Adaptive behaviour deficits in individuals with 3q29 deletion syndrome.

BACKGROUND: 3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric phenotypes. Mild to moderate intellectual disability (ID) is common in this population, and previous work by our team identified substantial deficits in adaptive behaviour. However, the full profile of adaptive function in 3q29del has not been described nor has it been compared with other genomic syndromes associated with elevated risk for neurodevelopmental and neuropsychiatric phenotypes. METHODS: Individuals with 3q29del (n = 32, 62.5% male) were evaluated using the Vineland Adaptive Behaviour Scales, Third Edition, Comprehensive Parent/Caregiver Form (Vineland-3). We explored the relationship between adaptive behaviour and cognitive function, executive function, and neurodevelopmental and neuropsychiatric comorbidities in our 3q29del study sample, and we compared subjects with 3q29del with published data on fragile X syndrome, 22q11.2 deletion syndrome and 16p11.2 deletion and duplication syndromes. RESULTS: Individuals with 3q29del had global deficits in adaptive behaviour that were not driven by specific weaknesses in any given domain. Individual neurodevelopmental and neuropsychiatric diagnoses had a small effect on adaptive behaviour, and the cumulative number of comorbid diagnoses was significantly negatively associated with Vineland-3 performance. Both cognitive ability and executive function were significantly associated with adaptive behaviour, and executive function was a better predictor of Vineland-3 performance than cognitive ability. Finally, the severity of adaptive behaviour deficits in 3q29del was distinct from previously published data on comparable genomic disorders. CONCLUSIONS: Individuals with 3q29del have significant deficits in adaptive behaviour, affecting all domains assessed by the Vineland-3. Executive function is a better predictor of adaptive behaviour than cognitive ability in this population and suggests that interventions targeting executive function may be an effective therapeutic strategy.

How do people with chronic low back pain perceive specific and general exercise? A mixed methods survey.

PURPOSE: Exercise prescriptions for chronic low back pain (CLBP) often utilize reductionistic, trunk-focused exercise aimed at addressing proposed pain mechanisms. It is unknown if the use of these trunk-focused exercises imply beliefs to people with CLBP about the rationale for their use (e.g., etiology), even without concurrent biomedical narratives. This study aimed to explore people's perceptions of specific and general exercise without an accompanying narrative when experiencing CLBP. METHODS: An anonymous online survey was distributed. Mixed methods were utilized for analysis. Six-point Likert scales categorized people's beliefs about individual exercises. Open-ended questions were used to gather further beliefs which were then coded into themes. RESULTS: People with CLBP perceived specific exercise as more beneficial than general exercise. Eight themes and five subthemes were defined. A high volume of positive beliefs were centered around strengthening the low back and abdominal musculature, emphasizing the importance of correct technique. Negative beliefs were held against spinal flexion and external load. Both positive and negative beliefs were underpinned by spinal/pelvic stability being important as well as certain exercises being achievable or not. CONCLUSION: This study demonstrated that people with CLBP consider specific exercises to be more beneficial than general exercises for CLBP. Specific exercises irrespective of an accompanying narrative can imply meaning about the intent of an exercise. Understanding this requires practitioners to be mindful when prescribing and communicating exercise.

A distinct cognitive profile in individuals with 3q29 deletion syndrome.

