Impact of procedure type on revisional surgery and secondary reconstruction after immediate breast reconstruction in a population-based cohort.

BACKGROUND: Women considering immediate breast reconstruction require high-quality information about the likely need for secondary reconstruction and the long-term risk of revisional surgery to make fully informed decisions about different reconstructive options. Such data are currently lacking. This study aimed to explore the impact of reconstruction type on the number of revisions and secondary reconstructions performed 3, 5, and 8 years after immediate breast reconstruction in a large population-based cohort. METHODS: Women undergoing unilateral mastectomy and immediate breast reconstruction for breast cancer or ductal carcinoma in situ in England between 1 April 2009 and 31 March 2015 were identified from National Health Service Hospital Episode Statistics. Numbers of revisions and secondary reconstructions in women undergoing primary definitive immediate breast reconstruction were compared by procedure type at 3, 5, and 8 years after index surgery. RESULTS: Some 16 897 women underwent immediate breast reconstruction with at least 3 years' follow-up. Of these, 14 069 had a definitive reconstruction with an implant only (5193), latissimus dorsi flap with (3110) or without (2373) an implant, or abdominal free flap (3393). Women undergoing implant-only reconstruction were more likely to require revision, with 69.5 per cent (747 of 1075) undergoing at least one revision by 8 years compared with 49.3 per cent (1568 of 3180) in other reconstruction groups. They were also more likely to undergo secondary reconstruction, with the proportion of women having further reconstructive procedures increasing over time: 12.8 per cent (663 of 5193) at 3 years, 14.3 per cent (535 of 3752) at 5 years, and 17.6 per cent (189 of 1075) at 8 years. CONCLUSION: Long-term rates of revisions and secondary reconstructions were considerably higher after primary implant-based reconstruction than autologous procedures. These results should be shared with patients to support informed decision-making.

BACKGROUND: Breast reconstruction is performed to improve well-being for women who need mastectomy (removal of the breast) as part of breast cancer treatment. There are many different types of breast reconstruction operation, and it can be difficult for women to decide which operation, if any, is right for them. Information about the number of extra operations that a woman is likely to need after breast reconstruction surgery is an important factor in helping them make this decision. This study aimed to investigate the number of extra operations that women who had breast reconstruction needed by 3, 5, and 8 years after surgery, and how this differed by the type of breast reconstruction surgery they had. Routinely collected hospital record data were used to identify women having breast reconstruction at the time of mastectomy for breast cancer, and identify any extra operations performed for problems related to the reconstruction in the 8 years after the first operation. The number of extra operations performed after different types of breast reconstructions was compared at 3, 5, and 8 years after the mastectomy. Women who had implant-based reconstruction required more extra operations than those having reconstruction using their own tissue. They were also more likely to have the implant replaced with another type of breast reconstruction than women undergoing tissue-based reconstruction at 3, 5, and 8 years after the first surgery. This information should be discussed with women thinking about breast reconstruction to help them decide what type of operation would be best for them.

Development of a brief, generic, modular resource-use measure (ModRUM): piloting with patients.

