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Abstract Background Compared to the general population, people who inject drugs have poor health and wellbeing. Longitudinal studies can provide insight into factors driving these worse health outcomes but are subject to methodological challenges, such as cohort attrition. The aim of this study was to assess and characterise attrition in a prospective cohort of people who inject drugs in Victoria, Australia. Methods Using annually collected self-reported data from The Melbourne Injecting Drug User Cohort Study (SuperMIX) from September 2008 to January 2021, we estimated the incidence of participants being lost-to-follow-up (LTFU), with an episode of being LTFU defined as participants not undertaking a follow-up interview within two years of their last interview. We utilised a multiple event discrete-time survival analysis on participant period-observation data to estimate the associations between key factors and LTFU. Key areas of exposure measurement in analyses were sociodemographic, drug use and mental health. Results A total of n = 1328 SuperMIX participants completed a baseline interview, with n = 489 (36.8%) LTFU, i.e. not completing a follow-up interview in the following two years. Increased attrition was observed among SuperMIX participants who were: born outside Australia, younger than 30 years, reporting having completed fewer years of education, not residing in stable accommodation, not in stable employment and not on opioid agonist therapy (OAT). Conclusions The attrition rate of the SuperMIX cohort has largely been stable throughout the duration of the study. Higher attrition rates among individuals at greater sociodemographic disadvantage and not on OAT suggest that additional efforts are required to retain these participants. Findings also suggest that SuperMIX might not be capturing data on adverse health and wellbeing outcomes among subpopulations at high risk of harm.

Background: Tumor-induced coagulation is widely observed in cancer patients. Moreover, it is associated with tumorigenesis, tumor progression and metastasis, by creating a proliferative and proangiogenic microenvironment. Therefore, D-dimer, a fibrin degradation product, correlates with tumor prognosis in several cancer types. Objectives: This study aims to investigate whether D-dimer levels can be a predictive and monitoring indicator for chemotherapy response in metastatic breast cancer (MBC) patients. Design: This was a prospective study. Methods: This study included two groups, 76 patients diagnosed with metastatic breast carcinoma and 25 patients with primary breast carcinoma. Plasma D-dimer levels were measured prospectively before chemotherapy initiation, and after the fourth treatment cycle in MBC patients. D-dimer levels before chemotherapy (D0) were analyzed using Receiver Operating Characteristic (ROC) curves to determine the optimal cut-off baseline values of D0, and to evaluate their discriminatory abilities in predicting response to chemotherapy. Results: In the preliminary response evaluation, the mean level of D-dimer significantly decreased by 0.65 μg/ml in patients with partial response patterns, and by 0.5 μg/ml in patients with stable disease. In the disease progression group, a marked increase was seen in D-dimer levels by 1.2 μg/ml. Analysis of ROC curves showed that D-dimer levels at D0 could discriminate the response to chemotherapy, whereas progressive disease rate correlated with higher levels of D-dimer. Conclusion: D-dimer level in plasma is a useful predictive and monitoring marker of response to chemotherapy in metastatic breast cancer.

Background: ACOVID-19, caused by the novel coronavirus SARS-CoV-2, presents with varying severity, from mild symptoms to severe disease, including ARDS and multi-organ failure. Identifying early biochemical markers to predict the severity of COVID-19 is crucial for improving patient outcomes. Aims and Objectives: The study aimed to identify distinct patient groups with COVID-19 and healthy controls using cluster analysis of multiple biomarkers. Specifically, it sought to determine if early detected levels of ferritin, D-dimer, and C-reactive protein (CRP) are associated with the severity of COVID-19. Materials and Methods: Biochemical profiles of sixty patients with SARS-CoV-2 RNA-positive testing and thirty healthy controls were collected and analyzed. Two-dimensional automated hierarchy clustering was performed on all biomarkers. The study focused on alterations in the biochemistry markers ferritin, D-dimer, and CRP. Additionally, levels of inflammatory cytokines, particularly interleukin-6 and tumor necrosis factor-alpha, were measured. Results: Ferritin, D-dimer, and CRP levels were significantly higher in COVID-19 patients compared to the control group. Early detected levels of these biomarkers were associated with a higher incidence of severe COVID-19. Elevated levels of inflammatory cytokines, especially interleukin-6 and tumor necrosis factor-alpha, were also observed in COVID-19 patients, indicating the presence of a cytokine storm, which is a major cause of organ dysfunction and mortality in severe cases. Conclusion: Our findings suggest that elevated levels of ferritin, D-dimer, and CRP are indicative of severe COVID-19. Early detection of these biomarkers can help predict the severity of the infection and guide clinical management. The study also underscores the significant role of inflammatory cytokines in the pathogenesis of COVID-19, contributing to the understanding of the cytokine storm that leads to severe disease outcomes.

Allison Maher,1 Michelle Bennett,1 Hsin-Chia Carol Huang,1,2 Philip Gaughwin,1,3 Mary Johnson,1 Madeleine Brady,1 Kacie Patterson,1,3 Tanya Buettikofer,1,3 Jo Morris,1 Veronica Mary Rainbird,3 Imogen Mitchell,1,2 Bernie Bissett1,3 1Rehabilitation and Community Services / Respiratory Medicine, Canberra Health Services, Canberra ACT, Australia; 2College of Health and Medicine, Australian National University, Canberra ACT, Australia; 3Faculty of Health, University of Canberra, Canberra ACT, Bruce, AustraliaCorrespondence: Bernie Bissett, Email Bernie.Bissett@canberra.edu.auObjective: To describe our methodology and share the practical tools we have developed to operationalize a multidisciplinary Long COVID clinic that incorporates progressive, personalized exercise prescription as a cornerstone feature.Background: There is a lack of evidence-based guidance regarding optimal rehabilitation strategies for people with Long COVID. Existing guidelines lack precision regarding exercise dosage. As one of Australia’s few established multidisciplinary Long COVID clinics, we describe our novel approach to safely incorporating exercise of both peripheral and respiratory muscles, with essential monitoring and management of post-exertional symptom exacerbation.Methods: Working closely with primary health-care providers, our multidisciplinary team screens referrals for people aged 16 and older with Long COVID. Staff apply a three tier model of triage, dependent on the consumer’s presenting problems. Exercise-based interventions necessitate detailed monitoring for post-exertional symptom exacerbation both in the clinic and at home. Personalized exercise prescription includes resistance training at a submaximal threshold (4– 6 exercises, 3 days/week); whole-body endurance exercise titrated to the individual’s progress, at an intensity 4– 6/10 (Rate of Perceived Exertion); and for those limited by dyspnoea, high-intensity inspiratory muscle training using a threshold-based handheld device (30 repetitions per day, ≥ 50% of their maximum inspiratory pressure).Discussion: We have used these approaches for the past 2 years in 250 consumers with no serious adverse events and promising consumer feedback. Our exercise prescription is less conservative than the methods advocated in international guidelines for people with Long COVID, and these more progressive tools may be valuable in other contexts.Conclusion: In our experience, a multidisciplinary clinic-based approach to safely prescribing progressive exercise in Long COVID is feasible. Both peripheral and inspiratory muscle exercise can be effectively titrated to each individual’s symptoms, and careful monitoring for post-exertional symptom exacerbation is crucial.Plain Language Summary: Long COVID affects 5-10% of people following COVID infection. There is little specific guidance on how exercise can be safely prescribed in Long COVID. This paper is the first to provide a detailed description of an Australian multidisciplinary Long COVID clinic, including specific tools and guidance about how exercise can be prescribed while minimising post-exertional symptom exacerbation. The tools described could be valuable to other health facilities striving to optimise multidisciplinary care for people with Long COVID, incorporating safe exercise prescription.Keywords: COVID, rehabilitation, multidisciplinary care, physiotherapy, respiratory muscle training

Abstract Background Wounds are a major health issue on a global scale, putting a great deal of financial, commercial, and social strain on healthcare organizations, patients, and individuals. So, this study aims to investigate the in vitro antioxidant activity of Paralemnalia thyrsoides soft coral total ethanolic extract. Also, bio-guided in vivo wound healing validation enhanced by the evaluation of related gene expression of Paralemnalia thyrsoides total extract, derived fractions, and three known metabolites was done. Furthermore, utilizing network pharmacology, we identified ten hub target genes associated with wound healing, including AKT1(RAC-alpha serine/threonine–protein kinase), IL6 (interleukin-6) , MAPK3 (mitogen-activated protein kinase 3), MMP9 (matrix metalloproteinase 9), and APP (amyloid P protein precursor). We conducted molecular docking to assess how the three compounds interact with these hub genes and inflammatory cytokines (IL-1β (interleukin-1 beta), TGF-β (transforming growth factor-beta), TNF-α (tumor necrosis factor-alpha), and NF-KB (nuclear factor-kappa B) linked to wound healing. Results In vitro antioxidant activity of the total ethanolic extract of Paralemnalia thyrsoides revealed potent scavenging activity against H2O2 with IC50 of 178.62 μg/mL. Additionally, the bio-guided scheme of the in vivo wound healing assay leads to the most active fraction, petroleum ether, with a healing percentage of 85% ± 4. Several chromatographic procedures upon petroleum ether fraction led to the isolation of three known compounds with significant in vivo wound healing potential which are recognized as triacontan-1-ol (1), 24-methylcholesterol (2) 6α-acetyl-7α-acetate-1(10)-α-13-nornardosine [C16H24O4] (3). Noteworthy downregulation in Cox-2 (Cyclooxygenase-2), Cox-1 (Cyclooxygenase-1), IL-1β, TGF-β, TNF-α, NF-KB, and INF-ϒ (interferon-ϒ) relative genes expression and upregulation in TGF-β, and IL-10 (interleukin-10) relative genes expression proved that compounds (3), (2), and (1) were, respectively, significant. The in silico study suggests that both C16H24O4 and 24-methyl cholesterol have potential in wound healing, possibly involving the regulation of RAC-alpha serine/threonine-protein kinase (AKT1). Conclusion Our study highlights the antioxidant and wound-healing potential of Paralemnalia thyrsoides soft coral that can be attributed to its diverse chemical metabolites. The in vivo and in silico findings highlighted that P. thyrsoides can be an effective remedy for wound restoration with the need for extensive future detailed clinical studies to prove these results.

Introduction Aid harmonisation is a key component of donor efforts to make aid more effective by improving coordination and simplifying and sharing information to avoid duplication. This study evaluates the harmonisation of health and humanitarian aid in Syria during acute humanitarian and health crises from 2011 to 2019.Methods Data on humanitarian and health aid for Syria between 2011 and 2019 was collected from the Organisation for Economic Cooperation and Development’s Creditor Reporting System to assess the harmonisation of aid. The data was linked to four key indicators of the conflict: the number of internally displaced persons; the number of people in need of humanitarian assistance; the number or frequency of internal movements (displacements) by individuals; and the decline in Syria’s population between 2011 and 2019. This was compared with data from highly fragile states and developing countries. Four focus group discussions, four key informants’ interviews and three consultations with humanitarian practitioners were also conducted.Results The findings suggest that overall aid harmonisation did not occur and importantly did not correlate with increased humanitarian needs. During the first 5 years, humanitarian and health pooled funds (which endorse aid harmonisation) in Syria were nearly entirely absent, far less than those in developing countries and highly fragile states. However, from 2016 to 2019, a visible surge in humanitarian pooled funds indicated an increase in the harmonisation of donors’ efforts largely influenced by adopting the Whole of Syria approach in 2015 as a positive result of the cross-border United Nation (UN) Security Council resolution in 2014.Conclusion Harmonisation of aid within the Syrian crisis was found to have little correlation with the crisis parameters and population needs, instead aligning more with donor policies. Assessing fragmentation solely at the donor level is also insufficient. Aid effectiveness should be assessed with the inclusion of community engagement and aid beneficiary perspectives. Harmonisation mechanisms must be disentangled from international politics to improve aid effectiveness. In Syria, this study calls for finding and supporting alternative humanitarian coordination and funding mechanisms that are not dependent on the persistent limitations of the UN Security Council.