BACKGROUND: 3q29 deletion syndrome is associated with mild to moderate intellectual disability as well as comorbid psychopathology such as ADHD, anxiety, ASD and schizophrenia. A greater understanding of specific profiles that could increase risk for psychopathology is necessary in order to best understand and support individuals with 3q29 deletion syndrome. The goal of this study was to thus carefully outline the strengths and weaknesses of these individuals. A second goal was to ask whether the cognitive impact of the deletion predicted psychopathology in other domains. METHODS: We systematically evaluated cognitive ability, adaptive behaviour and psychopathology in 32 individuals with the canonical 3q29 deletion using gold-standard instruments and a standardised phenotyping protocol. RESULTS: Mean full scale IQ was 73 (range 40-99). Verbal subtest score (mean 80, range 31-106) was slightly higher and had a greater range than non-verbal subtest score (mean 75, range 53-98). Spatial ability was evaluated in a subset (n = 24) and was lower than verbal and non-verbal ability (mean 71, range 34-108). There was an average 14-point difference between verbal and non-verbal subset scores; 60% of the time the verbal subset score was higher than the non-verbal subset score. Study subjects with a verbal ability subtest score lower than the non-verbal subtest score were four times more likely to have a diagnosis of intellectual disability (suggestive, P value 0.07). The age at which a child first spoke two-word phrases was strongly associated with measures of verbal ability (P value 2.56e-07). Cognitive ability was correlated with adaptive behaviour measures (correlation 0.42, P value 0.02). However, although group means found equivalent scores, there was, on average, a 10-point gap between these skills (range -33 to 33), in either direction, in about 50% of the sample, suggesting that cognitive measures only partially inform adaptive ability. Cognitive ability scores did not have any significant relationship to cumulative burden of psychopathology nor to individual neurodevelopmental or psychiatric diagnoses. CONCLUSIONS: Individuals with 3q29 deletion syndrome have a complex pattern of cognitive disability. Two-thirds of individuals with the deletion will exhibit significant strength in verbal ability; this may mask deficits in non-verbal reasoning, leading to an overestimation of overall ability. Deficits in verbal ability may be the driver of intellectual disability diagnosis. Cognitive ability is not a strong indicator of other neurodevelopmental or psychiatric impairment; thus, individuals with 3q29 deletion syndrome who exhibit IQ scores within the normal range should receive all recommended behavioural evaluations.

An internal pilot study of a novel rectal mucocellular sampling device to allow next-generation sequencing for colorectal disease.

BACKGROUND: The ORI-EGI-02 study was designed to test the hypothesis that rectal mucus collected using a novel rectal sampling device (OriCol™), contains sufficient human deoxyribonucleic acid (DNA) of the required quality for Next Generation Sequencing (NGS), for colorectal disease genetic signature discovery. METHODS: Using National Institute for Health and Care Research methodology, an internal pilot study was performed in January 2020-May 2021, at four sites in the United Kingdom, to assess the process of recruitment, consent, specimen acquisition and viability for analysis. Following an OriCol™ test, the sample was stabilized with a buffer solution to preserve the material, which was posted to the laboratory. Samples were processed using QIAamp® DNA Blood Midi kit to extract DNA and Quant-iT™ PicoGreen® dsDNA Reagent to quantify the retrieved DNA. DNA integrity was measured by Agilent TapeStation system. 25 ng of human amplifiable DNA was prepared for Next Generation Sequencing (NGS), which was performed on an Illumina NextSeq550 sequencer using the 300-cycle high output kit v2.5. RESULTS: This study assessed the first 300 patients enrolled to the ORI-EGI-02 Study (n = 800). 290/300 (96.67%) were eligible to undergo OriCol™ sampling procedure and 285/290 (98.27%) had a successful OriCol™ sample taken. After transportation, extraction and quantification of DNA, 96.20% (279/290) of the samples had NGS successfully performed for bioinformatic analysis. CONCLUSIONS: Our internal pilot study demonstrated that the OriCol™ sampling device can capture rectal mucus from unprepared bowel in subjects who could undergo a digital rectal examination. The technique could be applied irrespective of age, frailty, or co-morbidity. Completion of the study to 800 patients and analysis of NGS data for colorectal cancer mutations will now proceed.

Core outcome set for uncomplicated acute appendicitis in children and young people.

