Search

Wirachin Hoonpongsimanont,1 Maja Feldman,1 Nicholas Bove,1 Preet Kaur Sahota,1 Irene Velarde,1,2 Craig L Anderson,1 Warren Wiechmann1 1Department of Emergency Medicine, University of California, Irvine School of Medicine, Irvine, CA, USA; 2Touro University College of Osteopathic Medicine, Vallejo, CA, USA Purpose: Providing feedback to students in the emergency department during their emergency medicine clerkship can be challenging due to time constraints, the logistics of direct observation, and limitations of privacy. The authors aimed to evaluate the effectiveness of first-person video, captured via Google Glass™, to enhance feedback quality in medical student education. Material and methods: As a clerkship requirement, students asked patients and attending physicians to wear the Google Glass™ device to record patient encounters and patient presentations, respectively. Afterwards, students reviewed the recordings with faculty, who provided formative and summative feedback, during a private, one-on-one session. We introduced the intervention to 45, fourth-year medical students who completed their mandatory emergency medicine clerkships at a United States medical school during the 2015–2016 academic year.Results: Students assessed their performances before and after the review sessions using standardized medical school evaluation forms. We compared students’ self-assessment scores to faculty assessment scores in 14 categories using descriptive statistics and symmetric tests. The overall mean scores, for each of the 14 categories, ranged between 3 and 4 (out of 5) for the self-assessment forms. When evaluating the propensity of self-assessment scores toward the faculty assessment scores, we found no significant changes in all 14 categories. Although not statistically significant, one fifth of students changed perspectives of their clinical skills (history taking, performing physical exams, presenting cases, and developing differential diagnoses and plans) toward faculty assessments after reviewing the video recordings.Conclusion: First-person video recording still initiated the feedback process, allocated specific time and space for feedback, and possibly substituted for the direct observation procedure. Additional studies, with different outcomes and larger sample sizes, are needed to understand the effectiveness of first-person video in improving feedback quality. Keywords: clerkship, emergency medicine, feedback, medical student education, first-person video

Abstract Background Group B Streptococcus (GBS) infection remains a leading cause of newborn morbidity and mortality. The study aimed to determine the adherence rate to the universal screening policy a decade after its introduction. Secondly, whether the timing of antibiotics given in GBS carriers reduces the incidence of neonatal sepsis. Methods Delivery records at Hong Kong Baptist Hospital in 2022 were examined to retrieve antenatal and intrapartum details regarding maternal GBS carrier status, previous maternal GBS carrier status, antibiotic treatment, timing of treatment, neonatal condition at birth and whether the neonate had sepsis. Univariate statistics was used to assess the relationship between maternal GBS carrier and neonatal sepsis overall. Incidence of neonatal sepsis was stratified according to mode of delivery and timing of antibiotic. Results The adherence rate to the universal GBS screening policy was 97%. The risk of neonatal sepsis was 5.45 (95% CI 3.05 to 9.75) times higher in women who were GBS screened positive when compared to non-GBS carriers (p

Abstract Objectives Eating disorders (EDs) typically emerge during adolescence. Parental bonding has a lasting impact on a child’s mental health during those developmentally critical years. There remains uncertainty over whether parental bonding is a risk factor for developing or maintaining specifically EDs or, rather, general psychopathology and the associated underlying brain function. Methods Forty-one young adult healthy control individuals (HC, 26.6 ± 3.5 years) and 46 individuals with EDs (25 with anorexia nervosa, AN, 22.8 ± 6.4 years, and 21 with bulimia nervosa, BN, 23.5 ± 4.2 years) completed the parental bonding instrument (PBI), assessments for anxiety, depression, and ED behaviors, and underwent a conditioning paradigm during brain imaging. Results In both groups, perceived parental care and overprotection were correlated with state and trait anxiety and interpersonal alienation, and in HC only, with body dissatisfaction and drive for thinness. Individuals with an ED reported lower self-perceived parental care, but higher overprotection compared to the HC group. Nucleus accumbens (NAc) response was related to bonding measures in both groups and right NAc response mediated the relationship between maternal care and trait anxiety in HC. Conclusions Perceived parental bonding is associated with general psychopathology, including elevated anxiety and interpersonal difficulties across HC and ED groups. Lower perceived parental care and higher overprotection could predispose healthy individuals to develop problems with body shape or weight; however, other, maybe biological factors may determine whether a person will develop an ED. The link between perceived parental bonding, NAc valence processing and anxiety implicates dopaminergic circuits that should be studied further. Level of Evidence: Level III: Case–control analytic study

