Evaluating enhanced recovery after surgery: time to cover new ground and discover the missing patient voice

Multicomponent peri-operative interventions offer to accelerate patient recovery and improve cost-effectiveness. The recent National Institute of Health Research-commissioned evidence synthesis review by Nunns et al. considers the effectiveness and cost-effectiveness of all types of multicomponent interventions for older adults undergoing elective inpatient surgery. Enhanced recovery programmes (ERPs) were the most commonly evaluated intervention. An association between ERPs and decreased length of stay was observed, whilst complication rates and time to recovery were static or sometimes reduced. Important areas which lack research in the context of ERPs are patient-reported outcome measures, patients with complex needs and assessment of factors pertaining to successful ERP implementation. The next generation of ERP studies should seek to develop our understanding in these key areas

Multicomponent hospital-led interventions to reduce hospital stay for older adults following elective surgery: a systematic review

BackgroundElective older adult inpatient admissions are increasingly common. Older adults are at an elevated risk of adverse events in hospital, potentially increasing with lengthier hospital stay. Hospital-led organisational strategies may optimise hospital stay for elective older adult inpatients.ObjectivesTo evaluate the effectiveness and cost-effectiveness of hospital-led multicomponent interventions to reduce hospital stay for older adults undergoing elective hospital admissions.Data sourcesSeven bibliographic databases (MEDLINE, MEDLINE In-Process &amp; Other Non-Indexed Citations, EMBASE, Health Management Information Consortium, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature and Allied and Complementary Medicine Database) were searched from inception to date of search (August 2017), alongside carrying out of web searches, citation searching, inspecting relevant reviews, consulting stakeholders and contacting authors. This search was duplicated, with an additional cost-filter, to identify cost-effectiveness evidence.Review methodsComparative studies were sought that evaluated the effectiveness or cost-effectiveness of relevant interventions in elective inpatients with a mean or median age of ≥ 60 years. Study selection, data extraction and quality assessment were completed independently by two reviewers. The main outcome was length of stay, but all outcomes were considered. Studies were sorted by procedure, intervention and outcome categories. Where possible, standardised mean differences or odds ratios were calculated. Meta-analysis was performed when multiple randomised controlled trials had the same intervention, treatment procedure, comparator and outcome. Findings were explored using narrative synthesis.FindingsA total of 218 articles were included, with 80 articles from 73 effectiveness studies (n = 26,365 patients) prioritised for synthesis, including 34 randomised controlled trials conducted outside the UK and 39 studies from the UK, of which 12 were randomised controlled trials. Fifteen studies included cost-effectiveness data. The evidence was dominated by enhanced recovery protocols and prehabilitation, implemented to improve recovery from either colorectal surgery or lower limb arthroplasty. Six other surgical categories and four other intervention types were identified. Meta-analysis found that enhanced recovery protocols were associated with 1.5 days’ reduction in hospital stay among patients undergoing colorectal surgery (Cohen’sd = –0.51, 95% confidence interval –0.78 to –0.24;p &lt; 0.001) and with 5 days’ reduction among those undergoing upper abdominal surgery (Cohen’sd = –1.04, 95% confidence interval –1.55 to –0.53;p &lt; 0.001). Evidence from the UK was not pooled (owing to mixed study designs), but it echoed findings from the international literature. Length of stay usually was reduced with intervention or was no different. Other clinical outcomes also improved or were no worse with intervention. Patient-reported outcomes were not frequently reported. Cost and cost-effectiveness evidence came from 15 highly heterogeneous studies and was less conclusive.LimitationsStudies were usually of moderate or weak quality. Some intervention or treatment types were under-reported or absent. The reporting of variance data often precluded secondary analysis.ConclusionsEnhanced recovery and prehabilitation interventions were associated with reduced hospital stay without detriment to other clinical outcomes, particularly for patients undergoing colorectal surgery, lower limb arthroplasty or upper abdominal surgery. The impacts on patient-reported outcomes, health-care costs or additional service use are not well known.Future workFurther studies evaluating of the effectiveness of new enhanced recovery pathways are not required in colorectal surgery or lower limb arthroplasty. However, the applicability of these pathways to other procedures is uncertain. Future studies should evaluate the implementation of interventions to reduce service variation, in-hospital patient-reported outcomes, impacts on health and social care service use, and longer-term patient-reported outcomes.Study registrationThis study is registered as PROSPERO CRD42017080637.FundingThe National Institute for Health Research Health Services and Delivery Research programme.</jats:sec

