recorded lameness event during various time frames relative to the risk period amongst the potential explanatory variables. A separate simulation model was then constructed to evaluate the wider clinical implications of the model results (i.e. the potential for a herd’s incidence rate of lameness to influence its overall reproductive performance) using PSA. Although the discrete time survival analysis revealed some relatively large associations between lameness events and risk of pregnancy (for example, occurrence of a lameness case within 14 days of a risk period was associated with a 25% reduction in the risk of the cow becoming pregnant during that risk period), PSA revealed that, when viewed in the context of a realistic clinical situation, a herd’s lameness incidence rate is highly unlikely to influence its overall reproductive performance to a meaningful extent in the vast majority of situations. Construction of a simulation model within a PSA framework proved to be a very useful additional step to aid contextualisation of the results from a discrete time survival model, especially where the research is designed to guide on-farm management decisions at population (i.e. herd) rather than individual level

Bluebelle pilot randomised controlled trial of three wound dressing strategies to reduce surgical site infection in primary surgical wounds

Objective Surgical site infection (SSI) affects up to 25% of primary surgical wounds. Dressing strategies may influence SSI risk. The Bluebelle study assessed the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of different dressing strategies to reduce SSI in primary surgical wounds. Design A pilot, factorial RCT. Setting Five UK hospitals. Participants Adults undergoing abdominal surgery with a primary surgical wound. Interventions Participants were randomised to ‘simple dressing’, ‘glue-as-a-dressing’ or ‘no dressing’, and to the time at which the treatment allocation was disclosed to the surgeon (disclosure time, before or after wound closure). Primary and secondary outcome measures Feasibility outcomes focused on recruitment, adherence to randomised allocations, reference assessment of SSI and response rates to participant-completed and observer-completed questionnaires to assess SSI (proposed primary outcome for main trial), wound experience and symptoms, and quality of life (EQ-5D-5L). Results Between March and November 2016, 1115 patients were screened; 699 (73.4%) were eligible and approached, 415 (59.4%) consented and 394 (35.3%) were randomised (simple dressing=133, glue=129 and ‘no dressing’=132). Non-adherence to dressing allocation was 2% (3/133), 6% (8/129) and 15% (20/132), respectively. Adherence to disclosure time was 99% and 86% before and after wound closure, respectively. The overall rate of SSI (reference assessment) was 18.1% (51/281). Response rates to the Wound Healing Questionnaire and other questionnaires ranged from >90% at 4 days to 68% at 4–8 weeks. Conclusions A definitive RCT of dressing strategies including ‘no dressing’ is feasible. Further work is needed to optimise questionnaire response rates

Rationale and design of BISTRO: a randomized controlled trial to determine whether bioimpedance spectroscopy guided fluid management maintains residual kidney function in incident haemodialysis patients

Background: Preserved residual kidney function (RKF) and normal fluid status are associated with better patient outcomes in incident haemodialysis patients. The objective of this trial is to determine whether using bioimpedance technology in prescribing the optimal post-dialysis weight can reduce the rate of decline of RKF and potentially improve patient outcomes. Methods/Design: 516 patients commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine volume >500 ml per day or per the shorter inter-dialytic period will be consented and enrolled into a pragmatic, open label, randomized controlled trial. The intervention is incorporation of bioimpedance spectroscopy (BI) determination of normally hydrated weight to set a post-dialysis target weight that limits volume depletion, compared to current standard practice. Clinicians and participants will be blinded to BI measures in the control group and a standardized record capturing management of fluid status will be used in all participants. Primary outcome is preservation of residual kidney function assessed as time to anuria (≤100 ml/day or ≤200 ml urine volume in the short inter-dialytic period). A sample size of 516 was based upon a cumulative incidence of 30% anuria in the control group and 20% in the treatment group and 11% competing risks (death, transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes include rate of decline in small solute clearance, significant adverse events, hospitalization, loss of vascular access, cardiovascular events and interventions, dialysis efficacy and safety, dialysis-related symptoms and quality of life. Economic evaluation will be carried out to determine the cost-effectiveness of the intervention. Analyses will be adjusted for patient characteristics and dialysis unit practice patterns relevant to fluid management. Discussion: This trial will establish the added value of undertaking BI measures to support clinical management of fluid status and establish the relationship between fluid status and preservation of residual kidney function in incident haemodialysis patients. Trial registration: ISCCTN Number: 11342007, completed 26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University Keywords: Fluid status, Body composition, Residual kidney function, Haemodialysis, Bioimpedance, Fluid management, Health economic