Abstract Background Classic galactosemia (CG) is an inborn error of galactose metabolism caused by mutations in the GALT gene. Premature ovarian insufficiency (POI) is a later complication that affects 80% of women with CG due to a significant decline in ovarian reserve (primordial follicle pool). The definite mechanisms underlying the early onset of POI in CG patients are not fully understood. Methods In this study, we performed single‐nucleus RNA sequencing (snRNA‐seq) and spatial transcriptomics on ovary tissue biopsies from prepubertal girls diagnosed with CG to investigate dynamic changes in gene expression and altered signalling pathways in granulosa cells, oocytes, and stromal cells. Results We generated single‐nucleus and spatial transcriptomics atlas of human ovaries from prepubertal girls diagnosed with and without CG. snRNA‐seq profiling of the paediatric ovary revealed a diverse ovarian microenvironment with seven distinct major cell types. Our transcriptomic analysis revealed an increase in the expression of several endoplasmic reticulum stress and oxidative stress associated genes, which can promote apoptosis of granulosa cells in CG. PTEN/PI3K/AKT signalling, which is crucial for primordial follicle activation and survival was dysregulated as supported by upregulated PTEN transcripts and a significant reduction in phospho‐AKT levels in the granulosa cells and oocytes. We also found a marked increase in expression of phospho‐H2A.X, LC3A/B and CASP9 in the primordial follicles of CG ovaries suggesting DNA damage, autophagy, and accelerated follicular atresia. Furthermore, we noticed genes participating in extracellular matrix organisation, integrin and gap junction signalling, essential for structural support of the ovarian stroma were profoundly altered. Conclusions Our findings provide molecular insights into the dysregulated cellular signalling pathways essential for primordial follicle growth and survival that can explain the etiology of POI in CG patients. This study has implications in the development of future therapeutic interventions to preserve ovarian function and promote female reproductive health. Highlights Created a comprehensive single‐nucleus transcriptomic atlas and spatial landscape of paediatric ovary tissue from prepubertal girls diagnosed with classic galactosemia (CG). Our transcriptomic analysis revealed activation of genes associated with ER‐stress signalling, oxidative stress response and ATM signalling/DNA damage response as shown by significant increase in expression of p‐EIF2A, p‐H2A.X and LC3A/B in the primordial follicles of CG ovary. PTEN/PI3K/AKT signalling pathways was dysregulated evidenced by a significant reduction in phospho‐AKT expression in the primordial follicles of CG ovary, suggesting impaired follicle activation and survival.

Background & Objective: In the medical field, there is a growing emphasis on fostering creativity and innovation in medical students to prepare them for the unpredictable nature of patient care. This study aimed to explore the perspectives of both lecturers and medical students on the current teaching practices and their influence on the development of creative thinking skills Materials & Methods: The study was conducted as qualitative research at the Malaysian Faculty of Medicine and Health Sciences and included a purposeful sample of eight medical students and seven lecturers. Data were gathered through individual semi-structured interviews held via the Google Meet platform and analyzed using a thematic analysis approach. Results: The findings indicate that learner-centred approaches, such as problem-solving exercises and group discussions, seminars, debates, and dramas have a positive impact on enhancing their creative thinking abilities. The use of technology-assisted teaching methods, including e-learning and simulation labs, was also perceived as inspiring, however, limitations in technical infrastructure were noted. Challenging activities like assignments, games, competitions, and online tests encourage creative learning. Hands-on activities, such as bedside teaching and clinical skill learning, are also valuable in learning clinical skills in unique ways, but their effectiveness could be reduced by environmental and personal factors. Furthermore, practicing para-curriculum activities in a supportive and relaxed learning environment was identified as fostering a culture of original thought. Conclusion: This study suggests that a comprehensive approach to medical education that integrates creative pedagogy can be instrumental in fostering creativity in medical students. Providing opportunities for creative thinking through workshops and addressing technical infrastructure limitations in technology-assisted teaching methods could be considered in enhancing the creative curricula in the South East region. The findings underline the importance of a learner-centered approach and a supportive learning atmosphere in promoting creative learning.

Abstract Background Perinatal substance use can have significant adverse effects on maternal and child health and family stability. Few interventions are specifically designed to address this significant public health problem. The Parent–Child Assistance Program (PCAP) is a 3-year case management and home-visiting intervention that seeks to help birthing persons with at-risk substance use during pregnancy to achieve and maintain substance use disorder recovery and avoid exposing future children to substances prenatally. At-risk refers to a level of substance use that creates problems in the individuals’ lives or puts them or their children at risk of harm either prenatally or postnatally. Although the program has consistently shown substantial pre- to post-intervention improvements in its participants, PCAP remains to be tested with a rigorous randomized controlled trial (RCT). This study protocol describes a randomized controlled trial that aims to examine the effectiveness of the intervention compared to services as usual in affecting primary outcomes related to substance use and family planning. Secondary outcomes will concern connection to recovery support services and family preservation. Methods Using an intent-to-treat design, the study will recruit from two metro areas in Oklahoma and enroll 200 birthing individuals who are pregnant or up to 24 months postpartum with at-risk substance use during their current or most recent pregnancy. Participants will be randomly assigned, stratified by location, to receive either PCAP or services as usual for 3 years. Participants in the PCAP condition will meet with their case manager approximately biweekly over the course of the intervention period, in their local communities or in their own homes whenever possible. Case managers will assist with goal setting and provide practical assistance in support of participants’ goals. Primary and secondary outcomes will be assessed at baseline and 12, 24, and 36 months post-baseline using the Addiction Severity Index interview and a self-administered survey. Discussion Results from this trial will help to gauge the effectiveness of PCAP in improving parent and child well-being. Results will be reviewed by federal clearinghouses on home-visiting and foster care prevention to determine the strength of evidence of effectiveness with implications for federal financing of this program model at the state level. Trial registration ClinicalTrials.gov NCT05534568. Registered on 6/8/2022.