BACKGROUND: Bespoke self-report resource-use measures (RUMs) are commonly developed or adapted for each new randomised controlled trial. Consequently, RUMs lack standardisation and validation is rarely conducted. A new generic RUM, ModRUM, has been developed using a rigorous process, including consultation with health economists and patients. ModRUM includes a concise core healthcare module, designed to be included in all trials, and depth-adding questions, which can replace or be added to core questions as needed. Modules covering other sectors are under development. The aim of this study was to test the acceptability, feasibility, and criterion and construct validity of the healthcare module of ModRUM. METHODS: Patients who had a recent appointment at their GP practice were invited to complete ModRUM (core module or core module with depth questions), a characteristics form and the EQ-5D-5L. Acceptability was assessed via response rates and questionnaire completion time. Feasibility was assessed by reviewing issues observed in participants' responses and question completion rates. Construct validity was tested via hypothesis testing and known-group analyses, using Wilcoxon rank-sum and Kruskal-Wallis tests, and a generalised linear model. Criterion validity was tested by comparing ModRUM results with primary care medical records. Sensitivity, specificity, and agreement using Lin's concordance correlation coefficient (pc) were estimated. RESULTS: One hundred patients participated from five GP practices in the South-West of England. Acceptability was higher for the core module (20% versus 10% response rate). Question completion rates were high across both versions (> 90%). Some support was observed for construct validity, with results suggesting that healthcare costs differ dependent on the number of long-term conditions (p < 0.05) and are negatively associated with health-related quality of life (p < 0.01). Sensitivity was high for all questions (> 0.83), while specificity varied (0.33-0.88). There was a good level of agreement for GP contacts and costs, and prescribed medication costs (pc > 0.6). CONCLUSION: This study provided preliminary evidence of the acceptability, feasibility, and criterion and construct validity of ModRUM. Further testing is required within trials and with groups that were less well represented in this study.

Verbal fluency as a quick and simple tool to help in deciding when to refer patients with a possible brain tumour.

BACKGROUND: Patients with brain tumours often present with non-specific symptoms. Correctly identifying who to prioritise for urgent brain imaging is challenging. Brain tumours are amongst the commonest cancers diagnosed as an emergency presentation. A verbal fluency task (VFT) is a rapid triage test affected by disorders of executive function, language and processing speed. We tested whether a VFT could support identification of patients with a brain tumour. METHODS: This proof-of-concept study examined whether a VFT can help differentiate patients with a brain tumour from those with similar symptoms (i.e. headache) without a brain tumour. Two patient populations were recruited, (a) patients with known brain tumour, and (b) patients with headache referred for Direct-Access Computed-Tomography (DACT) from primary care with a suspicion of a brain tumour. Semantic and phonemic verbal fluency data were collected prospectively. RESULTS: 180 brain tumour patients and 90 DACT patients were recruited. Semantic verbal fluency score was significantly worse for patients with a brain tumour than those without (P < 0.001), whether comparing patients with headache, or patients without headache. Phonemic fluency showed a similar but weaker difference. Raw and incidence-weighted positive and negative predictive values were calculated. CONCLUSION: We have demonstrated the potential role of adding semantic VFT score performance into clinical decision making to support triage of patients for urgent brain imaging. A relatively small improvement in the true positive rate in patients referred for DACT has the potential to increase the timeliness and efficiency of diagnosis and improve patient outcomes.

Exploratory comparison of Healthcare costs and benefits of the UK's Covid-19 response with four European countries.

BACKGROUND: In responding to Covid-19, governments have tried to balance protecting health while minimizing gross domestic product (GDP) losses. We compare health-related net benefit (HRNB) and GDP losses associated with government responses of the UK, Ireland, Germany, Spain and Sweden from UK healthcare payer perspective. METHODS: We compared observed cases, hospitalizations and deaths under 'mitigation' to modelled events under 'no mitigation' to 20 July 2020. We thus calculated healthcare costs, quality adjusted life years (QALYs), and HRNB at £20,000/QALY saved by each country. On per population (i.e. per capita) basis, we compared HRNB with forecast reductions in 2020 GDP growth (overall or compared with Sweden as minimal mitigation country) and qualitatively and quantitatively described government responses. RESULTS: The UK saved 3.17 (0.32-3.65) million QALYs, £33 (8-38) billion healthcare costs and £1416 (220-1637) HRNB per capita at £20,000/QALY. Per capita, this is comparable to £1455 GDP loss using Sweden as comparator and offsets 46.1 (7.1-53.2)% of total £3075 GDP loss. Germany, Spain, and Sweden had greater HRNB per capita. These also offset a greater percentage of total GDP losses per capita. Ireland fared worst on both measures. Countries with more mask wearing, testing, and population susceptibility had better outcomes. Highest stringency responses did not appear to have best outcomes. CONCLUSIONS: Our exploratory analysis indicates the benefit of government Covid-19 responses may outweigh their economic costs. The extent that HRNB offset economic losses appears to relate to population characteristics, testing levels, and mask wearing, rather than response stringency.

