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Abstract Background Relative to country-specific epidemiological trends, Kuwait experiences a far greater burden of type 2 diabetes among its population. Information behaviours form a significant component of self-care management for patients diagnosed with type 2 diabetes, however this remains an understudied aspect of disease management. This study aims to investigate the information behaviours of patients with type 2 diabetes in Kuwait, and characterise the methods employed to manage their disease. Methods This qualitative study employed a grounded theory method. Semi-structured interviews were conducted with twenty-seven participants over three phases of data collection in primary, secondary and tertiary healthcare settings across Kuwait. These were complemented by in-depth interviews to detail the information behaviours of these participants. The interviews were translated where appropriate, transcripts, and analysed through qualitative coding to synthesise the information behaviour patterns. Results The findings demonstrated that living with type 2 diabetes involved a range of developmental and transformative stages, including changes to the patients’ emotional state, reconstruction of their lifestyle and identity, and changes in the ways they find and use information. Living with the chronic condition was viewed as a dynamic and transitional process, where patients’ information behaviours continually changed throughout the process across various identifiable stages. This dynamic pattern was reflected most prominently across the participants’ behavioural needs, sources and information-seeking patterns. Conclusion Patients with type 2 diabetes continuously adapted their information behaviours to optimise the self-management of their condition across a relatively predictable pattern. Greater understanding of these behaviours across a wider population would improve the provision of clinical care for patients with diabetes.

The dynamic behaviour of a spring-mounted symmetrical NACA0012 wing in a freestream flow of air is studied in the pre-stall region, over 0° to 12° angles of incidence. The primary aim of this work is for use within the automotive sector to reduce drag and fuel emissions. However, this work will also be of interest in the motorsport sector to improve performance, and also have some applications within the aerospace and renewable energy sectors. The general operation of the concept has previously been verified at these low angles in the pre-stall region with that of a theoretical estimation using finite and infinite wings. This paper provides a numerical solution of the same problem and is compared with the previous experimentation. At these low angles, the computations yield a dynamic response settling into a static equilibrium. The stable solutions match the start of a steady regime well, when compared with the experiment. The trends are also comparable with the experiment, but the velocities at which they occur are underestimated in the computation. The computations demonstrate a drag reduction of 59% when compared to a fixed wing, whereas the lift remains stable at a near constant value with increasing wind speed. Thence, downforce is maintained whilst drag is reduced, which will facilitate higher speeds on the straight whilst maintaining vehicle direction stability. Limitations to this proof-of-concept work are highlighted and future development work is suggested to achieve even further increases in performance.

Background: Atrial fibrillation (AF) significantly contributes to acute ischemic stroke, with undetected AF being a common culprit in cryptogenic strokes. N-terminal pro-B-type natriuretic peptide (NT-proBNP), indicative of myocardial stress, has been proposed as a biomarker for AF detection, aiding in the selection of patients for extended cardiac monitoring. However, the diagnostic accuracy of NT-proBNP remains uncertain. Methods: We conducted a meta-analysis to evaluate the diagnostic accuracy of NT-proBNP in detecting AF among cryptogenic stroke patients. A comprehensive literature search was conducted across PubMed, Embase, and Cochrane databases to identify relevant studies. Studies reporting NT-proBNP levels in stroke patients and data on the proportion of patients with AF above a specified cut-off were included. Meta-analyses were performed using the midas command in STATA. Results: Seven studies encompassing 2171 patients were included in the analysis, of which five studies contained cohorts with cryptogenic strokes. Among patients with cryptogenic stroke, NT-proBNP demonstrated a diagnostic accuracy of 80% (Area Under the Receiver Operating Curve 0.80 [95% CI 0.76–0.83]), with a sensitivity of 81% (95% CI 0.68–0.89) and a specificity of 68% (95% CI 0.60–0.75). Conclusion: Our meta-analysis indicates that NT-proBNP exhibits a good-to-very-good diagnostic accuracy for detecting AF in patients with cryptogenic stroke. These findings suggest potential implications for utilizing NT-proBNP in guiding the selection of patients for prolonged cardiac monitoring, thereby aiding in the management of cryptogenic stroke cases.

Abstract Objectives To predict and identify the key demographic and clinical exposure factors associated with dental anxiety among young adults, and to compare if the traditional statistical modelling approach provides similar results to the machine learning (ML) approach in predicting factors for dental anxiety. Methods A cross-sectional study of Western Illinois University students. Three survey instruments (sociodemographic questionnaire, modified dental anxiety scale (MDAS), and dental concerns assessment tool (DCA)) were distributed via email to the students using survey monkey. The dependent variable was the mean MDAS scores, while the independent variables were the sociodemographic and dental concern assessment variables. Multivariable analysis was done by comparing the classical statistical model and the machine learning model. The classical statistical modelling technique was conducted using the multiple linear regression analysis and the final model was selected based on Akaike information Criteria (AIC) using the backward stepwise technique while the machine learining modelling was performed by comparing two ML models: LASSO regression and extreme gradient boosting machine (XGBOOST) under 5-fold cross-validation using the resampling technique. All statistical analyses were performed using R version 4.1.3. Results The mean MDAS was 13.73 ± 5.51. After careful consideration of all possible fitted models and their interaction terms the classical statistical approach yielded a parsimonious model with 13 predictor variables with Akaike Information Criteria (AIC) of 2376.4. For the ML approach, the Lasso regression model was the best-performing model with a mean RMSE of 0.617, R2 of 0.615, and MAE of 0.483. Comparing the variable selection of ML versus the classical statistical model, both model types identified 12 similar variables (out of 13) as the most important predictors of dental anxiety in this study population. Conclusion There is a high burden of dental anxiety within this study population. This study contributes to reducing the knowledge gap about the impact of clinical exposure variables on dental anxiety and the role of machine learningin the prediction of dental anxiety. The predictor variables identified can be used to inform public health interventions that are geared towards eliminating the individual clinical exposure triggers of dental anxiety are recommended.

Clinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period.In this paper we describe how we modified the design of the RAMPART trial (NCT03288532) which was set up to investigate immune checkpoint inhibitor therapy in the adjuvant renal cancer setting. The trial had been initiated when no globally accepted adjuvant strategy after nephrectomy existed. A subsequent change in the standard of care for many patients with early renal cancer meant it was no longer feasible to continue to recruit. We needed to find a way to maximise the contribution that RAMPART participants could make to the evidence base for immune checkpoint inhibitor therapy without introducing bias or detriment to the integrity of the trial results. We describe how we agreed and incorporated all design and timeline changes while remaining blinded to accumulating data within the trial, thus protecting the reliability of the future results. We share details of our design modifications to guide others who may have similar experiences, particularly as more agents and combinations of agents are developed and investigated in similar adjuvant settings.

