Multimodal Medical Image Fusion Based on Content-based and PCA-sigmoid.

OBJECTIVE: The objective of any multimodal medical image fusion algorithm is to assist a radiologist for better decision-making during the diagnosis and therapy by integrating the anatomical (magnetic resonance imaging) and functional (positron emission tomography/ single-photon emission computed tomography) information. METHODS: We proposed a new medical image fusion method based on content-based decomposition, Principal Component Analysis (PCA), and sigmoid function. We considered Empirical Wavelet Transform (EWT) for content-based decomposition purposes since it can preserve crucial medical image information such as edges and corners. PCA is used to obtain initial weights corresponding to each detail layer. RESULTS: In our experiments, we found that direct usage of PCA for detail layer fusion introduces severe artifacts into the fused image due to weight scaling issues. In order to tackle this, we considered using the sigmoid function for better weight scaling. We considered 24 pairs of MRI-PET and 24 pairs of MRI-SPECT images for fusion, and the results are measured using four significant quantitative metrics. CONCLUSION: Finally, we compared our proposed method with other state-of-the-art transformbased fusion approaches, using traditional and recent performance measures. An appreciable improvement is observed in both qualitative and quantitative results compared to other fusion methods.

Schizophrenia Detection in Adolescents from EEG Signals using Symmetrically weighted Local Binary Patterns.

Schizophrenia is one of the most complex of all mental diseases. In this paper, we propose a symmetrically weighted local binary patterns (SLBP)-based automated approach for detection of schizophrenia in adolescents from electroencephalogram (EEG) signals. We extract SLBP-based histogram features from each of the EEG channels. These features are given to a correlation-based feature selection algorithm to get reduced feature vector length. Finally, the feature vector thus obtained is given to LogitBoost classifier to discriminate between schizophrenia and healthy EEG signals.The results validated on the publicly available database suggest that the SLBP effectively characterize the changes in EEG signals and are helpful for the classification of schizophrenia and healthy EEG signals with a classification accuracy of 91.66%. In addition, our approach has provided better results than the recently proposed approaches in schizophrenia detection.

Robotic complete mesocolic excision with central vascular ligation for right colonic tumours - a propensity score-matching study comparing with standard laparoscopy.

BACKGROUND: Laparoscopic complete mesocolic excision (CME) of the right colon with central vascular ligation (CVL) is a technically demanding procedure. This study retrospectively evaluated the feasibility, safety and oncological outcomes of the procedure when performed using the da Vinci® robotic system. METHODS: A prospective case series was collected over 3 years for patients with right colonic cancers treated by standardized robotic CME with CVL using the superior mesenteric vessels first approach. The CME group was compared to a 2 : 1 propensity score-matched non-CME group who had conventional laparoscopic right colectomy with D2 nodal dissection. Primary outcomes were total lymph node harvest and length of specimen. Secondary outcomes were operative time, postoperative complications, and disease-free and overall survival. RESULTS: The study included 120 patients (40 in the CME group and 80 in the non-CME group). Lymph node yield was higher (29 versus 18, P = 0.006), the specimen length longer (322 versus 260 mm, P = 0.001) and median operative time was significantly longer (180 versus 130 min, P < 0.001) with robotic CME versus laparoscopy, respectively. Duration of hospital stay was longer with robotic CME, although not significantly (median 6 versus 5 days, P = 0.088). There were no significant differences in R0 resection rate, complications, readmission rates and local recurrence. A trend in survival benefit with robotic CME for disease-free (P = 0.0581) and overall survival (P = 0.0454) at 3 years was documented. CONCLUSION: Robotic CME with CVL is feasible and, although currently associated with a longer operation time, it provides good specimen quality, higher lymph node yield and acceptable morbidity, with a disease-free survival advantage.

Obstructive sleep apnea detection using discrete wavelet transform-based statistical features.

MOTIVATION AND OBJECTIVE: Obstructive sleep apnea (OSA) is a sleep disorder identified in nearly 10% of middle-aged people, which deteriorates the normal functioning of human organs, notably that of the heart. Furthermore, untreated OSA is associated with increased hypertension, diabetes, stroke, and cardiovascular diseases, thereby increasing the mortality risk. Therefore, early identification of sleep apnea is of significant interest. METHOD: In this paper, an automated approach for OSA diagnosis using a single-lead electrocardiogram (ECG) has been reported. Three sets of features, namely moments of power spectrum density (PSD), waveform complexity measures, and higher-order moments, are extracted from the 1-min segmented ECG subbands obtained from discrete wavelet transform (DWT). Later, correlation-based feature selection with particle swarm optimization (PSO) search strategy is employed for getting an optimum feature vector. This process retained 18 significant features from initially computed 32 features. Finally, the acquired feature set is fed to different classifiers including, linear discriminant analysis, nearest neighbors, support vector machine, and random forest to perform per segment classification. RESULTS: Experiments on the publicly available physionet single-lead ECG dataset show that the proposed approach using the random forest classifier effectively discriminates normal and OSA ECG signals. Specifically, our method achieved an accuracy of 89% and 90%, with 50-50 hold-out validation and 10-fold cross-validation, respectively. Besides, in both these validation scenarios, our method obtained 96% of the area under ROC. Importantly, our proposed approach provided better performance results than most of the existing methodologies.

