Cholinesterase inhibitor to prevent falls in Parkinson's disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease.

BACKGROUND: Falls are a common complication of Parkinson's disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson's disease. METHODS: This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson's motor and non-motor symptoms, quality of life and cost-effectiveness. DISCUSSION: This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson's disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population. TRIAL REGISTRATION: REC reference: 19/SW/0043. EudraCT: 2018-003219-23. ISCRTN: 41639809 (registered 16/04/2019). ClinicalTrials.gov Identifier: NCT04226248 PROTOCOL AT TIME OF PUBLICATION: Version 7.0, 20th January 2021.

How does deprivation influence secondary care costs after hip fracture?

We studied the association between deprivation and healthcare costs after hip fracture. Hospital costs in the year following hip fracture were £1120 higher for those living in more deprived areas. Most of this difference was explained by pre-existing health inequalities which should be targeted to reduce this disparity. INTRODUCTION: To quantify differences in hospital costs following hip fracture between those living in higher and lower deprivation areas of England, we investigate pre- and post-fracture variables that explain the association. METHODS: We used English Hospital Episodes Statistics linked to the National Hip Fracture Database (April 2011-March 2015) and national mortality data to identify patients admitted with hip fracture aged 60+ years. Hospital care was costed using 2017/2018 national reference costs, by index of multiple deprivation quintile. Three generalised linear model regressions estimated associations between deprivation and costs and the pre- and post-fracture variables that mediate this relationship. RESULTS: Patients from the most deprived areas had higher hospital costs in the year post-fracture (£1,120; 95% CI £993 to £1,247) than those from the least deprived areas. If all patients could have incurred similar costs to those in the least deprived quintile, this would equate to an annual reduction in expenditure of £28.8 million. Pre-fracture characteristics, particularly comorbidities and anaesthetic risk grade, accounted for approximately 50% of the association between deprivation and costs. No evidence was found that post-fracture variables, such as transfer to a residential or nursing home, contributed to the association between deprivation and costs. CONCLUSIONS: Socioeconomic inequalities are associated with substantial costs for the NHS after hip fracture. We did not identify post-fracture targets for intervention to reduce the impact of inequalities on post-fracture costs. The case for interventions to reduce comorbid conditions, improve health-related behaviours and prevent falls in deprived areas is clear but challenging to implement.

Exploring the identification, validation, and categorization of the cost and benefits of criminal justice in mental health: the PECUNIA project.

BACKGROUND: Mental health disorders and their treatments produce significant costs and benefits in both healthcare and non-healthcare sectors. The latter are often referred to as intersectoral costs and benefits (ICBs). Little is known about healthcare-related ICBs in the criminal justice sector and how to include these in health economics research. OBJECTIVES: The triple aim of this study is (i) to identify healthcare-related ICBs in the criminal justice sector, (ii) to validate the list of healthcare-related ICBs in the criminal justice sector on a European level by sector-specific experts, and (iii) to classify the identified ICBs. METHODS: A scientific literature search in PubMed and an additional grey literature search, carried out in six European countries, were used to retrieve ICBs. In order to validate the international applicability of the ICBs, a survey was conducted with an international group of experts from the criminal justice sector. The list of criminal justice ICBs was categorized according to the PECUNIA conceptual framework. RESULTS: The full-text analysis of forty-five peer-reviewed journal articles and eleven grey literature sources resulted in a draft list of items. Input from the expert survey resulted in a final list of fourteen unique criminal justice ICBs, categorized according to the care atom. CONCLUSION: This study laid further foundations for the inclusion of important societal costs of mental health-related interventions within the criminal justice sector. More research is needed to facilitate the further and increased inclusion of ICBs in health economics research.

Direct access CT for suspicion of brain tumour: an analysis of referral pathways in a population-based patient group.