Objectives The study aimed to compare the risk of gastrointestinal infections among patients with and without metabolic dysfunction-associated fatty liver disease (MAFLD).Methods This was a population-based, retrospective, observational study using data from the National Inpatient Sample (NIS), the largest all-payer US inpatient care database.Setting Hospitalisation of adults aged ≥18 years old admitted in 2020 was identified using the NIS. Patients were stratified by the presence and absence of MAFLD.Participants 26.4 million adults aged ≥18 years old were included in the study. Patients younger than 18 and those with missing demographic or mortality data were excluded.Primary and secondary outcomes Primary outcome was to assess the overall risk of gastrointestinal infections in patients with and without MAFLD. Secondary outcomes were demographics and comorbidities stratified by the presence or absence of gastrointestinal infection, and the risk of specific gastrointestinal pathogens.Results Of 26.4 million patients admitted in 2020, 755 910 (2.85%) had the presence of MAFLD. There was a higher prevalence of bacterial gastrointestinal infections in patients with MAFLD than those without (1.6% vs 0.9%, p

Abstract Background Comprehensive geriatric assessment (CGA) involves a formal broad approach to assess frailty and creating a plan for management. However, the impact of CGA and its components on listing for kidney transplant in older adults has not been investigated. Methods We performed a single-center retrospective study of patients with end-stage renal disease who underwent CGA during kidney transplant candidacy evaluation between 2017 and 2021. All patients ≥ 65 years old and those under 65 with any team member concern for frailty were referred for CGA, which included measurements of healthcare utilization, comorbidities, social support, short physical performance battery, Montreal Cognitive Assessment (MoCA), and Physical Frailty Phenotype (FPP), and estimate of surgical risk by the geriatrician. Results Two hundred and thirty patients underwent baseline CGA evaluation; 58.7% (135) had high CGA (“Excellent” or “Good” rating for transplant candidacy) and 41.3% (95) had low CGA ratings (“Borderline,” “Fair,” or “Poor”). High CGA rating (OR 8.46; p

Abstract Introduction The private sector plays an important role in tuberculosis (TB) elimination by providing access to quality TB care services like diagnosis and treatment, advocacy for preventive measures, innovation to address challenges in TB elimination, vaccines etc. The study aims to understand the perspectives of private practitioners on patients’ TB care cascade to reinforce existing interventions by assuring the quality of care to TB patients. Methods The study utilized a qualitative design through in-depth interviews of private practitioners and was conducted in Ranchi and Purbi Singhbhum District of Jharkhand State from March-August 2021. The pilot-tested, semi-structured, open-ended interview guide questionnaire collected information from private practitioners on various aspects of the TB care cascade. The data from the provider interviews were transcribed into multiple codes and themes on the TB program. An inductive analysis was carried out with a focus on content credibility to eliminate bias. Ethical approval was received from the Institutional Ethics Committee of the Indian Institute of Public Health Gandhinagar (IIPHG), India. Written consent was taken from the private practitioners involved in the study. Result In-depth interviews of 17 private practitioners reveal various factors contributing to delays in TB care cascades, especially delay in access to TB diagnosis and TB Care, delay in providing treatment once after diagnosis and poor adherence to the TB treatment. According to the perception of private practitioners, there was an array of client, provider and system side factors affecting the TB care cascade gaps positively and negatively. Positive aspects mainly emerged from interviews: strong governance, consistent supply chain management, innovative PPP models and financial schemes reducing out-of-pocket expenditure (OOPE). Various factors affecting the TB care cascade negatively include awareness among the patient, socio-economic status, approach and decision-making power of providers, adverse effects of drugs, staff capacity building, etc. Conclusions Engaging private practitioner in TB elimination efforts is critical to achieving global targets and reducing the burden of TB. The study helps to determine geography-specific barriers and facilitators of the TB care cascade to achieve the aim of providing universal access to TB healthcare with the inclusion of private practitioners.

Introduction Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a core component of depression pathophysiology. The anaesthetic propofol can induce electroencephalographic (EEG) slow waves that resemble SWS. Propofol may enhance SWS and oral antidepressant therapy, but relationships are unclear. We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has been supported by a recent small case series.Methods and analysis SWIPED (Slow Wave Induction by Propofol to Eliminate Depression) phase I is an ongoing open-label, single-arm trial that assesses the safety and feasibility of using propofol to enhance SWS in older adults with LL-TRD. The study is enrolling 15 English-speaking adults over age 60 with LL-TRD. Participants will receive two propofol infusions 2–6 days apart. Propofol infusions are individually titrated to maximise the expression of EEG slow waves. Preinfusion and postinfusion sleep architecture are evaluated through at-home overnight EEG recordings acquired using a wireless headband equipped with dry electrodes. Sleep EEG recordings are scored manually. Key EEG measures include sleep slow wave activity, SWS duration and delta sleep ratio. Longitudinal changes in depression, suicidality and anhedonia are assessed. Assessments are performed prior to the first infusion and up to 10 weeks after the second infusion. Cognitive ability is assessed at enrolment and approximately 3 weeks after the second infusion.Ethics and dissemination The study was approved by the Washington University Human Research Protection Office. Recruitment began in November 2022. Dissemination plans include presentations at scientific conferences, peer-reviewed publications and mass media. Positive results will lead to a larger phase II randomised placebo-controlled trial.Trial registration number NCT04680910.

mEAK-7 (mammalian EAK-7 or MTOR-associated protein, eak-7 homolog), is an evolutionarily conserved lysosomal membrane protein that is highly expressed in several cancer cells. Multiple recent studies have identified mEAK-7 as a positive activator of mTOR (mammalian/mechanistic target of rapamycin) signaling via an alternative mTOR complex, implying that mEAK-7 plays an important role in the promotion of cancer proliferation and migration. In addition, structural analyses investigating interactions between mEAK-7 and V-ATPase, a protein complex responsible for regulating pH homeostasis in cellular compartments, have suggested that mEAK-7 may contribute to V-ATPase-mediated mTORC1 activation. The C-terminal α-helix of mEAK-7 binds to the D and B subunits of the V-ATPase, creating a pincer-like grip around its B subunit. This binding undergoes partial disruption during ATP hydrolysis, potentially enabling other proteins such as mTOR to bind to the α-helix of mEAK-7. mEAK-7 also promotes chemoresistance and radiation resistance by sustaining DNA damage-mediated mTOR signaling through interactions with DNA-PKcs (DNA-dependent protein kinase catalytic subunit). Taken together, these findings indicate that mEAK-7 may be a promising therapeutic target against tumors. However, the precise molecular mechanisms and signal transduction pathways of mEAK-7 in cancer remain largely unknown, motivating the need for further investigation. Here, we summarize the current known roles of mEAK-7 in normal physiology and cancer development by reviewing the latest studies and discuss potential future developments of mEAK-7 in targeted cancer therapy.

