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Genotype-first and within-family studies can elucidate factors that contribute to psychiatric illness. Combining these approaches, we investigated the patterns of influence of parental scores, a high-impact variant, and schizophrenia on dimensional neurobehavioral phenotypes implicated in major psychiatric disorders.
We quantitatively assessed cognitive (FSIQ, VIQ, PIQ), social, and motor functioning in 82 adult individuals with a de novo 22q11.2 deletion (22 with schizophrenia), and 148 of their unaffected parents. We calculated within-family correlations and effect sizes of the 22q11.2 deletion and schizophrenia, and used linear regressions to assess contributions to neurobehavioral measures.
Proband-parent intra-class correlations (ICC) were significant for cognitive measures (e.g. FSIQ ICC = 0.549, p < 0.0001), but not for social or motor measures. Compared to biparental scores, the 22q11.2 deletion conferred significant impairments for all phenotypes assessed (effect sizes −1.39 to −2.07 s.d.), strongest for PIQ. There were further decrements in those with schizophrenia. Regression models explained up to 37.7% of the variance in IQ and indicated that for proband IQ, parental IQ had larger effects than schizophrenia.
This study, for the first time, disentangles the impact of a high-impact variant from the modifying effects of parental scores and schizophrenia on relevant neurobehavioral phenotypes. The robust proband-parent correlations for cognitive measures, independent of the impact of the 22q11.2 deletion and of schizophrenia, suggest that, for certain phenotypes, shared genetic variation plays a significant role in expression. Molecular genetic and predictor studies are needed to elucidate shared factors and their contribution to psychiatric illness in this and other high-risk groups.
To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.
Pilot prospective multicenter surveillance study.
The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals.
All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data.
In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.
Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients).
Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.
Opioid use disorder is a major public health crisis, and evidence suggests ways of better serving patients who live with opioid use disorder in the emergency department (ED). A multi-disciplinary team developed a quality improvement project to implement this evidence.
The intervention was developed by an expert working group consisting of specialists and stakeholders. The group set goals of increasing prescribing of buprenorphine/naloxone and providing next day walk-in referrals to opioid use disorder treatment clinics. From May to September 2018, three Alberta ED sites and three opioid use disorder treatment clinics worked together to trial the intervention. We used administrative data to track the number of ED visits where patients were given buprenorphine/naloxone. Monthly ED prescribing rates before and after the intervention were considered and compared with eight nonintervention sites. We considered whether patients continued to fill opioid agonist treatment prescriptions at 30, 60, and 90 days after their index ED visit to measure continuity in treatment.
The intervention sites increased their prescribing of buprenorphine/naloxone during the intervention period and prescribed more buprenorphine/naloxone than the controls. Thirty-five of 47 patients (74.4%) discharged from the ED with buprenorphine/naloxone continued to fill opioid agonist treatment prescriptions 30 days and 60 days after their index ED visit. Thirty-four patients (72.3%) filled prescriptions at 90 days.
Emergency clinicians can effectively initiate patients on buprenorphine/naloxone when supports for this standardized evidence-based care are in place within their practice setting and timely follow-up in community is available.
Hydrogen lithography has been used to template phosphine-based surface chemistry to fabricate atomic-scale devices, a process we abbreviate as atomic precision advanced manufacturing (APAM). Here, we use mid-infrared variable angle spectroscopic ellipsometry (IR-VASE) to characterize single-nanometer thickness phosphorus dopant layers (δ-layers) in silicon made using APAM compatible processes. A large Drude response is directly attributable to the δ-layer and can be used for nondestructive monitoring of the condition of the APAM layer when integrating additional processing steps. The carrier density and mobility extracted from our room temperature IR-VASE measurements are consistent with cryogenic magneto-transport measurements, showing that APAM δ-layers function at room temperature. Finally, the permittivity extracted from these measurements shows that the doping in the APAM δ-layers is so large that their low-frequency in-plane response is reminiscent of a silicide. However, there is no indication of a plasma resonance, likely due to reduced dimensionality and/or low scattering lifetime.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n = 1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.
