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Background: Individuals with BRCA1/2 mutations have a notably higher than average lifetime risk of developing cancer as adults. Some parents with BRCA1/2 mutations wish to share this information with their children, yet they struggle to know how, when, and what information to share., Objective: The objective of this review was to identify what communication strategies/interventions exist for parents communicating their BRCA1/2 status to their minor children, and what communication interventions do healthcare professionals use to support parents' disclosure process., Methods: Scoping review on six databases search for studies with parents and/or healthcare professionals' interventions on supporting communication from parents to children. The review aligned PRISMA guidelines for scoping reviews and used the PAGER recommendations to guide charting and reporting., Results: 22 articles published from 2001 to 2020 were included. Multiple facilitators/motivators of disclosure, how and where parents disclosed, reactions to disclosure were identified. Also, there were no healthcare professionals' interventions in the disclosure process found., Conclusions: The review summarizes research on parents' disclosure of their BRCA1/2 status to their underage children and demonstrates a paucity of communication interventions for guiding parents in this difficult process. Parents experience many obstacles communicating the results to their children., Practice Implications: These findings equip healthcare professionals in their efforts to develop and test interventions which support the communication of genetic risk information. Furthermore, it is evident there is a need for more research to understand how the disclosure process occurs in the families., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Primary spontaneous pneumothorax occurs in patients with no underlying lung disease and guidelines recommend chest tube drainage for the first episode, with surgical intervention reserved for recurrent episodes, persistent air leak or failure of lung re-expansion. Modern surgical management is associated with reduced length of hospital stay and superior freedom from recurrence compared with chest tube drainage alone. The objective of this study was to identify risk factors for failed chest tube drainage in patients who present with first episode primary spontaneous pneumothorax., Methods: A retrospective analysis of patients who presented to Royal Prince Alfred Hospital, Australia with first episode PSP and underwent chest tube insertion was performed. Patient demographics and size of pneumothorax were examined in relation to the primary outcome, a composite of failed chest tube drainage and recurrent ipsilateral pneumothorax., Results: Fifty-five patients underwent chest tube drainage for first episode primary spontaneous pneumothorax between 1st January 2017 and 31st December 2020. Complete lung collapse on admission chest x-ray was associated with an increased risk of the primary outcome (63% versus 19%, OR 7.3 [96% CI 2.0-27.4), P = 0.004)., Conclusion: This small retrospective study found that patients that undergo chest drain insertion for first episode primary spontaneous pneumothorax who present with complete lung collapse on admission are at high risk of requiring pleurodesis and therefore may benefit from early surgical referral., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Social prescribing is a healthcare model designed to reduce loneliness and improve individuals' health by addressing unmet social needs. The present study adopted the Social Cure framework to provide an understanding of the psychosocial processes involved in helping participants to engage with social activities, from both the link workers' and clients' perspectives. Semi-structured interviews were conducted with 15 link workers ( M age = 40.12; 87% female) and 15 clients ( M age = 55.33; 73% female, 7% non-binary) of social prescribing programmes across Australia and the transcripts were analysed using reflexive thematic analysis. Three overarching themes were identified: (1) Breaking Down Barriers, (2) Finding Fit with Others, and (3) Rebuilding a Sense of Self. These findings communicate how social prescribing addressed the psychosocial barriers of clients, and how joining groups that fostered positive shared social identities resulted in meaningful improvements to clients' well-being., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Epilepsy surgery is an underutilized resource for children with drug-resistant epilepsy. Palliative and definitive surgical options can reduce seizure burden and improve quality of life. Palliative epilepsy surgery is often seen as a "last resort" compared to definitive surgical options. We compare patient characteristics between palliative and definitive epilepsy surgical patients and present palliative surgical outcomes from the Pediatric Epilepsy Research Consortium surgical database., Methods: The Pediatric Epilepsy Research Consortium Epilepsy Surgery database is a prospective registry of patients aged 0-18 years undergoing evaluation for epilepsy surgery at 20 pediatric epilepsy centers. We included all children with completed surgical therapy characterized as definitive or palliative. Demographics, epilepsy type, age of onset, age at referral, etiology of epilepsy, treatment history, time-to-referral/evaluation, number of failed anti-seizure medications (ASMs), imaging results, type of surgery, and postoperative outcome were acquired., Results: Six hundred forty patients undergoing epilepsy surgery were identified. Patients undergoing palliative procedures were younger at seizure onset (median: 2.1 vs 4 years, P= 0.0008), failed more ASM trials before referral for presurgical evaluation (P=<0.0001), and had longer duration of epilepsy before referral for surgery (P=<0.0001). During presurgical evaluation, patients undergoing palliative surgery had shorter median duration of video-EEG data collected (P=0.007) but number of cases where ictal data were acquired was similar between groups. The most commonly performed palliative procedure was corpus callosotmy (31%), followed by lobectomy (21%) and neuromodulation (82% responsive neurostimulation vs 18% deep brain stimulation). Palliative patients were further categorized into traditionally palliative procedures vs traditionally definitive procedures. The majority of palliative patients had 50% reduction or better in seizure burden. Seizure free outcomes were significantly higher among those with traditional definitive surgeries, 41% (95% confidence interval: 26% to 57%) compared with traditional palliative surgeries and 9% (95% confidence interval: 2% to 17%). Rate of seizure freedom was 46% at 24 months or greater of follow-up in the traditional definitive group., Conclusions: Patients receiving palliative epilepsy surgery trialed more ASMs, were referred later after becoming drug resistant, and had longer gaps between drug resistance and epilepsy surgery compared with patients undergoing definitive epilepsy surgery. The extent of surgical evaluation is impacted if surgery is thought to be palliative. A majority of palliative surgery patients achieved >50% seizure reduction at follow-up, both in groups that received traditionally palliative and traditionally definitive surgical procedures. Palliative surgical patients can achieve greater seizure control and should be referred to an epilepsy surgery center promptly after failing two appropriate anti-seizure medications., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hypothesis: The purpose of this study is to identify and compare demographic, clinical, historical, and intraoperative variables in patients who have received arthroscopic treatment for single vs. multiple anterior shoulder dislocations., Methods: This is a retrospective chart review of patients who underwent arthroscopic labral repair of the shoulder by six surgeons at a single institution between 2012 and 2020. Patients with a documented anterior shoulder dislocation were included. Patients with pain-only, subluxation-only, multidirectional or posterior instability, and prior shoulder surgeries of any kind were excluded. Studied variables included age, sex, laterality, body mass index, contact/collision sports, Charlson comorbidity index, tobacco use, number of dislocations (1, >1), labral tear size, time from first dislocation to surgery, anchor number, and concomitant procedures. Study groups were compared using student's t-tests and Mann-Whitney U test for continuous variables and chi-square or Fisher's exact tests for discrete variables with a significance of 0.05., Results: Six hundred thirty-three patients were identified, and 351 (85 single dislocators [SDs], 266 multiple dislocators [MDs]) met inclusion criteria (mean age: 27 years; range: 14-71 years). There were no demographic differences between the study groups. SD received surgery significantly sooner at 17 ± 44 months after injury, while MD received surgery 53 ± 74 months postinitial dislocation. SDs (30/85, 35%) were significantly more likely than MDs (56/266, 21%) to receive concomitant posterior labrum repair. MDs (46/266, 17%) were significantly more likely than SDs (5/85, 6%) to receive a remplissage. SDs (11/85, 13%) were significantly more likely than MDs (11/266, 4%) to receive a concomitant biceps tenotomy/tenodesis. There were no other significant differences in injury or surgery characteristics., Conclusion: MDs will have more time between their initial dislocation and arthroscopic labral repair and are more likely to receive a remplissage procedure, yet they are less likely than SDs to receive a concomitant posterior labral repair or biceps tenodesis/tenotomy despite no differences in age, sex, and activity level. Whether the greater extent of labrum injury in SD is due to a more severe initial injury vs. earlier recognition and intervention requires further study., (© 2024 The Authors.)