Atrial fibrillation (AF) significantly contributes to acute ischaemic stroke (AIS), yet its precise influence on clinical outcomes post-intravenous thrombolysis (IVT) and post-endovascular thrombectomy (EVT) has remained elusive. Furthermore, the overall prevalence of AF in AIS patients undergoing reperfusion therapy has not been clearly determined. Employing random-effects meta-analyses, this research aimed to estimate the pooled prevalence of AF among AIS patients undergoing reperfusion therapy, while also examining the association between AF and clinical outcomes such as functional outcomes, symptomatic intracerebral haemorrhage (sICH) and mortality. Studies comparing AF and non-AF patient groups undergoing reperfusion therapy were identified and included following an extensive database search. Forty-nine studies (n = 66,887) were included. Among IVT patients, the prevalence of AF was 31% (Effect Size [ES] 0.31 [95%CI 0.28–0.35], p < 0.01), while in EVT patients, it reached 42% (ES 0.42 [95%CI 0.38–0.46], p < 0.01), and in bridging therapy (BT) patients, it stood at 36% (ES 0.36 [95%CI 0.28–0.43], p < 0.01). AF was associated with significantly lower odds of favourable 90-day functional outcomes post IVT (Odds Ratio [OR] 0.512 [95%CI 0.376–0.696], p < 0.001), but not post EVT (OR 0.826 [95%CI 0.651–1.049], p = 0.117). Our comprehensive meta-analysis highlights the varying prevalence of AF among different reperfusion therapies and its differential impact on patient outcomes. The highest pooled prevalence of AF was observed in EVT patients, followed by BT and IVT patients. Interestingly, our analysis revealed that AF was significantly associated with poorer clinical outcomes following IVT. Such an association was not observed following EVT.

Obstructed hemivagina with ipsilateral renal agenesis (OHVIRA) syndrome is a rare congenital malformation of the Mullerian duct. We report on a 34-year-old female who presented to the emergency department for cramping lower abdominal pain and pelvic pressure with vaginal spotting. Physical exam showed marked swelling in the right adnexa, and laboratory exams were within normal limits except for positive Coronavirus disease 2019 (COVID-19) status. Transvaginal ultrasound revealed 3 well circumscribed, round hypoechoic complex cystic lesions with arterial doppler detected within the peripheral walls. Magnetic resonance imaging of the abdomen and pelvis showed a right hemivagina, right hematosalpinx, right hematometra and right renal agenesis, compatible with OHVIRA syndrome. The patient was informed of elective surgical procedure but was unable to undergo surgery at this time secondary to COVID status. The patient was therefore recommended oral contraceptive therapy for suppression of menses and protection of endometrial lining.

Vascular access is a crucial step, which every interventional cardiologist needs to be skilled with to consistently achieve excellent periprocedural outcomes. Some operators argue that it is the most important aspect of the entire intervention. Hence, careful planning of vascular access in an individualized fashion – based on the patient’s clinical status, anatomy, and technical requirements of the intervention – is the first step in securing optimal procedural safety and successful results. We briefly review multiple aspects of vascular access and management including site selection, ultrasound guidance, micro-puncture techniques, sheathless techniques, limb perfusion, clinical monitoring, large bore closure, and management of complications. Approaching every vascular access in a systematic way, even in emergent situations, allows operators to minimize the risk of complications, especially in an often severely ill patient population.

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

Background Spinal cord herniation into a traumatic pseudomeningocele is a rare clinical entity. We present the sixth known case and describe surgical management. Case Presentation A 44-year-old male presented with Brown-Sequard syndrome three decades after a cervical nerve root avulsion injury. Imaging revealed hemicord herniation into a C7/T1 pseudomeningocele in addition to extra-axial cord compression from further pseudomeningoceles. Significant clinical improvement was achieved following surgical repair. The radiological findings and technique for operative repair are described. Conclusion The case highlights this rare pathology and presentation, describes the surgical measures for repair of cord herniation, and provides evidence for the favorable outcome that can be achieved by surgical intervention.

BackgroundAchieving the target for eliminating tuberculosis (TB) in India by 2025, 5 years ahead of the global target, critically depends on strengthening the capacity of human resources as one of the key components of the health system. Due to the rapid updates of standards and protocols, the human resources for TB health care suffer from a lack of understanding of recent updates and acquiring necessary knowledge. ObjectiveDespite an increasing focus on the digital revolution in health care, there is no such platform available to deliver the key updates in national TB control programs with easy access. Thus, the aim of this study was to explore the development and evolution of a mobile health tool for capacity building of the Indian health system’s workforce to better manage patients with TB. MethodsThis study involved two phases. The first phase was based on a qualitative investigation, including personal interviews to understand the basic requirements of staff working in the management of patients with TB, followed by participatory consultative meetings with stakeholders to validate and develop the content for the mobile health app. Qualitative information was collected from the Purbi Singhbhum and Ranchi districts of Jharkhand and Gandhinagar, and from the Surat districts of Gujarat State. In the second phase, a participatory design process was undertaken as part of the content creation and validation exercises. ResultsThe first phase collected information from 126 health care staff, with a mean age of 38.4 (SD 8.9) years and average work experience of 8.9 years. The assessment revealed that more than two-thirds of participants needed further training and lacked knowledge of the most current updates to TB program guidelines. The consultative process determined the need for a digital solution in easily accessible formats and ready reckoner content to deliver practical solutions to address operational issues for implementation of the program. Ultimately, the digital platform named Ni-kshay SETU (Support to End Tuberculosis) was developed to support the knowledge enhancement of health care workers. ConclusionsThe development of staff capacity is vital to the success or failure of any program or intervention. Having up-to-date information provides confidence to health care staff when interacting with patients in the community and aids in making quick judgments when handling case scenarios. Ni-kshay SETU represents a novel digital capacity-building platform for enhancing human resource skills in achieving the goal of TB elimination.

