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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
Background: Our prior six-year review (n=2165) revealed 24% of patients undergoing posterior decompression surgeries (laminectomy or discectomy) sought emergency department (ED) care within three months post-surgery. We established an integrated Spine Assessment Clinic (SAC) to enhance patient outcomes and minimize unnecessary ED visits through pre-operative education, targeted QI interventions, and early post-operative follow-up. Methods: We reviewed 13 months of posterior decompression data (n=205) following SAC implementation. These patients received individualized, comprehensive pre-operative education and follow-up phone calls within 7 days post-surgery. ED visits within 90 days post-surgery were tracked using provincial databases and compared to our pre-SAC implementation data. Results: Out of 205 patients, 24 (11.6%) accounted for 34 ED visits within 90 days post-op, showing a significant reduction in ED visits from 24% to 11.6%, and decreased overall ED utilization from 42.1% to 16.6% (when accounting for multiple visits by the same patient). Early interventions including wound monitoring, outpatient bloodwork, and prescription adjustments for pain management, helped mitigate ED visits. Patient satisfaction surveys (n=62) indicated 92% were “highly satisfied” and 100% would recommend the SAC. Conclusions: The SAC reduced ED visits after posterior decompression surgery by over 50%, with pre-operative education, focused QI initiatives, and its individualized, proactive approach.
Improving Access to Psychological Therapies (IAPT), an NHS England service providing talking therapies, is meeting its target recovery rate of 50%. However, engagement in treatment, as well as recovery rates, may be lower for some groups.
Aims
To assess variation in treatment completion and recovery rates by demographic and socioeconomic group and to describe rates of further referrals for patients to IAPT and secondary mental health services.
Method
Using 121 548 administrative records for 2019–2020 and 2022–2023 for the Norfolk and Waveney area, we estimated associations of age, gender, ethnicity and deprivation with the likelihood of treatment completion and recovery using logistic regression modelling. We also described rates of further referrals.
Results
Younger people and those living in deprived areas were less likely to recover or complete treatment, with those aged 16–17 years (n = 735) having the lowest adjusted odds for recovery (adjusted odds ratio = 0.5, 95% CI: 0.5–0.6) compared with those aged 36–70 years, and those aged 18–24 years (n = 23 563) having the lowest rate of completion (adjusted odds ratio = 0.5, 95% CI: 0.5–0.6). Further referrals before April 2022 were recorded for 45.4% of 6513 patients who had completed treatment and 68.8% of 9469 who had not completed treatment, and for 39.4% of 2007 recovered patients in 2019–2020 and 53.1% of 1586 who had not recovered. Non-completers had relatively more further referrals to secondary mental health services compared with completers (43.6% v. 22.8%; P < 0.01).
Conclusions
Younger people and those living in deprived areas have lower recovery and completion rates. Those who have completed treatment and not recovered have higher rates of further referrals.
Multicenter clinical trials are essential for evaluating interventions but often face significant challenges in study design, site coordination, participant recruitment, and regulatory compliance. To address these issues, the National Institutes of Health’s National Center for Advancing Translational Sciences established the Trial Innovation Network (TIN). The TIN offers a scientific consultation process, providing access to clinical trial and disease experts who provide input and recommendations throughout the trial’s duration, at no cost to investigators. This approach aims to improve trial design, accelerate implementation, foster interdisciplinary teamwork, and spur innovations that enhance multicenter trial quality and efficiency. The TIN leverages resources of the Clinical and Translational Science Awards (CTSA) program, complementing local capabilities at the investigator’s institution. The Initial Consultation process focuses on the study’s scientific premise, design, site development, recruitment and retention strategies, funding feasibility, and other support areas. As of 6/1/2024, the TIN has provided 431 Initial Consultations to increase efficiency and accelerate trial implementation by delivering customized support and tailored recommendations. Across a range of clinical trials, the TIN has developed standardized, streamlined, and adaptable processes. We describe these processes, provide operational metrics, and include a set of lessons learned for consideration by other trial support and innovation networks.