Development of a brief, generic, modular resource-use measure (ModRUM): cognitive interviews with patients.

BACKGROUND: Self-report resource-use measures (RUMs) are often used to collect healthcare use data from participants in healthcare studies. However, RUMs are typically adapted from existing measures on a study-by-study basis, resulting in a lack of standardisation which limits comparability across studies. Psychometric testing of RUMs is rarely conducted. This paper reports on cognitive interviews with patients to test the content validity and acceptability of a new RUM (ModRUM). ModRUM is a brief, generic RUM with a core module on healthcare use and questions/modules to increase depth and breadth. METHODS: A purposeful sampling strategy with maximum variation was used to recruit patients from primary care to participate in "think-aloud" interviews with retrospective probing. Participants verbalised their thought processes as they completed ModRUM, which allowed errors (issues with completion) to be identified. The interviewer asked follow-up and probing questions to investigate errors, clarity and acceptability. Interviews were audio-recorded and transcribed verbatim. Research team members independently scored transcripts to identify errors in comprehension, recall, judgement and response. Members met to agree on final scores. Interview transcripts were analysed qualitatively using techniques of constant comparison, to identify common themes and ideas for improvement. Data collection and analysis were performed concurrently and in rounds. RESULTS: Twenty participants were interviewed between December 2019 and March 2020. Interviews were conducted in three rounds, with revisions made iteratively and in response to interview findings. Seven participants completed the core module and 13 completed the core module plus depth questions. Of 71 issues, 28 were in comprehension, 14 in retrieval, 10 in judgement, 18 in response and 1 uncategorised. Most issues (21 issues by 2 participants) were due to participants including family healthcare use. Other issues included using incorrect recall periods (5 issues) and overlooking questions leading to missing responses (9 issues). Common participant suggestions included highlighting important details and providing additional definition or examples for some terms. The length, content and layout were acceptable to most participants. CONCLUSIONS: A generic RUM is needed to increase study comparability. RUM development requires thorough testing to demonstrate and enhance validity. Cognitive interviewing has demonstrated the acceptability and content validity of ModRUM.

Establishing a large prospective clinical cohort in people with head and neck cancer as a biomedical resource: head and neck 5000.

BACKGROUND: Head and neck cancer is an important cause of ill health. Survival appears to be improving but the reasons for this are unclear. They could include evolving aetiology, modifications in care, improvements in treatment or changes in lifestyle behaviour. Observational studies are required to explore survival trends and identify outcome predictors. METHODS: We are identifying people with a new diagnosis of head and neck cancer. We obtain consent that includes agreement to collect longitudinal data, store samples and record linkage. Prior to treatment we give participants three questionnaires on health and lifestyle, quality of life and sexual history. We collect blood and saliva samples, complete a clinical data capture form and request a formalin fixed tissue sample. At four and twelve months we complete further data capture forms and send participants further quality of life questionnaires. DISCUSSION: This large clinical cohort of people with head and neck cancer brings together clinical data, patient-reported outcomes and biological samples in a single co-ordinated resource for translational and prognostic research.

The high-volume haemodiafiltration vs high-flux haemodialysis registry trial (H4RT): a multi-centre, unblinded, randomised, parallel-group, superiority study to compare the effectiveness and cost-effectiveness of high-volume haemodiafiltration and high-flux haemodialysis in people with kidney failure on maintenance dialysis using linkage to routine healthcare databases for outcomes.