BACKGROUND: Brain tumour patients see their primary care doctor on average three or more times before diagnosis, so there may be an opportunity to identify 'at risk' patients earlier. Suspecting a brain tumour diagnosis is difficult because brain tumour-related symptoms are typically non-specific. METHODS: We explored the predictive value of referral guidelines (Kernick and NICE 2005) for brain imaging where a tumour is suspected, in a population-based patient group referred for direct access CT of the head. A consensus panel reviewed whether non-tumour findings were clinically important or whether further investigation was necessary. RESULTS: Over a 5-year period, 3257 head scans were performed; 318 scans were excluded according to pre-specified criteria. 53 patients (1.8%) were reported to have intracranial tumours, of which 42 were significant (diagnostic yield of 1.43%). There were no false negative CT scans for tumour. With symptom-based referral guidelines primary care doctors can identify patients with a 3% positive predictive value (PPV). 559 patients had non-tumour findings, 31% of which were deemed clinically significant. In 34% of these 559 patients, referral for further imaging and/or specialist assessment from primary care was still thought warranted. CONCLUSION: Existing referral guidelines are insufficient to stratify patients adequately based on their symptoms, according to the likelihood that a tumour will be found on brain imaging. Identification of non-tumour findings may be significant for patients and earlier specialist input into interpretation of these images may be beneficial. Improving guidelines to better identify patients at risk of a brain tumour should be a priority, to improve speed of diagnosis, and reduce unnecessary imaging and costs. Future guidelines may incorporate groups of symptoms, clinical signs and tests to improve the predictive value.

Comparing hospital and telephone follow-up for patients treated for stage-I endometrial cancer (ENDCAT trial): a randomised, multicentre, non-inferiority trial.

OBJECTIVE: To evaluate the effectiveness of nurse-led telephone follow-up (TFU) for patients with stage-I endometrial cancer. DESIGN: Multicentre, randomised, non-inferiority trial. SETTING: Five centres in the North West of England. SAMPLE: A cohort of 259 women treated for stage-I endometrial cancer attending hospital outpatient clinics for routine follow-up. METHODS: Participants were randomly allocated to receive traditional hospital based follow-up (HFU) or nurse-led TFU. MAIN OUTCOME MEASURES: Primary outcomes were psychological morbidity (State Trait Anxiety Inventory, STAI-S) and patient satisfaction with the information provided. Secondary outcomes included patient satisfaction with service, quality of life, and time to detection of recurrence. RESULTS: The STAI-S scores post-randomisation were similar between groups [mean (SD): TFU 33.0 (11.0); HFU 35.5 (13.0)]. The estimated between-group difference in STAI-S was 0.7 (95% confidence interval, 95% CI -1.9 to 3.3); the confidence interval lies above the non-inferiority limit (-3.5), indicating the non-inferiority of TFU. There was no significant difference between groups in reported satisfaction with information (odds ratio, OR 0.9; 95% CI 0.4-2.1; P = 0.83). Women in the HFU group were more likely to report being kept waiting for their appointment (P = 0.001), that they did not need any information (P = 0.003), and were less likely to report that the nurse knew about their particular case and situation (P = 0.005). CONCLUSIONS: The TFU provides an effective alternative to HFU for patients with stage-I endometrial cancer, with no reported physical or psychological detriment. Patient satisfaction with information was high, with similar levels between groups. TWEETABLE ABSTRACT: ENDCAT trial shows effectiveness of nurse-led telephone follow-up for patients with stage-I endometrial cancer.

Randomized clinical trial of postoperative chewing gum versus standard care after colorectal resection.

BACKGROUND: Chewing gum may stimulate gastrointestinal motility, with beneficial effects on postoperative ileus suggested in small studies. The primary aim of this trial was to determine whether chewing gum reduces length of hospital stay (LOS) after colorectal resection. Secondary aims included examining bowel habit symptoms, complications and healthcare costs. METHODS: This clinical trial allocated patients randomly to standard postoperative care with or without chewing gum (sugar-free gum for at least 10 min, four times per day on days 1-5) in five UK hospitals. The primary outcome was LOS. Cox regression was used to calculate hazard ratios for LOS. RESULTS: Data from 402 of 412 patients, of whom 199 (49·5 per cent) were allocated to chewing gum, were available for analysis. Some 40 per cent of patients in both groups had laparoscopic surgery, and all study sites used enhanced recovery programmes. Median (i.q.r.) LOS was 7 (5-11) days in both groups (P = 0·962); the hazard ratio for use of gum was 0·94 (95 per cent c.i. 0·77 to 1·15; P = 0·557). Participants allocated to gum had worse quality of life, measured using the EuroQoL 5D-3L, than controls at 6 and 12 weeks after operation (but not on day 4). They also had more complications graded III or above according to the Dindo-Demartines-Clavien classification (16 versus 6 in the group that received standard care) and deaths (11 versus 0), but none was classed as related to gum. No other differences were observed. CONCLUSION: Chewing gum did not alter the return of bowel function or LOS after colorectal resection. REGISTRATION NUMBER: ISRCTN55784442 (http://www.controlled-trials.com).