The aerodynamic performance of an ultra-high aspect ratio strut-braced wing design is assessed for flight at cruise. The sensitivity of a selected airframe design from a recent CleanSky2 project to operating conditions around the design point is quantified using the adaptive-cut high-dimensional model representation (HDMR) method, which allows for the decomposition of the parameter space into smaller subdomains to isolate the parameter interactions and influence on the aerodynamic forces. A comparative analysis with a cantilever wing configuration is performed to identify the role of the strut on the sensitivity of the design. Insight into the transonic performance is gained by characterisation of buffet limits and drag rise. Results show that, for the selected optimised airframe configuration, small changes in freestream parameters can lead to significant reduction in performance due to drag divergence triggered by the shock wave generated at the strut-wing junction and at the fuselage-strut intersection. Cruise conditions can be achieved without buffet onset throughout much of the parameter space. Safety margins associated with buffeting are satisfied, but sensible limits are imposed on the flight envelope for this configuration.
Diet is a key modifiable factor for improving suboptimal lipoprotein profiles and reducing cardiovascular disease (CVD) risk(1). Dietary patterns like the Dietary Approaches to Stop Hypertension (DASH) or the Mediterranean Diet, with varying macronutrient components, have shown positive effects on total cholesterol and low-density lipoproteins (LDL)(2). However, limited research exists on the impact of different healthy diets on lipoprotein subclass profiles, which are increasingly known to influence CVD risk. This study aims to compare the nuclear magnetic resonance (NMR)-measured 112 lipoprotein profiles across three healthy dietary patterns: a carbohydrate-rich diet (CARB), similar to the DASH diet; a protein-rich diet (PROT); and an unsaturated fat-rich diet (USFA), similar to the Mediterranean diet. Lipoprotein parameters were generated using the Bruker IVDr Lipoprotein Subclass Analysis (B.I.LISA) method(3). The lipoprotein subclasses included different molecular components of very low-density lipoprotein (VLDL, 0.950–1.006 kg/L), low-density lipoprotein (LDL, density 1.09–1.63 kg/L), intermediate-density lipoprotein (IDL, density 1.006–1.019 kg/L), and high-density lipoprotein (HDL, density 1.063–1.210 kg/L). The LDL subfraction was further divided into six density classes, and the HDL subfractions were divided into four different density classes. Plasma samples from a randomised cross-over intervention study involving 156 individuals who completed more than two dietary patterns were included for the NMR analysis (registered at www.clinicaltrials.gov as NCT00051350 and NCT03369535). The Friedman’s test with post-hoc analysis, corrected for multiple testing, showed that all healthy dietary patterns led to a reduction in overall lipoprotein subclasses known to be associated with atherogenic risk. This reduction included large and medium-sized LDL subclasses, all intermediate-density IDL subclasses, as well as total plasma cholesterol, triglycerides, apolipoprotein-B100, apo-B100/apo-A1 ratio, and LDL-cholesterol (p < 0.05). Additional variations in lipoprotein subclasses specific to each diet were also observed. The PROT diet showed a decrease in small-sized and dense LDL, large to medium VLDL subclasses, and large-sized HDL subclasses. Conversely, the CARB diet exhibited an increase in smaller-sized and denser LDL, along with a decrease in large-sized HDL and an increase in smaller-sized HDL subclasses. The USFA diet led to decreases in LDL and overall VLDL subclasses, while increasing LDL and HDL subclasses (p < 0.05). The impact of different healthy diets with differential effects on lipoproteins suggests the possibility of targeting the cholesterol status of individuals to optimise lipoprotein profiles and thereby reduce CVD risk. Preliminary exploratory analyses based on linear mixed-effect models coupled with a latent profile analysis, adjusted for cholesterol status, showed that individual lipoprotein responses to specific diets varied. Inter-individual variations in lipoprotein responses to healthy diets were evident. A small proportion of individuals only responded to specific diets, suggesting potential of personalised nutrition based on individual lipoprotein profiles. These observed variations highlight the complexity of individual responses to dietary interventions.