BACKGROUND: More than a third of the 65,000 people living with kidney failure in the UK attend a dialysis unit 2-5 times a week to have their blood cleaned for 3-5 h. In haemodialysis (HD), toxins are removed by diffusion, which can be enhanced using a high-flux dialyser. This can be augmented with convection, as occurs in haemodiafiltration (HDF), and improved outcomes have been reported in people who are able to achieve high volumes of convection. This study compares the clinical- and cost-effectiveness of high-volume HDF compared with high-flux HD in the treatment of kidney failure. METHODS: This is a UK-based, multi-centre, non-blinded randomised controlled trial. Adult patients already receiving HD or HDF will be randomised 1:1 to high-volume HDF (aiming for 21+ L of substitution fluid adjusted for body surface area) or high-flux HD. Exclusion criteria include lack of capacity to consent, life expectancy less than 3 months, on HD/HDF for less than 4 weeks, planned living kidney donor transplant or home dialysis scheduled within 3 months, prior intolerance of HDF and not suitable for high-volume HDF for other clinical reasons. The primary outcome is a composite of non-cancer mortality or hospital admission with a cardiovascular event or infection during follow-up (minimum 32 months, maximum 91 months) determined from routine data. Secondary outcomes include all-cause mortality, cardiovascular- and infection-related morbidity and mortality, health-related quality of life, cost-effectiveness and environmental impact. Baseline data will be collected by research personnel on-site. Follow-up data will be collected by linkage to routine healthcare databases - Hospital Episode Statistics, Civil Registration, Public Health England and the UK Renal Registry (UKRR) in England, and equivalent databases in Scotland and Wales, as necessary - and centrally administered patient-completed questionnaires. In addition, research personnel on-site will monitor for adverse events and collect data on adherence to the protocol (monthly during recruitment and quarterly during follow-up). DISCUSSION: This study will provide evidence of the effectiveness and cost-effectiveness of HD as compared to HDF for adults with kidney failure in-centre HD or HDF. It will inform management for this patient group in the UK and internationally. TRIAL REGISTRATION: ISRCTN10997319 . Registered on 10 October 2017.

The feasibility and acceptability of an early intervention in primary care to prevent chronic fatigue syndrome (CFS) in adults: randomised controlled trial.

BACKGROUND: Chronic fatigue syndrome (CFS, also known as myalgic encephalomyelitis (ME)) is defined as fatigue that is disabling, is accompanied by additional symptoms and persists for ≥ 4 months. Treatment of CFS/ME aims to help patients manage their symptoms and make lifestyle adjustments. We do not know whether intervening early in primary care (< 4 months after onset of fatigue) can prevent the development of CFS/ME. METHODS: This was a feasibility randomised controlled trial with adults (age ≥ 18 years) comparing usual care with usual care plus an early intervention (EI; a combination of psycho-education and cognitive behavioural therapy, CBT). This study took place in fourteen primary care practices in Bristol, England and aimed to identify issues around recruitment and retention for a full-scale trial. It was not powered to support statistical analysis of differences in outcomes. Integrated qualitative methodology was used to explore the feasibility and acceptability of recruitment and randomisation to the intervention. RESULTS: Forty-four patients were recruited (1 August 2012-November 28, 2013), falling short of our predicted recruitment rate of 100 patients in 8 months. Qualitative data from GPs showed recruitment was not feasible because it was difficult to identify potential participants within 4 months of symptom onset. Some referring GPs felt screening investigations recommended by NICE were unnecessary, and they had difficulty finding patients who met the eligibility criteria. Qualitative data from some participant interviews suggested that the intervention was not acceptable in its current format. Although the majority of participants found parts of the intervention acceptable, many reported one or more problems with acceptability. Participants who discontinued the intervention or found it problematic did not relate to the therapeutic model, disliked telephone consultations or found self-reflection challenging. CONCLUSIONS: A randomised controlled trial to test an early intervention for fatigue in adults in primary care is not feasible using this intervention and recruitment strategy. TRIAL REGISTRATION: International Standard Randomised Controlled Trials, ISRCTN72645894. Retrospectively registered on 17 May 2013.

Factors associated with early postoperative feeding: An observational study in a colorectal surgery population.