Objective: Paroxysmal, rhythmic, and repetitive events (PRREs) during infancy can be concerning for possible seizures, especially following perinatal brain injuries. The workup for establishing whether a PRRE represents a seizure involves the use of continuous video-electroencephalography (cVEEG) for event characterization. This study aims to determine the diagnostic yield of cVEEG for evaluating events concerning for seizures in children aged 1-24 months., Methods: We performed a single-center retrospective chart review (January 1, 2019-December 31, 2020) and included all children aged 1-24 months admitted for PRRE capture and characterization using cVEEG. Chart abstraction included demographics, birth and family history, known brain injury, event semiology, duration, and frequency, as well as interictal electroencephalographic (EEG) features. For each of these variables, odds ratios for seizure prediction were calculated., Results: A total of 243 patients were identified for this study. On cVEEG, n = 160 (65.4%) had a target event of concern captured during an initial admission with cVEEG. Whereas n = 41 (25.8%) patients with events captured were confirmed to have seizures, most patients (n = 119) were confirmed to have nonepileptic events. Several variables predicted seizure likelihood during the initial admission with cVEEG, including event duration (>1 min), frequency (occurring ≥3 times per week), and presence of abnormal interictal findings on cVEEG. For patients who did not receive a diagnosis at the time of initial admission with cVEEG, the likelihood of a subsequent epilepsy diagnosis was associated with specific PRRE semiology (motor active or motor passive), longer event duration (>1 min duration), and the presence of interictal abnormal EEG features on initial cVEEG admission. Prediction tools utilizing scoring systems to stratify risk in infants with suspected seizures due to PRREs are included., Significance: Unique patient attributes and PRRE characteristics, as well as the presence of EEG interictal abnormalities, can provide valuable insights for discerning children with a higher likelihood of epilepsy diagnosis following cVEEG admission., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Methane is an important greenhouse gas 1 , but the role of trees in the methane budget remains uncertain 2 . Although it has been shown that wetland and some upland trees can emit soil-derived methane at the stem base 3,4 , it has also been suggested that upland trees can serve as a net sink for atmospheric methane 5,6 . Here we examine in situ woody surface methane exchange of upland tropical, temperate and boreal forest trees. We find that methane uptake on woody surfaces, in particular at and above about 2 m above the forest floor, can dominate the net ecosystem contribution of trees, resulting in a net tree methane sink. Stable carbon isotope measurement of methane in woody surface chamber air and process-level investigations on extracted wood cores are consistent with methanotrophy, suggesting a microbially mediated drawdown of methane on and in tree woody surfaces and tissues. By applying terrestrial laser scanning-derived allometry to quantify global forest tree woody surface area, a preliminary first estimate suggests that trees may contribute 24.6-49.9 Tg of atmospheric methane uptake globally. Our findings indicate that the climate benefits of tropical and temperate forest protection and reforestation may be greater than previously assumed., (© 2024. The Author(s).)

Introduction: There have been few controlled evaluations of Social Prescribing (SP), in which link workers support lonely individuals to engage with community-based social activities. This study reports early outcomes of a trial comparing General Practitioner treatment-as-usual (TAU) with TAU combined with Social Prescribing (SP) in adults experiencing loneliness in Queensland., Methods: Participants were 114 individuals who were non-randomly assigned to one of two conditions (SP, n  = 63; TAU, n  = 51) and assessed at baseline and 8 weeks, on primary outcomes (loneliness, well-being, health service use in past 2 months) and secondary outcomes (social anxiety, psychological distress, social trust)., Results: Retention was high (79.4%) in the SP condition. Time × condition interaction effects were found for loneliness and social trust, with improvement observed only in SP participants over the 8-week period. SP participants reported significant improvement on all other outcomes with small-to-moderate effect sizes (ULS-8 loneliness, wellbeing, psychological distress, social anxiety). However, interaction effects did not reach significance., Discussion: Social prescribing effects were small to moderate at the 8-week follow up. Group-based activities are available in communities across Australia, however, further research using well-matched control samples and longer-term follow ups are required to provide robust evidence to support a wider roll out., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dingle, Sharman, Hayes, Haslam, Cruwys, Jetten, Haslam, McNamara, Chua, Baker and Johnson.)

Visceral leishmaniasis is a potentially fatal disease caused by infection by the intracellular protist pathogens Leishmania donovani or Leishmania infantum. Present therapies are ineffective because of high costs, variable efficacy against different species, the requirement for hospitalization, toxicity and drug resistance. Detailed analysis of previously published hit molecules suggested a crucial role of 'guanidine' linkage for their efficacy against L. donovani. Here we report the design of 2-aminoquinazoline heterocycle as a basic pharmacophore-bearing guanidine linkage. The introduction of various groups and functionality at different positions of the quinazoline scaffold results in enhanced antiparasitic potency with modest host cell cytotoxicity using a physiologically relevant THP-1 transformed macrophage infection model. In terms of the ADME profile, the C7 position of quinazoline was identified as a guiding tool for designing better molecules. The good ADME profile of the compounds suggests that they merit further consideration as lead compounds for treating visceral leishmaniasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug-resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty-two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6-10 new RNS devices per year; all DBS programs implant <5 annually. The youngest RNS patient was 3 years old. Most centers (11/12) utilize MP2RAGE and/or FGATIR sequences for planning. Centromedian thalamic nuclei were the unanimous target for Lennox-Gastaut syndrome. Surgeon exposure to neuromodulation occurred mostly in clinical practice (14/17). Clinically significant hemorrhage (n = 2) or infection (n = 3) were rare. Meaningful seizure reduction (>50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. PLAIN LANGUAGE SUMMARY: We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug-resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

We present a rare case of a 39-year-old female with extramedullary relapse of acute myeloid leukaemia (AML) isolated to the left eye 2 months post allogeneic haematopoietic stem cell transplant. She initially presented with painless left eye erythema, swelling, and visual impairment. Initial ophthalmology review revealed conjunctival chemosis, raised intraocular pressure, and serous retinal detachments. She was initially treated for suspected orbital cellulitis with intravenous antibiotic and antifungal therapy but clinically progressed so was then treated with intravenous corticosteroids. One week later, she progressed to angle-closure glaucoma with development of a hypopyon and an enlarging subconjunctival mass. She proceeded to urgent subconjunctival biopsy and drainage of subretinal fluid which confirmed extramedullary relapse of AML. Notably, further investigation found no evidence of bone marrow or central nervous system relapse. She proceeded to localized radiotherapy with gradual resolution of the subconjunctival mass and serous retinal detachment and was for consideration of donor lymphocyte infusions and azacitidine therapy; unfortunately, she developed respiratory sepsis and passed away despite maximal efforts. This case represents a rare and unusual presentation of isolated ocular extramedullary relapse of AML and emphasises the importance of early ophthalmology involvement and tissue biopsy when there is high clinical suspicion of the disease., Competing Interests: The authors have no relevant financial or nonfinancial interests to disclose., (Copyright © 2024 M. H. Tong et al.)

Objective: This study assesses current practices and outcomes of epilepsy surgery in children with a genetic etiology. It explores the pre-surgical workup, types of surgeries, and post-surgical outcomes in a broad array of disorders., Methods: Patients ≤18 years who completed epilepsy surgery and had a known genetic etiology prior to surgical intervention were extrapolated from the Pediatric Epilepsy Research Consortium (PERC) surgery database, across 18 US centers. Data were assessed univariably by neuroimaging and EEG results, genetic group (structural gene, other gene, chromosomal), and curative intent. Outcomes were based on a modified International League Against Epilepsy (ILAE) outcome score., Results: Of 81 children with genetic epilepsy, 72 % had daily seizures when referred for surgery evaluation, which occurred a median of 2.2 years (IQR 0.3, 5.2) after developing drug resistance. Following surgery, 68 % of subjects had >50 % seizure reduction, with 33 % achieving seizure freedom [median follow-up 11 months (IQR 6, 17). Seizure freedom was most common in the monogenic structural group, but significant palliation was present across all groups. Presence of a single EEG focus was associated with a greater likelihood of seizure freedom (p=0.02)., Significance: There are meaningful seizure reductions following epilepsy surgery in the majority of children with a genetic etiology, even in the absence of a single structural lesion and across a broad spectrum of genetic causes. These findings highlight the need for expedited referral for epilepsy surgery and support of a broadened view of which children may benefit from epilepsy surgery, even when the intent is palliative., Competing Interests: Declaration of Competing Interest Allyson Alexander, MD is a consultant for NuXceland. All additional authors report no declarations of interest., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Gaming disorder is a growing concern affecting adolescents, exacerbated by the impact of recent COVID-19 restrictions. The World Health Organization has recently included gaming disorder in the 11th International Classification of Diseases (ICD-11). However, there is still an ongoing debate about the validity and reliability of the proposed clinical criteria, despite growing neurobiological evidence in this cohort. Systematic reviews in this area have focused mainly on adults or mixed adult/adolescent populations. Therefore, this systematic review explored the neuroimaging literature in adolescents (under 18 years old) with gaming disorder., Methods: Using PRISMA 2020 guidelines, 3288 primary studies were identified from PubMed, CINAHL Plus, PsycINFO and Web of Science. After applying inclusion and exclusion criteria (appropriate title, abstract, comparison group used within study, English-language, neuroimaging and mean age under 18), 24 studies were included in this review., Results: Functional and structural brain alterations in adolescent gaming disorder were noted across several imaging modalities, including electroencephalogram (EEG), functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging (MRI). Compared with healthy controls, adolescents with gaming disorder demonstrated neurological changes comparable to substance addiction, namely impairments in emotional regulation, reward-seeking, inhibition and increased risky decision-making. Positive brain adaptations in the areas of visuospatial processing and memory were observed., Conclusions: A number of key brain regions are affected in adolescent gaming disorder. These findings can help clinicians understand adolescent presentations with gaming disorder from a neurobiological perspective. Future studies should focus on forming a robust neurobiological and clinical framework for adolescent gaming disorder.