BACKGROUND: Research studies to inform clinical practice and policy in children and young people with appendicitis are hampered by inconsistent selection and reporting of outcomes. The aim of this study was to develop a core outcome set for reporting all studies of uncomplicated acute appendicitis in children and young people. METHODS: Systematic literature reviews, qualitative interviews with parents and patients treated for uncomplicated acute appendicitis, and a Study-Specific Advisory Group informed a long list of outcomes. Outcomes were then prioritized by stakeholders based in the UK (patients, parents, and paediatric and general surgeons) in an online three-round Delphi consensus process, followed by face-to-face consensus meetings. RESULTS: A long list of 40 items was scored by 147 key stakeholders in the first Delphi round, of whom 90 completed the two subsequent Delphi rounds. The final core outcome set comprises 14 outcomes: intra-abdominal abscess, reoperation (including interventional radiology procedure), readmission to hospital, bowel obstruction, wound infection, antibiotic failure, wound complication, negative appendicectomy, recurrent appendicitis, death, patient stress/psychological distress, length of hospital stay, time away from full activity and child's quality of life. CONCLUSION: A core outcome set comprising 14 outcomes across five key domains has been developed for reporting studies in children and young people with uncomplicated acute appendicitis. Further work is required to determine how and when to measure these outcomes.

ANTECEDENTES: Los estudios de investigación que sirvan de base para la práctica clínica y la política en niños y adultos jóvenes con apendicitis se ven obstaculizados por inconsistencias en la selección y descripción de los resultados. El objetivo de este estudio fue desarrollar un conjunto central de resultados para todos los estudios de apendicitis aguda no complicada en niños y adultos jóvenes. MÉTODOS: Para establecer una lista de resultados se efectuaron revisiones sistemáticas de la literatura, entrevistas cualitativas con padres y pacientes tratados por apendicitis aguda no complicada, y consulta con un Grupo de Asesoramiento Específico para el Estudio. Seguidamente, los resultados se priorizaron de acuerdo con los intereses de las partes interesadas (pacientes, padres, y cirujanos pediátricos y generales) en el Reino Unido a través de un proceso de consenso Delphi de tres rondas en Internet, seguido de reuniones personales de consenso. RESULTADOS: Un total de 147 participantes puntuaron una larga lista de 40 ítems en la primera ronda Delphi, de los cuales 90 completaron las dos rondas Delphi subsiguientes. El conjunto final incluye 14 resultados: absceso intra-abdominal, reoperación (incluyendo procedimientos radiológicos intervencionistas), reingreso, obstrucción intestinal, infección de herida, otras complicaciones de la herida, fracaso del tratamiento con antibióticos, apendicectomía blanca, apendicitis recidivante, muerte, estrés del paciente/sufrimiento psicológico, duración de la estancia hospitalaria, tiempo alejado de todas sus actividades y calidad de vida. CONCLUSIÓN: Se ha desarrollado un conjunto central de resultados que incluye 14 resultados en cinco dominios clave para la descripción de estudios en niños y adultos jóvenes con apendicitis aguda no complicada. Se requieren más trabajos para determinar cómo y cuándo conviene medir estos resultados.

Nonreciprocal Linear Transmission of Sound in a Viscous Environment with Broken P Symmetry.

Reciprocity is a fundamental property of the wave equation in a linear medium that originates from time-reversal symmetry, or T symmetry. For electromagnetic waves, reciprocity can be violated by an external magnetic field. It is much harder to realize nonreciprocity for acoustic waves. Here we report the first experimental observation of linear nonreciprocal transmission of ultrasound through a water-submerged phononic crystal consisting of asymmetric rods. Viscosity of water is the factor that breaks the T symmetry. Asymmetry, or broken P symmetry along the direction of sound propagation, is the second necessary factor for nonreciprocity. Experimental results are in agreement with numerical simulations based on the Navier-Stokes equation. Our study demonstrates that a medium with broken PT symmetry is acoustically nonreciprocal. The proposed passive nonreciprocal device is cheap, robust, and does not require an energy source.

