Alison Scope

Independent component analysis reveals atypical electroencephalographic activity during visual perception in individuals with autism.

BACKGROUND Individuals with autistic spectrum disorder (ASD) experience atypical visual perception, yet the etiology of this remains unknown. The aim of this study was to investigate the neural correlates of visual perception in individuals with and without ASD by carrying out a detailed analysis of the dynamic brain processes elicited by perception of a simple visual stimulus. METHODS We investigated perception in 20 individuals with ASD and 20 control subjects with electroencephalography (EEG). Visual evoked potentials elicited by Gabor patches of varying spatial frequency and stimulus-induced changes in alpha- and gamma-frequency bands of independent components were compared in those with and without ASD. RESULTS By decomposing the EEG data into independent components, we identified several processes that contributed to the average event related potential recorded at the scalp. Differences between the ASD and control groups were found only in some of these processes. Specifically, in those components that were in or near the striate or extrastriate cortex, stimulus spatial frequency exerted a smaller effect on induced increases in alpha- and gamma-band power, and time to peak alpha-band power was reduced, in the participants with ASD. Induced alpha-band power of components that were in or near the cingulate gyrus was increased in the participants with ASD, and the components that were in or near the parietal cortex did not differ between the two groups. CONCLUSIONS Atypical processing is evident in individuals with ASD during perception of simple visual stimuli. The implications of these data for existing theories of atypical perception in ASD are discussed.

Hemiarthroplasty and Total Hip Arthroplasty for Treating Primary Intracapsular Fracture of the Hip: A Systematic Review and Cost-Effectiveness Analysis

BACKGROUND Hip fracture is a common problem in people aged > 60 years. The treatment options for individuals with high pre-fracture mobility, function and independence are hemiarthroplasty (HA) and total hip arthroplasty (THA). OBJECTIVE The aim of this report is to assess the clinical effectiveness and cost-effectiveness evidence of THA compared with HA in patients with displaced intracapsular fracture who are cognitively intact with high pre-fracture mobility or function. DATA SOURCES A systematic search was made of 11 databases of published and unpublished literature from their inception to december 2010: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, Biological Science Citation Index, Social Science Citation Index, Conference Proceedings Citation Index - Science, UK Clinical Trials Research Network and the National Research Register archive, Current Controlled Trials and ClinicalTrials.gov. REVIEW METHODS A systematic review of randomised controlled trials (RCTs) to assess the effectiveness of THA compared with HA in terms of dislocations, revisions, pain and function, and quality of life. Meta-analysis, independent subgroup analyses and exploratory cost-effectiveness modelling were performed. RESULTS The literature search identified 532 unique citations, of which eight RCTs with almost 1000 participants satisfied the criteria for the effectiveness review. Meta-analysis found a statistically significant increased risk of dislocation for patients treated with THA compared with HA (p = 0.01), but a reduced risk of revision (p = 0.0003). There were no differences in terms of mortality. In all trials, individuals treated with THA reported better function and mobility and less pain than those treated with HA. Four trials reporting utility data found similar trends. Sensitivity analyses indicated that there were no statistically significant differences in outcomes based on follow-up, study quality, surgical approach taken, type of head or the use of cement. Four papers reported a cost-utility analysis or the cost-effectiveness of THA compared with HA. Exploratory modelling was undertaken that showed that THA is likely to be cost-effective compared with HA even when the limitations of the data and methodology are considered. LIMITATIONS The costs and disutilities associated with revisions and dislocations were not included in the economic evaluation. CONCLUSIONS THA appears to be more cost-effective than HA. It is likely that THA will be associated with increased costs in the initial 2-year period, but lower longer-term costs, owing to potentially lower revision rates. However, these longer-term costs have not been modelled. The capacity and experience of surgeons to perform THA have not been explored and these would need to be addressed at local level were THA to become recommended for active, elderly patients in whom THA is not contraindicated. Further studies examining the impact of surgeon experience on performing the two procedures may offer more robust evidence on outcomes. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Gene expression profiling and expanded immunohistochemistry tests to guide the use of adjuvant chemotherapy in breast cancer management: a systematic review and cost-effectiveness analysis

