Diagnostic accuracy of cross-sectional and endoscopic imaging in ampullary tumours: systematic review.

BACKGROUND: Differentiation between adenomas and carcinomas of the ampulla of Vater is crucial for therapy and prognosis. This was a systematic review of the literature on the accuracy of diagnostic modalities used to differentiate between benign and malignant ampullary tumours. METHODS: A literature search was conducted in PubMed, Embase, CINAHL, and the Cochrane Library. Studies were included if they reported diagnostic test accuracy information among benign and malignant ampullary tumours, and used pathological diagnosis as the reference standard. Risk of bias was assessed using Quality Assessment on Diagnostic Accuracy Studies (QUADAS) 2 and QUADAS-C. RESULTS: Ten studies comprising 397 patients were included. Frequently studied modalities were (CT; 2 studies), endoscopic ultrasonography (EUS; 3 studies), intraductal ultrasonography (IDUS; 2 studies), and endoscopic forceps biopsy (3 studies). For CT, the reported sensitivity for detecting ampullary carcinoma was 44 and 95%, and the specificity 58 and 60%. For EUS, the sensitivity ranged from 63 to 89% and the specificity between 50 and 100%. A sensitivity of 88 and 100% was reported for IDUS, with a specificity of 75 and 93%. For forceps biopsy, the sensitivity ranged from 20 to 91%, and the specificity from 75 to 86%. The overall risk of bias was scored as moderate to poor. Data were insufficient for meta-analysis. CONCLUSION: To differentiate benign from malignant ampullary tumours, EUS and IDUS seem to be the best diagnostic modalities. Sufficient high-quality evidence, however, is lacking.

Treatment options for resectable hypopharyngeal squamous cell carcinoma: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: There is uncertainty in the treatment options for resectable hypopharyngeal squamous cell carcinoma. METHODS: A systematic review of randomised controlled trials (RCTs) was performed. Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, Science Citation Index, and Conference Proceedings databases and trial registries were searched until November 2020 for randomized controlled trials performed on resectable hypopharyngeal squamous cell carcinoma. Two systematic review authors independently identified studies and extracted data. The primary outcomes evaluated were overall survival, disease-free survival, any recurrence, local recurrence, loco-regional recurrence, distal recurrence and laryngectomy-free survival. The secondary outcomes were response rates following neoadjuvant treatment and comparison of treatment-related toxicity. Assessment of risk of bias was performed for the selected studies using Cochrane's tool for assessing risk of bias. The studies were evaluated for the quality of evidence using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). Risk ratios (RR), rate ratios, and hazard ratios (HR) were calculated along with 95% confidence intervals (95% CI). The Meta-analysis was performed using a random-effects model. RESULTS: Five RCTs met the inclusion criteria for this review. The risk of bias was unclear or high for the trials. Non-organ preservation(n = 140) versus organ preservation (n = 144) (two trials): no statistically significant difference could be identified for any of the primary outcomes. Concurrent chemoradiotherapy (n = 37) versus sequential chemotherapy followed by radiotherapy (n = 34) (one trial): no statistically significant difference was noted between the two treatment arms for overall survival, disease-free survival and loco-regional recurrence. Laryngectomy-free survival was found to be superior in concurrent chemoradiotherapy arm (HR:0.28, 95% CI 0.13, 0.57). Induction chemotherapy followed by concurrent chemoradiotherapy (n = 53) versus induction chemotherapy followed by radiotherapy (n = 60) (one trial): no statistically significant difference was noted between the treatment arms for overall survival, disease-free survival and laryngectomy-free survival. Preoperative radiotherapy (n = 24) versus postoperative radiotherapy (n = 23) (one trial): overall survival was found to be better in the postoperative radiotherapy arm (HR:2.44, 95% CI1.18, 5.03). No statistically significant difference was noted in terms of treatment-related toxicity. CONCLUSIONS: There are considerable uncertainties in the management of resectable hypopharyngeal cancer. TRAIL REGISTRATION: PROSPERO registration: CRD42019155613.

