Guidance for the gastrointestinal evaluation and management of iron deficiency in Sub-Saharan Africa.

BACKGROUND: Over 30% of the world's population is anaemic, with a significant proportion of these being iron deficient. As iron deficiency (ID) anaemia in men and post-menopausal women is mostly caused by gastrointestinal blood loss or malabsorption, the initial evaluation of a patient with ID anaemia involves referral to a gastroenterologist. The current drive towards patient blood management in sub-Saharan Africa (SSA)prescribes that we regulate not only the use of blood transfusion but also the management of patients in whom the cause of iron loss or inadequate iron absorption is sought. Recommendations have been developed to: (i) aid clinicians in the evaluation of suspected gastrointestinal iron loss and iron malabsorption, and often a combination of these; (ii) improve clinical outcomes for patients with gastrointestinal causes of ID; (iii) provide current, evidence-based, context-specific recommendations for use in the management of ID; and (iv) conserve resources by ensuring rational utilisation of blood and blood products. METHOD: Development of the guidance document was facilitated by the Gastroenterology Foundation of Sub-Saharan Africa and the South African Gastroenterology Society. The consensus recommendations are based on a rigorous process involving 21 experts in gastroenterology and haematology in SSA. Following discussion of the scope and purpose of the guidance document among the experts, an initial review of the literature and existing guidelines was undertaken. Thereafter, draft recommendation statements were produced to fulfil the outlined purpose of the guidance document. These were reviewed in a round-table discussion and were subjected to two rounds of anonymised consensus voting by the full committee in an electronic Delphi exercise during 2022 using the online platform, Research Electronic Data Capture. Recommendations were modified by considering feedback from the previous round, and those reaching a consensus of over 80% were incorporated into the final document. Finally, 44 statements in the document were read and approved by all members of the working group. CONCLUSION: The recommendations incorporate six areas, namely: general recommendations and practice, Helicobacter pylori, coeliac disease, suspected small bowel bleeding, inflammatory bowel disease, and preoperative care. Implementation of the recommendations is aimed at various levels from individual practitioners to healthcare institutions, departments and regional, district, provincial and national platforms. It is intended that the recommendations spur the development of centre-specific guidelines and that they are integrated with the relevant patient blood management protocols. Integration of the recommendations is intended to promote optimal evaluation and management of patients with ID, regardless of the presence of anaemia.

Therapeutic potential of highly diluted antibodies in antibiotic-resistant infection.

Klebsiella pneumoniae is one of the main causes of hospital-acquired infections. Its rate of antimicrobial resistance is rapidly increasing, while there are no licensed human vaccines against it. A novel therapeutic approach involves modulation of the host immune response combined with antibiotic treatment. One of the approaches to immunomodulation can be the use of antibodies (Abs) in a specific technological form of high dilutions (hd). The aim of the study was to assess whether hd-Abs could affect the antibacterial activity of AMC against a bacterial strain resistant to it. The study was performed on an in vivo model of K. pneumoniae BAA-1705 multiresistant strain lethal infection in neutropenic RjOrl:Swiss mice. The efficacy of hd-Abs combined with AMC was assessed based on survival and lung bacterial burden. Additionally, we evaluated the direct effect of the drugs on the growth of bacteria in vitro. hd-Abs in combination with AMC increased survival of mice infected with K. pneumoniae up to 50%, whereas all animals in the AMC group died. Hd-Abs had no direct effect on K. pneumoniae sensitivity to AMC in vitro. The survival rate in mice treated with hd-Abs combined with AMC was comparable to that in animals treated with the reference drug gentamicin. Thus, hd-Abs increased the antibacterial activity of AMC against the strain resistant to it. The mechanism of action of hd-Abs remains to be elucidated in future studies.

A METHOD TO IDENTIFY AND LOCALIZE A SINGLE HOT PARTICLE IN THE LUNGS USING AN ARRAY OF HIGH-PURITY GERMANIUM DETECTORS FOR IMPROVED ESTIMATE OF THE DEPOSITED ACTIVITY.