Evaluating enhanced recovery after surgery: time to cover new ground and discover the missing patient voice

AbstractMulticomponent peri-operative interventions offer to accelerate patient recovery and improve cost-effectiveness. The recent National Institute of Health Research-commissioned evidence synthesis review by Nunns et al. considers the effectiveness and cost-effectiveness of all types of multicomponent interventions for older adults undergoing elective inpatient surgery. Enhanced recovery programmes (ERPs) were the most commonly evaluated intervention. An association between ERPs and decreased length of stay was observed, whilst complication rates and time to recovery were static or sometimes reduced. Important areas which lack research in the context of ERPs are patient-reported outcome measures, patients with complex needs and assessment of factors pertaining to successful ERP implementation. The next generation of ERP studies should seek to develop our understanding in these key areas.</jats:p

The Heritability of Aptitude and Exceptional Talent Across Different Domains in Adolescents and Young Adults

The origin of individual differences in aptitude, defined as a domain-specific skill within the normal ability range, and talent, defined as a domain specific skill of exceptional quality, is under debate. The nature of the variation in aptitudes and exceptional talents across different domains was investigated in a population based twin sample. Self-report data from 1,685 twin pairs (12–24 years) were analyzed for Music, Arts, Writing, Language, Chess, Mathematics, Sports, Memory, and Knowledge. The influence of shared environment was small for both aptitude and talent. Additive and non-additive genetic effects explained the major part of the substantial familial clustering in the aptitude measures with heritability estimates ranging between .32 and .71. Heritability estimates for talents were higher and ranged between .50 and .92. In general, the genetic architecture for aptitude and talent was similar in men and women. Genetic factors contribute to a large extent to variation in aptitude and talent across different domains of intellectual, creative, and sports abilities

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

BACKGROUND: A systems approach to understanding the etiology of schizophrenia requires a theory which is able to integrate genetic as well as neurodevelopmental factors. PRESENTATION OF THE HYPOTHESIS: Based on a co-localization of loci approach and a large amount of circumstantial evidence, we here propose that a functional deficiency of glial growth factors and of growth factors produced by glial cells are among the distal causes in the genotype-to-phenotype chain leading to the development of schizophrenia. These factors include neuregulin, insulin-like growth factor I, insulin, epidermal growth factor, neurotrophic growth factors, erbB receptors, phosphatidylinositol-3 kinase, growth arrest specific genes, neuritin, tumor necrosis factor alpha, glutamate, NMDA and cholinergic receptors. A genetically and epigenetically determined low baseline of glial growth factor signaling and synaptic strength is expected to increase the vulnerability for additional reductions (e.g., by viruses such as HHV-6 and JC virus infecting glial cells). This should lead to a weakening of the positive feedback loop between the presynaptic neuron and its targets, and below a certain threshold to synaptic destabilization and schizophrenia. TESTING THE HYPOTHESIS: Supported by informed conjectures and empirical facts, the hypothesis makes an attractive case for a large number of further investigations. IMPLICATIONS OF THE HYPOTHESIS: The hypothesis suggests glial cells as the locus of the genes-environment interactions in schizophrenia, with glial asthenia as an important factor for the genetic liability to the disorder, and an increase of prolactin and/or insulin as possible working mechanisms of traditional and atypical neuroleptic treatments

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23.This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.National Institutes of Mental Health (NIMH, USA) ACE Network Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) The Autism Genome Project (AGP) from Autism Speaks (USA) Canadian Institutes of Health Research (CIHR), Genome Canada Health Research Board (Ireland) Hilibrand Foundation (USA) Medical Research Council (UK) National Institutes of Health (USA) Ontario Genomics Institute University of Toronto McLaughlin Centre Simons Foundation Johns Hopkins Autism Consortium of Boston NLM Family foundation National Institute of Health grants National Health Medical Research Council Scottish Rite Spunk Fund, Inc. Rebecca and Solomon Baker Fund APEX Foundation National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) endowment fund of the Nancy Pritzker Laboratory (Stanford) Autism Society of America Janet M. Grace Pervasive Developmental Disorders Fund The Lundbeck Foundation universities and university hospitals of Aarhus and Copenhagen Stanley Foundation Centers for Disease Control and Prevention (CDC) Netherlands Scientific Organization Dutch Brain Foundation VU University Amsterdam Trinity Centre for High Performance Computing through Science Foundation Ireland Autism Genome Project (AGP) from Autism Speak

Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

International audienceAutism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs

Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways