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Atraumatic splenic rupture is a complex surgical pathology owing to its rarity, non-specificity of symptoms and gravity of possible outcomes. This case outlines the investigation and management of a patient with atraumatic splenic rupture secondary to undiagnosed hairy cell leukaemia. While the patient was initially managed conservatively, they went on to have a splenectomy owing to ongoing transfusion requirements. A review of the literature has also been performed and presented to highlight the potential causes of atraumatic splenic rupture and the various options for confirming diagnosis and definitive management. [ABSTRACT FROM AUTHOR]

Abstract Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein (NTNH) with which they form a 300 kDa complex, to resist acidic and proteolytic attack from the digestive tract. We have previously identified a new botulinum neurotoxin serotype, BoNT/X, that has unique and therapeutically attractive properties. We present the cryo-EM structure of the BoNT/X-NTNH/X complex and the crystal structure of the isolated NTNH protein. Unexpectedly, the BoNT/X complex is stable and protease-resistant at both neutral and acidic pH and disassembles only in alkaline conditions. Using the stabilizing effect of NTNH, we isolated BoNT/X and showed that it has very low potency both in vitro and in vivo. Given the high catalytic activity and translocation efficacy of BoNT/X, low activity of the full toxin is likely due to the receptor-binding domain, which presents very weak ganglioside binding and exposed hydrophobic surfaces.

Objective: The study objective was to determine whether adequately delivered bilateral remote ischemic preconditioning is cardioprotective in young children undergoing surgery for 2 common congenital heart defects with or without cyanosis. Methods: We performed a prospective, double-blind, randomized controlled trial at 2 centers in the United Kingdom. Children aged 3 to 36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomized 1:1 to receive bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analyzed by intention-to-treat. Right atrial biopsies were obtained in selected participants. Results: Between October 2016 and December 2020, 120 eligible children were randomized to receive bilateral preconditioning (n = 60) or sham intervention (n = 60). The primary outcome, area under the curve for high-sensitivity troponin-T, was higher in the preconditioning group (mean: 70.0 ± 50.9 μg/L/h, n = 56) than in controls (mean: 55.6 ± 30.1 μg/L/h, n = 58) (mean difference, 13.2 μg/L/h; 95% CI, 0.5-25.8; P = .04). Subgroup analyses did not show a differential treatment effect by oxygen saturations (pinteraction = .25), but there was evidence of a differential effect by underlying defect (pinteraction = .04). Secondary outcomes and myocardial metabolism, quantified in atrial biopsies, were not different between randomized groups. Conclusions: Bilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot. The routine use of remote ischemic preconditioning cannot be recommended for myocardial protection during pediatric cardiac surgery.

Abstract Background Supra aortic obstruction in children is uncommon and is seen in certain unique conditions. While intraluminal obstruction due to heavy calcification is seen in older populations, it is not described in pediatric populations. The coral reef aorta is a rare and distinct calcifying disease causing luminal obstruction of the suprarenal aorta in adults. The definition of this diagnosis relies entirely on the unique aspects and consistency of the lesions, which are rock-hard, irregular, gritty plaques with a white luminal surface resembling a coral reef. However, no such case has been described in children. Case presentation We present an adolescent boy who presented with a heavily calcified ascending aortic lesion associated with aortopathy and hypertension, 12 years after an aortic coarctation repair. The investigations included echocardiography, magnetic resonance and computer-tomographic imaging. A 3-D model was printed in order to visualize and plan surgical steps in advance for safe placement of clamps and defining the extent of resection. In addition, it provided an idea about tissue quality, thickness, spatial relationship, and orientation in relation to surrounding structures. Successful resection and replacement of the diseased segment of the aorta were achieved on cardiopulmonary bypass support. Post-operative recovery was uneventful, and at 6-month follow-up, the patient is doing well. In this report, various aspects of such lesions have been discussed, including clinical presentations, complications, planning and conduct of a safe cardiopulmonary bypass, and precautions during surgery for a successful outcome. Conclusion Complicated obstructive aortic lesions in children require careful assessment, appropriate advanced imaging, and the use of 3-D printing technology in order to plan and perform safe and effective surgical management. The etiology of severe calcified aorta in children may be related to metabolic factors, previous surgery, use of a homograft, or an inflammatory process. However, it has yet to be proven.

