New horizons in frailty identification via electronic frailty indices: early implementation lessons from experiences in England and the United States.

Frailty represents an integrative prognostic marker of risk that associates with a myriad of age-related adverse outcomes in older adults. As a concept, frailty can help to target scarce resources and identify subgroups of vulnerable older adults that may benefit from interventions or changes in medical management, such as pursing less aggressive glycaemic targets for frail older adults with diabetes. In practice, however, there are several operational challenges to implementing frailty screening outside the confines of geriatric medicine. Electronic frailty indices (eFIs) based on the theory of deficit accumulation, derived from routine data housed in the electronic health record, have emerged as a rapid, feasible and valid approach to screen for frailty at scale. The goal of this paper is to describe the early experience of three diverse groups in developing, implementing and adopting eFIs (The English National Health Service, US Department of Veterans Affairs and Atrium Health-Wake Forest Baptist). These groups span different countries and organisational complexity, using eFIs for both research and clinical care, and represent different levels of progress with clinical implementation. Using an implementation science framework, we describe common elements of successful implementation in these settings and set an agenda for future research and expansion of eFI-informed initiatives.

The prevalence of mental health conditions in healthcare workers during and after a pandemic: Systematic review and meta-analysis.

AIMS: This review aims to explore the prevalence and incidence rates of mental health conditions in healthcare workers during and after a pandemic outbreak and which factors influence rates. BACKGROUND: Pandemics place considerable burden on care services, impacting on workers' health and their ability to deliver services. We systematically reviewed the prevalence and incidence of mental health conditions in care workers during pandemics. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Searches of MEDLINE, Embase, Cochrane Library and PsychINFO for cohort, cross-sectional and case-control studies were undertaken on the 31 March 2020 (from inception to 31 March 2020). REVIEW METHODS: Only prevalence or incidence rates for mental health conditions from validated tools were included. Study selection, data extraction and quality assessment were carried out by two reviewers. Meta-analyses and subgroup analyses were produced for pandemic period (pre- and post), age, country income, country, clinical setting for major depression disorder (MDD), anxiety disorder and post-traumatic stress disorder (PTSD). RESULTS: No studies of incidence were found. Prevalence estimates showed that the most common mental health condition was PTSD (21.7%) followed by anxiety disorder (16.1%), MDD (13.4%) and acute stress disorder (7.4%) (low risk of bias). For symptoms of these conditions there was substantial variation in the prevalence estimates for depression (95% confidence interval [CI]:31.8%; 60.5%), anxiety (95% CI:34.2%; 57.7%) and PTSD symptoms (95% CI,21.4%; 65.4%) (moderate risk of bias). Age, level of exposure and type of care professional were identified as important moderating factors. CONCLUSION: Mental disorders affect healthcare workers during and after infectious disease pandemics, with higher proportions experiencing symptoms. IMPACT: This review provides prevalence estimates of mental health conditions during and after a pandemic which could be used to inform service staffing impact and formulation of preventative strategies, by identifying clinical populations who may be at high risk of developing mental health symptoms and conditions.

The effectiveness of quality improvement collaboratives in improving stroke care and the facilitators and barriers to their implementation: a systematic review.