Demystifying the factors associated with rural-urban gaps in severe acute malnutrition among under-five children in low- and middle-income countries: a decomposition analysis.

What explains the underlying causes of rural-urban differentials in severe acute malnutrition (SAM) among under-five children is poorly exploited, operationalized, studied and understood in low- and middle-income countries (LMIC). We decomposed the rural-urban inequalities in the associated factors of SAM while controlling for individual, household, and neighbourhood factors using datasets from successive demographic and health survey conducted between 2010 and 2018 in 51 LMIC. The data consisted of 532,680 under-five children nested within 55,823 neighbourhoods across the 51 countries. We applied the Blinder-Oaxaca decomposition technique to quantify the contribution of various associated factors to the observed rural-urban disparities in SAM. In all, 69% of the children lived in rural areas, ranging from 16% in Gabon to 81% in Chad. The overall prevalence of SAM among rural children was 4.8% compared with 4.2% among urban children. SAM prevalence in rural areas was highest in Timor-Leste (11.1%) while the highest urban prevalence was in Honduras (8.5%). Nine countries had statistically significant pro-rural (significantly higher odds of SAM in rural areas) inequality while only Tajikistan and Malawi showed statistically significant pro-urban inequality (p < 0.05). Overall, neighbourhood socioeconomic status, wealth index, toilet types and sources of drinking water were the most significant contributors to pro-rural inequalities. Other contributors to the pro-rural inequalities are birth weight, maternal age and maternal education. Pro-urban inequalities were mostly affected by neighbourhood socioeconomic status and wealth index. Having SAM among under-five children was explained by the individual-, household- and neighbourhood-level factors. However, we found variations in the contributions of these factors. The rural-urban dichotomy in the prevalence of SAM was generally significant with higher odds found in the rural areas. Our findings suggest the need for urgent intervention on child nutrition in the rural areas of most LMIC.

Decomposing the educational inequalities in the factors associated with severe acute malnutrition among under-five children in low- and middle-income countries.

BACKGROUND: Low- and Middle-Income Countries (LMIC) have remained plagued with the burden of severe acute malnutrition (SAM). The decomposition of the educational inequalities in SAM across individual, household and neighbourhood characteristics in LMIC has not been explored. This study aims to decompose educational-related inequalities in the development of SAM among under-five children in LMIC and identify the risk factors that contribute to the inequalities. METHODS: We pooled successive secondary data from the Demographic and Health Survey conducted between 2010 and 2018 in 51 LMIC. We analysed data of 532,680 under-five children nested within 55,823 neighbourhoods. Severe acute malnutrition was the outcome variable while the literacy status of mothers was the main exposure variable. The explanatory variables cut across the individual-, household- and neighbourhood-level factors of the mother-child pair. Oaxaca-Blinder decomposition method was used at p = 0.05. RESULTS: The proportion of children whose mothers were not educated ranged from 0.1% in Armenia and Kyrgyz Republic to as much as 86.1% in Niger. The overall prevalence of SAM in the group of children whose mothers had no education was 5.8% compared with 4.2% among those whose mothers were educated, this varied within each country. Fourteen countries (Cameroon(p < 0.001), Chad(p < 0.001), Comoro(p = 0.047), Burkina Faso(p < 0.001), Ethiopia(p < 0.001), India(p < 0.001), Kenya(p < 0.001), Mozambique(p = 0.012), Namibia(p = 0.001), Nigeria(p < 0.001), Pakistan(p < 0.001), Senegal(p = 0.003), Togo(p = 0.013), and Timor Leste(p < 0.001) had statistically significant pro-illiterate inequality while no country showed statistically significant pro-literate inequality. We found significant differences in SAM prevalence across child's age (p < 0.001), child's sex(p < 0.001), maternal age(p = 0.001), household wealth quintile(p = 0.001), mother's access to media(p = 0.001), birth weight(p < 0.001) and neighbourhood socioeconomic status disadvantage(p < 0.001). On the average, neighbourhood socioeconomic status disadvantage, location of residence were the most important factors in most countries. Other contributors to the explanation of educational inequalities are birth weight, maternal age and toilet type. CONCLUSIONS: SAM is prevalent in most LMIC with wide educational inequalities explained by individual, household and community-level factors. Promotion of women education should be strengthened as better education among women will close the gaps and reduce the burden of SAM generally. We recommend further studies of other determinate causes of inequalities in severe acute malnutrition in LMIC.

Advantages of using a robotic stapler in rectal cancer surgery.