The Hippoboscidae are ectoparasites of birds and mammals, which, as a group, are known to vector multiple diseases. Avipoxvirus (APV) is mechanically vectored by various arthropods and causes seasonal disease in wild birds in the United Kingdom (UK). Signs of APV and the presence of louse flies (Hippoboscidae) on Dunnocks Prunella modularis were recorded over a 16·5-year period in a rural garden in Somerset, UK. Louse flies collected from this site and other sites in England were tested for the presence of APV DNA and RNA sequences. Louse flies on Dunnocks were seen to peak seasonally three weeks prior to the peak of APV lesions, an interval consistent with the previously estimated incubation period of APV in Dunnocks. APV DNA was detected on 13/25 louse flies, Ornithomya avicularia and Ornithomya fringillina, taken from Dunnocks, both with and without lesions consistent with APV, at multiple sites in England. Collectively these data support the premise that louse flies may vector APV. The detection of APV in louse flies, from apparently healthy birds, and from sites where disease has not been observed in any host species, suggests that the Hippoboscidae could provide a non-invasive and relatively cheap method of monitoring avian diseases. This could provide advanced warnings of disease, including zoonoses, before they become clinically apparent.
We construct a Divisia money measure for U.K. households and private non-financial corporations and a corresponding dual user cost index employing a consistent methodology from 1977 up to the present. Our joint construction of both the Divisia quantity index and the Divisia price dual facilitates an investigation of structural vector autoregresssion models (SVARs) over a long sample period of the type of non-recursive identifications explored by Belongia and Ireland (2016, 2018), as well as the block triangular specification advanced by Keating et al. (2019). An examination of the U.K. economy reveals that structures that consider a short-term interest rate to be the monetary policy indicator generate unremitting price puzzles. In contrast, we find sensible economic responses in various specifications that treat our Divisia measure as the indicator variable.
The primary purpose of this study was to assess perceived burdens and benefits of participating in implementation research among staff employed in resource-constrained healthcare settings. Another objective was to use findings to generate considerations for engaging staff in research across different phases of implementation research.
Methods:
This qualitative focus group and consensus building study involved researchers affiliated with the National Cancer Institute Implementation Science Centers in Cancer Control program and nine Community Health Centers (CHCs) in Massachusetts. Six focus groups (n = 3 with CHC staff; n = 3 with researchers) assessed barriers and facilitators to staff participation in implementation research. During consensus discussions, we used findings to develop considerations for engaging staff as participants and partners throughout phases of implementation research.
Results:
Sixteen researchers and 14 staff participated in separate focus groups; nine researchers and seven staff participated in separate consensus discussions. Themes emerged across participant groups in three domains: (1) influences on research participation; (2) research burdens and benefits; and (3) ways to facilitate staff participation in research. Practical considerations included: (a) aligning research with organizational and staff values and priorities; (b) applying user-centered design to research methods; (c) building organizational and individual research capacity; and (d) offering equitable incentives for staff participation.
Conclusions:
Engaging staff as participants and partners across different phases of implementation research requires knowledge about what contributes to research burden and benefits and addressing context-specific burdens and benefits.
Dysphagia is common in infants born with critical CHD. Thickened liquids are often used to treat dysphagia, but associated risks limit widespread use among feeding specialists. This survey aims to assess dysphagia treatment patterns and thickened liquid use across paediatric cardiac surgical centres.
Methods:
A 24-question, cross-sectional survey. Convenience and snowball sampling methods were used to engage 52 paediatric cardiac surgical centres affiliated with the Cardiac Newborn Neuroprotective Network. Descriptive statistics were used to analyse and compare responses.
Results:
Twenty-six individual respondents represented 21 unique paediatric cardiac surgical centres. Most responses were from experienced, speech–language pathologists (78%) at medium size centres (88%). Ninety-three percent of responding centres used thickened liquids to treat dysphagia and 81% only after formal instrumental assessment of swallowing. Thickened oral feeding was used for single-ventricle patients by 85% versus 69% for two-ventricle patients. Barriers to recommending thickened oral feedings included the cost of thickening agents, parental non-adherence, and gastrointestinal concerns.