The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.
Neurocognitive and functional neuroimaging studies point to frontal lobe abnormalities in schizophrenia. Molecular and behavioural genetic studies suggest that the frontal lobe is under significant genetic influence. We carried out structural magnetic resonance imaging (MRI) of the frontal lobe in monozygotic (MZ) twins concordant or discordant for schizophrenia and healthy MZ control twins.
The sample comprised 21 concordant pairs, 17 discordant affected and 18 discordant unaffected twins from 19 discordant pairs, and 27 control pairs. Groups were matched on sociodemographic variables. Patient groups (concordant, discordant affected) did not differ on clinical variables. Volumes of superior, middle, inferior and orbital frontal gyri were calculated using the Cavalieri principle on the basis of manual tracing of anatomic boundaries. Group differences were investigated covarying for whole-brain volume, gender and age.
Results for superior frontal gyrus showed that twins with schizophrenia (i.e. concordant twins and discordant affected twins) had reduced volume compared to twins without schizophrenia (i.e. discordant unaffected and control twins), indicating an effect of illness. For middle and orbital frontal gyrus, concordant (but not discordant affected) twins differed from non-schizophrenic twins. There were no group differences in inferior frontal gyrus volume.
These findings suggest that volume reductions in the superior frontal gyrus are associated with a diagnosis of schizophrenia (in the presence or absence of a co-twin with schizophrenia). On the other hand, volume reductions in middle and orbital frontal gyri are seen only in concordant pairs, perhaps reflecting the increased genetic vulnerability in this group.
Major depression is a significant problem for people with a traumatic brain injury (TBI) and its treatment remains difficult. A promising approach to treat depression is Mindfulness-based cognitive therapy (MBCT), a relatively new therapeutic approach rooted in mindfulness based stress-reduction (MBSR) and cognitive behavioral therapy (CBT). We conducted this study to examine the effectiveness of MBCT in reducing depression symptoms among people who have a TBI.
Twenty individuals diagnosed with major depression were recruited from a rehabilitation clinic and completed the 8-week MBCT intervention. Instruments used to measure depression symptoms included: BDI-II, PHQ-9, HADS, SF-36 (Mental Health subscale), and SCL-90 (Depression subscale). They were completed at baseline and post-intervention.
All instruments indicated a statistically significant reduction in depression symptoms post-intervention (p < .05). For example, the total mean score on the BDI-II decreased from 25.2 (9.8) at baseline to 18.2 (11.7) post-intervention (p=.001). Using a PHQ threshold of 10, the proportion of participants with a diagnosis of major depression was reduced by 59% at follow-up (p=.012).
Most participants reported reductions in depression symptoms after the intervention such that many would not meet the criteria for a diagnosis of major depression. This intervention may provide an opportunity to address a debilitating aspect of TBI and could be implemented concurrently with more traditional forms of treatment, possibly enhancing their success. The next step will involve the execution of multi-site, randomized controlled trials to fully demonstrate the value of the intervention.
Psychiatry in the UK has longstanding recruitment problems (1). Evidence suggests the positive effects of clinical attachments on attitudes towards psychiatry are often transient (2). We therefore created the Psychiatry Early Experience Programme (PEEP) where year 1 medical students are paired with psychiatry trainees and shadow them at work. Students will ideally remain in PEEP throughout medical school, providing consistent exposure to psychiatry and a broad experience of its subspecialties.
1. To present PEEP
2. To assess:
a. Students’ baseline attitudes to psychiatry
b. PEEPs’ impact on students’ attitudes to psychiatry
A prospective survey based cohort study of King’s College London medical students.
PEEP started in 2013. In this cohort all students that signed up were accepted.
Students’ attitudes towards psychiatry were assessed on recruitment using the ATP-30 questionnaire (3), and will be re-assessed annually.
127 students were recruited. Attitudes were positive overall. 73% listed psychiatry in their top three specialities. 95.3% agreed or strongly agreed that ‘psychiatric illness deserves at least as much attention as physical illness.’ 84.3% disagreed or strongly disagreed that ‘at times it is hard to think of psychiatrists as equal to other doctors.’