Fluctuation, invisibility, fatigue - the barriers to maintaining employment with systemic lupus erythematosus: results of an online survey.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with high levels of workplace disability and unemployment. The objective of this study was to understand the reasons for this and to describe the barriers and facilitators of employment identified by people with SLE to develop appropriate solutions. Unemployment, as well as unsuitable work, has adverse health outcomes. METHODS: Adults with SLE completed a UK-specific online survey, through the LUPUS UK website, designed to find out more about the difficulties and successes that people with SLE have in maintaining employment. The survey was predominantly qualitative, to understand participants' employment experiences to generate possible solutions. RESULTS: Three hundred and ninety-three people gave detailed responses to the survey within eight weeks. Every respondent reported a detrimental effect of SLE on their ability to work: 40.45% had left employment because of it. The themes of concern to respondents were unambiguous: (i) the difficulties of working (and career damage) with SLE, (ii) fear and anxiety overshadowing work/family life, (iii) the greater potential to remain in some employment or stay in full employment when modifications of work pattern and support from management and colleagues were available. SLE-related fatigue, its invisibility and fluctuating nature were felt to be the main barriers to maintaining employment. Numerous respondents could work only part-time and anxiety was high regarding their future ability to continue working. Many had taken substantial pay reductions and refused offered promotions to preserve their health. Distress due to loss of work and the benefits it brings were reported by every respondent who had left work. CONCLUSION: SLE presents specific difficulties for maintaining employment - fatigue, fluctuation and invisibility - not addressed by current anti-discrimination legislation or currently available 'reasonable adjustments'. This study demonstrates that (i) employment is an important area of concern for people with SLE, (ii) SLE has significant detrimental effects on individuals' ability to participate and progress in employment, (iii) legislators and employers need information about SLE as invisibility and fluctuation cause hidden problems, and (iv) more data is needed to inform workplace adjustments if individual distress and societal loss of skills are to be addressed.

Power outages and refrigerated medicines: The need for better guidelines, awareness and planning.

WHAT IS KNOWN AND OBJECTIVE: Vaccines and other pharmaceuticals are essential medical supplies that require continuous storage at specific temperatures to maintain viability. Power outages can lead to a break in the cold chain, resulting in the degradation of essential medicines. COMMENT: After a power outage, the stability of vaccines and other medicines can be difficult to ascertain. Many public health guidelines therefore recommend discarding potentially compromised pharmaceuticals unless the cold chain can be guaranteed-a costly endeavour. There are government guidelines aimed at minimizing exposure to high temperatures in the event of a power outage; however, the usefulness of these guidelines is uncertain. WHAT IS NEW AND CONCLUSION: The actual cost of vaccine and pharmaceutical loss due to a break in the cold chain is poorly studied and requires further research. Additional recommendations regarding the stability of specific medicines would also be a valuable resource.

Scabies-An ancient itch that is still rampant today.

WHAT IS KNOWN AND OBJECTIVE: Scabies is recognized as a neglected tropical disease responsible for a substantial health and economic burden, especially in resource-poor communities around the world. COMMENT: There are relatively few current treatment options for scabies, and they possess important limitations. The treatments are ineffective in preventing relapse, inflammatory skin reactions and associated bacterial skin infections. There are also safety concerns, especially in children and pregnant women. Furthermore, there has been the emergence of resistance among scabies mites to the classical acaricides. WHAT IS NEW AND CONCLUSION: More research needs to be devoted to developing new treatments for scabies.

Innovative strategies to improve diabetes outcomes in disadvantaged populations.

Diabetes disproportionately affects disadvantaged populations. Eighty percent of deaths directly caused by diabetes occurred in low- and middle-income countries. In high-income countries, there are marked disparities in diabetes control among racial/ethnic minorities and those with low socio-economic status. Innovative, effective and cost-effective strategies are needed to improve diabetes outcomes in these populations. Technological advances, peer educators and community health workers have expanded methodologies to reach, educate and monitor individuals with diabetes. In the present manuscript we review the outcomes of these strategies, and describe the barriers to and facilitators of these approaches for improving diabetes outcomes.

Impact of Pdx1-associated chromatin modifiers on islet ß-cells.