BACKGROUND Gene expression profiling (GEP) and expanded immunohistochemistry (IHC) tests aim to improve decision-making relating to adjuvant chemotherapy for women with early breast cancer. OBJECTIVE The aim of this report is to assess the clinical effectiveness and cost-effectiveness of nine GEP and expanded IHC tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer in England and Wales. The nine tests are BluePrint, Breast Cancer Index (BCI), IHC4, MammaPrint, Mammostrat, NPI plus (NPI+), OncotypeDX, PAM50 and Randox Breast Cancer Array. DATA SOURCES Databases searched included MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. Databases were searched from January 2009 to May 2011 for the OncotypeDX and MammaPrint tests and from January 2002 to May 2011 for the other tests. REVIEW METHODS A systematic review of the evidence on clinical effectiveness (analytical validity, clinical validity and clinical utility) and cost-effectiveness was conducted. An economic model was developed to evaluate the cost-effectiveness of adjuvant chemotherapy treatment guided by four of the nine test (OncotypeDX, IHC4, MammaPrint and Mammostrat) compared with current clinical practice in England and Wales, using clinicopathological parameters, in women with oestrogen receptor-positive (ER+), lymph node-negative (LN-), human epidermal growth factor receptor type 2-negative (HER2-) early breast cancer. RESULTS The literature searches for clinical effectiveness identified 5993 citations, of which 32 full-text papers or abstracts (30 studies) satisfied the criteria for the effectiveness review. A narrative synthesis was performed. Evidence for OncotypeDX supported the prognostic capability of the test. There was some evidence on the impact of the test on decision-making and to support the case that OncotypeDX predicts chemotherapy benefit; however, few studies were UK based and limitations in relation to study design were identified. Evidence for MammaPrint demonstrated that the test score was a strong independent prognostic factor, but the evidence is non-UK based and is based on small sample sizes. Evidence on the Mammostrat test showed that the test was an independent prognostic tool for women with ER+, tamoxifen-treated breast cancer. The three studies appeared to be of reasonable quality and provided data from a UK setting (one study). One large study reported on clinical validity of the IHC4 test, with IHC4 score a highly significant predictor of distant recurrence. This study included data from a UK setting and appeared to be of reasonable quality. Evidence for the remaining five tests (PAM50, NPI+, BCI, BluePrint and Randox) was limited. The economic analysis suggests that treatment guided using IHC4 has the greatest potential to be cost-effective at a £20,000 threshold, given the low cost of the test; however, further research is needed on the analytical validity and clinical utility of IHC4, and the exact cost of the test needs to be confirmed. Current limitations in the evidence base produce significant uncertainty in the results. OncotypeDX has a more robust evidence base, but further evidence on its impact on decision-making in the UK and the predictive ability of the test in an ER+, LN-, HER- population receiving current drug regimens is needed. For MammaPrint and Mammostrat there were significant gaps in the available evidence and the estimates of cost-effectiveness produced were not considered to be robust by the External Assessment Group. LIMITATIONS Methodological weaknesses in the clinical evidence base relate to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence. Further evidence is required on the clinical utility of all of the tests and on UK-based populations. A key area of uncertainty relates to whether the tests provide prognostic or predictive ability. CONCLUSIONS The clinical evidence base for OncotypeDX is considered to be the most robust. The economic analysis suggested that treatment guided using IHC4 has the most potential to be cost-effective at a threshold of £20,000; however, the evidence base to support IHC4 needs significant further research. STUDY REGISTRATION PROSPERO 2011:CRD42011001361, available from www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42011001361.

Vision in Children and Adolescents with Autistic Spectrum Disorder: Evidence for Reduced Convergence

Evidence of atypical perception in individuals with ASD is mainly based on self report, parental questionnaires or psychophysical/cognitive paradigms. There have been relatively few attempts to establish whether binocular vision is enhanced, intact or abnormal in those with ASD. To address this, we screened visual function in 51 individuals with autistic spectrum disorder and 44 typically developing individuals by measuring visual acuity, stereoacuity, convergence, divergence, ocular motility, incidence of strabismus and integrity of the optokinetic response. The data suggest that many aspects of vision, including visual acuity, are unaffected in ASD, but that convergence is an aspect of visual function that merits further research in those with ASD.

