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Abstract Background The ongoing global crisis of Higher Education (HE) institutions during the post-COVID-19 pandemic period has increased the likelihood of enduring psychological stressors for staff. This study aimed to identify factors associated with job insecurity, burnout, psychological distress and coping amongst staff working at HE institutions globally. Methods An anonymous cross-sectional study was conducted in 2023 with staff at HE institutions across 16 countries. Job insecurity was measured using the Job Insecurity Scale (JIS), burnout using the Perceived Burnout measure question, psychological distress using the Kessler Psychological Distress Scale (K10), and coping using the Brief Resilient Coping Scale. Multivariable logistic regression with a stepwise variable selection method was used to identify associations. Results A total of 2,353 staff participated; the mean age (± SD) was 43(± 10) years and 61% were females. Most staff (85%) did not feel job insecurity, one-third (29%) perceived burnout in their jobs, more than two-thirds (73%) experienced moderate to very high levels of psychological distress, and more than half (58%) exhibited medium to high resilient coping. Perceived job insecurity was associated with staff working part-time [Adjusted Odds Ratio 1.53 (95% Confidence Intervals 1.15–2.02)], having an academic appointment [2.45 (1.78–3.27)], having multiple co-morbidities [1.86 (1.41–2.48)], perceived burnout [1.99 (1.54–2.56)] and moderate to very high level of psychological distress [1.68 (1.18–2.39)]. Perceived burnout was associated with being female [1.35 (1.12–1.63)], having multiple co-morbidities [1.53 (1.20–1.97)], perceived job insecurity [1.99 (1.55–2.57)], and moderate to very high levels of psychological distress [3.23 (2.42–4.30)]. Staff with multiple co-morbidities [1.46 (1.11–1.92)], mental health issues [2.73 (1.79–4.15)], perceived job insecurity [1.61 (1.13–2.30)], and perceived burnout [3.22 (2.41–4.31)] were associated with moderate to very high levels of psychological distress. Staff who perceived their mental health as good to excellent [3.36 (2.69–4.19)] were more likely to have medium to high resilient coping. Conclusions Factors identified in this study should be considered in reviewing and updating current support strategies for staff at HE institutions across all countries to reduce stress and burnout and improve wellbeing.

Abstract Background Supported self-management interventions for patients with musculoskeletal (MSK) conditions may not adequately support those with limited health literacy, leading to inequalities in care and variable outcomes. The aim of this study was to develop a model for inclusive supported self-management intervention(s) for MSK pain that take account of health literacy. Methods A mixed methods study with four work-packages was conducted: work package 1: secondary analysis of existing data to identify potential targets for intervention; work package 2: evidence synthesis to assess effective components of self-management interventions taking into account health literacy; work package 3: views of community members and healthcare professionals (HCPs) on essential components; work package 4: triangulation of findings and an online modified Delphi approach to reach consensus on key components of a logic model. Findings Findings identified targets for intervention as self-efficacy, illness perceptions, and pain catastrophizing. A range of intervention components were identified (e.g. information in diverse formats offered at specific times, action planning and visual demonstrations of exercise). Support should be multi-professional using a combination of delivery modes (e.g. remote, face-to-face). Conclusions This research has developed a patient-centred model for a multi-disciplinary, multi-modal approach to supported self-management for patients with MSK pain and varying levels of health literacy. The model is evidence-based and acceptable to both patients and HCPs, with potential for significant impact on the management of MSK pain and for improving patient health outcomes. Further work is needed to establish its efficacy.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease (ILD) with limited treatment options. Interleukin-33 (IL-33) is proposed to play a role in the development of IPF however the exclusive use of prophylactic dosing regimens means that the therapeutic benefit of targeting this cytokine in IPF is unclear. Methods IL-33 expression was assessed in ILD lung sections and human lung fibroblasts (HLFs) by immunohistochemistry and gene/protein expression and responses of HLFs to IL-33 stimulation measured by qPCR. In vivo, the fibrotic potential of IL-33:ST2 signalling was assessed using a murine model of bleomycin (BLM)-induced pulmonary fibrosis and therapeutic dosing with an ST2-Fc fusion protein. Lung and bronchoalveolar lavage fluid were collected for measurement of inflammatory and fibrotic endpoints. Human precision-cut lung slices (PCLS) were stimulated with transforming growth factor-β (TGFβ) or IL-33 and fibrotic readouts assessed. Results IL-33 was expressed by fibrotic fibroblasts in situ and was increased by TGFβ treatment in vitro. IL-33 treatment of HLFs did not induce IL6, CXCL8, ACTA2 and COL1A1 mRNA expression with these cells found to lack the IL-33 receptor ST2. Similarly, IL-33 stimulation had no effect on ACTA2, COL1A1, FN1 and fibronectin expression by PCLS. Despite having effects on inflammation suggestive of target engagement, therapeutic dosing with the ST2-Fc fusion protein failed to reduce BLM-induced fibrosis measured by hydroxyproline content or Ashcroft score. Conclusions Together these findings suggest the IL-33:ST2 axis does not play a central fibrogenic role in the lungs with therapeutic blockade of this pathway unlikely to surpass the current standard of care for IPF.

Abstract Background Despite successful control efforts in China over the past 60 years, zoonotic schistosomiasis caused by Schistosoma japonicum remains a threat with transmission ongoing and the risk of localised resurgences prompting calls for a novel integrated control strategy, with an anti-schistosome vaccine as a core element. Anti-schistosome vaccine development and immunisation attempts in non-human mammalian host species, intended to interrupt transmission, and utilising various antigen targets, have yielded mixed success, with some studies highlighting variation in schistosome antigen coding genes (ACGs) as possible confounders of vaccine efficacy. Thus, robust selection of target ACGs, including assessment of their genetic diversity and antigenic variability, is paramount. Tetraspanins (TSPs), a family of tegument-surface antigens in schistosomes, interact directly with the host’s immune system and are promising vaccine candidates. Here, for the first time to our knowledge, diversity in S. japonicum TSPs (SjTSPs) and the impact of diversifying selection and sequence variation on immunogenicity in these protiens were evaluated. Methods SjTSP sequences, representing parasite populations from seven provinces across China, were gathered by baiting published short-read NGS data and were analysed using in silico methods to measure sequence variation and selection pressures and predict the impact of selection on variation in antigen protein structure, function and antigenic propensity. Results Here, 27 SjTSPs were identified across three subfamilies, highlighting the diversity of TSPs in S. japonicum. Considerable variation was demonstrated for several SjTSPs between geographical regions/provinces, revealing that episodic, diversifying positive selection pressures promote amino acid variation/variability in the large extracellular loop (LEL) domain of certain SjTSPs. Accumulating polymorphisms in the LEL domain of SjTSP-2, -8 and -23 led to altered structural, functional and antibody binding characteristics, which are predicted to impact antibody recognition and possibly blunt the host’s ability to respond to infection. Such changes, therefore, appear to represent a mechanism utilised by S. japonicum to evade the host’s immune system. Conclusion Whilst the genetic and antigenic geographic variability observed amongst certain SjTSPs could present challenges to vaccine development, here we demonstrate conservation amongst SjTSP-1, -13 and -14, revealing their likely improved utility as efficacious vaccine candidates. Importantly, our data highlight that robust evaluation of vaccine target variability in natural parasite populations should be a prerequisite for anti-schistosome vaccine development. Graphical abstract

Abstract Background Therapeutic footwear and insoles are preventative strategies to reduce elevated plantar pressures associated with diabetic foot ulcer risk. An insole intervention appropriate for chairside delivery optimising plantar foot pressure reduction in people with diabetes has been developed. Aim To explore the feasibility and acceptability of testing an optimised insole compared with an active control insole to reduce plantar pressures for people with diabetic peripheral neuropathy. Methods A double-blinded multi-centre feasibility RCT with an embedded qualitative study. Participants were randomised to either an optimised insole group (intervention) or a standard cushioned insole group (active control). Participants were assessed at baseline, 3, 6, and 12 months with clinical outcomes of foot ulceration and mean peak plantar pressure (MPPP) reduction. An embedded qualitative study involved semi-structured interviews with 12 study participants and three podiatrists to explore their experiences of the intervention and trial procedures. Data were analysed using descriptive statistics (quantitative data) and thematic analysis (qualitative data). Results Screened were142 patients from which 61 were recruited; 30 participants were randomised to the intervention group and 31 to the active control group. Forty-two participants completed the study. At 12 months, 69% of the patient-reported questionnaires were returned and 68% of the clinical outcomes were collected. There were 17 incidences of foot ulceration occurring in 7/31 of the active control group and 10/30 in the intervention group. Mean difference in MPPP between the intervention and active control groups for all regions-of-interest combined favoured the intervention. Thematic analysis revealed three themes; accepting the study, behaviour and support during study procedures, and impact from study participation. Conclusion The results of the feasibility RCT suggest that the optimised insole holds promise as an intervention, and that a full RCT to evaluate the clinical and cost-effectiveness of this intervention is feasible and warranted for people with diabetic peripheral neuropathy. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN16011830 . Registered 9th October 2017.

Abstract Archival (data-storage) and telemetry (acoustic and radio) tags are commonly used to provide data on the behavior and physiology of organisms, as well as data on their surrounding environment. For fishes, it is often advantageous to implant tags in the peritoneal cavity (i.e., intracoelomic implantation). The literature on best practices is limited for marine species, and near absent for tunas despite their regular application. We identify recommended practices using laparotomy in tropical tuna species following observations from thousands of tags implantations undertaken during implementation of several tagging programs across the Pacific. These recommended practices include descriptions of preferred tagging stations and equipment, fish selection, surgical procedures, and return of the fish to the wild. While these recommended practices were developed specifically for tropical tuna species, they are also likely applicable for other pelagic fishes. We present these guidelines to guide and promote the development of best practices for such procedures on pelagic species.

Abstract Background The STarT MSK cluster randomised controlled trial (RCT) investigated the clinical- and cost-effectiveness of risk-based stratified primary care versus usual care for patients with back, neck, shoulder, knee or multi-site pain. Trial quantitative results showed risk-based stratified care was not superior to usual care for patients’ clinical outcomes, but the intervention led to some changes in GP clinical decision-making. This paper reports a linked qualitative study exploring how risk-based stratified care was perceived and used in the trial, from the perspectives of clinicians and patients. Methods Semi-structured interviews were conducted with 27 patients, and focus groups and interviews with 20 clinicians (GPs and physiotherapists) in the intervention arm of the trial. Data were analysed thematically and findings explored using Normalisation Process Theory (NPT) and the COM-B model. Main findings Risk-based stratified care (subgrouping and matching treatments) was found to have ‘coherence’ (i.e. made sense) to several clinicians and patients, in that it was well-integrated in practice, and supported clinical decision-making. However, for some GPs stratified care was less ‘meaningful’, as the risk-stratification tool did not fit with usual ways of consulting and added to already time-pressured consultations. GPs reported giving more patients written information/advice due to easier access to electronic information leaflets through the trial template and were motivated to refer patients to physiotherapy as they believed the trial resulted in faster physiotherapy access (although this was not the case). Patients and clinicians reported that risk-based stratified care influenced conversations in the consultation, prompting greater attention to psychosocial factors, and facilitating negotiation of treatment options. Physiotherapists saw benefits in receiving information about patients’ risk subgroup on referral forms. Conclusion These findings provide context for interpreting some of the trial outcomes, particularly in relation to changes in clinical decision-making when risk-based stratified care was used. Findings also indicate potential reasons for lack of GP engagement with risk-based stratified care. Positive outcomes were identified that were not captured in the quantitative data, specifically that risk-based stratified care positively influenced some GP-patient conversations and facilitated negotiation of treatment options. Trial registration ISRCTN15366334 (26/04/2016).

Abstract Background Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are the most common prostate disorders in the UK, which cause considerable ill health in older men. Transperineal template prostate biopsy (TTPB) has emerged as a reliable procedure for the histopathological diagnosis of PCa and BPH due to its higher cancer detection rates. Although antiseptic preparation and antibiotic prophylaxis are used to ensure safety in patients undergoing surgical intervention, post-operative complications, such as infection and bleeding are still unavoidable, resulting in re-admissions, with resource implications. Currently, there is no biomarker profile to predict outcomes or monitor patients during the post-operative course. The main aim of this single-centre observational clinical pilot-study was to investigate the role of inflammatory and infection biomarkers following TTPB and their association with post-operative complications. Methods Forty-five patients scheduled for elective TTPB were recruited after informed consent at the Wrexham Maelor and Glan Clwyd Hospitals, North Wales, UK (n = 45). Prior to surgery, venous blood samples were collected at baseline and subsequently at 30, 120, and 240 min post-operatively. Urine samples were collected before and 120 min after the procedure. Serum procalcitonin (PCT), serum ferritin, and urine B2MG analysis were done using enzyme-linked fluorescent assay (ELFA) and the magnetic Luminex® multiplex performance assay was used to analyse IL-6, IL-8, IL-10 and TNF-α plasma concentrations. Data on clinical outcomes were collected from patients’ medical records. Results Following TTPB, significant (p ≤ 0.05) increases were observed in uB2MG, IL-6, IL-8, IL-10 and TNF-α. Significant decreases were observed in ferritin (p ≤ 0.05). No significant change was observed in PCT concentration (p ≥ 0.05). One patient developed an infection and severe haematuria post-operatively following TTPB. Conclusion Although not confirmative, changes seen in biomarkers such as uB2MG, IL-10 and TNF-α in our observational clinical pilot-study may warrant further investigation, involving larger cohorts, to fully understand the role of these biomarkers and their potential association with post-operative complications such as infection and bleeding which can develop following TTPB for the diagnosis of PCa and BPH.

Abstract Background Angular cheilitis, an infection mainly caused by Candida yeasts, is featured by the appearance of inflammatory lesions at the bilateral corners of the mouth, particularly in patients with poor oral hygiene, ill-fitting dentures and old age. The first isolation of an atypical yeast, Cystobasidium calyptogenae, from oral samples of a patient presenting with angular cheilitis is discussed in this study. Case presentation Angular cheilitis was diagnosed in a 60-year-old denture-wearing woman who presented with an irritation fibroma on her right lower buccal sulcus over the premolar region. Primary cultures of her oral swab and oral rinse samples grew a pure culture of an uncommon yeast strain resembling Rhodotorula sp. Sequence analysis of the yeast internal transcribed spacer (ITS) gene region and D1D2 domain showed highest similarity (99.6% and 100%, respectively) to C. calyptogenae CBS 9125 type strain. Following 2 weeks of treatment with miconazole/fusidic acid and mouthwash, the oral lesion showed improvement with less erythema. C. calyptogenae was not isolated from the patient’s oral samples upon repeat sampling. Conclusion This is the first report on the isolation of C. calyptogenae from human oral samples. The ability of C. calyptogenae to grow at 37 °C and the fact that it was the only yeast species isolated from the patient’s oral samples suggests its pathogenic potential and possible involvement in angular cheilitis. The ubiquitous nature of the Cystobasidium yeast is believed to increase the likelihood of opportunistic infections among immunocompromised individuals. As Cystobasidium is phenotypically indistinguishable from Rhodotorula, an emerging opportunistic pathogen, surveillance using molecular identification in clinical settings is essential in providing accurate diagnosis and treatment of uncommon yeast infections.

Abstract Background Schistosomiasis is a disease that poses major threats to human and animal health, as well as the economy, especially in sub-Saharan Africa (SSA). Whilst many studies have evaluated the economic impact of schistosomiasis in humans, to date only one has been performed in livestock in SSA and none in Senegal. This study aimed to estimate the financial impact of livestock schistosomiasis in selected regions of Senegal. Methods Stochastic partial budget models were developed for traditional ruminant farmers in 12 villages in northern Senegal. The models were parameterised using data from a cross-sectional survey, focus group discussions, scientific literature and available statistics. Two scenarios were defined: scenario 1 modelled a situation in which farmers tested and treated their livestock for schistosomiasis, whilst scenario 2 modelled a situation in which there were no tests or treatment. The model was run with 10,000 iterations for 1 year; results were expressed in West African CFA francs (XOF; 1 XOF was equivalent to 0.0014 GBP at the time of analysis). Sensitivity analyses were conducted to assess the impact of uncertain variables on the disease costs. Results Farmers surveyed were aware of schistosomiasis in their ruminant livestock and reported hollowing around the eyes, diarrhoea and weight loss as the most common clinical signs in all species. For scenario 1, the median disease costs per year and head of cattle, sheep and goats were estimated at 13,408 XOF, 27,227 XOF and 27,694 XOF, respectively. For scenario 2, the disease costs per year and head of cattle, sheep and goats were estimated at 49,296 XOF, 70,072 XOF and 70,281 XOF, respectively. Conclusions Our findings suggest that the financial impact of livestock schistosomiasis on traditional subsistence and transhumance farmers is substantial. Consequently, treating livestock schistosomiasis has the potential to generate considerable benefits to farmers and their families. Given the dearth of data in this region, our study serves as a foundation for further in-depth studies to provide estimates of disease impact and as a baseline for future economic analyses. This will also enable One Health economic studies where the burden on both humans and animals is estimated and included in cross-sectoral cost–benefit and cost-effectiveness analyses of disease control strategies. Graphical Abstract