To compare short-term postoperative outcomes in patients undergoing robotic total mesorectal excision (TME) after the use of robotic and laparoscopic staplers. Over a 5-year period, 196 patients were divided into 2 groups according to the use of laparoscopic (LS) or robotic stapler (RS). Patient demographics and postoperative complications were compared. A total of 145 (74%) robotic TME were performed using the LS and 51 (26%) the RS. No conversions to laparoscopy or laparotomy were observed, in either group. Transection of the rectum using one or two firings was achieved in a higher proportion of RS cases (91%) compared with LS cases (60%; p < 0.001). The anastomotic leakage (AL) rate was 4% in the RS group vs. 7% in the LS group (p > 0.05). However, when three or more firings were needed for the rectal transection, the risk of AL increased (3.4% with ≤ 2 firings vs. 10.7% with ≥ 3 firings, p = 0.006). Our data confirm that multiple stapler firings for rectal transection have a major impact on AL. The robotic stapler simplifies the transaction, so that rectal division requires fewer stapler firings, with a potential reduction in the incidence of AL.

The impact of robotic total mesorectal excision on survival of patients with rectal cancer-a propensity matched analysis.

INTRODUCTION: Robotic surgery can overcome some limitations of laparoscopic total mesorectal excision (L-TME), improving the quality of the surgery. We aim to compare the medium-term oncological outcomes of L-TME vs. robotic total mesorectal excision (R-TME) for rectal cancer. METHODS: A retrospective analysis was performed including patients who underwent L-TME or R-TME between 2011 and 2017. Patients presenting with metastatic disease or R1 resection were excluded. From a total of 680 patients, 136 cases of R-TME were matched based on age, gender, stage and time of follow-up with an equal number of patients who underwent L-TME. We compared 3-year disease-free survival (DFS) and overall survival (OS). RESULTS: Major complications were lower in the robotic group (13.2% vs. 22.8%, p = 0.04), highlighting the anastomotic leakage rate (7.4% vs. 16.9%, p = 0.01). The 3-year DFS rate for all stages was 69% for L-TME and 84% for R-TME (p = 0.02). For disease stage III, the 3-year DFS was significantly higher in the R-TME group. OS was also significantly superior in the robotic group for every stage, reaching 86% in stage III. In the multivariate analysis, R-TME was a significant positive prognostic factor for distant metastasis (OR 0.2 95% CI 0.1, 0.6, p = 0.001) and OS (OR 0.2 95% CI 0.07, 0.4, p = 0.000). Moreover, major complications were also found to have a negative impact on OS (OR 8.3 95% CI 3.2, 21.6, p = 0.000). CONCLUSION: R-TME for rectal cancer can achieve better oncological outcomes compared with L-TME, especially in stage III rectal cancers. However, a longer follow-up period is needed to confirm these findings.

[Clinical cases of multiple sclerosis in children with cerebral palsy]. / Klinicheskie sluchai rasseiannogo skleroza u detei s detskim tserebral'nym paralichom.

The careful differential diagnosis is very important in pediatric cases of multiple sclerosis (MS). It has special difficulties, if MS started in patients with residual neurological pathology. Two cases of development of MS in children with cerebral palsy (CP) are presented. The clinical features and diagnostic difficulties in such comorbid situations are discussed .

Classification of ECG heartbeats using nonlinear decomposition methods and support vector machine.

Classifying electrocardiogram (ECG) heartbeats for arrhythmic risk prediction is a challenging task due to minute variations in the amplitude, duration and morphology of the ECG signal. In this paper, we propose two feature extraction approaches to classify five types of heartbeats: normal, premature ventricular contraction, atrial premature contraction, left bundle branch block and right bundle branch block. In the first approach, ECG beats are decomposed into intrinsic mode functions (IMFs) using ensemble empirical mode decomposition (EEMD). Later four parameters, namely the sample entropy, coefficient of variation, singular values, and band power of IMFs are extracted as features. In the second approach, the same features are computed from IMFs extracted using an empirical mode decomposition (EMD) algorithm. The features obtained from the two approaches are independently fed to the sequential minimal optimization-support vector machine (SMO-SVM) for classification. We used two arrhythmia databases for our evaluation: MIT-BIH and INCART. We compare the proposed approaches with existing methods using the performance measures given by the average values of (i) specificity, (ii) sensitivity, and (iii) accuracy. The first approach demonstrates significant performance with 98.01% sensitivity, 99.49% specificity, and 99.20% accuracy for the MIT-BIH database and 95.15% sensitivity, 98.37% specificity, and 97.57% accuracy for the INCART database.

The first national clinical audit for rheumatoid arthritis.

The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first 3 months of follow-up activity from first presentation to a rheumatology service. Access to care, management of early rheumatoid arthritis and support for self care were measured against National Institute for Health and Care Excellence quality standards; impact of early arthritis and experience of care were measured using patient-reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient-reported outcomes within 3 months and high levels of overall satisfaction were reported but these results were affected by low response rates. This article presents a summary of the national data from the audit and discusses the implications for nursing practice.