Can you trust clinical practice guidelines for laparoscopic surgery? A systematic review of clinical practice guidelines for laparoscopic surgery.

BACKGROUND: Clinical practice guidelines aim to support clinicians in providing clinical care and should be supported by evidence. There is currently no information on whether clinical practice guidelines in laparoscopic surgery are supported by evidence. METHODS: We performed a systematic review and identified clinical practice guidelines of laparoscopic surgery published in PubMed and Embase between March 2016 and February 2019. We performed an independent assessment of the strength of recommendation based on the evidence provided by the guideline authors. We used the 'Appraisal of Guidelines for Research & Evaluation II' (AGREE-II) Tool's 'rigour of development', 'clarity of presentation', and 'editorial independence' domains to assess the quality of the guidelines. We performed a mixed-effects generalised linear regression modelling. RESULTS: We retrieved 63 guidelines containing 1905 guideline statements. The median proportion of 'difference in rating' of strength of recommendation between the guideline authors and independent assessment was 33.3% (quartiles: 18.3%, 55.8%). The 'rigour of development' domain score (odds ratio 0.06; 95% confidence intervals 0.01-0.48 per unit increase in rigour score; P value = 0.0071) and whether the strength of recommendation was 'strong' by independent evaluation (odds ratio 0.09 (95% confidence intervals 0.06-0.13; P value < 0.001) were the only determinants of difference in rating between the guideline authors and independent evaluation. CONCLUSION: A considerable proportion of guideline statements in clinical practice guidelines in laparoscopic surgery are not supported by evidence. Guideline authors systematically overrated the strength of the recommendation (i.e., even when the evidence points to weak recommendation, guideline authors made strong recommendations).

QUADAS-C: A Tool for Assessing Risk of Bias in Comparative Diagnostic Accuracy Studies.

Comparative diagnostic test accuracy studies assess and compare the accuracy of 2 or more tests in the same study. Although these studies have the potential to yield reliable evidence regarding comparative accuracy, shortcomings in the design, conduct, and analysis may bias their results. The currently recommended quality assessment tool for diagnostic test accuracy studies, QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2), is not designed for the assessment of test comparisons. The QUADAS-C (Quality Assessment of Diagnostic Accuracy Studies-Comparative) tool was developed as an extension of QUADAS-2 to assess the risk of bias in comparative diagnostic test accuracy studies. Through a 4-round Delphi study involving 24 international experts in test evaluation and a face-to-face consensus meeting, an initial version of the tool was developed that was revised and finalized following a pilot study among potential users. The QUADAS-C tool retains the same 4-domain structure of QUADAS-2 (Patient Selection, Index Test, Reference Standard, and Flow and Timing) and comprises additional questions to each QUADAS-2 domain. A risk-of-bias judgment for comparative accuracy requires a risk-of-bias judgment for the accuracy of each test (resulting from QUADAS-2) and additional criteria specific to test comparisons. Examples of such additional criteria include whether participants either received all index tests or were randomly assigned to index tests, and whether index tests were interpreted with blinding to the results of other index tests. The QUADAS-C tool will be useful for systematic reviews of diagnostic test accuracy addressing comparative questions. Furthermore, researchers may use this tool to identify and avoid risk of bias when designing a comparative diagnostic test accuracy study.

Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation.

BACKGROUND: Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. METHODS: We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. RESULTS: This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. CONCLUSION: We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.

Top research priorities in liver and gallbladder disorders in the UK.