Tuberculosis (TB) is a major killer and cause of human suffering worldwide and imposes a substantial reduction in patients’ health-related quality of life (HRQoL). HRQoL indicates the consciousness of patients regarding their physical and mental health. It is, therefore, very relevant in comprehending and measuring the exact impact of the disease state. Therefore, we undertook this review to summarize the available evidence on the impact of TB and its treatment on HRQoL. An in-depth understanding of HRQoL in TB patients can identify the existing management gaps. We undertook a systematic search through PubMed and CENTRAL. Data were extracted and tabulated for study design, targeted population, QoL instrument used, QoL domain assessed, and key findings. We included studies that assessed the effect of TB on the QoL both during and after treatment. There are no specific HRQoL assessment tools for utilization among TB patients. HRQoL is markedly impaired in patients with TB. The factors affecting HRQoL differ with active and latent TB, socio-demographics, socio-economic status, presence of co-infections, etc. This review’s findings can help to frame appropriate policies for tackling HRQoL issues in TB patients.

Summary: Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods: In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings: In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1–9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3–25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation: There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained. Funding: Bill & Melinda Gates Foundation.

Abstract Background Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.

Reperfusion therapy in the form of intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) has revolutionised the field of stroke medicine. Atrial fibrillation (AF) patients constitute a major portion of the overall stroke population; however, the prevalence of AF amongst acute ischemic stroke (AIS) patients receiving reperfusion therapy remains unclear. Limitations in our understanding of prevalence in this group of patients are exacerbated by difficulties in appropriately diagnosing AF. Additionally, the benefits of reperfusion therapy are not consistent across all subgroups of AIS patients. More specifically, AIS patients with AF often tend to have poor prognoses despite treatment relative to those without AF. This article aims to present an overview of the diagnostic and therapeutic management of AF and how it mediates outcomes following stroke, most specifically in AIS patients treated with reperfusion therapy. We provide unique insights into AF prevalence and outcomes that could allow healthcare professionals to optimise the treatment and prognosis for AIS patients with AF. Specific indications on acute neurovascular management and secondary stroke prevention in AIS patients with AF are also discussed.

Abstract Background Lenabasum is a cannabinoid type 2 receptor (CB2R) reverse agonist that demonstrates anti-inflammatory effects in vivo and in vitro in dermatomyositis (DM) and is currently being investigated for therapeutic potential. The purpose of our study is to investigate CB2R distribution as well as the effects of lenabasum in DM. Methods Immunohistochemistry staining (IHC) was utilized to examine immune cell and cytokine production changes in lesional DM skin biopsies from lenabasum and placebo-treated patients. CB2R expression in various immune cell populations within DM skin was investigated with image mass cytometry (IMC), whereas flow cytometry elucidated CB2R expression in DM peripheral blood mononuclear cells (PBMCs) as well as cytokine production by CB2R-expressing cell populations. Results After 12 weeks of lenabasum treatment, IHC staining showed that CD4+ T cells, CB2R, IL-31, IFN-γ, and IFN-β cytokines were downregulated. IFN-γ and IFN-β mRNA decreased in lesional DM skin but not in PBMCs. IMC findings revealed that CB2R was upregulated in DM lesional skin compared to HC skin and DM PBMCs (p

Abstract Background The functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of common alleles that are often commercially produced at great expense, with costs and technical challenges associated with production of intersectional mouse lines hindering customized approaches to many researchers. Here, we present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production. Results Briefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study the way functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase-responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle. Conclusions The lines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.

Tuberculosis (TB) is the second leading cause of death due to infectious diseases globally, and delay in the TB care cascade is reported as one of the major challenges in achieving the goals of the TB control programs. The main aim of this study was to investigate the delay and responsible factors for the delay in the various phases of care cascade among TB patients in two Indian states, Jharkhand and Gujarat. This cross-sectional study was conducted among 990 TB patients from the selected tuberculosis units (TUs) of two states. This study adopted a mixed-method approach for the data collection. The study targeted a diverse profile of TB patients, such as drug-sensitive TB (DSTB), drug resistance TB (DRTB), pediatric TB, and extra-pulmonary TB. It included both public and private sector patients. The study findings suggested that about 41% of pulmonary and 51% of extra-pulmonary patients reported total delay. Delay in initial formal consultation is most common, followed by a delay in diagnosis and treatment initiation in pulmonary patients. While in extra-pulmonary patients, delay in treatment initiation is most common, followed by the diagnosis and first formal consultation. DR-TB patients are more prone to total delay and delay in the treatment initiation among pulmonary patients. Addiction, co-morbidity and awareness regarding monetary benefits available for TB patients contribute significantly to the total delay among pulmonary TB patients. There were system-side factors like inadequacy in active case findings, poor infrastructure, improper adverse drug reaction management and follow-up, resulting in delays in the TB care cascade in different phases. Thus, the multi-disciplinary strategies covering the gambit of both system and demand side attributes are recommended to minimize the delays in the TB care cascade.

BackgroundCarcinoid heart disease (CnHD) is a frequent cause of morbidity and mortality in patients with neuroendocrine tumors and carcinoid syndrome. Although valve replacement surgery appears to decrease all-cause mortality in patients with advanced CnHD, few studies have investigated the outcomes of patients after valve replacement.MethodsWe conducted a multi-institution retrospective registry of patients who received both tricuspid and pulmonic bioprosthetic valve (TV/PV) replacements for advanced CnHD from November 2005 to March 2021. Patients were followed post-operatively with echocardiographic studies every 3 months. Carcinoid valvular heart disease scores were used to monitor valve degeneration. Neuroendocrine tumor treatment, their administration times, and associations with echocardiographic findings were recorded.ResultsOf 87 patients with CnHD, 22 patients underwent simultaneous surgical TV and PV replacement. In 6 patients (27.3%), increased PV Vmax was the first echocardiographic manifestation of valve degeneration in the setting of occult neurohormonal release. Post-operative telotristat ethyl and peptide receptor radionuclide therapy appeared to stabilize PV Vmax. The PV Vmax showed consistent elevation in the entire patient population when compared to baseline, while bioprosthetic TV echocardiographic parameters were relatively unchanged throughout. Post-operative warfarin therapy did not affect the rate of PV degeneration, and no major bleeding was recorded during or after post-operative anticoagulation therapy.ConclusionBioprosthetic valve degeneration is common in CnHD. Monitoring with echocardiographic studies every 3 months, focusing on PV velocities, could identify patients with occult disease that very likely promotes valve degeneration. Novel neuroendocrine tumor therapies may have a beneficial impact on valve degeneration.