Cost effectiveness of total hip arthroplasty in osteoarthritis: comparison of devices with differing bearing surfaces and modes of fixation.

Many different designs of total hip arthroplasty (THA) with varying performance and cost are available. The identification of those which are the most cost-effective could allow significant cost-savings. We used an established Markov model to examine the cost effectiveness of five frequently used categories of THA which differed according to bearing surface and mode of fixation, using data from the National Joint Registry for England and Wales. Kaplan-Meier analyses of rates of revision for men and women were modelled with parametric distributions. Costs of devices were provided by the NHS Supply Chain and associated costs were taken from existing studies. Lifetime costs, lifetime quality-adjusted-life-years (QALYs) and the probability of a device being cost effective at a willingness to pay £20 000/QALY were included in the models. The differences in QALYs between different categories of implant were extremely small (< 0.0039 QALYs for men or women over the patient's lifetime) and differences in cost were also marginal (£2500 to £3000 in the same time period). As a result, the probability of any particular device being the most cost effective was very sensitive to small, plausible changes in quality of life estimates and cost. Our results suggest that available evidence does not support recommending a particular device on cost effectiveness grounds alone. We would recommend that the choice of prosthesis should be determined by the rate of revision, local costs and the preferences of the surgeon and patient.

Estimating areas of common risk in low birth weight and infant mortality in Namibia: a joint spatial analysis at sub-regional level.

There is lots of literature documenting a positive association between low birth weight (LBW) and infant mortality (IM), however, little is known how the risk of LBW and IM are geographically co-distributed. We fitted joint spatial models of LBW and IM, and used data from Namibia, to examine their geographical variability. We used a Bayesian approach to measure and rank areas according to specific and shared risk of LBW and IM. Our findings show some degree of similarities in the spatial pattern of LBW and IM, with high risk in the central and north-eastern parts of the country. Results suggest a need for comprehensive programming of maternal and newborn interventions that reach areas of spatially concentrated risk of LBW and IM. It further presents an opportunity for generating hypotheses for further research aimed at improving child health, especially in higher risk constituencies thus identified.

Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation.

BACKGROUND: Irritable bowel syndrome (IBS) is common, and causes pain, bloating and diarrhoea and/or constipation. It is a troublesome condition that reduces the quality of life but causes no permanent damage. Inflammatory bowel disease (IBD) comprises mainly ulcerative colitis (UC) and Crohn's disease (CD). Both cause serious complications and may lead to sections of the bowel having to be removed, although this is more common with CD. The presenting symptoms of IBS and IBD can be similar. Distinguishing them on clinical signs and symptoms can be difficult. Until recently, colonoscopy was often required to rule out IBD. In younger people, > 60% of colonoscopies showed no abnormality. Faecal calprotectin (FC) is a protein released by the white blood cells, neutrophils, found in inflamed areas of the bowel in IBD. Determining the level of FC in stool samples may help distinguish IBS from IBD. OBJECTIVE: To review the value of FC for distinguishing between IBD and non-IBD. DATA SOURCES: Sources included MEDLINE, EMBASE, The Cochrane Library, Web of Science, websites of journals and the European Crohn's and Colitis Organisation (conference abstracts 2012 and 2013), and contact with experts. REVIEW METHODS: Systematic review and economic modelling. Review Manager (RevMan) version 5.2 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) was used for most analysis, with statistical analyses done in Stata version 12 (StataCorp LP, College Station, TX, USA). Forest plots and receiver operating characteristic curves were produced. Quality Assessment of Diagnostic Accuracy Studies was used for quality assessment. Economic modelling was done in Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA, USA). LIMITATIONS: Studies were often small, most used only one calprotectin cut-off level, and nearly all came from secondary care populations. RESULTS: Twenty-eight studies provided data for 2 × 2 tables and were included in meta-analyses, with seven in the most important comparison in adults (IBS vs. IBD) and eight in the key comparison in paediatrics (IBD vs. non-IBD). Most studies used laboratory enzyme-linked immunosorbent assay (ELISA) tests. For distinguishing between IBD and IBS in adults, these gave pooled sensitivity of 93% and specificity of 94% at FC cut-off level of 50 µg/g. Sensitivities at that cut-off ranged from 83% to 100%, and specificities from 60% to 100%. For distinguishing between IBD and non-IBD in paediatric populations with ELISA tests, sensitivities ranged from 95% to 100% at cut-off of 50 µg/g and specificities of 44-93%. Few studies used point-of-care testing but that seemed as reliable as ELISA, though perhaps less specific. The evidence did not provide any grounds for preferring one test over others on clinical effectiveness grounds. FC testing in primary care could reduce the need for referral and colonoscopies. Any quality-adjusted life-year gains are likely to be small because of the low prevalence of IBD and the high sensitivities of all of the tests, resulting in few false negatives with IBD. However, considerable savings could accrue. Areas of uncertainty include the optimum management of people with borderline results (50-150 µg/g), most of whom do not have IBD. Repeat testing may be appropriate before referral. CONCLUSIONS: Faecal calprotectin can be a highly sensitive way of detecting IBD, although there are inevitably trade-offs between sensitivity and specificity, with some false positives (IBS with positive calprotectin) if a low calprotectin cut-off is used. In most cases, a negative calprotectin rules out IBD, thereby sparing most people with IBS from having to have invasive investigations, such as colonoscopy. STUDY REGISTRATION: PROSPERO CRD 42012003287. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Clinical effectiveness and cost-effectiveness of second- and third-generation left ventricular assist devices as either bridge to transplant or alternative to transplant for adults eligible for heart transplantation: systematic review and cost-effectiveness model.