Abstract Background Posttraumatic stress disorder (PTSD) and substance use disorder (SUD) have high comorbidity. Although prior research indicated that PTSD can effectively be treated with Prolonged Exposure (PE) in these patients, reported effects are small and treatment dropout rates high. Eye Movement Desensitization and Reprocessing (EMDR) and Imagery Rescripting (ImRs) are other promising treatment options for PTSD, that have not yet been examined in this patient group. Furthermore, it is unclear whether PTSD treatment is most effective when offered simultaneous to or after SUD treatment. Methods In this article, the Treatment Of PTSD and Addiction (TOPA) study is described: a Dutch randomized controlled trial (RCT) that studies the effectiveness of PTSD treatment as an add-on to regular SUD treatment in patients with SUD and co-occurring PTSD. Effects of PE, EMDR, ImRs, and a 3-month SUD treatment only condition will be compared, as well as simultaneous SUD/PTSD treatment to sequential SUD/PTSD treatment. The primary outcome measure is PTSD symptoms. Secondary outcomes are: treatment completion, psychological distress, substance use, interpersonal problems, emotion dysregulation, and trauma-related emotions guilt, shame, and anger. Discussion This study is the first to compare effects of PE, EMDR, and ImRs in one study and to compare simultaneous SUD/PTSD treatment to sequential SUD/PTSD treatment as well. This RCT will provide more knowledge about the effectiveness of different treatment strategies for PTSD in patients with co-occurring SUD and will ultimately improve treatment outcomes for patients with this common co-morbidity worldwide. Trial registration Netherlands Trial Register (NTR), Identifier: NL7885 . Registered 22 July 2019.

Abstract Background Low back pain is a leading cause of disability worldwide. Health literacy has been associated with pain intensity and pain control. However, there is a paucity of evidence regarding this association. In the field of low back pain research, inconsistent reporting of outcomes has been highlighted. To address this issue a Core Outcome Set has been developed. Objectives The objectives of this scoping review were: (1) The health literacy measures currently employed for low back pain and the aspects of health literacy they include. (2) The low back pain health outcomes included in such work. (3) The extent to which these health outcomes reflect the Core Outcome Set for Clinical Trials in Non-Specific Low Back Pain. Methods The search included thirteen bibliographic databases, using medical subject heading terms for low back pain and health literacy, and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. The eligibility criteria were defined by the Joanna Briggs Institute PCC mnemonic. A thematic framework approach was used for analysis. Results The search yielded ten relevant studies for inclusion, amongst which a total of nine health literacy measures and 50 health outcome measures were used. Most health literacy measures focused on functional health literacy, with few assessing communicative and critical health literacy. The health outcomes assessed by the included studies could be broadly categorised into: Pain, Disability, Behaviour, Knowledge and Beliefs, and Resource Utilisation. Most of these outcome measures studied (36 out of 50) did not directly reflect the Core Outcome Set for Clinical Trials in Non-Specific Low Back Pain. Conclusions To allow for comparison across findings and the development of a rigorous evidence base, future work should include the Core Outcome Set for Clinical Trials in Non-Specific Low Back Pain. There is an urgent need to broaden the evidence-base to include regions where low back pain morbidity is high, but data is lacking. Such work demands the incorporation of comprehensive measures of health literacy that have both generic and culturally sensitive components.

Abstract Background Stratified care involves subgrouping patients based on key characteristics, e.g. prognostic risk, and matching these subgroups to early treatment options. The STarT-MSK programme developed and tested a new stratified primary care intervention for patients with common musculoskeletal (MSK) conditions in general practice. Stratified care involves changing General Practitioners’ (GPs) behaviour, away from the current ‘stepped’ care approach to identifying early treatment options matched to patients’ risk of persistent pain. Changing healthcare practice is challenging, and to aid the successful delivery of stratified care, education and support for GPs was required. This paper details the iterative development of a clinician support package throughout the lifespan of the programme, to support GPs in delivering the stratified care intervention. We argue that clinician support is a crucial aspect of the intervention itself, which is often overlooked. Methods Qualitative research with patients and GPs identified barriers and facilitators to the adoption of stratified care, which were mapped onto the Theoretical Domains Framework (TDF). Identified domains were ‘translated’ into an educational paradigm, and an initial version of the support package developed. This was further refined following a feasibility and pilot RCT, and a finalised support package was developed for the main RCT. Results The clinician support package comprised face-to-face sessions combining adult-learning principles with behaviour change theory in a multimethod approach, which included group discussion, simulated consultations, patient vignettes and model consultation videos. Structured support for GPs was crucial to facilitate fidelity and, ultimately, a successful trial. Clinician support is a two-way process– the study team can learn from and adapt to specific local factors and issues not previously identified. The support from senior clinicians was required to ensure ‘buy in’. Monitoring of GP performance, provision of regular feedback and remedial support are important aspects of effective clinician support. Conclusion Designing effective clinician support from the onset of trial intervention design, in an evidence-based, theory-informed manner, is crucial to encourage active engagement and intervention fidelity within the trial, enabling the delivery of a robust and reliable proof-of-principle trial. We offer practical recommendations for future general practice interventions.

Abstract Background The U937 cell line is widely employed as a research tool. It has a complex karyotype. A PICALM-MLLT10 fusion gene formed by the recurrent t(10;11) translocation is present, and the myeloid common deleted region at 20q12 has been lost from its near-triploid karyotype. We carried out a detailed investigation of U937 genome reorganisation including the chromosome 20 rearrangements and other complex rearrangements. Results SNP array, G-banding and Multicolour FISH identified chromosome segments resulting from unbalanced and balanced rearrangements. The organisation of the abnormal chromosomes containing these segments was then reconstructed with the strategic use of targeted metaphase FISH. This provided more accurate karyotype information for the evolving karyotype. Rearrangements involving the homologues of a chromosome pair could be differentiated in most instances. Centromere capture was demonstrated in an abnormal chromosome containing parts of chromosomes 16 and 20 which were stabilised by joining to a short section of chromosome containing an 11 centromere. This adds to the growing number of examples of centromere capture, which to date have a high incidence in complex karyotypes where the centromeres of the rearranged chromosomes are identified. There were two normal copies of one chromosome 20 homologue, and complex rearrangement of the other homologue including loss of the 20q12 common deleted region. This confirmed the previously reported loss of heterozygosity of this region in U937, and defined the rearrangements giving rise to this loss. Conclusions Centromere capture, stabilising chromosomes pieced together from multiple segments, may be a common feature of complex karyotypes. However, it has only recently been recognised, as this requires deliberate identification of the centromeres of abnormal chromosomes. The approach presented here is invaluable for studying complex reorganised genomes such as those produced by chromothripsis, and provides a more complete picture than can be obtained by microarray, karyotyping or FISH studies alone. One major advantage of SNP arrays for this process is that the two homologues can usually be distinguished when there is more than one rearrangement of a chromosome pair. Tracking the fate of each homologue and of highly repetitive DNA regions such as centromeres helps build a picture of genome evolution. Centromere- and telomere-containing elements are important to deducing chromosome structure. This study confirms and highlights ongoing evolution in cultured cell lines.

Abstract Background Physical inactivity (PI) is associated with the development of non-communicable chronic diseases. The purposes of this study were to estimate the extent to which the 31% relative increase in PI among 35–64 years old Mexicans between 2006 and 2012 influenced diabetes (T2D) and cardiovascular disease (CVD) incidence and mortality, and to estimate the impact of the World Health Organization recommended 10% and 15% relative decrease in PI on CVD and T2D incidence and mortality by 2025 and 2030, respectively. Methods Estimates were derived using the Cardiovascular Disease Policy Model-Mexico, a computer simulation, Markov model. Model inputs included cross-national data on PI levels from 2006 and 2012 measured using the International Physical Activity Questionnaire and the published literature review on the independent relationship between PI and cardiometabolic risk. Results The models estimated that the 31% increase in PI resulted in an increase in the number of cases of T2D (27,100), coronary heart disease (10,300), stroke (2200), myocardial infarction (1500), stroke deaths (400) and coronary heart disease deaths (350). A hypothetical 10% lowering of PI by 2025 compared to status quo is projected to prevent 8400 cases of T2D, 4200 cases of CHD, 1000 cases of stroke, 700 cases of MI, and 200 deaths of CHD and stroke, respectively. A 15% reduction resulted in larger decreases. Conclusions While the burden of T2D and CVD raised from 2006 to 2012 in association with increased PI, achieving the WHO targets by 2030 could help reverse these trends.