BACKGROUND: To successfully reduce the negative impacts of stroke, high-quality health and care practices are needed across the entire stroke care pathway. These practices are not always shared across organisations. Quality improvement collaboratives (QICs) offer a unique opportunity for key stakeholders from different organisations to share, learn and 'take home' best practice examples, to support local improvement efforts. This systematic review assessed the effectiveness of QICs in improving stroke care and explored the facilitators and barriers to implementing this approach. METHODS: Five electronic databases (MEDLINE, CINAHL, EMBASE, PsycINFO, and Cochrane Library) were searched up to June 2020, and reference lists of included studies and relevant reviews were screened. Studies conducted in an adult stroke care setting, which involved multi-professional stroke teams participating in a QIC, were included. Data was extracted by one reviewer and checked by a second. For overall effectiveness, a vote-counting method was used. Data regarding facilitators and barriers was extracted and mapped to the Consolidated Framework for Implementation Research (CFIR). RESULTS: Twenty papers describing twelve QICs used in stroke care were included. QICs varied in their setting, part of the stroke care pathway, and their improvement focus. QIC participation was associated with improvements in clinical processes, but improvements in patient and other outcomes were limited. Key facilitators were inter- and intra-organisational networking, feedback mechanisms, leadership engagement, and access to best practice examples. Key barriers were structural changes during the QIC's active period, lack of organisational support or prioritisation of QIC activities, and insufficient time and resources to participate in QIC activities. Patient and carer involvement, and health inequalities, were rarely considered. CONCLUSIONS: QICs are associated with improving clinical processes in stroke care; however, their short-term nature means uncertainty remains as to whether they benefit patient outcomes. Evidence around using a QIC to achieve system-level change in stroke is equivocal. QIC implementation can be influenced by individual and organisational level factors, and future efforts to improve stroke care using a QIC should be informed by the facilitators and barriers identified. Future research is needed to explore the sustainability of improvements when QIC support is withdrawn. TRIAL REGISTRATION: Protocol registered on PROSPERO ( CRD42020193966 ).

The effectiveness of psychological support interventions for those exposed to mass infectious disease outbreaks: a systematic review.

BACKGROUND: Mass outbreaks such as pandemics are associated with mental health problems requiring effective psychological interventions. Although several forms of psychological interventions may be advocated or used, some may lack strong evidence of efficacy and some may not have been evaluated in mass infectious disease outbreaks. This paper reports a systematic review of published studies (PROSPERO CRD:42020182094. Registered: 24.04.2020) examining the types and effectiveness of psychological support interventions for the general population and healthcare workers exposed to mass infectious disease outbreaks. METHODS: A systematic review was conducted. Randomised Controlled Trials (RCT) were identified through searches of electronic databases: Medline (Ovid), Embase (Ovid), PsycINFO (EBSCO) and the Cochrane Library Database from inception to 06.05.2021 using an agreed search strategy. Studies were included if they assessed the effectiveness of interventions providing psychological support to the general population and / or healthcare workers exposed to mass infectious disease outbreaks. Studies were excluded if they focused on man-made or natural disasters or if they included armed forces, police, fire-fighters or coastguards. RESULTS: Twenty-two RCTs were included after screening. Various psychological interventions have been used: therapist-guided therapy (n = 1); online counselling (n = 1); 'Emotional Freedom Techniques' (n = 1); mobile phone apps (n = 2); brief crisis intervention (n = 1); psychological-behavioural intervention (n = 1); Cognitive Behavioural Therapy (n = 3); progressive muscle relaxation (n = 2); emotional-based directed drawing (n = 1); psycho-educational debriefing (n = 1); guided imagery (n = 1); Eye Movement Desensitization and Reprocessing (EMDR) (n = 1); expressive writing (n = 2); tailored intervention for patients with a chronic medical conditions (n = 1); community health workers (n = 1); self-guided psychological intervention (n = 1), and a digital behaviour change intervention (n = 1). Meta-analyses showed that psychological interventions had a statistically significant benefit in managing depression (Standardised Mean Difference [SMD]: -0.40; 95% Confidence Interval [CI]: - 0.76 to - 0.03), and anxiety (SMD: -0.72; 95% CI: - 1.03 to - 0.40). The effect on stress was equivocal (SMD: 0.16; 95% CI: - 0.19 to 0.51). The heterogeneity of studies, studies' high risk of bias, and the lack of available evidence means uncertainty remains. CONCLUSIONS: Further RCTs and intervention studies involving representative study populations are needed to inform the development of targeted and tailored psychological interventions for those exposed to mass infectious disease outbreaks.

Systematic Review and Meta-Analysis of the Effectiveness of Mental Practice for the Upper Limb After Stroke: Imagined or Real Benefit?