BACKGROUND: Advanced heart failure (HF) is a debilitating condition for which heart transplant (HT) offers the best treatment option. However, the supply of donor hearts is diminishing and demand greatly exceeds supply. Ventricular assist devices (VADs) are surgically implanted pumps used as an alternative to transplant (ATT) or as a bridge to transplant (BTT) while a patient awaits a donor heart. Surgery and VADs are costly. For the NHS to allocate and deliver such services in a cost-effective way the relative costs and benefits of these alternative treatments need to be estimated. OBJECTIVES: To investigate for patients aged ≥ 16 years with advanced HF eligible for HT: (1) the clinical effectiveness and cost-effectiveness of second- and third-generation VADs used as BTT compared with medical management (MM); and (2) the clinical effectiveness and cost-effectiveness of second- and third-generation VADs used as an ATT in comparison with their use as BTT therapy. DATA SOURCES: Searches for clinical effectiveness studies covered years from 2003 to March 2012 and included the following data bases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), HTA databases [NHS Centre for Reviews and Dissemination (CRD)], Science Citation Index and Conference Proceedings (Web of Science), UK Clinical Research Network (UKCRN) Portfolio Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and National Library of Medicine (NLM) Gateway, Cochrane Central Register of Controlled Trials (CENTRAL), Current Controlled Trials and ClinicalTrials.gov. Reference lists of relevant articles were checked, and VAD manufacturers' websites interrogated. For economic analyses we made use of individual patient data (IPD) held in the UK Blood and Transplant Database (BTDB). REVIEW METHODS: Systematic reviews of evidence on clinical effectiveness and cost-effectiveness of second- and third-generation US Food and Drug Administration (FDA) and/or Conformité Européenne (CE) approved VADs. Publications from the last 5 years with control groups, or case series with 50 or more patients were included. Outcomes included survival, functional capacity (e.g. change in New York Heart Association functional classification), quality of life (QoL) and adverse events. Data from the BTDB were obtained. A discrete-time, semi-Markov, multistate model was built. Deterministic and probabilistic methods with multiple sensitivity analyses varying survival, utilities and cost inputs to the model were used. Model outputs were incremental cost-effectiveness ratios (ICERs), cost/quality-adjusted life-years (QALYs) gained and cost/life-year gained (LYG). The discount rate was 3.5% and the time horizon varied over 3 years, 10 years and lifetime. RESULTS: Forty publications reported clinical effectiveness of VADs and one study reported cost-effectiveness. We found no high-quality comparative empirical studies of VADs as BTT compared with MM or as ATT compared with BTT. Approximately 15-25% of the patients receiving a device had died by 12 months. Studies reported the following wide ranges for adverse events: 4-27% bleeding requiring transfusion; 1.5-40% stroke; 3.3-48% infection; 1-14% device failure; 3-30% HF; 11-32% reoperation; and 3-53% renal failure. QoL and functional status were reported as improved in studies of two devices [HeartMate II (HMII; Thoratec Inc., Pleasanton, CA, USA) and HeartWare (HW; HeartWare Inc., Framingham, MA, USA)]. At 3 years, 10 years and lifetime, the ICERs for VADs as BTT compared with MM were £122,730, £68,088 and £55,173 respectively. These values were stable to changes in survival of the MM group. Both QoL and costs were reduced by VADs as ATT compared with VADs as BTT giving ICERs in south-west quadrant of the cost effectiveness plain (cost saving/QALY sacrificed) of £353,467, £31,685 and £20,637 over the 3 years, 10 years and lifetime horizons respectively. Probabilistic analyses yielded similar results for both research questions. LIMITATIONS: Conclusions about the clinical effectiveness were limited by the lack of randomised controlled trials (RCTs) comparing the effectiveness of different VADs for BTT or comparing BTT with any alternative treatment and by the overlapping populations in published studies. Although IPD from the BTDB was used to estimate the cost-effectiveness of VADs compared with MM for BTT, the lack of randomisation of populations limited the interpretation of this analysis. CONCLUSIONS: At 3 years, 10 years and lifetime the ICERs for VADs as BTT compared with MM are higher than generally applied willingness-to-pay thresholds in the UK, but at a lifetime time horizon they approximate threshold values used in end of life assessments. VADs as ATT have a reduced cost but cause reduced QALYs relative to BTT. Future research should direct attention towards two areas. First, how any future evaluations of second- or third-generation VADs might be conducted. For ethical reasons a RCT offering equal probability of HT for each group would not be feasible; future studies should fully assess costs, long-term patient survival, QoL, functional ability and adverse events, so that these may be incorporated into economic evaluation agreement on outcomes measures across future studies. Second, continuation of accurate data collection in the UK database to encompass QoL data and comparative assessment of performance with other international centres. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Aspirin for prophylactic use in the primary prevention of cardiovascular disease and cancer: a systematic review and overview of reviews.