Diabetes mellitus arises from insufficient insulin secretion from pancreatic islet ß-cells. In type 2 diabetes (T2D), ß-cell dysfunction is associated with inactivation and/or loss of transcription factor (TF) activity, including Pdx1. Notably, this particular TF is viewed as a master regulator of pancreas development and islet ß-cell formation, identity and function. TFs, like Pdx1, recruit coregulators to transduce activating and/or repressing signals to the general transcriptional machinery for controlling gene expression, including modifiers of DNA, histones and nucleosome architecture. These coregulators impart a secondary layer of control that can be exploited to modulate TF activity. In this review, we describe Pdx1-recruited coregulators that impact chromatin structure, consequently influencing normal ß-cell function and likely Pdx1 activity in pathophysiological settings.

Measuring quality of recovery-15 after day case surgery.

BACKGROUND: 'Quality of recovery' scores are patient-reported outcome measures evaluating recovery after surgery and anaesthesia. However, they are not widely used in the clinical or research setting. The Quality of Recovery-15 (QoR-15) is a recently developed, psychometrically tested and validated questionnaire. METHODS: We conducted a prospective study of all adult patients undergoing orthopaedic day case surgery over a period of six months (June 2013-November 2013). Patients completed the QoR-15 score preoperatively, and then were asked to repeat the score by telephone at 24 h, 48 h and seven days after surgery. RESULTS: 633 patients from a possible 714 (89%) completed the preoperative questionnaire and data from 437 patients who completed scores at all four time points were analysed. Most patients returned to their preoperative score by 48 h, and had exceeded it by seven days. Construct validity was supported by a negative correlation with duration of surgery and total inpatient opioid use. There was also excellent internal consistency (Cronbach's alpha 0.80-0.83). CONCLUSION: The QoR-15 is a clinically acceptable and feasible patient-centred outcome measure after day case surgery. The score demonstrated good validity, reliability and responsiveness. However, measurement of the QoR-15 score on the day of surgery may not provide a true baseline value. We suggest one follow-up call at 48 h would enable an adequate patient-centred assessment of postoperative recovery after day case orthopaedic surgery.

Patient reported outcome of adult perioperative anaesthesia in the United Kingdom: a cross-sectional observational study.

BACKGROUND: Understanding the patient perspective on healthcare is central to the evaluation of quality. This study measured selected patient-reported outcomes after anaesthesia in order to identify targets for research and quality improvement. METHODS: This cross-sectional observational study in UK National Health Service hospitals, recruited adults undergoing non-obstetric surgery requiring anaesthesia care over a 48 h period. Within 24 h of surgery, patients completed the Bauer questionnaire (measuring postoperative discomfort and satisfaction with anaesthesia care), and a modified Brice questionnaire to elicit symptoms suggestive of accidental awareness during general anaesthesia (AAGA). Patient, procedural and pharmacological data were recorded to enable exploration of risk factors for these poor outcomes. RESULTS: 257 hospitals in 171 NHS Trusts participated (97% of eligible organisations). Baseline characteristics were collected on 16,222 patients; 15,040 (93%) completed postoperative questionnaires. Anxiety was most frequently cited as the worst aspect of the perioperative experience. Thirty-five per cent of patients reported severe discomfort in at least one domain: thirst (18.5%; 95% CI 17.8-19.1), surgical pain (11.0%; 10.5-11.5) and drowsiness (10.1%; 9.6-10.5) were most common. Despite this, only 5% reported dissatisfaction with any aspect of anaesthesia-related care. Regional anaesthesia was associated with a reduced burden of side-effects. The incidence of reported AAGA was one in 800 general anaesthetics (0.12%) CONCLUSIONS: Anxiety and discomfort after surgery are common; despite this, satisfaction with anaesthesia care in the UK is high. The inconsistent relationship between patient-reported outcome, patient experience and patient satisfaction supports using all three of these domains to provide a comprehensive assessment of the quality of anaesthesia care.

Using genetic data to estimate diffusion rates in heterogeneous landscapes.