OBJECTIVES: This systematic review sought to determine the effectiveness of mental practice (MP) on the activity limitations of the upper limb in individuals after stroke, as well as when, in whom, and how MP should be delivered. DATA SOURCES: Ten electronic databases were searched from November 2009 to May 2020. Search terms included: Arm, Practice, Stroke rehabilitation, Imagination, Paresis, Recovery of function, and Stroke. Studies from a Cochrane review of MP (up to November 2009) were automatically included. The review was registered with the PROSPERO database of systematic reviews (reference no.: CRD42019126044). STUDY SELECTION: Randomized controlled trials of adults after stroke using MP for the upper limb were included if they compared MP to usual care, conventional therapy, or no treatment and reported activity limitations of the upper limb as outcomes. Independent screening was conducted by 2 reviewers. DATA EXTRACTION: One reviewer extracted data using a tool based on the Template for Intervention Description and Replication. Data extraction was independently verified by a second reviewer. Quality was assessed using the PEDro tool. DATA SYNTHESIS: Fifteen studies (n=486) were included and 12 (n=328) underwent meta-analysis. MP demonstrated significant benefit on upper limb activities compared with usual treatment (standardized mean difference [SMD], 0.6; 95% confidence interval [CI], 0.32-0.88). Subgroup analyses demonstrated that MP was most effective in the first 3 months after stroke (SMD, 1.01; 95% CI, 0.53-1.50) and in individuals with the most severe upper limb deficits (weighted mean difference, 7.33; 95% CI, 0.94-13.72). CONCLUSIONS: This review demonstrates that MP is effective in reducing activity limitations of the upper limb after stroke, particularly in the first 3 months after stroke and in individuals with the most severe upper limb dysfunction. There was no clear pattern of the ideal dosage of MP.

Barriers and facilitators to deprescribing in primary care: a systematic review.

BACKGROUND: Managing polypharmacy is a challenge for healthcare systems globally. It is also a health inequality concern as it can expose some of the most vulnerable in society to unnecessary medications and adverse drug-related events. Care for most patients with multimorbidity and polypharmacy occurs in primary care. Safe deprescribing interventions can reduce exposure to inappropriate polypharmacy. However, these are not fully accepted or routinely implemented. AIM: To identify barriers and facilitators to safe deprescribing interventions for adults with multimorbidity and polypharmacy in primary care. DESIGN & SETTING: A systematic review of studies published from 2000, examining safe deprescribing interventions for adults with multimorbidity and polypharmacy. METHOD: A search of electronic databases: MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature (CINHAL), Cochrane, and Health Management Information Consortium (HMIC) from inception to 26 Feb 2019, using an agreed search strategy. This was supplemented by handsearching of relevant journals, and screening of reference lists and citations of included studies. RESULTS: In total, 40 studies from 14 countries were identified. Cultural and organisational barriers included: a culture of diagnosing and prescribing; evidence-based guidance focused on single diseases; a lack of evidence-based guidance for the care of older people with multimorbidities; and a lack of shared communication, decision-making systems, tools, and resources. Interpersonal and individual-level barriers included: professional etiquette; fragmented care; prescribers' and patients' uncertainties; and gaps in tailored support. Facilitators included: prudent prescribing; greater availability and acceptability of non-pharmacological alternatives; resources; improved communication, collaboration, knowledge, and understanding; patient-centred care; and shared decision-making. CONCLUSION: A whole systems, patient-centred approach to safe deprescribing interventions is required, involving key decision-makers, healthcare professionals, patients, and carers.

The effectiveness of continuous quality improvement for developing professional practice and improving health care outcomes: a systematic review.