The aim of the present systematic review was to assess the antinociceptive efficacy of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) therapy in rats with experimentally induced temporomandibular joint (TMJ) arthritis. The focused question was “Is 15d-PGJ2 therapy effective in the management of TMJ nociception?” Indexed databases were searched without time and language restrictions up to and including September 2023 using different key words. Original studies were included. Risk of Bias (RoB) was assessed using the SYRCLE tool. Six studies performed in male Wistar rats with experimentally induced TMJ arthritis were included. The observation or follow-up period ranged between 45 min and 14 days. Four studies reported that 15d-PGJ2 therapy retards the production of proinflammatory cytokines in TMJ tissues. Four studies reported that 15d-PGJ2 therapy inhibits leukocyte migration and plasma extravasation in TMJ tissues. In one study, the expression of decay-accelerating factor in TMJ tissues increased after 15d-PGJ2 therapy. One study showed that 15d-PGJ2 inhibits nociception in a dose-dependent manner via the activation of peripheral kappa/delta opioid receptors. Prior sample-size-estimation (SSE) was performed in none of the studies and all studies had a high RoB. Due to a high RoB, methodological variations, and the absence of prior SSE within the included studies, it is demanding to derive an absolute verdict regarding the antinociceptive efficacy of 15d-PGJ2 therapy in response to experimentally induced TMJ arthritis.

This study aimed to characterize and describe the different lymphoma types and anatomical forms in cats in Hong Kong. The clinical and histopathological data of cats diagnosed with lymphoma by cytology and/or histopathology were collected from a large diagnostic laboratory in Hong Kong. In total, 444 cats were diagnosed with lymphoma over four years (2019–2022). Like other countries where there is a low prevalence of FeLV infection, the predominant form of lymphoma was gastrointestinal (abdominal). Nasopharyngeal and peripheral nodal lymphoma were the second and third most common forms of lymphoma. The large cell/high-grade lymphoma type was much more common than the low-grade/small cell lymphoma in the study population. Domestic short hair was the most commonly affected breed in our study (n = 259/444). Among the cats with identified T/B-cell status, B-cell lymphoma (n = 61/81) prevailed as the most common phenotype. This study describes and characterizes the different types of feline lymphoma in cats in Hong Kong, adding valuable information to the body of knowledge.

Botulinum neurotoxin A (BoNT/A) is a potent neurotoxin that silences cholinergic neurotransmission through the cleavage of the synaptic protein SNAP-25. Previous studies have shown that, in addition to its paralytic effects, BoNT/A can inhibit sensory nerve activity. The aim of this study was to identify how BoNT/A inhibits afferent signalling from the bladder. To investigate the role of SNAP-25 cleavage in the previously reported BoNT/A-dependent inhibition of sensory signalling, we developed a recombinant form of BoNT/A with an inactive light chain, rBoNT/A (0), unable to paralyse muscle. We also developed recombinant light chain (LC)-domain-only proteins to better understand the entry mechanisms, as the heavy chain (HC) of the protein is responsible for the internalisation of the light chain. We found that, despite a lack of catalytic activity, rBoNT/A (0) potently inhibited the afferent responses to bladder distension to a greater degree than catalytically active rBoNT/A. This was also clear from the testing of the LC-only proteins, as the inactive rLC/A (0) protein inhibited afferent responses significantly more than the active rLC/A protein. Immunohistochemistry for cleaved SNAP-25 was negative, and purinergic and nitrergic antagonists partially and totally reversed the sensory inhibition, respectively. These data suggest that the BoNT/A inhibition of sensory nerve activity in this assay is not due to the classical well-characterised ‘double-receptor’ mechanism of BoNT/A, is independent of SNAP25 cleavage and involves nitrergic and purinergic signalling mechanisms.