BACKGROUND: Prophylactic aspirin has been considered to be beneficial in reducing the risks of heart disease and cancer. However, potential benefits must be balanced against the possible harm from side effects, such as bleeding and gastrointestinal (GI) symptoms. It is particularly important to know the risk of side effects when aspirin is used as primary prevention--that is when used by people as yet free of, but at risk of developing, cardiovascular disease (CVD) or cancer. In this report we aim to identify and re-analyse randomised controlled trials (RCTs), systematic reviews and meta-analyses to summarise the current scientific evidence with a focus on possible harms of prophylactic aspirin in primary prevention of CVD and cancer. OBJECTIVES: To identify RCTs, systematic reviews and meta-analyses of RCTs of the prophylactic use of aspirin in primary prevention of CVD or cancer. To undertake a quality assessment of identified systematic reviews and meta-analyses using meta-analysis to investigate study-level effects on estimates of benefits and risks of adverse events; cumulative meta-analysis; exploratory multivariable meta-regression; and to quantify relative and absolute risks and benefits. METHODS: We identified RCTs, meta-analyses and systematic reviews, and searched electronic bibliographic databases (from 2008 September 2012) including MEDLINE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, NHS Centre for Reviews and Dissemination, and Science Citation Index. We limited searches to publications since 2008, based on timing of the most recent comprehensive systematic reviews. RESULTS: In total, 2572 potentially relevant papers were identified and 27 met the inclusion criteria. Benefits of aspirin ranged from 6% reduction in relative risk (RR) for all-cause mortality [RR 0.94, 95% confidence interval (CI) 0.88 to 1.00] and 10% reduction in major cardiovascular events (MCEs) (RR 0.90, 95% CI 0.85 to 0.96) to a reduction in total coronary heart disease (CHD) of 15% (RR 0.85, 95% CI 0.69 to 1.06). Reported pooled odds ratios (ORs) for total cancer mortality ranged between 0.76 (95% CI 0.66 to 0.88) and 0.93 (95% CI 0.84 to 1.03). Inclusion of the Women's Health Study changed the estimated OR to 0.82 (95% CI 0.69 to 0.97). Aspirin reduced reported colorectal cancer (CRC) incidence (OR 0.66, 95% CI 0.90 to 1.02). However, including studies in which aspirin was given every other day raised the OR to 0.91 (95% CI 0.74 to 1.11). Reported cancer benefits appeared approximately 5 years from start of treatment. Calculation of absolute effects per 100,000 patient-years of follow-up showed reductions ranging from 33 to 46 deaths (all-cause mortality), 60-84 MCEs and 47-64 incidents of CHD and a possible avoidance of 34 deaths from CRC. Reported increased RRs of adverse events from aspirin use were 37% for GI bleeding (RR 1.37, 95% CI 1.15 to 1.62), between 54% (RR 1.54, 95% CI 1.30 to 1.82) and 62% (RR 1.62, 95% CI 1.31 to 2.00) for major bleeds, and between 32% (RR 1.32, 95% CI 1.00 to 1.74) and 38% (RR 1.38, 95% CI 1.01 to 1.82) for haemorrhagic stroke. Pooled estimates of increased RR for bleeding remained stable across trials conducted over several decades. Estimates of absolute rates of harm from aspirin use, per 100,000 patient-years of follow-up, were 99-178 for non-trivial bleeds, 46-49 for major bleeds, 68-117 for GI bleeds and 8-10 for haemorrhagic stroke. Meta-analyses aimed at judging risk of bleed according to sex and in individuals with diabetes were insufficiently powered for firm conclusions to be drawn. LIMITATIONS: Searches were date limited to 2008 because of the intense interest that this subject has generated and the cataloguing of all primary research in so many previous systematic reviews. A further limitation was our potential over-reliance on study-level systematic reviews in which the person-years of follow-up were not accurately ascertainable. However, estimates of number of events averted or incurred through aspirin use calculated from data in study-level meta-analyses did not differ substantially from estimates based on individual patient data-level meta-analyses, for which person-years of follow-up were more accurate (although based on less-than-complete assemblies of currently available primary studies). CONCLUSIONS: We have found that there is a fine balance between benefits and risks from regular aspirin use in primary prevention of CVD. Effects on cancer prevention have a long lead time and are at present reliant on post hoc analyses. All absolute effects are relatively small compared with the burden of these diseases. Several potentially relevant ongoing trials will be completed between 2013 and 2019, which may clarify the extent of benefit of aspirin in reducing cancer incidence and mortality. Future research considerations include expanding the use of IPD meta-analysis of RCTs by pooling data from available studies and investigating the impact of different dose regimens on cardiovascular and cancer outcomes. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A systematic review of evidence on malignant spinal metastases: natural history and technologies for identifying patients at high risk of vertebral fracture and spinal cord compression.