BACKGROUND: Efforts to improve the quality, safety, and efficiency of health care provision have often focused on changing approaches to the way services are organized and delivered. Continuous quality improvement (CQI), an approach used extensively in industrial and manufacturing sectors, has been used in the health sector. Despite the attention given to CQI, uncertainties remain as to its effectiveness given the complex and diverse nature of health systems. This review assesses the effectiveness of CQI across different health care settings, investigating the importance of different components of the approach. METHODS: We searched 11 electronic databases: MEDLINE, CINAHL, EMBASE, AMED, Academic Search Complete, HMIC, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, LISTA, and NHS EED to February 2019. Also, we searched reference lists of included studies and systematic reviews, as well as checking published protocols for linked papers. We selected randomized controlled trials (RCTs) within health care settings involving teams of health professionals, evaluating the effectiveness of CQI. Comparators included current usual practice or different strategies to manage organizational change. Outcomes were health care professional performance or patient outcomes. Studies were published in English. RESULTS: Twenty-eight RCTs assessed the effectiveness of different approaches to CQI with a non-CQI comparator in various settings, with interventions differing in terms of the approaches used, their duration, meetings held, people involved, and training provided. All RCTs were considered at risk of bias, undermining their results. Findings suggested that the benefits of CQI compared to a non-CQI comparator on clinical process, patient, and other outcomes were limited, with less than half of RCTs showing any effect. Where benefits were evident, it was usually on clinical process measures, with the model used (i.e., Plan-Do-Study-Act, Model of Improvement), the meeting type (i.e., involving leaders discussing implementation) and their frequency (i.e., weekly) having an effect. None considered socio-economic health inequalities. CONCLUSIONS: Current evidence suggests the benefits of CQI in improving health care are uncertain, reflecting both the poor quality of evaluations and the complexities of health services themselves. Further mixed-methods evaluations are needed to understand how the health service can use this proven approach. TRIAL REGISTRATION: Protocol registered on PROSPERO (CRD42018088309).

Etiologic Workup in Cases of Cryptogenic Stroke: A Systematic Review of International Clinical Practice Guidelines.

Background and Purpose- Identifying the etiology of acute ischemic stroke is essential for effective secondary prevention. However, in at least one third of ischemic strokes, existing investigative protocols fail to determine the underlying cause. Establishing etiology is complicated by variation in clinical practice, often reflecting preferences of treating clinicians and variable availability of investigative techniques. In this review, we systematically assess the extent to which there exists consensus, disagreement, and gaps in clinical practice recommendations on etiologic workup in acute ischemic stroke. Methods- We identified clinical practice guidelines/consensus statements through searches of 4 electronic databases and hand-searching of websites/reference lists. Two reviewers independently assessed reports for eligibility. We extracted data on report characteristics and recommendations relating to etiologic workup in acute ischemic stroke and in cases of cryptogenic stroke. Quality was assessed using the AGREE II tool (Appraisal of Guidelines for Research & Evaluation). Recommendations were synthesized according to a published algorithm for diagnostic evaluation in cryptogenic stroke. Results- We retrieved 16 clinical practice guidelines and 7 consensus statements addressing acute stroke management (n=12), atrial fibrillation (n=5), imaging (n=5), and secondary prevention (n=1). Five reports were of overall high quality. For all patients, guidelines recommended routine brain imaging, noninvasive vascular imaging, a 12-lead ECG, and routine blood tests/laboratory investigations. Additionally, ECG monitoring (>24 hours) was recommended for patients with suspected embolic stroke and echocardiography for patients with suspected cardiac source. Three reports recommended investigations for rarer causes of stroke. None of the reports provided guidance on the extent of investigation needed before classifying a stroke as cryptogenic. Conclusions- While consensus exists surrounding standard etiologic workup, there is little agreement on more advanced investigations for rarer causes of acute ischemic stroke. This gap in guidance, and in the underpinning evidence, demonstrates missed opportunities to better understand and protect against ongoing stroke risk. Registration- URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019127822.

Etiologic workup in cases of cryptogenic stroke: protocol for a systematic review and comparison of international clinical practice guidelines.