Background Staff sickness absenteeism and presenteeism (attending work while unwell) incur high costs to the NHS, are associated with adverse patient outcomes and have been exacerbated by the COVID-19 pandemic. The main causes are mental and musculoskeletal ill health with cardiovascular risk factors common. Objectives To undertake a feasibility study to inform the design of a definitive randomised controlled trial of the effectiveness and cost effectiveness of a health screening clinic in reducing absenteeism and presenteeism amongst the National Health Service staff. Design Individually randomised controlled pilot trial of the staff health screening clinic compared with usual care, including qualitative process evaluation. Setting Four United Kingdom National Health Service hospitals from two urban and one rural Trust. Participants Hospital employees who had not previously attended a pilot health screening clinic at Queen Elizabeth Hospital Birmingham. Interventions Nurse-led staff health screening clinic with assessment for musculoskeletal health (STarT musculoskeletal; STarT Back), mental health (patient health questionnaire-9; generalised anxiety disorder questionnaire-7) and cardiovascular health (NHS health check if aged ≥ 40, lifestyle check if < 40 years). Screen positives were given advice and/or referral to services according to UK guidelines. Main outcome measures The three coprimary outcomes were recruitment, referrals and attendance at referred services. These formed stop/go criteria when considered together. If any of these values fell into the ‘amber’ zone, then the trial would require modifications to proceed to full trial. If all were ‘red’, then the trial would be considered unfeasible. Secondary outcomes collected to inform the design of the definitive randomised controlled trial included: generalisability, screening results, individual referrals required/attended, health behaviours, acceptability/feasibility of processes, indication of contamination and costs. Outcomes related to the definitive trial included self-reported and employee records of absenteeism with reasons. Process evaluation included interviews with participants, intervention delivery staff and service providers. Descriptive statistics were presented and framework analysis conducted for qualitative data. Due to the COVID-19 pandemic, outcomes were captured up to 6 months only. Results Three hundred and fourteen participants were consented (236 randomised), the majority within 4 months. The recruitment rate of 314/3788 (8.3%) invited was lower than anticipated (meeting red for this criteria), but screening identified that 57/118 (48.3%) randomised were eligible for referral to either general practitioner (81%), mental health (18%) and/or physiotherapy services (30%) (green). Early trial closure precluded determination of attendance at referrals, but 31.6% of those eligible reported intending to attend (amber). Fifty-one of the 80 (63.75%) planned qualitative interviews were conducted. Quantitative and qualitative data from the process evaluation indicated that the electronic database-driven screening intervention and data collection were efficient, promoting good fidelity, although needing more personalisation at times. Recruitment and delivery of the full trial would benefit from a longer development period to better understand local context, develop effective strategies for engaging with underserved groups, provide longer training and better integration with referral services. Delivery of the pilot was limited by the impact of COVID-19 with staff redeployment, COVID-research prioritisation and reduced availability of community and in-house referral services. While recruitment was rapid, it did not fully represent ethnic minority groups and truncated follow-up due to funding limitations prevented full assessment of attendance at recommended services and secondary outcomes. Conclusions There is both a clinical need (evidenced by 48% screened eligible for a referral) and perceived benefit (data from the qualitative interviews) for this National Health Service staff health screening clinic. The three stop/go criteria were red, green and amber; therefore, the Trial Oversight Committee recommended that a full-scale trial should proceed, but with modifications to adapt to local context and adopt processes to engage better with underserved communities. Trial registration This trial is registered as ISRCTN10237475. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/42/42) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 23. See the NIHR Funding and Awards website for further award information. Plain language summary Sickness absenteeism and presenteeism (attendance at work while ill, with poor work performance) are major problems in the NHS and associated with worse patient health care. The most common causes of NHS staff sickness absenteeism and presenteeism are muscular complaints and mental ill health. Poor lifestyle and illnesses associated with heart disease are also important factors. Staff health checks might improve the health of NHS staff, but no studies have included screening tests to address the most common causes of poor staff health. This pilot study tested whether it would be possible to deliver a randomised controlled trial of an NHS staff health screening clinic, where some people get the screening check and others do not (chosen at random, like flipping a coin). We used an electronic database to capture all data. Participants completed initial questionnaires either at home or at work, then attended a face-to-face screening clinic using recognised screening questionnaires and tests to detect problems with muscular, mental or heart health. We considered how NHS staff and healthcare organisations would want the screening clinic and trial to run, how a diverse range of NHS staff could best be approached, how many staff might need to be invited and what their healthcare needs would be. The study ran in four UK NHS hospitals during the COVID-19 pandemic. Two hundred and thirty-six NHS staff participated, but early trial closure due to the pandemic meant that some results were unavailable. For the primary feasibility outcomes, although recruitment rates of around 8% were lower than anticipated, half of staff screened needed referral for further health care and one-third reported intending to attend. Staff felt that the clinic addressed an important health need. The Trial Oversight Committee recommended proceeding to a full-scale trial but with modifications to address findings from the process evaluation, including ways to encourage a wider group of NHS staff to take part. Scientific summary Background Staff sickness absenteeism and presenteeism (attending work while unwell) incur high costs to the NHS, are associated with adverse patient outcomes and have been exacerbated by the COVID-19 pandemic. The main causes are mental and musculoskeletal ill health with cardiovascular risk factors also common. Objectives The aim of this pilot trial was to assess the feasibility of a definitive randomised controlled trial (RCT) evaluating the clinical and cost effectiveness of a health screening clinic compared to usual care, in reducing sickness absenteeism and presenteeism amongst NHS staff. The key objectives were to: describe recruitment rates describe participant characteristics and assess generalisability compared to the hospital workforce describe intervention screening assessment results describe recommended referrals and their uptake assess the feasibility of measuring the outcomes relating to the definitive trial, and obtain an estimate of the standard deviation of the proposed primary outcomes for a full RCT assess levels of contamination between intervention and usual care arms to inform RCT design (individual vs. cluster RCT) describe and explain the fidelity to the intervention and evaluate the barriers and enablers to participation describe the views, experiences and satisfaction of participants and those delivering the health checks quantify the costs of undertaking the screening service and its consequences. Design A multicentre, two-arm, parallel group, open-label, 1 : 1 individually randomised pilot RCT of a complex intervention comparing a staff health screening clinic with usual care. Setting Three large urban hospitals and one rural district general hospital in the West Midlands. Participants All employees in the participating hospitals were eligible to participate except those who had previously attended a pilot health screening clinic at Queen Elizabeth Hospital Birmingham (QEHB) or who were currently taking part in another non-COVID drug trial or similar health and well-being trial. Participants were informed of the trial through staff meetings, noticeboards, posters and ward champions, and invited (with up to three reminders) through multiple approaches including e-mail and personal invitation. Wards were chosen to reflect the characteristics of the hospital. Data collection Potential participants joined the trial via weblink to a custom-designed electronic trial data collection platform hosted by the Birmingham Clinical Trials Unit. Eligibility questions, consent and a baseline questionnaire were completed prior to randomisation. Randomisation and blinding Participants were randomised to intervention or usual care (1 : 1 ratio) using an integrated randomisation module on the trial database, using a minimisation algorithm (with random element) to ensure balance on key characteristics. Interventions Intervention Staff health screening clinic with two stages: screening assessment for three components: mental health, musculoskeletal health and cardiovascular health, followed by appropriate advice and/or referral, according to level of risk, to appropriate services for management according to NHS/National Institute for Health and Care Excellence (NICE) recommendations. The screening assessment was delivered by trained research nurses using a standardised protocol. All data were captured by a customised database with prompts to guide the research nurses. Local pathways were used for referrals to lifestyle, physiotherapy, psychological and primary care services. Participants reporting relevant conditions already being treated did not receive the referral element of that component. A results letter detailing findings and recommendations was sent to participants and their general practitioners (GPs) for appropriate action. Usual care Standard access to medical services for management of any presenting condition. Main outcome measures This pilot trial was originally planned to have a 52-week follow-up period to fully test the processes for a definitive trial, but this was reduced to 26 weeks due to the pandemic delays and funding restrictions. Primary outcomes and stop/go criteria Three coprimary outcomes were originally planned to inform progression to the definitive trial: Recruitment (consented) as a proportion of those invited. Referral to any recommended services as a result of the three screening components (usually GP, local physiotherapy/community psychological services) – intervention arm only. Attendance at any recommended services at 26 weeks (self-report) – intervention arm only. We defined ‘referral’ as anyone who was eligible for a referral, that is they recorded a suitable risk value and were not already being treated for that condition. Due to the pandemic, only a small number of participants completed the 26-week follow-up assessment. Therefore, acceptance of the referral (signifying intention), which was collected during the screening assessment, was used as a proxy for attendance. The three coprimary outcomes formed stop/go criteria when considered together. If any of these values fell into the ‘amber’ zone, then the trial would require modifications to proceed to full trial. If all were ‘red’, then the trial would be considered unfeasible. Secondary outcomes were collected to inform the design of the definitive RCT and any modifications required. Secondary outcomes Comparison of baseline characteristics of included participants and hospital population. Description of intervention screening assessments results. Number/type of referrals to recommended services (intervention arm only). Attendance at each individual recommended service (intervention arm only). Lifestyle relevant to screening intervention advice and referrals (self-report at 26 weeks compared with baseline). Acceptability of intervention to participants and health screening clinic staff (interviews). Feasibility of trial processes (completeness of relevant data items, interviews). Indication of contamination (comparing pre/post data for health behaviours and health care/other service utilisation in control arm). Outcomes related to the definitive trial Absenteeism at 26 weeks with reasons, measured by days and spells. Self-reported absolute absenteeism, relative absenteeism and relative hours of work – for last 7 days and last 28 days [World Health Organization Health and Work Performance Questionnaire (WHO-HPQ)]. Self-reported absenteeism (6-month recall period). Employee records of absenteeism, the proposed primary outcome of the definitive trial. Routinely collected linked data from the NHS Electronic Staff Record Programme. Presenteeism at 26 weeks [self-reported absolute presenteeism and relative presenteeism for last 28 days (WHO-HPQ)]. Attendance at occupational health service at 26 weeks (self-report). Healthcare utilisation at 26 weeks (self-report) including GP consultations and hospital admissions. EuroQol-5 Dimensions, five-level version (EQ-5D-5L) index value measuring health-related quality of life (HRQoL) (EuroQol EQ-5D 5-level) at 26 weeks. Resource use and costs collected by self-report questionnaire to participants on health service utilisation and information from the screening assessment regarding duration and resources used. Sample size We aimed to recruit 480 participants (20 per week) in 24 weeks. With this sample size, the 95% confidence interval (CI) for the proportion of staff recruited could be estimated to be 4% either side of the estimate. Statistical methods Analyses were mainly descriptive. No statistical modelling was undertaken, and no p-values are reported. No subgroup analyses were planned. Process evaluation A mixed-methods process evaluation explored programme reach, fidelity of screening delivery, attendance at referrals and participants’ views of the intervention to support any modifications required for the design of the definitive trial. Quantitative data to support the process evaluation were obtained as above. Semistructured qualitative interviews/focus groups were conducted (choice of Zoom, telephone, face-to-face) to obtain views of relevant stakeholders [trial participants, enhancing the Health of NHS Staff (eTHOS) nurses, referral providers, outside agencies] on the feasibility and acceptability of the staff health screening intervention and trial and inform any protocol adaptations needed for a full trial. Due to the COVID-19 delays, a pragmatic approach was taken to sampling; all eligible participants in the intervention arm were invited to participate, and invitations were sent to all controls until the target number of participants had been reached. Data were recorded either on Zoom or an encrypted recorder and transferred via secure file transfer to an external company for transcription. Interviews were transcribed intelligent/clean verbatim and anonymised. A thematic analysis of content was informed by the framework analytical approach. Data collection and analysis ran concurrently so that the emergent analytical themes could inform further data collection. Health economic analysis A descriptive analysis was presented with average costs of screening per participant and quality of life obtained in the baseline questionnaire. Information was obtained from participating centres on estimated time taken for each screening clinic task, grade of the member of staff responsible and cost of individual blood tests. Staff time required for each task was then multiplied by the relevant unit costs obtained from standard source. The total cost of blood tests per participant was weighted according to the proportion who received each type of blood test. Quality of life of all participants was estimated using the EQ-5D-5L. Patient and public involvement Four to six clinical, administrative and retired NHS staff met on a regular basis throughout the project to provide advice. One hospital healthcare worker was included on the Trial Oversight Committee (TOC). Similarly, we consulted a stakeholder advisory group representing a wider body of professionals relevant to the trial, for example, GPs. Impact of COVID-19 pandemic on trial delivery It was not possible to commence the trial in March 2020 due to the COVID-19 pandemic. Two hospital sites commenced the trial in December 2020, but after 3–4 weeks, recruitment was paused. The trial recommenced in May 2021 in all four sites. The original trial was planned to include a 52-week follow-up; however, due to the delays, a 26-week follow-up was agreed with the funder, but only a few people reached this time point before trial closure. Results Three thousand seven hundred and eighty-eight of the 24,344 NHS staff across the four sites were invited to take part. Of the 353 eligible respondents, 314 consented (8.3% of those invited and 65.4% of our planned target of n = 480). Two hundred and thirty-six were randomised into the study; n = 118 to the intervention screening arm and 118 to usual care. One hundred and one (85.6%) attended and completed the screening clinic. Only 26/236 (11.0%) participants reached the 26-week follow-up. Primary outcomes and stop/go criteria Three hundred and fourteen of the 3788 [8.3% (95% CI 7.4% to 9.2%)] invited staff gave their consent to participate, which meets the red stop/go criterion for recruitment. Fifty-seven of the 118 [48.3% (95% CI 39.0% to 57.7%)] participants randomised to the intervention arm were eligible for referral to at least one service, which meets the green stop/go criterion for referral. Eighteen of the 57 [31.6% (95% CI 19.9% to 45.2%)] participants eligible for a referral accepted a referral to at least one service, which meets the amber stop–go progression criterion for attendance, although the CIs were wide. Secondary outcomes Assessing generalisability (programme reach) The invited population was similar to the hospital population, although those who participated in the trial were more likely to be white British (78.0% compared to 59.7%), allied health professionals (14.0% compared to 6.9%) and healthcare scientists (11.9% compared to 5.0%), and less likely to be from estates/ancillary, medical/dental and nursing/midwifery registered staff groups. Results of intervention screening assessments Most reported minimal/mild anxiety, but 11 (10.9%) were classified as having moderate and 5 (5.0%) severe anxiety. Most people reported minimal/mild depression, but 13 (12.9%) reported moderate/moderately severe depression and 4 (4.0%) severe depression. Most participants had no significant back pain, although eight (7.9%) were at medium risk and two (2.0%) at high risk on the StarT Back tool. Twenty-seven (27.0%) scored with medium risk for other types of pain and five (5.0%) high risk. Thirty-eight (38.0%) participants were classified as overweight and 32 (32.0%) obese. Forty-six (46.0%) were self-reported as physically active. Twelve (11.9%) reported increasing/higher risk of alcohol dependence and 10 (9.9%) were current smokers. Of those eligible for the cardiovascular risk score (QRISK2), nine (14.5%) had medium risk (10–19.9%) and two (3.2%) had a high risk of developing cardiovascular disease (CVD) in the next 10 years. Completeness of data items and attendance at screening clinic (fidelity) Sixty-six of the 314 (21.0%) consented participants did not complete the baseline questionnaire. One hundred and one of the 118 (86%) participants randomised to the intervention arm attended and completed the screening clinic. Individual data items were generally well completed and deoxyribonucleic acid (DNA) rates low. Costs and quality of life The maximum screening cost per participant (including blood tests) was £107.48 if the highest band staff were used and £99.98 if the lowest band staff ran the clinic. Complete EQ-5D-5L data were available for 233/236 randomised participants [mean score 0.793 (SD 0.168)]. Process evaluation We conducted 51 (63.8%) out of the 80 originally planned interviews. Four different hospital sites utilised a nurse-led screening intervention with prompts and electronic data collection, which was efficient and promoted good fidelity, although this was viewed as impersonal at times. Participants appreciated the convenience of the onsite service and valued time to focus on their own needs. However, some felt that it did not reflect or address their stress levels appropriately or meet their expectations in providing faster access to additional services. There were also concerns that it would not address the wider determinants of ill health and problems in the workplace, that it was just a ‘sticking plaster’. The eTHOS staff delivering the intervention generally found the delivery of the study feasible, although there were a number of suggestions from staff both delivering and receiving the intervention to adapt the approach for a full trial. Conclusions Despite significant delays, truncation and amendments required due to the COVID-19 pandemic, we were able to assess the most important aspects of the feasibility of a RCT to evaluate the clinical and cost effectiveness of a novel hospital-based staff health screening clinic in reducing absenteeism and presenteeism. Recruitment was feasible in a short space of time, and delivery of the intervention feasible, efficient and acceptable. Although a lower proportion of staff were recruited than anticipated, this was offset by the findings of the screening assessments which revealed significant health needs of those attending with 48% requiring referral to additional services. The three stop/go criteria were red, green and amber; therefore, the TOC recommended that a full-scale trial should proceed, but with modifications (see below) to adapt to local context and adopt processes to engage better with underserved communities, to improve both reach and effectiveness. Implications/modifications for full trial design There was no evidence of contamination; therefore, an individual RCT would remain the design of choice. Wait-list controls might also be a potential option to encourage people to participate. While our approach to recruitment was successful for many (most people responded to an e-mail), additional strategies would be needed to recruit the underserved groups, and specific minority staff network groups and leaders should be engaged in order to do so. Messaging to potential participants needs to be clearer in order to reduce concerns about confidentiality, optimise recruitment and manage expectations. More flexible clinic times/alternative options could be explored to improve inclusion. Electronic data capture was considered convenient, but extra training and practice should be provided to ensure sufficient familiarity and personalisation. Consideration (on a site-by-site basis) of clearer referral pathways is important for the full trial, in order to optimise attendance at referrals and realise health outcomes. Further consideration should also be given to the mental health screening tools used, as qualitative interviews with staff revealed their concerns that occupational stress and burnout may not be adequately identified and treated. There was no evidence from this study that self-reported absenteeism data should replace human resources (HR) data as the potential primary outcome as correlation between the two was poor. Acknowledging the 25% dropout between consent and randomisation, the amount of data collected and length of questionnaires should be reviewed prior to a full trial. Resource use and cost data were relatively straightforward to collect, although it was evident that more detailed site-by-site data collection would be required in a full trial, to reflect the full range of clinic organisation scenarios. Trial registration This trial is registered as ISRCTN10237475. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/42/42) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 23. See the NIHR Funding and Awards website for further award information.