Background: Young adult (18-30 years) people who inject drugs (PWID) face high hepatitis C virus (HCV) prevalence. In San Francisco, where >60% of PWID lack stable housing, barriers hinder HCV treatment access. We assessed progress towards the World Health Organization's (WHO) HCV elimination goal of an 80% reduction in incidence over 2015-2030, focusing on young (YPWID) and unstably housed PWID in San Francisco., Methods: We developed a dynamic HCV transmission model among PWID, parameterized and calibrated using bio-behavioural survey datasets from San Francisco. This included 2018 estimates for the antibody-prevalence among PWID (77%) and care cascade estimates for HCV for YPWID (72% aware of their status and 33% ever initiating treatment). Based on programmatic data, we assumed a 53.8% reduction in testing and 40.7% decrease in treatment from 2020 due to the COVID-19 pandemic, which partially rebounded from April 2021 with testing rates then being 31.1% lower than pre-pandemic rates and treatment numbers being 19.5% lower. We simulated different scenarios of how services changed after the pandemic to project whether elimination goals would be met., Results: Continuing post-pandemic rates of testing and treatment, the model projects an 83.3% (95% credibility interval [95% CrI]:60.6-96.9%) decrease in incidence among PWID over 2015-2030 to 1.5/100pyrs (95% CrI:0.3-4.4) in 2030. The probability of achieving the elimination goal by 2030 is 62.0%. Among YPWID and unstably housed PWID, the probability of achieving the elimination goal by 2030 is 54.8 and 67.6%, respectively. Importantly, further increasing testing and treatment rates to pre-pandemic levels by 2025 only results in a small increase in the probability (67.5%) of the elimination goal being achieved among all PWID by 2030, while increased coverage of medication for opioid use disorder among YPWID and/or housing interventions results in the probability of achieving elimination increasing to over 75%., Conclusion: The COVID-19 pandemic impeded progress toward achieving HCV elimination. Our findings indicate that existing partial rebounds in HCV testing and treatment may achieve the elimination goal by 2030, with an additional scale-up of interventions aimed at YPWID or unstably housed PWID ensuring San Francisco is likely to achieve elimination by 2030., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: P.V. received an unrestricted research grant from Gilead that is not related to this study. M.D.M .received investigator sponsored research (ISR) funding from Gilead Sciences for research not related to this study. S.N.F. acknowledges consulting support from Gilead Sciences and from End Hep C SF; neither are related to this study. All other authors have no competing interests to report. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Variable expressivity of disease-associated variants implies a role for secondary variants that modify clinical features. We assessed the effects of modifier variants towards clinical outcomes of 2,252 individuals with primary variants. Among 132 families with the 16p12.1 deletion, distinct rare and common variant classes conferred risk for specific developmental features, including short tandem repeats for neurological defects and SNVs for microcephaly, while additional disease-associated variants conferred multiple genetic diagnoses. Within disease and population cohorts of 773 individuals with the 16p12.1 deletion, we found opposing effects of secondary variants towards clinical features across ascertainments. Additional analysis of 1,479 probands with other primary variants, such as 16p11.2 deletion and CHD8 variants, and 1,084 without primary variants, showed that phenotypic associations differed by primary variant context and were influenced by synergistic interactions between primary and secondary variants. Our study provides a paradigm to dissect the genomic architecture of complex disorders towards personalized treatment., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