BACKGROUND: Stroke is a leading cause of death and disability worldwide. Identifying the aetiology of ischaemic stroke is essential in order to initiate appropriate and timely secondary prevention measures to reduce the risk of recurrence. For the majority of ischaemic strokes, the aetiology can be readily identified, but in at least 30% of cases, the exact aetiology cannot be determined using existing investigative protocols. Such strokes are classed as 'cryptogenic' or as a stroke of unknown origin. However, there exists substantial variation in clinical practice when investigating cases of seemingly cryptogenic stroke, often reflecting local service availability and the preferences of treating clinicians. This variation in practice is compounded by the lack of international consensus as to the optimum level and timing of investigations required following a stroke. To address this gap, we aim to systematically review and compare recommendations in evidence-based clinical practice guidelines (CPGs) that relate to the assessment and investigation of the aetiology of ischaemic stroke, and any subsequent diagnosis of cryptogenic stroke. METHOD: We will search for CPGs using electronic databases (MEDLINE, Health Management Information Consortium (HMIC), EMBASE, and CINAHL), relevant websites and search engines (e.g. guideline specific websites, governmental, charitable, and professional practice organisations) and hand-searching of bibliographies and reference lists. Two reviewers will independently screen titles, abstracts and CPGs using a pre-defined relevance criteria form. From each included CPG, we will extract definitions and terms for cryptogenic stroke; recommendations related to assessment and investigation of the aetiology of stroke, including the grade of recommendations and underpinning evidence. The quality of the included CPGs will be assessed using the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. Recommendations across the CPGs will be summarised descriptively highlighting areas of convergence and divergence between CPGs. DISCUSSION: To our knowledge, this will be the first review to systematically compare recommendations of international CPGs on investigating the aetiology of ischaemic stroke. The findings will allow for a better understanding of international perspectives on the optimum level of investigations required following a stroke and thus contribute to achieving greater international consensus on best practice in this important and complex area. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019127822.

Comparing new treatments for idiopathic pulmonary fibrosis--a network meta-analysis.

BACKGROUND: The treatment landscape for idiopathic pulmonary fibrosis, a devastating lung disease, is changing. To investigate the effectiveness of treatments for idiopathic pulmonary fibrosis we undertook a systematic review, network meta-analysis and indirect comparison. METHODS: We searched MEDLINE, EMBASE and The Cochrane library for relevant studies. Randomised controlled trials of pirfenidone, nintedanib or N-acetylcysteine were eligible. Predefined processes for selecting references, extracting data and assessing study quality were applied. Our network meta-analysis of published data used a fixed effect model. For forced vital capacity measures a standardised mean difference approach was used and converted to odds ratios for interpretation. RESULTS: Of 1076 references, 67 were retrieved and 11 studies included. Studies were of reasonable size, populations were similar, and the overall quality was good. Only two treatments, pirfenidone (odds ratio 0.62, 95% credible interval 0.52, 0.74) and nintedanib (0.41, 95% credible interval 0.34, 0.51) produced a statistically significant slowing in the rate of forced vital capacity decline compared with placebo. In an indirect comparison, results indicate that nintedanib is statistically significantly better than pirfenidone in slowing forced vital capacity decline (odds ratio 0.67, 95% credible interval 0.51, 0.88). Results were stable in scenario analysis and random effects models. Indirect comparisons of mortality were not statistically significant between nintedanib and pirfenidone. CONCLUSIONS: Two treatments show beneficial effects and when compared indirectly nintedanib appears to have superior benefit on forced vital capacity. Limitations to indirect comparisons should be considered when interpreting these results, however, our findings can be useful to inform treatment decisions.

Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation.

BACKGROUND: This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF). OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions. DATA SOURCES: Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers' submissions to the National Institute for Health and Care Excellence. REVIEW METHODS: Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon. RESULTS: A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY. LIMITATIONS: Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups. CONCLUSIONS: In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony. STUDY REGISTRATION: This study is registered as PROSPERO number CRD42012002062. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The clinical effectiveness and cost-effectiveness of ablative therapies in the management of liver metastases: systematic review and economic evaluation.