Rivaroxaban for the prevention of venous thromboembolism: a single technology appraisal.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of rivaroxaban for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery based upon a review of the manufacturers submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submissions evidence came from four randomised controlled trials (RCTs) comparing rivaroxaban with enoxaparin [RECORD (Regulation of Coagulation in Orthopedic surgery to pRevent Deep venous thrombosis and pulmonary embolism) 1-4] and three comparing dabigatran with enoxaparin [RE-NOVATE (the prevention of venous thromboembolism after total hip replacement trial), RE-MODEL (the prevention of venous thromboembolism after total knee replacement trial) and RE-MOBILIZE (the prevention of venous thromboembolism after total knee arthroplasty trial)]. The evidence from the four RECORD trials indicates that rivaroxaban had superior efficacy over enoxaparin after total hip replacement (THR) and total knee replacement (TKR). For the composite primary outcome of any deep vein thrombosis (DVT), non-fatal pulmonary embolism (PE) and death from all causes the relative risk reductions were 70-79% in THR and 31-49% in TKR. Rivaroxaban also had superior efficacy over enoxaparin for the secondary outcome major VTE. Rivaroxaban was not inferior to enoxaparin on the safety outcome of major bleeding. After the correction of some errors found by the ERG, the manufacturers economic model represented a reasonable model of patients receiving prophylaxis for THR or TKR. In the base-case analyses rivaroxaban dominated both enoxaparin and dabigatran. The incremental costs saved and quality-adjusted life-years (QALYs) gained were small (below 200 pounds and 0.005, respectively, per person). Analyses were conducted sampling from the distributions observed from the RCTs. When all parameters were sampled rivaroxaban dominated enoxaparin in all scenarios except for two, in which enoxaparin produced more QALYs than rivaroxaban and had an incremental cost per QALY gained of 5000 pounds and 8000 pounds respectively. Rivaroxaban dominated dabigatran when RECORD 1 and RECORD 2, individually or pooled, were compared with RE-NOVATE and when all four rivaroxaban RCTs pooled were compared with all three dabigatran RCTs. Dabigatran dominated rivaroxaban comparing RECORD 4 with RE-MODEL and RE-MOBILIZE, and was more cost-effective than rivaroxaban comparing RECORD 3 (incremental cost per QALY gained of rivaroxaban compared with dabigatran of 123,000 pounds) or RECORD 3 and RECORD 4 pooled (incremental cost per QALY gained of dabigatran compared with rivaroxaban of 400 pounds) with RE-MODEL and RE-MOBILIZE. In conclusion, the evidence indicates that rivaroxaban is not inferior to enoxaparin in terms of the primary and secondary outcomes. The submission presents a reasonable estimation of the cost-effectiveness of rivaroxaban compared with enoxaparin and dabigatran, although the uncertainty in the decision has been underestimated. The results are particularly sensitive to any assumed difference in the number of fatal PEs, but the ERG does not believe there is sufficient evidence to support a difference between interventions. The NICE guidance issued as a result of the STA states that: riveroxaban, within its marketing authorisation, is recommended as an option for the prevention of venous thromboembolism in adults having elective THR or elective TKB.

A systematic review, evidence synthesis and meta-analysis of quantitative and qualitative studies evaluating the clinical effectiveness, the cost-effectiveness, safety and acceptability of interventions to prevent postnatal depression.