Abstract Background Mobile Health (mHealth) is becoming an important tool to improve health outcomes in maternal, newborn and child health (MNCH). Studies of mHealth interventions, have demonstrated their effectiveness in improving uptake of recommended maternal services such as antenatal visits. However, evidence of impact on maternal health outcomes is still limited. Methods A pseudo-randomized controlled trial (single blind) was conducted to assess the impact of a voice-message based maternal intervention on maternal health knowledge, attitudes, practices and outcomes over time: Pregnancy (baseline/Time 1); Post-partum (Time 2) and when the infant turned one year old (Time 3). Women assigned to the mMitra intervention arm received gestational age- and stage-based educational voice messages via mobile phone in Hindi and Marathi, while those assigned to the control group did not. Both groups received standard care. Results Two thousand sixteen women were enrolled. Interviews were conducted with 1516 women in the intervention group and 500 women in the control group at baseline and post-partum. The intervention group performed significantly better than controls on four maternal health practice indicators: receiving the tetanus toxoid injection (OR: 1.6, 95% Confidence Interval (CI): 1.05–2.4, p = 0.028), consulting a doctor if spotting or bleeding (OR: 1.72, 95%CI: 1.07–2.75, p = 0.025), saving money for delivery expenses (OR: 1.79, 95%CI: 1.38–2.33, p = 0.0001), and delivering in hospital (OR: 2.5, 95%CI: 1.49–4.35, p = 0.001). The control group performed significantly better than the intervention group on two practice indicators: resting regularly during pregnancy (OR: 0.7, 95%CI: 0.54–0.88, p = 0.002) and having at-home deliveries attended by a skilled birth attendant (OR: 0.46, 95%CI: 0.23–0.91, p = 0.027). Both groups’ knowledge improved from Time 1 to Time 2. Only one knowledge indicator, on seeking medical care during pregnancy, was statistically increased in the intervention group compared to controls. Anemia status at or near the time of delivery was unable to be assessed due to missing data from maternal health cards. Conclusions This study provides evidence that in low-resource settings, mobile voice messages providing tailored and timed information about pregnancy can positively impact maternal health care practices proven to improve maternal health outcomes. Additional research is needed to assess whether voice messaging can motivate behavior change better than text messaging, particularly in low literacy settings. Trial registration The mMitra impact evaluation is registered with ISRCTN under Registration # 88968111, assigned on 6 September 2018 (See https://www.isrctn.com/ISRCTN88968111 ).

Abstract Background Pregnant women and their unborn babies are at increased risk of complications as a result of flu, yet uptake of the flu vaccination in the UK remains low. Digital interventions have proven effectiveness in changing health behaviour, but their effectiveness in increasing flu vaccination amongst pregnant women has not been examined. This protocol details the design and methodology of a systematic review and meta-analysis, examining the effectiveness of digital interventions in increasing flu vaccination amongst pregnant women. Methods Bibliographic databases will be searched using appropriate search terms related to vaccination, pregnancy and flu. Randomised, non-randomised, quasi randomised controlled trials and other quantitative study designs will be eligible for inclusion, and studies will present the rate of flu vaccination amongst pregnant women of digital interventions compared to non-digital interventions, or usual care. No date or study country restrictions will be put on included studies, but studies will be published in English. Discussion This is the first known systematic review to examine the effectiveness of digital interventions in increasing the rate of flu vaccination amongst pregnant women. This review has the potential to inform whether digital interventions are an appropriate and successful method of increasing flu vaccination amongst pregnant women, and to determine which mode of digital intervention is most effective. Trial registration This systematic review is registered on the international prospective register of systematic reviews (PROSPERO). Registration number pending.

Abstract Background Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is endemic in Niger but complicated by the presence of Schistosoma bovis, Schistosoma curassoni and S. haematobium group hybrids along with various Bulinus snail intermediate host species. Establishing the schistosomes and snails involved in transmission aids disease surveillance whilst providing insights into snail-schistosome interactions/compatibilities and biology. Methods Infected Bulinus spp. were collected from 16 villages north and south of the Niamey region, Niger, between 2011 and 2015. From each Bulinus spp., 20–52 cercariae shed were analysed using microsatellite markers and a subset identified using the mitochondrial (mt) cox1 and nuclear ITS1 + 2 and 18S DNA regions. Infected Bulinus spp. were identified using both morphological and molecular analysis (partial mt cox1 region). Results A total of 87 infected Bulinus from 24 sites were found, 29 were molecularly confirmed as B. truncatus, three as B. forskalii and four as B. globosus. The remaining samples were morphologically identified as B. truncatus (n = 49) and B. forskalii (n = 2). The microsatellite analysis of 1124 cercariae revealed 186 cercarial multilocus genotypes (MLGs). Identical cercarial genotypes were frequently (60%) identified from the same snail (clonal populations from a single miracidia); however, several (40%) of the snails had cercariae of different genotypes (2–10 MLG’s) indicating multiple miracidial infections. Fifty-seven of the B. truncatus and all of the B. forskalii and B. globosus were shedding the Bovid schistosome S. bovis. The other B. truncatus were shedding the human schistosomes, S. haematobium (n = 6) and the S. haematobium group hybrids (n = 13). Two B. truncatus had co-infections with S. haematobium and S. haematobium group hybrids whilst no co-infections with S. bovis were observed. Conclusions This study has advanced our understanding of human and bovid schistosomiasis transmission in the Niger River Valley region. Human Schistosoma species/forms (S. haematobium and S. haematobium hybrids) were found transmitted only in five villages whereas those causing veterinary schistosomiasis (S. bovis), were found in most villages. Bulinus truncatus was most abundant, transmitting all Schistosoma species, while the less abundant B. forskalii and B. globosus, only transmitted S. bovis. Our data suggest that species-specific biological traits may exist in relation to co-infections, snail-schistosome compatibility and intramolluscan schistosome development.

Abstract Background Stratified care involves subgrouping patients based on key characteristics, e.g. prognostic risk, and matching these subgroups to appropriate early treatment options. The STarT MSK feasibility and pilot cluster randomised controlled trial (RCT) examined the feasibility of a future main trial and of delivering prognostic stratified primary care for patients with musculoskeletal pain. The pilot RCT was conducted in 8 UK general practices (4 stratified care; 4 usual care) with 524 patients. GPs in stratified care practices were asked to use i) the Keele STarT MSK development tool for risk-stratification and ii) matched treatment options for patients at low-, medium- and high-risk of persistent pain. This paper reports on a nested qualitative study exploring the feasibility of delivering stratified care ahead of the main trial. Methods ‘Stimulated-recall’ interviews were conducted with patients and GPs in the stratified care arm (n = 10 patients; 10 GPs), prompted by consultation recordings. Data were analysed thematically and mapped onto the COM-B behaviour change model; exploring the Capability, Opportunity and Motivation GPs and patients had to engage with stratified care. Results Patients reported positive views that stratified care enabled a more ‘structured’ consultation, and felt tool items were useful in making GPs aware of patients’ worries and concerns. However, the closed nature of the tool’s items was seen as a barrier to opening up discussion. GPs identified difficulties integrating the tool within consultations (Opportunity), but found this easier as it became more familiar. Whilst both groups felt the tool had added value, they identified ‘cumbersome’ items which made it more difficult to use (Capability). Most GPs reported that the matched treatment options aided their clinical decision-making (Motivation), but identified some options that were not available to them (e.g. pain management clinics), and other options that were not included in the matched treatments but which were felt appropriate for some patients (e.g. consider imaging). Conclusion This nested qualitative study, using the COM-B model, identified amendments required for the main trial including changes to the Keele STarT MSK tool and matched treatment options, targeting the COM-B model constructs, and these have been implemented in the current main trial. Trial registration ISRCTN 15366334 .

