Revision knee replacement surgery in the NHS: A BASK surgical practice guideline.

BACKGROUND: Revision knee replacement (KR) is both challenging for the surgical team and expensive for the healthcare provider. Limited high quality evidence is available to guide decision-making. AIM: To provide guidelines for surgeons and units delivering revision KR services. METHODS: A formal consensus process was followed by BASK's Revision Knee Working Group, which included surgeons from England, Wales, Scotland and Northern Ireland. This was supported by analysis of National Joint Registry data. RESULTS: There are a large number of surgeons operating at NHS sites who undertake a small number of revision KR procedures. To optimise patient outcomes and deliver cost-effective care high-volume revision knee surgeons working at high volume centres should undertake revision KR. This document outlines practice guidelines for units providing a revision KR service and sets out: The current landscape of revision KR in England, Wales and Northern Ireland. Service organisation within a network model. The necessary infrastructure required to provide a sustainable revision service. Outcome metrics and auditable standards. Financial mechanisms to support this service model. CONCLUSIONS: Revision KR patients being treated in the NHS should be provided with the best care available. This report sets out a framework to both guide and support revision KR surgeons and centres to achieve this aim.

The use of patient-reported outcome measures to guide referral for hip and knee arthroplasty.

AIMS: To assess how the cost-effectiveness of total hip arthroplasty (THA) and total knee arthroplasty (TKA) varies with age, sex, and preoperative Oxford Hip or Knee Score (OHS/OKS); and to identify the patient groups for whom THA/TKA is cost-effective. METHODS: We conducted a cost-effectiveness analysis using a Markov model from a United Kingdom NHS perspective, informed by published analyses of patient-level data. We assessed the cost-effectiveness of THA and TKA in adults with hip or knee osteoarthritis compared with having no arthroplasty surgery during the ten-year time horizon. RESULTS: THA and TKA cost < £7,000 per quality-adjusted life-year (QALY) gained at all preoperative scores below the absolute referral thresholds calculated previously (40 for OHS and 41 for OKS). Furthermore, THA cost < £20,000/QALY for patients with OHS of ≤ 45, while TKA was cost-effective for patients with OKS of ≤ 43, since the small improvements in quality of life outweighed the cost of surgery and any subsequent revisions. Probabilistic and one-way sensitivity analyses demonstrated that there is little uncertainty around the conclusions. CONCLUSION: If society is willing to pay £20,000 per QALY gained, THA and TKA are cost-effective for nearly all patients who currently undergo surgery, including all patients at and above our calculated absolute referral thresholds. Cite this article: Bone Joint J 2020;102-B(7):950-958.

Intranasal cautery for the management of adult epistaxis: systematic review.

BACKGROUND: Cauterisation techniques are commonly used and widely accepted for the management of epistaxis. This review assesses which methods of intranasal cautery should be endorsed as optimum treatment on the basis of benefits, risks, patient tolerance and economic assessment. METHOD: A systematic review of the literature was performed using a standardised methodology and search strategy. RESULTS: Eight studies were identified: seven prospective controlled trials and one randomised controlled trial. Pooling of data was possible from 3 studies, yielding a total of 830 patients. Significantly lower re-bleed rates were identified (p < 0.01) using electrocautery (14.5 per cent) when compared to chemical cautery (35.1 per cent). No evidence suggested that electrocautery was associated with more adverse events or discomfort. Limited evidence supported the use of a vasoconstrictor agent and operating microscope during the procedure. The included studies had considerable heterogeneity in terms of design and outcome measures. CONCLUSION: Consistent evidence suggests that electrocautery has higher success rates than chemical cautery, and is not associated with increased complications or patient discomfort. Lower quality evidence suggests that electrocautery reduces costs and duration of hospital stay.

A Study of the Incidence and Management of Admissions for Cancer-related Symptoms in a District General Hospital: the Potential Role of an Acute Oncology Service.