Understanding factors leading to death following the onset of symptoms of tuberculosis (TB) is important to predict prognosis among patients with TB. With aiming the End TB strategy, mortality is declining not as expected globally and in India. Although India is one of the highest incidence countries globally, India lacks evidence of understanding of the factors for TB death. Thus, this study aims to document the characteristics of deaths due to TB in the Western state of India, Gujarat.About 74 deaths were randomly documented from 7 different geographic regions of Gujarat through a community-based death review from Oct 2021 to February 2022. The trained researchers administered a semi-structured questionnaire to capture the demographic, socioeconomic, history of comorbidity and addiction, medical history, case records, and chronology of events preceding death.Most deaths happened within 24 weeks from the onset of symptoms, which reduced to half (12 weeks) in the other cascades, i.e., diagnosis and treatment initiation to the death. Out of 74 reviewed deaths, 47 (64%) deaths had the cause of death as TB, with an average duration of 87 days from onset of symptoms to death. The study observed the time, place, and person distribution on different epidemiological parameters. While analyzing narratives from the relative, the gaps between the system (service provider) and demand (patient perspective) sides were synthesized.It is recommended to conduct such kind of community-based death reviews in the routine practices of the National TB Elimination Program to ensure the appropriate review of the underlying causes of deaths due to TB. The matrix developed in this study is easy to replicate in any other death reviews to understand the intercept of the supply-demand side determinants for the deaths.

Introduction: Mortality and morbidity due to infectious disease have got reduced in the last couple of decades. Diphtheria is one of the infectious diseases which can be preventable with a complete immunization. Objective: To understand trends and identify factors affecting the outbreak of diphtheria in Banaskantha district of Gujarat. Method: A retrospective study based on the available case records for the years 2019, 2020 and 2021(till June). The study was conducted after the reported diphtheria cases in a district. The study was a public health response and intended to provide specific geographical recommendations to the district. The data was recorded from the reported case record and immunization registers. The data were analyzed for defined variables. Results: Out of the 366 cases identified during years 2019-2021.Almost 74% cases have occurred during 2019, with a 7.7% mortality rate. Total 48% of cases were among the age group of 5-10 years, with an increasing number of cases during August-December with specific geographical distribution. Among all the cases, 164 (44.5%) have never taken any vaccine in their lifetime or are unaware of the vaccination status, and 87.9% of cases have not taken third dose of DPT or Pentavalent Vaccine, which is associated statistically with the mortality. Conclusion: The prevalence of diphtheria cases was high in children who have not taken all three doses of DPT or Pentavalent vaccine. These have shown an essential role of immunization, focusing on the vaccine for all doses and need to create a customized awareness communication plan.

Acute abdominal pain is a common presenting symptom that possesses a wide differential. Congenital internal hernias are a rare condition that often presents with abdominal pain and can lead to obstruction. Early diagnosis is often difficult and therefore can present acutely and in an emergent setting. Prompt recognition of symptoms and evaluation are important to prevent poor prognosis. We are presenting a case of a congenital internal hernia in a patient presenting with nonspecific symptoms. Prompt diagnosis and subsequent surgical intervention allowed for appropriate management and resolution of symptoms.

Category: Trauma; Ankle Introduction/Purpose: External fixation is a common initial management strategy for complex ankle injuries. The purpose of this study was to evaluate external fixation frame constructs for risk of sharp exposure to the health care team at the receiving institution when patients were received in transfer for definitive care after an external fixator was applied at an outside institution. Methods: Patients with an ankle external fixator applied prior to transfer to the senior author over a 3 year period were included. Injuries represented- included pilon fractures, complex ankle fractures and other injuries with significant soft tissue swelling. External fixation constructs were evaluated for sharp pin ends when the patient was received in transfer. Frame constructs were assessed for pins that were cut resulting in sharp ends or pins that were never cut, resulting in an exposed sharp pin end. The location of sharp pins was recorded as a tibial shaft pin, foot pin, or calcaneal pin. calcaneal pins were recorded as either monolateral or transcalcaneal. Results: 39 patients with ankle external fixation were received in transfer by the senior author over a 3- year period. 16/39 external fixation constructs had sharp pins that presented potential for injury at the receiving institution. Of the external fixation constructs with sharp pin ends 2/16 had tibial pins that were cut in a manner that resulted in a sharp pin end. 14/16 of the external fixation frames with sharp pin ends exposed were transcalcaneal pins where the leading sharp point was not cut after the pin was inserted through the calcaneus and the external fixator was assembled. No foot pins or monolateral calcaneal pins resulted in sharp pin ends. Conclusion: External fixation plays an important role in staged management of complex ankle injuries. All external fixation pins should be cut in a manner that results in blunt pin ends to reduce potential for injury to all members of the health care team. Pin cutters that result in blunt pin ends are commercially available and should be used to prevent potential sharp injury in all external fixation cases

A novel strain gauge force transducer was developed to minimize the number of strain gauges needed to determine the magnitudes of loads when the locations are known. This innovative methodology requires only one strain gauge for each force magnitude desired, reducing the complexity and cost associated with traditional approaches. The theory was verified with laboratory experiments. Seven uniaxial strain gauges were attached to the underside of a simply supported, slender, aluminum beam. One or more loads were applied either directly atop strain gauges or in known positions between strain gauges. Experiments were conducted on several different single and double-load configurations to evaluate the extent of the new methodology which yielded average errors under 5% for the cases where loads were direct atop strain gauges and 6.6% for the cases where the loads were between strain gauges. These findings indicate the potential of this novel strain gauge force transducer to revolutionize load measurement in scenarios where load locations are predetermined.

Background: Six million Americans suffer from atrial fibrillation (AF), a heart rhythm abnormality that significantly increases the risk of stroke. AF is responsible for 15% of ischemic strokes, which lead to permanent disability in 60% of cases and death in up to 20%. Anticoagulation (AC) is the mainstay for stroke prevention in patients with AF. Despite guidelines recommending AC for patients, up to half of eligible patients are not on AC. Clinical decision support tools in the electronic health record (EHR) can help bridge the disparity in AC prescription for patients with AF. Objective: To enhance and assess the effectiveness of our previous rule-based alert on AC initiation and persistence in a diverse patient population from UMass-Memorial Medical Center and University of Florida at Jacksonville. Methods/Results: Using the EHR, we will track AC initiation and persistence. We will interview both patients and providers to determine a measure of satisfaction with AC management. We will track digital crumbs to better understand the alert’s mechanism of effect and further add enhancements. These enhancements will be used to refine the alert and aid in developing an implementation toolkit to facilitate use of the alert at other health systems. Conclusion: If the number of AC starts, the likelihood of persisting on AC, and the frequency alert use are found to be higher among intervention vs control providers, we believe such findings will confirm our hypothesis on the effectiveness of our alert.