BACKGROUND Postnatal depression (PND) is a major depressive disorder in the year following childbirth, which impacts on women, their infants and their families. A range of interventions has been developed to prevent PND. OBJECTIVES To (1) evaluate the clinical effectiveness, cost-effectiveness, acceptability and safety of antenatal and postnatal interventions for pregnant and postnatal women to prevent PND; (2) apply rigorous methods of systematic reviewing of quantitative and qualitative studies, evidence synthesis and decision-analytic modelling to evaluate the preventive impact on women, their infants and their families; and (3) estimate cost-effectiveness. DATA SOURCES We searched MEDLINE, EMBASE, Science Citation Index and other databases (from inception to July 2013) in December 2012, and we were updated by electronic alerts until July 2013. REVIEW METHODS Two reviewers independently screened titles and abstracts with consensus agreement. We undertook quality assessment. All universal, selective and indicated preventive interventions for pregnant women and women in the first 6 postnatal weeks were included. All outcomes were included, focusing on the Edinburgh Postnatal Depression Scale (EPDS), diagnostic instruments and infant outcomes. The quantitative evidence was synthesised using network meta-analyses (NMAs). A mathematical model was constructed to explore the cost-effectiveness of interventions contained within the NMA for EPDS values. RESULTS From 3072 records identified, 122 papers (86 trials) were included in the quantitative review. From 2152 records, 56 papers (44 studies) were included in the qualitative review. The results were inconclusive. The most beneficial interventions appeared to be midwifery redesigned postnatal care [as shown by the mean 12-month EPDS score difference of -1.43 (95% credible interval -4.00 to 1.36)], person-centred approach (PCA)-based and cognitive-behavioural therapy (CBT)-based intervention (universal), interpersonal psychotherapy (IPT)-based intervention and education on preparing for parenting (selective), promoting parent-infant interaction, peer support, IPT-based intervention and PCA-based and CBT-based intervention (indicated). Women valued seeing the same health worker, the involvement of partners and access to several visits from a midwife or health visitor trained in person-centred or cognitive-behavioural approaches. The most cost-effective interventions were estimated to be midwifery redesigned postnatal care (universal), PCA-based intervention (indicated) and IPT-based intervention in the sensitivity analysis (indicated), although there was considerable uncertainty. Expected value of partial perfect information (EVPPI) for efficacy data was in excess of £150M for each population. Given the EVPPI values, future trials assessing the relative efficacies of promising interventions appears to represent value for money. LIMITATIONS In the NMAs, some trials were omitted because they could not be connected to the main network of evidence or did not provide EPDS scores. This may have introduced reporting or selection bias. No adjustment was made for the lack of quality of some trials. Although we appraised a very large number of studies, much of the evidence was inconclusive. CONCLUSIONS Interventions warrant replication within randomised controlled trials (RCTs). Several interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty. FUTURE WORK RECOMMENDATIONS Several interventions appear to be cost-effective relative to usual care, but this is subject to considerable uncertainty. Future research conducting RCTs to establish which interventions are most clinically effective and cost-effective should be considered. STUDY REGISTRATION This study is registered as PROSPERO CRD42012003273. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Are Children with Autistic Spectrum Disorders Susceptible to Contour Illusions

Children with autism have been shown to be less susceptible to Kanisza type contour illusions than children without autism (Happe, 1996). Other authors have suggested that this finding could be explained by the fact that participants with autism were required to make a potentially ambiguous verbal response which may have masked whether or not they actually perceived the illusory contours (Ropar & Mitchell, 1999). The present study tested perception of illusory contours in children with autism using a paradigm that requires participants to make a forced choice about the dimensions of a shape defined by illusory contours. It was reasoned that accuracy of the participant on this task would indicate whether or not children with autism could perceive illusory contours. A total of 18 children with autistic spectrum disorder, 16 children with special educational needs not including autism and 20 typically developing children completed an experimental task which assessed perception of Kanisza-style rectangles defined by illusory contours. There were no significant differences between the performance of the children with autism and either of the two control groups, suggesting that perception of illusory contours is intact in autism.

