Review Of Appraisal Research Articles

Identifying Molecular Biomarkers in Attention-Deficit/Hyperactivity Disorder (ADHD) – a Systematic Review of Literature and Appraisal of Evidence

Identifying Molecular Biomarkers in Attention-Deficit/Hyperactivity Disorder (ADHD) – a Systematic Review of Literature and Appraisal of Evidence

Impact of the COVID-19 pandemic on employment and inequalities: a systematic review of international evidence and critical appraisal of statistical methods.

To assess the impact of the COVID-19 pandemic on individual labour market outcomes and how these vary over time and between different groups of individuals. Searches were conducted using Medline, Scopus and EconLit. Grey literature searches used Google Scholar and Econpapers. Study quality was assessed using the risk of bias in non-randomised studies of exposure tool (ROBINS-E), accompanied by a directed acyclic graph (DAG) to identify relevant mediators, moderators and confounders. A total of 85 studies (77 peer-reviewed articles, 8 working papers) were included. The ROBINS-E showed that the overall risk of bias varied between studies from low (n = 14), moderate (n = 56) to serious (n = 15). Studies also varied in terms of outcome measures, study designs and the academic disciplines of researchers. Generally, studies using data collected before and during the pandemic showed large negative effects on employment, working hours and income. Studies that assessed moderators (e.g. by industry, occupation, age, gender, race and country of birth) indicated the pandemic has likely worsened pre-existing disparities in health and work. Generally, women, less educated, non-whites and young workers were affected the most, perhaps due to their jobs involving high levels of personal contact (e.g. hospitality, sales and entertainment) and being less amenable to remote working. The DAG highlighted methodological challenges in drawing robust inferences about COVID-19's impact on employment, including the lack of an unexposed control group. The COVID-19 health crisis caused unanticipated and unprecedented changes to employment opportunities around the world, with potential long-term health consequences. Further research should investigate the longer-term impact of COVID-19, with greater attention given to low- and middle-income countries. Our study provides guidance on the design and critical appraisal of future studies.

Current social impact assessment practices for transport projects and plans in Chinese cities

ABSTRACT The importance of sustainable transport development is being increasingly realised in China. However, the understanding of social sustainability in the transport sector remains inadequate. Transport social impact assessment (SIA) at the local level, especially for small- to medium-sized cities, lacks systematic guidance. As a starting point for improving social sustainability in the transport sector, this research explores transport SIA practices in different-sized Chinese cities. Following a critical review of transport planning and appraisal documents collected from 83 sample cities in mainland China, 5 categories were identified based on the characteristics of their transport SIA practices. It was found that except for a few megacities, transport SIA in Chinese cities is generally weak, compared to developed countries. SIA has received little attention and had limited influence on decision-making in transport planning in China. Current guidance on transport SIA in China is relatively general and ambiguous compared to many developed countries, an established transport SIA framework and indicator set for local governments to refer to are lacking. The disparities in transport SIA among different-sized Chinese cities and different project types are significant. Interviews with Chinese transport practitioners were conducted to further explore the gaps in transport SIA practices and the potential for improvement. Based on the interview analysis, key aspects for improving transport SIA practices in China have been provided.

Physical activity in people diagnosed with cancer: a rapid review of recommendations and critical appraisal of international guidelines.

There are numerous guidelines that recommend physical activity (PA) in people diagnosed with cancer, but the quality of these guidelines is unknown. The aim of this study was to identify existing PA guidelines for cancer survivors, describe the recommendations, and assess their methodology quality. A rapid review of the literature was conducted in PubMed and EMBASE, supplemented by a search of the grey literature. The methodological quality of the guidelines was assessed using the AGREE II checklist. A descriptive synthesis of the recommendations from guidelines judged to be of good quality has been performed. A total of nine guidelines published between 2006 and 2019 were included. Of nine guidelines, five achieved a high enough AGREE II score and were judged to be of good quality for use in clinical practice. We found that the recommendations from the five guidelines converged on the prescription of supervised PA (aerobic and resistance exercise) of at least 75 min per week of high intensity or 150 min per week of moderate intensity, spread over two to five sessions per week, equating to a PA dose between 8.70 and 17.5 MET.h/week. The recommendations were applicable to address the most common side effects of cancer and its treatment, namely fatigue, lymphedema, anxiety, depressive symptoms, health-related quality of life (QoL), survival, and physical function. However, no guideline recommends PA to improve other cancer-related outcomes, such as cognitive impairment, falls, sexual function, and peripheral neuropathy frequently experienced by cancer survivors. No guideline also referred to work outcomes (i.e., work ability, return to work, etc.). Most PA guidelines for cancer survivors are of good quality. However, specific PA guidelines are needed for a given cancer site (e.g., location, stage), at a particular phase of the cancer trajectory, and for specific outcomes including return to work (RTW) in order to tailor PA to each cancer survivor.