BACKGROUND: Many deaths from cancer are caused by metastatic burden. Prognosis and survival rates vary, but survival beyond 5 years of patients with untreated metastatic disease in the liver is rare. Treatment for liver metastases has largely been surgical resection, but this is feasible in only approximately 20-30% of people. Non-surgical alternatives to treat some liver metastases can include various forms of ablative therapies and other targeted treatments. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of the different ablative and minimally invasive therapies for treating liver metastases. DATA SOURCES: Electronic databases including MEDLINE, EMBASE and The Cochrane Library were searched from 1990 to September 2011. Experts were consulted and bibliographies checked. REVIEW METHODS: Systematic reviews of the literature were undertaken to appraise the clinical effectiveness and cost-effectiveness of ablative therapies and minimally invasive therapies used for people with liver metastases. Studies were any prospective study with sample size greater than 100 participants. A probabilistic model was developed for the economic evaluation of the technologies where data permitted. RESULTS: The evidence assessing the clinical effectiveness and cost-effectiveness of ablative and other minimally invasive therapies was limited. Nine studies of ablative therapies were included in the review; each had methodological shortcomings and few had a comparator group. One randomised controlled trial (RCT) of microwave ablation versus surgical resection was identified and showed no improvement in outcomes compared with resection. In two prospective case series studies that investigated the use of laser ablation, mean survival ranged from 41 to 58 months. One cohort study compared radiofrequency ablation with surgical resection and five case series studies also investigated the use of radiofrequency ablation. Across these studies the median survival ranged from 44 to 52 months. Seven studies of minimally invasive therapies were included in the review. Two RCTs compared chemoembolisation with chemotherapy only. Overall survival was not compared between groups and methodological shortcomings mean that conclusions are difficult to make. Two case series studies of laser ablation following chemoembolisation were also included; however, these provide little evidence of the use of these technologies in combination. Three RCTs of radioembolisation were included. Significant improvements in tumour response and time to disease progression were demonstrated; however, benefits in terms of survival were equivocal. An exploratory survival model was developed using data from the review of clinical effectiveness. The model includes separate analyses of microwave ablation compared with surgery and radiofrequency ablation compared with surgery and one of radioembolisation in conjunction with hepatic artery chemotherapy compared with hepatic artery chemotherapy alone. Microwave ablation was associated with an incremental cost-effectiveness ratio (ICER) of £3664 per quality-adjusted life-year (QALY) gained, with microwave ablation being associated with reduced cost but also with poorer outcome than surgery. Radiofrequency ablation compared with surgical resection for solitary metastases < 3 cm was associated with an ICER of -£266,767 per QALY gained, indicating that radiofrequency ablation dominates surgical resection. Radiofrequency ablation compared with surgical resection for solitary metastases ≥ 3 cm resulted in poorer outcomes at lower costs and a resultant ICER of £2538 per QALY gained. Radioembolisation plus hepatic artery chemotherapy compared with hepatic artery chemotherapy was associated with an ICER of £37,303 per QALY gained. CONCLUSIONS: There is currently limited high-quality research evidence upon which to base any firm decisions regarding ablative therapies for liver metastases. Further trials should compare ablative therapies with surgery, in particular. A RCT would provide the most appropriate design for undertaking any further evaluation and should include a full economic evaluation, but the group to be randomised needs careful selection. SOURCE OF FUNDING: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.

Weight loss surgery for mild to moderate obesity: a systematic review and economic evaluation.

BACKGROUND: A systematic review and economic evaluation was commissioned to determine the effectiveness and cost-effectiveness of bariatric surgery for mild [class I, body mass index (BMI) 30 to 34.99] or moderate (class II, BMI 35 to 39.99) obesity. METHODS: We searched 17 electronic resources (to February 2010) and other sources. Studies meeting predefined criteria were identified, data-extracted and assessed for risk of bias using standard methodology. A model was developed to estimate cost-effectiveness. RESULTS: Two RCTs were included. Evidence from both indicated a statistically significant benefit from laparoscopic adjustable banding (LAGB) compared to a non-surgical comparator for weight loss and in obesity-related comorbidity. Both interventions were associated with adverse events. LAGB costs more than non-surgical management. For people with class I or II obesity and type 2 diabetes (T2D), the incremental cost-effectiveness ratio (ICER) at 2 years is £20,159, reducing to £4,969 at 5 years and £1,634 at 20 years. Resolution of T2D makes the greatest contribution to this reduction. In people with class I obesity, the ICER is £63,156 at 2 years, £17,158 at 5 years, and £13,701 at 20 years. Cost-effectiveness results are particularly sensitive to utility gain from reduction in BMI, factors associated with poorer surgical performance and diabetes health state costs. CONCLUSIONS: Bariatric surgery appears to be a clinically effective and cost-effective intervention for people with class I or II obesity who also have T2D but is less likely to be cost-effective for people with class I obesity.