Abstract Background A key component of schistosomiasis control is mass drug administration with praziquantel. While control interventions have been successful in several endemic regions, mass drug administration has been less effective in others. Here we focus on the impact of repeated praziquantel treatment on the population structure and genetic diversity of Schistosoma mansoni. Methods We examined S. mansoni epidemiology, population genetics, and variation in praziquantel susceptibility in parasites isolated from children across three primary schools in a high endemicity region at the onset of the Ugandan National Control Programme. Children were sampled at 11 timepoints over two years, including one week and four weeks post-praziquantel treatment to evaluate short-term impacts on clearance and evidence of natural variation in susceptibility to praziquantel. Results Prevalence of S. mansoni was 85% at baseline. A total of 3576 miracidia larval parasites, isolated from 203 individual children, were genotyped at seven loci. Overall, genetic diversity was high and there was low genetic differentiation, indicating high rates of parasite gene flow. Schistosome siblings were found both pre-treatment and four weeks post-treatment, demonstrating adult worms surviving treatment and natural praziquantel susceptibility variation in these populations at the beginning of mass drug administration. However, we did not find evidence for selection on these parasites. While genetic diversity decreased in the short-term (four weeks post-treatment), diversity did not decrease over the entire period despite four rounds of mass treatment. Furthermore, within-host genetic diversity was affected by host age, host sex, infection intensity and recent praziquantel treatment. Conclusions Our findings suggest that praziquantel treatments have short-term impacts on these parasite populations but impacts were transient and no long-term reduction in genetic diversity was observed. High gene flow reduces the likelihood of local adaptation, so even though parasites surviving treatment were observed, these were likely to be diluted at the beginning of the Ugandan National Control Programme. Together, these results suggest that MDA in isolation may be insufficient to reduce schistosome populations in regions with high genetic diversity and gene flow.

Abstract Background Customary medicine of Australia’s Indigenous peoples draws upon knowledge developed through millennia of interaction with Australia’s unique flora and fauna. Many Indigenous Australians are interested in developing modern medicinal and commercial translations of traditional knowledge; however, barriers of trust and benefit sharing often thwart progress. Methods Using a participatory action research framework, university researchers collaborated with members of two Australian Indigenous communities to investigate selected medicinal plants and locally made bush products. A trusted community liaison facilitated the collaboration that was fostered through bilateral site visits. Material transfer and confidentiality agreements ensured that the plant materials were only used for the agreed purpose. Plain language written reports of the laboratory results were provided to the communities with follow up discussions. Results In case study 1, only some of the traditional uses for the raw plants were shared with the researchers. Deidentified plants were assessed for antioxidant and antimicrobial properties. In case study 2, the plant names, traditional uses, and preparation methods were shared with the aim of learning more about their plants, potential uses, and optimising their bush products. Literature reviews were conducted that also helped guide in vitro testing of the crude and solvent partitioned extracts. These differences reflected the community’s reasons for conducting the research and intellectual property considerations. In both cases, observed benefits included building trust and strengthening working relationships for ongoing collaboration, fostering enthusiasm for linking traditional and scientific knowledge, promoting cross-cultural learning about scientific methods and traditional medicine, maintaining the relevance of traditional knowledge in the modern world, and initiating community discussions around their bush medicine product development. Conclusions Community-driven scientific investigation of traditional medicinal knowledge can facilitate culturally meaningful outcomes, with potentially wide-reaching direct and indirect benefits. Community liaisons were invaluable for establishment of strong relationships and ensured that the research was culturally and locally appropriate. The need for clearer guidelines and regulation around community-driven biomedical research of their plants was identified. Australia would benefit from a user-friendly, open-source toolkit that promotes use of local traditional medicines, contains information about processes and protocols that communities and scientists could use to develop collaborative projects, and guides regulation and ethical commercialisation. Close consultation and collaboration with communities and researchers will be needed to ensure that such a toolkit is culturally appropriate and fit-for-purpose.

Abstract Background Schistosomiasis and food-borne trematodiases are not only of major public health concern, but can also have profound implications for livestock production and wildlife conservation. The zoonotic, multi-host nature of many digenean trematodes is a significant challenge for disease control programmes in endemic areas. However, our understanding of the epidemiological role that animal reservoirs, particularly wild hosts, may play in the transmission of zoonotic trematodiases suffers a dearth of information, with few, if any, standardised, reliable diagnostic tests available. We combined qualitative and quantitative data derived from post-mortem examinations, coprological analyses using the Mini-FLOTAC technique, and molecular tools to assess parasite community composition and the validity of non-invasive methods to detect trematode infections in 89 wild Hubert’s multimammate mice (Mastomys huberti) from northern Senegal. Results Parasites isolated at post-mortem examination were identified as Plagiorchis sp., Anchitrema sp., Echinostoma caproni, Schistosoma mansoni, and a hybrid between Schistosoma haematobium and Schistosoma bovis. The reports of E. caproni and Anchitrema sp. represent the first molecularly confirmed identifications for these trematodes in definitive hosts of sub-Saharan Africa. Comparison of prevalence estimates derived from parasitological analysis at post-mortem examination and Mini-FLOTAC analysis showed non-significant differences indicating comparable results between the two techniques (P = 1.00 for S. mansoni; P = 0.85 for E. caproni; P = 0.83 for Plagiorchis sp.). A Bayesian model, applied to estimate the sensitivities of the two tests for the diagnosis of Schistosoma infections, indicated similar median posterior probabilities of 83.1% for Mini-FLOTAC technique and 82.9% for post-mortem examination (95% Bayesian credible intervals of 64.0–94.6% and 63.7–94.7%, respectively). Conclusions Our results showed that the Mini-FLOTAC could be applied as an alternative diagnostic technique for the detection of the zoonotic S. mansoni and other trematodes in rodent reservoirs. The implementation of non-invasive diagnostics in wildlife would offer numerous advantages over lethal sampling methodologies, with potential impact on control strategies of zoonotic helminthiases in endemic areas of sub-Saharan Africa and on fostering a framework of animal use reduction in scientific practice.

Abstract Background Sibship reconstruction is a form of parentage analysis that can be used to identify the number of helminth parental genotypes infecting individual hosts using genetic data on only their offspring. This has the potential to be used for estimating individual worm burdens when adult parasites are otherwise inaccessible, the case for many of the most globally important human helminthiases and neglected tropical diseases. Yet methods of inferring worm burdens from sibship reconstruction data on numbers of unique parental genotypes are lacking, limiting the method’s scope of application. Results We developed a novel statistical method for estimating female worm burdens from data on the number of unique female parental genotypes derived from sibship reconstruction. We illustrate the approach using genotypic data on Schistosoma mansoni (miracidial) offspring collected from schoolchildren in Tanzania. We show how the bias and precision of worm burden estimates critically depends on the number of sampled offspring and we discuss strategies for obtaining sufficient sample sizes and for incorporating judiciously formulated prior information to improve the accuracy of estimates. Conclusions This work provides a novel approach for estimating individual-level worm burdens using genetic data on helminth offspring. This represents a step towards a wider scope of application of parentage analysis techniques. We discuss how the method could be used to assist in the interpretation of monitoring and evaluation data collected during mass drug administration programmes targeting human helminthiases and to help resolve outstanding questions on key population biological processes that govern the transmission dynamics of these neglected tropical diseases.

Abstract Background People with low health literacy (HL) are at increased risk of poor health outcomes, and receive less benefit from healthcare services. However, healthcare practitioners can effectively adapt healthcare information if they are aware of their patients’ HL. Measurements are available to assess HL levels but may not be practical for use within primary care settings. New alternative methods based on demographic indicators have been successfully developed, and we aim to test if such methodology can be applied to routinely collected consultation records. Methods Secondary analysis was carried out from a recently completed prospective cohort study that investigated a primary care population who had consulted about a musculoskeletal pain problem. Participants completed questionnaires (assessing general health, HL, pain, and demographic information) at baseline and 6 months, with linked data from the participants’ consultation records. The Single Item Literacy Screener was used as a benchmark for HL. We tested the performance of an existing demographic assessment of HL, whether this could be refined/improved further (using questionnaire data), and then test the application in primary care consultation data. Tests included accuracy, sensitivity, specificity, and area under the curve (AUC). Finally, the completed model was tested prospectively using logistic regression producing odds ratios (OR) in the prediction of poor health outcomes (physical health and pain intensity). Results In total 1501 participants were included within the analysis and 16.1% were categorised as having low HL. Tests for the existing demographic assessment showed poor performance (AUC 0.52), refinement using additional components derived from the questionnaire improved the model (AUC 0.69), and the final model using data only from consultation data remained improved (AUC 0.64). Tests of this final consultation model in the prediction of outcomes showed those with low HL were 5 times more likely to report poor health (OR 5.1) and almost 4 times more likely to report higher pain intensity (OR 3.9). Conclusions This study has shown the feasibility of the assessment of HL using primary care consultation data, and that people indicated as having low HL have poorer health outcomes. Further refinement is now required to increase the accuracy of this method.