A historical review of performance appraisal of public hospitals in China from the perspective of historical institutionalism.

The government performance appraisal of public hospitals serves as an effective management tool to promote high-quality development. It is also an important means of realizing the “Healthy China” initiative. Since the founding of the People's Republic of China, changes in performance appraisal have been divided into the following four periods: the early stage of performance appraisal (1949–1977), the exploration period (1978–2008), the development period (2009–2018), and the integration period (2019–present). This clarifies the regional practice of public hospital performance and identifies the institutional factors of the evolution. It also demonstrates that administrative forces, market-driving forces, and mission-driving forces combine to bring about change in the public hospital performance appraisal system. However, problems such as insufficient application of performance appraisal and coordination between health administrative departments and medical insurance departments still loom large.

Quality of Palliative Care Guidelines in Patients with Heart Failure: A Systematic Review of Quality Appraisal using AGREE II Instrument.

While the principles for developing clinical practice guidelines (CPGs) are well established, the quality of published guidelines is very diverse. The present study was conducted to evaluate the quality of existing CPGs in palliative care for heart failure patients. The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analyses. A systematic search was conducted in the Excerpta Medica Database, MEDLINE/PubMed, CINAHL databases and Guideline internet sites: National Institute for Clinical Excellence, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, Guidelines International Network and National Health and Medical Research Council for CPGs published through April 2021. Criteria for including CPGs were: Containing palliative measures for patients with heart failure over 18 years old and preferably interprofessional guidelines that focus on only one dimension of palliative care or focus on diagnosis, definition and treatment were excluded from the study. After initial screening, five appraisers rated the quality of the final selection of CPGs using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II). From 1501 records, seven guidelines were selected for analysis. The 'scope and purpose' and 'clarity of presentation' domains obtained the highest mean and 'rigor of development' and 'applicability' domains obtained the lowest mean scores. Three categories of recommendations were: (1) Strongly recommended (guidelines 1, 3, 6 and 7); (2) recommended with modifications (guideline 2) and (3) not recommended (guidelines 4 and 5). Clinical guidelines for palliative care in patients with heart failure were of moderate-to-high quality, with the main deficiencies occurring in the rigor of development and applicability domains. The results inform clinicians and guideline developers of the strengths and weaknesses of each CPG. To improve the quality of palliative care CPGs in the future, it is recommended that developers pay detailed attention to all domains of the AGREE II criteria. Funding agent: Isfahan University of Medical Sciences. (IR.MUI.NUREMA.REC.1400.123).

Facial Fat Grafting (FFG): Worth the Risk? A Systematic Review of Complications and Critical Appraisal.