Background: A human immunodeficiency virus (HIV) outbreak was identified among people who inject drugs (PWID) in Glasgow in 2015, with >150 diagnoses by the end of 2019. The outbreak response involved scaling up HIV testing and improving HIV treatment initiation and retention., Methods: We parameterized and calibrated a dynamic, deterministic model of HIV transmission among PWID in Glasgow to epidemiological data. We use this model to evaluate HIV testing and treatment interventions. We present results in terms of relative changes in HIV prevalence, incidence, and cases averted., Results: If the improvements in both testing and treatment had not occurred, we predict that HIV prevalence would have reached 17.8% (95% credible interval [CrI], 14.1%-22.6%) by the beginning of 2020, compared to 5.9% (95% CrI, 4.7%-7.4%) with the improvements. If the improvements had been made on detection of the outbreak in 2015, we predict that peak incidence would have been 26.2% (95% CrI, 8.8%-49.3%) lower and 62.7% (95% CrI, 43.6%-76.6%) of the outbreak cases could have been averted. The outbreak could have been avoided if the improvements had already been in place., Conclusions: Our modeling suggests that the HIV testing and treatment interventions successfully brought the HIV outbreak in Glasgow under control by the beginning of 2020., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiologic mechanism, heterogeneity and origin of common cardiometabolic comorbidities for depression. Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n=7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%). We examined associations of these trajectories with: i) anthropometric, cardiometabolic and psychiatric phenotypes using multivariable regression (n=1709-3410); ii) 67 blood immunological proteins and 57 metabolomic features using empirical Bayes moderated linear models (n=2059 and n=2240 respectively); and iii) 28 blood cell counts and biochemical measures using multivariable regression (n=2256). Relative to the low-stable group, risk of depression and anxiety in adulthood was higher for all other groups, especially in the adolescent-persistent (OR depression =22.80, 95% CI 15.25-34.37; OR GAD =19.32, 95% CI 12.86-29.22) and adulthood-onset (OR depression =7.68, 95% CI 5.31-11.17; OR GAD =5.39, 95% CI 3.65-7.94) groups. The three depression-related trajectories vary in their immunometabolic profile, with evidence of little or no alterations in the adolescent-limited group. The adulthood-onset group shows widespread classical immunometabolic changes (e.g., increased immune cell counts and insulin resistance), while the adolescent-persistent group is characterised by higher BMI both in childhood and adulthood with few other immunometabolic changes. These findings point to distinct mechanisms and intervention opportunities for adverse cardiometabolic profile in different groups of young people with depression., Competing Interests: Conflict of Interest None

An HCV treatment trial was initiated in September 2019 to address the opioid/hepatitis C virus (HCV) syndemic in rural Kentucky. The focus of the current analysis is on participation in diagnostic screening for the trial. Initial eligibility (≥18 years of age, county resident) was established by phone followed by in-person HCV viremia testing. 900 rural residents met the inclusion criteria and comprised the analytic sample. Generalized linear models were specified to estimate the relative risk of non-attendance at the in-person visit determining HCV eligibility. Approximately one-quarter (22.1%) of scheduled participants were no-shows. People who inject drugs were no more likely than people not injecting drugs to be a no-show; however, participants ≤35 years of age were significantly less likely to attend. While the median time between phone screening and scheduled in-person screening was only 2 days, each additional day increased the odds of no-show by 3% (95% confidence interval: 2%-3%). Finally, unknown HCV status predicted no-show even after adjustment for age, gender, days between screenings and injection status. We found that drug injection did not predict no-show, further justifying expanded access to HCV treatment among people who inject drugs. Those 35 years and younger were more likely to no-show, suggesting that younger individuals may require targeted strategies for increasing testing and treatment uptake. Finally, streamlining the treatment cascade may also improve outcomes, as participants in the current study were more likely to attend if there were fewer days between phone screening and scheduled in-person screening., (© 2024 John Wiley & Sons Ltd.)