BACKGROUND AND AIMS: Early post-operative feeding is recommended within enhanced recovery after surgery programmes. This study aimed to describe post-operative feeding patterns and associated factors among patients following colorectal surgery, using a post-hoc analysis of observational data from a previous RCT on chewing gum after surgery. METHODS: Data from 301 participants (59% male, median age 67 years) were included. Amounts of meals consumed on post-operative days (POD) 1-5 were recorded as: none, a quarter, half, three-quarters, all. 'Early' consumers were those who ate ≥a quarter of a meal on POD1. 'Early' tolerance was the consumption of at least half of three meals on POD1 or 2 without vomiting. Exploration of selected peri-operative factors with early feeding and tolerance were assessed using logistic regression. RESULTS: 222 people (73.8%) consumed solid food early, and 109 people (36.2%) tolerated solid food early. Several factors were associated with postoperative feeding: provision of pre-operative bowel preparation was associated with delayed consumption [odds ratio (OR) 0.34, 95% confidence interval (CI) 0.14-0.83] and tolerance (OR 0.35, 95% CI 0.16-0.81) of food; and laparoscopic/laparoscopic assisted (vs. open/converted to open surgery) was associated with early tolerance of food (OR 1.99, 95% CI 1.17-3.39). CONCLUSIONS: While three-quarters of the study population ate solid food early, only one-third tolerated solid food early. Findings suggest that bowel preparation and surgery type are factors warranting further investigation in future studies to improve uptake of early post-operative feeding.

Cost effectiveness of an intervention to increase uptake of hepatitis C virus testing and treatment (HepCATT): cluster randomised controlled trial in primary care.

OBJECTIVE: To evaluate the effectiveness and cost effectiveness of a complex intervention in primary care that aims to increase uptake of hepatitis C virus (HCV) case finding and treatment. DESIGN: Pragmatic, two armed, practice level, cluster randomised controlled trial and economic evaluation. SETTING AND PARTICIPANTS: 45 general practices in South West England (22 randomised to intervention and 23 to control arm). Outcome data were collected from all intervention practices and 21/23 control practices. Total number of flagged patients was 24 473 (about 5% of practice list). INTERVENTION: Electronic algorithm and flag on practice systems identifying patients with HCV risk markers (such as history of opioid dependence or HCV tests with no evidence of referral to hepatology), staff educational training in HCV, and practice posters/leaflets to increase patients' awareness. Flagged patients were invited by letter for an HCV test (with one follow-up) and had on-screen pop-ups to encourage opportunistic testing. The intervention lasted one year, with practices recruited April to December 2016. MAIN OUTCOME MEASURES: Primary outcome: uptake of HCV testing. SECONDARY OUTCOMES: number of positive HCV tests and yield (proportion HCV positive); HCV treatment assessment at hepatology; cost effectiveness. RESULTS: Baseline HCV testing of flagged patients (six months before study start) was 608/13 097 (4.6%) in intervention practices and 380/11 376 (3.3%) in control practices. During the study 2071 (16%) of flagged patients in the intervention practices and 1163 (10%) in control practices were tested for HCV: overall intervention effect as an adjusted rate ratio of 1.59 (95% confidence interval 1.21 to 2.08; P<0.001). HCV antibodies were detected in 129 patients from intervention practices and 51 patients from control practices (adjusted rate ratio 2.24, 1.47 to 3.42) with weak evidence of an increase in yield (6.2% v 4.4%; adjusted risk ratio 1.40, 0.99 to 1.95). Referral and assessment increased in intervention practices compared with control practices (adjusted rate ratio 5.78, 1.6 to 21.6) with a risk difference of 1.3 per 1000 and a "number needed to help" of one extra HCV diagnosis, referral, and assessment per 792 (95% confidence interval 558 to 1883) patients flagged. The average cost of HCV case finding was £4.03 (95% confidence interval £2.27 to £5.80) per at risk patient and £3165 per additional patient assessed at hepatology. The incremental cost effectiveness ratio was £6212 per quality adjusted life year (QALY), with 92.5% probability of being below £20 000 per QALY. CONCLUSION: HepCATT had a modest impact but is a low cost intervention that merits optimisation and implementation as part of an NHS strategy to increase HCV testing and treatment. TRIAL REGISTRATION: ISRCTN61788850.