Baseline attitudes to psychiatry were positive. By March 2015 we aim to collect and analyse data on students’ attitudes after one year in PEEP. Through on-ongoing analysis of this and future cohorts, we aim to assess the impact of PEEP on improving attitudes to psychiatry and whether this will ultimately improve recruitment.
Traumatic brain injuries (TBI) may lead to persistent depression symptoms. We conducted several pilot studies to examine the efficacy of mindfulness-based interventions to deal with this issue; all showed strong effect sizes. The logical next step was to conduct a randomized controlled trial (RCT).
We sought to determine the efficacy of mindfulness-based cognitive therapy for people with depression symptoms post-TBI (MBCT-TBI).
Using a multi-site RCT design, participants (mean age = 47) were randomized to intervention or control arms. Treatment participants received a group-based, 10-week intervention; control participants waited. Outcome measures, administered pre- and post-intervention, and after three months, included: Beck Depression Inventory-II (BDI-II), Patient Health Questionnaire-9 (PHQ-9), and Symptom Checklist-90-Revised (SCL-90-R). The Philadelphia Mindfulness Scale (PHLMS) captured present moment awareness and acceptance.
BDI-II scores decreased from 25.47 to 18.84 in treatment groups while they stayed relatively stable in control groups (respectively 27.13 to 25.00; p = .029). We did not find statistically significant differences on the PHQ-9 and SCL-90R post- treatment. However, after three months, all scores were statistically significantly lower than at baseline (ps < .01). Increases in mindfulness were associated with decreases in BDI-II scores (r = -.401, p = .025).
MBCT-TBI may alleviate depression symptoms up to three months post-intervention. Greater mindfulness may have contributed to the reduction in depression symptoms although the association does not confirm causality. More work is required to replicate these findings, identify subgroups that may better respond to the intervention, and refine the intervention to maximize its effectiveness.
At Guy's King's and St Thomas’ School of Medicine, a unique initiative is the Psychiatry Early Experience Programme (PEEP), which allows students to shadow psychiatry trainees at work several times a year. The students’ attitudes towards psychiatry and the scheme are regularly assessed and initial results are already available.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Given the common view that pre-exercise nutrition/breakfast is important for performance, the present study investigated whether breakfast influences resistance exercise performance via a physiological or psychological effect. Twenty-two resistance-trained, breakfast-consuming men completed three experimental trials, consuming water-only (WAT), or semi-solid breakfasts containing 0 g/kg (PLA) or 1·5 g/kg (CHO) maltodextrin. PLA and CHO meals contained xanthan gum and low-energy flavouring (approximately 122 kJ), and subjects were told both ‘contained energy’. At 2 h post-meal, subjects completed four sets of back squat and bench press to failure at 90 % ten repetition maximum. Blood samples were taken pre-meal, 45 min and 105 min post-meal to measure serum/plasma glucose, insulin, ghrelin, glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations. Subjective hunger/fullness was also measured. Total back squat repetitions were greater in CHO (44 (sd 10) repetitions) and PLA (43 (sd 10) repetitions) than WAT (38 (sd 10) repetitions; P < 0·001). Total bench press repetitions were similar between trials (WAT 37 (sd 7) repetitions; CHO 39 (sd 7) repetitions; PLA 38 (sd 7) repetitions; P = 0·130). Performance was similar between CHO and PLA trials. Hunger was suppressed and fullness increased similarly in PLA and CHO, relative to WAT (P < 0·001). During CHO, plasma glucose was elevated at 45 min (P < 0·05), whilst serum insulin was elevated (P < 0·05) and plasma ghrelin suppressed at 45 and 105 min (P < 0·05). These results suggest that breakfast/pre-exercise nutrition enhances resistance exercise performance via a psychological effect, although a potential mediating role of hunger cannot be discounted.
Healthcare personnel (HCP) were recruited to provide serum samples, which were tested for antibodies against Ebola or Lassa virus to evaluate for asymptomatic seroconversion.