Aims and Objectives: To systematically identify and synthesise the experiences reported by women with a breast cancer mutation who do not have cancer as reported in qualitative research published between 2013 and 2020., Background: Women carrying a BReast CAncer (BRC) genetic mutation have an increased risk for breast and ovarian cancer. They must engage in emotional decision-making regarding risk management strategies to prevent cancer, including risk-reducing bilateral mastectomy and bilateral salpingo-oophorectomy., Design and Methods: The ENTREQ statement guided this review. Eight databases were systematically searched (CINAHL, Pubmed, Embase, Psychinfo [Ovid], Web of Science, Scopus, Proquest and Lenus). Synthesis was guided by "best fit" framework. The Critical Appraisal Skills Programme guided assessment of methodological limitations and confidence in the review findings was informed by GRADE-CERQual., Results: Twenty studies met the inclusion criteria for synthesis. Six themes were synthesised from the included studies (anxiety; family planning; it's a family affair; empowerment; actions; pragmatic adjustments)., Conclusions: The multidimensional experiences of women living with a BRCA1/2 mutation require an individualised response based on women's needs at their life stages. A decision coaching model adopted during consultations could support women to guide decision-making regarding cancer risk-reducing strategies., (© 2022 John Wiley & Sons Ltd.)

Social prescribing (or community referral) is a model of healthcare designed to address social needs that contribute to poor health. At the heart of social prescribing programs is the link worker, who liaises between clients, health professionals and community organisations. Social prescribing is newly emerging in Australia but there are already calls for a large-scale roll out. This research, therefore, aimed to understand Australian link workers' role and skills required, to determine where such a workforce could be drawn from in Australia, and to identify what training and resources are needed to support this potential new workforce. To explore these questions, interviews were conducted with 15 link workers in Queensland, New South Wales and Victoria, and the transcripts were analysed using thematic analysis. Participants were predominantly female (87%); and primarily had qualifications in social work (47%) or nursing (27%). Three overarching themes were identified: (1) skills of successful social prescribing, identifying that link work requires multifaceted social and emotional skills; (2) workforce issues, presenting that link workers experienced challenges such as a lack of available support and training, lack of public awareness of social prescribing and a lack of sustained funding; and (3) job fulfilment, related to link workers' sense of reward and accomplishment from the job. We suggest that fostering job fulfilment in conjunction with the provision of increased support, training and security will reduce feelings of overwork and burnout among link workers and likely lead to longevity in the role. Social prescribing has the potential to be hugely beneficial to clients and the community and fulfilling for link workers, provided that sufficient advocacy and resources are put in place., (© 2022 The Authors. Health and Social Care in the Community published by John Wiley & Sons Ltd.)

Importance: Children commonly experience physical, cognitive, or emotional sequelae after sepsis. However, little is known about the development or progression of medical conditions after pediatric sepsis., Objective: To quantify the development and progression of 4 common conditions in the 6 months after sepsis and to assess whether they differed after hospitalization for sepsis vs nonsepsis among critically ill children., Design, Setting, and Participants: This cohort study of 101 511 children (<19 years) with sepsis or nonsepsis hospitalization used a national administrative claims database (January 1, 2010, to June 30, 2018). Data management and analysis were conducted from April 1, 2020, to July 7, 2022., Exposures: Intensive care unit hospitalization for sepsis vs all-cause intensive care unit hospitalizations, excluding sepsis., Main Outcomes and Measures: Primary outcomes were the development of 4 target conditions (chronic respiratory failure, seizure disorder, supplemental nutritional dependence, and chronic kidney disease) within 6 months of hospital discharge. Secondary outcomes were the progression of the 4 target conditions among children with the condition before hospitalization. Outcomes were identified via diagnostic and procedural codes, durable medical equipment codes, and prescription medications. Differences in the development and the progression of conditions between pediatric patients with sepsis and pediatric patients with nonsepsis who survived intensive care unit hospitalization were assessed using logistic regression with matching weights., Results: A total of 5150 survivors of pediatric sepsis and 96 361 survivors of nonsepsis intensive care unit hospitalizations were identified; 2593 (50.3%) were female. The median age was 9.5 years (IQR, 3-15 years) in the sepsis cohort and 7 years (IQR, 2-13 years) in the nonsepsis cohort. Of the 5150 sepsis survivors, 670 (13.0%) developed a new target condition, and 385 of 1834 (21.0%) with a preexisting target condition had disease progression. A total of 998 of the 5150 survivors (19.4%) had development and/or progression of at least 1 condition. New conditions were more common among sepsis vs nonsepsis hospitalizations (new chronic respiratory failure: 4.6% vs 1.9%; odds ratio [OR], 2.54 [95% CI, 2.19-2.94]; new supplemental nutritional dependence: 7.9% vs 2.7%; OR, 3.17 [95% CI, 2.80-3.59]; and new chronic kidney disease: 1.1% vs 0.6%; OR, 1.65 [95% CI, 1.25-2.19]). New seizure disorder was less common (4.6% vs 6.0%; OR, 0.77 [95% CI, 0.66-0.89]). Progressive supplemental nutritional dependence was more common (1.5% vs 0.5%; OR, 2.95 [95% CI, 1.60-5.42]), progressive epilepsy was less common (33.7% vs 40.6%; OR, 0.74 [95% CI, 0.65-0.86]), and progressive respiratory failure (4.4% vs 3.3%; OR, 1.35 [95% CI, 0.89-2.04]) and progressive chronic kidney disease (7.9% vs 9.2%; OR, 0.84 [95% CI, 0.18-3.91]) were similar among survivors of sepsis vs nonsepsis admitted to an intensive care unit., Conclusions and Relevance: In this national cohort of critically ill children who survived sepsis, 1 in 5 developed or had progression of a condition of interest after sepsis hospitalization, suggesting survivors of pediatric sepsis may benefit from structured follow-up to identify and treat new or worsening medical comorbid conditions.

Visceral leishmaniasis is a potentially fatal disease caused by the parasitic protists, Leishmania donovani and L. infantum. Current treatments remain unsuitable due to cost, the need for hospitalization, variable efficacy against different species, toxicity and emerging resistance. Herein, we report the SAR exploration of the novel hit 4-Fluoro-N-(5-(4-methoxyphenyl)-1-methyl-1H-imidazole-2-yl)benzamide [1] previously identified from a high throughput screen against Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani. An extensive and informative set of analogues were synthesized incorporating key modifications around the scaffold resulting in improved potency, whilst the majority of compounds maintained low cytotoxicity against human THP-1 macrophages that are target cells for these pathogens. New lead compounds identified within this study also maintained desirable physicochemical properties, improved metabolic stability in vitro and displayed no significant mitotoxicity against HepG2 cell lines. This compound class warrants continued investigation towards development as a novel treatment for Visceral Leishmaniasis., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Previous research has demonstrated that reversing the contrast of the eye region, which includes the eyebrows, affects the N170 ERP. To selectively assess the impact of just the eyes, the present study evaluated the N170 in response to reversing contrast polarity of just the iris and sclera in upright and inverted face stimuli. Contrast reversal of the eyes increased the amplitude of the N170 for upright faces, but not for inverted faces, suggesting that the contrast of eyes is an important contributor to the N170 ERP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jantzen, McNamara, Harris, Schubert, Brooks, Seifert and Symons.)

Importance: There are no approved medications for the core symptoms of autism spectrum disorder (ASD), socialization and communication difficulties., Objective: To evaluate the efficacy and safety of balovaptan, an oral selective vasopressin 1a receptor antagonist, compared with placebo in children and adolescents with ASD., Design, Setting, and Participants: The aV1ation study was a randomized, double-blind, 24-week, parallel-group, placebo-controlled phase 2 trial. Between November 22, 2016, and September 3, 2019, individuals were screened and randomly assigned to treatment groups. The primary efficacy analysis population comprised participants taking age-adjusted balovaptan equivalent to a 10-mg adult dose and participants from the concurrently randomized placebo group. This multicenter trial took place across 41 sites in the US. Participants were aged 5 to 17 years with diagnosed ASD and an IQ of 70 or greater. Data were analyzed from April 8 to November 16, 2020., Interventions: Participants were randomly assigned to daily 4-mg or 10-mg adult-equivalent balovaptan or placebo, until the 4-mg group was discontinued., Main Outcomes and Measures: The primary end point was change from baseline on the Vineland-II two-domain composite (2DC; socialization and communication domains) score at week 24., Results: Between November 2016 and September 2019, a total of 599 individuals were screened and 339 participants were randomly assigned to receive 4-mg balovaptan adult-equivalent dose (91 [26.8%]), 10-mg balovaptan adult-equivalent dose (126 [37.2%]), or placebo (122 [36.0%]). Primary analysis included 86 participants assigned to receive 10-mg balovaptan adult-equivalent dose and 81 assigned to receive placebo (mean [SD] age, 12.1 [3.4] years; 139 male participants [83.2%]). No statistically significant differences were observed between the balovaptan and placebo groups in change from baseline on the Vineland-II 2DC score at week 24 (difference in adjusted least-squares mean, -0.16; 90% CI, -2.56 to 2.23; P = .91). No improvements for balovaptan vs placebo were observed at week 24 for any secondary end points. Balovaptan was well tolerated with no emerging safety concerns. Similar proportions of participants reported adverse events (balovaptan, 66 of 86 [76.7%] vs placebo, 61 of 81 [75.3%]) and serious adverse events (balovaptan, 1 of 86 [1.2%] vs placebo, 4 of 81 [4.9%])., Conclusions and Relevance: In this randomized clinical trial, balovaptan did not demonstrate efficacy in improvement of socialization and communication in this population with pediatric ASD. Balovaptan was well tolerated in children 5 years or older. Further development of robust, sensitive, and objective outcome measures may help to improve future studies in the assessment of therapies targeting communication and socialization in pediatric ASD., Trial Registration: ClinicalTrials.gov Identifier: NCT02901431.