Summary: Background: Abdominal obesity increases the risk for non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: To elucidate the directional cell-type level biological mechanisms underlying the association between abdominal obesity and MASLD, we integrated adipose and liver single nucleus RNA-sequencing and bulk cis-expression quantitative trait locus (eQTL) data with the UK Biobank genome-wide association study (GWAS) data using colocalization. Then we used colocalized cis-eQTL variants as instrumental variables in Mendelian randomization (MR) analyses, followed by functional validation experiments on the target genes of the cis-eQTL variants. Findings: We identified 17 colocalized abdominal obesity GWAS variants, regulating 17 adipose cell-type marker genes. Incorporating these 17 variants into MR discovers a putative tissue-of-origin, cell-type-aware causal effect of abdominal obesity on MASLD consistently with multiple MR methods without significant evidence for pleiotropy or heterogeneity. Single cell data confirm the adipocyte-enriched mean expression of the 17 genes. Our cellular experiments across human adipogenesis identify risk variant -specific epigenetic and transcriptional mechanisms. Knocking down two of the 17 genes, PPP2R5A and SH3PXD2B, shows a marked decrease in adipocyte lipidation and significantly alters adipocyte function and adipogenesis regulator genes, including DGAT2, LPL, ADIPOQ, PPARG, and SREBF1. Furthermore, the 17 genes capture a characteristic MASLD expression signature in subcutaneous adipose tissue. Interpretation: Overall, we discover a significant cell-type level effect of abdominal obesity on MASLD and trace its biological effect to adipogenesis. Funding: NIH grants R01HG010505, R01DK132775, and R01HL170604; the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant No. 802825), Academy of Finland (Grants Nos. 333021), the Finnish Foundation for Cardiovascular Research the Sigrid Jusélius Foundation and the Jane and Aatos Erkko Foundation; American Association for the Study of Liver Diseases (AASLD) Advanced Transplant Hepatology award and NIH/NIDDK (P30DK41301) Pilot and Feasibility award; NIH/NIEHS F32 award (F32ES034668); Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (EVO/VTR grants 2005-2021), the Academy of Finland grant (Contract no. 138006); Academy of Finland (Grant Nos 335443, 314383, 272376 and 266286), Sigrid Jusélius Foundation, Finnish Medical Foundation, Finnish Diabetes Research Foundation, Novo Nordisk Foundation (#NNF20OC0060547, NNF17OC0027232, NNF10OC1013354) and Government Research Funds to Helsinki University Hospital; Orion Research Foundation, Maud Kuistila Foundation, Finish Medical Foundation, and University of Helsinki.

Background Breast cancer, particularly triple-negative breast cancer (TNBC), poses a significant global health burden. Chemotherapy was the mainstay treatment for TNBC patients until immunotherapy was introduced. Studies indicate a noteworthy prevalence (0.2% to 18.6%) of mismatch repair protein (MMRP) deficiency in TNBC, with recent research highlighting the potential of immunotherapy for MMRP-deficient metastatic breast cancer. This study aims to identify MMRP deficiency in TNBC patients using immunohistochemistry. Methods A retrospective cohort study design was used and included TNBC patients treated between 2015 and 2021 at King Hussein Cancer Center. Immunohistochemistry was conducted to assess MMRP expression Results Among 152 patients, 14 (9.2%) exhibited deficient MMR (dMMR). Loss of PMS2 expression was observed in 13 patients, 5 of whom showed loss of MLH1 expression. Loss of MSH6 and MSH2 expression was observed in one patient. The median follow-up duration was 44 (3–102) months. Despite the higher survival rate (80.8%, 5 years) of dMMR patients than of proficient MMR patients (62.3%), overall survival did not significantly differ between the two groups. Conclusion Approximately 9% of TNBC patients exhibit dMMR. dMMR could be used to predict outcomes and identify patients with TNBC who may benefit from immunotherapy.

Background: Recruitment of low risk blood donors can be challenging. Efforts should be made to increase the level of awareness and positive attitude towards blood donation. An essential step to achieve this is obtaining comprehensive data about the current situation of awareness, knowledge and attitudes of the population towards blood donation. Methods/materials: The present study was conducted at two blood donation centres in Amman, Jordan, during 2021. A total of 536 whole blood donors were included. Data regarding their demographic characteristics, blood donation history as well as their knowledge and attitudes regarding blood donation were collected by a questionnaire. Results: Four hundred ninety participants (91.4%) were males, whereas only 46 participants (8.6%) were females. Ninety seven subjects (18.1%) were first time donors, whereas 431 subjects (81.9%) had previous donations. The participants’ median score in the knowledge section was 19.0 points (range 5–25 points). Based on a cut-off of 15 out of 28: 84% of the participants were knowledgeable. Similarly 97% of the participants had a positive attitude based on a cut-off of 17 out of 32 points. Multivariate analysis revealed that high knowledge score was significantly associated with study major and employment status, whereas a positive attitude was significantly associated with a higher income. More than half of first time donors stated lack of awareness as being the reason for not donating blood before. Conclusion: Measures to improve awareness, knowledge and attitudes towards blood donation should be implemented in order to meet the increasing demand for blood and blood components. Targeted campaigns, correction of some misconceptions and using different motivations are suggested.

The oxytosis/ferroptosis regulated cell death pathway is an emerging field of research owing to its pathophysiological relevance to a wide range of neurological disorders, including Alzheimer's and Parkinson's diseases and traumatic brain injury. Developing novel neurotherapeutics to inhibit oxytosis/ferroptosis offers exciting opportunities for the treatment of these and other neurological diseases. Previously, we discovered cannabinol (CBN) as a unique, potent inhibitor of oxytosis/ferroptosis by targeting mitochondria and modulating their function in neuronal cells. To further elucidate which key pharmacophores and chemical space are essential to the beneficial effects of CBN, we herein introduce a fragment-based drug discovery strategy in conjunction with cell-based phenotypic screens using oxytosis/ferroptosis to determine the structure-activity relationship of CBN. The resulting information led to the development of four new CBN analogs, CP1-CP4, that not only preserve the sub-micromolar potency of neuroprotection and mitochondria-modulating activities seen with CBN in neuronal cell models but also have better druglike properties. Moreover, compared to CBN, the analog CP1 shows improved in vivo efficacy in the Drosophila model of mild traumatic brain injury. Together these studies identify the key molecular scaffolds of cannabinoids that contribute to neuroprotection against oxytosis/ferroptosis. They also highlight the advantageous approach of combining in vitro cell-based assays and rapid in vivo studies using Drosophila models for evaluating new therapeutic compounds.

Abstract Background Breast cancer (BC) is the most common female cancers in many countries including Syria. Familial breast cancer or previous family cancer history are considered significant risk factors. Therefore, detecting the prevalence and founder mutations in the population facilitates genetic counselling, risk assessment and the development of a cost-effective screening strategy. In this study, we investigated the three germ-line founder mutations in the BRCA1/2 genes: [NM_007294.4 (BRCA1):c.68_69del (p.Glu23fs), NM_007294.4 (BRCA1):c.5266dup (p.Gln1756fs) and NM_000059.4 (BRCA2):c.5946del (p.Ser1982fs)], to examine their incidence and frequency in early-onset breast cancer cases and determine if they are connected to familial breast cancer. One hundred early diagnosed BC females (≤ 40 years old) with no other type of cancer were recruited. Genomic DNA was isolated from peripheral blood samples, and mutations were investigated using the Amplification-Created Restriction Site (ACRS) method. Results The family history of cancer was observed in 61% of the cases, of which 35% were breast cancer; however, none of the screened mutations were detected among BC patients. Conclusions The investigated germ-line mutations were not common among Syrian female patients with early-onset BC and were not associated with familial BC. Other mutations in the BRCA1/2 genes or other genes may have a contributing role. Future studies and the need to launch nationwide mutation screening tests for BRCA 1/BRCA2 in the Syrian population are recommended.

Abstract Introduction Non-compliance is a common challenge for researchers and may reduce the power of an intention-to-treat analysis. Whilst a per protocol approach attempts to deal with this issue, it can result in biased estimates. Several methods to resolve this issue have been identified in previous reviews, but there is limited evidence supporting their use. This review aimed to identify simulation studies which compare such methods, assess the extent to which certain methods have been investigated and determine their performance under various scenarios. Methods A systematic search of several electronic databases including MEDLINE and Scopus was carried out from conception to 30th November 2022. Included papers were published in a peer-reviewed journal, readily available in the English language and focused on comparing relevant methods in a superiority randomised controlled trial under a simulation study. Articles were screened using these criteria and a predetermined extraction form used to identify relevant information. A quality assessment appraised the risk of bias in individual studies. Extracted data was synthesised using tables, figures and a narrative summary. Both screening and data extraction were performed by two independent reviewers with disagreements resolved by consensus. Results Of 2325 papers identified, 267 full texts were screened and 17 studies finally included. Twelve methods were identified across papers. Instrumental variable methods were commonly considered, but many authors found them to be biased in some settings. Non-compliance was generally assumed to be all-or-nothing and only occurring in the intervention group, although some methods considered it as time-varying. Simulation studies commonly varied the level and type of non-compliance and factors such as effect size and strength of confounding. The quality of papers was generally good, although some lacked detail and justification. Therefore, their conclusions were deemed to be less reliable. Conclusions It is common for papers to consider instrumental variable methods but more studies are needed that consider G-methods and compare a wide range of methods in realistic scenarios. It is difficult to make conclusions about the best method to deal with non-compliance due to a limited body of evidence and the difficulty in combining results from independent simulation studies. PROSPERO registration number CRD42022370910.

Abstract Although placebo-controlled trials are considered the gold standard for evaluating the efficacy of healthcare interventions, they can be perceived to be controversial and challenging to conduct for surgical treatments. The SUcceSS trial is the first placebo-controlled trial of lumbar decompression surgery for symptomatic lumbar canal stenosis. The SUcceSS trial has experienced common issues affecting the implementation of randomised placebo-controlled surgery trials, accentuated by the COVID-19 pandemic. Using the SUcceSS trial as an example, we discuss key challenges and mitigation strategies specific to the conduct of a randomised placebo-controlled surgical trial. Overall, the key lessons learned were (i) involving key stakeholders early and throughout the trial design phase may increase clinician and patient willingness to participate in a placebo-controlled trial of surgical interventions, (ii) additional resources (e.g. budget, staff time) are likely required to successfully operationalise trials of this nature, (iii) the level of placebo fidelity, timing of randomisation relative to intervention delivery, and nuances of the surgical procedure under investigation should be considered carefully. Findings are based on one example of a placebo-controlled surgical trial; however, researchers may benefit from employing or building from the strategies described and lessons learned when designing or implementing future trials of this nature.

الملخص: تعد المملكة العربية السعودية من أعلى البلدان في معدلات السمنة والأمراض المرتبطة بها، وكذلك تعاني المملكة من نسب تدخين عالية بين الشباب والكبار وحتى المراهقين من الجنسين، حيث جاء في آخر إصدارات هيئة الصحة العامة أن السمنة كانت مسئولة عن أكثر من 70% من معدل الوفيات العام سنة 2020، وأن متوسط نسبة التدخين بالمملكة تصل إلى 20% تقريبا.يعد ''طب نمط الحياة'' من الفروع المستحدثة في الممارسة الطبية المستندة إلى البراهين العلمية والأبحاث الطبية، بل إن كثيرا من الأدلة الارشادية الحديثة تذكر نمط الحياة الصحي كأول خطوة على طريق العلاج لمعظم أمراض القلب والشرايين والأمراض المزمنة.في هذه الورقة العلمية نشرح تجربتنا -بإسهاب- في إنشاء عيادة لممارسة طب نمط الحياة وسط خدمات الرعاية الصحية الأولية والثانوية التي تتم بمركز طب الأسرة حي الوزارات، والذي يعتبر أكبر مراكز طب الأسرة بمدينة الأمير سلطان العسكرية الطبية.هذه قصة نجاح نعرض فيها الدروس المستفادة وكيفية استغلال الظروف والواقع المتاح، وأيضا نتعرض للتحديات والصعوبات، مع وضع خطة امتداد طموحة لخدمة المرضى المستهدفين، ونعتقد أن هذه التجربة قد تفيد غيرنا لمحاولة تكرارها في ظروف وأماكن خدمة صحية أخرى. Abstract: On an international level, for more than 30 years, Lifestyle Medicine (LSM) Practice has had a great impact on both health Promotion and disease prevention. A practice which on a national KSA level, we are in eager need to adopt, due to the high prevalence of chronic diseases and unhealthy lifestyles. The establishment of the LSM clinic inside the Wazarat Health Center (WHC) more than one and half year ago, was a great advancement towards offering very important preventive and promotive services for people in real high need to these underutilized main elements in Primary Health Care (PHC) features. We identified quality oriented Key Performance Indicators and the clinically important outcomes for our patients. Our initial data showed great achievement on both fronts. We are currently studying the satisfaction of our customers and working on improving their level of health awareness and help seeking behavior. Furthermore, we are looking to benchmark our results. From our pilot project in WHC, we are preparing for an expansion plan to branch out other Primary Care centers in the Riyadh area to serve more people, and we aim to share the experience with other similar services and within the PHC centers allover KSA.