From 2014 to 2016, 4 patients with Ebola virus disease (EVD) and 1 patient with Lassa fever (LF) were treated in the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital. Strict infection control and clinical biosafety practices were implemented to prevent nosocomial transmission of EVD or LF to HCP.
All personnel who entered the SCDU who were required to measure their temperatures and complete a symptom questionnaire twice daily were eligible.
No employee developed symptomatic EVD or LF. EVD and LF antibody studies were performed on sera samples from 42 HCP. The 6 participants who had received investigational vaccination with a chimpanzee adenovirus type 3 vectored Ebola glycoprotein vaccine had high antibody titers to Ebola glycoprotein, but none had a response to Ebola nucleoprotein or VP40, or a response to LF antigens.
Patients infected with filoviruses and arenaviruses can be managed successfully without causing occupation-related symptomatic or asymptomatic infections. Meticulous attention to infection control and clinical biosafety practices by highly motivated, trained staff is critical to the safe care of patients with an infection from a special pathogen.
Cardiac Fibromas are primary cardiac tumours more common in children than in adults. Surgical intervention is often not required except in the case of limited cardiac output or significant arrhythmia burden. We present a symptomatic 3-month-old infant who had successful surgical intervention for a giant right ventricle fibroma found on prenatal imaging.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Using existing data from clinical registries to support clinical trials and other prospective studies has the potential to improve research efficiency. However, little has been reported about staff experiences and lessons learned from implementation of this method in pediatric cardiology.
We describe the process of using existing registry data in the Pediatric Heart Network Residual Lesion Score Study, report stakeholders’ perspectives, and provide recommendations to guide future studies using this methodology.
The Residual Lesion Score Study, a 17-site prospective, observational study, piloted the use of existing local surgical registry data (collected for submission to the Society of Thoracic Surgeons-Congenital Heart Surgery Database) to supplement manual data collection. A survey regarding processes and perceptions was administered to study site and data coordinating center staff.
Survey response rate was 98% (54/55). Overall, 57% perceived that using registry data saved research staff time in the current study, and 74% perceived that it would save time in future studies; 55% noted significant upfront time in developing a methodology for extracting registry data. Survey recommendations included simplifying data extraction processes and tailoring to the needs of the study, understanding registry characteristics to maximise data quality and security, and involving all stakeholders in design and implementation processes.
Use of existing registry data was perceived to save time and promote efficiency. Consideration must be given to the upfront investment of time and resources needed. Ongoing efforts focussed on automating and centralising data management may aid in further optimising this methodology for future studies.
A computational study was performed both of a single agglomerate and of the collision of two agglomerates in a shear flow. The agglomerates were extracted from a direct numerical simulation of a turbulent agglomeration process, and had the loosely packed fractal structure typical of agglomerate structures formed in turbulent agglomeration processes. The computation was performed using a discrete-element method for adhesive particles with four-way coupling, accounting both for forces between the fluid and the particles (and vice versa) as well as force transmission directly between particles via particle collisions. In addition to understanding and characterizing the particle dynamics, the study focused on illuminating the fluid flow field induced by the agglomerate in the presence of a background shear and the effect of collisions on this particle-induced flow. Perhaps the most interesting result of the current work was the observation that the flow field induced by a particle agglomerate rotating in a shear flow has the form of two tilted vortex rings with opposite-sign circulation. These rings are surrounded by a sea of stretched vorticity from the background shear flow. The agglomerate rotates in the shear flow, but at a slower rate than the ambient fluid elements. In the computations with two colliding agglomerates, we observed cases resulting in agglomerate merger, bouncing and fragmentation. However, the bouncing cases were all observed to also result in an exchange of particles between the two colliding agglomerates, so that they were influenced both by elastic rebound of the agglomerate structures as well as by tearing away of particulate matter between the agglomerates. Overall, the problems of agglomerate–flow interaction and of the collision of two agglomerates in a shear flow are considerably richer in physical phenomena and more complex than can be described by the common approximation that represents each agglomerate by an ‘equivalent sphere’.