Background: In social prescribing, link workers support individuals whose persistent health problems are exacerbated by loneliness by connecting them to community-based social activities. This approach is well established in the UK and is gaining attention in Australia. However, a major limitation of research to date has been a lack of theoretically informed and rigorous evaluations of social prescribing. We will address these points in this study, applying a social identity framework to examine the effects of group-based social prescribing (SP) activity compared to primary care treatment as usual (TAU)., Methods: Ninety participants experiencing loneliness recruited from primary care services and community centres across five sites in Southeast Queensland will be assigned to one of two conditions (SP, TAU) and assessed at two timepoints (baseline, + 8 weeks). Individuals will be aged 18 years and over, have sufficient English language skills to provide consent, and at the time of recruitment they will not be experiencing acute symptoms or social issues that require urgent intervention. Primary outcomes are loneliness, mental well-being, and health service use (total number of GP, hospital, and allied health visits in the past 3 months). Secondary outcomes will assess social group processes, including number of important social groups, new group identification, multiple identity compatibility, and group-based support and emotion regulation., Discussion: This study will provide comprehensive data about the extent to which, and how, social prescribing to community-based group activities may help people to feel less lonely, more socially integrated, and healthy over the first 8 weeks. If effective, this social identity-informed model of social prescribing can be disseminated in communities across Australia., Trial Registration: ANZCTR, Registered 8 June 2022 - Retrospectively registered, https://www.anzctr.org.au/ACTRN12622000801718.aspx., (© 2022. The Author(s).)

Background: Autism spectrum disorder (ASD) is a common and heterogeneous neurodevelopmental condition that is characterized by the core symptoms of social communication difficulties and restricted and repetitive behaviors. At present, there is an unmet medical need for therapies to ameliorate these core symptoms in order to improve quality of life of autistic individuals. However, several challenges are currently faced by the ASD community relating to the development of pharmacotherapies, namely in the conduct of clinical trials. Balovaptan is a V1a receptor antagonist that has been investigated to improve social communication difficulties in individuals with ASD. In this viewpoint, we draw upon our recent first-hand experiences of the balovaptan clinical development program to describe current challenges of ASD trials., Discussion Points: The balovaptan trials were conducted in a wide age range of individuals with ASD with the added complexities associated with international trials. When summarizing all three randomized trials of balovaptan, a placebo response was observed across several outcome measures. Placebo response was predicted by greater baseline symptom severity, online recruitment of participants, and less experienced or non-academic trial sites. We also highlight challenges relating to selection of outcome measures in ASD, the impact of baseline characteristics, and the role of expectation bias in influencing trial results., Conclusion: Taken together, the balovaptan clinical development program has advanced our understanding of the key challenges facing ASD treatment research. The insights gained can be used to inform and improve the design of future clinical trials with the collective aim of developing efficacious therapies to support individuals with ASD., (© 2022. The Author(s).)

Communities are vital sources of support during crisis, providing collective contexts for shared identity and solidarity that predict supportive, prosocial responses. The COVID-19 pandemic has presented a global health crisis capable of exerting a heavy toll on the mental health of community members while inducing unwelcome levels of social disconnection. Simultaneously, lockdown restrictions have forced vulnerable community members to depend upon the support of fellow residents. Fortunately, voluntary helping can be beneficial to the well-being of the helper as well as the recipient, offering beneficial collective solutions. Using insights from social identity approaches to volunteering and disaster responses, this study explored whether the opportunity to engage in helping fellow community members may be both unifying and beneficial for those engaging in coordinated community helping. Survey data collected in the UK during June 2020 showed that coordinated community helping predicted the psychological bonding of community members by building a sense of community identification and unity during the pandemic, which predicted increased well-being and reduced depression and anxiety. Implications for the promotion and support of voluntary helping initiatives in the context of longer-term responses to the COVID-19 pandemic are provided. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. Journal of Community & Applied Social Psychology published by John Wiley & Sons Ltd.)

OCCUPATIONAL APPLICATIONSResults of the current exploratory study suggest that use of an exoskeleton (EXO) has the potential to be accepted by workers as an intervention in diverse manufacturing environments. Also evident were that the major factors contributing to EXO-use-intention are perceived comfort, task-technology fit, perceived safety, and perceived usefulness. A user's perception of perceived usability may be established by using an exoskeleton during actual job tasks, yet some aspects of perceived usability likely require multiple exposures to an EXO for an accurate assessment. Many negative comments regarding EXO use were related to physical constraints (e.g., restricted movements, bulkiness), and to the EXO interface (e.g., straps, cuff designs), suggesting a need for further research on EXO design to minimize discomfort. In practice, there is likely value in having workers use and explore candidate EXOs during their actual job, both to accurately assess the usefulness of an EXO and to find the most effective EXO.

The economic crisis precipitated by the coronavirus disease (COVID-19) pandemic has placed considerable financial pressures on households across the world. These are compounded by the enforced isolation accompanying pandemic restrictions, during which individuals can struggle to access external assistance and often need to rely heavily on the social, emotional, and financial support of other family members. Previous research indicates that family financial stress has negative consequences for the mental health and well-being of members, but that heightened family identification can provide individuals with a stronger sense of collective financial resilience. In the present study, an online longitudinal survey of U.K. residents ( N = 172) shows that, in summer 2020, the positive relationship between individuals' family identification and their well-being 1 month later was mediated by levels of perceived family financial efficacy and financial stress. These findings build upon existing evidence of the pivotal role of the family in financial well-being and suggest that supporting family units to cope with shared financial challenges may have psychological benefits over and above supporting individual family members. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Pulmonary thromboendarterectomy (PTE) is the gold standard treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, the results are poorly quantified outside a few registry reports and several individual centers., Methods: A systematic review was performed searching five electronic databases assessing the outcomes for adult patients undergoing PTE for CTEPH. All articles that reported mortality data were included. Primary outcome measures were early/inpatient mortality; secondary outcomes were survival, pulmonary haemodynamics, morbidity and functional status following PTE for CTEPH. Results were pooled via a meta-analysis of proportions and meta-regression., Results: A total of 5,717 studies were identified, yielding sixty-one relevant papers. Thirty-day mortality ranged from 0.8% to 24.4%, and on meta-analysis was 8.4% [95% confidence interval (CI): 7.2-9.6%]. Mortality was noted to decrease with increasing center volume of PTE cases (P<0.01). Residual pulmonary hypertension was reported in 8.2% to 44.5% of patients., Conclusions: CTEPH is associated with acceptable short-term mortality and an improvement in pulmonary hemodynamics. With increasing volume of experience and ongoing developments over time peri-operative mortality continues to decrease., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2022 Annals of Cardiothoracic Surgery. All rights reserved.)

We examined whether the Social Cure (SC) perspective explains the efficacy of a Social Prescribing (SP) pathway which addresses healthcare needs through enhancing social connections. Data were collected at pathway entry from patients with long-term health conditions, or who felt isolated/lonely/anxious ( N = 630), then again 4 months later ( N = 178), and 6-9 months later ( N = 63). Being on the pathway was associated with increased group memberships between T0 and T1. The relationship between increased group memberships and quality-of-life was serially mediated by belonging, support and loneliness. This study is the first to show SP enhances health/well-being via SC mechanisms.

