Background. We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. Methods. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. Results. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Conclusion. In the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841; Funding: South African Medical Research Council (SAMRC) and South African Department of Health (SA DoH).
Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neuropathologically-defined disease that affects 40% of persons in advanced age, but its associated neurological syndrome is not defined. LATE neuropathological changes (LATE-NC) are frequently comorbid with Alzheimers disease neuropathologic changes (ADNC). When seen in isolation, LATE-NC have been associated with a predominantly amnestic profile and slow clinical progression. We propose a set of clinical criteria for a limbic-predominant amnestic neurodegenerative syndrome (LANS) that is highly associated with LATE-NC but also other pathologic entities. The LANS criteria incorporate core, standard and advanced features that are measurable in vivo, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degenerative patterns and low likelihood of neocortical tau, with degrees of certainty (highest, high, moderate, low). We operationalized this set of criteria using clinical, imaging and biomarker data to validate its associations with clinical and pathologic outcomes. We screened autopsied patients from Mayo Clinic (n = 922) and ADNI (n = 93) cohorts and applied the LANS criteria to those with an antemortem predominant amnestic syndrome (Mayo, n = 165; ADNI, n = 53). ADNC, ADNC/LATE-NC and LATE-NC accounted for 35%, 37% and 4% of cases in the Mayo cohort, respectively, and 30%, 22%, and 9% of cases in the ADNI cohort, respectively. The LANS criteria effectively categorized these cases, with ADNC having the lowest LANS likelihoods, LATE-NC patients having the highest likelihoods, and ADNC/LATE-NC patients having intermediate likelihoods. A logistic regression model using the LANS features as predictors of LATE-NC achieved a balanced accuracy of 74.6% in the Mayo cohort, and out-of-sample predictions in the ADNI cohort achieved a balanced accuracy of 73.3%. Patients with high LANS likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods. Stratifying ADNC/LATE-NC patients from the Mayo cohort according to their LANS likelihood revealed that those with higher likelihoods had more temporo-limbic degeneration and a slower rate of cognitive decline, and those with lower likelihoods had more lateral temporo-parietal degeneration and a faster rate of cognitive decline. The implementation of LANS criteria has implications to disambiguate the different driving etiologies of progressive amnestic presentations in older age and guide prognosis, treatment, and clinical trials. The development of in vivo biomarkers specific to TDP-43 pathology are needed to refine molecular associations between LANS and LATE-NC and precise antemortem diagnoses of LATE.
Background: Subthreshold depression is a risk factor for major depression and is associated with increased morbidity and mortality, especially in poorly resourced settings. There is emerging evidence that digital interventions may be effective at improving depressive symptoms in High Income Countries but not Low- and Middle-Income settings. We aimed to evaluate the effectiveness of the Viva Vida digital intervention at improving symptoms of subthreshold depression among older adults in socioeconomically deprived settings in Brazil. Methods: PRODIGITAL was a single blind, two-arm, individually randomised controlled trial conducted in 46 primary care clinics in Guarulhos, Brazil. Individuals aged 60+ years were randomly contacted by phone for a screening assessment. Those who presented with anhedonia and/or depressed mood (Patient Health Questionnaire (PHQ)-2), and who subsequently scored between 5 and 9 on the PHQ-9 were invited to participate. The intervention (Viva Vida) arm received a self-help fully automated programme sent via WhatsApp with no support from healthcare professionals. Forty-eight audio and visual messages based on psychoeducation and behavioural activation approaches were delivered over six weeks. The control arm received a single message with information about depression. The primary outcome was the PHQ-9 at three months follow-up. All primary analyses were performed according to allocated arm with imputed data. The trial is registered with ReBEC, RBR-6c7ghfd. Findings: Participants were recruited between 8 September 2021 and 19 August 2022. Of the 454 participants enrolled, 223 were randomised to the intervention arm and 231 to receive the single message. A total of 385 (84.8%) completed the three-month follow-up assessment; no difference in mean PHQ-9 scores between the arms (adjusted difference: -0.61; 95% CI: -1.76, 0.53; p=0.290) was observed. Interpretation: These results demonstrate that a fully automated digital programme did not help to improve subthreshold depressive symptoms amongst older adults. More research is needed to understand how such interventions can be adapted to reduce depressive symptoms as well as prevent against major depression in low-resourced settings.
Background: Preterm birth, defined as birth at <37 weeks of gestation, is the leading cause of neonatal death globally and, together with low birthweight, the second leading cause of infant mortality in the United States. There is mounting evidence that COVID-19 infection during pregnancy is associated with an increased risk of preterm birth; however, data remain limited by trimester of infection. The ability to study COVID-19 infection during the earlier stages of pregnancy has been limited by available sources of data. The objective of this study was to use self-reports in large-scale, longitudinal social media data to assess the association between trimester of COVID-19 infection and preterm birth. Methods: In this retrospective cohort study, we used natural language processing and machine learning, followed by manual validation, to identify pregnant Twitter users and to search their longitudinal collection of publicly available tweets for reports of COVID-19 infection during pregnancy and, subsequently, a preterm birth or term birth (i.e., a gestational age [≥]37 weeks) outcome. Among the users who reported their pregnancy on Twitter, we also identified a 1:1 age-matched control group, consisting of users with a due date prior to January 1, 2020 (i.e., without COVID-19 infection during pregnancy). We calculated the odds ratios (ORs) with 95% confidence intervals (CIs) to compare the overall rates of preterm birth for pregnancies with and without COVID-19 infection and by timing of infection: first trimester (weeks 1-13), second trimester (weeks 14-27), or third trimester (weeks 28-36). Results: Through August 2022, we identified 298 Twitter users who reported COVID-19 infection during pregnancy, a preterm birth or term birth outcome, and maternal age: 94 (31.5%) with first-trimester infection, 110 (36.9%) second-trimester infection, and 95 (31.9%) third-trimester infection. In total, 26 (8.8%) of these 298 users reported preterm birth: 8 (8.5%) were infected during the first trimester, 7 (6.4%) were infected during the second trimester, and 12 (12.6%) were infected during the third trimester. In the 1:1 age-matched control group, 13 (4.4%) of the 298 users reported preterm birth. Overall, the risk of preterm birth was significantly higher for pregnancies with COVID-19 infection compared to those without (OR 2.1, 95% CI 1.06-4.16). In particular, the risk of preterm birth was significantly higher for pregnancies with COVID-19 infection during the third trimester (OR 3.17, CI 1.39-7.21). Conclusion: The results of our study suggest that COVID-19 infection particularly during the third trimester is associated with an increased risk of preterm birth.
Streptococcus pneumoniae colonization in the upper respiratory tract is linked to pneumococcal disease development, predominantly affecting the very young and older adults. As the global population ages and comorbidities increase, there is a heightened concern about this infection. We investigated the immunological responses of older adults to pneumococcal controlled human infection by analysing the cellular composition and gene expression in the nasal mucosa. Our comparative analysis with younger adults revealed distinct gene expression patterns in older individuals susceptible to colonization, highlighted by neutrophil activation and elevated levels of CXCL9 and CXCL10. Unlike younger adults challenged with pneumococcus, older adults did not show recruitment of monocytes into the nasal mucosa following nasal colonization. These findings suggest age-associated cellular changes, in particular enhanced mucosal inflammation, that may predispose older adults to pneumococcal colonization. If similar changes are observed in the lung of susceptible older adults, these may explain the increased risk of pneumococcal disease in vulnerable populations.
In order to mitigate the inequities in health outcomes and healthcare access for vulnerable populations during the COVID-19 pandemic, the government of India introduced antigen-based SARS-CoV-2 self-testing kits for self-administered use. In this study, we aimed to determine the usability of these nasal-sampling-based self-tests in a peer-assisted model among factory workers in Bengaluru. The mixed-method cross-sectional study was conducted with 106 factory workers, spanning two sites from February to March 2022 in Bengaluru, India. Panbio COVID-19 Antigen Self-Test kit and the mobile application NAVICA for self-reporting results were used. A peer assistant distributed test kits, guided participants on conducting tests and using the app, and offered demonstrations with their own kit, ensuring no contact with the participants' kits. Findings were encapsulated by an observer, who used standardized product-specific usability checklists and pictures of contrived results to assess the usability of the kit and mobile application, result interpretation, and the efficiency of peer instruction/demonstration. Additionally, a post-test survey and focus group discussions with selected participants and peer assistants were conducted to understand user perceptions of the facilitators and barriers to usability. Study findings show that the overall usability score of the test kit with peer assistance was 75.9%, rising to 80.7% for critical steps and 33.8% for all critical steps in uploading results through NAVICA. Additionally, it was seen that peer assistants provided accurate instructions and support for 93.4% of the tests. Among the critical steps in test kit use, maximum errors were made in sample collection and using the correct amount of buffer solution. Concordance between the participant and observer/NAVICA was 97.9%. 62.0% and 56.6% of the participants reported confidence in a) performing and interpreting the test and b) capturing and uploading their results using the mobile application with the assistance of a peer, respectively. Less than half the participants reported confidence in performing these steps independently. The study indicates that the COVID-19 nasal self-testing kit has good usability in factories' peer-assisted workplace testing model. Such models can empower vulnerable worker groups to access early detection and self-care tools equitably.