OBJECTIVES: There is a mismatch between research questions considered important by patients, carers and healthcare professionals and the research performed in many fields of medicine. The non-alcohol-related liver and gallbladder disorders priority setting partnership was established to identify the top research priorities in the prevention, diagnostic and treatment of gallbladder disorders and liver disorders not covered by the James-Lind Alliance (JLA) alcohol-related liver disease priority setting partnership. DESIGN: The methods broadly followed the principles of the JLA guidebook. The one major deviation from the JLA methodology was the final step of identifying priorities: instead of prioritisation by group discussions at a consensus workshop involving stakeholders, the prioritisation was achieved by a modified Delphi consensus process. RESULTS: A total of 428 unique valid diagnostic or treatment research questions were identified. A literature review established that none of these questions were considered 'answered' that is, high-quality systematic reviews suggest that further research is not required on the topic. The Delphi panel achieved consensus (at least 80% Delphi panel members agreed) that a research question was a top research priority for six questions. Four additional research questions with highest proportion of Delphi panel members ranking the question as highly important were added to constitute the top 10 research priorities. CONCLUSIONS: A priority setting process involving patients, carers and healthcare professionals has been used to identify the top 10priority areas for research related to liver and gallbladder disorders. Basic, translational, clinical and public health research are required to address these uncertainties.

WSES Jerusalem guidelines for diagnosis and treatment of acute appendicitis.

Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics.

Medical Therapies for Uterine Fibroids - A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Uterine fibroids are common, often symptomatic and a third of women need repeated time off work. Consequently 25% to 50% of women with fibroids receive surgical treatment, namely myomectomy or hysterectomy. Hysterectomy is the definitive treatment as fibroids are hormone dependent and frequently recurrent. Medical treatment aims to control symptoms in order to replace or delay surgery. This may improve the outcome of surgery and prevent recurrence. PURPOSE: To determine whether any medical treatment can be recommended in the treatment of women with fibroids about to undergo surgery and in those for whom surgery is not planned based on currently available evidence. STUDY SELECTION: Two authors independently identified randomised controlled trials (RCT) of all pharmacological treatments aimed at the treatment of fibroids from a list of references obtained by formal search of MEDLINE, EMBASE, Cochrane library, Science Citation Index, and ClinicalTrials.gov until December 2013. DATA EXTRACTION: Two authors independently extracted data from identified studies. DATA SYNTHESIS: A Bayesian network meta-analysis was performed following the National Institute for Health and Care Excellence-Decision Support Unit guidelines. Odds ratios, rate ratios, or mean differences with 95% credible intervals (CrI) were calculated. RESULTS AND LIMITATIONS: A total of 75 RCT met the inclusion criteria, 47 of which were included in the network meta-analysis. The overall quality of evidence was very low. The network meta-analysis showed differing results for different outcomes. CONCLUSIONS: There is currently insufficient evidence to recommend any medical treatment in the management of fibroids. Certain treatments have future promise however further, well designed RCTs are needed.

A network meta-analysis comparing perioperative outcomes of interventions aiming to decrease ischemia reperfusion injury during elective liver resection.

OBJECTIVE: This study sought to compare the perioperative outcomes of interventions aiming to decrease ischemia-reperfusion (IR) injury during elective liver resection. METHOD: A comprehensive literature search was performed to identify randomized controlled trials. A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS following the guidelines of the National Institute for Health and Clinical Excellence Decision Support Unit. Odds ratios for binary outcomes and mean differences for continuous outcomes were calculated using a fixed effect model or a random effects model according to model fit. RESULTS: Forty-four trials with 2,457 patients having undergone liver resection were included and were divided into 8 classes of interventions aimed at decreasing IR injury and a control group, which was hepatectomy alone. There was no difference between the different interventions in mortality, quantity of blood transfusion, and durations of stay in an intensive therapy unit between any pairwise comparisons. Patients treated with ischemic preconditioning, cardiovascular modulators, and miscellaneous interventions had significantly fewer serious adverse events compared with patients undergoing liver resection alone. Ischemic preconditioning patients had significantly fewer transfusion proportions and shorter operative time than patients treated with steroids. Ischemic preconditioning had significantly less operative blood loss compared with all other interventions, and a lesser duration of hospital stay than hepatectomy alone. Sensitivity analysis showed that the drugs sevoflurane (a volatile anesthetic), verapamil (a calcium channel blocker), and gabexate mesilate (a thrombin inhibitor) produced fewer serious adverse events compared with hepatectomy alone. CONCLUSION: Ischemic preconditioning resulted in multiple beneficial clinical endpoints and further RCTs seem to be needed to confirm its clinical benefits.