AIMS: The non-specialist management of cancer patients is becoming increasingly complex. Acute oncology services (AOS), aiming to provide rapid access to specialist advice, have been shown to improve patient experience and reduce length of inpatient stay. The present study aimed to inform service provision in a district general hospital (DGH) by investigating cancer patients, not on active anti-cancer treatment, where the disease itself precipitated admission. This is a vulnerable group who are potentially disenfranchised of focused oncological input due to having less robust care pathways established to date. MATERIALS AND METHODS: A record was available of all cancer patients, not on active anti-cancer treatment, admitted to a Scottish DGH over a 3 month period. All but five of these patient records were retrospectively reviewed. RESULTS: The study group (n=63) comprised 31 males and 32 females; median age was 70 years (range 30-90). The most common reasons for admission were pain (33%), breathlessness (29%) and nausea/vomiting (27%). Symptoms/signs were experienced a median of 4.0 days (range 0.1-35.0) before admission. The median length of stay was 6 days (range 0-39). Ten, 27 and 46% of patients were referred to a cancer nurse specialist, oncologist and palliative care team, respectively. Seventy-six per cent died within 6 months of admission. CONCLUSIONS: About one patient/day was admitted with cancer complications, many of whom will have contacted primary care in the week preceding admission. An AOS, integrating primary and secondary care, would benefit cancer patients by (i) optimising community care, potentially reducing hospital admissions and (ii) increasing inpatient specialist input to reduce length of inpatient stay. Implementation of an AOS would probably have a significant impact on both cancer patients at an individual level and service provision at a regional and national level.

From Dyadic Ties to Information Infrastructures: Care-Coordination between Patients, Providers, Students and Researchers. Contribution of the Health Informatics Education Working Group.

OBJECTIVE: To share how an effectual merging of local and online networks in low resource regions can supplement and strengthen the local practice of patient centered care through the use of an online digital infrastructure powered by all stakeholders in healthcare. User Driven Health Care offers the dynamic integration of patient values and evidence based solutions for improved medical communication in medical care. INTRODUCTION: This paper conceptualizes patient care-coordination through the lens of engaged stakeholders using digital infrastructures tools to integrate information technology. We distinguish this lens from the prevalent conceptualization of dyadic ties between clinician-patient, patient-nurse, clinician-nurse, and offer the holistic integration of all stakeholder inputs, in the clinic and augmented by online communication in a multi-national setting. METHODS: We analyze an instance of the user-driven health care (UDHC), a network of providers, patients, students and researchers working together to help manage patient care. The network currently focuses on patients from LMICs, but the provider network is global in reach. We describe UDHC and its opportunities and challenges in care-coordination to reduce costs, bring equity, and improve care quality and share evidence. CONCLUSION: UDHC has resulted in coordinated global based local care, affecting multiple facets of medical practice. Shared information resources between providers with disparate knowledge, results in better understanding by patients, unique and challenging cases for students, innovative community based research and discovery learning for all.

An alert system for triggering different levels of coastal management urgency: Tunisia case study using rapid environmental assessment data.

Rapid environmental assessment (REA) involves scoring abundances of ecosystems/species groups and magnitude of pressures, concurrently, using the same logarithmic (0-6) assessment scale. We demonstrate the utility of REA data for an alert system identifying different levels of coastal management concern. Thresholds set for abundances/magnitudes, when crossed, trigger proposed responses. Kerkennah, Tunisia, our case study, has significant natural assets (e.g. exceptional seagrass and invertebrate abundances), subjected to varying levels of disturbance and management concern. Using REA thresholds set, fishing, green algae/eutrophication and oil occurred at 'low' levels (scores 0-1): management not (currently) necessary. Construction and wood litter prevailed at 'moderate' levels (scores 2-4): management alerted for (further) monitoring. Solid waste densities were 'high' (scores 5-6): management alerted for action; quantities of rubbish were substantial (20-200 items m⁻¹ beach) but not unprecedented. REA is considered a robust methodology and complementary to other rapid assessment techniques, environmental frameworks and indicators of ecosystem condition.

An automated voxelized dosimetry tool for radionuclide therapy based on serial quantitative SPECT/CT imaging.