Systematic review and economic modelling of the clinical effectiveness and cost-effectiveness of art therapy among people with non-psychotic mental health disorders

BACKGROUND Mental health problems account for almost half of all ill health in people under 65 years. The majority are non-psychotic (e.g. depression, anxiety and phobias). For some people, art therapy may provide more profound and long-lasting healing than more standard forms of treatment, perhaps because it can provide an alternative means of expression and release from trauma. As yet, no formal evaluation of art therapy for non-psychotic mental health disorders has been conducted. AIM This review aimed to evaluate evidence for the clinical effectiveness and cost-effectiveness of art therapy for non-psychotic mental health disorders. METHODS Comprehensive literature searches for studies examining art therapy in populations with non-psychotic mental health disorders were performed in major health-related and social science bibliographic databases including MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Allied and Complementary Medicine Database (AMED) and Applied Social Sciences Index and Abstracts (ASSIA) from inception up to May 2013. A quantitative systematic review of clinical effectiveness, a qualitative review to explore the acceptability, relative benefits and potential harms, and a cost-utility analysis of studies evaluating cost-effectiveness of art therapy were conducted. RESULTS In the quantitative review, 15 randomised controlled trials (RCTs) were included (n = 777). Meta-analysis was not possible because of clinical heterogeneity and insufficient comparable data on outcome measures across studies. A narrative synthesis reports that art therapy was associated with significant positive changes relative to the control group in mental health symptoms in 10 out of the 15 studies. The control groups varied between studies but included wait-list/no treatment, attention placebo controls and psychological therapy comparators. Four studies reported improvement from baseline but no significant difference between groups. One study reported that outcomes were more favourable in the control group. The quality of included RCTs was generally low. In the qualitative review, 12 cohort studies were included (n = 188 service users; n = 16 service providers). Themes relating to benefits of art therapy for service users included the relationship with the therapist, personal achievement and distraction. Areas of potential harms were related to the activation of emotions that were then unresolved, lack of skill of the art therapist and sudden termination of art therapy. The quality of included qualitative studies was generally low to moderate. In the cost-effectiveness review, a de novo model was constructed and populated with data identified from the clinical review. Scenario analyses were conducted allowing comparisons of group art therapy with wait-list control, group art therapy with group verbal therapy, and individual art therapy versus control. Art therapy appeared cost-effective compared with wait-list control with high certainty, although generalisability to the target population was unclear. Verbal therapy appeared more cost-effective than art therapy but there was considerable uncertainty and a sizeable probability that art therapy was more clinically effective. The cost-effectiveness of individual art therapy was uncertain and dependent on assumptions regarding clinical benefit and duration of benefit. CONCLUSIONS From the limited available evidence, art therapy was associated with positive effects when compared with a control in a number of studies in patients with different clinical profiles, and it was reported to be an acceptable treatment and was associated with a number of benefits. Art therapy appeared to be cost-effective compared with wait-list but further studies are needed to confirm this finding as well as evidence to inform future cost-effective analyses of art therapy versus other treatments. STUDY REGISTRATION The study is registered as PROSPERO CRD42013003957. FUNDING The National Institute for Health Research Health Technology Assessment programme.

The clinical and cost effectiveness of group art therapy for people with non-psychotic mental health disorders: a systematic review and cost-effectiveness analysis

BackgroundThe majority of mental health problems are non-psychotic (e.g., depression, anxiety, and phobias). For some people, art therapy may be a more acceptable alternative form of psychological therapy than standard forms of treatment, such as talking therapies. This study was part of a health technology assessment commissioned by the National Institute for Health Research, UK and aimed to systematically appraise the clinical and cost-effective evidence for art therapy for people with non-psychotic mental health disorders.MethodsComprehensive literature searches for studies examining art therapy in populations with non-psychotic mental health disorders were performed in May 2013. A quantitative systematic review of clinical effectiveness and a systematic review of studies evaluating the cost-effectiveness of group art therapy were conducted.ResultsEleven randomised controlled trials were included (533 patients). Meta-analysis was not possible due to clinical heterogeneity and insufficient comparable data on outcome measures across studies. The control groups varied between studies but included: no treatment/wait-list, attention placebo controls and psychological therapy comparators. Art therapy was associated with significant positive changes relative to the control group in mental health symptoms in 7 of the 11 studies. A de novo model was constructed and populated with data identified from the clinical review. Scenario analyses were conducted allowing comparisons of group art therapy with wait-list control and group art therapy with group verbal therapy. Group art-therapy appeared cost-effective compared with wait-list control with high certainty although generalisability to the target population was unclear; group verbal therapy appeared more cost-effective than art therapy but there was considerable uncertainty and a sizeable probability that art therapy was more cost effective.ConclusionsFrom the limited available evidence art therapy was associated with positive effects compared with control in a number of studies in patients with different clinical profiles. The included trials were generally of poor quality and are therefore likely to be at high risk of bias. Art therapy appeared to be cost-effective versus wait-list but further studies are needed to confirm this finding in the target population. There was insufficient evidence to make an informed comparison of the cost-effectiveness of group art therapy with group verbal therapy.Trial registrationHTA project no. 12/27/16; PROSPERO registration no. CRD42013003957.