Surgery for obesity.

BACKGROUND: Bariatric (weight loss) surgery for obesity is considered when other treatments have failed. The effects of the available bariatric procedures compared with medical management and with each other are uncertain. This is an update of a Cochrane review first published in 2003 and previously updated in 2005. OBJECTIVES: To assess the effects of bariatric surgery for obesity. SEARCH STRATEGY: Studies were obtained from computerized searches of multiple electronic bibliographic databases, supplemented with searches of reference lists and consultation with experts in obesity research. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing different surgical procedures, and RCTs, controlled clinical trials and prospective cohort studies comparing surgery with non-surgical management for obesity. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked independently by two reviewers. Two reviewers independently assessed trial quality. MAIN RESULTS: Twenty six studies were included. Three RCTs and three prospective cohort studies compared surgery with non-surgical management, and 20 RCTs compared different bariatric procedures. The risk of bias of many trials was uncertain; just five had adequate allocation concealment. A meta-analysis was not appropriate.Surgery results in greater weight loss than conventional treatment in moderate (body mass index greater than 30) as well as severe obesity. Reductions in comorbidities, such as diabetes and hypertension, also occur. Improvements in health-related quality of life occurred after two years, but effects at ten years are less clear.Surgery is associated with complications, such as pulmonary embolism, and some postoperative deaths occurred.Five different bariatric procedures were assessed, but some comparisons were assessed by just one trial. The limited evidence suggests that weight loss following gastric bypass is greater than vertical banded gastroplasty or adjustable gastric banding, but similar to isolated sleeve gastrectomy and banded gastric bypass. Isolated sleeve gastrectomy appears to result in greater weight loss than adjustable gastric banding. Evidence comparing vertical banded gastroplasty with adjustable gastric banding is inconclusive. Data on the comparative safety of the bariatric procedures was limited.Weight loss and quality of life were similar between open and laparoscopic surgery. Conversion from laparoscopic to open surgery may occur. AUTHORS' CONCLUSIONS: Surgery is more effective than conventional management. Certain procedures produce greater weight loss, but data are limited. The evidence on safety is even less clear. Due to limited evidence and poor quality of the trials, caution is required when interpreting comparative safety and effectiveness.

Cost-effectiveness of left ventricular-assist devices in end-stage heart failure.

With a limited supply of donor hearts, individuals with end-stage heart failure have been offered hope through the use of mechanical devices. Left ventricular-assist devices (LVADs) are a technology designed to work in parallel with the heart but have yet to see widespread use since uncertainty remains as to the cost-effectiveness of this evolving new technology. We have systematically reviewed evidence of cost-effectiveness for LVADs in the bridge-to-transplant and long-term chronic support indications. A total of 18 studies reporting costs were identified. Of these, only four studies reported results in cost-effectiveness terms; two in cost per life-year saved and two in cost per quality-adjusted life-year (QALY). The majority of the other studies were simple cost summations (cost per day or incremental cost) without consideration of efficacy. In the bridge-to-transplant indication, a Danish abstract reported a cost per life-year saved of DKK270k (US$48,000), a UK study reported a cost per QALY of GB pound39,787 (US$78,000) and a Canadian study reported a cost per life-year saved of Can$91,332 (US$86,000). Regarding the long-term chronic support indication, the same Canadian study reported a cost per life-year saved of Can$59,842 (US$56,000), whereas a US study reported a cost per QALY of $36,255-60,057. Assuming a willingness to pay the threshold of GB pound30,000 (US$59,000) per QALY, there is arguably stronger evidence to support the cost-effectiveness of LVAD technology for the long-term chronic support indication. However, the methodological quality of the majority of studies was poor, as was their generalizability, raising concerns over the reliability of these figures. With the limited and declining availability of donor hearts for transplantation, it appears that the future of this technology is in its use as long-term chronic support. Further analyses should be undertaken, particularly alongside randomized, controlled trials and utilizing second- and third-generation devices.

Clinical and cost-effectiveness of left ventricular assist devices as destination therapy for people with end-stage heart failure: a systematic review and economic evaluation.