Making the case for investment in public health: experiences of Directors of Public Health in English local government.

BACKGROUND: Amid local government budget cuts, there is concern that the ring-fenced public health grant is being appropriated, and Directors of Public Health (DsPH) find it difficult to make the case for investment in public health activity. This paper describes what DsPH are making the case for, the components of their case and how they present the case for public health. METHODS: Thirteen semi-structured telephone interviews and a group discussion were carried out with DsPH (November 2013 to May 2014) in the Southern region of England. RESULTS: DsPH make the case for control of the public health grant and investing in action on wider determinants of health. The cases they present incorporate arguments about need, solutions and their effectiveness, health outcomes, cost and economic impact but also normative, political arguments. Many types of evidence were used to substantiate the cases; evidence was carefully framed to be accessible and persuasive. CONCLUSIONS: DsPH are responding to a new environment; economic arguments and evidence of impact are key components of the case for public health, although multiple factors influence local government (LG) decisions around health improvement. Further evidence of economic impact would be helpful in making the case for public health in LG.

Study protocol for an evaluation of the effectiveness of 'care bundles' as a means of improving hospital care and reducing hospital readmission for patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease is one of the commonest respiratory diseases in the United Kingdom, accounting for 10% of unplanned hospital admissions each year. Nearly a third of these admitted patients are re-admitted to hospital within 28 days of discharge. Whilst there is a move within the NHS to ensure that people with long-term conditions receive more co-ordinated care, there is little research evidence to support an optimum approach to this in COPD. This study aims to evaluate the effectiveness of introducing standardised packages of care i.e. care bundles, for patients with acute exacerbations of COPD as a means of improving hospital care and reducing re-admissions. METHODS / DESIGN: This mixed-methods evaluation will use a controlled before-and-after design to examine the effect of, and costs associated with, implementing care bundles for patients admitted to hospital with an acute exacerbation of COPD, compared with usual care. It will quantitatively measure a range of patient and organisational outcomes for two groups of hospitals - those who deliver care using COPD care bundles, and those who deliver care without the use of COPD care bundles. These care bundles may be provided for patients with COPD following admission, prior to discharge or at both points in the care pathway. The primary outcome will be re-admission to hospital within 28 days of discharge, although the study will additionally investigate a number of secondary outcomes including length of stay, total bed days, in-hospital mortality, costs of care and patient / carer experience. A series of nested qualitative case studies will explore in detail the context and process of care as well as the impact of COPD bundles on staff, patients and carers. DISCUSSION: The results of the study will provide information about the effectiveness of care bundles as a way of managing in-hospital care for patients with an acute exacerbation of COPD. Given the number of unplanned hospital admissions for this patient group and their rate of subsequent re-admission, it is hoped that this evaluation will make a timely contribution to the evidence on care provision, to the benefit of patients, clinicians, managers and policy-makers. TRIAL REGISTRATION: International Standard Randomised Controlled Trials - ISRCTN13022442 - 11 February 2015.

A systematic review of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry compared to routine microbiological methods for the time taken to identify microbial organisms from positive blood cultures.

Bloodstream infections are a significant source of mortality and morbidity. Patient outcomes are improved by rapid identification of the causative pathogen and administration of appropriate antimicrobial therapy. Matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry has recently emerged as an alternative to microbiological identification. It is important to establish whether the costs of MALDI-TOF are justified by more timely identification and appropriate therapy, reduced length of stay and reduced hospital costs. We undertook a systematic review of the literature comparing MALDI-TOF and routine methods for the identification of the aetiological agent in patients with known or suspected bloodstream infection. The primary outcome of the review was the 'time to identify' organisms. Information on related measures such as 'time to appropriate antimicrobial treatment' and downstream hospital cost was also collected where reported. Ten of 775 articles identified met the inclusion criteria. All included studies were observational. MALDI-TOF identification was at least 24 h faster than routine methods in most circumstances. MADLI-TOF was associated with a reduction in downstream hospital costs and length of stay in studies reporting these outcomes. The observational studies reviewed provide evidence of potentially substantial time savings of MALDI-TOF in pathogen identification and instigation of appropriate therapy, which may also reduce hospital stay. Due to the small number of studies, all at relatively high risk of bias, this cannot be considered as definitive evidence of the impact of MALDI-TOF. More and better evidence, including impact on patient health and cost-effectiveness, is required.