Background: Health and social care workers (HSCWs) are at risk of experiencing adverse mental health outcomes (e.g. higher levels of anxiety and depression) because of the COVID-19 pandemic. This can have a detrimental effect on quality of care, the national response to the pandemic and its aftermath., Aims: A longitudinal design provided follow-up evidence on the mental health (changes in prevalence of disease over time) of NHS staff working at a remote health board in Scotland during the COVID-19 pandemic, and investigated the determinants of mental health outcomes over time., Method: A two-wave longitudinal study was conducted from July to September 2020. Participants self-reported levels of depression (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7) and mental well-being (Warwick-Edinburgh Mental Well-being Scale) at baseline and 1.5 months later., Results: The analytic sample of 169 participants, working in community (43%) and hospital (44%) settings, reported substantial levels of depression and anxiety, and low mental well-being at baseline (depression, 30.8%; anxiety, 20.1%; well-being, 31.9%). Although mental health remained mostly constant over time, the proportion of participants meeting the threshold for anxiety increased to 27.2% at follow-up. Multivariable modelling indicated that working with, and disruption because of, COVID-19 were associated with adverse mental health changes over time., Conclusions: HSCWs working in a remote area with low COVID-19 prevalence reported substantial levels of anxiety and depression, similar to those working in areas with high COVID-19 prevalence. Efforts to support HSCW mental health must remain a priority, and should minimise the adverse effects of working with, and disruption caused by, the COVID-19 pandemic., Competing Interests: None., (© The Author(s) 2022.)

Background: Given the limited treatment options for younger children with attention-deficit/hyperactivity disorder (ADHD), a clinical study for SHP465 treatment was warranted., Objectives: We aimed to evaluate the pharmacokinetics, safety, and tolerability of SHP465 mixed amphetamine salts (MAS) 6.25 mg after multiple once-daily doses in children aged 4-5 years with ADHD., Methods: In this open-label multicenter study, SHP465 MAS 6.25 mg once daily was administered for 28 days to children aged 4-5 years with ADHD; baseline ADHD Rating Scale-5 total score ≥ 28 (boys) or ≥ 24 (girls) and Clinical Global Impression-Severity scale score ≥ 4. Blood samples were collected in the pharmacokinetic-rich group predose on day 1 week 1 and day 7 week 4 (predose, postdose at 2, 5, 8, 12, 16, 24, and 48 hours); and in the pharmacokinetic-sparse group predose on day 1 weeks 1, 2, and 3 and 24 hours postdose on day 7 week 4 . Key pharmacokinetic parameters included maximum plasma drug concentration (C max ), plasma trough drug concentration, time to C max during a dosing interval (t max ), area under the concentration-time curve from time 0 to time of last collected sample, area under the concentration-time curve over the dosing interval (24 h) at steady state (AUC tau,ss ), first-order rate constant associated with the terminal phase of elimination, terminal half-life (t 1/2 ), total clearance of drug from plasma after oral administration, and apparent volume of distribution at steady state. Safety endpoints included treatment-emergent adverse events and vital signs., Results: Mean ± standard deviation age and body mass index of 24 participants (66.7% male) were 4.8 ± 0.41 years and 17.2 ± 3.18 kg/m 2 , respectively. The most common ADHD was the combined presentation (91.7%); ratings were 50% markedly ill and 45.8% moderately ill on the Clinical Global Impression-Severity scale. Plasma d-amphetamine and l-amphetamine steady state was attained by predose on treatment day 8, consistent with the half-life. Peak steady-state plasma concentration (median t max ) for both d-amphetamine and l-amphetamine occurred at 7.92 h postdose on day 7 week 4 and thereafter declined monoexponentially, with a geometric mean t 1/2 of 10.4 and 12.3 h for d-amphetamine and l-amphetamine, respectively. For both d-amphetamine and l-amphetamine, C max and AUC tau,ss were comparable between children aged 4 years (n = 3) and children aged 5 years (n = 8) regardless of sex. In total, 14 treatment-emergent adverse events were reported by 45.8% (11/24) of participants. Five treatment-emergent adverse events, reported for four (16.7%) participants, were considered treatment related; affect lability occurred in two (8.3%) participants, and insomnia, accidental overdose, and increased blood pressure each occurred in one (4.2%) participant., Conclusions: In children aged 4-5 years with ADHD, following multiple once-daily administrations of SHP465 MAS 6.25 mg, the pharmacokinetic profile of plasma d-amphetamine and l-amphetamine was generally consistent among participants. Between-individual variability of plasma d-amphetamine and l-amphetamine steady-state exposure was low to moderate. SHP465 MAS was generally well tolerated in this study., Trial Registration: ClinicalTrials.gov, NCT03327402 (31 October, 2017)., (© 2021. The Author(s).)

Background: The role of change in fractional flow reserve derived from CT (FFR CT ) across coronary stenoses (ΔFFR CT ) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown., Objectives: To investigate the incremental value of ΔFFR CT in predicting early revascularization and improving efficiency of catheter laboratory utilization., Materials: Patients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFR CT was measured 2 ​cm distal to stenosis. ΔFFR CT was manually measured as the difference of FFR CT across visible stenosis., Results: Of 4730 patients (66 ​± ​10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFR CT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26-1.35]; p ​< ​0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFR CT . Among the 3 models (model 1: risk factors ​+ ​stenosis type and location ​+ ​CAD-RADS; model 2: model 1 ​+ ​FFR CT ; model 3: model 2 ​+ ​ΔFFR CT ), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86-0.88] vs 0.85 [0.84-0.86]; p ​< ​0.001), with the greatest incremental value for FFR CT 0.71-0.80. ΔFFR CT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFR CT ≤0.8, a diagnostic strategy incorporating ΔFFR CT >0.13, would potentially reduce ICA by 32.2% (1638-1110, p ​< ​0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%., Conclusions: ΔFFR CT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFR CT , particularly for those with FFR CT 0.71-0.80. ΔFFR CT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization., Competing Interests: Declaration of competing interest This study was supported by HeartFlow, Inc., Redwood City, California, via individual Clinical Study Agreements with each enrolling institution and with the Duke Clinical Research Institute (DCRI) for Core Laboratory activities and Clinical Event Committee adjudication of adverse events. Dr. Leipsic receives institutional grants to provide core lab services to Edwards Life Sciences, Medtronic and is a consultant to Circle CVI and HeartFlow. Dr. Fairbairn is on the Speakers Bureau for HeartFlow. Dr. Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr. Berman has received unrestricted research support from HeartFlow. Dr. Chinnaiyan has received institutional grants from HeartFlow. Dr. Hurwitz-Koweek is on the Speakers Bureau for HeartFlow; and has unrestricted grant funding from Siemens and HeartFlow. Dr. Pontone is a consultant for GE Healthcare; and has research grants from GE Healthcare and HeartFlow. Dr. Rabbat has received institutional grants from HeartFlow. Dr. Mullen is an employee of HeartFlow. Dr. Rogers is an employee of and has equity in HeartFlow. Dr. Bax has received unrestricted research grants from Edwards Lifescience, Medtronic, Boston Scientific, Biotronik, and GE Healthcare; and is on the Speakers Bureau with Abbott. Dr. Douglas receives an institutional research grant from HeartFlow. Dr. Patel has received grants from HeartFlow, Jansen, Bayer, AstraZeneca, and NHLBI; and has served as a consultant for Jansen, Bayer, AstraZeneca, Genzyme, and Merck. Dr. Nieman reports institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc. and is a consultant to Siemens Medical Solutions USA. Dr. Ihdayhid is supported by the National Health and Medical Research Council of Australia and National Heart Foundation Scholarships; and has received honoraria from Canon Medical and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: At present, the optimal management strategy for chronic type B aortic dissection (CTBAD) remains unknown, as equipoise remains regarding medical management versus endovascular treatment versus open surgery. However, the results over recent years of thoracic endovascular aortic repair (TEVAR) in CTBAD appear promising. The aim of this systematic review was to provide a comprehensive analysis of the available data reporting outcomes and survival rates for TEVAR in CTBAD., Methods: Electronic searches of six databases were performed from inception to April 2021. All studies reporting outcomes, specifically 30-day mortality rates, for endovascular repair of CTBAD were identified. Relevant data were extracted, and a random-effects meta-analysis of proportions or means was performed to aggregate the data. Survival data were pooled using data derived from original Kaplan-Meier curves, which allows reconstruction of individual patient data., Results: Forty-eight studies with 2,641 patients were identified. Early (<30 days) all-cause and aortic-related mortality rates were low at 1.6% and 0.5%, respectively. Incidence of retrograde type A dissection in the post-operative period was only 1.4%. There were also low rates of cerebrovascular accidents and spinal cord injury (1.1% and 0.9%, respectively). Late follow-up all-cause mortality was 8.0%, however, late aortic-related mortality was only 2.4%. Reintervention rates were 10.1% for endovascular and 6.7% for surgical reintervention. Pooled rates of overall survival at 1-, 3-, 5- and 10-year were 91.5%, 84.7%, 77.7% and 56.3%, respectively., Conclusions: The significant heterogeneity in the available evidence and absence of consensus reporting standards are important considerations and concern when interpreting the data. Evaluation of the evidence suggests that TEVAR for CTBAD is a safe procedure with low rates of complications. However, the optimal treatment strategy for CTBAD remains debatable and requires further research. Evidence from high-quality registries and clinical trials are required to address these challenges., Competing Interests: Conflicts of Interest: Dr. OP provides consultation for and participates in clinical trials with Medtronic and W.L. Gore & Associates. The other authors have no conflicts of interest to declare., (2022 Annals of Cardiothoracic Surgery. All rights reserved.)