BACKGROUND: Spinal metastases can lead to significant morbidity and reduction in quality of life due to spinal cord compression (SCC). Between 5% and 20% of patients with spinal metastases develop metastatic spinal cord compression during the course of their disease. An early study estimated average survival for patients with SCC to be between 3 and 7 months, with a 36% probability of survival to 12 months. An understanding of the natural history and early diagnosis of spinal metastases and prediction of collapse of the metastatic vertebrae are important. OBJECTIVES: To undertake a systematic review to examine the natural history of metastatic spinal lesions and to identify patients at high risk of vertebral fracture and SCC. DATA SOURCES: The search strategy covered the concepts of metastasis, the spine and adults. Searches were undertaken from inception to June 2011 in 13 electronic databases [MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; Cochrane Database of Systematic Reviews; Cochrane Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), HTA databases (NHS Centre for Reviews and Dissemination); Science Citation Index and Conference Proceedings (Web of Science); UK Clinical Research Network (UKCRN) Portfolio Database; Current Controlled Trials; ClinicalTrials.gov]. REVIEW METHODS: Titles and abstracts of retrieved studies were assessed by two reviewers independently. Disagreement was resolved by consensus agreement. Full data were extracted independently by one reviewer. All included studies were reviewed by a second researcher with disagreements resolved by discussion. A quality assessment instrument was used to assess bias in six domains: study population, attrition, prognostic factor measurement, outcome measurement, confounding measurement and account, and analysis. Data were tabulated and discussed in a narrative review. Each tumour type was looked at separately. RESULTS: In all, 2425 potentially relevant articles were identified, of which 31 met the inclusion criteria. No study examined natural history alone. Seventeen studies reported retrospective data, 10 were prospective studies, and three were other study designs. There was one systematic review. There were no randomised controlled trials (RCTs). Approximately 5782 participants were included. Sample sizes ranged from 41 to 859. The age of participants ranged between 7 and 92 years. Types of cancers reported on were lung alone (n= 3), prostate alone (n= 6), breast alone (n= 7), mixed cancers (n= 13) and unclear (n= 1). A total of 93 prognostic factors were identified as potentially significant in predicting risk of SCC or collapse. Overall findings indicated that the more spinal metastases present and the longer a patient was at risk, the greater the reported likelihood of development of SCC and collapse. There was an increased risk of developing SCC if a cancer had already spread to the bones. In the prostate cancer studies, tumour grade, metastatic load and time on hormone therapy were associated with increased risk of SCC. In one study, risk of SCC before death was 24%, and 2.37 times greater with a Gleason score ≥ 7 than with a score of < 7 (p= 0.003). Other research found that patients with six or more bone lesions were at greater risk of SCC than those with fewer than six lesions [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.012 to 8.35, p= 0.047]. For breast cancer patients who received a computerised tomography (CT) scan for suspected SCC, multiple logistic regression in one study identified four independent variables predictive of a positive test: bone metastases ≥ 2 years (OR 3.0 95% CI 1.2 to 7.6; p= 0.02); metastatic disease at initial diagnosis (OR 3.4, 95% CI 1.0 to 11.4; p= 0.05); objective weakness (OR 3.8, 95% CI 1.5 to 9.5; p= 0.005); and vertebral compression fracture on spine radiograph (OR 2.6, 95% CI 1.0 to 6.5; p= 0.05). A further study on mixed cancers, among patients who received surgery for SCC, reported that vertebral body compression fractures were associated with presurgery chemotherapy (OR 2.283, 95% CI 1.064 to 4.898; p= 0.03), cancer type [primary breast cancer (OR 4.179, 95% CI 1.457 to 11.983; p= 0.008)], thoracic involvement (OR 3.505, 95% CI 1.343 to 9.143; p= 0.01) and anterior cord compression (OR 3.213, 95% CI 1.416 to 7.293; p= 0.005). LIMITATIONS: Many of the included studies provided limited information about patient populations and selection criteria and they varied in methodological quality, rigour and transparency. Several studies identified type of cancer (e.g. breast, lung or prostate cancer) as a significant factor in predicting SCC, but it remains difficult to determine the risk differential partly because of residual bias. Consideration of quantitative results from the studies does not easily allow generation of a coherent numerical summary, studies were heterogeneous especially with regard to population, results were not consistent between studies, and study results almost universally lacked corroboration from other independent studies. CONCLUSION: No studies were found which examined natural history. Overall burden of metastatic disease, confirmed metastatic bone involvement and immediate symptomatology suggestive of spinal column involvement are already well known as factors for metastatic SCC, vertebral collapse or progression of vertebral collapse. Although we identified a large number of additional possible prognostic factors, those which currently offer the most potential are unclear. Current clinical consensus favours magnetic resonance imaging and CT imaging modalities for the investigation of SCC and vertebral fracture. Future research should concentrate on: (1) prospective randomised designs to establish clinical and quality-of-life outcomes and cost-effectiveness of identification and treatment of patients at high risk of vertebral collapse and SCC; (2) Service Delivery and Organisation research on magnetic resonance imaging (MRI) scans and scanning (in tandem with research studies on use of MRI to monitor progression) in order to understand best methods for maximising use of MRI scanners; and (3) investigation of prognostic algorithms to calculate probability of a specified event using high-quality prospective studies, involving defined populations, randomly selected and clearly identified samples, and with blinding of investigators. FUNDING: This report was commissioned by the National Institute for Health Research Health Technology Assessment Programme NIHR HTA Programme as project number HTA 10/91/01.