Comparative safety and efficacy of vasopressors for mortality in septic shock: A network meta-analysis.

INTRODUCTION: Septic shock is a life-threatening condition requiring vasopressor agents to support the circulatory system. Several agents exist with choice typically guided by the specific clinical scenario. We used a network meta-analysis approach to rate the comparative efficacy and safety of vasopressors for mortality and arrhythmia incidence in septic shock patients. METHODS: We performed a comprehensive electronic database search including Medline, Embase, Science Citation Index Expanded and the Cochrane database. Randomised trials investigating vasopressor agents in septic shock patients and specifically assessing 28-day mortality or arrhythmia incidence were included. A Bayesian network meta-analysis was performed using Markov chain Monte Carlo methods. RESULTS: Thirteen trials of low to moderate risk of bias in which 3146 patients were randomised were included. There was no pairwise evidence to suggest one agent was superior over another for mortality. In the network meta-analysis, vasopressin was significantly superior to dopamine (OR 0.68 (95% CI 0.5 to 0.94)) for mortality. For arrhythmia incidence, standard pairwise meta-analyses confirmed that dopamine led to a higher incidence of arrhythmias than norepinephrine (OR 2.69 (95% CI 2.08 to 3.47)). In the network meta-analysis, there was no evidence of superiority of one agent over another. CONCLUSIONS: In this network meta-analysis, vasopressin was superior to dopamine for 28-day mortality in septic shock. Existing pairwise information supports the use of norepinephrine over dopamine. Our findings suggest that dopamine should be avoided in patients with septic shock and that other vasopressor agents should continue to be based on existing guidelines and clinical judgement of the specific presentation of the patient.

A Cochrane systematic review and network meta-analysis comparing treatment strategies aiming to decrease blood loss during liver resection.

INTRODUCTION: Intraoperative haemorrhage remains one of the major risks during liver resection, and perioperative blood loss and blood transfusion are important factors affecting perioperative morbidity and mortality. The aim of this study is to compare treatment strategies aiming to decrease blood loss during hepatectomy. METHODS: A systematic review of the literature was performed to identify randomised controlled trials reporting on the method of vascular occlusion, parenchymal transection, and management of the cut surface during liver resection. A Bayesian network meta-analysis was performed using WinBUGS. RESULTS: Seven trials reporting on 496 participants randomised to seven treatment strategies were analysed. Continuous vascular occlusion resulted in lower blood loss compared to no vascular occlusion when parenchymal transection was performed with clamp-crush and no fibrin sealant was used for the cut surface. People undergoing liver resection by continuous vascular occlusion had decreased amounts of blood transfused than people with intermittent vascular occlusion when parenchymal transection was performed with clamp-crush and no fibrin sealant. There was no significant difference in proportion of people transfused, mortality, or hospital stay between the different strategies. There were significantly more serious adverse events when surgery was performed using radiofrequency dissecting sealer compared with standard clamp-crush method in the absence of vascular occlusion and fibrin sealant. CONCLUSIONS: Continuous vascular occlusion during hepatectomy results in decreased blood loss and decreased blood transfusion requirements. Further studies are needed to compare treatment strategies aiming to decrease blood loss, defined by their method of vascular occlusion, parenchymal transection, and management of the cut surface.

Impact of Preoperative Anaemia and Blood Transfusion on Postoperative Outcomes in Gynaecological Surgery.