Abstract Background and Aims Frail older adults are more than twice as likely to experience postoperative complications. Preoperative exercise may better prepare these patients through improved stamina and mobility experienced in the days following surgery. We measured the impact of a walking intervention using an activity tracker and coaching on postoperative stamina, and mobility in older adults with frailty traits. Methods We included patients aged 60+ and scoring 4+ on the Edmonton Frailty Scale. We then randomized patients to intervention versus control stratified by anticipated hospital stay (1 night vs. 2+ night) and baseline stamina (i.e., 6‐min walk distance [6MWD]). Intervention patients received an activity tracker and linked smart phone. An athletic trainer (AT) prescribed a daily step count goal and titrated this up after checking in with patients during weekly telephone calls. Controls received general walking recommendations. We then measured postoperative 6MWD 1–3 days after surgery. We also assessed postoperative mobility by measuring steps walked the day after surgery using a thigh‐worn monitor. Because many patients could not walk postoperatively, we compared intervention‐control difference in both 6MWD and steps using Wilcoxon rank testing and Tobit and ordinal logistic regression adjusting for several patient characteristics. Results We randomized 104 eligible patients; 80 patients remained for final analysis. There was no difference in intervention versus control postoperative 6MWD (median 72 vs. 74 m Wilcoxon p = 0.54) or postoperative steps taken (median 128 vs. 51 steps Wilcoxon p = 0.76). Analysis adjusting for patient characteristics was consistent with these findings. Conclusion Our intervention consisting of goal setting with an activity tracker and telephonic coaching by an AT did not appear to improve stamina or mobility measured in the days after surgery. Small sample size limited our ability to examine this impact in subsets defined by surgical specialty or baseline stamina.

Cystadenoma of the tunica of the adult male testis has rarely been reported in the literature. We report a case of an adult serous cystadenoma along with the radiological and pathological findings. The patient was a 40-year-old male with a slowly growing mass on the left testis. An ultrasound scan of left testis showed features highly suspicious for malignancy. Lactate dehydrogenase (LDH) was mildly elevated. Alpha feta-protein (AFP) and beta-human chorionic gonadotropin (beta hCG) were negative. We performed left radical orchiectomy. The pathological findings showed serous cystadenoma of the tunica of the testis. The patient remains asymptomatic.

Increased cancer prevalence and survival rates coupled with earlier patient discharges from hospitals have created a greater need for social support. Cancer care is both short term and long term, requiring acute treatments, treatments for remission, and long-term screenings and treatment regimens. Health care systems are already overwhelmed and often struggle to provide social support systems for everyone. Caregivers are limited in number, and even when they are available, they often lack necessary information, skills, or resources to meet the needs of patients with cancer. The act of caregiving presents various challenges, and caregivers themselves often need social support as well. Despite these needs, most social support programs are targeted toward patients alone. Given the prevalence of cancer and known needs of these patients and their caregivers, the ability to identify those who need social support is crucial. Further, the scalability and overall availability of social support programs is vital for successful patient care. This paper establishes the benefits of social support for both patients and caregivers coping with cancer treatments, explores innovative ways of identifying patients who may need social support using digital tools, and reviews potential advantages of digital social support programs.

Background: Thoracic spine fractures (TSFs) are rarely isolated injuries, and they tend to present with a characteristic set of vertebral and non-vertebral injuries based on mechanism of injury. There is limited research on the rates and distribution of injuries that occur concurrently with TSFs. The purpose of this study is to characterize the distributions of these injuries by region of the body and by mechanisms of injury, so that trauma and spine surgeons can efficiently evaluate and treat patients presenting with TSFs. Methods: We retrospectively reviewed the trauma database records of 683 patients presenting with a TSFs at a single institution from 2015 to 2019. We recorded patient demographics, comorbidities, and associated injuries by body region. We characterized the TSFs using the AO classification system, as well as the presenting physical exam and treatment. All associated injuries among the TSF patients were classified into the following categories: head injury (HI), thoracic injury (TI), non-thoracic vertebral injury (NTVI), abdominal injury (AI), upper extremity injury (UEI), lower extremity injury (LEI), and spinal cord injury (SCI). Results: The three leading causes of TSFs were mechanical falls (38.4%), falls from height (24.9%), and motor vehicle crashes (MVCs) (23.4%). Patients with a TSF from MVC were statistically more likely to have concomitant injuries of TI, NTVI, AI, HI, UEI, and LEI. TSFs from fall from height were statistically more likely to have TI, NTVI, and LEI. TSFs from mechanical falls had significantly lower rates of all injury locations, but still presented with high rates of additional injury. TSFs from motorcycle crashes (MCCs) presented with TI, AI, UEI, and LEI. There were high rates of treatment for TSFs, with surgery ranging from 5.3% to 20.0% and bracing from 52.3% to 65.7% depending on mechanism of injury. Conclusions: TSFs after MVCs, mechanical falls, falls from height, and MCCs presented with a predictable pattern of injuries and were rarely an isolated injury. This cross-sectional data may help spine and trauma surgeons better understand patterns of injury associated with TSFs, with the hope of preventing missed injuries and better advising patients with TSFs on severity of injuries.

Abstract. To characterize outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19) who present with gastrointestinal (GI) symptoms. Clinical outcomes in patients with COVID-19 associated with GI symptoms have been inconsistent in the literature. The study design is a retrospective analysis of patients, age 18 years or older, admitted to the hospital after testing positive for COVID-19. Clinical outcomes included intensive care unit requirements, rates of discharges to home, rates of discharges to outside facilities, and mortality. Seven hundred fifty patients met the inclusion criteria. Three hundred seventy three (49.7%) patients presented with at least one GI symptom and 377 (50.3%) patients presented with solely non-GI symptoms. Patients who presented with at least one GI symptom had significantly lower ICU requirements (17.4% vs 20.2%), higher rates of discharges home (77.2% vs 67.4%), lower rates of discharges to other facilities (16.4% vs 22.8%), and decreased mortality (6.4% vs 9.8%) compared with patients with non-GI symptoms. However, patients who presented with solely GI symptoms had significantly higher ICU requirements (23.8% vs 17.0%), lower rates of discharges home (52.4% vs 78.7%), higher rates of discharges to facilities (28.6% vs 15.6%), and higher mortality (19.0% vs 5.7%) compared with those with mixed GI and non-GI symptoms. Although patients with COVID-19 requiring hospitalization with GI symptoms did better than those without GI symptoms, those with isolated GI symptoms without extra-GI symptoms had worse clinical outcomes. COVID-19 should be considered in patients who present with new onset or worsening diarrhea, nausea, vomiting, and abdominal pain even without pulmonary symptoms.