A cross-sectional survey of 5-year-old children with non-syndromic unilateral cleft lip and palate: the Cleft Care UK study. Part 1: background and methodology.

OBJECTIVES: We describe the methodology for a major study investigating the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after an initial survey, detailed in the Clinical Standards Advisory Group (CSAG) report in 1998, had informed government recommendations on centralization. SETTING AND SAMPLE POPULATION: This is a UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Children born between 1 April 2005 and 31 March 2007 were seen in cleft centre audit clinics. MATERIALS AND METHODS: Consent was obtained for the collection of routine clinical measures (speech recordings, hearing, photographs, models, oral health, psychosocial factors) and anthropometric measures (height, weight, head circumference). The methodology for each clinical measure followed those of the earlier survey as closely as possible. RESULTS: We identified 359 eligible children and recruited 268 (74.7%) to the study. Eleven separate records for each child were collected at the audit clinics. In total, 2666 (90.4%) were collected from a potential 2948 records. The response rates for the self-reported questionnaires, completed at home, were 52.6% for the Health and Lifestyle Questionnaire and 52.2% for the Satisfaction with Service Questionnaire. CONCLUSIONS: Response rates and measures were similar to those achieved in the previous survey. There are practical, administrative and methodological challenges in repeating cross-sectional surveys 15 years apart and producing comparable data.

Does the cancer drugs fund lead to faster uptake of cost-effective drugs? A time-trend analysis comparing England and Wales.

BACKGROUND: The Cancer Drugs Fund (CDF) provides £200 million annually in England for 'anti-cancer' drugs. METHODS: We used a controlled pre-/post-intervention design to compare IMS Health dispensing data for 15 cancer drugs (2007-2012) in England vs Wales, stratified by pre-CDF NICE drug approval status (rejected, mixed recommendations, recommended, not appraised). RESULTS: The CDF was associated with increased prescribing in England for three of five drugs rejected or with mixed NICE recommendations. The prescribing volume ratios (PVR) ranged from 1.29 (95% CI 1.00, 1.67) for sorafenib to 3.28 (2.59, 4.14) for bevacizumab (NICE rejected) and 0.93 (0.81, 1.06) and 1.35 (1.21, 1.49) for sunitinib and imatinib respectively (mixed recommendations). Post CDF prescribing in England increased for both drugs awaiting NICE appraisal pre-CDF (lapatinib PVR=7.44 (5.81, 9.54), panitumumab PVR=5.40 (1.20, 24.42)) and subsequently rejected. The CDF was not associated with increased prescribing in England of NICE-recommended drugs. The three most recently launched, subsequently recommended drugs were adopted faster in Wales (from pazopanib PVR=0.51 (0.28, 0.96) to abiraterone PVR=0.78 (0.61-0.99)). INTERPRETATION: These data indicate that the CDF is used to access drugs deemed not cost-effective by NICE. The CDF did not expedite access to new cost-effective cancer agents prior to NICE approval.

Feasibility RCT of definitive chemoradiotherapy or chemotherapy and surgery for oesophageal squamous cell cancer.