Abstract Background Musculoskeletal (MSK) pain represents a considerable worldwide healthcare burden. This study aimed to gain consensus from practitioners who work with MSK pain patients, on the most appropriate primary care treatment options for subgroups of patients based on prognostic risk of persistent disabling pain. Agreement was sought on treatment options for the five most common MSK pain presentations: back, neck, knee, shoulder and multisite pain, across three risk subgroups: low, medium and high. Methods Three consensus group meetings were conducted with multi-disciplinary groups of practitioners (n = 20) using Nominal Group Technique, a systematic approach to building consensus using structured in-person meetings of stakeholders which follows a distinct set of stages. Results For all five pain presentations, “education and advice” and “simple oral and topical pain medications” were agreed to be appropriate for all subgroups. For patients at low risk, across all five pain presentations “review by primary care practitioner if not improving after 6 weeks” also reached consensus. Treatment options for those at medium risk differed slightly across pain-presentations, but all included: “consider referral to physiotherapy” and “consider referral to MSK-interface-clinic”. Treatment options for patients at high risk also varied by pain presentation. Some of the same options were included as for patients at medium risk, and additional options included: “opioids”; “consider referral to expert patient programme” (across all pain presentations); and “consider referral for surgical opinion” (back, knee, neck, shoulder). “Consider referral to rheumatology” was agreed for patients at medium and high risk who have multisite pain. Conclusion In addressing the current lack of robust evidence on the effectiveness of different treatment options for MSK pain, this study generated consensus from practitioners on the most appropriate primary care treatment options for MSK patients stratified according to prognostic risk. These findings can help inform future clinical decision-making and also influenced the matched treatment options in a trial of stratified primary care for MSK pain patients.

Abstract Objective People living with spinal cord injuries are at a high risk to experience preventable secondary health conditions in their lifetime, which can lead to rehospitalisation and death. Given the fact that spinal cord injury is a long term disability requiring on-going care, there is need to strengthen prevention of secondary health conditions. This study aims to establish factors influencing prevention care for secondary health conditions among people living with spinal cord injuries in a metropolitan area in order to develop a prevention model of care. Results A record review of patients living with spinal cord injuries will be conducted to identify the prevalence of secondary health conditions and associated factors. Semi-structured interviews will be conducted on patients living with spinal cord injuries, their caregivers and therapists to explore the contextual factors (personal and environmental factors) influencing the prevention of secondary health conditions. Thematic analysis will be used to identify the themes. Nominal group technique will be used to develop the prevention model of care for secondary health conditions. This study will be conducted at a tertiary and specialised rehabilitation hospital in South Africa.

Abstract Objectives As the global access of antiretrovirals for HIV-infected infants improves, so the body of perinatally HIV-infected adolescents (PHIVA) grows. The neurological and physical complications of HIV, both in children and in adults, are well established, however there is a paucity of data pertaining to PHIVA, a group of people who have had a lifetime exposure to the virus and to antiretrovirals. There has been a resounding call for further research in this area, as well as for the development of policies and programmes for this population. The aim of this study is to determine the physical sequelae in PHIVA and to propose a model of care for this population. Methods Through interviews with PHIVA, the perceived physical challenges will be established. Thereafter a cohort study with age-matched participants will determine if PHIVA have any limitations in fatigue, endurance, motor function and muscle strength, body mass index, peripheral neuropathy, level of disability and quality of life. Using these results, a model of care will be proposed through the nominal group technique with both PHIVA and clinicians working in HIV and adolescence.

Abstract Background This study aimed to describe recruitment challenges encountered during a phase IIa study of vixotrigine, a state and use-dependent Nav1.7 channel blocker, in individuals with trigeminal neuralgia. Methods This was an international, multicenter, placebo-controlled, randomized withdrawal study that included a 7-day run-in period, a 21-day open-label phase, and a 28-day double-blind phase in which patients (planned n = 30) were randomized to vixotrigine or placebo. Before recruitment, all antiepileptic drugs had to be stopped, except for gabapentin or pregabalin. After the trial, patients returned to their original medications. Patient recruitment was expanded beyond the original five planned (core) centers in order to meet target enrollment (total recruiting sites N = 25). Core sites contributed data related to patient identification for study participation (prescreening data). Data related to screening failures and study withdrawal were also analyzed using descriptive statistics. Results Approximately half (322/636; 50.6%) of the patients who were prescreened at core sites were considered eligible for the study and 56/322 (17.4%) were screened. Of those considered eligible, 26/322 (8.1%) enrolled in the study and 6/322 (1.9%) completed the study. In total, 125 patients were screened across all study sites and 67/125 (53.6%) were enrolled. At prescreening, reasons for noneligibility varied by site and were most commonly diagnosis change (78/314; 24.8%), age > 80 years (75/314; 23.9%), language/distance/mobility (61/314; 19.4%), and noncardiac medical problems (53/314; 16.9%). At screening, frequently cited reasons for noneligibility included failure based on electrocardiogram, insufficient pain, and diagnosis change. Conclusions Factors contributing to recruitment challenges encountered in this study included diagnosis changes, anxiety over treatment changes, and issues relating to distance, language, and mobility. Wherever possible, future studies should be designed to address these challenges. Trial registration ClinicalTrials.gov, NCT01540630. EudraCT, 2010-023963-16. 07 Aug 2015.

Abstract Objective Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodeficiency virus (HIV) pandemic coupled with negative environmental factors. Childhood developmental stimulation programmes can mitigate adverse outcomes. Methods Neonates testing HIV positive at birth will be initiated on antiretroviral treatment (ART) and receive an age-appropriate stimulation program, updated at 3 monthly intervals through the first year of life. Neurodevelopment at 12 months of age will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Outcomes will be compared with HIV-infected and HIV-exposed uninfected children (HEU) not having received the stimulatory intervention. Associations between neurodevelopmental outcomes, environmental factors, and parental stress will be investigated. The study will take place at a single site in Johannesburg, South Africa. This non-randomised controlled intervention study, with a single non-blinded comparative intervention group, aims to investigate whether an early childhood stimulation programme used in conjunction with ART initiated at birth can positively impact neurodevelopmental outcomes at 1 year of age in children infected with HIV. Trial registration 15 January 2018, Pan African Clinical Trial Registry PACTR201801002967587

Abstract Background Musculoskeletal disease is a common cause of morbidity, but there is a paucity of musculoskeletal research focusing on paediatric populations, particularly in primary care settings. In particular, there is limited information on population consultation frequency in paediatric populations, and frequency varies by age and sex. Few studies have examined paediatric musculoskeletal consultation frequency for different body regions. The objective was to determine the annual consultation prevalence of regional musculoskeletal problems in children in primary care. Methods Musculoskeletal codes within the Read morbidity Code system were identified and grouped into body regions. Consultations for children aged three to seventeen in 2006 containing these codes were extracted from recorded consultations at twelve general practices contributing to a general practice consultation database (CiPCA). Annual consultation prevalence per 10,000 registered persons for the year 2006 was determined, stratified by age and sex, for problems in individual body regions. Results Over 8 % (8.27%, 95% CI 7.86 to 8.68%) of the 16,862 children consulted with a musculoskeletal problem during 2006. Annual consultation prevalence for any musculoskeletal problem was significantly higher in males than females (male: female prevalence ratio 1.18, 95% CI 1.06 to 1.31). Annual consultation prevalence increased with age and the most common body regions consulted for were the foot, knee and back all of which had over 100 consultations (109, 104 and 101 respectively) per 10,000 persons per year. Conclusions This study provides new and detailed information on patterns of paediatric musculoskeletal consultations in primary care. Musculoskeletal problems in children are varied and form a significant part of the paediatric primary care workload. The findings of this study may be used as a resource for planning future studies.