PURPOSE: To create an accurate map of the distribution of radiation dose deposition in healthy and target tissues during radionuclide therapy. METHODS: Serial quantitative SPECT∕CT images were acquired at 4, 24, and 72 h for 28 (177)Lu-octreotate peptide receptor radionuclide therapy (PRRT) administrations in 17 patients with advanced neuroendocrine tumors. Deformable image registration was combined with an in-house programming algorithm to interpolate pharmacokinetic uptake and clearance at a voxel level. The resultant cumulated activity image series are comprised of values representing the total number of decays within each voxel's volume. For PRRT, cumulated activity was translated to absorbed dose based on Monte Carlo-determined voxel S-values at a combination of long and short ranges. These dosimetric image sets were compared for mean radiation absorbed dose to at-risk organs using a conventional MIRD protocol (OLINDA 1.1). RESULTS: Absorbed dose values to solid organs (liver, kidneys, and spleen) were within 10% using both techniques. Dose estimates to marrow were greater using the voxelized protocol, attributed to the software incorporating crossfire effect from nearby tumor volumes. CONCLUSIONS: The technique presented offers an efficient, automated tool for PRRT dosimetry based on serial post-therapy imaging. Following retrospective analysis, this method of high-resolution dosimetry may allow physicians to prescribe activity based on required dose to tumor volume or radiation limits to healthy tissue in individual patients.

The effects of age on patient-reported outcome measures in total knee replacements.

We present a comparison of patient-reported outcomes (PROMs) in relation to patient age, in patients who had received a total (TKR) or unicompartmental knee replacement (UKR). The outcome was evaluated using the Oxford knee score (OKS), EuroQol (EQ-5D) and satisfaction scores. Patients aged 65 to 84 years demonstrated better pre-operative function scores than those aged < 65 years (OKS, p = 0.03; EQ-5D, p = 0.048) and those aged ≥ 85 years (OKS, p = 0.03). Post-operative scores were comparable across age groups, but a linear trend for greater post-operative improvement in OKS and EQ-5D was seen with decreasing age (p < 0.033). The overall mean satisfaction score at six months was 84.9, but those aged < 55 years exhibited a lower mean level of satisfaction (78.3) compared with all other age groups (all p < 0.031). The cumulative overall two-year revision rate was 1.3%. This study demonstrates that good early outcomes, as measured by the OKS and EQ-5D, can be anticipated following knee replacement regardless of the patient's age, although younger patients gain greater improvement. However, the lower satisfaction in those aged < 55 years is a concern, and suggests that outcome is not fully encapsulated by the OKS and EQ-5D evaluation, and raises the question whether the OKS alone is an appropriate measure of pain and function in younger, more active individuals.

Long-term trends in the Oxford knee score following total knee replacement.

The Oxford knee score (OKS) is a validated and widely accepted disease-specific patient-reported outcome measure, but there is limited evidence regarding any long-term trends in the score. We reviewed 5600 individual OKS questionnaires (1547 patients) from a prospectively-collected knee replacement database, to determine the trends in OKS over a ten-year period following total knee replacement. The mean OKS pre-operatively was 19.5 (95% confidence interval (CI) 18.8 to 20.2). The maximum post-operative OKS was observed at two years (mean score 34.4 (95% CI 33.7 to 35.2)), following which a gradual but significant decline was observed through to the ten-year assessment (mean score 30.1 (95% CI 29.1 to 31.1)) (p < 0.001). A similar trend was observed for most of the individual OKS components (p < 0.001). Kneeling ability initially improved in the first year but was then followed by rapid deterioration (p < 0.001). Pain severity exhibited the greatest improvement, although residual pain was reported in over two-thirds of patients post-operatively, and peak improvement in the night pain component did not occur until year four. Post-operative OKS was lower for women (p < 0.001), those aged < 60 years (p < 0.003) and those with a body mass index > 35 kg/m(2) (p < 0.014), although similar changes in scores were observed. This information may assist surgeons in advising patients of their expected outcomes, as well as providing a comparative benchmark for evaluating longer-term outcomes following knee replacement.

Simple visual parameters for objective assessment of arthroscopic skill.