A 79-year-old female presented with a 3-week history of dysphagia and vomiting, and an upper abdominal mass which had increased in size over the previous 2 weeks. CT scan showed a partial gastric outlet obstruction secondary to an epigastric hernia. This was assessed further on fluoroscopy, showing the distal stomach in the hernial sac and a delay in gastric emptying. We present the CT and fluoroscopic findings of this rare cause of gastric outlet obstruction.

Objective: To evaluate the performance of maternal factors, biophysical and biochemical markers at 11–13 + 6 weeks’ gestation in the prediction of gestational diabetes mellitus with or without large for gestational age (GDM ± LGA) fetus and great obstetrical syndromes (GOS) among singleton pregnancy following in-vitro fertilisation (IVF)/embryo transfer (ET). Materials and methods: A prospective cohort study was conducted between December 2017 and January 2020 including patients who underwent IVF/ET. Maternal mean arterial pressure (MAP), ultrasound markers including placental volume, vascularisation index (VI), flow index (FI) and vascularisation flow index (VFI), mean uterine artery pulsatility index (mUtPI) and biochemical markers including placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 11–13 + 6 weeks’ gestation. Logistic regression analysis was performed to determine the significant predictors of complications. Results: Among 123 included pregnancies, 38 (30.9%) had GDM ± LGA fetus and 28 (22.8%) had GOS. The median maternal height and body mass index were significantly higher in women with GDM ± LGA fetus. Multivariate logistic regression analysis demonstrated that in the prediction of GDM ± LGA fetus and GOS, there were significant independent contributions from FI MoM (area under curve (AUROC) of 0.610, 95% CI 0.492–0.727; p = 0.062) and MAP MoM (AUROC of 0.645, 95% CI 0.510–0.779; p = 0.026), respectively. Conclusion: FI and MAP are independent predictors for GDM ± LGA fetus and GOS, respectively. However, they have low predictive value. There is a need to identify more specific novel biomarkers in differentiating IVF/ET pregnancies that are at a higher risk of developing complications.

Objective Routine screening for cardiovascular disease before kidney transplantation remains controversial. This study aims to compare cardiac testing rates in patients with end-stage renal disease, referred and not referred for transplantation, and assess the impact of testing on transplant wait times.Methods This is a retrospective cohort study of 22 687 end-stage renal disease patients from 2011 to 2022, within an integrated health system. Cardiac testing patterns, and the association between cardiac testing and transplant wait times and post-transplant mortality were evaluated.Results Of 22 687 patients (median age 66 years, 41.1% female), 6.9% received kidney transplants, and 21.0% underwent evaluation. Compared with dialysis patients, transplant patients had a 5.6 times higher rate of stress nuclear myocardial perfusion imaging with single-photon emission (rate ratio (RR) 5.64, 95% CI 5.37 to 5.92), a 6.5 times higher rate of stress echocardiogram (RR 6.51, 95% CI 5.65 to 7.51) and 16% higher cardiac catheterisation (RR 1.16, 95% CI 1.06 to 1.27). In contrast, revascularisation rates were significantly lower in transplant patients (RR 0.46, 95% CI 0.36 to 0.58). Transplant wait times were longer for patients who underwent stress testing (median 474 days with no testing vs 1053 days with testing) and revascularisation (1796 days for percutaneous intervention and 2164 days for coronary artery bypass surgery). No significant association was observed with 1-year post-transplant mortality (adjusted OR 1.99, 95% CI 0.46 to 8.56).Conclusions This study found a higher rate of cardiac testing in dialysis patients evaluated for kidney transplants. Cardiac testing was associated with longer transplant wait time, but no association was observed between testing and post-transplant mortality.