Directly Acting Oral Anticoagulants for the Prevention of Stroke in Atrial Fibrillation in England and Wales: Cost-Effectiveness Model and Value of Information Analysis.

Objectives. Determine the optimal, licensed, first-line anticoagulant for prevention of ischemic stroke in patients with non-valvular atrial fibrillation (AF) in England and Wales from the UK National Health Service (NHS) perspective and estimate value to decision making of further research. Methods. We developed a cost-effectiveness model to compare warfarin (international normalized ratio target range 2-3) with directly acting (or non-vitamin K antagonist) oral anticoagulants (DOACs) apixaban 5 mg, dabigatran 150 mg, edoxaban 60 mg, and rivaroxaban 20 mg, over 30 years post treatment initiation. In addition to death, the 17-state Markov model included the events stroke, bleed, myocardial infarction, and intracranial hemorrhage. Input parameters were informed by systematic literature reviews and network meta-analysis. Expected value of perfect information (EVPI) and expected value of partial perfect information (EVPPI) were estimated to provide an upper bound on value of further research. Results. At willingness-to-pay threshold £20,000, all DOACs have positive expected incremental net benefit compared to warfarin, suggesting they are likely cost-effective. Apixaban has highest expected incremental net benefit (£7533), followed by dabigatran (£6365), rivaroxaban (£5279), and edoxaban (£5212). There was considerable uncertainty as to the optimal DOAC, with the probability apixaban has highest net benefit only 60%. Total estimated population EVPI was £17.94 million (17.85 million, 18.03 million), with relative effect between apixaban versus dabigatran making the largest contribution with EVPPI of £7.95 million (7.66 million, 8.24 million). Conclusions. At willingness-to-pay threshold £20,000, all DOACs have higher expected net benefit than warfarin but there is considerable uncertainty between the DOACs. Apixaban had the highest expected net benefit and greatest probability of having highest net benefit, but there is considerable uncertainty between DOACs. A head-to-head apixaban versus dabigatran trial may be of value.

Incidence of hypo- and hypercarbia in severe traumatic brain injury before and after 2003 pediatric guidelines.

OBJECTIVE: To examine the incidence of severe hypocarbia (PaCO2 <30 mm Hg) in patients with severe pediatric traumatic brain injury before and after publication of the 2003 pediatric guidelines (PG). DESIGN: Retrospective cohort analysis. SETTING: Harborview Medical Center, Seattle, Washington (January 1, 1995, to December 31, 2005). PATIENTS: Children <15 yrs of age with severe pediatric traumatic brain injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pre-PG group (before August 1, 2003) included 375 patients and the post-PG group included 89 patients. Post PG guidelines, there was a trend toward earlier (45 vs. 32 mins; p = .05) and more frequent (7.1 vs. 8.4 samples; p = .06) PaCO2 sampling within 48 hrs of admission. Children 0-2 yrs had a longer time (75.0 mins) between admission and first PaCO2 sample than older children (44.3 mins; p < .01). The youngest children also had the highest incidence of severe hypocarbia on the first PaCO2 sample (31% vs. 19%; p = .02). Incidence of severe hypocarbia was high and did not decline (60% vs. 52%; p = .2) after the PG guidelines. However, over the 11 yrs, the odds of severe hypocarbia decreased (adjusted odds ratio 0.9; 95% confidence interval 0.84-0.96). During both periods, the incidence of severe hypocarbia was highest during the first 2 hrs after hospital admission. Intracranial pressure monitors were used more frequently post-PG. In 62 of 82 (77%) patients with severe hypocarbia in whom an intracranial pressure monitor was in place, the preceding intracranial pressure was <20 mm Hg. Severe hypocarbia independently predicted inpatient mortality (adjusted odds ratio 2.8; 95% confidence interval 1.3-5.9). CONCLUSIONS: Although PaCO2 sampling was more frequent during the post-PG period and severe hypocarbia decreased during successive study years, the incidence of severe hypocarbia remained high during the first 48 hrs after hospital admission during the post-PG period. Time to PaCO2 sampling was longer in young children and associated with more severe hypocarbia. The presence of severe hypocarbia predicted mortality.