Background: Internationally, the response to the COVID-19 pandemic has resulted in fewer cardiac surgical procedures being performed and an increase in the proportion of non-elective cases. To date there has been no study examining the impact of COVID-19 on the provision of cardiac surgery in Australia., Aim: The aim of this study was to evaluate the impact that the COVID-19 pandemic has had on the provision of cardiac surgery in a single, large major cardiac centre and dedicated COVID-19 hospital. A retrospective cohort study was undertaken utilising prospectively collected data., Methods: Prospectively collected patient and operative data was examined to assess whether there was a reduction in the number of cases performed and whether there was a difference in patient demographics, surgical procedures or case urgency. Data was examined from the period of COVID-restrictions in 2020 and compared with data from the same time period in 2019., Results: From 3 March 2020 to 30 June 2020, 136 adults underwent cardiac surgery at our institution, representing an overall reduction in operative caseload of 21%. The largest impact was noticed in May and April and coincided with statewide restrictions on elective surgery. Surgical acuity was unchanged with 58% of operations classified as non-elective procedures performed during the index admission. There was a small non-significant increase in the proportion of isolated coronary artery bypass surgery and aortic valve surgeries performed., Conclusion: From March to June 2020 our local hospital response to the COVID-19 pandemic resulted in a reduction in cardiac surgery service delivery. No change was seen in the urgency or type of surgeries performed., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

To perform a systematic review evaluating reported outcomes for epilepsy surgery in pediatric patients with pharmacoresistant epilepsy beyond seizure control, including impact on quality of life, behavioral, neurocognitive outcomes as well as complications, and death. We reviewed articles from both EMBASE and MEDLINE/PubMed articles that met formal criteria (patients ≤18 years, those with intractable epilepsy, at least 5 patients in the case series, published in peer-reviewed journal). Each reviewer independently reviewed the articles and those with discrepancies were discussed and consensus was reached. Out of a total of 536 abstracts obtained from EMBASE and MEDLINE/PubMed searches combined with additional cross-referencing, a total of 98 manuscripts ultimately met all inclusion criteria. The manuscripts were divided into 3 outcomes categories: Quality of Life (16), Cognitive Outcomes (60), and Deficits and Complications (50). Several papers fell into more than 1 category. These were separated by surgical types and evaluated. We found that overall reporting in all domains was variable and inconsistent amongst the different studies. This systematic review highlights the lack of completeness in reporting outcomes and complications involving pediatric epilepsy surgery and discordant results. This underscores the importance of multicenter systematic prospective data collection in pediatric patients who undergo pediatric epilepsy surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Levels of loneliness across the world have reached epidemic proportions, and their impact upon population health is increasingly apparent. In response, policies and initiatives have attempted to reduce loneliness by targeting social isolation among residents of local communities. Yet, little is known about the social psychological processes underpinning the relationships between community belonging, loneliness, and well-being. We report three studies which apply the Social Identity Approach to Health to examine the mechanisms underpinning the relationships between community identity, health, and loneliness. Hypotheses were tested through secondary analyses of the 2014-2015 UK Community Life Survey (N = 4,314) as well as bespoke household surveys in a more (N = 408) and less (N = 143) affluent community at high risk of loneliness. Studies 1 and 2a demonstrated that the relationship between community identification and well-being was mediated by increased social support and reduced loneliness. In Study 2b, community identification predicted well-being through reduced loneliness, but not through social support. Our results are the first to evidence these relationships and suggest that community-level interventions that enhance community identification and peer support can promote a potential Social Cure for loneliness., (© 2021 The Authors. British Journal of Social Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Objective: People with bipolar disorder (BD) often have difficulty with medication adherence. This pilot trial combined a behavioral customized adherence enhancement (CAE) approach with long-acting injectable (LAI) antipsychotic medication and assessed effects on adherence, BD symptoms, and functional status., Methods: This 6-month prospective, uncontrolled trial of the intervention (CAE with LAI) in 30 poorly adherent individuals with BD assessed adherence using the Tablets Routine Questionnaire (TRQ) and symptoms using the Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), and Clinical Global Impressions (CGI). Functioning was assessed via the Social and Occupational Functioning Assessment Scale (SOFAS) and Global Assessment of Functioning (GAF). Assessments were conducted at screening, baseline, week 12, and week 24 (6 months). The LAI was aripiprazole once monthly. The study was conducted between April 2018 and May 2020., Results: The mean age of the sample was 49.5 years (SD = 9.3), and 56.7% were Black. Nine individuals (30%) terminated the study prematurely, 1 due to side effects (tremor). The mean LAI dose was 314.3 mg (SD = 96.4). The proportion of missed medications in the past week (mean TRQ) from screen to 24 weeks significantly improved from 50.1% (SD 24.8) to 16.9% (SD = 27.0) ( P  < .001), and past month TRQ improved from 40.6% (SD = 23.8) to 19.2% (SD = 24.0) (a trend for significance, P  = .0599). TRQ change from baseline to 24 weeks was not significant. There were significant improvements on the BPRS ( P  < .001), MADRS ( P  = .01), YMRS ( P  < .001), CGI ( P  < .001), SOFAS ( P  < .001), and GAF ( P  < .001)., Conclusion: A personalized intervention to address adherence barriers combined with LAI can improve recovery outcomes in high-risk individuals with BD., Trial Registration: ClinicalTrials.gov Identifier: NCT03408873., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Objectives: Recovery from anorexia nervosa (AN) is difficult to define, and efforts to establish recovery criteria have led to several versions being proposed. Using the perspectives of people with histories of AN and therapists working in the field, we sought to explore the face validity of Khalsa et al (2017) as one of the most recent examples of proposed systematic recovery criteria., Design: We interviewed 11 health service users (SUs) with histories of AN who had previously received treatment alongside 8 eating disorder therapists (EDTs), exploring their views on the proposed AN recovery criteria., Methods: Data from verbal and written interviews were analysed thematically. Separate thematic analyses of SU and EDT interviews highlighted where concerns converged and diverged across participants., Results: Both groups saw some merits of having universally recognized recovery criteria, and the multidimensional approach was welcomed, but EDTs were uncomfortable with considering their use in therapy and SUs felt key components were missing around emotional coping and life quality. SUs disliked the prominence of body mass index (BMI) in the criteria, and all struggled with the proposed duration for recovery. Conceptually, the notion of recovery as an endpoint rather than a journey was contested., Conclusions: Our findings indicate disparities between academically derived recovery criteria and lived experiences and indicate perceived challenges in using such criteria in therapeutic settings. Including SUs and EDTs in the development of criteria may improve the likelihood of consolidating AN recovery criteria, but conceptual challenges remain., Practitioner Points: AN recovery is complex, and the use of research-based AN recovery criteria in therapeutic settings could have a detrimental effect on SUs' outcomes. EDTs should be aware of efforts to define AN recovery criteria. EDTs should engage with debates on defining AN recovery and seek to promote participation in such debates to SUs., (© 2021 The Authors. Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Background: Public opinion research shows that eating disorders (EDs) are a major target of stigmatisation. To understand the implications of this stigma, research investigating how stigma is experienced by individuals with EDs is critical., Aim: This paper aims to collate, evaluate and synthesise the extant empirical research illuminating how people with EDs experience the stigma associated with their condition., Method: A systematic mixed-methods literature search was performed. Articles that met a specified set of inclusion criteria underwent a quality assessment and thematic synthesis., Results: Twenty-nine articles were included in the review. Studies were mostly qualitative and of reasonable methodological quality. The literature was characterised by five research themes, illuminating (i) the nature and prevalence of stigma experienced, (ii) stigma in families, (iii) stigma in healthcare contexts, (iv) self-stigmatisation and illness concealment, and (v) stigma resistance., Conclusions: The reviewed research showed that people with EDs have extensive experience of stigma in diverse settings. They report that stigma has negative implications for their psychological wellbeing and likelihood of help-seeking. However, research also shows that people with EDs actively seek to resist and challenge stigma. The review identifies the outstanding gaps and weaknesses in this literature.

The stressors of immigration detention and negative host country experiences make effective access to health care vital for migrant detainees, but little is known regarding the health experiences of this populations and the barriers to healthcare access. The present research investigates immigration detainees' experiences of health-related help-seeking in the distressing and stigmatised environment of UK immigration removal centres (IRCs), as well as staff members' experiences of providing help. Semi-structured interviews were conducted with 40 detainees and 21 staff and analysed using theoretical thematic analysis guided by the social identity approach. The findings indicate that the practical constraints on help provision (e.g. lack of time and resources, the unpredictable nature of detention) are exacerbated by the complex and conflictual intergroup relationships within which these helping transactions occur. These transactions are negatively affected by stigma, mutual distrust and reputation management concerns, as well as detainees' feelings of powerlessness and confusion around eligibility to receive health care. Some detainees argued that the help ignores the systematic inequalities associated with their detainee status, thereby making it fundamentally inappropriate and ineffective. The intergroup context (of inequality and illegitimacy) shapes the quality of helping transactions, care experiences and health service engagement in groups experiencing chronic low status, distress and uncertainty., (© 2021 The Authors. Applied Psychology: Health and Well-Being published by John Wiley & Sons Ltd on behalf of International Association of Applied Psychology.)