Introduction: Autologous fat is ideal soft tissue filler. It is easily accessible, biocompatible, cheap, and it provides both volume augmentation and skin quality improvement. Fat grafting has been used since 1893, but it has only gained widespread popularity since the development of modern liposuction by Colemann and Illouz in the 1980s. Every year more than half a million facial fat grafting procedures are carried out worldwide and the trend is rapidly increasing. Overall, general complications associated with facial fat grafting are assumed to be around 2%. Is that true? Material and Methods: Until July 2021, a systematic search of the literature was performed interrogating PubMed search engines. The following algorithm was used for the research: (fat graft OR lipofilling) AND face AND complications. Exclusion criteria applied hierarchically were review articles, not reporting recipient site complications; not in English and paediatric population. s were manually screened by LS, GS, JM and PDS separately and subsequently matched for accuracy. Pertinent full-text articles were retrieved and analysed and data were extracted from the database. The flow chart of article selection is described following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: In total, 462 papers were identified by PubMed search. A total of 359 were excluded: 38 papers were not in English, 41 were review articles, 279 articles did not report recipient site complications and 1 was not on human subjects. Average complication rate ranged from 1.5% to 81.4%. A total of 298 adverse events were identified: 40 (13.4%) intravascular injections, 13 (4.3%) asymmetry, 57 (19.1%) irregularities, 22 (7.4%) graft hypertrophy, 21 (7%) fat necrosis, 73 (24.5%) prolonged oedema, 1 (0.3%) infection, 6 (2%) prolonged erythema, 15 (5%) telangiectasia and 50 (16.8%) cases of acne activation. Conclusions: FFG related side effects could be resumed in three categories: severe, moderate, and minor. Severe (13.4%) side effects such as intravascular injection or migration require neurological or neurosurgical management and often lead to permanent disability or death. Moderate (38.3%) side effects such as fat hypertrophy, necrosis, cyst formation, irregularities and asymmetries require a retouch operation. Minor (48.3%) side effects such as prolonged oedema or erythema require no surgical management. Despite the fact that the overall general complication rate of facial fat grafting is assumed to be around 2%, the real complication rate of facial fat grafting is unknown due to a lack of reporting and the absence of consensus on side effect definition and identification. More RCTs are necessary to further determine the real complication rate of this procedure.

Review of Contemporary Invasive Treatment Approaches and Critical Appraisal of Guidelines on Hypertrophic Obstructive Cardiomyopathy: State-of-the-Art Review.

Background: Hypertrophic obstructive cardiomyopathy (HOCM) is a heterogeneous disease with different clinical presentations, albeit producing similar dismal long-term outcomes if left untreated. Several approaches are available for the treatment of HOCM; e.g., alcohol septal ablation (ASA) and surgical myectomy (SM). The objectives of the current review were to (1) discuss the place of the standard invasive treatment modalities (ASA and SM) for HOCM; (2) summarize and compare novel techniques for the management of HOCM; (3) analyze current guidelines addressing HOCM management; and (4) offer suggestions for the treatment of complex HOCM presentations. Methods: We searched the literature and attempted to gather the most relevant and impactful available evidence on ASA, SM, and other invasive means of treatment of HOCM. The literature search yielded thousands of results, and 103 significant publications were ultimately included. Results: We critically analyzed available guidelines and provided context in the setting of patient selection for standard and novel treatment modalities. This review offers the most comprehensive analysis to-date of available invasive treatments for HOCM. These include the standard treatments, SM and ASA, as well as novel treatments such as dual-chamber pacing and radiofrequency catheter ablation. We also account for complex pathoanatomic presentations and current guidelines to offer suggestions for tailored care of patients with HOCM. Finally, we consider promising future therapies for HOCM. Conclusions: HOCM is a heterogeneous disease associated with poor outcomes if left untreated. Several strategies for treatment of HOCM are available but patient selection for the procedure is crucial.

Which features of ambulatory healthcare are preferred by people aged 80 and over? Findings from a systematic review of qualitative studies and appraisal of confidence using GRADE-CERQual

BackgroundDespite healthcare providers’ goal of patient-centeredness, current models for the ambulatory (i.e., outpatient) care of older people have not as yet systematically incorporated their views. Moreover, there is no systematic overview of the preferable features of ambulatory care from the perspective of people aged 80 and over. Therefore, the aim of this study was to summarize their specific wishes and preferences regarding ambulatory care from qualitative studies.MethodsThe study was based on qualitative studies identified in a prior systematic review. Firstly, the findings of the qualitative studies were meta-summarized, following Sandelowski and Barroso. Secondly, a list of preferred features of care from the perspective of older people was derived from the included studies’ findings through inductive coding. Thirdly, the review findings were appraised using the GRADE-CERQual tool to determine the level of confidence in the qualitative evidence. The appraisal comprised four domains: methodological limitations, coherence, data adequacy, and data relevance. Two reviewers independently evaluated every review finding in each domain. The final appraisals were discussed and ultimately summarized for the respective review finding (high, moderate, low, or very low confidence).ResultsThe 22 qualitative studies included in the systematic review were mainly conducted in Northern and Western Europe (n = 15). In total, the studies comprised a sample of 330 participants (n = 5 to n = 42) with a mean or median age of 80 and over. From the studies’ findings, 23 preferred features of ambulatory care were identified. Eight features concerned care relationships (e.g., “Older people wish to receive personal attention”), and 15 features concerned healthcare structures (e.g., “Older want more time for their care”). The findings emphasized that older people wish to build strong relationships with their care providers. The majority of the review findings reached a moderate or high confidence appraisal.ConclusionsWhile the listed features of healthcare structures are common elements of care models for older people (e.g., Geriatric Care Model), aspects of care relationships are somewhat underrepresented or are not addressed explicitly at all. Future research should further explore the identified preferred features and their impact on patient and care outcomes.