Screening strategies for atrial fibrillation: a systematic review and cost-effectiveness analysis.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of thromboembolic events. Anticoagulation therapy to prevent AF-related stroke has been shown to be cost-effective. A national screening programme for AF may prevent AF-related events, but would involve a substantial investment of NHS resources. OBJECTIVES: To conduct a systematic review of the diagnostic test accuracy (DTA) of screening tests for AF, update a systematic review of comparative studies evaluating screening strategies for AF, develop an economic model to compare the cost-effectiveness of different screening strategies and review observational studies of AF screening to provide inputs to the model. DESIGN: Systematic review, meta-analysis and cost-effectiveness analysis. SETTING: Primary care. PARTICIPANTS: Adults. INTERVENTION: Screening strategies, defined by screening test, age at initial and final screens, screening interval and format of screening {systematic opportunistic screening [individuals offered screening if they consult with their general practitioner (GP)] or systematic population screening (when all eligible individuals are invited to screening)}. MAIN OUTCOME MEASURES: Sensitivity, specificity and diagnostic odds ratios; the odds ratio of detecting new AF cases compared with no screening; and the mean incremental net benefit compared with no screening. REVIEW METHODS: Two reviewers screened the search results, extracted data and assessed the risk of bias. A DTA meta-analysis was perfomed, and a decision tree and Markov model was used to evaluate the cost-effectiveness of the screening strategies. RESULTS: Diagnostic test accuracy depended on the screening test and how it was interpreted. In general, the screening tests identified in our review had high sensitivity (> 0.9). Systematic population and systematic opportunistic screening strategies were found to be similarly effective, with an estimated 170 individuals needed to be screened to detect one additional AF case compared with no screening. Systematic opportunistic screening was more likely to be cost-effective than systematic population screening, as long as the uptake of opportunistic screening observed in randomised controlled trials translates to practice. Modified blood pressure monitors, photoplethysmography or nurse pulse palpation were more likely to be cost-effective than other screening tests. A screening strategy with an initial screening age of 65 years and repeated screens every 5 years until age 80 years was likely to be cost-effective, provided that compliance with treatment does not decline with increasing age. CONCLUSIONS: A national screening programme for AF is likely to represent a cost-effective use of resources. Systematic opportunistic screening is more likely to be cost-effective than systematic population screening. Nurse pulse palpation or modified blood pressure monitors would be appropriate screening tests, with confirmation by diagnostic 12-lead electrocardiography interpreted by a trained GP, with referral to a specialist in the case of an unclear diagnosis. Implementation strategies to operationalise uptake of systematic opportunistic screening in primary care should accompany any screening recommendations. LIMITATIONS: Many inputs for the economic model relied on a single trial [the Screening for Atrial Fibrillation in the Elderly (SAFE) study] and DTA results were based on a few studies at high risk of bias/of low applicability. FUTURE WORK: Comparative studies measuring long-term outcomes of screening strategies and DTA studies for new, emerging technologies and to replicate the results for photoplethysmography and GP interpretation of 12-lead electrocardiography in a screening population. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013739. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements. OBJECTIVE: To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE. DESIGN: Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials. SETTING: Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention). PARTICIPANTS: Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE). INTERVENTIONS: NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network. MAIN OUTCOME MEASURES: Efficacy Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness. DATA SOURCES: MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on 15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014. REVIEW METHODS: Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models. RESULTS: Apixaban (Eliquis®, Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana®, Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > £5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication. CONCLUSIONS: NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE. LIMITATIONS: These relate mainly to shortfalls in the primary data: in particular, there were no head-to-head comparisons between different NOAC drugs. FUTURE WORK: Calculating the expected value of sample information to clarify whether or not it would be justifiable to fund one or more head-to-head trials. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005324, CRD42013005331 and CRD42013005330. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The incidence and risk factors for hypotension during emergent decompressive craniotomy in children with traumatic brain injury.