Background: Balance dysfunction is a debilitating feature of advanced Parkinson's disease (PD), potentially improved by deep brain stimulation (DBS). This systematic review and meta-analysis pooled evidence from randomized controlled trials (RCTs) on DBS effectiveness in improving balance in PD., Methods: A systematic search was conducted to identify eligible RCTs investigating the effectiveness of DBS on improving balance in people with PD. Meta-analysis was performed using random effects models and reported as mean difference and 95% confidence intervals. Risk of bias was assessed using Cochrane's ROB-2 tool., Results: Seventeen RCTs were eligible (n = 333), utilizing a range of stimulation sites, parameters, reporting tools for balance outcomes, and control/comparator groups, making the identification of clear trends and recommendations difficult. Eleven studies were deemed as having some risk of bias, 4 having low risk of bias and 2 having high risk of bias. One small meta-analysis was conducted and found no significant difference in balance outcomes. Most studies reported no significant improvement in Timed Up-and-Go scores, Berg Balance Scale scores, frequency of falls, and balance-related items of the Movement Disorder Society's Unified Parkinson's Disease Rating Scales. Some studies reported improvements in the Tinetti balance test, posturography readings, and reduction in falls though these were not supported by other studies due to a lack of reporting on these items or conflicting findings., Conclusions: Current research suggests that DBS results in no significant improvement in balance dysfunction for people with PD, though such assertions require larger RCTs with clear reporting methods using validated reporting tools., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

HL7 FHIR was created almost a decade ago and is seeing increasingly wide use in high income settings. Although some initial work was carried out in low and middle income (LMIC) settings there has been little impact until recently. The need for reliable and easy to implement interoperability between health information systems in LMICs is growing with large scale deployments of EHRs, national reporting systems and mHealth applications. The OpenMRS open source EHR has been deployed in more than 44 LMIC with increasing needs for interoperability with other HIS. We describe here the development and deployment of a new FHIR module supporting the latest standards and its use in interoperability with laboratory systems, mHealth applications, pharmacy dispensing system and as a tool for supporting advanced user interface designs. We also show how it facilitates date science projects and deployment of machine leaning based CDSS and precision medicine in LMICs., (©2024 AMIA - All rights reserved.)

Background: The persistence of symptoms for ≥12 weeks after a COVID-19 infection is known as Long COVID (LC), a condition with unclear pathophysiology and no proven treatments to date. Living with obesity is a risk factor for LC and has symptoms which may overlap with and aggravate LC., Methods: ReDIRECT is a remotely delivered trial assessing whether weight management can reduce LC symptoms. We recruited people with LC and BMI >27kg/m 2 . The intervention was delivered remotely by dietitians, with online data collection (medical and dietary history, COVID-19 infection and vaccination, body composition, LC history/symptoms, blood pressure, quality of life, sociodemographic data). Participants self-selected the dominant LC symptoms they most wanted to improve from the intervention., Results: Participants (n=234) in England (64%) and Scotland (30%) were mainly women (85%) of white ethnicity (90%), with 13% living in the 20% most deprived areas, a mean age of 46 (SD10) years, and median BMI of 35kg/m 2 (IQR 32-40). Before starting the study, 30% reported more than one COVID-19 infection (82% confirmed with one or more positive tests). LC Diagnosis was mainly by GPs (71%), other healthcare professionals (9%), or self-diagnosed (21%). The median total number of symptoms was 6 (IQR 4-8). Self-selected dominant LC symptoms included fatigue (54%), breathlessness (16%), pain (12%), anxiety/depression (1%) and "other" (17%). At baseline, 82% were taking medication, 57% reported 1+ other medical conditions. Quality of life was poor; 20% were on long-term sick leave or reduced working hours. Most (92%) reported having gained weight since contracting COVID-19 (median weight change +11.5 kg, range -11.5 to +45.3 kg)., Conclusions: Symptoms linked to LC and overweight are diverse and complex. Remote trial delivery enabled rapid recruitment across the UK yet certain groups (e.g. men and those from ethnic minority groups) were under-represented., Trial Registration: ISRCTN registry ( ISRCTN12595520, 25/11/2021)., Competing Interests: Competing interests: NB is an employee and shareholder of Counterweight Ltd., subcontracted to the University of Glasgow to deliver the ReDIRECT intervention. AM is a member of Clinical Steering Committee for ARC Medical Inc. NS has received institutional grant support from AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics and honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Sanofi. ML has consulted for Novo Nordisk, Nestle, Oviva, Merck, and Sanofi and is an unpaid medical advisor to Counterweight Ltd. No other competing interests were disclosed., (Copyright: © 2024 Haag L et al.)