BACKGROUND: The optimal treatment for localised oesophageal squamous cell carcinoma (SCC) is uncertain. We assessed the feasibility of an RCT comparing neoadjuvant treatment and surgery with definitive chemoradiotherapy. METHODS: A feasibility RCT in three centres examined incident patients and reasons for ineligibility using multi-disciplinary team meeting records. Eligible patients were offered participation in the RCT with integrated qualitative research involving audio-recorded recruitment appointments and interviews with patients to inform recruitment training for staff. RESULTS: Of 375 patients with oesophageal SCC, 42 (11.2%) were eligible. Reasons for eligibility varied between centres, with significantly differing proportions of patients excluded because of total tumour length (P=0.002). Analyses of audio-recordings and patient interviews showed that recruiters had challenges articulating the trial design in simple terms, balancing treatment arms and explaining the need for randomisation. Before analyses of the qualitative data and recruiter training no patients were randomised. Following training in one centre 5 of 16 eligible patients were randomised. CONCLUSIONS: An RCT of surgical vs non-surgical treatment for SCC of the oesophagus is not feasible in the UK alone because of the low number of incident eligible patients. A trial comparing diverse treatment approaches may be possible with investment to support the recruitment process.

Uptake of carotid artery stenting in England and subsequent vascular admissions: an appropriate response to emerging evidence?

OBJECTIVE: We report the uptake, length of stay and vascular readmission rates of carotid endarterectomy (CEA) and CAS among patients with symptomatic or asymptomatic carotid artery disease in the English National Health Service (NHS). METHODS: Retrospective cohort study based on routinely collected Hospital Episode Statistics (HES) inpatient data. We identified individual admissions for CEA (n = 15996) or CAS (n = 632) between 2006 and 2009. Summary data were used to describe procedure volumes between 2009 and 2012. We analysed trends in procedure use over time and used ordinary least squares regression to evaluate patient, clinical and organisational characteristics associated with longer length of stay for revascularisation. RESULTS: CAS made up less than 5% of carotid revascularisation procedures; there was no trend for increasing use between 2006 and 2012. Patients treated with CAS were on average younger, lived in areas of higher deprivation and were more likely to have amaurosis fugax or a comorbidity of heart disease. CAS patients had a 19% (95% CI 14-24) shorter stay in hospital than CEA patients. CONCLUSION: Despite the early promise of CAS and numerous randomised controlled trials evaluating efficacy, it has not been rapidly adopted in England. Cautious adoption may be appropriate given the higher periprocedural risk of stroke or death after CAS, particularly in recently symptomatic patients.

Parents' perspectives on centralized cleft services for children: the development of a DCE questionnaire.

OBJECTIVE: Incorporating user's perspectives in healthcare delivery is important. Simple questionnaires may not capture these as well as a discrete choice experiment (DCE) which enables the exploration of users' trade-offs between different service attributes. Qualitative methods are increasingly used to improve a DCE's face validity, but few studies adequately describe them. This paper describes the qualitative investigations in the development of a DCE questionnaire to elicit parents' perspectives on centralized services for children with cleft lip and palate. METHODS: Semi-structured telephone interviews were conducted with 16 parents from across the UK, except Wales. Data analysis was carried out by the constant comparative method. RESULTS: Five attributes and their levels were inductively identified: usefulness and amount of information (four levels); staff attitude at cleft centres (two levels); continuity of care (two levels); personal costs of attending appointments (four levels); and cleft centres facilities (two levels). An unexpected finding was that parents' sense of responsibility towards their child made a 'willingness-to-travel' attribute unacceptable to them, but they were receptive to a 'willingness-to-pay' attribute. CONCLUSION: Using qualitative methods with service users in attribute development for a DCE helps to uncover issues that may not be apparent to researchers or health service staff.

Methods for think-aloud interviews in health-related resource-use research: the PECUNIA RUM instrument.

BACKGROUND: The think-aloud (TA) approach is a qualitative research method that allows for gaining insight into thoughts and cognitive processes. It can be used to incorporate a respondent's perspective when developing resource-use measurement (RUM) instruments. Currently, the application of TA methods in RUM research is limited, and so is the guidance on how to use them. Transparent publication of TA methods for RUM in health economics studies, which is the aim of this paper, can contribute to reducing the aforementioned gap. METHODS: Methods for conducting TA interviews were iteratively developed by a multi-national working group of health economists and additional qualitative research expertise was sought. TA interviews were conducted in four countries to support this process. A ten-step process was outlined in three parts: Part A 'before the interview' (including translation, recruitment, training), Part B 'during the interview' (including setting, opening, completing the instrument, open-ended questions, closing), and part C 'after the interview' (including transcription and data analysis, trustworthiness). CONCLUSIONS: This manuscript describes the step-by-step approach for conducting multi-national TA interviews with potential respondents of the PECUNIA RUM instrument. It increases the methodological transparency in RUM development and reduces the knowledge gap of using qualitative research methods in health economics.