Sarcoidosis is a chronic multi-system disorder with an unknown etiology that can affect the cardiac tissue, resulting in Cardiac Sarcoidosis (CS). The majority of these CS cases are clinically silent, and when there are symptoms, the symptoms are vague and can have a lot in common with other common cardiac diseases. These symptoms can range from arrhythmias to heart failure. If CS goes undetected, it can lead to detrimental outcomes for patients. Diagnosis depends on timely utilization of imaging modalities and non-invasive testing, while in some cases, it does necessitate biopsy. Early diagnosis and treatment with immunosuppressive agents are crucial, and it is essential that follow-up testing be performed to ensure resolution and remission. This manuscript provides an in-depth review of CS and the current literature regarding CS diagnosis and treatment.

Introduction: Glomerular filtration rate (GFR) is routinely estimated with cystatin C. In June 2010, the International Federation of Clinical Chemistry (IFCC) released a certified cystatin C reference material (ERM-DA471/IFCC), and new cystatin C glomerular filtration rate estimation (eGFR) equations were developed with the IFCC standard. Early in 2018, Siemens discontinued their nonstandardized cystatin C reagent kits and replaced them with IFCC-calibrated kits in the US market. The aim of the current study was to assess the effect of IFCC calibration on cystatin C values and corresponding GFR estimations. Methods: Cystatin C concentration was measured in 81 pediatric patients using a plasma sample from their nuclear GFR measurement with 99mTc-diethylenetriaminepentaaccetic acid. Calibration curves were generated using Siemens nonstandardized and IFCC-standardized kits to measure paired cystatin C concentrations in each sample. GFR-estimating equations using pre-IFCC and IFCC cystatin C values were compared using Bland-Altman analyses. Results: The IFCC-standardized assay resulted in a mean increase in the measured cystatin C value of 24%. Estimating equations consistently overestimated GFR prior to IFCC standardization. Following incorporation of the IFCC standard, the Full Age Spectrum equation demonstrated the best overall performance, whereas the Chronic Kidney Disease in Children (CKiD) equation was more accurate in children with decreased GFR. Conclusion: Incorporation of the IFCC standard significantly increased cystatin C values and affected the performance of GFR estimating equations. Clinical laboratories and providers may need to update the equation used for cystatin C–based estimation of GFR following adoption of the IFCC reference standard.

Summary: Background: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 – 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432–912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9–412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (–29·1%;23·8-38·5). YLLs decreased in self-harm (–27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. Funding: The Bill and Melinda Gates Foundation

Introduction: The natural history of venous thromboembolism (VTE) in sickle cell disease (SCD) is incompletely understood. We hypothesized that VTE recurrence is common in SCD and associated with increased disease severity. We sought to understand the short- and long-term clinical outcomes of VTE in SCD. Methods: We conducted a single-center retrospective chart review study of patients with SCD 18 years and older at our institution between 2003 and 2018. Demographics, hemoglobin (Hb) genotype, medical history, and laboratory values were collected. We recorded VTE occurrence and potential provoking factors, duration of anti-coagulation and subsequent recurrence of VTE. We compared rates of emergency department (ED) visits, and hospitalizations for five years post-VTE to rates of ED visits and hospitalizations among those without VTE. Results: Fifty-five (23.6%) of 233 individuals with SCD in our cohort (69% HbSS/HbS-β0) had a VTE. Increased BMI, prior splenectomy, and white blood cell count were significantly associated with increased risk of VTE while Hb genotype, and severity of anemia were not. Recurrent VTE occurred in 27/55 (49%); 13 VTE recurrences occurred during active treatment with anticoagulants. Patients with a VTE had significantly higher rates of ED visits and hospital admissions than those without a VTE. Conclusion: Nearly a quarter of our single institution cohort had a VTE with a high recurrence rate even in those receiving anti-coagulation therapy. SCD patients had a higher rate of healthcare utilization after a VTE suggesting a link to disease severity.

Introduction: Articular cartilage lacks the capacity for self-repair due to its relative avascularity. Regenerative medicine approaches are now widely investigated, but optimal solutions have not been identified. This is partially attributable to challenges in identifying appropriate engineered constructs for implantation, and in assessing the repair trajectory in pre-clinical models. Objective: We investigated non-destructive near-infrared (NIR) fiber optic spectroscopy-derived parameters to inform (1) identification of optimal tissue engineered cartilage constructs prior to implantation and (2) assessment of repair tissue composition in a Yucatan mini-pig chondral defect model. Methods: Tissue engineered cartilage (TEC) was developed using a co-culture system of bone marrow mesenchymal stem cells and chondrocytes encapsulated in a hyaluronic acid-based hydrogel. Near-infrared spectroscopy (NIRS)data were obtained from the TECs pre- and post-implantation and from repair tissue post-surgery. Healing response of the defects were compared to microfracture at 3 months post-implantation based on ICRS II scoring, mechanical testing, and NIRS. Results: No significant differences were found between the tissue engineered cartilage and microfracture repair tissue. Some NIR-determined properties of the developing TECs correlated significantly with aspects of the ICRS II repair tissue score, including the surface architecture and subchondral bone integration. Further, NIR-derived metrics to non-destructively assess repair tissue composition, in the presence of subchondral bone, were defined (5200/7000 cm−1 ratio), providing a valuable approach for future studies. Conclusion: Together, these data demonstrate the utility of NIR spectroscopy to identify developing TECs that may result in functional repair tissue and to facilitate repair tissue evaluation.

Introduction: Neonatal hyperbilirubinemia is one of the most common problem encountered during the neonatal period. Phototherapy is a widely accepted, cheap, non-invasive relatively safe and effective method of treatment for neonatal hyperbilirubinemia. Aim: To compare the efficacy of Light Emitting Diode (LED) phototherapy vs Conventional Phototherapy for treatment of neonatal hyperbilirubinemia in healthy term neonates. Materials and Methods: A quasi experimental study was conducted in Neonatal Intensive Care Unit and Post-natal wards in a tertiary care hospital affiliated to Medical College and Hospital, Ahmedabad, Gujarat from July 2018 to April 2019 with a sample size of 135 in each group. They were assessed clinically by Kramers method just before initiation of phototherapy, then using Transcutaneous Bilirubinometer (TCB) Total Serum Bilirubin (TSB) level was measured. Bilirubin assessment by these methods were done for every neonate before initiation of phototherapy and then again repeated after 24 and 48 hours of phototherapy. Data was collected and analysed in Microsoft (MS) excel Statistical Package for the Social Sciences (SPSS) 0.26. Chi-square test was used for comparison. Results: In the present study, 158 (58.51%) babies were male and 112 (41.48%) babies were female. Initially, LED was found to be better than Compact Fluorescent (CFL) conventional phototherapy on comparing the average fall in the serum bilirubin level from baseline during the first 24 hours however no such difference in the efficacy between the two light sources was seen after a period of 48 hours. Total 9 (6.66%) patients developed rebound hyperbilirubinemia after completion of conventional phototherapy whereas 14 (10.37%) developed rebound hyperbilirubinemia after completion of 48 hours of LED phototherapy. Conclusion: LED and conventional phototherapy were equally efficacious in managing non haemolytic hyperbilirubinemia in healthy term neonates.