A new method has been developed to identify and localize a single hot particle in the lungs using an array of four high-purity germanium detectors. The method is based upon calculating a set of three count rate ratios (generated by each individual detector in the array) that are evaluated in sequence to designate whether the measured deposition can be associated with a hot particle rather than the default assumption of a uniform activity distribution. Identification and localization of the hot particle are determined from a single in vivo measurement in which detectors are positioned above and below the thorax. The method was tested using an anthropomorphic thorax phantom in which point sources of 241Am, 137Cs and 60Co were individually inserted in the lungs at 15 different locations and were measured using a scanning bed whole-body counter. Depending upon source location and photon energy, a bias of -35% up to +76% could be introduced by falsely assuming a uniform activity distribution in the lungs. This bias would directly translate to an erroneous dose estimate to the lungs. It was demonstrated that by using the appropriate detector efficiencies for the single hot particle, the bias associated with the activity determination is reduced to <10% and ~2% in average.

Recruiting for research on sensitive topics in schools: an experience with Vaxcards, a collectable vaccine card game.

Undertaking recruitment for research in schools is an effective way to recruit young people for research participation but it is not without its challenges. Gaining access and coordinating many levels of different organisations and stakeholders whose cooperation and approval are crucial all add time and sometimes logistical challenges for the research team. In addition, recruiting around sensitive research topics can elicit additional barriers to successful research. The research team aimed to conduct a pragmatic cluster randomised controlled trial involving schools in a local government region in Victoria, Australia, to assess the effect of a vaccination-based educational card game called "Vaxcards" on vaccine consent returns. Schools were contacted via phone and email to determine which staff member would best be a contact point for a face-to-face meeting to discuss the methods and purpose of the study. Email follow-ups were scheduled to follow up non-responsive schools and consent forms. The minimum required sample size was 13. Of 31 eligible schools, 13 were recruited. The research team encountered several unanticipated challenges before achieving the recruitment target. The most common reasons for non-participation were being too busy with other commitments, concerns regarding the topic of vaccination being too sensitive, and concerns that key stakeholders in the school would not approve of the research topic of vaccination. One school required a review by a private research ethics board that rejected the study. Significant hesitancy and misinformation about vaccine science was observed that affected engagement with a small number of schools. This paper highlights the challenges of recruiting schools in the context of public anxieties about vaccines and has several important learning lessons for successful recruitment about sensitive topics. This includes navigating approval processes for research in schools, the importance of local champions, dealing with misinformation and the importance of strong relationships and organisational trust. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618001753246 . Prospectively registered on 25 October 2018 8:24:21 AM.

Epidemiology of inflammatory bowel disease in sub-Saharan Africa: A review of the current status.

While inflammatory bowel disease (IBD) has been well characterised in the West and other parts of the world, there are little data from sub-Saharan Africa (SSA). To throw light on the current status of IBD in SSA, we performed a systematic review of the literature, extracting relevant publications. We found only 210 documented IBD cases in SSA (excluding South Africa (SA)), which were reported in 34 publications until August 2019. The majority were cases of ulcerative colitis. Only three reports, all from SA, attempted to determine IBD incidence rates. The rest were mostly case reports or small case series; the largest from Nigeria comprised 32 patients. The paucity of documented cases possibly reflects under-diagnosis and under-reporting. Major deficiencies in diagnostic and clinical capacity were noted, which need to be addressed going forward.

Patient chosen gap payments in primary care: Predictions of patient acceptability, uptake and willingness to pay from a discrete choice experiment.