Summary: Diagnosis of respiratory tract infections (RTIs), especially in primary care, is typically made on clinical features and in the absence of quick and reliable diagnostic tests. Even in secondary care, where diagnostic microbiology facilities are available, these tests take 24–48 h to provide an indication of the etiology. This multicentre study used a portable gas chromatography-ion mobility spectrometer (GC-IMS) for the diagnosis of bacterial RTIs. Breath samples taken from 570 participants with 149 clinically validated bacterial and 421 non-bacterial RTIs were analyzed to distinguish bacterial from non-bacterial RTIs. Through the integration of a sparse logistic regression model, we identified a moderate diagnostic accuracy of 0.73 (95% CI 0 · 69, 0 · 77) alongside a sensitivity of 0 · 85 (95% CI 0 · 79, 0 · 91) and a specificity of 0 · 55 (95% CI 0 · 50, 0 · 60). The GC-IMS diagnostic device provides a promising outlook in distinguishing bacterial from non-bacterial RTIs and was also favorably viewed by participants.

Background: Health policies and programs in India are put into practice at the local level, where the frontline managers -Medical Officers in Charges (MOICs) use data for evidence-based decision-making (EBDM) and implementing these programs. However, there are various organizational, technical, and individual determinants that can impact data use. The study aims to recognize the determinants of data-driven decision-making at the grassroots level. Methods: The cross-sectional study collected primary empirical data from 120 MOICs from six identified districts in Haryana, India. Data utilization was the variable of interest and was measured through Data Utilization Score (DUS). Determinants affecting DUS were extracted through Principal Component Analysis (PCA). Hierarchical multiple regression analysis was used to identify predictors of data utilization from the extracted factors. Results: MOICs used routine data to plan, implement, manage, and monitor health programs, and administrative activities. Actual skill for data usage (65 %) was less than the anticipated skill (82 %). Twenty-seven reliable organizational, technical, and individual factors were generated from the 154 variables explaining 57.7 %–68 % of the total variance. Regression analysis showed that management meetings with superiors/subordinates, data-conducive and promotive culture, perceived data quality, incentivization, basic software knowledge/skills, and training needs were among the most significant predictors of data usage. Conclusion: Although a disparity exists between the expected and actual data utilization skills of MOICs, still data-based decisions can be enhanced by effective management meetings, fostering a robust data culture, prioritizing skill development, and incentivizing data use.

BackgroundThe effects of climate change are seen with a rise of extreme weather and climate events (EWCEs) which lead to the closures of many healthcare facilities, such as community pharmacies. Pharmacists in community pharmacies are seen as the most accessible healthcare professional to the public and are responsible for the continued delivery of care to patients. However, amid closures due to EWCEs and the emergence of pharmacy deserts, there is decreased access to pharmacies and a disruption of care.ObjectiveIt is important to address the preparedness and accessibility of pharmacies post-EWCEs to guide future research and policy. Additionally, to tackle health disparities that arise due to pharmacy deserts, the populations most affected by a decreased access to pharmacies should be identified. We conducted a scoping review to assess the preparedness and accessibility of pharmacies post-EWCEs and to identify populations most affected by pharmacy deserts.MethodsWe searched PubMed, Embase, and Web of Science from January 1, 2012 to September 30, 2022 and included all English-language, peer-reviewed primary literature that examined the preparedness and accessibility of community pharmacies in the United States post-EWCEs and addressed disparities within pharmacy deserts. Studies meeting these criteria were screened of their titles and abstracts by the first author and discrepancies were resolved with co-authors. We used Covidence for data extraction.ResultsA total of 472 studies were identified (196 duplicates removed) and after screening, 53 studies were assessed for eligibility. The results of included publications (N = 26) showed that pharmacists and pharmacies are not equipped with the necessary emergency protocols which could lead to decreased access of pharmacies in the wake of EWCEs. Pharmacy deserts disproportionately affect residents living in rural, lower income, and Black/African American and Hispanic/Latino neighborhoods. The lack of preparedness of pharmacies post-EWCEs could worsen medication access.ConclusionThis scoping review addresses challenges impacting pharmacies and patients post-EWCEs and within pharmacy deserts. In times of increased need, these challenges implicate the well-being of communities affected by EWCEs by breaking the continuum of care and access to medications. Here we offer suggestions for future research and directions for policy change.

IntroductionDespite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.MethodsWe screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.ResultsWe screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.ConclusionsThis analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Remote sensing technology currently facilitates the monitoring of crop development, enabling detailed analysis and monitoring throughout the crop’s growing stages. This research analyzed the winter wheat growth dynamics of experimental plots at the Lakehead University Agricultural Research Station, Thunder Bay, Canada using high spatial and temporal resolution remote sensing images. The spectral signatures for five growing stages were prepared. NIR reflectance increased during the growing stages and decreased at the senescence, indicating healthy vegetation. The space–time cube provided valuable insight into how canopy height changed over time. The effect of nitrogen treatments on wheat did not directly influence the plant count (spring/autumn), and height and volume at maturity. However, the green and dry weights were different at several treatments. Winter wheat yield was predicted using the XGBoost algorithm, and moderate results were obtained. The study explored different techniques for analyzing winter wheat growth dynamics and identified their usefulness in smart agriculture.

Abstract Background Dementia has been the leading cause of death in the UK since 2015. Increasing evidence supports an association between socioeconomic position (SEP) and dementia onset in later life. However, limited studies have examined how life-course SEP influences the development of mild cognitive impairment (MCI), an intermediate state potentially preceding dementia. Therefore, the present study aims to examine the relationship between life-course SEP and MCI amongst adults aged 50 years in Great Britain. Methods We employed data from the National Child Development Study (NCDS), also known as the 1958 British Birth Cohort, to determine the associations between SEP and MCI in 6590 participants. We categorised life-course measures of SEP as stable high/low or moving upward/downward over the life course. We assessed MCI at age 50 using one standard deviation below the averaged combined scores from all cognitive tests available. We then used binary logistic regression to estimate the longitudinal associations between life-course SEP and MCI. Results Relative to those of a high SEP across the life course, participants who moved upward, downward, or remained at a low SEP were significantly associated with 25% (95% CI 1.02–1.54, p = 0.035), 70% (95% CI 1.27–2.27, p

Abstract A changing climate offers new opportunities to expand agriculture in northern latitudes, and understanding forest‐to‐agriculture land conversion impacts is critical to ensure soil sustainability. Using the Comprehensive Assessment of Soil Health (CASH) framework, we identified a minimum suite of indicators with little collinearity to reliably predict soil impacts during the conversion of boreal forest to agriculture and a time since conversion gradient (forest, 10 and 50 years since conversion). We sampled paired forest and agricultural sites and used multiple linear regression to assess 16 indicators and found four‐ and six‐indicator models predicted the CASH score with varying but reasonable accuracy depending on conversion class. Organic matter, water aggregate stability, and pH were consistent predictors across all classes, as well as one or more micronutrients. The CASH framework appears to be more suitable for agricultural soils and as time since conversion proceeds.

Introduction Panic disorder (PD) and agoraphobia (AG) are highly comorbid anxiety disorders with an increasing prevalence that have a significant clinical and public health impact but are not adequately recognized and treated. Although the current functional neuroimaging literature has documented a range of neural abnormalities in these disorders, primary studies are often not sufficiently powered and their findings have been inconsistent. Objectives This meta-analysis aims to advance our understanding of the neural underpinnings of PD and AG by identifying the most robust patterns of differential neural activation that differentiate individuals diagnosed with one of or both these disorders from age-matched healthy controls. Methods We conducted a comprehensive literature search in the PubMed database for all peer-reviewed, whole-brain, task-based functional magnetic resonance imaging (fMRI) activation studies that compared adults diagnosed with PD and/or AG with age-matched healthy controls. Each of these articles was screened by two independent coding teams using formal inclusion criteria and according to current PRISMA guidelines. We then performed a voxelwise, whole-brain, meta-analytic comparison of PD/AG participants with age-matched healthy controls using multilevel kernel density analysis (MKDA) with ensemble thresholding (p