Background: Significant right ventricular failure (RVF) complicating left ventricular assist device (LVAD) placement has been reported at 10-30%. Although primarily indicated for left ventricular failure, ventricular assist devices (VADs) have become utilized in a biventricular setup to combat right ventricular failure (RVF) following LVAD implantation. With the advent of continuous-flow LVADs (CF-LVADs) superseding their pulsatile predecessors, the shift towards CF-biventricular assist devices (CF-BiVADs) come with the prospect of improved outcomes over previous pulsatile BiVADs. We aim to review the literature and determine the outcomes of CF-BiVAD recipients., Methods: A systematic review was performed to determine the outcomes of CF-BiVADs. Pre-operative demographics and device configuration data was collected. Primary outcomes evaluated were short-term survival, long-term survival, duration of support, and survival to transplant. Secondary outcomes evaluated included intensive care unit (ICU) and hospital length of stay (ICU-LOS and HLOS, respectively), pump thrombosis, pump exchange. Median and interquartile range was reported where appropriate. A major limitation was the likely overlap of cohorts across publications, which may have contributed to some selection bias., Results: Of 1,282 screened, 12 publications were evaluated. Sample size ranged from 4 to 93 CF-BiVAD recipients, and follow-up ranged from 6 to 24 months. Mean age ranged from 34 to 52 years old. Forty-five percent of CF-BiVADs had right atrial (RA-) inflow cannulation, with the remaining being right ventricular (RV). Thirty-day survival was a median of 90% (IQR 82-97.8%) and 12-month survival was a median of 58.5% (IQR 47.5-62%). Where reported, rate of pump thrombosis (predominantly the right VAD) was a median of 31% (IQR 14-36%), although pump exchange was only 9% (IQR 1.5-12.5%)., Conclusions: RVF post-LVAD implantation is a high morbidity and mortality complication. There is no on-label continuous-flow RVAD currently available. Thus, the modifications of LVADs for right ventricular support to combat pump thrombosis has resulted in various techniques. BiVAD recipients are predominantly transplant candidates, and complications of pump thrombosis and driveline infection whilst on wait-list are of great consequence. This study demonstrates the need for an on-label CF-BiVAD., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2021 Annals of Cardiothoracic Surgery. All rights reserved.)

We describe the surgical management of a rare pulmonary angiomatoid fibrous histiosarcoma (AFH). A 62-year-old lady presented with shortness of breath and found to have a large left main pulmonary artery defect that was positron emission tomography-avid. Following discussion in a thoracic multidisciplinary team meeting it was deemed unsafe to biopsy considering its intravascular position. The patient proceeded to theatre for a left pneumonectomy. She was successfully discharged home by Day 7. On follow-up the patient is well, and free of malignancy. AFH is an incredibly rare form of sarcoma, and in particular in the thoracic region. We have demonstrated successful oncological resection of a rare intravascular lesion in the pulmonary artery., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2021.)

Background: End stage heart failure is a major cause of morbidity and mortality, and its prevalence is expected to rise with the ageing population. For suitable patients, orthotopic heart transplantation remains the gold standard therapy, however, a paucity of donor organs has led to the development of left ventricular assist devices (LVAD). These devices can be utilized as either a bridge-to-transplant (BTT) or as an alternative to heart transplantation. While these devices can prolong life and improve quality of life, they are associated with a significant number of adverse events. We aim to systematically review the literature to quantify survival and the incidence of adverse events following implantation of continuous-flow LVADs (cf-LVAD)., Methods: A systematic review was performed to determine outcomes following implantation of a cf-LVAD. Primary outcomes were survival and frequency of adverse events (such as bleeding, infection, thrombosis, stroke and right ventricular failure). Secondary outcomes included quality of life and assessment of functional status., Results: Sixty-three studies reported clinical outcomes of 9,280 patients. Survival after cf-LVAD varied between studies. Industry-funded trials generally reported better overall survival than the single- and multi-center case series, which showed significant variation. The largest registry report documented twelve, twenty-four and forty-eight-month survival rates of 82%, 72% and 57% respectively. The most commonly reported adverse events were gastrointestinal bleeding (GIB), device-related infection, neurological events and right heart failure (RHF). Bleeding, RHF and infection were the most frequent complications experienced by those supported with cf-LVAD, occurring in up to 35%, 40% and 55% of patients, respectively. Quality of life as measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and functional status as measured with the 6-minute walk test (6MWT) improved after cf-LVAD implantation with no decline evident two years after implantation., Conclusions: The paucity of donor hearts has led to the development of left-ventricular assist devices as a BTT or as a destination therapy (DT). Outcomes after cf-LVAD implantation are excellent, with short-term survival comparable to heart transplantation, but long-term survival remains limited due to the incidence of post-implantation adverse events. Despite these complications, quality of life and functional status improve significantly post-implantation and remain improved over the long-term. This study demonstrates the potential benefits of cf-LVAD therapy whilst also identifying adverse events as an area of increased morbidity and mortality., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2021 Annals of Cardiothoracic Surgery. All rights reserved.)

Background: Both anxiety and depression have been identified as negative health outcomes associated with the distressing nature of the Covid-19 pandemic, especially among young people. Within this age demographic, trans and gender diverse people may be particularly vulnerable to pandemic-related mental health outcomes, such as anxiety and depression, due to the social challenges, gender dissonance, and poor mental health they experience. Furthermore, the social distancing measures impose several unique social and help-seeking challenges which may further contribute to the worsening of mental health. While there has been acknowledgment that vulnerable populations may be disproportionally affected by the pandemic, the experiences of trans and gender diverse youth have received very little empirical attention., Aims: To explore the mental health impact of Covid-19 on the lives of young trans and gender diverse people in the UK., Method: In total, 243 people took part in an online survey between May and July in 2020. Eighty-two people were removed due to providing insufficient data. The analyzed dataset therefore comprised of 161 respondents ranging from 16 to 25 years ( M  = 20; SD  = 2.68). Participants were asked how social distancing measures had impact on their social lives, mental health and access to health services. They were also asked to complete validated measures of anxiety and depression., Results: This study found that those who experienced a greater impact of the Covid-19 outbreak and its associated social distancing measures, reported poorer mental health. Lack of social support, negative interpersonal interactions, unsupportive and non-affirming living environments and the inability to access mental health support and gender-affirming interventions were all factors that were associated with poor mental health., Conclusion: The findings provide specific direction for the tailoring of mental health service delivery to this population, noting the need for private, safe spaces in which young people can feel supported and have their gender identity affirmed., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Attention is being given to healthcare initiatives with the potential to save money and improve lives. One example is social prescribing, which supports patients whose ill-health is exacerbated by loneliness. While evidence has accumulated attesting to social prescribing's efficacy, one limitation has been the lack of a theoretical framework, which limits understanding of how tackling loneliness improves health. In our evaluation of a social prescribing pathway, we adopt a 'Social Cure' approach, which posits that social relations affect health. Our study will evaluate the efficacy of the pathway and determine the extent to which group processes are responsible for health improvements.

Introduction: All major international guidelines for the management of infective endocarditis (IE) have undergone major revisions, recommending antibiotic prophylaxis (AP) restriction to high-risk patients or foregoing AP completely. We performed a systematic review to investigate the effect of these guideline changes on the global incidence of IE., Methods: Electronic database searches were performed using Ovid Medline, EMBASE and Web of Science. Studies were included if they compared the incidence of IE prior to and following any change in international guideline recommendations. Relevant studies fulfilling the predefined search criteria were categorized according to their inclusion of either adult or pediatric patients. Incidence of IE, causative microorganisms and AP prescription rates were compared following international guideline updates., Results: Sixteen studies were included, reporting over 1.3 million cases of IE. The crude incidence of IE following guideline updates has increased globally. Adjusted incidence increased in one study after European guideline updates, while North American rates did not increase. Cases of IE with a causative pathogen identified ranged from 62% to 91%. Rates of streptococcal IE varied across adult and pediatric populations, while the relative proportion of staphylococcal IE increased (range pre-guidelines 16-24.8%, range post-guidelines 26-43%). AP prescription trends were reduced in both moderate and high-risk patients following guideline updates., Discussion: The restriction of AP to only high-risk patients has not resulted in an increase in the incidence of streptococcal IE in North American populations. The evidence of the impact of AP restriction on IE incidence is still unclear for other populations. Future population-based studies with adjusted incidence of IE, AP prescription rates and accurate pathogen identification are required to delineate findings further in these other regions.