Abstract Background Schistosoma mansoni is a parasite of profound medical importance. Current control focusses on mass praziquantel (PZQ) treatment of populations in endemic areas, termed Preventative Chemotherapy (PC). Large-scale PC programmes exert prolonged selection pressures on parasites with the potential for, direct and/or indirect, emergence of drug resistance. Molecular methods can help monitor genetic changes of schistosome populations over time and in response to drug treatment, as well as estimate adult worm burdens through parentage analysis. Furthermore, methods such as in vitro drug sensitivity assays help phenotype in vivo parasite genotypic drug efficacy. Methods We conducted combined in vitro PZQ efficacy testing with population genetic analyses of S. mansoni collected from children from two schools in 2010, five years after the introduction of a National Control Programme. Children at one school had received four annual PZQ treatments and the other school had received two mass treatments in total. We compared genetic differentiation, indices of genetic diversity, and estimated adult worm burden from parasites collected in 2010 with samples collected in 2005 (before the control programme began) and in 2006 (six months after the first PZQ treatment). Using 2010 larval samples, we also compared the genetic similarity of those with high and low in vitro sensitivity to PZQ. Results We demonstrated that there were individual parasites with reduced PZQ susceptibility in the 2010 collections, as evidenced by our in vitro larval behavioural phenotypic assay. There was no evidence, however, that miracidia showing phenotypically reduced susceptibility clustered together genetically. Molecular analysis also demonstrated a significant reduction of adult worm load over time, despite little evidence of reduction in parasite infection intensity, as measured by egg output. Genetic diversity of infections did not reduce over time, despite changes in the genetic composition of the parasite populations. Conclusions Genotypic and phenotypic monitoring did not indicate a selective sweep, as may be expected if PZQ treatment was selecting a small number of related “resistant” parasites, but there was evidence of genetic changes at the population level over time. Genetic data were used to estimate adult worm burdens, which unlike parasite infection intensity, showed reductions over time, suggesting the relaxation of negative density-dependent constraints on parasite fecundity with PZQ treatment. We thereby demonstrated that density-dependence in schistosome populations may complicate evaluation and monitoring of control programmes.

Abstract Background Mass drug administration of praziquantel is the World Health Organization’s endorsed control strategy for schistosomiasis. A decade of annual treatments across sub-Saharan Africa has resulted in significant reductions of infection prevalence and intensity levels, although ‘hotspots’ remain. Repeated drug treatments place strong selective pressures on parasites, which may affect life-history traits that impact transmission dynamics. Understanding drug treatment responses and the evolution of such traits can help inform on how to minimise the risk of drug resistance developing, maximise sustainable control programme success, and improve diagnostic protocols. Methods We performed a four-generation Schistosoma mansoni praziquantel selection experiment in mice and snails. We used three S. mansoni lines: a praziquantel-resistant isolate (R), a praziquantel-susceptible isolate (S), and a co-infected line (RS), under three treatment regimens: untreated, 25 mg/kg praziquantel, or 50 mg/kg praziquantel. Life-history traits, including parasite adult-worm establishment, survival, reproduction (fecundity), and associated morbidity, were recorded in mice across all four generations. Predictor variables were tested in a series of generalized linear mixed effects models to determine which factors had a significant influence on parasite life-history traits in definitive hosts under different selection regimes. Results Praziquantel pressure significantly reduced adult-worm burdens across all generations and isolates, including within R-lines. However, previous drug treatment resulted in an increase in adult-worm establishment with increasing generation from P1 to F3. The highest worm numbers were in the co-infected RS line. Praziquantel treatment decreased adult-worm burden, but had a larger negative impact on the mean daily number of miracidia, a proxy for fecundity, across all three parasite isolates. Conclusions Our predicted cost of resistance was not supported by the traits we measured within the murine host. We did not find evidence for negative adult worm density-dependent effects on fecundity. In contrast, of the adult worms that survived treatment, even low doses of praziquantel significantly reduced adult-worm fecundity. Such reductions in worm fecundity post treatment suggest that egg - based measures of drug efficacy, such as Kato-Katz, may overestimate the short-term effect of praziquantel on adult - worm burdens. These findings have important implications for S. mansoni transmission control, diagnostic protocols, and the potential for undetected selection toward drug resistance.

Abstract Background Knee problems are common in children and adolescents. Despite this, little is known about the epidemiology of knee problems in children and adolescents who consult in general practice. The aim of this study was to describe consultations by children and adolescents about knee problems in general practice, and examine patterns of patient presentations and consultations by age group, sex and area of socio-economic deprivation. Methods Consultations records specific to the knee region were extracted from a general practice consultation database (CiPCA) over a one year period. Knee consultation codes were organised into ‘symptom’ or ‘diagnosis’ (sub-categorised: ‘trauma’, ‘non-trauma’) categories. Descriptive statistics were used to describe patient presentations and number of consultations overall, and stratified analysis carried out on age group, sex, and ar ea of socio-economic deprivation. Results Out of all musculoskeletal consultations, knee problems were the fourth most common patient presentation, responsible for the second highest number of consultations. Patient presentations and consultations increased up to age 12–15 years and then stabilised. Symptoms codes e.g. ‘knee pain’ were used more commonly than diagnosis codes e.g. ‘knee sprain’ overall. However, symptom code use declined as age increased, more symptom codes were used in girls compared to boys, and more diagnosis codes were used in patients from areas of high socio-economic deprivation. Conclusions This study provides insight into the epidemiology of knee problems in children and adolescents in general practice. Future research is needed to improve our understanding of the knee problems encountered by GPs, and the influence socio-economic deprivation has on consultations.

Abstract Background Understanding and quantifying the sources and implications of error in the measurement of helminth egg intensity using Kato-Katz (KK) and the newly emerging “gold standard” quantitative polymerase chain reaction (qPCR) technique is necessary for the appropriate design of epidemiological studies, including impact assessments for deworming programs. Methods Repeated measurements of Ascaris lumbricoides infection intensity were made from samples collected in western Kenya using the qPCR and KK techniques. These data were combined with data on post-treatment worm expulsions. Random effects regression models were used to quantify the variability associated with different technical and biological factors for qPCR and KK diagnosis. The relative precision of these methods was compared, as was the precision of multiple qPCR replicates. Results For both KK and qPCR, intensity measurements were largely determined by the identity of the stool donor. Stool donor explained 92.4% of variability in qPCR measurements and 54.5% of observed measurement variance for KK. An additional 39.1% of variance in KK measurements was attributable to having expelled adult A. lumbricoides worms following anthelmintic treatment. For qPCR, the remaining 7.6% of variability was explained by the efficiency of the DNA extraction (2.4%), plate-to-plate variability (0.2%) and other residual factors (5%). Differences in replicate measurements by qPCR were comparatively small. In addition to KK variability based on stool donor infection levels, the slide reader was highly statistically significant, although it only explained 1.4% of the total variation. In a comparison of qPCR and KK variance to mean ratios under ideal conditions, the coefficient of variation was on average 3.6 times larger for KK highlighting increased precision of qPCR. Conclusions Person-to-person differences explain the majority of variability in egg intensity measurements by qPCR and KK, with very little additional variability explained by the technical factors associated with the practical implementation of these techniques. qPCR provides approximately 3.6 times more precision in estimating A. lumbricoides egg intensity than KK, and could potentially be made more cost-effective by testing each sample only once without diminishing the power of a study to assess population-level intensity and prevalence.

Abstract Background Colorectal cancer (CRC) diagnosed at

Abstract Background The last decade has seen an expansion of national schistosomiasis control programmes in Africa based on large-scale preventative chemotherapy. In many areas this has resulted in considerable reductions in infection and morbidity levels in treated individuals. In this paper, we quantify changes in the force of infection (FOI), defined here as the per (human) host parasite establishment rate, to ascertain the impact on transmission of some of these programmes under the umbrella of the Schistosomiasis Control Initiative (SCI). Methods A previous model for the transmission dynamics of Schistosoma mansoni was adapted here to S. haematobium. These models were fitted to longitudinal cohort (infection intensity) monitoring and evaluation data. Changes in the FOI following up to three annual rounds of praziquantel were estimated for Burkina Faso, Mali, Niger, Tanzania, Uganda, and Zambia in sub-Saharan Africa (SSA) according to country, baseline endemicity and schistosome species. Since schistosomiasis transmission is known to be highly focal, changes in the FOI at a finer geographical scale (that of sentinel site) were also estimated for S. mansoni in Uganda. Results Substantial and statistically significant reductions in the FOI relative to baseline were recorded in the majority of, but not all, combinations of country, parasite species, and endemicity areas. At the finer geographical scale assessed within Uganda, marked heterogeneity in the magnitude and direction of the relative changes in FOI was observed that would not have been appreciated by a coarser-scale analysis. Conclusions Reductions in the rate at which humans acquire schistosomes have been achieved in many areas of SSA countries assisted by the SCI, while challenges in effectively reducing transmission persist in others. Understanding the underlying heterogeneity in the impact and performance of the control intervention at the level of the transmission site will become increasingly important for programmes transitioning from morbidity reduction to elimination of infection. Such analyses will require a fine-scale approach. The lack of association found between programmatic variables, such as therapeutic treatment coverage (recorded at district level) and changes in FOI (at sentinel site level) is discussed and recommendations are made.