The epidemiology of HIV infection in Zambia.

Population surveys of health and fertility are an important source of information about demographic trends and their likely impact on the HIV/AIDS epidemic. In contrast to groups sampled at health facilities they can provide nationally and regionally representative estimates of a range of variables. Data on HIV-sero-status were collected in the 2001 Zambia Demographic and Health Survey (ZDHS) and made available in a separate data file in which HIV status was linked to a very limited set of demographic variables. We utilized this data set to examine associations between HIV prevalence, gender, age and geographical location. We applied the generalized geo-additive semi-parametric model as an alternative to the common linear model, in the context of analyzing the prevalence of HIV infection. This model enabled us to account for spatial auto-correlation, non-linear, location effects on the prevalence of HIV infection at the disaggregated provincial level (nine provinces) and assess temporal and geographical variation in the prevalence of HIV infection, while simultaneously controlling for important risk factors. Of the overall sample of 3950, 54% was female. The overall HIV-positivity rate was 565 (14.3%). The mean age at HIV diagnosis for male was 30.3 (SD=11.2) and 27.7 (SD=9.3) for female respectively. Lusaka and Copperbelt have the first and second highest prevalence of AIDS/HIV (marginal odds ratios of 3.24 and 2.88, respectively) but when the younger age of the urban population and the spatial auto-correlation was taken into account, Lusaka and Copperbelt were no longer among the areas with the highest prevalence. Non-linear effects of age at HIV diagnosis are also discussed and the importance of spatial residual effects and control of confounders on the prevalence of HIV infection. The study was conducted to assess the spatial pattern and the effect of confounding risk factors on AIDS/HIV prevalence and to develop a means of adjusting estimates of AIDS/HIV prevalence on the important risk factors. Controlling for important risk factors, such as geographical location (spatial auto-correlation), age structure of the population and gender, gave estimates of prevalence that are statistically robust. Researchers should be encouraged to use all available information in the data to account for important risk factors when reporting AIDS/HIV prevalence. Where this is not possible, correction factors should be applied, particularly where estimates of AIDS/HIV prevalence are pooled in systematic reviews. Our maps can be used for policy planning and management of AIDS/HIV in Zambia.

Morbidity from diarrhoea, cough and fever among young children in Nigeria.

Diarrhoea, cough and fever are the leading causes of childhood morbidity and mortality in sub-Saharan Africa. Despite it being a determinant of mortality in many developing countries, geographical location has seldom been considered as an explanatory factor for the large regional variations seen in the childhood morbidity attributed to these causes in this area. The relevant data collected in two Nigerian Demographic and Health Surveys, one in 1999 and the other in 2003, have now therefore been analysed and compared. The aim was to reveal and explore inequalities in the health of Nigerian children by mapping the spatial distribution of childhood morbidity associated with recent diarrhoea, cough and fever and accounting for important risk factors, using a Bayesian geo-additive model based on Markov-chain-Monte-Carlo techniques. Although the overall prevalences of recent diarrhoea, cough and fever recorded in 1999 (among children aged <3 years) were similar to those seen in 2003 (among children aged <5 years), the mapping of residual spatial effects indicated that, in each survey, the morbidity attributable to each of these causes varied, differently, at state level. Place of birth (hospital v. other), type of feeding (breastfed only v. other), parental education, maternal visits to antenatal clinics, household economic status, marital status of mother and place of residence were each significantly associated with the childhood morbidity investigated. In both surveys, children from urban areas were found to have a significantly lower risk of fever than their rural counterparts. Most other factors affecting diarrhoea, cough and fever differed in the two surveys. The risk of developing each of these three conditions increased in the first 6-8 months after birth but then gradually declined. The analysis explained a significant share of the pronounced residual spatial effects. Maps showing the prevalences of diarrhoea, cough and fever in young children across Nigeria were generated during this study. Such maps should facilitate the development of policies to fulfil the Millennium Development Goals in Nigeria and throughout sub-Saharan Africa.