Abstract Consumption of non-nutritive sweeteners (NNS) has been consistently associated with obesity and cardiometabolic disease in epidemiologic studies. Herein, we investigated effects of sucralose, a widely used NNS, at a cellular level. We wanted to investigate effect of sucralose on reactive oxygen species accumulation and adipogenesis in a human adipocyte tissue-derived mesenchymal stromal cells (MSCs) in a controlled fashion. Methods In vitro experiments were conducted on commercially available MSCs obtained from human adipose tissue. hMSCs were exposed with sucralose at 0.2 mM (a concentration which could plausibly be observed in the circulatory system of high NNS consumers) up to 1.0 mM (supra-physiologic concentration) in the presence of both normal and high glucose media to detect a dose response based on the outcome measures. Reactive oxygen species (ROS) were detected using Mitosox Red staining and further analyzed by ImageJ and gene expression analysis. Effect of sucralose on adipogenic differentiation was observed in different concentrations of sucralose followed by gene expression analysis and Oil Red O staining. Results Increased ROS accumulation was observed within 72 h of exposure. Increased adipogenesis was also noted when exposed to higher dose of sucralose. Conclusion Sucralose promotes ROS accumulation and adipogenesis in human adipose tissue derived mesenchymal stromal cells.

A four-element compact wide-band optically transparent MIMO antenna with a full ground plane is proposed. The four elements transparent MIMO system has a compact size of 24 × 20 mm2 with the undivided ground plane as most of the real-time systems demand a common reference. The complete antenna system achieves around 85% transparency due to a combination of AgHT-8 and Plexiglas which forms the transparent conductive patch/ground and substrate, respectively. The antenna geometry leads dual-band operation ranging from 24.10 - 27.18 GHz (Impedance bandwidth = 12%) and 33 - 44.13 GHz (Impedance bandwidth =28.86$ %) targeting the mm-wave 5G applications. The 4-element antenna system achieves isolation between inter-elements >16 dB and maximum gain value of greater than 3 dBi with more than 75% efficiency. The proposed transparent MIMO antenna is evaluated in terms of diversity gain (DG), envelope correlation coefficient (ECC), total active reflection coefficient (TARC), and mean effective gain (MEG) where decent MIMO performance with isolation more than >16 dB between the adjacent and other elements is achieved. Transparent MIMO antenna achieves directional patterns for the operating band with the value of DG >9, ECC

Background: Barth syndrome (BTHS) is a rare X-linked genetic disease that affects multiple systems and leads to complex clinical manifestations. Although a considerable amount of research has focused on the physical aspects of the disease, less has focused on the psychosocial impact and quality of life (QoL) in BTHS. Methods: The current study investigated caregiver- (n = 10) and self-reported (n = 16) psychological well-being and QoL in a cohort of BTHS-affected patients and families. Participants completed the depression and anxiety components of the Patient-Reported Outcomes Information System (PROMIS) Short Form 8A and Health-related quality of life (HRQoL) surveys at enrollment and again during a follow-up period ranging from 6 to 36 months after baseline. Results: Quality of life changed significantly over time and the various domains with some improvement and some decline. Among the available caregiver-patient dyad data, there was a trend toward discordance between caregiver and self-reported outcomes. Most notably, patients reported improvement in HRQoL, while caregivers reported declines. This suggests that there may be differences in perceived quality of life between the patients and parents, though our study is limited by small sample size. Conclusion: Our study provides valuable insights into the impacts of psychosocial and mental health aspects of BTHS. Implications of these findings include incorporating longitudinal assessment of QoL and screening for psychological symptoms in BTHS care to identify interventions that may drastically impact health status and the course of the disease.

BackgroundAlthough the American Heart Association and other professional societies have recommended shared decision-making as a way for patients with atrial fibrillation (AF) or atrial flutter to make informed decisions about using anticoagulation (AC), the best method for facilitating shared decision-making remains uncertain. ObjectiveThe aim of this study is to assess the AFib 2gether mobile app for usability, perceived usefulness, and the extent and nature of shared decision-making that occurred for clinical encounters between patients with AF and their cardiology providers in which the app was used. MethodsWe identified patients visiting a cardiology provider between October 2019 and May 2020. We measured usability from patients and providers using the Mobile App Rating Scale. From the 8 items of the Mobile App Rating Scale, we reported the average score (out of 5) for domains of functionality, esthetics, and overall quality. We administered a 3-item questionnaire to patients relating to their perceived usefulness of the app and a separate 3-item questionnaire to providers to measure their perceived usefulness of the app. We performed a chart review to track the occurrence of AC within 6 months of the index visit. We also audio recorded a subset of the encounters to identify evidence of shared decision-making. ResultsWe facilitated shared decision-making visits for 37 patients visiting 13 providers. In terms of usability, patients’ average ratings of functionality, esthetics, and overall quality were 4.51 (SD 0.61), 4.26 (SD 0.51), and 4.24 (SD 0.89), respectively. In terms of usefulness, 41% (15/37) of patients agreed that the app improved their knowledge regarding AC, and 62% (23/37) agreed that the app helped clarify to their provider their preferences regarding AC. Among providers, 79% (27/34) agreed that the app helped clarify their patients’ preferences, 82% (28/34) agreed that the app saved them time, and 59% (20/34) agreed that the app helped their patients make decisions about AC. In addition, 32% (12/37) of patients started AC after their shared decision-making visits. We audio recorded 25 encounters. Of these, 84% (21/25) included the mention of AC for AF, 44% (11/25) included the discussion of multiple options for AC, 72% (18/25) included a provider recommendation for AC, and 48% (12/25) included the evidence of patient involvement in the discussion. ConclusionsPatients and providers rated the app with high usability and perceived usefulness. Moreover, one-third of the patients began AC, and approximately 50% (12/25) of the encounters showed evidence of patient involvement in decision-making. In the future, we plan to study the effect of the app on a larger sample and with a controlled study design. Trial RegistrationClinicalTrials.gov NCT04118270; https://clinicaltrials.gov/ct2/show/NCT04118270 International Registered Report Identifier (IRRID)RR2-21986