Abstract Background Front-of-pack (FOP) warning labels have demonstrated effectiveness for reducing sugar-sweetened beverage (SSB) consumption and switching to water. However, an unintended consequence is that they may also increase switching to non-sugar-sweetened beverages (NSSBs). A non-hypothetical experimental study examined the effectiveness of combining sugar and sweetener FOP warning labels to reduce sugary drink consumption and prevent NSSB substitution. The study also examined potential integration with Australia and New Zealand’s existing Health Star Rating (HSR) system to determine suitability for local context and other jurisdictions with interpretive labelling schemes already in place. Methods Participants (N = 414) accessed an online convenience store app via an on-campus laptop to select one drink from an array of 10 beverages, on three occasions. Drink options included a variety of SSBs, 100% fruit juice, NSSBs, and water. Following an escalating exposure procedure, drinks were presented (1) without any additional labelling, (2) with warning labels added to sugary drinks or to both sugary drinks and NSSBs (according to allocated condition), then (3) with HSR icons added to all drinks. Participants were informed they would receive a complementary drink, based on their selections, following the completion of a brief questionnaire. Results Baseline results indicated that SSBs and water were the most and least popular drink choices, respectively. Placing FOP warning labels on sugary drinks decreased selection of SSBs and increased NSSB and water choices. Water became the most popular individual drink choice in response to warnings on sugary drinks. Placing FOP warning labels on both sugary drinks and NSSBs successfully avoided an increase in NSSB choices, whilst also increasing water selections, but did not significantly decrease selection of SSBs until HSR ratings were added. The incorporation of HSR icons consolidated warning label effects on NSSB and water selection across both conditions. Conclusions Results demonstrate the potential of FOP sugar warning labels for addressing beverage consumption behaviours. The incorporation of sweetener warning labels may successfully avoid substitution towards NSSBs, whilst still promoting water choices, but may also dilute the impact of the sugary drinks warning labels. Warning labels were complementary to existing interpretive FOP labels.

Abstract Within physiotherapy and occupational therapy practice placements, there is a predominance of the one-to-one supervision model which creates limitations for placement capacity expansion. Alternative placement models must be explored to meet training requirements for these professions and ensure the availability of a future workforce. The aim of this review is to explore the experiences and perceptions of practice educators and learners regarding alternative placement models, to inform future planning and the adoption of these opportunities. This qualitative systematic review followed the Joanna Briggs Institute methodology. A comprehensive search was conducted across six databases (CINAHL, MEDLINE, PubMed, Scopus, ERIC, PsycINFO), covering the period from January 2010 to December 2022. Meta-aggregation was used to synthesise the findings from the included studies. A total of 16 articles were included within this review. The learner voice was represented in 14 categories aggregated to five synthesised findings: professional growth and development, personal and psychological adaptation, alliances within collaborative learning, educational and learning process, and managing professional relationships. The practice educator voice was represented in 11 categories aggregated into four synthesised findings: providing the right support; professional identity; peer relationships and levels of satisfaction. This review highlights positive aspects associated with skill development, personal growth, and the formation of professional identity following alternative placement experiences. However, it also reveals concerns including uncertainty and anxiety related to role clarity, expectations, and the structure within these environments. This understanding of the perceptions and experiences of both learners and practice educators can inform the development of targeted support and guidance from universities, addressing these challenges and enhancing overall satisfaction. Further adoption of alternative placement models has the potential to expand practice placement capacity for learners offering a promising environment for healthcare education. These models provide learners with invaluable experiences and skills essential for their future careers.

Abstract Background Adolescence is a crucial period for establishing healthy behaviours that can reduce the risk of noncommunicable diseases. However, limited data exist on the clustering of health-related behaviours, in adolescents from low- and middle-income countries (LMICs). This study examined how diet and physical activity behaviours cluster and how they are influenced by home and school area-level deprivation. Methods The study surveyed 527 adolescents in Yaoundé (Cameroon), Kingston (Jamaica), and Cape Town (South Africa) and grouped them into three categories according to the socioeconomic status (SES) of their homes and school areas (low-low, low-high, and high-high). A k-median algorithm defined three clusters and measured dietary attributes including Dietary Habit Score (DHS), Healthy Food Score (HFS), Nutritional Knowledge Questionnaire (NKQ), moderate-to-vigorous physical activity (MVPA), and sedentary time using validated questionnaires. The clusters were ranked based on their physical activity levels and compared them within each city using statistical tests. Results The scores on the NKQ and HFS indicated a poor level of both nutritional knowledge and healthy food consumption across sites. Cluster analysis revealed a consistent pattern of high screen time clustering with lower (less healthy) dietary scores across sites. This pattern was consistent regardless of SES in Kingston, and SES and school socioeconomic areas in Cape Town and Yaoundé. Conclusion An inverse clustering of sedentary behaviour duration and eating habits remained consistent across different strata for at least two sites, suggesting that interventions to reduce sedentary time could have a ripple effect on multiple NCD risk factors in adolescence.

Abstract Background Incurable cancer is a major contributor to societal suffering and disability, and palliative rehabilitation is recommended to be integrated within and between cancer services at all healthcare levels. However, little knowledge exists on how integration of palliative rehabilitation in cancer is understood and achieved in clinical practice. INSPIRE (Integrated short-term palliative rehabilitation to improve quality of life and equitable care access in incurable cancer) is a large European-funded project that aims to promote quality of life through a novel rehabilitation model for people disabled by advanced cancer. Aim To compare the existing integration of palliative rehabilitation in cancer within official documents and in clinical practice across five European countries including United Kingdom, France, Denmark, Norway, and Italy. Methods Mixed methods study with a concurrent research design, comprising a document analysis (N = 23), stakeholder interviews (N = 22), and an online survey (N = 225). Data from each sub-study were analysed separately before results were merged. Results There was limited integration of palliative rehabilitation in cancer in official documents and in clinical practice, though some indicators of integration, including participation in multidisciplinary teams and adherence to standardised pathways, were identified in the survey. Notably, integration of palliative rehabilitation in cancer in clinical practice was observed within limited organisations in secondary healthcare systems, without widespread adoption. Although palliative rehabilitation in cancer as a concept was sparingly used by stakeholders, they recognised the need for a comprehensive approach including multidisciplinary teams that aligns with the individual patient’s needs and goals. Moreover, the ambiguous distinction between the terms ‘palliative rehabilitation’ and ‘palliative care’, insufficient funding, lack of well-defined care pathways and competence gaps among healthcare professionals represented barriers to integration of palliative rehabilitation in cancer into clinical practice. Conclusion Integration of palliative rehabilitation in cancer was limited in the five EU partnership countries investigated. Clarifying the concept of palliative rehabilitation, including adoption of the concept into official documents and delineating it from palliative care, is essential for more successful integration. This can possibly be achieved by addressing the barriers identified and fostering close collaboration across disciplines.

Abstract Background The prevention of type 2 diabetes (T2DM) is recognised as a health care priority in the UK. In people living with T2DM, lifestyle changes (e.g. increasing physical activity) have been shown to slow disease progression and protect from the development of associated comorbidities. The use of digital health technologies provides a strategy to increase physical activity in patients with chronic disease. Furthermore, behaviour economics suggests that financial incentives may be a useful strategy for increasing the maintenance and effectiveness of behaviour change intervention, including physical activity intervention using digital health technologies. The Milton Keynes Activity Rewards Programme (MKARP) is a 24-month intervention which combines the use of a mobile health app, smartwatch (Fitbit or Apple watch) and financial incentives to encourage people living with T2DM to increase physical activity to improve health. Therefore, this randomised controlled trial aims to examine the long-term acceptability, health effects and cost-effectiveness of the MKARP on HbA1c in patients living with T2DM versus a waitlist usual care comparator. Methods A two-arm, single-centre, randomised controlled trial aiming to recruit 1018 participants with follow-up at 12 and 24 months. The primary outcome is the change in HbA1c at 12 months. Secondary outcomes included changes in markers of metabolic, cardiovascular, anthropometric, and psychological health along with cost-effectiveness. Recruitment will be via annual diabetes review in general practices, retinal screening services and social media. Participants aged 18 or over, with a diagnosis of type 2 diabetes and a valid HbA1c measurement in the last 2 months are invited to take part in the trial. Participants will be individually randomised (1:1 ratio) to receive either the Milton Keynes Activity Rewards Programme or usual care. The intervention will last for 24 months with assessment for outcomes at baseline, 12 and 24 months. Discussion This study will provide new evidence of the long-term effectiveness of an activity rewards scheme focused on increasing physical activity conducted within routine care in patients living with type 2 diabetes in Milton Keynes, UK. It will also investigate the cost-effectiveness of the intervention. Trial registration ISRCTN 14925701. Registered on 30 October 2023.