Conclusions:
This is the first survey to report multi-institutional dysphagia treatment practice variation at United States congenital cardiac surgical centres. Thickened oral feedings are frequently used across centres in high-risk critical CHD patients but treatment benefit remains unclear. This survey highlights a broad scientific community poised to direct dysphagia research in critical CHD to address practice variation, short- and long-term impact of thickened oral feeding on feeding outcomes, and barriers to use and access of thickening agents.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
In September 2023, the UK Health Security Agency’s (UKHSA) South West Health Protection Team received notification of patients with Pseudomonas aeruginosa perichondritis. All five cases had attended the same cosmetic piercing studio and a multi-disciplinary outbreak control investigation was subsequently initiated. An additional five cases attending the same studio were found. Seven of the ten cases had isolates available for Variable Number Tandem Repeat (VNTR) typing at the UKHSA national reference laboratory. Clinical and environmental P. aeruginosa isolates from the patients, handwash sink, tap water and throughout the wall-mounted point-of-use water heater (including outlet water) were indistinguishable by VNTR typing (11,6,2,2,1,3,6,3,11). No additional cases were identified after control measures were implemented, which included replacing the sink and point-of-use heater.
The lack of specific recommendations to control for P. aeruginosa within Council-adopted ear-piercing byelaws or national guidance means that a cosmetic piercing artist could inadvertently overlook the risks from this bacterial pathogen despite every intention to comply with the law and follow industry best practice advice. Clinicians, Environmental Health Officers and public health professionals should remain alert for single cases of Pseudomonas perichondritis infections associated with piercings and have a low threshold for notification to local health protection teams.
Similarity judgments of three-dimensional stimuli were simulated, with the hypothetical subject attending to only some dimensions of stimulus variation (i.e., “subsampling”) on each trial. Recovery of the stimulus configuration by non-metric multidimensional scaling was investigated as a function of subsampling, the amount of random error in the judgments, and the number of stimuli being scaled.
It was found that: (1) dimensions to which the subject often attends were well recovered even when dimensions seldom attended to were not, and (2) measures of recovery based on interpoint distances were inadequate. Several previous Monte Carlo studies were evaluated in light of the results.
Stigma of mental health conditions hinders recovery and well-being. The Honest, Open, Proud (HOP) program shows promise in reducing stigma but there is uncertainty about the feasibility of a randomized trial to evaluate a peer-delivered, individual adaptation of HOP for psychosis (Let's Talk).
Methods
A multi-site, Prospective Randomized Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing the peer-delivered intervention (Let's Talk) to treatment as usual (TAU). Follow-up was 2.5 and 6 months. Randomization was via a web-based system, with permuted blocks of random size. Up to 10 sessions of the intervention over 10 weeks were offered. The primary outcome was feasibility data (recruitment, retention, intervention attendance). Primary outcomes were analyzed by intention to treat. Safety outcomes were reported by as treated status. The study was prospectively registered: https://doi.org/10.1186/ISRCTN17197043.
Results
149 patients were referred to the study and 70 were recruited. 35 were randomly assigned to intervention + TAU and 35 to TAU. Recruitment was 93% of the target sample size. Retention rate was high (81% at 2.5 months primary endpoint), and intervention attendance rate was high (83%). 21% of 33 patients in Let's talk + TAU had an adverse event and 16% of 37 patients in TAU. One serious adverse event (pre-randomization) was partially related and expected.
Conclusions
This is the first trial to show that it is feasible and safe to conduct a RCT of HOP adapted for people with psychosis and individual delivery. An adequately powered trial is required to provide robust evidence.
To explore the meanings that newly arrived refugee adolescents residing in the Southeastern USA attribute to foods.
Design:
We used methods from cognitive anthropology to assess whether adolescents from different countries share a cultural model of eating behaviours.