Implant stability can be compromised by factors such as inadequate bone quality and infection, leading to potential implant failure. Ensuring implant stability and longevity is crucial for patient satisfaction and quality of life. In this multicenter, randomized, double-blind clinical trial, we assessed the impact of a bone bioactive liquid (BBL) on the Galaxy TS implant’s performance, stability, and osseointegration. We evaluated the impact stability, osseointegration, and pain levels using initial stability quotient (ISQ) measurements, CBCT scans, and pain assessment post-surgery. Surface analysis was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). In vitro studies examined the BBL’s effects on dental pulp pluripotent stem cells’ (DPPSCs’) osteogenesis and inflammation modulation in human macrophages. All implants successfully osseointegrated, as demonstrated by the results of our clinical and histological studies. The BBL-treated implants showed significantly lower pain scores by day 7 (p < 0.00001) and improved stability by day 30 (ISQ > 62.00 ± 0.59, p < 8 × 10−7). By day 60, CBCT scans revealed an increased bone area ratio in BBL-treated implants. AFM images demonstrated the BBL’s softening and wettability effect on implant surfaces. Furthermore, the BBL promoted DPPSCs’ osteogenesis and modulated inflammatory markers in human primary macrophages. This study presents compelling clinical and biological evidence that BBL treatment improves Galaxy TS implant stability, reduces pain, and enhances bone formation, possibly through surface tension modulation and immunomodulatory effects. This advancement holds promise for enhancing patient outcomes and implant longevity.

BackgroundPregnancy introduces significant physiological changes, notably impacting respiratory dynamics, especially during the second trimester. Data remain inconclusive about how body posture might influence lung function in pregnant women. We aimed to examine the impact of body position on slow vital capacity in pregnant women during their second trimester.MethodsThis observational study was carried out at King Khalid Hospital in Saudi Arabia, involving pregnant women in their second trimester, from 14 to 26 weeks of gestation. We utilized the KoKo® Legend Portable Office Spirometer to measure slow vital capacity (SVC) in both sitting and standing positions. Participants’ demographic details were recorded, ensuring a comprehensive analysis that accounted for age, BMI, and gestational age.Results136 pregnant women participated in this study, a paired-sample t-test revealed no statistically significant difference between sitting (M = 2.31, SD = 0.49) and standing (M = 2.33, SD = 0.5) positions, p = 0.24, However; the mean value of SVC in sitting position was significantly different between 4th month of pregnancy (M = 2.17, SD = 0.44) and 6th month of pregnancy (M = 2.45, SD = 0.48), p = 0.016.ConclusionThe performance of the SVC in both positions was not significantly affected. However, an increase in gestational age had a notable impact on SVC performance, particularly during sitting positions, due to the changes in respiratory physiology during pregnancy.

In 2022, the Wits Transplant Unit performed 57 liver transplants: 33/57 adult (58%) and 24/57 paediatric (42%) recipients. At the beginning of 2022, 28 candidates were on the adult waitlist. Forty-six candidates were added to the waitlist during the year. Sixty-five percent of waitlisted candidate were transplanted. Adult candidates remained on the waitlist for longer than previous years, with 52% of them waitlisted for less than one year before undergoing liver transplantation. There was a decrease in adult pretransplant mortality to 9% in 2021 from 25% in 2020. The most common aetiology in waitlist candidates was alcoholic steatohepatitis (ASH)/non-alcoholic steatohepatitis (NASH) (36%) and in recipients cholestatic (primary sclerosing cholangitis (PSC) and primary biliary sclerosis (PBC)) (40%). Most adult recipients received a deceased donor graft (79%). Unadjusted recipient one- and three-year survivals were 75% (95% confidence interval (CI) 65 - 83) and 74% (95% CI 65 - 81), respectively. In the paediatric population, the most common aetiologies for both pretransplant candidates and transplant recipients remained cholestatic disease and acute liver failure. There was a decrease in paediatric pretransplant mortality from 27% in 2017 to 6% in 2021. Unlike the adult cohort, most paediatric recipients received a living donor graft (79%). Unadjusted one-year and three-year survival rates were 85% (95% CI 75 - 92) and 68% (95% CI 56 - 77), respectively.

Background: The Wits Transplant Unit performed its first paediatric liver transplant in 2005. Initial experiences from the unit were published in 2012 and 2014. Since then, significant progress has been made in capacity-building the unit, improving outcomes and enhancing service delivery. This paper presents a broad overview and update of the unit’s 17-year experience. Methods: We conducted a retrospective review of all paediatric liver transplants performed in Johannesburg from 1 January 2005 to 31 December 2021 with a minimum one-year follow-up. Data were accessed from the Wits Donald Gordon Medical Centre Paediatric Liver Transplant Research Database (University of the Witwatersrand Human Research Ethics approval: M190749). The following data were collected: donor and recipient sociodemographic and clinical characteristics, details of transplant procedures, donor grafts and recipient outcomes (post-operative complications, graft and recipient survival). Results: A total of 270 transplants were performed during the review period. Two thirds of recipients (n=180, 67%) were younger than 5 years at time of transplant and half (n=135, 50%) received a living donor graft. The most common indication for liver transplant was biliary atresia, followed by acute liver failure. Unadjusted recipient survival was 80% (95% CI: 75-85%) at one year, and 68% (95% CI: 59-75%) at five years. Waiting list mortality decreased from 27.3% in 2017 to 5.9% in 2021. One hundred and fifty-four (57.0%) recipients experienced at least one type of intervention requiring surgical complication - the most common being biliary in nature (n = 91; 33.7%). Conclusion: Over last seventeen years, a sustainable paediatric liver transplantation service has been established in Johannesburg. Living donor, split and ABO incompatible liver transplants have been incorporated in response to the severe organ shortage in South Africa. However, our outcomes can be improved. Additionally, a national transplant initiative to coordinate timeous referrals and expand access to liver transplantation for children with severe acute and chronic liver failure is advised.

Background. Liver transplantation is the definitive management for severe acute liver failure refractory to supportive management, and end- stage chronic liver failure. Owing to a shortage of deceased liver donors, South Africa requires innovative techniques to broaden the donor pool. Objectives. This study evaluated the outcomes of the Wits Transplant Unit ABO-incompatible liver transplant (ABOi-LT) programme. Methods. This retrospective record review compared all adult and paediatric patients receiving ABO-compatible (ABOc) and ABO-incompatible (ABOi) liver transplants from January 2014 to December 2021 with a minimum one-year follow-up. Primary outcomes were recipient and graft survival and secondary outcomes included vascular, enteric and biliary complications, relook surgery, acute cellular rejection (ACR) and lenghth of hospital stay. Cox proportional hazards regression was performed to examine the effect of ABO-compatibility group on recipient and graft survival. The relationship between the ABO-compatibility group and categorical outcomes was assessed by binomial regression. Results. During the study period, 532 liver transplants were performed; 44/532 (8%) were ABOi of which 14/44 (32%) were paediatric and 30/44 (68%) adult recipients. Within the pediatric group, the proportion of transplants performed for acute liver failure was significantly higher in the ABOi group (7/14; 50%) compared with the ABOc group (33/207; 16%) (p=0.005). Comparable recipient and graft survival estimates were noted: one-, three- and five-year recipient survival in the ABOi group was 77% (95% confidence interval (CI) 44 - 92), 58% (95% CI 17 - 84) and 58% (95% CI 17 - 84) respectively. There were significantly increased relative risks of relook surgery for the ABOi group compared with the ABOc group, both overall (relative risk (RR) 1.74; 95% CI 1.10 - 2.75) and at 90 days (RR 2.28; 95% CI 1.27 - 4.11); and also, for pre-discharge bloodstream infection (BSI), (RR 1.84; 95% CI 1.11 - 3.06). In adults, there were significantly more acute indications for liver transplantation in the ABOi (10/30; 33%) compared with the ABOc group (26/281; 9%) (p=0.0007) with the most common cause being drug or toxin ingestion (16/36; 44%). For the ABOi group, recipient survival estimates (95% CI) at 1, 3 and 5 years were 71% (50 - 84), 63% (41 - 78) and 58% (37 - 75) which, as noted with complication rates, were similar between ABO groups. Conclusion. This study confirms ABOi-LT as a feasible option to increase the liver donor pool in this organ-depleted setting as recipient survival and complication rates were similar between ABO-compatibility groups.

The COVID-19 pandemic saw rapid adoption of telehealth, including remote patient monitoring (RPM). There is limited evidence about how patients and staff experience such services in New Zealand. This study aimed to understand the acceptability of the RPM experience, particularly for Maori and Pacific peoples, and identify strengths, gaps, and limitations to inform future delivery of services. A mixed methods study was undertaken between 4 July and 11 September 2022 in Auckland. We conducted telephone surveys with patients and semi-structured interviews with patients and staff. Survey, and clinical and administrative data were analysed descriptively using SPSS. Interviews were analysed using Directed Content Analysis. 121 patients took part in the study, with the majority identifying as Maori and Pacific peoples (40% and 17%, respectively). We conducted 75 telephone surveys (62% response rate), and 30 semi-structured interviews (18 patients and 12 staff). Patients reported feeling safe and reassured while in the RPM service and that they would be willing to use it again. Staff reflected on a range of potential benefits that RPM offers, identified learnings and would like to see a more widespread rollout of RPM. This study demonstrated that remote monitoring of patients infected with Covid-19 can provide an acceptable model for a culturally diverse population. Future research could focus on applying this model to other patient groups, such as people with chronic conditions.

Summary: Background: The multifactorial nature of inflammatory bowel disease (IBD), which manifests differently in individuals creates a need for a better understanding of the behaviour and pattern of the disease due to environmental factors. The current study aimed to study the changes in IBD behaviour, presentation, and characteristics in patients over the past two decades with a goal of improving patients’ diagnosis, management and outcomes. Methods: During a 6-month period (1/02/2022–30/07/2022), the information of patients with IBD who attended IBD outpatient clinics of 11 referral centre's in six countries was collected, and based on the first time of diagnosis with IBD, they were allocated as group A (those who were diagnosed more than 15 years ago), group B (those who were diagnosed with IBD between 5 and 15 years ago) and group C (IBD cases who diagnosed in recent 5 years). Then the most prevalent subtypes and characters of the disease are evaluated and compared to make clear if the presenting pattern and behaviour of the disease has changed in the last 2 decades. Findings: Overall 1430 patients with IBD including 1207 patients with ulcerative colitis (UC) (84.5%) and 205 patients with Crohn's disease (CD; 14.3%) included. Mean age of participants at the first time of diagnosis with IBD was 30 years. The extra-intestinal involvement of IBD in groups A and B was more prevalent in comparison with group C. Most of those in groups A & B had academic education but in group C, the most prevalent educational status was high school or diploma (P = 0.012). In contrast to groups A and B, the relative prevalence of medium socioeconomic level in group C had decreased (65%). Relative prevalence of UC subtypes was similar among groups A and B (extensive colitis as most prevalent) but in group C, the most prevalent subtype is left side colitis (38.17%). The most prevalent subtype of CD in groups A and B was ileocolic involvement while in group C, upper GI involvement is significantly increased. The rate of food sensitivity among groups A and B was more than group C (P = 0.00001). The relative prevalence of patients with no flare has increased with a steady slope (P

Key Clinical Message Abdominal migraine (AM) is a prevalent pediatric condition that rarely affects adults. Multiple diagnostic criteria have been established, but in general, AM is characterized by unprovoked episodes of acute central abdominal pain with migrainous characteristics and periods of respite. Recurrent stomach pain is a prevalent symptom globally, with a significant portion of cases falling under the category of functional gastrointestinal disorders (FGIDs) due to the absence of identified biological causes. There is a notable prevalence of migraines among individuals with a family history of the condition, indicating a genetic predisposition. A descriptive report has been prepared on the participant who had AM associated with acute watery diarrhea (AWD) on January 2023. The patient's parents had given written informed consent for publishing this case report. In this case report, we present the clinical scenario of a 12‐year‐old male child who experienced AM symptoms alongside a history of absence seizures. The child presented with episodes of abdominal pain and AWD. Despite extensive investigation and treatment, there was no improvement in abdominal pain. However, after 1 week of oral valproic acid administration, the patient remained symptom‐free during the follow‐up period. Dehydration, along with other factors, has been identified as a triggering factor for AM. Acute watery diarrhea has the potential to disrupt the normal functioning of the gastrointestinal system, and dehydration may lead to subsequent abdominal symptoms.