Compulsory co-payments limit access and may compromise quality in primary care. Patient Chosen Gap Payments (PCGPs) allow patients to specify a (voluntary) out-of-pocket contribution, creating an incentive for patient-centred care without the need for complex outcomes-based funding formulae. It is not yet known if widespread use of PCGP services is consistent with consumer preferences. We conducted a discrete choice experiment (DCE) in a sample of the adult Australian general population (n = 1457) during April 2019 to simulate patient choice between alternative primary care services and describe preferences for PCGP services. Participants also completed a supplementary valuation task in which participants reported their intended PCGP contribution for PCGP services. Finally, we conducted policy-simulations to predict market shares when PCGP clinics operate alongside the two existing models of primary care funding in Australia. Results suggest that patients prefer shorter wait time, longer consults, lower compulsory copayments, services with higher patient satisfaction ratings, choice of doctor and $0 suggested voluntary contribution for PCGP services. Policy-simulations suggest that high-quality PCGP services could obtain market share of up to 39% and voluntary contributions of up to $25.36 per service (95%CI: $10.24, $40.47), potentially adding $1.48 billion AUD in revenues and funding for primary care at no cost to government. Low-quality PCGP services are unlikely to capture significant market share and PCGP contributions were lowest for low-quality PCGP services ($12.12, 95%CI: $2.09, $26.34). Further field testing is recommended where (i) patients make consequential choices (e.g. real payments for simulated services), and (ii) dynamic effects on quality of care and utilisation can be observed; particularly in vulnerable populations. We conclude that PCGP services aligned with patient preferences could capture significant market share and substantially increase revenue to general practice.

A systematic review of short metaphyseal loading cementless stems in hip arthroplasty.

AIMS: Short-stemmed femoral implants have been used for total hip arthroplasty (THA) in young and active patients to conserve bone, provide physiological loading, and reduce the incidence of thigh pain. Only short- to mid-term results have been presented and there have been concerns regarding component malalignment, incorrect sizing, and subsidence. This systematic review reports clinical and radiological outcomes, complications, revision rates, and implant survival in THA using short-stemmed femoral components. MATERIALS AND METHODS: A literature review was performed using the EMBASE, Medline, and Cochrane databases. Strict inclusion and exclusion criteria were used to identify studies reporting clinical and radiological follow-up for short-stemmed hip arthroplasties. RESULTS: A total of 28 studies were eligible for inclusion. This included 5322 hips in 4657 patients with a mean age of 59 years (13 to 94). The mean follow-up was 6.1 years (0.5 to 20). The mean Harris Hip Score improved from 46 (0 to 100) to 92 (39 to 100). The mean Oxford Hip Score improved from 25 (2 to 42.5) to 35 (12.4 to 48). The mean Western Ontario & McMaster Universities Osteoarthritis Index improved from 54 (2 to 95) to 22 (0 to 98). Components were aligned in a neutral coronal alignment in up to 90.9% of cases. A total of 15 studies reported component survivorship, which was 98.6% (92% to 100%) at a mean follow-up of 12.1 years. CONCLUSION: Short-stemmed femoral implants show similar improvement in clinical and radiological outcomes compared with conventional length implants. Only mid-term survivorship, however, is known. An abundance of short components have been developed and used commercially without staged clinical trials. Long-term survival is still unknown for many of these components. There remains tension between innovation and the moral duty to ensure that the introduction of new implants is controlled until safety and patient benefit are demonstrated. Implant innovation and subsequent use should be driven by proven clinical outcomes, rather than market and financial forces, and ethical practice must be ensured. Cite this article: Bone Joint J 2019;101-B:502-511.

Cost-effectiveness analysis of a randomized clinical trial of early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration.

BACKGROUND: Treatment of superficial venous reflux in addition to compression therapy accelerates venous leg ulcer healing and reduces ulcer recurrence. The aim of this study was to evaluate the costs and cost-effectiveness of early versus delayed endovenous treatment of patients with venous leg ulcers. METHODS: This was a within-trial cost-utility analysis with a 1-year time horizon using data from the EVRA (Early Venous Reflux Ablation) trial. The study compared early versus deferred endovenous ablation for superficial venous truncal reflux in patients with a venous leg ulcer. The outcome measure was the cost per quality-adjusted life-year (QALY) over 1 year. Sensitivity analyses were conducted with alternative methods of handling missing data, alternative preference weights for health-related quality of life, and per protocol. RESULTS: After early intervention, the mean(s.e.m.) cost was higher (difference in cost per patient £163(318) (€184(358))) and early intervention was associated with more QALYs at 1 year (mean(s.e.m.) difference 0·041(0·017)). The incremental cost-effectiveness ratio (ICER) was £3976 (€4482) per QALY. There was an 89 per cent probability that early venous intervention is cost-effective at a threshold of £20 000 (€22 546)/QALY. Sensitivity analyses produced similar results, confirming that early treatment of superficial reflux is highly likely to be cost-effective. CONCLUSION: Early treatment of superficial reflux is highly likely to be cost-effective in patients with venous leg ulcers over 1 year. Registration number: ISRCTN02335796 (http://www.isrctn.com).