OBJECTIVES: The clinical and cost-effectiveness of left ventricular assist devices as destination therapy for people with end-stage heart failure is assessed through a systematic review and economic evaluation. METHODS: Systematic review was performed of randomized controlled trials, quasiexperimental studies, case series, and case studies identified through searching eighteen electronic databases, bibliographies, and consultation with experts and manufacturers. Studies assessed survival, functional capacity, and quality of life. Cost-effectiveness was assessed through a 5-year decision analytic model to estimate the incremental cost-effectiveness ratio for using left ventricular assist devices compared with usual care. RESULTS: Six studies met the inclusion criteria, showing that left ventricular assist devices appear beneficial, improving survival and quality of life. Adverse events are a serious concern. The economic evaluation showed that left ventricular assist devices had a cost per quality adjusted life year of 170,616 pounds. Sensitivity analysis showed that the cost-effectiveness was not sensitive to changes in costs or utility. CONCLUSIONS: Although left ventricular assist devices appear clinically effective as destination therapy, it is unlikely they will be cost-effective unless costs decrease or the benefits of their use increase.

Clinical and cost-effectiveness of left ventricular assist devices as a bridge to heart transplantation for people with end-stage heart failure: a systematic review and economic evaluation.

AIMS: To evaluate the clinical and cost-effectiveness of left ventricular (LV) assist devices (LVADs) as a bridge to transplant (BTT) for people with end-stage heart failure (ESHF) through a systematic review and economic evaluation. METHODS AND RESULTS: The systematic review and economic evaluation was conducted according to internationally recognized methods. The search strategy identified systematic reviews, randomized controlled trials, quasi-experimental studies, and observational studies evaluating the effects of LVADs on survival, functional capacity, and quality of life. Cost-effectiveness was assessed through a 5-year decision analytic model to estimate the incremental cost-effectiveness ratio of LVADs compared with usual care. Despite the poor methodological quality of the 18 studies included, LVADs appear beneficial improving survival, functional status, and quality of life. Adverse events are a serious concern. The economic evaluation showed that LVADs had a cost per quality adjusted life year of pound 65,242 (95% confidence interval pound 34,194-364,564). Sensitivity analysis showed that post-heart transplant survival gains, pre-heart transplant patient utility, and one-off costs associated with implantation determine cost-effectiveness. CONCLUSION: Although LVADs appear clinically effective as a BTT for people with ESHF, it is unlikely that they will be cost-effective unless costs decrease or the benefits of their use increase.

A case-control study of childhood environmental risk factors for the development of inflammatory bowel disease.

OBJECTIVE: To clarify the relationship between childhood environment and the risk of subsequent development of Crohn's disease or ulcerative colitis. DESIGN AND OUTCOME MEASURES: A case-control study, assessing the risk of inflammatory bowel disease in relation to a series of historical and serological markers of childhood circumstance, analysed using the maximum likelihood form of conditional logistic regression. SETTING: District general hospital (secondary care institution). PARTICIPANTS: Subjects with Crohn's disease (n = 139) or ulcerative colitis (n = 137) aged between 16 and 45 years, each matched for sex and age with an outpatient control. RESULTS: Helicobacter seroprevalence was substantially reduced in Crohn's disease (OR 0.18; 95% CI, 0.06-0.52) but not in ulcerative colitis (OR 0.91; 95% CI, 0.38-2.16). In ulcerative colitis, a strong negative association with childhood appendectomy was confirmed (OR 0.05; 95% CI, 0.01-0.51). Crohn's disease was associated with childhood eczema (OR 2.81; 95% CI, 1.23-6.42) and the frequent use of a swimming pool (OR 2.90; 95% CI 1.21-6.91). There was no association between hepatitis A seroprevalence and either disease. CONCLUSION: The findings are consistent with the hypothesis that improved childhood living conditions are associated with increased risk of Crohn's disease. The study confirms that the negative association between appendectomy and ulcerative colitis relates primarily to events in childhood. Overall, the findings strongly support the assertion that childhood environment is an important determinant of the risk of inflammatory bowel disease in later life, with quite distinct risk factors for ulcerative colitis and Crohn's disease.