OBJECTIVE: To evaluate the effect of preoperative anaemia and blood transfusion on 30-day postoperative morbidity and mortality in patients undergoing gynecological surgery. STUDY DESIGN: Data were analyzed from 12,836 women undergoing operation in the American College of Surgeons National Surgical Quality Improvement Program. Outcomes measured were; 30-day postoperative mortality, composite and specific morbidities (cardiac, respiratory, central nervous system, renal, wound, sepsis, venous thrombosis, or major bleeding). Multivariate logistic regression models were performed using adjusted odds ratios (ORadj) to assess the independent effects of preoperative anaemia (hematocrit <36.0%) on outcomes, effect estimates were performed before and after adjustment for perioperative transfusion requirement. RESULTS: The prevalence of preoperative anaemia was 23.9% (95%CI: 23.2-24.7). Adjusted for confounders by multivariate logistic regression; preoperative anaemia was independently and significantly associated with increased odds of 30-day mortality (OR: 2.40, 95%CI: 1.06-5.44) and composite morbidity (OR: 1.80, 95%CI: 1.45-2.24). This was reflected by significantly higher adjusted odds of almost all specific morbidities including; respiratory, central nervous system, renal, wound, sepsis, and venous thrombosis. Blood Transfusion increased the effect of preoperative anaemia on outcomes (61% of the effect on mortality and 16% of the composite morbidity). CONCLUSIONS: Preoperative anaemia is associated with adverse post-operative outcomes in women undergoing gynecological surgery. This risk associated with preoperative anaemia did not appear to be corrected by use of perioperative transfusion.

Cost-effectiveness of diagnostic laparoscopy for assessing resectability in pancreatic and periampullary cancer.

BACKGROUND: Surgical resection is the only curative treatment for pancreatic and periampullary cancer, but many patients undergo unnecessary laparotomy because tumours can be understaged by computerised tomography (CT). A recent Cochrane review found diagnostic laparoscopy can decrease unnecessary laparotomy. We compared the cost-effectiveness of diagnostic laparoscopy prior to laparotomy versus direct laparotomy in patients with pancreatic and periampullary cancer with resectable disease based on CT scanning. METHOD: Model based cost-utility analysis estimating mean costs and quality-adjusted life years (QALYs) per patient from the perspective of the UK National Health Service. A decision tree model was constructed using probabilities, outcomes and cost data from published sources. One-way and probabilistic sensitivity analyses were undertaken. RESULTS: When laparotomy following diagnostic laparoscopy occurred in a subsequent admission, diagnostic laparoscopy incurred similar mean costs per patient to direct laparotomy (£7470 versus £7480); diagnostic laparoscopy costs (£995) were offset by avoiding unnecessary laparotomy costs. Diagnostic laparoscopy produced significantly more mean QALYs per patient than direct laparotomy (0.346 versus 0.337). Results were sensitive to the accuracy of diagnostic laparoscopy and the probability that disease was unresectable. Diagnostic laparoscopy had 63 to 66% probability of being cost-effective at a maximum willingness to pay for a QALY of £20 000 to £30 000. When laparotomy was undertaken in the same admission as diagnostic laparoscopy the mean cost per patient of diagnostic laparoscopy increased to £8224. CONCLUSIONS: Diagnostic laparoscopy prior to laparotomy in patients with CT-resectable cancer appears to be cost-effective in pancreatic cancer (but not in periampullary cancer), when laparotomy following diagnostic laparoscopy occurs in a subsequent admission.

Cost-effectiveness analysis of endoscopic ultrasound versus magnetic resonance cholangiopancreatography in patients with suspected common bile duct stones.

BACKGROUND: Patients with suspected common bile duct (CBD) stones are often diagnosed using endoscopic retrograde cholangiopancreatography (ERCP), an invasive procedure with risk of significant complications. Using endoscopic ultrasound (EUS) or Magnetic Resonance CholangioPancreatography (MRCP) first to detect CBD stones can reduce the risk of unnecessary procedures, cut complications and may save costs. AIM: This study sought to compare the cost-effectiveness of initial EUS or MRCP in patients with suspected CBD stones. METHODS: This study is a model based cost-utility analysis estimating mean costs and quality-adjusted life years (QALYs) per patient from the perspective of the UK National Health Service (NHS) over a 1 year time horizon. A decision tree model was constructed and populated with probabilities, outcomes and cost data from published sources, including one-way and probabilistic sensitivity analyses. RESULTS: Using MRCP to select patients for ERCP was less costly than using EUS to select patients or proceeding directly to ERCP ($1299 versus $1753 and $1781, respectively), with similar QALYs accruing to each option (0.998, 0.998 and 0.997 for EUS, MRCP and direct ERCP, respectively). Initial MRCP was the most cost-effective option with the highest monetary net benefit, and this result was not sensitive to model parameters. MRCP had a 61% probability of being cost-effective at $29,000, the maximum willingness to pay for a QALY commonly used in the UK. CONCLUSION: From the perspective of the UK NHS, MRCP was the most cost-effective test in the diagnosis of CBD stones.

Cost-effectiveness of preoperative biliary drainage for obstructive jaundice in pancreatic and periampullary cancer.

BACKGROUND: A recent Cochrane Review found that preoperative biliary drainage (PBD) in patients with resectable pancreatic and periampullary cancer undergoing surgery for obstructive jaundice is associated with similar mortality but increased serious morbidity compared with no PBD. Despite this clinical evidence of its lack of effectiveness, PBD is still in use. We considered the economic implications of PBD versus direct surgery for obstructive jaundice in patients with pancreatic and periampullary cancer. MATERIALS AND METHODS: Model-based cost-utility analysis estimating mean costs and quality-adjusted life years (QALYs) per patient from the perspective of the UK National Health Service over a 6-month time horizon. A decision tree model was constructed and populated with probabilities, outcomes, and cost data from published sources. One-way and probabilistic sensitivity analyses were undertaken. RESULTS: PBD was more costly than direct surgery (mean cost per patient £10,775 [$15,616] versus £8221 [$11,914]) and produced fewer QALYs (mean QALYs per patient 0.337 versus 0.343). Not performing PBD would result in cost savings of approximately £2500 ($3623) per patient to the National Health Service. PBD had <10% probability of being cost-effective at a maximum willingness to pay for a QALY of £20,000 ($28,986) to £30,000 ($43,478). CONCLUSIONS: There are significant cost savings to be gained by avoiding routine PBD in patients with resectable pancreatic and periampullary cancer where PBD is still routinely used in this context; this economic evidence should be used to support the clinical argument for a change in practice.

Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?

BACKGROUND: Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs. METHODS: We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality "wears off"). RESULTS: The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR. CONCLUSIONS: SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker.

Cemented versus uncemented hemiarthroplasty for hip fractures: a systematic review of randomised controlled trials.

We performed a systematic review of randomised controlled trials in order to identify the best available evidence to compare the outcome between cemented and uncemented hemiarthroplasty for treatment of intracapsular hip fractures. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, MEDLINE and the National Research Register (UK) to retrieve all of the published randomised controlled trials designed to address these issues, in order to perform a meta-analysis. Eight studies involving 1169 patients were determined to be appropriate for meta-analysis. The following statistically significant differences were found between the cemented and uncemented prostheses: (1) longer operative time for cemented prosthesis; (2) lower reduction in mobility score for those treated with cemented prosthesis; (3) fewer patients with residual pain in the hip and lower pain score (signifying less pain) for those treated with a cemented prosthesis. Our meta-analysis has shown that there is good evidence that the use of cement during hemiarthroplasty will reduce the amount of residual hip pain and also allow better restoration of function. There is no evidence of significant adverse effects of cement on mortality or other complications encountered. These observations apply to older designs, and there is a need for randomised trials comparing hydroxyapatite-coated modern stems with cemented prostheses.