Introduction: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that may be punctuated by episodes of worsening symptoms, called exacerbations. Acute exacerbations of COPD (AECOPD) are detrimental to clinical outcomes, reduce patient quality of life and often result in hospitalisation and cost for the health system. Improved diagnosis and management of COPD may reduce the incidence of hospitalisation and death among this population. This scoping review aims to identify improvement interventions designed to standardise the hospital care of patients with AECOPD at presentation, admission and discharge, and/or aim to reduce unnecessary admissions/readmissions., Methods: The review followed a published protocol based on methodology set out by Arksey and O'Malley and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic database searches for peer-reviewed primary evidence were conducted in Web of Science, EMBASE (Elsevier) and PubMed. Abstract, full-text screening and data extraction were completed independently by a panel of expert reviewers. Data on type of intervention, implementation supports and clinical outcomes were extracted. Findings were grouped by theme and are presented descriptively., Results: 21 articles met the inclusion criteria. Eight implemented a clinical intervention bundle at admission and/or discharge; six used a multidisciplinary care pathway; five used coordinated case management and two ran a health coaching intervention with patients., Conclusion: The findings indicate that when executed reliably, improvement initiatives are associated with positive outcomes, such as reduction in length of stay, readmissions or use of health resources. Most of the studies reported an improvement in staff compliance with the initiatives and in the patient's understanding of their disease. Implementation supports varied and included quality improvement methodology, multidisciplinary team engagement, staff education and development of written or in-person delivery of patient information. Consideration of the implementation strategy and methods of support will be necessary to enhance the likelihood of success in any future intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Autoimmune-mediated dry eye disease is a pathological feature of multiple disorders including Sjögren's syndrome, lupus and rheumatoid arthritis that has a life-long, detrimental impact on vision and overall quality of life. Although late stage disease outcomes such as epithelial barrier dysfunction, reduced corneal innervation and chronic inflammation have been well characterized in both human patients and mouse models, there is little to no understanding of early pathological processes. Moreover, the mechanisms underlying the loss of cornea homeostasis and disease progression are unknown. Here, we utilize the autoimmune regulatory (Aire)-deficient mouse model of autoimmune-mediated dry eye disease in combination with genome wide transcriptomics, high-resolution imaging and atomic force microscopy to reveal a potential extracellular matrix (ECM)-biomechanical-based mechanism driving cellular and morphological changes at early disease onset. Early disease in the Aire-deficient mouse model is associated with a mild reduction in tear production and moderate immune cell infiltration, allowing for interrogation of cellular, molecular and biomechanical changes largely independent of chronic inflammation. Using these tools, we demonstrate for the first time that the emergence of autoimmune-mediated dry eye disease is associated with an alteration in the biomechanical properties of the cornea. We reveal a dramatic disruption of the synthesis and organization of the extracellular matrix as well as degradation of the epithelial basement membrane during early disease. Notably, we provide evidence that the nerve supply to the cornea is severely reduced at early disease stages and that this is independent of basement membrane destruction or significant immune cell infiltration. Furthermore, diseased corneas display spatial heterogeneity in mechanical, structural and compositional changes, with the limbal compartment often exhibiting the opposite response compared to the central cornea. Despite these differences, however, epithelial hyperplasia is apparent in both compartments, possibly driven by increased activation of IL-1R1 and YAP signaling pathways. Thus, we reveal novel perturbations in corneal biomechanics, matrix organization and cell behavior during the early phase of dry eye that may underlie disease development and progression, presenting new potential targets for therapeutic intervention., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Seizures are an under-reported feature of the SATB2-associated syndrome phenotype. We describe the electroencephalographic findings and seizure semiology and treatment in a population of individuals with SATB2-associated syndrome., Methods: We performed a retrospective review of 101 individuals with SATB2-associated syndrome who were reported to have had a previous electroencephalographic study to identify those who had at least one reported abnormal result. For completeness, a supplemental survey was distributed to the caregivers and input from the treating neurologist was obtained whenever possible., Results: Forty-one subjects were identified as having at least one prior abnormal electroencephalography. Thirty-eight individuals (93%) had epileptiform discharges, 28 (74%) with central localization. Sleep stages were included as part of the electroencephalographies performed in 31 individuals (76%), and epileptiform activity was recorded during sleep in all instances (100%). Definite clinical seizures were diagnosed in 17 individuals (42%) with a mean age of onset of 3.2 years (four months to six years), and focal seizures were the most common type of seizure observed (42%). Six subjects with definite clinical seizures needed polytherapy (35%). Delayed myelination and/or abnormal white matter hyperintensities were seen on neuroimaging in 19 individuals (61%)., Conclusions: Epileptiform abnormalities are commonly seen in individuals with SATB2-associated syndrome. A baseline electroencephalography that preferably includes sleep stages is recommended during the initial evaluation of all individuals with SATB2-associated syndrome, regardless of clinical suspicion of epilepsy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Various sulfone tetrazoles were activated via iridium photoredox catalysis in the presence of DMAP to give dialkyl sulfones. The presumed sulfone radical intermediates were trapped by a range of electron-deficient olefins in generally good to excellent yields.

Context: Preterm birth is associated with incident heart failure in children and young adults., Objective: To determine the effect size of preterm birth on cardiac remodeling from birth to young adulthood., Data Sources: Data sources include Medline, Embase, Scopus, Cochrane databases, and clinical trial registries (inception to March 25, 2020)., Study Selection: Studies in which cardiac phenotype was compared between preterm individuals born at <37 weeks' gestation and age-matched term controls were included., Data Extraction: Random-effects models were used to calculate weighted mean differences with corresponding 95% confidence intervals., Results: Thirty-two observational studies were included (preterm = 1471; term = 1665). All measures of left ventricular (LV) and right ventricular (RV) systolic function were lower in preterm neonates, including LV ejection fraction ( P = .01). Preterm LV ejection fraction was similar from infancy, although LV stroke volume index was lower in young adulthood. Preterm LV peak early diastolic tissue velocity was lower throughout development, although preterm diastolic function worsened with higher estimated filling pressures from infancy. RV longitudinal strain was lower in preterm-born individuals of all ages, proportional to the degree of prematurity ( R 2 = 0.64; P = .002). Preterm-born individuals had persistently smaller LV internal dimensions, lower indexed LV end-diastolic volume in young adulthood, and an increase in indexed LV mass, compared with controls, of 0.71 g/m 2 per year from childhood ( P = .007)., Limitations: The influence of preterm-related complications on cardiac phenotype could not be fully explored., Conclusions: Preterm-born individuals have morphologic and functional cardiac impairments across developmental stages. These changes may make the preterm heart more vulnerable to secondary insults, potentially underlying their increased risk of early heart failure., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Trypanosoma cruzi and Trypanosoma brucei are the parasitic causative agents of Chagas disease and human African trypanosomiasis (HAT), respectively. The drugs currently used to treat these diseases are not efficacious against all stages and/or parasite sub-species, often displaying side effects. Herein, we report the SAR exploration of a novel hit, 2-(4-chlorophenyl)- N -(1-propyl-1 H -benzimidazol-2-yl)acetamide previously identified from high throughput screens against T. cruzi , Trypanosoma brucei brucei and Leishmania donovani. An informative set of analogues was synthesized incorporating key modifications of the scaffold resulting in improved potency whilst the majority of compounds retained low cytotoxicity against H9c2 and HEK293 cell lines. The SAR observed against T. cruzi broadly matches that observed against T.b. brucei , suggesting the possibility for a broad-spectrum candidate. This class of compounds therefore warrants further investigation towards development as a treatment for Chagas disease and HAT., (This journal is © The Royal Society of Chemistry 2020.)

Objectives: This study aimed to assess the degree to which the 'social cure' model of psychosocial health captures the understandings and experiences of healthcare staff and patients in a social prescribing (SP) pathway and the degree to which these psychosocial processes predict the effect of the pathway on healthcare usage., Design: Mixed-methods: Study 1: semistructured interviews; study 2: longitudinal survey., Setting: An English SP pathway delivered between 2017 and 2019., Participants: Study 1: general practitioners (GPs) (n=7), healthcare providers (n=9) and service users (n=19). Study 2: 630 patients engaging with SP pathway at a 4-month follow-up after initial referral assessment., Intervention: Chronically ill patients experiencing loneliness referred onto SP pathway and meeting with a health coach and/or link worker, with possible further referral to existing or newly created relevant third-sector groups., Main Outcome Measure: Study 1: health providers and users' qualitative perspectives on the experience of the pathway and social determinants of health. Study 2: patients' primary care usage., Results: Healthcare providers recognised the importance of social factors in determining patient well-being, and reason for presentation at primary care. They viewed SP as a potentially effective solution to such problems. Patients valued the different social relationships they created through the SP pathway, including those with link workers, groups and community. Group memberships quantitatively predicted primary care usage, and this was mediated by increases in community belonging and reduced loneliness., Conclusions: Methodological triangulation offers robust conclusions that 'social cure' processes explain the efficacy of SP, which can reduce primary care usage through increasing social connectedness (group membership and community belonging) and reducing loneliness. Recommendations for integrating social cure processes into SP initiatives are discussed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)