Background: Illicit drug use results in considerable global morbidity, but there is little data on its trends and factors associated with it in sub-Saharan Africa. We consider these questions using national data from South Africa for 2002-2017., Methods: We analysed data among individuals aged 15 years or older from five national population-based household surveys in South Africa (2002-2017; n = 89,113). Recent drug use was defined as the last three-months use of illicit drugs, i.e., any use of cannabis, cocaine, amphetamine, inhalants, sedatives, hallucinogens, opioids, and/or other illicit drugs. Time trends in recent drug use were assessed using logistic regression. Multivariable logistic regression assessed the association between recent drug use and socio-demographic factors and between drug use and sexual risk behaviours, HIV-related and other well-being variables., Results: The prevalence of recent drug use increased from 1·5% to 10·0% from 2002 to 2017, driven by increases in cannabis use (1·5% to 7·8%) and use of opioids (0·01% to 1·6%), cocaine (0·02% to 1·8%), or amphetamines (0·1% to 1·5%). In adjusted analyses, male gender, younger age, living in urban areas, mixed-ancestry or white ethnicity (compared to black-African), and unemployment were positively associated with recent drug use. Recent drug use was associated with: multiple sexual partners (adjusted odds ratio [aOR] 2·13, 95% confidence interval [CI]: 1·80-2·51); sexual debut before 15 years old (aOR 1·70, 95%CI: 1·29-2·23); hazardous/harmful alcohol use (aOR 2·50, 95%CI: 2·14-2·93) or alcohol dependence (aOR 3·33, 95%CI 2·92-3·80); ever experiencing intimate partner violence (aOR 1·56, 95%CI 1·12-2·17); psychological distress (aOR 1·53, 95%CI: 1·28-1·82); and lower chance of ever testing for HIV (aOR 0·89, 95%CI 0·80-1·00). Recent drug use was not associated with HIV positivity, condom use or being on antiretroviral therapy., Conclusion: Illicit drug use has increased substantially in South Africa and is associated with numerous socio-demographic characteristics, higher sexual risk behaviours and other well-being variables., Competing Interests: Declaration of competing interest Peter Vickerman, Jack Stone and Hannah Fraser acknowledge funding from the NIHR Health Protection Research Unit in Behavioural Science and Evaluation at the University of Bristol and the US National Institute of Allergy and Infectious Diseases and National Institute for Drug Abuse (NIAID/NIDA R01AI147490). Jack Stone and Peter Vickerman acknowledge funding from NIDA (R01DA033679, R21 DA047902). Peter Vickerman acknowledges funding from NIDA (R21DA046809, R01DA047952). Kennedy Kipkoech Mutai acknowledge funding from the University of Bristol's (i) PVC-Research and Enterprise Strategic Research Fund and (ii) QRGCRF Strategy funded by Research England., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: Adding gene expression profiles (GEPs) to the current diagnostic work-up of aggressive large B-cell lymphomas may lead to the reclassification of patients, treatment changes and improved outcomes. A GEP test is in development using TempO-Seq ® technology to distinguish Burkitt lymphoma (BL) and primary mediastinal large B-cell lymphoma (PMBCL) from diffuse large B-cell lymphoma (DLBCL), and to classify patients with DLBLC and to predict the benefit of (e.g.) adding bortezomib to R-CHOP therapy (RB-CHOP). This study aims to estimate the potential impact of a GEP test on costs and health outcomes to inform pricing and evidence generation strategies., Methods: Three decision models were developed comparing diagnostic strategies with and without GEP signatures over a lifetime horizon using a UK health and social care perspective. Inputs were taken from a recent clinical trial, literature and expert opinion. We estimated the maximum price of the test using a threshold of Great Britain Pound (GBP) 30,000 per quality-adjusted life-year (QALY). Sensitivity analyses were conducted., Results: The estimated maximum threshold price for a combined test to be cost effective is GBP 15,352. At base-case values, the BL signature delivers QALY gains of 0.054 at an additional cost of GBP 275. This results in a net monetary benefit at a threshold of GBP 30,000 per QALY of GBP 1345. For PMBCL, the QALY gain was 0.0011 at a cost saving of GBP 406 and the net monetary benefit was GBP 437. The hazard ratio for the impact of treating BL less intensively must be at least 1.2 for a positive net monetary benefit. For identifying patients with the DLBCL subtype responsive to bortezomib, QALY gain was 0.2465 at a cost saving of GBP 6175, resulting in a net monetary benefit of GBP 13,570. In a probabilistic sensitivity analysis using 1000 simulations, a testing strategy was superior to a treat all with R-CHOP strategy in 81% of the simulations and with a cost saving in 92% assuming a cost price of zero., Conclusions: Our estimates show that the combined test has a high probability of being cost effective. There is good quality evidence for the benefit of subtyping DLBCL but the evidence on the number of patients reclassified to or from BL and PMBCL and the impact of a more precise diagnosis and the cost of treatment is weak. The developers can use the price estimate to inform a return on investment calculations. Evidence will be required of how well the TempO-Seq ® technology performs compared to the testing GEP technology used for subtyping in the recent clinical trial. For BL and PMBCL elements of the test, evidence would be required of the number of patients reclassified and improved costing information would be useful. The diagnostic and therapeutic environment in haematological malignancies is fast moving, which increases the risk for developers of diagnostic tests., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Despite wide recognition of the benefits of sharing research data, public availability rates have not increased substantially in oncology or medicine more broadly over the last decade., Methods: We surveyed 285 cancer researchers to determine their prior experience with sharing data and views on known drivers and inhibitors., Results: We found that 45% of respondents had shared some data from their most recent empirical publication, with respondents who typically studied non-human research participants, or routinely worked with human genomic data, more likely to share than those who did not. A third of respondents added that they had previously shared data privately, with 74% indicating that doing so had also led to authorship opportunities or future collaborations for them. Journal and funder policies were reported to be the biggest general drivers toward sharing, whereas commercial interests, agreements with industrial sponsors and institutional policies were the biggest prohibitors. We show that researchers' decisions about whether to share data are also likely to be influenced by participants' desires., Conclusions: Our survey suggests that increased promotion and support by research institutions, alongside greater championing of data sharing by journals and funders, may motivate more researchers in oncology to share their data.