Advanced approach to activity evaluation for released-active forms of antibodies to interferon-gamma by enzyme-linked immunoassay.

Selection of a suitable assay to measure the activity of drugs based on released-active forms (RA forms of Abs) is an important step during their investigation. In this study, ELISA was utilized to examine the effect of RA forms of Abs to interferon gamma on the interaction between monoclonal anti-interferon gamma antibodies and human interferon gamma. The data showed that such RA forms of Abs are able to modulate the antibody interaction with interferon gamma, and it was suggested that the observed influence of RA forms of Abs on 'antibody-antigen' interaction could be used to analyze the activity of this kind of drugs.

Primary prevention of cardiovascular disease: an umbrella review of non-pharmacological interventions / Prevención primaria de enfermedades cardiovasculares: una revisión de revisiones de intervenciones no farmacológicas

Background: The aim of this study is to determine the effectiveness of non-pharmacological interventions for prevention of cardiovascular disease (CVD) events and mortality in healthy adults or those at high risk of CVD. Methods: An umbrella review about primary prevention of non-pharmacological interventions was undertaken in key databases as PubMed Health, Effective Health Care Program AHRQ, McMaster University and the Cochrane Plus until July 2017. The primary outcomes were the relative risk of fatal and non-fatal CVD events, and mortality. Secondary outcomes were adverse events. Results: Twenty-four reviews were included of which thirteen reported outcomes of interest. Four of these found a pooled statistically significant risk reduction: dietary supplements of vitamin D, increased consumption of omega 3 fatty acids, Qigong, and counselling or education to modify more than one cardiovascular risk factor. Seven studies reported adverse events but minor or insignificant with respect to the control group. Conclusions: Four non-pharmacological interventions have been shown to provide a statistically significant reduction in risk of CVD events or overall mortality, with minor adverse events if any. Further research should aim for higher methodological quality and longer follow-up of interventions to establish if these interventions, alone or in combination, translate into definite long-term health benefits

Fundamento: El objetivo de este estudio es determinar la efectividad de intervenciones no farmacológicas para la prevención de eventos relacionados con enfermedad cardiovascular (CVD), y mortalidad en adultos sanos o con alto riesgo de CVD. Método: Revisión de revisiones sobre prevención primaria de intervenciones no farmacológicas en las bases de datos de PubMed Health, Effective Health Care Program AHRQ, McMaster University and the Cochrane Plus hasta Julio de 2017. Los resultados primarios fueron el riesgo relativo de eventos CVD, fatales y no fatales, y de mortalidad; los efectos adversos fueron los eventos secundarios. Resultados: Se incluyeron veinticuatro revisiones, de las cuales trece informan resultados de interés. Cuatro observaron una reducción significativa del riesgo: suplementación de vitamina D, incremento del consumo de ácidos grasos omega 3, Qigong, y educación para la modificación de factores de riesgo cardiovascular. Siete revisiones informaron sobre eventos adversos menores y/o no significativos respecto del grupo control. Conclusiones: Cuatro intervenciones no farmacológicas son las que muestran una reducción estadísticamente significativa en eventos CVD o mortalidad total, con escasos o nulos efectos adversos. Se requiere de una investigación de mayor calidad metodológica y de mayor seguimiento de las intervenciones para establecer si estas, combinadas o por separado, conducen a claros beneficios en salud a largo plazo

Primary prevention of cardiovascular disease: an umbrella review.