Summary: Background: Childhood obesity is a pressing health crisis of epidemic proportions. Bariatric surgery (BS) is an effective weight loss solution however its role in the paediatric population is contentious owing to the paucity of weight specific and generalised health outcomes. This systematic review and meta-analysis aimed to assess the impact of paediatric BS on bone health. Methods: This prospectively registered systematic review (PROSPERO ID: CRD42023432035) was performed in accordance with PRISMA guidelines. We searched MEDLINE (1946–1928 September 2023), EMBASE (1947–1928 September 2023) via the Ovid platform, and the Cochrane Review Library to identify scientific publications reporting bone outcome measures in patients under the age of 18 years who underwent BS. Meta-analysis was undertaken on post-operative weight and bone parameters in paediatric patients following BS. Outcomes were reported as weighted or standardized mean difference with 95 percent confidence intervals. Subgroup analysis by intervention, quality scoring and risk of bias were assessed. Findings: Twelve studies with 681 patients across 5 countries (mean age 17 ± 0.57 years) were included. The quality of included studies was rated as high and there was substantial between-study heterogeneity for most factors included in the meta-analysis (I2 from 0% to 99.1%). Patients underwent Roux-en-Y gastric bypass (RYGB, n = 216), sleeve gastrectomy (SG, n = 257), gastric band (n = 184) or intragastric balloon placement (n = 24). BS was associated with significant weight reduction, body mass index (BMI) −12.7 kg/m2 (95% CI −14.5 to −10.9, p

Abstract Background Patient and public involvement (PPI) ensures that research is designed and conducted in a manner that is most beneficial to the individuals whom it will impact. It has an undisputed place in applied research and is required by many funding bodies. However, PPI in statistical methodology research is more challenging and work is needed to identify where and how patients and the public can meaningfully input in this area. Methods A descriptive cross-sectional research study was conducted using an online questionnaire, which asked statistical methodologists about themselves and their experience conducting PPI, either to inform a grant application or during a funded statistical methodology project. The survey included both closed-text responses, which were reported using summary statistics, and open-ended questions for which common themes were identified. Results 119 complete responses were recorded. Individuals who completed the survey displayed an even range of ages, career lengths and positions, with the majority working in academia. 40.3% of participants reported undertaking PPI to inform a grant application and the majority reported that the inclusion of PPI was received positively by the funder. Only 21.0% of participants reported undertaking PPI during a methodological project. 31.0% of individuals thought that PPI was “very” or “extremely” relevant to statistical methodology research, with 45.5% responding “somewhat” and 24.4% answering “not at all” or “not very”. Arguments for including PPI were that it can provide the motivation for research and shape the research question. Negative opinions included that it is too technical for the public to understand, so they cannot have a meaningful impact. Conclusions This survey found that the views of statistical methodologists on the inclusion of PPI in their research are varied, with some individuals having particularly strong opinions, both positive and negative. Whilst this is clearly a divisive topic, one commonly identified theme was that many researchers are willing to try and incorporate meaningful PPI into their research but would feel more confident if they had access to resources such as specialised training, guidelines, and case studies.

Abstract Background The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors — age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death. Methods Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care. Results The external validation showed the risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Furthermore, accounting for the competing risk of death improved prediction. Using criteria of 5 years ≥ 5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. Hybrid criteria of predicted risk using the competing risks model and ACR ≥ 70 mg/mmol should be used in referrals to secondary care. Conclusions The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce unnecessary referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities.

Abstract Background Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. Methods The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. Discussion This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. Trial registration EudraCT number: 2020–003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

In Egypt, hepatocellular carcinoma (HCC) is the most prevalent cancer in men and the second most prevalent cancer in women. In addition, Egypt has one of the highest prevalences of hepatitis C infection in the world. The aim of the present work was to study the potential role of the 16 KIR genes in the outcome of individuals with chronic hepatitis C virus (HCV) infection in Egypt. The study was carried out under an IRB-approved protocol. Sequence-Specific-Primer-PCR (SSP-PCR) was used for KIR genotyping of germline DNA extracted from peripheral blood leukocytes or from the non-tumor liver of 83 HCC patients, 100 patients with chronic HCV infection without HCC, and 120 matched healthy controls. Out of the 83 HCC patients, only 7 (8.4%) were treated by interferon and/or interferon Ribavirin combination, while for the remaining patients 50 (60.2%) received no prior HCV therapy and 26 (31.3%) were treated with direct-acting antiviral (DAA). Our results showed that KIR haplotype AA that contains more inhibitory KIR genes and fewer activating genes was observed with a significantly lower frequency in HCC patients (6/83, 7.2%) compared to chronic HCV (27/100, 27.0%) (p = 0.0005, OR = 0.21 [0.08–0.53]) and healthy controls (29/119, 24.4%) (p = 0.001, OR = 0.24 [0.09–0.61]). In addition, the frequency of genotype 6 (G6) which contains all the KIR genes was significantly high in the HCC patients (16/83, 19.3%) compared to chronic HCV (8/100, 8.0%) (p = 0.02, OR = 2.7 [1.11–6.79]) and healthy controls (8/119, 6.7%) (p = 0.006, OR = 3.31 [1.35–8.16]). Activating KIR genes 2DS1 and 3DS1 were significantly higher in HCC patients (48/83, 57.83% and 45/83, 54.22%) compared to the chronic HCV patients (36/100, 36% and 34/100, 34%), p = 0.028, 0.027, respectively. Our results are contrary to a prior work on HCC from patients with HCV who were mostly treated by interferon-based therapies. In conclusion, KIR haplotype AA has an important role in host defense against HCC progression especially in patients treated by DAA, suggesting an important role of the KIR genotype status on the outcome of chronic HCV infection.

Objectives: To determine the frequency of bacterial infections and their sensitivity to various antibiotics in paediatric cancer patients having chemotherapy-induced neutropenia. Study Design: Cross-sectional study Place and Duration of Study: Paediatric Oncology ward, Combined Military Hospital, Rawalpindi Pakistan, from Jul 2018 to Jan 2019. Methodology: A total of 205 children aged one year to 12 years undergoing chemotherapy and having neutropenic fever were included. Complete history, full physical examination and related blood, microbiological and radiological investigations were undertaken. Antibiotics were given as per protocol. Results: In our study, the bacterial infections in paediatric cancer patients with chemotherapy-induced neutropenia was found in 45(21.95%) patients. Of these, gram-positive organisms were found in 25(55.5%) patients and gram-negative in 20(44.4%). Conclusion: The frequency of bacterial infections in paediatric patients with chemotherapy-induced febrile neutropenia is quite high, with a high percentage of gram-positive bacteria.

Abstract Background Exercise for the prevention of low back pain recurrences is recommended, but under-researched. The effectiveness and cost-effectiveness of a walking program for preventing low back pain recurrence remains unknown. This a priori statistical analysis plan describes the methods of analysis for the WalkBack trial. Methods WalkBack is a prospectively registered, pragmatic, randomised controlled trial. The aim is to investigate the effectiveness and cost-effectiveness of a 6-month progressive and individualised walking and education program (intervention) for the prevention of low back pain recurrences, compared to a no-treatment control group. The primary outcome is days to the first recurrence of an episode of activity-limiting low back pain. Key secondary outcomes include days to any recurrence of low back pain, days to a care-seeking recurrence of low back pain, disability level, health-related quality of life, costs associated with low back pain and adverse events. All participants will be followed for a minimum of 12 months. Analysis will follow the intention-to-treat principle. Cox regression is planned to assess the effects for the outcomes of time to activity-limiting, minimal and care-seeking recurrence. Hazard ratios and median survival times with 95% confidence intervals will be calculated. The effect of the intervention on continuous outcomes will be estimated with repeated-measure linear mixed models. An economic evaluation will be performed from the societal perspective for recurrence prevented (yes/no) and quality-adjusted life years. The proportion of adverse events between groups will be compared using Fisher’s exact test. Discussion The WalkBack trial will provide evidence on the effectiveness and cost-effectiveness of a walking intervention to prevent low back pain recurrences. This statistical analysis plan provides transparency on the analysis of the trial. Trial registration WalkBack - Effectiveness and cost-effectiveness of a progressive individualised walking and education program for the prevention of a recurrence of low back pain. ACTRN12619001134112 . Date Registered: 14/08/2019.

Background and Objectives: Human papillomavirus (HPV) was previously investigated in lung cancer with wide inter-geographic discrepancies. p16INK4a has been used as a surrogate for detecting high-risk HPV (HR-HPV) in some cancer types. This study assessed the evidence of HPV in non-small-cell lung cancer (NSCLC) among Jordanian patients, investigated the expression of p16INK4a, and evaluated its prognostic value and association with HPV status. Materials and Methods: The archived samples of 100 patients were used. HPV DNA detection was performed by real-time polymerase chain reaction (RT-PCR). p16INK4a expression was assessed by immunohistochemistry (IHC). The Eighth American Joint Committee on Cancer protocol (AJCC) of head and neck cancer criteria were applied to evaluate p16INK4a positivity considering a moderate/strong nuclear/cytoplasmic expression intensity with a distribution in ≥75% of cells as positive. Results: HPV DNA was detected in 5% of NSCLC cases. Three positive cases showed HR-HPV subtypes (16, 18, 52), and two cases showed the probable HR-HPV 26 subtype. p16INK4a expression was positive in 20 (20%) NSCLC cases. None of the HPV-positive tumors were positive for p16INK4a expression. A statistically significant association was identified between p16INK4a expression and the pathological stage (p = 0.029) but not with other variables. No survival impact of p16INK4a expression was detected in NSCLC cases as a group; however, it showed a statistically significant association with overall survival (OS) in squamous cell carcinoma (SqCC) cases (p = 0.033). Conclusions: This is the first study to assess HPV and p16INK4a expression in a Jordanian population. HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 INK4a reliability as a surrogate marker for HPV infection in lung cancer must be revisited.

Abstract Medication‐related osteonecrosis of the jaws (MRONJ) is a serious debilitating disease resulting from long‐term treatment with Antiresorptive drugs such as Bisphosphonates or Denosumab, which significantly affects patients' quality of life. A 43‐year‐old female patient with stage 4 breast cancer and treated with Zoledronic Acid for bone metastases was referred to the Department of Oral Medicine at the Faculty of Dentistry, Damascus University. The main complaint was pain in the right maxilla. Intraoral examination showed an exposure of necrotic bone in the right maxillary region with presence of purulent exudate. The treatment plan was discussed with the patient. Treatment included resection of all necrotic bone and application of Advanced platelet‐rich fibrin (A‐PRF) clots and membranes. Follow‐up and outcome were conducted by clinical measures to assess healing and recurrence (6‐month follow‐up). Topical treatment with A‐PRF demonstrated a reduction in pain and resulted in complete wound healing within 30 days. A‐PRF stimulates the release of growth factors and chemotaxis involved in tissue repair mechanisms. This method seemed to be effective in the treatment of MRONJ.