Comparison of the effects of velocity-based vs. traditional resistance training methods on adaptations in strength, power, and sprint speed: A systematic review, meta-analysis, and quality of evidence appraisal

ABSTRACT We estimated the effectiveness of using velocity feedback to regulate resistance training load on changes in muscle strength, power, and linear sprint speed in apparently healthy participants. Academic and grey literature databases were systematically searched to identify randomised trials that compared a velocity-based training intervention to a ‘traditional' resistance training intervention that did not use velocity feedback. Standardised mean differences (SMDs) were pooled using a random effects model. Risk of bias was assessed with the Risk of Bias 2 tool and the quality of evidence was evaluated using the GRADE approach. Four trials met the eligibility criteria, comprising 27 effect estimates and 88 participants. The main analyses showed trivial differences and imprecise interval estimates for effects on muscle strength (SMD 0.06, 95% CI −0.51–0.63; I2 = 42.9%; 10 effects from 4 studies; low-quality evidence), power (SMD 0.11, 95% CI −0.28–0.49; I2 = 13.5%; 10 effects from 3 studies; low-quality evidence), and sprint speed (SMD −0.10, 95% CI −0.72–0.53; I2 = 30.0%; 7 effects from 2 studies; very low-quality evidence). The results were robust to various sensitivity analyses. In conclusion, there is currently no evidence that VBT and traditional resistance training methods lead to different alterations in muscle strength, power, or linear sprint speed.

Review of green building movement and appraisal of rating systems in Indian context

Mounting issues of resource scarcities and socio-economic development demands sustainable development in the construction sector. Architecture, Engineering and Construction industry though incohesive, but is undergoing profound transformation by adopting Green Building guidelines. With roughly 17.2% of the world's total populace and an urban populace of 372 million (bigger than the whole US populace), India faces mammoth task. India has two programs: LEED-India and GRIHA which are in their nascent stages and need to be appraised. This study presents a brief background of Green Building evolution and an objective summary of LEED-India and GRIHA mapped to proven rating tools US-LEED and BREEAM. It also examines how structural impacts are addressed and how structural engineers, as being one of the stakeholders of Integrated Design Team, can contribute to assessments through sustainable construction. In the end, the probable criterions to be included in the GBRS for the sustainability of structure design are also discussed.

Preschool wheezing and asthma in children: A systematic review of guidelines and quality appraisal with the AGREE II instrument.

Asthma-like symptoms in preschool children, such as wheezing and dyspnea, are common time- and resource-consuming diagnostic and management challenges. Quality of wheezing and asthma recommendations varies. The purpose of this study, carried out by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force for Preschool Wheeze, was to systematically review and assess the quality of guidelines for diagnosis and treatment of preschool wheezing and/or asthma. The Cochrane Library, MEDLINE, and EMBASE were searched until June 2018. The methodological rigor, quality, and transparency of relevant guidelines were assessed with the use of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. We identified 26 guidelines. The quality scores for each domain varied. Of all domains, clarity and presentation had the highest mean score, whereas applicability and stakeholder involvement had the lowest. The scores (median) for individual domains were as follows: score and purpose 86%; stakeholder involvement 49%; rigor of development 54%; clarity of presentation 85%; applicability 51%; and editorial independence 63%. Although several guidelines on asthma management in children are available, however, their quality varies. Additionally, there is a considerable gap in reliable recommendations on the management and treatment of non-asthmatic preschool wheeze.