BACKGROUND: Restrictions placed on the working hours of doctors over the past decade have resulted in substantial changes to the training and assessment of orthopaedic surgical residents. Many who are responsible for training the surgeons of the future have become concerned that this reduced clinical exposure is having a detrimental impact on technical skill acquisition. Consequently, there is a need for surgical educators to develop more objective methods for assessing surgical skill. The primary aim of this study was to determine whether a novel set of visual parameters assessing visuospatial ability, fine motor dexterity, and gaze control could objectively discriminate among various levels of arthroscopic experience. The secondary aim was to evaluate the correlations between these new parameters and previously established technical skill assessment methods. METHODS: Twenty-seven subjects were divided into a novice group (n = 7), a resident group (n = 15), and an expert group (n = 5) on the basis of arthroscopic experience. All subjects performed a diagnostic knee arthroscopy task on a simulator. Their performance was assessed with use of novel simple visual parameters that included the prevalence of instrument loss, triangulation time, and prevalence of lookdowns. Performance was also evaluated with use of previously validated technical skill assessment methods (a global rating scale and motion analysis). RESULTS: A significant difference in performance among the groups was demonstrated with use of all three novel visual parameters, the global rating scale, and motion analysis (p < 0.05). There were strong and highly significant correlations (p < 0.0001) between each of the novel parameters and the previously validated skill assessment methods. CONCLUSIONS: This study demonstrates the construct validity of three novel visual parameters for objectively assessing arthroscopic performance. These parameters are simple, can be used easily in the operating room, and are strongly correlated with current validated methods of technical skill assessment.

Interpretation of patient-reported outcomes for hip and knee replacement surgery: identification of thresholds associated with satisfaction with surgery.

We obtained information from the Elective Orthopaedic Centre on 1523 patients with baseline and six-month Oxford hip scores (OHS) after undergoing primary hip replacement (THR) and 1784 patients with Oxford knee scores (OKS) for primary knee replacement (TKR) who completed a six-month satisfaction questionnaire. Receiver operating characteristic curves identified an absolute change in OHS of 14 points or more as the point that discriminates best between patients' satisfaction levels and an 11-point change for the OKS. Satisfaction is highest (97.6%) in patients with an absolute change in OHS of 14 points or more, compared with lower levels of satisfaction (81.8%) below this threshold. Similarly, an 11-point absolute change in OKS was associated with 95.4% satisfaction compared with 76.5% below this threshold. For the six-month OHS a score of 35 points or more distinguished patients with the highest satisfaction level, and for the six-month OKS 30 points or more identified the highest level of satisfaction. The thresholds varied according to patients' pre-operative score, where those with severe pre-operative pain/function required a lower six-month score to achieve the highest levels of satisfaction. Our data suggest that the choice of a six-month follow-up to assess patient-reported outcomes of THR/TKR is acceptable. The thresholds help to differentiate between patients with different levels of satisfaction, but external validation will be required prior to general implementation in clinical practice.

Assessing patients for joint replacement: can pre-operative Oxford hip and knee scores be used to predict patient satisfaction following joint replacement surgery and to guide patient selection?

We obtained pre-operative and six-month post-operative Oxford hip (OHS) and knee scores (OKS) for 1523 patients who underwent total hip replacement and 1784 patients who underwent total knee replacement. They all also completed a six-month satisfaction question. Scatter plots showed no relationship between pre-operative Oxford scores and six-month satisfaction scores. Spearman's rank correlation coefficients were -0.04 (95% confidence interval (CI) -0.09 to 0.01) between OHS and satisfaction and 0.04 (95% CI -0.01 to 0.08) between OKS and satisfaction. A receiver operating characteristic (ROC) curve analysis was used to identify a cut-off point for the pre-operative OHS/OKS that identifies whether or not a patient is satisfied with surgery. We obtained an area under the ROC curve of 0.51 (95% CI 0.45 to 0.56) for hip replacement and 0.56 (95% CI 0.51 to 0.60) for knee replacement, indicating that pre-operative Oxford scores have no predictive accuracy in distinguishing satisfied from dissatisfied patients. In the NHS widespread attempts are being made to use patient-reported outcome measures (PROMs) data for the purpose of prioritising patients for surgery. Oxford hip and knee scores have no predictive accuracy in relation to post-operative patient satisfaction. This evidence does not support their current use in prioritising access to care.

Development of micro-electrode array based tests for neurotoxicity: assessment of interlaboratory reproducibility with neuroactive chemicals.