Background Bisphosphonates are a class of medication commonly used to treat osteoporosis. Alendronate is recommended as the first-line treatment; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates are available, which can be given intravenously and have been shown to improve long-term adherence. However, the most clinically effective and cost-effective alternative bisphosphonate regimen remains unclear. What is the most cost-effective bisphosphonate in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice. Objectives Explore patient, clinician and stakeholder views, experiences and preferences of alendronate compared to alternative bisphosphonates. Update and refine the 2016 systematic review and cost-effectiveness analysis of bisphosphonates, and estimate the value of further research into their benefits. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities. Methods The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: Stage 1A – we elicited patient and healthcare experiences to understand their preferences of bisphosphonates for the treatment of osteoporosis. This was undertaken by performing a systematic review and framework synthesis of qualitative studies, followed by semistructured qualitative interviews with participants. Stage 1B – we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effectiveness model, incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence. Stage 2 – we identified and ranked further research questions that need to be answered about the effectiveness and acceptability of bisphosphonates. Results Patients and healthcare professionals identified a number of challenges in adhering to bisphosphonate medication, balancing the potential for long-term risk reduction against the work involved in adhering to oral alendronate. Intravenous zoledronate treatment was generally more acceptable, with such regimens perceived to be more straightforward to engage in, although a portion of patients taking alendronate were satisfied with their current treatment. Intravenous zoledronate was found to be the most effective, with higher adherence rates compared to the other bisphosphonates, for reducing the risk of fragility fracture. However, oral bisphosphonates are more cost-effective than intravenous zoledronate due to the high cost of zoledronate administration in hospital. The importance of including patients and healthcare professionals when setting research priorities is recognised. Important areas for research were related to patient factors influencing treatment selection and effectiveness, how to optimise long-term care and the cost-effectiveness of delivering zoledronate in an alternative, non-hospital setting. Conclusions Intravenous zoledronate treatment was generally more acceptable to patients and found to be the most effective bisphosphonate and with greater adherence; however, the cost-effectiveness relative to oral alendronate is limited by its higher zoledronate hospital administration costs. Future work Further research is needed to support people to make decisions influencing treatment selection, effectiveness and optimal long-term care, together with the clinical and cost-effectiveness of intravenous zoledronate administered in a non-hospital (community) setting. Limitations Lack of clarity and limitations in the many studies included in the systematic review may have under-interpreted some of the findings relating to effects of bisphosphonates. Trial registration This trial is registered as ISRCTN10491361. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127550) and is published in full in Health Technology Assessment; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information. Plain language summary Background Bisphosphonates are drug treatments commonly used to treat osteoporosis. Alendronate is the most used and is taken by mouth, weekly at a specific time of the week, which can be challenging. Less than one in four people continue this treatment beyond 2 years. Alternative bisphosphonates are available, which vary in frequency and how they are administered. The most acceptable and best value-for-money regimen is unclear. Aim Our aim was to determine how effective alternative bisphosphonates are compared to alendronate at preventing fractures and whether reduction in fracture risk was achieved at a reasonable financial cost, but acceptable to patients. Design and methods The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: Stage 1A: a review of the published evidence on patients’ and doctors’ views, experiences and preferences regarding different bisphosphonate treatment regimens, followed by interviews with patients and healthcare professionals. Stage 1B: an update of an existing study on how effective bisphosphonates are in preventing fragility fractures caused by osteoporosis and whether they are good value for money. Stage 2: identification of questions that need to be answered about the effectiveness and acceptability of bisphosphonate treatments. Results Taking bisphosphonate medication often involves quite a lot of effort by patients, particularly when taking alendronate tablets. A yearly infusion of zoledronate treatment was more acceptable, easier to engage with and the most effective treatment compared to alendronate. However, the cost of administering zoledronate in hospital made alendronate better value for money. Conclusions Bisphosphonates are effective in reducing the risk of fracture, but ‘continuing with treatment’, particularly alendronate tablets, remains a challenge. A yearly infusion of zoledronate offers an acceptable and effective treatment, but further research is needed to support patients and healthcare professionals in making decisions about the various treatments, benefits and cost savings of administering zoledronate outside of hospital and in the community. Scientific summary Background Alendronate (ALN) is recommended as the first-line osteoporosis treatment to prevent osteoporotic fractures; however, long-term adherence (both treatment compliance and persistence) is poor. Alternative bisphosphonates (BP) are available, which vary in frequency of use and/or route of administration and have been shown to improve long-term adherence compared to ALN. However, the most clinically effective and cost-effective alternative regimen remains unclear. Furthermore, clinicians should optimise dosing regimens on the basis of the patient’s understanding, preference and characteristics. What is the most cost-effective BP in clinical trials may not be the most cost-effective or acceptable to patients in everyday clinical practice. Objectives Explore patient, clinician and stakeholder views, experiences and preferences of ALN compared to alternative BP. Update and refine the 2016 systematic review and cost-effectiveness analysis of BP and estimate the value of further research into the relative benefits. Undertake stakeholder/consensus engagement to identify important research questions and further rank research priorities. Methods The study was conducted in two stages, stages 1A and 1B in parallel, followed by stage 2: Stage 1A: we elicited patient and clinician experiences of different BP regimens to understand their preferences and those of other stakeholders compared to ALN. This was undertaken by performing a systematic review and framework synthesis of qualitative studies around clinician and patient views, followed by semistructured qualitative interviews with multidisciplinary stakeholders. Stage 1B: we updated and expanded the existing Health Technology Assessment systematic review and clinical and cost-effective health economic model (2016), incorporating a more comprehensive review of treatment efficacy, safety, side effects, compliance and long-term persistence. The model takes a NHS and Personal Social Services perspective, with future costs and quality-adjusted life-years (QALYs) discounted at 3.5% per annum. Costs are reported in pound sterling based on 2021 prices. Stage 2: using an approach based on the James Lind methodology for identification and prioritisation of research questions, we identified questions that needed to be answered about the effectiveness and acceptability of BP. Findings from stages 1A and 1B, together with multidisciplinary meetings, identified areas of uncertainty. These questions were then ranked in a multidisciplinary, nationally representative stakeholder event, conducted online over MS Teams. Results We identified, through a systematic review of previous studies on patient and clinician experiences of BP treatment, how patients and healthcare professionals make sense (coherence) of BP by balancing perceptions of need against concerns, how uncertainty prevails about BP-perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to BP. The qualitative interview study examining experiences of alternate BP regimens found that intravenous (IV) BP zoledronate (ZOL) treatment was generally more acceptable to patients. Such IV regimens were perceived to be more straightforward to engage in, although a portion of patients taking ALN were satisfied with their current treatment. The systematic review and network meta-analysis of previous studies of effectiveness found that IV ZOL was the most effective BP compared to ALN, risedronate and oral ibandronate for reducing the risk of fragility fractures. Adherence was higher in IV ZOL users. It was found that clinical decision-making could be facilitated by considering adherence patterns in BP users who were at increased risk of fracture. However, the higher hospital administration costs for IV ZOL meant that the incremental cost-effectiveness ratios for IV ZOL compared to ALN were greater than £30,000 per QALY across all risk categories. This was despite the fact that IV ZOL was predicted to result in fewer fractures than ALN, due to its higher treatment persistence and a longer offset period. The prioritisation exercise highlighted a need for further research to tackle the issues relating to patient factors influencing treatment selection and effectiveness, including in younger adults, how to optimise long-term care and support patient and clinician decision-making and the clinical and cost-effectiveness of giving IV ZOL in alternate settings to hospital care. Conclusions We have identified the factors that influence how patients and clinicians make sense of BP, described the experience of BP taking in terms of burden and identified factors that both facilitate and hinder confidence in taking and prescribing and monitoring BP. IV ZOL treatment was generally more acceptable to patients. IV ZOL was found to be the most effective BP and with greater adherence; however, the cost-effectiveness of IV ZOL relative to ALN was limited by the high hospital administration costs. Further research is needed to support people to make decisions influencing treatment selection and effectiveness and establish how to optimise long-term care. In addition, research is needed to explore the clinical and cost-effectiveness of IV ZOL delivered in alternate settings, such as in the community, compared to ALN treatment. Patient and public involvement We have worked closely with the Royal Osteoporosis Society (ROS) and the Nottingham ROS (NotROS) Support Group, who together have influenced the design of this application, choice of study outcomes and were involved throughout the study. Trial registration This trial is registered as ISRCTN10491361. 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: NIHR127550) and is published in full in Health and Social Care Delivery Research; Vol. 28, No. 21. See the NIHR Funding and Awards website for further award information.