Review of green building movement and appraisal of rating systems in the Indian context

India has two green building programmes: LEED-India and GRIHA, which are in their nascent stages and need to be appraised. This article presents an account of the background to the evolution of the Green Building movement, and compares LEED-India and GRIHA to proven rating tools applied in the United States (US-LEED) and the United Kingdom (BREEAM). It also examines how structural impacts are addressed in the rating tools and how structural engineers, who are one of the stakeholders of Integrated Design Team, can contribute towards assessments of sustainable construction initiatives. The probable criteria to be included in the green building rating systems (GBRS) for the sustainability of structure design are also discussed.

Regional therapies for the treatment of primary and metastatic hepatic tumors: A disease-based review of techniques and critical appraisal of current evidence

The practice of hepatic surgery has become increasingly complex as additional therapeutic options emerge to treat both primary and metastatic tumors of the liver. Liver-directed therapy options include selective internal radiation therapy (SIRT), stereotactic body radiation therapy, chemoembolization, bland embolization, hepatic artery infusion chemotherapy (HAIC), and ablative techniques such as microwave or radiofrequency ablation. Hepatocellular carcinoma has been treated with many of these therapies for palliation of symptoms, definitive treatment, and as a bridge to transplantation. Intrahepatic cholangiocarcinoma, particularly patients with unresectable disease, have demonstrated clinical responses to both SIRT as well as HAIC. Colorectal liver metastases have been treated with all of these techniques with varying degrees of success depending on the clinical scenario. A detailed understanding of these technologies and the evidence supporting their use is essential for the modern hepatic surgeon to properly sequence therapies and provide salvage options when first-line treatment has failed. This review describes these techniques and their appropriate usage based on the disease of interest and the respective evidence currently available.

The clinical effectiveness and cost-effectiveness of cetuximab (review of technology appraisal no. 176) and panitumumab (partial review of technology appraisal no. 240) for previously untreated metastatic colorectal cancer: a systematic review and economic evaluation.

Colorectal cancer is the fourth most commonly diagnosed cancer in the UK after breast, lung and prostate cancer. People with metastatic disease who are sufficiently fit are usually treated with active chemotherapy as first- or second-line therapy. Targeted agents are available, including the antiepidermal growth factor receptor (EGFR) agents cetuximab (Erbitux®, Merck Serono UK Ltd, Feltham, UK) and panitumumab (Vecitibix®, Amgen UK Ltd, Cambridge, UK). To investigate the clinical effectiveness and cost-effectiveness of panitumumab in combination with chemotherapy and cetuximab in combination with chemotherapy for rat sarcoma (RAS) wild-type (WT) patients for the first-line treatment of metastatic colorectal cancer. The assessment included a systematic review of clinical effectiveness and cost-effectiveness studies, a review and critique of manufacturer submissions, and a de novo cohort-based economic analysis. For the assessment of effectiveness, a literature search was conducted up to 27 April 2015 in a range of electronic databases, including MEDLINE, EMBASE and The Cochrane Library. Studies were included if they were randomised controlled trials (RCTs) or systematic reviews of RCTs of cetuximab or panitumumab in participants with previously untreated metastatic colorectal cancer with RAS WT status. All steps in the review were performed by one reviewer and checked independently by a second. Narrative synthesis and network meta-analyses (NMAs) were conducted for outcomes of interest. An economic model was developed focusing on first-line treatment and using a 30-year time horizon to capture costs and benefits. Costs and benefits were discounted at 3.5% per annum. Scenario analyses and probabilistic and univariate deterministic sensitivity analyses were performed. The searches identified 2811 titles and abstracts, of which five clinical trials were included. Additional data from these trials were provided by the manufacturers. No data were available for panitumumab plus irinotecan-based chemotherapy (folinic acid + 5-fluorouracil + irinotecan) (FOLFIRI) in previously untreated patients. Studies reported results for RAS WT subgroups. First-line treatment with anti-EGFR therapies in combination with chemotherapy appeared to have statistically significant benefits for patients who are RAS WT. For the independent economic evaluation, the base-case incremental cost-effectiveness ratio (ICER) for RAS WT patients for cetuximab plus oxaliplatin-based chemotherapy (folinic acid + 5-fluorouracil + oxaliplatin) (FOLFOX) compared with FOLFOX was £104,205 per quality-adjusted life-year (QALY) gained; for panitumumab plus FOLFOX compared with FOLFOX was £204,103 per QALY gained; and for cetuximab plus FOLFIRI compared with FOLFIRI was £122,554 per QALY gained. The ICERs were sensitive to treatment duration, progression-free survival, overall survival (resected patients only) and resection rates. The trials included RAS WT populations only as subgroups. No evidence was available for panitumumab plus FOLFIRI. Two networks were used for the NMA and model, based on the different chemotherapies (FOLFOX and FOLFIRI), as insufficient evidence was available to the assessment group to connect these networks. Although cetuximab and panitumumab in combination with chemotherapy appear to be clinically beneficial for RAS WT patients compared with chemotherapy alone, they are likely to represent poor value for money when judged by cost-effectiveness criteria currently used in the UK. It would be useful to conduct a RCT in patients with RAS WT. This study is registered as PROSPERO CRD42015016111. The National Institute for Health Research Health Technology Assessment programme.