Key Clinical Message Primary intestinal lymphangiectasia is a rare disease that affects children and young adults, causing mainly gastrointestinal disorders that lead to edema and immunologic abnormalities. The majority of patients typically present bilateral lower limb edema, along with pericarditis, pleural effusion, or chylous ascites. The goal of the treatment is to restrict the consumption of long‐chain fats and administer a formula that includes protein and medium‐chain triglycerides. Here, we report 11‐year‐old Syrian girl presented to the hospital with 2 years history of diarrhea and generalized edema. Furthermore, investigation showed ascites and pleural effusion. The disease was detected by several biopsies from duodenum that showed dilation of the lymph vessels within the lamina propria without any evidence for inflammation. She was managed by modifying her diet and albumin transfusion, which caused significant improvement in the child's condition.

Key clinical message Congenital anorectal malformation (ARM) is a diverse group of anomalies affecting the development of the anal and rectal regions, with an estimated incidence of one in every 5000 live births. The colostomy is commonly performed as part of the staged management of children with ARM to prevent complications. However, the presence of acute watery diarrhea in children with ARM and colostomy poses significant management challenges due to the altered anatomy and physiology affecting stool regulation and absorption, exacerbated by various factors including infections, dietary issues, medication side effects, and underlying gastrointestinal complications.This case study explores the complexities involved in managing acute watery diarrhea in children with congenital ARM and colostomy. A comprehensive literature review was conducted to examine the existing evidence on the subject. The study highlights the multidisciplinary approach required, involving pediatricians, surgeons, and other specialists, to provide comprehensive care and support for these children. Effective management of acute watery diarrhea in children with congenital ARM and colostomy necessitates collaboration between pediatricians and surgeons. Pediatricians play a crucial role in assessing hydration status, monitoring electrolyte balance, and providing appropriate fluid and nutritional management. Surgeons address the surgical aspects of care and coordinate interventions with the management of acute diarrhea. The study underscores the importance of a multidisciplinary approach to deliver comprehensive care, optimize outcomes, and improve the quality of life for affected children. The management of acute watery diarrhea in children with congenital ARM and colostomy presents significant challenges due to the complex interplay of anatomical, physiological, and clinical factors. A multidisciplinary approach involving pediatricians, surgeons, and other specialists is vital for providing comprehensive care and support. This case study emphasizes the need for further research, guidelines, and collaborative efforts to enhance the management strategies for this vulnerable population.

Abstract Background Fatal blast injuries are generally reported as a consequence of explosions, mainly in terrorist events, work-related detonations, or domestic settings. Although quite rare, blast injuries of high kinetic energy can be seen in tyre blowouts and are very dangerous and potentially lethal because of their unpredictability. This phenomenon is rarely reported in the existing forensic literature. The aim of this study was to report two cases of fatal truck tyre bursts and to discuss the mechanisms leading to the burst and the pattern of injuries. Case presentations Case 1 was of a 58-year-old truck driver man who was standing nearby a detached tyre that was being inflated in a repair shop when the burst occurred. The tyre struck him in the face and threw him. The medicolegal autopsy showed a right periorbital haematoma, a large wound of the left parietal scalp, a diffuse subarachnoid haemorrhage, an atlanto-occipital dislocation, a fracture of the hyoid bone, multiple rib fractures, and lacerations of the ascending aorta and the pulmonary arteries. Case 2 involved a young man of 24-year-old, a worker in a tyre repair shop, who was inflating a truck’s tyre when it burst violently. The injuries sustained included bleeding from the right ear, fractures of the facial bones, a left hemispheric subdural haematoma associated with the fracture of the skull base, a rib fracture, and diffuse areas of contusions to the lungs. Toxicological analyses were negative in both cases. Conclusion Fatalities related to tyre blowout accidents are uncommon. The mechanisms leading to a blowout can be mechanical or chemical in origin, and the main danger of a burst often occurs when air enters the tyre during inflation. Internal damage caused by the pressure waves of the blast often exceeds what would be expected based on external signs alone.

Abstract Background General medical practitioner (GP) recruitment and subsequent data collection in clinical practice are challenging and may limit successful completion of a large-scale trial. The aim of this study was to assess the feasibility of undertaking a cluster randomised controlled trial to test an intervention to reduce non-indicated imaging for low back pain in general medical practice. Methods A pilot cluster randomised controlled trial was performed, with recruitment of GPs and randomisation of GP clinics. All GPs attended a training session and were asked to record low back pain codes in electronic medical records for any low back pain presentations. Intervention group GPs were trained in the use of a patient education booklet to be used during low back pain patient visits. Control group GPs provided usual care. Outcomes for the proposed trial were collected to determine feasibility. GP recruitment was assessed as the proportion of GPs approached who consented to participate. Low back pain imaging outcomes were collected from electronic medical records (counts of patients presenting with low back pain) and from Australian healthcare administrative (Medicare) data (counts of imaging use). GP compliance with study procedures was assessed and qualitative data reported. Results Thirty-four GP clinics were approached, with four participating (12%). At these clinics, 13/19 (68%) GPs consented to participate, and 10/19 (53%) started the study. Outcome data were collected from medical records for all GPs. Three GPs (30%) withdrew consent to access Medicare data, limiting reporting of imaging outcome measures. Three GPs (30%) self-reported low compliance entering low back pain codes. Conclusions This pilot cluster randomised controlled trial demonstrated the feasibility of many aspects of a full-scale effectiveness study, while also identifying a number of challenges that need to be resolved. Recommendations related to GP recruitment, study compliance, data collection, and outcome measures were made to increase the success of a future trial. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR), Trial ID: ACTRN12619000991112; Registered 11 July 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376973

Abstract Background Patient and Public Involvement (PPI) in research aims to improve the quality, relevance and appropriateness of research. PPI has an established role in clinical research where there is evidence of benefit, and where policymakers and funders place continued emphasis on its inclusion. However, for preclinical research, PPI has not yet achieved the same level of integration. As more researchers, including our team, aim to include PPI in preclinical research, the development of an evidence‐based approach is important. Therefore, this scoping review aimed to identify and map studies where PPI has been used in preclinical research and develop principles that can be applied in other projects. Methods A scoping review was conducted to search the literature in Medline (PubMed), EMBASE, CINAHL, PsycInfo and Web of Science Core Collection to identify applied examples of preclinical PPI. Two independent reviewers conducted study selection and data extraction separately. Data were extracted relating to PPI in terms of (i) rationale and aims, (ii) approach used, (iii) benefits and challenges, (iv) impact and evaluation and (v) learning opportunities for preclinical PPI. Findings were reviewed collaboratively by PPI contributors and the research team to identify principles that could be applied to other projects. Results Nine studies were included in the final review with the majority of included studies reporting PPI to improve the relevance of their research, using approaches such as PPI advisory panels and workshops. Researchers report several benefits and challenges, although evidence of formal evaluation is limited. Conclusion Although currently there are few examples of preclinical research studies reporting empirical PPI activity, their findings may support those aiming to use PPI in preclinical research. Through collaborative analysis of the scoping review findings, several principles were developed that may be useful for other preclinical researchers. Patient or Public Contribution This study was conducted as part of a broader project aiming to develop an evidence base for preclinical PPI that draws on a 5‐year preclinical research programme focused on the development of advanced biomaterials for spinal cord repair as a case study. A PPI Advisory Panel comprising seriously injured rugby players, clinicians, preclinical researchers and PPI facilitators collaborated as co‐authors on the conceptualization, execution and writing of this review, including refining the findings into the set of principles reported here.

Tiffany M Pouldar,1 Dermot P Maher,2 Alexander W Betz,1 Jeffrey J Wiegers,1 Jeremy A Friedman,1 Sameer S Zaidi,1 Ali Rejali,3 Hai P Tran,3 Roya Yumul,1,4 Charles Louy1 1Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; 2Department of Anesthesiology and Critical Care Medicine, Pain Medicine Division, Johns Hopkins Hospital, Baltimore, MD, 21205, USA; 3Department of Pharmacy, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; 4Department of Anesthesiology, David Geffen School of Medicine-UCLA, Los Angeles, CA, 90095, USACorrespondence: Charles Louy, Department of Anesthesiology, Cedars-Sinai Medical Center, 8700 Beverly Blvd #8211, Los Angeles, CA, 90048, USA, Tel +1 310-423-5841, Email CHLOUY@gmail.comObjective: There has been increasing use of ketamine at subanesthetic doses as an adjunct to opioids in perioperative pain management. There are several known adverse drug effects (ADEs) associated with ketamine. However, the incidence of ADEs with ketamine infusions with patient-controlled analgesia (PCA) boluses compared with combined opioid and ketamine PCAs is not well described. The objectives of this study were to compare the incidence and type of ADEs in postoperative spine surgery patients on ketamine infusions with as-needed PCA boluses to patients on combined opioid and ketamine PCAs.Methods: The medical records of patients who underwent spine surgery between March 2016 and March 2020 who were postoperatively treated with a ketamine infusion and as-needed PCA boluses and parenteral opioids or treated with a combined opioid and ketamine PCA were reviewed. Perioperative information including patient characteristics and preoperative morphine equivalent daily dose (MEDD) were collected. Patient charts were reviewed for ADEs including psychological and neurological side effects, nausea, and new-onset tachycardia.Results: A total of 315 patients met the inclusion criteria and were included in the final analysis. Of these patients, 121 experienced at least one ADE (38%). Sixteen of the 68 ketamine infusion with PCA bolus patients (24%), 77 of the 203 hydromorphone and ketamine patients (38%), and 28 of the 44 morphine and ketamine patients (64%) experienced an ADE [p< 0.01]. In patients with preoperative MEDD ≤ 90, nausea was the only ADE that differed significantly among the three groups.Conclusion: This retrospective analysis suggests that postoperative spine patients treated with a ketamine infusion with as-needed PCA boluses and parenteral opioids were associated with fewer ADEs when compared to an intravenous combined opioid and ketamine PCA. In patients with preoperative MEDD ≤ 90, nausea with and without emesis was the only ADE that showed statistically significant difference amongst the three groups.Keywords: ketamine, opioid, patient-controlled analgesia, adverse drug effects, postoperative, retrospective

Abstract Background Congenital diaphragmatic hernia (CDH) is a congenital malformation of the diaphragm, resulting in the herniation of the abdominal organs into the thoracic cavity. If not properly diagnosed before or at birth, CDH represents a life-threatening pathology in infants and a major cause of death. We present a fatal case of congenital diaphragmatic hernia corresponding to Bochdalek hernia, discovered incidentally during a sudden death’s autopsy of an infant. To achieve a better view of the range of these anomalies, we also conducted a literature review on this subject describing the pathogenesis, manifestations, diagnosis, and autopsy contribution to addressing these CDH. Case presentation The case involved a 4-month-old female infant who presented sudden respiratory difficulties after breastfeeding. External examination found marked cyanosis with no evidence of trauma. Upon opening the chest cavity, the stomach, markedly distended, was occupying much of the left pleural cavity. The left lung was compressed and displaced superiorly, and the heart was also compressed and deviated to the right. This mediastinal deviation was due to an ascension of the stomach into the chest cavity through a 2 × 1.5 cm defect in the posterior left hemidiaphragm. Further examination remarked an ecchymotic appearance of the stomach portion entrapped in the hernia defect suggesting recent strangulation of the stomach. The lungs showed atelectasis with signs of pulmonary infection in the histology study. Conclusions CDH might be considered uncommon and not always mentioned in the list of sudden death in infant causes. Forensic pathologists should know of this malformation in order to apply the best autopsy techniques and thus allow positive feedback to pediatricians considering the possible legal implications.

Key Clinical Message Hydatid disease is a zoonotic disease endemic in developing regions. It is usually caused by infection with the tapeworm Echinococcus granulosus due to contaminated food or drinks or by close contact with dogs. The lungs are the second most affected organ (25%) after the liver (>65%). Cyst rupture is the most frequent complication. Enlarging pulmonary cysts are more vulnerable to rupture, with rupturing in the bronchial tree being the most common (20%–40%). Hydropneumothorax is a consequence of complete cyst rupture into the pleural cavity and occurs in rare cases (2%–4%). Superinfection is a common complication of the ruptured cyst, which might lead to empyema. A 26‐year‐old male presented to our clinic with dyspnea that had progressed recently and made him unable to walk a few meters. He had a history of cough and exertional dyspnea and was examined by three different clinics without performing a chest X‐Ray. Physical examination revealed fever and a sick appearance. Chest X‐ray revealed complete pneumothorax with an air‐fluid level in the left hemithorax. Computerized tomography demonstrated two cysts, and one of them was ruptured, causing hydropneumothorax and empyema. The patient was treated with surgery, and follow‐up showed recovery with a fully re‐expanded lung. Rupture of pulmonary hydatid cyst is seen in the most of cases, the clinicians must be aware of such presentation and management of the pulmonary hydatid disease.