Economic evaluation of lifestyle interventions to treat overweight or obesity in children.

OBJECTIVE: To estimate lifetime cost effectiveness of lifestyle interventions to treat overweight and obese children, from the UK National Health Service perspective. DESIGN: An adaptation of the National Heart Forum economic model to predict lifetime health service costs and outcomes of lifestyle interventions on obesity-related diseases. SETTING: Hospital or community-based weight-management programmes. POPULATION: Hypothetical cohorts of overweight or obese children based on body mass data from the National Child Measurement Programme. INTERVENTIONS: Lifestyle interventions that have been compared with no or minimal intervention in randomized controlled trials (RCTs). MAIN OUTCOME MEASURES: Reduction in body mass index (BMI) standard deviation score (SDS), intervention resources/costs, lifetime treatment costs, obesity-related diseases and cost per life year gained. RESULTS: Ten RCTs were identified by our search strategy. The median effect of interventions versus control from these 10 RCTs was a difference in BMI SDS of -0.13 at 12 months, but the range in effects among interventions was broad (0.04 to -0.60). Indicative costs per child of these interventions ranged from £108 to £662. For obese children aged 10-11 years, an intervention that resulted in a median reduction in BMI SDS at 12 months at a moderate cost of £400 increased life expectancy by 0.19 years and intervention costs were offset by subsequent undiscounted savings in treatment costs (net saving of £110 per child), though this saving did not emerge until the sixth or seventh decade of life. The discounted cost per life year gained was £13 589. Results were broadly similar for interventions aimed at children aged 4-5 years and which targeted both obese and overweight children. For more costly interventions, savings were less likely. CONCLUSION: Interventions to treat childhood obesity are potentially cost effective although cost savings and health benefits may not appear until the sixth or seventh decade of life.

The costs of centralisation: a systematic review of the economic impact of the centralisation of cancer services.

While evidence suggests that within specific cancer sites centralisation of services improves outcomes and quality of care, the economic impact of centralisation is unclear. This systematic review identified 19 studies that have investigated whether or not the centralisation of cancer services results in economies of scale, or is cost-effective, or increases the costs of accessing care for patients and their carers. Evidence from 13 studies suggests that increasing surgeon volumes are associated with cost reductions, although one study suggested that this relationship is U-shaped and the evidence is not consistent for hospital volumes and costs. Only one study demonstrated that centralisation was cost-effective with an incremental cost utility ratio of $5029 (€3616) per quality-adjusted life year gained. Consistent evidence from four studies suggested that centralised services increase the costs of accessing care for patients and their carers. Current evidence on the economic impact of centralisation of cancer services is limited and of poor quality. Therefore, it remains unclear whether centralisation results in economies of scale and is cost-effective. Future research should be based on a clear definition of the different components of centralisation in order to determine which aspects of centralisation are efficient and for which cancer subgroups.

The financial and psychological impacts on mothers of children with chronic fatigue syndrome (CFS/ME).

BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalopathy (CFS/ME) is relatively common and children can be severely affected attending little or no school for extended periods. There are no studies quantifying the financial impact of having a child with CFS/ME and there is little information of the impact on parental mood. METHODS: Forty mothers of children with CFS/ME from a regional specialist CFS/ME service completed inventories to assess their psychological well-being (Hospital Anxiety and Depression Scale, General Health Questionnaire-12) loss of earnings and increased expenditure. In addition, eight mothers took part in a semi-structured qualitative interview. RESULTS: Most parents of children with CFS/ME experience loss of monthly income (mean = £247) and increase in monthly expenditure (mean = £206). Twenty-eight (72%) mothers were above the cut-off for the General Health Questionnaire-12 compared with 20% in the healthy population (95% CI 55, 85, P < 0.001) suggesting they probably have a mental health problem. This may be explained by the qualitative interviews where mothers described five areas contributing to poor parental health: lack of understanding from others; marital tension; concern about their child's distress; concern about the impact on siblings and emotional distress causing physical symptoms. CONCLUSIONS: The majority of families of children with CFS/ME experience decreased income and increased expenditure with a marked impact on maternal psychological health. Clinicians need to be aware of this to provide appropriate support to families who care for children with CFS/ME.