Cognitive Biases in Performance Appraisal: Experimental Evidence on Anchoring and Halo Effects With Public Sector Managers and Employees

A systematic literature review of performance appraisal in a selection of public administration journals revealed a lack of investigations on the cognitive biases that affect raters’ evaluation of ratees’ performance. To address this gap, we conducted two artefactual field experiments on a sample of 600 public sector managers and employees. Results show that anchoring and halo effects systematically biased performance ratings. For the former, average scores were higher when subjects were exposed to a high rather than a low anchor. For the latter, higher ability on one performance dimension led participants to provide a higher average score on another performance dimension. Halo effect was moderated by rater’s gender. We conclude by discussing the study limitations and providing suggestions for future work in this area.

The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model.

Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia (CIA). To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment (specifically chemotherapy). The following databases were searched from 2004 to 2013: The Cochrane Library, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, Health Management Information Consortium, Current Controlled Trials and ClinicalTrials.gov. The US Food and Drug Administration and European Medicines Agency websites were also searched. Bibliographies of included papers were scrutinised for further potentially includable studies. The clinical effectiveness review followed principles published by the NHS Centre for Reviews and Dissemination. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care, placebo or other ESAs. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL) and adverse events (AEs) were evaluated. When appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment with no ESA treatment. The model comprised two components: one evaluating short-term costs and quality-adjusted life-years (QALYs) (while patients are anaemic) and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. Of 1457 titles and abstracts screened, 23 studies assessing ESAs within their licensed indication (based on start dose administered) were included in the review. None of the RCTs were completely aligned with current European Union licenses. The results suggest a clinical benefit from ESAs for anaemia-related outcomes and an improvement in HRQoL scores. The impact of ESAs on AEs and survival remains highly uncertain, although point estimates are lower, confidence intervals are wide and not statistically significant. Base-case incremental cost-effectiveness ratios (ICERs) for ESA treatment compared with no ESA treatment ranged from £ 19,429 to £ 35,018 per QALY gained, but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs, including the possibility of overall health disbenefit. All ICERs were sensitive to survival and cost. The relative effectiveness of ESAs was not addressed; all ESAs were assumed to have equivalent efficacy. No studies were completely aligned with their European labelling beyond the starting dose evaluated. There is questionable generalisability given that the included trials were published >20 years ago and there have been many changes to chemotherapy as well as to the quality of supportive treatment. Trial quality was moderate or poor and there was considerable unexplained heterogeneity for a number of outcomes, particularly survival, and evidence of publication bias. Adjustments were not made to account for multiple testing. ESAs could be cost-effective when used closer to licence, but there is considerable uncertainty, mainly because of unknown impacts on overall survival. This study is registered as PROSPERO CRD42013005812. The National Institute for Health Research Health Technology Assessment programme.