Neuronal assemblies within the nervous system produce electrical activity that can be recorded in terms of action potential patterns. Such patterns provide a sensitive endpoint to detect effects of a variety of chemical and physical perturbations. They are a function of synaptic changes and do not necessarily involve structural alterations. In vitro neuronal networks (NNs) grown on micro-electrode arrays (MEAs) respond to neuroactive substances as well as the in vivo brain. As such, they constitute a valuable tool for investigating changes in the electrophysiological activity of the neurons in response to chemical exposures. However, the reproducibility of NN responses to chemical exposure has not been systematically documented. To this purpose six independent laboratories (in Europe and in USA) evaluated the response to the same pharmacological compounds (Fluoxetine, Muscimol, and Verapamil) in primary neuronal cultures. Common standardization principles and acceptance criteria for the quality of the cultures have been established to compare the obtained results. These studies involved more than 100 experiments before the final conclusions have been drawn that MEA technology has a potential for standard in vitro neurotoxicity/neuropharmacology evaluation. The obtained results show good intra- and inter-laboratory reproducibility of the responses. The consistent inhibitory effects of the compounds were observed in all the laboratories with the 50% Inhibiting Concentrations (IC(50)s) ranging from: (mean ± SEM, in µM) 1.53 ± 0.17 to 5.4 ± 0.7 (n = 35) for Fluoxetine, 0.16 ± 0.03 to 0.38 ± 0.16 µM (n = 35) for Muscimol, and 2.68 ± 0.32 to 5.23 ± 1.7 (n = 32) for Verapamil. The outcome of this study indicates that the MEA approach is a robust tool leading to reproducible results. The future direction will be to extend the set of testing compounds and to propose the MEA approach as a standard screen for identification and prioritization of chemicals with neurotoxicity potential.

Fitness costs associated with mounting a social immune response.

Social immune systems comprise immune defences mounted by individuals for the benefit of others (sensuCotter & Kilner 2010a). Just as with other forms of immunity, mounting a social immune response is expected to be costly but so far these fitness costs are unknown. We measured the costs of social immunity in a sub-social burying beetle, a species in which two or more adults defend a carrion breeding resource for their young by smearing the flesh with antibacterial anal exudates. Our experiments on widowed females reveal that a bacterial challenge to the breeding resource upregulates the antibacterial activity of a female's exudates, and this subsequently reduces her lifetime reproductive success. We suggest that the costliness of social immunity is a source of evolutionary conflict between breeding adults on a carcass, and that the phoretic communities that the beetles transport between carrion may assist the beetle by offsetting these costs.

The effectiveness and cost-effectiveness of behavioural interventions for the prevention of sexually transmitted infections in young people aged 13-19: a systematic review and economic evaluation.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of schools-based skills-building behavioural interventions to encourage young people to adopt and maintain safer sexual behaviour and to prevent them from acquiring sexually transmitted infections (STIs). DATA SOURCES: Electronic bibliographic databases (e.g. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, PsycINFO, CCRCT, NHS EED and DARE) were searched for the period 1985 to March 2008. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify additional published and unpublished references. REVIEW METHODS: A systematic review of effectiveness and economic evaluation of cost-effectiveness were carried out. A descriptive map of studies that met inclusion criteria was produced, and keywords were developed and systematically applied to these studies to identify a policy-relevant subset of studies for the systematic review. Outcome data for variables including sexual behaviour were extracted. An economic model was developed to compare the costs and consequences of the behavioural interventions. A Bernoulli statistical model was constructed to describe the probability of STI infection. RESULTS: There were few significant differences between the interventions and comparators in terms of changes in sexual behaviour outcomes, although there were some significant differences for knowledge and some measures of self-efficacy. The studies included in this review conducted relatively short follow-up assessments at a time when many young people were becoming sexually active. It is therefore possible that favourable behaviour change may have occurred, and become more cost-effective, with time, as sexual activity becomes more routine in young people's lives. The quality of the intervention provider influenced whether or not young people found the interventions to be acceptable and engaging; enthusiasm and considerable expertise were important for effective class management and delivery of skills-building activities, and a supportive school culture was also helpful. Recognition of young people's individual needs in relation to sexual health was another important factor. No conclusions could be drawn on the impact of the interventions on sexual health inequalities due to a lack of relevant data on socioeconomic status, gender and ethnicity. The results of the economic evaluation were considered to be illustrative, mainly due to the uncertainty of the effect of intervention on behavioural outcomes. The results were most sensitive to changes in parameter values for the intervention effect, the transmission probability of STIs and the number of sexual partners. The costs of teacher-led and peer-led behavioural interventions, based on the resources estimated from the relevant randomised controlled trials in our systematic review, were 4.30 pounds and 15 pounds per pupil, respectively. Teacher-led interventions were more cost-effective than peer-led interventions due to the less frequent need for training. The incremental cost-effectiveness of the teacher-led and peer-led interventions was 20,223 pounds and 80,782 pounds per quality-adjusted life-year gained, respectively. An analysis of individual parameters revealed that future research funding should focus on assessing the intervention effect for condom use from a school-based intervention. CONCLUSIONS: School-based behavioural interventions for the prevention of STIs in young people can bring about improvements in knowledge and increased self-efficacy, but the interventions did not significantly influence sexual risk-taking behaviour or infection rates. Future investigation should include long-term follow-up to assess the extent to which safer sexual behaviour is adopted and maintained into adulthood, and prospective cohort studies are needed to look at the parameters that describe the transmission of STIs between partners. Funding should focus on the effectiveness of the interventions on influencing behaviour.