Cost-effectiveness of pharmacy-led versus conventionally delivered antiviral treatment for hepatitis C in patients receiving opioid substitution therapy: An economic evaluation alongside a pragmatic cluster randomised trial.

BACKGROUND: Elimination targets for hepatitis C have been set across the world. In the UK almost 90% of infections are in people who inject drugs. Evidence shows community case-finding is effective at identifying and treating undiagnosed patients. The aim of this analysis was to assess, from a healthcare provider perspective, the cost-effectiveness of a new pharmacist-led test and treat pathway for hepatitis C in opioid agonist treatment (OAT) patients attending community pharmacies compared to conventional care. METHODS: In a cluster randomised controlled trial, pharmacies were randomised to the pharmacist-led or conventional care pathway. Mean cost per OAT patient and per patient initiating treatment was identified for each pathway. A Markov model tracking disease progression was developed, with a 50-year time horizon and 3·5% time discount rate, to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained and the probability of being cost-effective at a £30,000 per QALY willingness-to-pay threshold. Probabilistic sensitivity analysis was performed for a range of drug discounts, re-infection rates, and model assumptions. FINDINGS: Mean cost per OAT patient (£3,674 vs £1,965) and per patient initiating treatment (£863 vs £404) was higher in the pharmacist-led pathway, due to higher uptake of testing and pharmacist time requirements. Over a 50-year time horizon the ICER per QALY gained was £31,612 at NHS indicative price for treatment (£38,979 for 12 weeks) and 12·1/100 person-years re-infection rate, reducing to £21,027/£10,220/-£501 per QALY gained with 30%/60%/90% drug price discounts and £25,373/£21,738/£14,912 per QALY gained at re-infection rates of 8/5/2 per 100 person-years. At 30%/60%/90% drug discount rates, the pharmacist-led pathway has an 80%/98%/100% probability of being cost-effective. INTERPRETATION: The pharmacist-led pathway is effective at increasing testing and treatment uptake, with cost-effectiveness being highly dependent on drug price discounts. FUNDING: Trial funding provided by the Scottish Government, Gilead Sciences, and Bristol-Myers Squibb.

Magnitude of terminological bias in international health services research: a disambiguation analysis in mental health.

AIMS: Health services research (HSR) is affected by a widespread problem related to service terminology including non-commensurability (using different units of analysis for comparisons) and terminological unclarity due to ambiguity and vagueness of terms. The aim of this study was to identify the magnitude of the terminological bias in health and social services research and health economics by applying an international classification system. METHODS: This study, that was part of the PECUNIA project, followed an ontoterminology approach (disambiguation of technical and scientific terms using a taxonomy and a glossary of terms). A listing of 56 types of health and social services relevant for mental health was compiled from a systematic review of the literature and feedback provided by 29 experts in six European countries. The disambiguation of terms was performed using an ontology-based classification of services (Description and Evaluation of Services and DirectoriEs - DESDE), and its glossary of terms. The analysis focused on the commensurability and the clarity of definitions according to the reference classification system. Interrater reliability was analysed using κ. RESULTS: The disambiguation revealed that only 13 terms (23%) of the 56 services selected were accurate. Six terms (11%) were confusing as they did not correspond to services as defined in the reference classification system (non-commensurability bias), 27 (48%) did not include a clear definition of the target population for which the service was intended, and the definition of types of services was unclear in 59% of the terms: 15 were ambiguous and 11 vague. The κ analyses were significant for agreements in unit of analysis and assignment of DESDE codes and very high in definition of target population. CONCLUSIONS: Service terminology is a source of systematic bias in health service research, and certainly in mental healthcare. The magnitude of the problem is substantial. This finding has major implications for the international comparability of resource use in health economics, quality and equality research. The approach presented in this paper contributes to minimise differentiation between services by taking into account key features such as target population, care setting, main activities and type and number of professionals among others. This approach also contributes to support financial incentives for effective health promotion and disease prevention. A detailed analysis of services in terms of cost measurement for economic evaluations reveals the necessity and usefulness of defining services using a coding system and taxonomical criteria rather than by 'text-based descriptions'.