IntroductionOptical stimulation has been suggested for neural stimulation to improve cochlear implants. Light allows for more spatially selective activation of neuron populations than electrical current, offering more independent frequency bands along the spiral ganglion. These bands are available to encode acoustic information with anticipated better frequency resolution, improving cochlear implant user performance in noisy listening environments, tonal languages, and music perception.MethodsOptical cochlear implants (oCIs) can deliver light either directly via small emitters within the cochlea or via waveguides from external optical sources. We investigated three waveguide designs made from OrmoComp®, a polymer that cures through ultraviolet (UV) radiation. Waveguides were fabricated via injection molding and coated using dip-coating or thermal reflow, or through aspiration of OrmoComp® into polyimide tubing that served as the cladding of the waveguide. The choice of fabrication technique directly determined the waveguides' total diameter: thermal reflow yielded ≈940 μm, dip-coating produced ≈306 μm, and aspiration resulted in ≈132 μm core diameter waveguides. Given the human cochlea's small size, we focused on analyzing the 306-μm and 132-μm waveguides, evaluating their optical performance (propagation and bending losses) and mechanical properties (bending stiffness and insertion forces). Furthermore, we evaluated some of these designs in in-vivo guinea pigs experiments.ResultsFor the 100-μm core diameter waveguides, the propagation losses were 12.34 ± 1.26, 1.18 ± 0.88, 1.49 ± 0.58, and 3.43 ± 0.68 dB/cm at 534, 1,375, 1,460, and 1,550 nm, respectively. The respective bending losses at a 2 mm radius of curvature were 5.50 ± 1.32, 0.56 ± 0.26, 0.79 ± 0.18, and 0.64 ± 0.23 dB, and at 1 mm 8.54 ± 1.30, 2.05 ± 0.84, 2.11 ± 0.50, and 1.44 ± 0.37 dB. The bending stiffness of a 1 mm segment of the 100-μm-diameter waveguides was 18.9 ± 2.2 N/m. Insertion forces for the 100-μm-diameter waveguides into an acrylic human-size scala tympani model were < 25 mN. For the waveguides with 306 and 940 μm total diameter, the propagation losses ranged between 0.43 and 2.40 dB/cm at 534, 680, 1,375, and 1,550 nm, between 2.19 and 3.78 dB/cm at 450 and 1,460 nm. Bending losses for 360 degrees at 1,375 nm were 5.0, 2.4, and 0.46 for a bending radius of 2.5-, 3-, and 4-mm.DiscussionOur study demonstrated that the polymer OrmoComp® is suitable for fabricating waveguides to transmit near-infrared radiation. In-vivo experiments showed optically evoked auditory responses originating from optical stimulation in the guinea pigs' first cochlear turn while radiation was delivered. Incoming experiments will focus on evaluating long-term performance of these waveguides in guinea pigs and cats. This study will be designed to provide insights into the waveguides' performance and biocompatibility over extended periods, essential for their potential clinical application in future oCIs.