Temporal trends in hip and knee replacement in the United Kingdom: 1991 to 2006.

Using the General Practice Research Database, we examined the temporal changes in the rates of primary total hip (THR) and total knee (TKR) replacement, the age at operation and the female-to-male ratio between 1991 and 2006 in the United Kingdom. We identified 27 113 patients with THR and 23 843 with TKR. The rate of performance of THR and TKR had increased significantly (p < 0.0001 for both) during the 16-year period and was greater for TKR, especially in the last five years. The mean age at operation was greater for women than for men and had remained stable throughout the period of study. The female-to-male ratio was higher for THR and TKR and had remained stable. The data support the notion that the rate of joint replacement is increasing in the United Kingdom with the rate of TKR rising at the highest rate. The perception that the mean age for TKR has decreased over time is not supported.

Computer-assisted navigation for the assessment of fixed flexion in knee arthroplasty.

BACKGROUND: Correction of a fixed flexion deformity is an important goal when performing total knee arthroplasty. The purpose of this study was to assess the accuracy of clinical assessment compared with imageless computer navigation in determining the degree of fixed flexion. METHODS: We performed navigation anatomy registration using 14 cadaver knees.The knees were held in various degrees of flexion with 2 crossed pins. The degree of flexion was first recorded on the computer and then on lateral radiographs. The cadaver knees were draped as they would be for a total knee arthroplasty, and 9 examiners were asked to clinically assess by visual observation the amount of fixed flexion.Three examiners repeated the process 1 week later. RESULTS: The mean error from the radiographs in the navigation group was 2.18 degrees (95% confidence interval [CI] 1.23 degrees -3.01 degrees) compared with 5.57 degrees (95% CI 4.86 degrees -6.29 degrees) in the observer group. The navigation was more consistent, with a range of error of -5 degrees to +5.5 degrees compared with -18.5 degrees to +17.5 degrees in the observer group. The observers tended to underestimate the amount of knee flexion (median error -4 degrees), whereas the navigation group was more evenly distributed (median error 0). The highest concordance coefficient was found between navigation and radiography (0.96). The concordance coefficient was 0.88 for the 3 surgeons who repeated the measurements 1 week later (mean error 3.5 degrees , range 15 degrees ). CONCLUSION: The use of computer navigation appears to be a more accurate method for assessing the degree of knee flexion, with a reduced range of error compared with clinical assessment. The use of computer-assisted surgery may therefore provide surgeons with the information required to more consistently restore full extension during total knee arthroplasty.

The effectiveness and cost-effectiveness of cochlear implants for severe to profound deafness in children and adults: a systematic review and economic model.