Having a precise knowledge of the dispersal ability of a population in a heterogeneous environment is of critical importance in agroecology and conservation biology as it can provide management tools to limit the effects of pests or to increase the survival of endangered species. In this paper, we propose a mechanistic-statistical method to estimate space-dependent diffusion parameters of spatially-explicit models based on stochastic differential equations, using genetic data. Dividing the total population into subpopulations corresponding to different habitat patches with known allele frequencies, the expected proportions of individuals from each subpopulation at each position is computed by solving a system of reaction-diffusion equations. Modelling the capture and genotyping of the individuals with a statistical approach, we derive a numerically tractable formula for the likelihood function associated with the diffusion parameters. In a simulated environment made of three types of regions, each associated with a different diffusion coefficient, we successfully estimate the diffusion parameters with a maximum-likelihood approach. Although higher genetic differentiation among subpopulations leads to more accurate estimations, once a certain level of differentiation has been reached, the finite size of the genotyped population becomes the limiting factor for accurate estimation.

Critical components of the pluripotency network are targets for the p300/CBP interacting protein (p/CIP) in embryonic stem cells.

p/CIP, also known as steroid receptor coactivator 3 (SRC-3)/Nuclear Receptor Coactivator 3 (NCoA3), is a transcriptional coactivator that binds liganded nuclear hormone receptors, as well as other transcription factors, and facilitates transcription through direct recruitment of accessory factors. We have found that p/CIP is highly expressed in undifferentiated mouse embryonic stem cells (mESCs) and is downregulated during differentiation. siRNA-mediated knockdown of p/CIP decreased transcript levels of Nanog, but not Oct4 or Sox2. Microarray expression analysis showed that Klf4, Tbx3, and Dax-1 are significantly downregulated in mESCs when p/CIP is knocked down. Subsequent chromatin immunoprecipitation (ChIP) analysis demonstrated that Tbx3, Klf4, and Dax-1 are direct transcriptional targets of p/CIP. Using the piggyBac transposition system, a mouse ESC line that expresses Flag-p/CIP in a doxycycline-dependent manner was generated. p/CIP overexpression increased the level of target genes and promoted the formation of undifferentiated colonies. Collectively, these results indicate that p/CIP contributes to the maintenance of ESC pluripotency through direct regulation of essential pluripotency genes. To better understand the mechanism by which p/CIP functions in ESC pluripotency, we integrated our ChIP and transcriptome data with published protein-protein interaction and promoter occupancy data to draft a p/CIP gene regulatory network. The p/CIP gene regulatory network identifies various feed-forward modules including one in which p/CIP activates members of the extended pluripotency network, demonstrating that p/CIP is a component of this extended network.

Substance use in individuals at clinical high risk of psychosis.

BACKGROUND: A series of research reports has indicated that the use of substances such as cannabis, alcohol and tobacco are higher in youth at clinical high risk (CHR) of developing psychosis than in controls. Little is known about the longitudinal trajectory of substance use, and findings on the relationship between substance use and later transition to psychosis in CHR individuals are mixed. METHOD: At baseline and 6- and 12-month follow-ups, 735 CHR and 278 control participants completed the Alcohol and Drug Use Scale and a cannabis use questionnaire. The longitudinal trajectory of substance use was evaluated with linear mixed models. RESULTS: CHR participants endorsed significantly higher cannabis and tobacco use severity, and lower alcohol use severity, at baseline and over a 1-year period compared with controls. CHR youth had higher lifetime prevalence and frequency of cannabis, and were significantly younger upon first use, and were more likely to use alone and during the day. Baseline substance use did not differentiate participants who later transitioned to psychosis (n = 90) from those who did not transition (n = 272). Controls had lower tobacco use than CHR participants with a prodromal progression clinical outcome and lower cannabis use than those with a psychotic clinical outcome at the 2-year assessment. CONCLUSIONS: In CHR individuals cannabis and tobacco use is higher than in controls and this pattern persists across 1 year. Evaluation of clinical outcome may provide additional information on the longitudinal impact of substance use that cannot be detected through evaluation of transition/non-transition to psychosis alone.

Successful self-management among non-insulin-treated adults with Type 2 diabetes: a self-regulation perspective.