Setting:
A school-based study in a community in the Southeastern USA.
Participants:
Adolescents (10–17 years) who arrived in the USA on a refugee visa in the previous year.
Results:
Adolescents showed consensus in grouping items and in identifying some foods as associated with adults and others with children. There was evidence of a shared model of eating practices across age, gender and number of siblings. Adolescents who had lived in a refugee camp were significantly different in how they grouped items.
Conclusions:
Adolescents from nine countries shared a model of eating behaviours; these patterns are consistent with rapid dietary acculturation within 1 year of arrival or with shared models held from pre-arrival. Our finding that adolescents who recently arrived in the USA generally agree about how foods relate to one another holds promise for generalised nutrition and dietary interventions across diverse adolescent groups.
Coastal landforms and associated archaeological records are at risk of erosion from a combination of rising sea levels and increasingly frequent high-intensity storms. Improved understanding of this risk can be gained by braiding archaeological and geomorphological methodologies with Indigenous knowledge.1 In this article, archaeological, geomorphological and mātauranga (a form of Indigenous knowledge) are used to analyse a prograded Holocene foredune barrier in northern Aotearoa/New Zealand. Anthropogenic deposits within dune stratigraphy are radiocarbon-dated and used as chronological markers to constrain coastal evolution, alongside geomorphological analyses of topographic data, historical aerial photographs and satellite imagery. These investigations revealed that the barrier is eroding at a rate of 0.45 m/year. A midden in the foredune, which has been radiocarbon dated to 224–270 B.P. (95% Confidence), has been exposed by coastal erosion, confirming that the barrier is in the most eroded state it has been within the past ~300 years. Vertical stratigraphy reveals the presence of midden and palaeosol deposits capped by dune sand deposits in the foredune, indicating that vertical accretion of the foredune continued over the last ~200 years, despite the barrier now being in an eroding state. Mātauranga played a vital role in this project, as it was the coastal taiao (environmental) monitoring unit of Patuharakeke (a Māori sub-tribe) that discovered the midden. The ecological mātauranga shared also played a vital role in this project, adding experiential evidence to empirical observations. The work of local Indigenous groups, like Patuharakeke, demonstrates the active use of mātauranga, woven with Western science methods to preserve or capture the knowledge contained within archaeological sites at risk of being lost to coastal erosion. In this study, we present a method for weaving mātauranga, geomorphological and archaeological approaches to gain a deeper understanding of coastal landscape development.
We aimed to explore participant perspectives on social prescribing (SP) for mental health and well-being and the acceptability of community pharmacists (CP) as members of SP pathways that support people with mild to moderate depression and anxiety.
Background:
SP aims to support people with poor health related to socio-demographic determinants. Positive effects of SP on self-belief, mood, well-being, and health are well documented, including a return to work for long-term unemployed.
Methods:
The study was set in a city in southwest England with diverse cultural and socio-demographics. We recruited SP stakeholders, including CP, to either one of 17 interviews or a focus group with nine members of the public.
Findings:
An inductive iterative approach to thematic analysis produced four superordinate themes: (1) offering choice a non-pharmacological option, (2) supporting pharmacy communities – ‘it is an extension of what we do’, (3) stakeholder perspectives – pharmacists are very busy and their expertise unknown by some, and (4) potential for pharmacy in primary care.
Stakeholders viewed CP as local to and accessible by their community. Pharmacists perceived referral to SP services as part of their current role. General practitioner participants considered pharmacy involvement could reduce their workload and expand the primary healthcare team. Importantly, general practitioners and CP viewed SP as a non-pharmacological alternative to prescribing unnecessary antidepressants and reduce associated adverse effects. All participants voiced concerns about pharmacy dispensing busyness as a potential barrier to involvement and pharmacists requesting mental health training updates.
Key findings suggest CP offer a potential alternative to the general practitioner for people with mild to moderate depression and anxiety seeking access to support and health information. However, CP need appropriately commissioned and funded involvement in SP, including backfill for ongoing dispensing, medicines optimization, and mental health first aid training.