BACKGROUND: The aim of this study is to determine the effectiveness of non-pharmacological interventions for prevention of cardiovascular disease (CVD) events and mortality in healthy adults or those at high risk of CVD. METHODS: An umbrella review about primary prevention of non-pharmacological interventions was undertaken in key databases as PubMed Health, Effective Health Care Program AHRQ, McMaster University and the Cochrane Plus until July 2017. The primary outcomes were the relative risk of fatal and non-fatal CVD events, and mortality. Secondary outcomes were adverse events. RESULTS: Twenty-four reviews were included of which thirteen reported outcomes of interest. Four of these found a pooled statistically significant risk reduction: dietary supplements of vitamin D, increased consumption of omega 3 fatty acids, Qigong, and counselling or education to modify more than one cardiovascular risk factor. Seven studies reported adverse events but minor or insignificant with respect to the control group. CONCLUSIONS: Four non-pharmacological interventions have been shown to provide a statistically significant reduction in risk of CVD events or overall mortality, with minor adverse events if any. Further research should aim for higher methodological quality and longer follow-up of interventions to establish if these interventions, alone or in combination, translate into definite long-term health benefits.

Cost-effectiveness of treatments for superficial venous reflux in patients with chronic venous ulceration.

BACKGROUND: Venous leg ulcers impair quality of life significantly, with substantial costs to health services. The aim of this study was to estimate the cost-effectiveness of interventional procedures alongside compression therapy versus compression therapy alone for the treatment of chronic venous leg ulceration. METHODS: A Markov decision analytical model was developed. The main outcome measures were quality-adjusted life-years (QALYs) and lifetime costs per patient, from the perspective of the UK National Health Service at 2015 prices. Resource use included the initial procedures, compression therapy, primary care and outpatient consultations. The interventional procedures included superficial venous surgery, endothermal ablation and ultrasound-guided foam sclerotherapy (UGFS). The study population was patients with a chronic venous ulcer who were eligible for either compression therapy or an interventional procedure. Data were obtained from systematic review and meta-analysis of RCTs. RESULTS: Surgery gained 0·112 (95 per cent c.i. -0·011 to 0·213) QALYs compared with compression therapy alone, with a difference in lifetime costs of €-1330 (-3570 to 1262). Given the expected savings in community care, the procedure would pay for itself within 4 years. There was insufficient evidence regarding endothermal ablation and UGFS to draw conclusions. DISCUSSION: This modelling study found surgery to be more effective and less costly than compression therapy alone. Further RCT evidence is required for both endothermal ablation and UGFS.

Short-term efficacy and safety of new biological agents targeting the interleukin-23-T helper 17 pathway for moderate-to-severe plaque psoriasis: a systematic review and network meta-analysis.

A new generation of biologics targeting the interleukin-23-T helper 17 pathway has been developed. This study aimed to assess the short-term effectiveness and safety of these new agents using a network meta-analysis. Twenty-seven randomized clinical trials (10 629 patients) were identified by a comprehensive systematic literature review (PROSPERO 2015: CRD42015025472). Quality of evidence was assessed following Cochrane-compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations approach. Efficacy and safety outcomes at weeks 10-16 were compared using a random-effects network meta-analysis within a frequentist framework to estimate pooled odds ratios (ORs) of direct and indirect comparisons among the therapeutic options. There were six direct drug-to-drug comparisons in the network, with a high degree of consistency between the direct and indirect evidence. From the available evidence, infliximab 5 mg kg-1 every 8 weeks [OR 118·89, 95% confidence interval (CI) 60·91-232·04] and secukinumab 300 mg every 4 weeks (OR 87·07, 95% CI 55·01-137·82) are shown to be among the most effective short-term treatments, but are ranked as the biologics most likely to produce any adverse event or an infectious adverse event, respectively. Ustekinumab 90 mg every 12 weeks, the third most efficacious treatment (OR 73·67, 95% CI 46·97-115·56), was the only agent that did not show increased risk of adverse events compared with placebo. Treatment recommendations should also consider long-term outcomes and costs.

Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model.

The assessment of dose-response is an essential part of drug development in terms of the determination of a drug's effective dose, finding the safety endpoint, estimation of the pharmacokinetic profile, and even validation of drug activity, especially for therapeutic agents with a principally novel mechanism of action. Drugs based on released-active forms of antibodies are a good example of such a target. In this study, the efficacy of the antiviral drug Anaferon for children (released-active form of antibodies to interferon-gamma) was tested in a dose-dependent manner (at doses of 0.13, 0.2, 0.4, 0.8 ml/mouse/day) in a murine model of acute pneumonia induced by influenza virus pandemic strain A/California/07/09 (H1N1). Administration of the drug at the two highest doses led to: a reduction in the virus infectious titer in lung tissue up to 4.2 lgEID50/20 mg of tissue; infected animals' life prolongation up to 6.7 days; an increase in the survival rate of up to 40% and a decrease in morphological signs of inflammation when compared to the control animals. In this study, the dose-response effect of Anaferon for Children was demonstrated on mice for the first time. This finding is especially important for drugs with a principally novel mechanism of action like drugs based on released-active forms of antibodies. J. Med. Virol. 89:759-766, 2017. © 2016 Wiley Periodicals, Inc.

The phenomenon of released-activity. Reply on comment on Don et al.: Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model.

This text is aimed to provide the readers with detailed information about phenomenon of released-activity and reply on the specific risen questions.

Long-term cost-effectiveness analysis of endovascular versus open repair for abdominal aortic aneurysm based on four randomized clinical trials.

BACKGROUND: A number of published economic evaluations of elective endovascular aneurysm repair (EVAR) versus open repair for abdominal aortic aneurysm (AAA) have come to differing conclusions about whether EVAR is cost-effective. This paper reviews the current evidence base and presents up-to-date cost-effectiveness analyses in the light of results of four randomized clinical trials: EVAR-1, DREAM, OVER and ACE. METHODS: Markov models were used to estimate lifetime costs from a UK perspective and quality-adjusted life-years (QALYs) based on the results of each of the four trials. The outcomes included in the model were: procedure costs, surveillance costs, reintervention costs, health-related quality of life, aneurysm-related mortality and other-cause mortality. Alternative scenarios about complications, reinterventions and deaths beyond the trial were explored. RESULTS: Models based on the results of the EVAR-1, DREAM or ACE trials did not find EVAR to be cost-effective at thresholds used in the UK (up to £30,000 per QALY). EVAR seemed cost-effective according to models based on the OVER trial. These results seemed robust to alternative model scenarios about events beyond the trial intervals. CONCLUSION: These analyses did not find that EVAR is cost-effective compared with open repair in the long term in trials conducted in European centres. EVAR did appear to be cost-effective based on the OVER trial, conducted in the USA. Caution must be exercised when transferring the results of economic evaluations from one country to another.

Clinical and economic evaluation of laparoscopic surgery compared with medical management for gastro-oesophageal reflux disease: 5-year follow-up of multicentre randomised trial (the REFLUX trial).

BACKGROUND: Despite promising evidence that laparoscopic fundoplication provides better short-term relief of gastro-oesophageal reflux disease (GORD) than continued medical management, uncertainty remains about whether benefits are sustained and outweigh risks. OBJECTIVE: To evaluate the long-term clinical effectiveness, cost-effectiveness and safety of laparoscopic surgery among people with GORD requiring long-term medication and suitable for both surgical and medical management. DESIGN: Five-year follow-up of a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. Cost-effectiveness was assessed alongside the trial using a NHS perspective for costs and expressing health outcomes in terms of quality-adjusted life-years (QALYs). SETTING: Follow-up was by annual postal questionnaire and selective hospital case notes review; initial recruitment in 21 UK hospitals. PARTICIPANTS: Questionnaire responders among the 810 original participants. At entry, all had documented evidence of GORD and symptoms for > 12 months. Questionnaire response rates (years 1-5) were from 89.5% to 68.9%. INTERVENTIONS: Three hundred and fifty-seven participants were recruited to the randomised comparison (178 randomised to surgical management and 179 randomised to continued medical management) and 453 to the preference groups (261 surgical management and 192 medical management). The surgeon chose the type of fundoplication. MAIN OUTCOME MEASURES: Primary: disease-specific outcome measure (the REFLUX questionnaire); secondary: Short Form questionnaire-36 items (SF-36), European Quality of Life-5 Dimensions (EQ-5D), NHS resource use, reflux medication, complications. RESULTS: The randomised groups were well balanced. By 5 years, 63% in the randomised surgical group and 13% in the randomised medical management group had received a total or partial wrap fundoplication (85% and 3% in the preference groups), with few perioperative complications and no associated deaths. At 1 year (and 5 years) after surgery, 36% (41%) in the randomised surgical group - 15% (26%) of those who had surgery - were taking proton pump inhibitor medication compared with 87% (82%) in the randomised medical group. At each year, differences in the REFLUX score significantly favoured the randomised surgical group (a third of a SD; p< 0.01 at 5 years). SF-36 and EQ-5D scores also favoured surgery, but differences attenuated over time and were generally not statistically significant at 5 years. The worse the symptoms at trial entry, the larger the benefit observed after surgery. Those randomised to medical management who subsequently had surgery had low baseline scores that markedly improved after surgery. Following fundoplication, 3% had surgical treatment for a complication and 4% had subsequent reflux-related operations - most often revision of the wrap. Dysphagia, flatulence and inability to vomit were similar in the two randomised groups. The economic analysis indicated that surgery was the more cost-effective option for this patient group. The incremental cost-effectiveness ratio for surgery in the base case was £7028 per additional QALY; these findings were robust to changes in approaches and assumptions. The probability of surgery being cost-effective at a threshold of £20,000 per additional QALY was > 0.80 for all analyses. CONCLUSIONS: After 5 years, laparoscopic fundoplication continues to provide better relief of GORD symptoms with associated improved health-related quality of life. Complications of surgery were uncommon. Despite being initially more costly, a surgical policy is highly likely to be cost-effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15517081. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 22. See the HTA programme website for further project information.

Cost-effectiveness of laparoscopic fundoplication versus continued medical management for the treatment of gastro-oesophageal reflux disease based on long-term follow-up of the REFLUX trial.

BACKGROUND: Laparoscopic fundoplication surgery has been shown to be a cost-effective alternative to continued medical management over 1 year for patients with gastro-oesophageal reflux disease (GORD). The longer-term cost-effectiveness is, however, uncertain. This study evaluated the long-term health benefits, costs and cost-effectiveness of laparoscopic fundoplication compared with continued medical management in patients with GORD. METHODS: Individual patient data were used from the 5-year follow-up of the REFLUX trial, a large multicentre, pragmatic, randomized trial in which 357 patients with GORD for at least 12 months at trial entry were allocated randomly to early laparoscopic fundoplication or continued medical management. Health outcomes were expressed in quality-adjusted life-years (QALYs). A UK National Health Service perspective was used for costs. RESULTS: The group randomized to surgery experienced better health outcomes in each year of follow-up, but the difference narrowed over time. At 5 years, the surgery group had experienced 0.216 (95 per cent confidence interval 0.021 to 0.412) more QALYs but also accrued €1832 (1214 to 2448) more costs. The incremental cost-effectiveness ratio was €8481 per QALY gained. The probability that surgery is the most cost-effective intervention was 0.932 at a threshold of €24,134/QALY (£20,000/QALY). Results were robust to most sensitivity analyses, except where patients with missing data randomized to surgery were assumed to have worse health outcomes. CONCLUSION: Laparoscopic fundoplication is a cost-effective alternative to continued medical management over 5 years. No evidence was found to suggest that the cost-effectiveness of laparoscopic fundoplication diminishes over time.