AIMS: To clarify the role of self-monitoring of blood glucose (SMBG) in the self-management of Type 2 diabetes from the patient's perspective, using in-depth interviews with non-insulin-treated adults to investigate how they learned to manage their diabetes effectively and whether SMBG played a significant role in this process. METHODS: Individual interviews were conducted with 14 non-insulin-treated adults with Type 2 diabetes who had significantly improved their glycaemic control [64% women; 50% black; 21% Hispanic; mean age 60 years; mean HbA(1c) concentration 43 mmol/mol (6.1%)]. Interviews were transcribed and analysed by a coding team, applying the concept of illness coherence from the Common Sense Model of Self-Regulation. RESULTS: The majority of participants relied on SMBG to evaluate their self-management efforts. Key themes included: adopting an experimental approach; experiencing 'a-ha' moments; provider-assisted problem-solving; using SMBG and other feedback to evaluate when their efforts were working; and normalizing diabetes-specific behaviour changes as being healthy for everyone. CONCLUSIONS: Our qualitative data are consistent with the argument that SMBG, if implemented appropriately with enough education and provider access, can be a powerful tool for non-insulin-treated adults with Type 2 diabetes to monitor their self-management. Establishing sufficient conditions for illness coherence to develop while individuals are learning to use SMBG could increase their sense of personal control in managing a complex and demanding illness.

Alcohol confounds relationship between cannabis misuse and psychosis conversion in a high-risk sample.

OBJECTIVE: Cannabis use has been examined as a predictor of psychosis in clinical high-risk (CHR) samples, but little is known about the impact of other substances on this relationship. METHOD: Substance use was assessed in a large sample of CHR participants (N = 370, mean age = 18.3) enrolled in the multisite North American Prodrome Longitudinal Study Phase 1 project. Three hundred and forty-one participants with cannabis use data were divided into groups: No Use (NU, N = 211); Cannabis Use without impairment (CU, N = 63); Cannabis Abuse/Dependence (CA/CD, N = 67). Participants (N = 283) were followed for ≥2 years to determine psychosis conversion. RESULTS: Alcohol (45.3%) and cannabis (38.1%) were the most common substances. Cannabis use groups did not differ on baseline attenuated positive symptoms. Seventy-nine of 283 participants with cannabis and follow-up data converted to psychosis. Survival analysis revealed significant differences between conversion rates in the CA/CD group compared with the No Use (P = 0.031) and CU group (P = 0.027). CA/CD also significantly predicted psychosis in a regression analysis, but adjusting for alcohol use weakened this relationship. CONCLUSION: The cannabis misuse and psychosis association was confounded by alcohol use. Non-impairing cannabis use was not related to psychosis. Results highlight the need to control for other substance use, so as to not overstate the cannabis/psychosis connection.

Risk assessment tools validated for patients undergoing emergency laparotomy: a systematic review.

Emergency laparotomies are performed commonly throughout the world, but one in six patients die within a month of surgery. Current international initiatives to reduce the considerable associated morbidity and mortality are founded upon delivering individualised perioperative care. However, while the identification of high-risk patients requires the routine assessment of individual risk, no method of doing so has been demonstrated to be practical and reliable across the commonly encountered spectrum of presentations, co-morbidities and operative procedures. A systematic review of Embase and Medline identified 20 validation studies assessing 25 risk assessment tools in patients undergoing emergency laparotomy. The most frequently studied general tools were APACHE II, ASA-PS and P-POSSUM. Comparative, quantitative analysis of tool performance was not feasible due to the heterogeneity of study design, poor reporting and infrequent within-study statistical comparison of tool performance. Reporting of calibration was notably absent in many prognostic tool validation studies. APACHE II demonstrated the most consistent discrimination of individual outcome across a variety of patient groups undergoing emergency laparotomy when used either preoperatively or postoperatively (area under the curve 0.76-0.98). While APACHE systems were designed for use in critical care, the ability of APACHE II to generate individual risk estimates from objective, exclusively preoperative data items may lead to better-informed shared decisions, triage and perioperative management of patients undergoing emergency laparotomy. Future endeavours should include the recalibration of APACHE II and P-POSSUM in contemporary cohorts, modifications to enable prediction of morbidity and assessment of the impact of adoption of these tools on clinical practice and patient outcomes.