We conducted a retrospective cohort study in children <13 yr with traumatic brain injury (TBI) at a Level 1 pediatric trauma center to describe risk factors for intraoperative hypotension (IH) during emergent decompressive craniotomy. Between 1994 and 2004, 108 children underwent emergent decompressive craniotomy for TBI. Overall, 56 (52%) patients had IH. Independent risk factors for IH were each 10 mL estimated blood loss/kg (ARR 1.15 95% CI 1.08-1.22), each mm of computed tomography (CT) midline shift (ARR 1.04 95%CI 1.01-1.07), each 10 mL of CT lesion volume (ARR 1.03 95%CI 1.01-1.05), and emergency department (ED) hypotension (5/5 patients with ED hypotension had IH). CT midline shift > or =4 mm predicted IH (ARR 1.67 95% CI 1.06-2.63), independent of blood loss. IH occurred frequently during emergent decompressive craniotomy in children with TBI. ED hypotension, blood loss, CT lesion volume, and CT midline shift predicted IH. Anesthesiologists can expect children with preoperative CT midline shift > or =4 mm to have IH during this procedure.

Comparing specialist medical care with specialist medical care plus the Lightning Process for chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME): study protocol for a randomised controlled trial (SMILE Trial).

BACKGROUND: Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and potentially serious condition with a limited evidence base for treatment. Specialist treatment for paediatric CFS/ME uses interventions recommended by National Institute for Health and Clinical Excellence (NICE) including cognitive behavioural therapy, graded exercise therapy and activity management. The Lightning Process (LP) is a trademarked intervention derived from osteopathy, life-coaching and neuro-linguistic programming, delivered over three consecutive days as group sessions. Although over 250 children with CFS/ME attend LP courses each year, there are no reported studies on the effectiveness or cost-effectiveness. METHODS: This pragmatic randomised controlled trial is set within a specialist paediatric CFS/ME service in the south west of England. Children and young people with CFS/ME (n = 80 to 112), aged 12 to 18 years old will be randomised to specialist medical care (SMC) or SMC plus the LP. The primary outcome will be physical function (SF-36 physical function short form) and fatigue (Chalder Fatigue Scale). DISCUSSION: This study will tell us whether adding the LP to SMC is effective and cost-effective compared to SMC alone. This study will also provide detailed information on the implementation of the LP and SMC. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81456207 (31 July 2012).

What is the most cost-effective treatment for 1 to 2-cm bulbar urethral strictures: societal approach using decision analysis.

OBJECTIVES: Direct vision internal urethrotomy (DVIU) and urethroplasty are the primary methods of managing urethral stricture disease. Using decision analysis, we determine the cost-effectiveness of different management strategies for short, bulbar urethral strictures 1 to 2 cm in length. METHODS: A decision tree was constructed, with the number of planned possible DVIUs before attempting urethroplasty defined for each primary branch point. Success rates were obtained from published reports. Costs were estimated from a societal perspective and included the costs of the procedures and office visits and lost wages from convalescence. Sensitivity analyses were conducted, varying the success rates of the procedures and cost estimates. RESULTS: The most cost-effective approach was one DVIU before urethroplasty. The incremental cost of performing a second DVIU before attempting urethroplasty was $141,962 for each additional successfully voiding patient. In the sensitivity analysis, urethroplasty as the primary therapy was cost-effective only when the expected success rate of the first DVIU was less than 35%. CONCLUSIONS: The most cost-effective strategy for the management of short, bulbar urethral strictures is to reserve urethroplasty for patients in whom a single endoscopic attempt fails. For longer strictures for which the success rate of DVIU is expected to be less than 35%, urethroplasty as primary therapy is cost-effective. Future prospective, multicenter studies of DVIU and urethroplasty outcomes would help enhance the accuracy of our model.