Mixed sex cord–stromal tumors, which consist of poorly differentiated Sertoli cells and Leydig cells and juvenile granulosa cell tumor tissue, are extremely rare. Most of these tumors are unilateral and stage I at the time of diagnosis; nonetheless, according to the available relevant English-language literature, these tumors maintain a malignant potential. We herein report a case involving a 15-year-old girl diagnosed with a mixed sex cord–stromal tumor (gynandroblastoma with juvenile granulosa cell tumor component). Left salpingo-oophorectomy was initially performed, and the diagnosis of a juvenile granulosa cell tumor was established. Right salpingo-oophorectomy was performed 1 year later, at which time the specimen showed a different growth pattern involving epithelioid cells and tubules, resembling a Sertoli–Leydig cell tumor. Immunohistochemical staining was performed and the specimen was compared with that obtained 1 year earlier. We concluded that the tumors were linked and most likely constituted a gynandroblastoma (mixed form of sex cord–stromal tumor). Although this is an extremely uncommon ovarian tumor, it should be considered when diverse tumor morphology is identified. Bilateral metachronous involvement of the ovaries is possible. The grade of the Sertoli–Leydig cell component may influence the prognosis of such a tumor.

Summary: Background: Non-alcoholic fatty liver disease (NAFLD) is a fast-growing, underdiagnosed, epidemic. We hypothesise that obesity-related inflammation compromises adipose tissue functions, preventing efficient fat storage, and thus driving ectopic fat accumulation into the liver. Methods: To identify adipose-based mechanisms and potential serum biomarker candidates (SBCs) for NAFLD, we utilise dual-tissue RNA-sequencing (RNA-seq) data in adipose tissue and liver, paired with histology-based NAFLD diagnosis, from the same individuals in a cohort of obese individuals. We first scan for genes that are differentially expressed (DE) for NAFLD in obese individuals’ subcutaneous adipose tissue but not in their liver; encode proteins secreted to serum; and show preferential adipose expression. Then the identified genes are filtered to key adipose-origin NAFLD genes by best subset analysis, knockdown experiments during human preadipocyte differentiation, recombinant protein treatment experiments in human liver HepG2 cells, and genetic analysis. Findings: We discover a set of genes, including 10 SBCs, that may modulate NAFLD pathogenesis by impacting adipose tissue function. Based on best subset analysis, we further follow-up on two SBCs CCDC80 and SOD3 by knockdown in human preadipocytes and subsequent differentiation experiments, which show that they modulate crucial adipogenesis genes, LPL, SREBPF1, and LEP. We also show that treatment of the liver HepG2 cells with the CCDC80 and SOD3 recombinant proteins impacts genes related to steatosis and lipid processing, including PPARA, NFE2L2, and RNF128. Finally, utilizing the adipose NAFLD DE gene cis-regulatory variants associated with serum triglycerides (TGs) in extensive genome-wide association studies (GWASs), we demonstrate a unidirectional effect of serum TGs on NAFLD with Mendelian Randomization (MR) analysis. We also demonstrate that a single SNP regulating one of the SBC genes, rs2845885, produces a significant MR result by itself. This supports the conclusion that genetically regulated adipose expression of the NAFLD DE genes may contribute to NAFLD through changes in serum TG levels. Interpretation: Our results from the dual-tissue transcriptomics screening improve the understanding of obesity-related NAFLD by providing a targeted set of 10 adipose tissue-active genes as new serum biomarker candidates for the currently grossly underdiagnosed fatty liver disease. Funding: The work was supported by NIH grants R01HG010505 and R01DK132775. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The KOBS study (J. P.) was supported by the Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (EVO/VTR grants 2005–2019), and the Academy of Finland grant (Contract no. 138006). This study was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant No. 802825 to M. U. K.). K. H. P. was funded by the Academy of Finland (grant numbers 272376, 266286, 314383, and 335443), the Finnish Medical Foundation, Gyllenberg Foundation, Novo Nordisk Foundation (grant numbers NNF10OC1013354, NNF17OC0027232, and NNF20OC0060547), Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, University of Helsinki, and Helsinki University Hospital and Government Research Funds. I. S. was funded by the Instrumentarium Science Foundation. Personal grants to U. T. A. were received from the Matti and Vappu Maukonen Foundation, Ella och Georg Ehrnrooths Stiftelse and the Finnish Foundation for Cardiovascular Research.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a complex and serious form of heart failure caused by the accumulation of transthyretin amyloid protein in the heart muscle. Variable symptoms of ATTR-CM can lead to a delayed diagnosis. Recognizing the diagnostic indicators is crucial to promptly detect this condition. A targeted literature review was conducted to examine the latest international consensus recommendations on a comprehensive diagnosis of ATTR-CM. Additionally, a panel consisting of nuclear medicine expert consultants (n = 10) and nuclear imaging technicians (n = 2) convened virtually from the Kingdom of Saudi Arabia (KSA) to formulate best practices for ATTR-CM diagnosis. The panel reached a consensus on a standard diagnostic pathway for ATTR-CM, which commences by evaluating the presence of clinical red flags and initiating a cardiac workup to assess the patient’s echocardiogram. Cardiac magnetic resonance imaging may be needed, in uncertain cases. When there is a high suspicion of ATTR-CM, patients undergo nuclear scintigraphy and hematologic tests to rule out primary or light-chain amyloidosis. The expert panel emphasized that implementing best practices will support healthcare professionals in KSA to improve their ability to detect and diagnose ATTR-CM more accurately and promptly. Diagnosing ATTR-CM accurately and early can reduce morbidity and mortality rates through appropriate treatment.

Abstract Background Although mass vaccination has reduced the severity of COVID-19, mortality is still high among hospitalized patients. Being a sepsis-like disease, an anti-inflammatory drug as atorvastatin would reduce mortality and severity in COVID-19. Methods We designed a randomized clinical trial that recruited 220 COVID-19 patients admitted in the COVID-19 isolation hospital at Mansoura University, Egypt. One hundred ten cases were assigned to receive 40 mg atorvastatin once daily for 28 days, and 110 were assigned to receive placebo. Delta Pharm company supported the study with the drug and the placebo, which mimics the drug as regards the drug package, the tablet color, consistency, and size. All patients received the standard treatment as per the hospital protocol. The Institutional Review Board approval and the informed consent from all participants were obtained. The primary outcome is the 28-day all-cause mortality. Additionally, we will collect the in-hospital mortality, the need for mechanical ventilation, time to clinical improvement, in-hospital thrombo-embolic events, acute kidney injury, and the hospital and the intensive care duration of stay. We plan to follow the patients up for 6 months for reporting mortality and long-term neurological, psychological, and respiratory consequences. We will report the un-adjusted 28-mortality using χ 2 . Then, we will report the adjusted odds ratio with a pre-planned multiple logistic regression model. We will report our results using the point estimate and the 95% confidence interval and the P-value. Discussion The additional issue that we would like to discuss is the added workload on the clinicians and the allied healthcare workers who performed research at the time of the pandemic. Therefore, doing research at the pandemic era was, indeed, challenging. Trial registration The study was registered at the Clinical Trial Registry ( NCT04952350 ) on July 1st, 2021.

Abstract Background Imaging is overused in the management of low back pain, resulting in overdiagnosis, increased healthcare utilisation, and increased costs. Few effective interventions to decrease inappropriate use have been developed and have typically not been developed using behaviour change theory. An intervention to reduce non-indicated imaging for low back pain was developed using behavioural change theory, incorporating a novel low back pain management booklet to facilitate patient education and reassurance. The aim of this study was to assess the adoption and feasibility of use of the developed intervention within clinical practice and to determine appropriate implementation strategies to address identified barriers to use. Methods Fourteen general medical practitioners were recruited and trained to use the booklet with low back pain patients over a minimum 5-month period. Quantitative data on use of the booklet were collected and analysed descriptively. Qualitative data on use of the booklet and training session were collected in general medical practitioner interviews and thematically analysed. Barriers to use were identified and mapped to suitable implementation strategies using the Behaviour Change Wheel. Results Practitioners used the booklet with 73 patients. The booklet was used with 63% of patients presenting with low back pain. Facilitators for using the booklet included patient’s requesting imaging and lower practitioner confidence in managing low back pain. Barriers included accessible storage and remembering to use the booklet. Implementation strategies were identified to increase adoption and feasibility of use, including development of a digital version of the booklet. Conclusions General medical practitioners reported that the low back pain management booklet and training were useful for clinical practice, particularly with patients requesting imaging. Barriers to use were identified and implementation strategies to address these barriers will be incorporated into future effectiveness studies. This study forms one of a series of studies to thoroughly develop and test an intervention to reduce non-indicated imaging for low back pain; a successful intervention would decrease healthcare costs and improve patient management.

Summary: Background: The accuracy of diagnostic tests available in primary care to identify the disc, sacroiliac joint, and facet joint as the source of low back pain is uncertain. Methods: Systematic review of diagnostic tests available in primary care. MEDLINE, CINAHL, and EMBASE were searched between March 2006 and 25th January 2023. Pairs of reviewers independently screened all studies, extracted data, and assessed risk of bias using QUADAS-2. Pooling was performed for homogenous studies. Positive likelihood ratios (+LR) ≥2 and negative likelihood ratios (−LR) ≤0.5 were considered informative. This review is registered with PROSPERO (CRD42020169828). Findings: We included 62 studies: 35 investigated the disc, 14 the facet joint, 11 the sacroiliac joint, and 2 investigated all three structures in patients with persistent low back pain. For risk of bias, the domain ‘reference standard’ scored worst, however approximately half the studies were of low risk of bias for every other domain. For the disc, pooling demonstrated MRI findings of disc degeneration and annular fissure resulted in informative +LRs: 2.53 (95% CI: 1.57–4.07) and 2.88 (95% CI: 2.02–4.10) and −LRs: 0.15 (95% CI: 0.09–0.24) and 0.24 (95% CI: 0.10–0.55) respectively. Pooled results for Modic type 1, Modic type 2, and HIZ on MRI, and centralisation phenomenon yielded informative +LRs: 10.00 (95% CI: 4.20–23.82), 8.03 (95% CI: 3.23–19.97), 3.10 (95% CI: 2.27–4.25), and 3.06 (95% CI: 1.44–6.50) respectively, but uninformative −LRs: 0.84 (95% CI: 0.74–0.96), 0.88 (95% CI: 0.80–0.96), 0.61 (95% CI: 0.48–0.77), and 0.66 (95% CI: 0.52–0.84) respectively. For the facet joint, pooling demonstrated facet joint uptake on SPECT resulted in informative +LRs: 2.80 (95% CI: 1.82–4.31) and −LRs: 0.44 (95% CI: 0.25–0.77). For the sacroiliac joint, a combination of pain provocation tests and absence of midline low back pain resulted in informative +LRs of 2.41 (95% CI: 1.89–3.07) and 2.44 (95% CI: 1.50–3.98) and −LRs of 0.35 (95% CI: 0.12–1.01) and 0.31 (95% CI: 0.21–0.47) respectively. Radionuclide imaging yielded an informative +LR 7.33 (95% CI: 1.42–37.80) but an uninformative −LR 0.74 (95% CI: 0.41–1.34). Interpretation: There are informative diagnostic tests for the disc, sacroiliac joint, and facet joint (only one test). The evidence suggests a diagnosis may be possible for some patients with low back pain, potentially guiding targeted and specific treatment approaches. Funding: There was no funding for this study.

Abstract Epithelioid trophoblastic tumor (ETT) is a rare malignancy arising from neoplastic proliferation of chorionic‐type intermediate trophoblasts. ETT poses significant challenges to clinicians in the diagnosis and treatment and can hence lead to a poor prognosis. We report a unique case of metastatic ETT in a HIV‐positive patient.