OBJECTIVES: To investigate whether it is clinically effective and cost-effective to provide (i) a unilateral cochlear implant for severely to profoundly deaf people (using or not using hearing aids), and (ii) a bilateral cochlear implant for severely to profoundly deaf people with a single cochlear implant (unilateral or unilateral plus hearing aid). DATA SOURCES: Main electronic databases [MEDLINE; EMBASE; Cochrane Database of Systematic Reviews; CENTRAL; NHS EED; DARE; HTA (NHS-CRD); EconLit; National Research Register; and ClinicalTrials.gov] searched in October 2006, updated July 2007. REVIEW METHODS: A systematic review of the literature was undertaken according to standard methods. A state-transition (Markov) model of the main care pathways deaf people might follow and the main complications and device failures was developed. RESULTS: The clinical effectiveness review included 33 papers, of which only two were RCTs. They used 62 different outcome measures and overall were of moderate to poor quality. All studies in children comparing one cochlear implant with non-technological support or an acoustic hearing aid reported gains on all outcome measures, some demonstrating greater gain from earlier implantation. The strongest evidence for an advantage from bilateral over unilateral implantation was for understanding speech in noisy conditions (mean improvement 13.2%, p < 0.0001); those receiving their second implant earlier made greater gains. Comparison of bilateral with unilateral cochlear implants plus an acoustic hearing aid was compromised by small sample sizes and poor reporting, but benefits were seen with bilateral implants. Cochlear implants improved children's quality of life, and those who were implanted before attending school were more likely to do well academically and attend mainstream education than those implanted later. In adults, there was a greater benefit from cochlear implants than from non-technological support in terms of speech perception. Increased age at implantation may reduce effectiveness and there is a negative correlation between duration of deafness and effectiveness. Speech perception measures all showed benefits for cochlear implants over acoustic hearing aids [e.g. mean increase in score of 37 points in noisy conditions (p < 0.001) with BKB sentences]; however, prelingually deafened adults benefited less than those postlingually deafened (mean change scores 20% versus 62%). For unilateral versus bilateral implantation, benefits in speech perception were significant in noisy conditions on all measures [e.g. 76% for HINT sentences (p < 0.0001)]. Quality of life measured with generic and disease-specific instruments or by interview mostly showed significant gains or positive trends from using cochlear implants. The Markov model base-case analysis estimated that, for prelingually profoundly deaf children, the incremental cost-effectiveness ratio (ICER) for unilateral implantation compared with no implantation was 13,413 pounds per quality-adjusted life-year (QALY). Assuming the utility gain for bilateral implantation is the same for adults and children, the ICERs for simultaneous and sequential bilateral implantation versus unilateral implantation were 40,410 pounds and 54,098 pounds per QALY respectively. For postlingually sensorineurally profoundly deaf adults, the corresponding ICERs were 14,163 pounds, 49,559 pounds and 60,301 pounds per QALY respectively. Probabilistic threshold analyses suggest that unilateral implants are highly likely to be cost-effective for adults and children at willingness to pay thresholds of 20,000 pounds or 30,000 pounds per QALY. There are likely to be overall additional benefits from bilateral implantation, enabling children and adults to hold conversations more easily in social situations. CONCLUSIONS: Unilateral cochlear implantation is safe and effective for adults and children and likely to be cost-effective in profoundly deaf adults and profoundly and prelingually deaf children. However, decisions on the cost-effectiveness of bilateral cochlear implants should take into account the high degree of uncertainty within the model regarding the probable utility gain.

Adefovir dipivoxil and pegylated interferon alpha for the treatment of chronic hepatitis B: an updated systematic review and economic evaluation.