Purpose: To explore the views of clinicians and researchers about the challenges of measuring health-related quality of life (HRQoL) in children (5-11 years) and to explore whether digital ecological momentary assessment (EMA) could enhance HRQoL measurement., Methods: Semi-structured qualitative interviews with 18 professionals (10 academics/researchers, four clinicians, four with both professional backgrounds) experienced in child HRQoL measurement. We analysed data thematically., Results: Theme One describes the uncertainty around conceptualising HRQoL for children and which domains to include; the greater immediacy and sensitivity of children's reflections on their HRQoL, leading to high variability of the construct; and the wide individual differences across childhood, incongruent with fixed HRQoL measures. Theme Two describes the challenges of proxy reporting, questioning whether proxies can meaningfully report a child's HRQoL and reflecting on discrepancies between child and proxy reporting. Theme Three covers the challenge of interpreting change in HRQoL over time; does a change in HRQoL reflect a change in health, or does this reflect developmental changes in how children report HRQoL. Theme Four discusses digital EMA for HRQoL data capture. In-the-moment, repeated measurement could provide rich data and address challenges of recall, ecological validity and variability; passive data could provide objective markers to supplement subjective responses; and technology could enable personalisation and child-centred design. However, participants also raised methodological, practical and ethical challenges of digital approaches., Conclusion: Digital EMA may address some of the challenges of HRQoL data collection with children. We conclude by discussing potential future research to explore and develop this approach., (© 2023. Crown.)

In this case series, we demonstrate how open-source software has been widely adopted as the primary health information system in many low- and middle-income countries, and for government-developed applications in high-income settings. We discuss the concept of Digital Global Goods and how the general approach of releasing software developed through public funding under open-source licences could improve the delivery of healthcare in all settings through increased transparency and collaboration as well as financial efficiency.