The clinical effectiveness and cost-effectiveness of cetuximab (mono- or combination chemotherapy), bevacizumab (combination with non-oxaliplatin chemotherapy) and panitumumab (monotherapy) for the treatment of metastatic colorectal cancer after first-line chemotherapy (review of technology appraisal No.150 and part review of technology appraisal No. 118): a systematic review and economic model

Colorectal cancer is the third most commonly diagnosed cancer in the UK after breast and lung cancer. People with metastatic disease who are sufficiently fit are usually treated with active chemotherapy as first- or second-line therapy. Recently, targeted agents have become available including anti-epidermal growth factor receptor (EGFR) agents, for example cetuximab and panitumumab, and anti-vascular endothelial growth factor (VEGF) receptor agents, for example bevacizumab. To investigate the clinical effectiveness and cost-effectiveness of panitumumab monotherapy and cetuximab (mono- or combination chemotherapy) for Kirsten rat sarcoma (KRAS) wild-type (WT) patients, and bevacizumab in combination with non-oxaliplatin chemotherapy, for the treatment of metastatic colorectal cancer after first-line chemotherapy. The assessment comprises a systematic review of clinical effectiveness and cost-effectiveness studies, a review and critique of manufacturer submissions and a de novo cohort-based economic analysis. For the assessment of effectiveness, a literature search was conducted in a range of electronic databases, including MEDLINE, EMBASE and The Cochrane Library, from 2005 to November 2010. Studies were included if they were randomised controlled trials (RCTs) or systematic reviews of RCTs of cetuximab, bevacizumab or panitumumab in participants with EGFR-expressing metastatic colorectal cancer with KRAS WT status that has progressed after first-line chemotherapy (for cetuximab and panitumumab) or participants with metastatic colorectal cancer that has progressed after first-line chemotherapy (bevacizumab). All steps in the review were performed by one reviewer and checked independently by a second. Synthesis was mainly narrative. An economic model was developed focusing on third-line and subsequent lines of treatment. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. The searches identified 7745 titles and abstracts. Two clinical trials (reported in 12 papers) were included. No data were available for bevacizumab in combination with non-oxaliplatin-based chemotherapy in previously treated patients. Neither of the included studies had KRAS status performed prospectively, but the studies did report retrospective analyses of the results for the KRAS WT subgroups. Third-line treatment with cetuximab plus best supportive care or panitumumab plus best supportive care appears to have statistically significant advantages over treatment with best supportive care alone in patients with KRAS WT status. For the economic evaluation, five studies met the inclusion criteria. The base-case incremental cost-effectiveness ratio (ICER) for KRAS WT patients for cetuximab compared with best supportive care is £98,000 per quality-adjusted life-year (QALY), for panitumumab compared with best supportive care is £150,000 per QALY and for cetuximab plus irinotecan compared with best supportive care is £88,000 per QALY. All ICERs are sensitive to treatment duration. In the specific populations of interest, there is a lack of evidence on bevacizumab, cetuximab and cetuximab plus irinotecan used second line and on bevacizumab and cetuximab plus irinotecan used third line. For cetuximab plus irinotecan treatment for KRAS WT people, there is no direct evidence on progression-free survival, overall survival and duration of treatment. Although cetuximab and panitumumab appear to be clinically beneficial for KRAS WT patients compared with best supportive care, they are likely to represent poor value for money when judged by cost-effectiveness criteria currently used in the UK. It would be useful to conduct a RCT for patients with KRAS WT status receiving cetuximab plus irinotecan. The National Institute for Health Research Health Technology Assessment programme.

Ethics Commentary: Ethical Use of Power in High-Risk Situations

Ethics Commentary: Ethical Use of Power in High-Risk Situations

The role of lateral lymph node dissection in the management of lower rectal cancer

Lateral lymph node involvement is a problem encountered in patients with low rectal cancers. This has been documented in both anatomical and pathological studies. Currently, the vast majority of centers have concentrated on the use of chemoradiation to obtain better local control and manage these nodes indirectly. In Japan, extended nodal dissection for the control of pelvic nodal disease has seen further advancement. This paper discusses the key issues involved in the management of pelvic lateral nodes in low rectal cancers. A review of available literature and critical appraisal of the entity of lateral nodes in low rectal cancers, the treatment options, and oncological and functional results were performed. There are good data showing that the entity of pelvic lateral nodes in low rectal cancers should not be ignored. Recent data have emerged showing that radiotherapy is associated with significant long-term functional side effects. Refinement of the technique, lateral node dissection, has led to good local control as well as good functional outcomes. In this context, there needs to be a reevaluation of the role of chemoradiation as the sole treatment for lateral nodal disease in centers outside of Japan. Individualization of the treatment of rectal cancer may require all centers to be able to offer both modalities.