Echocardiography in newly diagnosed atrial fibrillation patients: a systematic review and economic evaluation

OBJECTIVE To investigate the clinical effectiveness and cost-effectiveness of transthoracic echocardiography (TTE) in all patients who are newly diagnosed with atrial fibrillation (AF). DESIGN Narrative synthesis reviews were conducted on the prognostic and diagnostic accuracy of TTE for, and prevalence of, pathologies in patients with AF. Databases were searched from inception. MEDLINE searches were conducted from March to August 2010, and reference lists of articles checked. There were 44 diagnostic accuracy studies, five prognostic studies, and 16 prevalence studies accepted into the review. Given the complexity of the many pathologies identified by TTE, the variety of potential changes to clinical management, and paucity of data, the model focused on changes to oral anticoagulation (OAC). The mathematical model assessed the cost-effectiveness of TTE for patients with AF who were not routinely given OAC, assuming, if left atrial abnormality was detected, that the higher risk of stroke warranted OAC; this meant that patients with a CHADS2 (cardiac failure, hypertension, age, diabetes, stroke doubled) score of 0 [dabigatran etexilate (Pradaxa, Boehringer Ingelheim)/rivaroxaban (Xarelto, Bayer Schering)] or 0/1 (warfarin) were included. A simplified approach evaluated the additional quality-adjusted life-years (QALYs) required in order for TTE to be perceived as cost-effective at a threshold of £20,000 per QALY. SETTING Transthoracic echocardiography is usually performed in cardiology clinics but may be used in primary or non-specialist secondary care. PARTICIPANTS Patients with newly diagnosed AF. INTERVENTION Transthoracic echocardiography. MAIN OUTCOME MEASURES Prognosis, diagnostic sensitivity or specificity of TTE, prevalence of pathologies in patients with AF, cost-effectiveness and QALYs. RESULTS Prognostic studies indicated that TTE-diagnosed left ventricular dysfunction, increased left atrial diameter and valvular abnormality were significantly associated with an increased risk of stroke, mortality or thromboembolism. There was a high prevalence (around 25-30%) of ischaemic heart disease, valvular heart disease and heart failure in patients with AF. Diagnostic accuracy of TTE was high, with most pathologies having specificity of ≥ 0.8 and sensitivity of ≥ 0.6. The mathematical model predicted that when the CHADS2 tool is used the addition of TTE in identifying patients with left atrial abnormality appears to be cost-effective for informing some OAC decisions. In the simplified approach a threshold of 0.0033 was required for a TTE to be cost-effective. CONCLUSIONS When CHADS2 was used, the addition of TTE in identifying patients with left atrial abnormality was cost-effective for informing some OAC decisions. A simple analysis indicates that the number of QALYs required for TTE to be cost-effective is small, and that if benefits beyond those associated with a reduction in stroke are believed probable then TTE is likely to be cost-effective in all scenarios. Our findings suggest that further research would be useful, following up newly diagnosed patients with AF who have undergone TTE, to study treatments given as a result of TTE diagnoses and subsequent cardiovascular events. This could identify additional benefits of routine testing, beyond stroke prevention. Studies assessing the proportion of people with a CHADS2 score of 0 or 1 that have left atrial abnormality would provide better estimates of the cost-effectiveness of TTE, and allow more accurate estimates of the sensitivity and specificity of TTE for identifying left atrial abnormality in AF to be obtained. STUDY REGISTRATION PROSPERO CRD42011001354. FUNDING The National Institute for Health Research Health Technology Assessment programme.