OBJECTIVE: To update and extend a 2006 report on the clinical effectiveness and cost-effectiveness of adefovir dipivoxil (ADV) and pegylated interferon alpha (PEG-alpha) for the treatment of chronic hepatitis B (CHB). DATA SOURCES: Thirteen bibliographic databases were searched including MEDLINE, EMBASE and the Cochrane Library. Searches were run from the beginning of 2005 to September 2007. REVIEW METHODS: For the clinical effectiveness review, randomised controlled trials (RCTs) comparing ADV, PEG-alpha-2a and PEG-alpha-2b with currently licensed treatments for CHB, including non-pegylated interferon alpha (IFN-alpha) and lamivudine (LAM), were included. Outcomes included biochemical, histological and virological response to treatment, drug resistance and adverse effects. A systematic review of economic evaluations of antiviral treatments for CHB was conducted. The economic Markov model used in the 2006 report was updated in terms of utility values, discount rates and costs. RESULTS: Of the 82 papers retrieved for detailed screening, eight RCTs were included. Three evaluated ADV, four evaluated PEG-alpha-2b and one (from the original literature search) compared PEG-alpha-2b plus LAM with PEG-alpha-2b monotherapy. No RCTs of PEG-alpha-2a were identified. One ADV trial showed a statistically significant difference between ADV and placebo in terms of ALT response and HBV DNA levels, favouring ADV. Following withdrawal of ADV, levels were similar to those in placebo patients. In the ADV versus ADV plus LAM trial, there was a statistically significant difference in favour of the combination treatment. In the PEG-alpha trials, there were statistically significant differences favouring PEG-alpha-2b plus LAM compared with either one of the drugs given as monotherapy. For the comparison between PEG-alpha-2b and IFN-alpha and the comparison between different staggered regimens of the commencement of PEG-alpha-2b and LAM, there were no statistically significant differences between groups. Four full economic evaluations were identified, in addition to one identified in the original report. Two assessed PEG-alpha-2a; the remainder assessed ADV. PEG-alpha-2a was associated with increased treatment costs and gains in quality-adjusted life expectancy. In a UK study, the incremental cost-effectiveness ratio (ICER) for PEG-alpha-2a was 10,444 pounds per QALY gained compared with LAM. Evaluations of ADV found that LAM monotherapy was dominated; the ICER for ADV monotherapy compared with 'doing nothing' was $19,731. The results of the updated analysis were generally robust to changes in deterministic sensitivity analysis. In a probabilistic sensitivity analysis, the same sequence of treatments was identified as optimal. In a probabilistic sensitivity analysis, PEG-alpha-2b had a probability of being cost-effective of 79% at a willingness-to-pay threshold of 20,000 pounds per QALY, and 86% at a willingness-to-pay threshold of 30,000 pounds per QALY. CONCLUSIONS: Both ADV and PEG-alpha are beneficial for patients with CHB in terms of suppressing viral load, reducing liver damage-associated biochemical activity, inducing HBeAg seroconversion, and reducing liver fibrosis and necroinflammation. The effects of long-term treatment with ADV are generally durable, with relatively low rates of resistance. In most cases, cost-effectiveness estimates were within acceptable ranges. Further research should assess the clinical effectiveness and cost-effectiveness of newer antiviral agents in relation to existing drugs, including the role of initiating treatment with combination therapy.

Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is more prevalent in US American minority populations of African or Native American descent than it is in European Americans. However, the proportion of this epidemiological difference that can be ascribed to genetic or environmental factors is unknown. To determine whether genetic ancestry is correlated with diabetes risk in Latinos, we estimated the proportion of European ancestry in case-control samples from Mexico and Colombia in whom socioeconomic status had been carefully ascertained. METHODS: We genotyped 67 ancestry-informative markers in 499 participants with type 2 diabetes and 197 controls from Medellín (Colombia), as well as in 163 participants with type 2 diabetes and 72 controls from central Mexico. Each participant was assigned a socioeconomic status scale via various measures. RESULTS: Although European ancestry was associated with lower diabetes risk in Mexicans (OR [95% CI] 0.06 [0.02-0.21], p = 2.0 x 10(-5)) and Colombians (OR 0.26 [0.08-0.78], p = 0.02), adjustment for socioeconomic status eliminated the association in the Colombian sample (OR 0.64 [0.19-2.12], p = 0.46) and significantly attenuated it in the Mexican sample (OR 0.17 [0.04-0.71], p = 0.02). Adjustment for BMI did not change the results. CONCLUSIONS/INTERPRETATION: The proportion of non-European ancestry is associated with both type 2 diabetes and lower socioeconomic status in admixed Latino populations from North and South America. We conclude that ancestry-directed search for genetic markers associated with type 2 diabetes in Latinos may benefit from information involving social factors, as these factors have a quantitatively important effect on type 2 diabetes risk relative to ancestry effects.