Introduction Pre-eclampsia (PE) affects about 5% of Chinese pregnant women and is a major cause of maternal and perinatal morbidity and mortality. The first trimester screening model developed by the Fetal Medicine Foundation, which uses the Bayes theorem to combine maternal characteristics and medical history together with measurements of biomarkers, has been proven to be effective and has superior screening performance to that of the traditional risk factor-based approach for the prediction of PE. Prophylactic use of low-dose aspirin in women at risk for PE has resulted in a lower incidence of preterm-PE. However, there is no consensus on the preferred aspirin dosage for the prevention of preterm-PE. Evidence has also suggested that metformin has the potential benefit in preventing PE in pregnant women who are at high risk of the disorder.Method and analysis We present a protocol (V.2.0, date 17 March 2022) for the AVERT trial, which is a multicentre, double-blinded, 3-arm randomised controlled trial (RCT) that uses an effective PE screening programme to explore the optimal dosage of aspirin and the role of metformin for the prevention of PE among high-risk pregnant women in China. We intend to recruit 66 000 singleton pregnancies without treatment of low-dose aspirin and metformin at 11–13 weeks’ gestation and all eligible women attending for their first trimester routine scan will be invited to undergo screening for preterm-PE by the combination of maternal factors, mean arterial pressure and placental growth factor. Women found to be at high risk of developing preterm-PE will be invited to take part in the RCT. This study will compare the incidence of preterm-PE with delivery at