The persistence of measles in many regions demonstrates large immunity gaps, resulting from incomplete or ineffective immunization with measles-containing vaccines (MCVs). A key factor affecting MCV impact is age, with infants receiving dose 1 (MCV1) at older ages having a reduced risk of vaccine failure, but also an increased risk of contracting infection before vaccination. Here, we designed a new method - based on a transmission model incorporating realistic vaccination delays and age variations in MCV1 effectiveness - to capture this risk trade-off and estimate the optimal age for recommending MCV1. We predict a large heterogeneity in the optimal ages (range: 6-20 months), contrasting the homogeneity of observed recommendations worldwide. Furthermore, we show that the optimal age depends on the local epidemiology of measles, with a lower optimal age predicted in populations suffering higher transmission. Overall, our results suggest the scope for public health authorities to tailor the recommended schedule for better measles control.
Background The Middle Eastern population is characterized by increased prevalence of various Mendelian disorders owing to increased rates of consanguinity. Especially in disease conditions which require chronic transfusion support, it becomes important to know the blood group characteristics of potential donors to increase the likelihood of transfusion success. As there prevails a gap in knowledge about the population specific overall blood antigen profiles, this study seeks to utilize next generation sequencing datasets to unravel the comprehensive landscape of clinically significant minor blood group alleles in the middle eastern population. Methods This study utilizes the genetic variation data from a range of public datasets including the Greater Middle East Variome, the Qatar genome and exomes and the Iranome datasets to estimate the genotypic and phenotypic frequencies of blood group alleles in the Middle Easterners. The estimated frequencies were duly compared with major global populations to identify significant similarities or differences if any. Results A total of 77 unique ISBT approved blood group alleles were found commonly in all datasets. 8 variants (rs8176058, rs1058396, rs565898944, rs28362692, rs2071699, rs34783571, rs60322991 and rs57467915) belonging to KELL, KIDD, COLTON, H, JUNIOR and LANGEREIS blood groups were found clinically significant with previously reported evidence on transfusion complications. 730 variants were found to span exonic or splicing regions out of which 70 were predicted to be potentially deleterious by at least four computational tools. Conclusions This study serves first of its kind to extensively characterize the known and novel blood alleles in the Middle Easterners. A comprehensive user-friendly online resource named alnasab - Alleles and antigens in Arab and Persian populations associated with blood groups was also developed as a dependable reference for future transfusion research. The resource is accessible at https://clingen.igib.res.in/alnasab/
Transdermal drug delivery is suitable for low-molecular-weight drugs with specific lipophilicity, like fentanyl, which is widely used for cancer-induced pain management. However, fentanyl's transdermal therapy displays high intra-individual variability. Factors like skin characteristics at application sites and ambient temperature contribute to this variation. In this study, we developed a physics-based digital twin of the human body to cope with this variability and propose better adapted setups. This twin includes an in-silico skin model for drug penetration, a pharmacokinetic model, and a pharmacodynamic model. Based on the results of our simulations, applying the patch on the flank (side abdominal area) showed a 15.3% higher maxi-mum fentanyl concentration in the plasma than on the chest. Additionally, the time to reach this maximum concentration when delivered through the flank was 19.8 h, which was 10.3 h earlier than via the upper arm. Finally, this variation led to an 18% lower minimum pain intensity for delivery via the flank than the chest. Moreover, the impact of seasonal changes on ambient temperature and skin temperature by considering the activity level was investigated. Based on our result, the fentanyl uptake flux by capillaries increased by up to 11.8% from an inactive state in winter to an active state in summer. We also evaluated the effect of controlling fentanyl delivery by adjusting the temperature of the patch to alleviate the pain to reach a mild pain intensity (rated three on the VAS scale). By implementing this strategy, the average pain intensity decreased by 1.1 points, and the standard deviation for fentanyl concentration in plasma and average pain intensity reduced by 37.5% and 33.3%, respectively. Therefore, our digital twin demonstrated the efficacy of controlled drug release through temperature regulation, ensuring the therapy toward the intended target outcome and reducing therapy outcome variability. This holds promise as a potentially useful tool for physicians.
Significance: The analysis of the wavefront phase of keratoconus eyes has become increasingly important due to its impact on the assessment of visual quality loss, irrecoverable with conventional optical treatments, and the understanding of morphological changes in corneal structures. Aim: The aim of this work is to quantitatively assess the wavefront phase of keratoconic eyes measured by the novel high-resolution ocular aberrometer t-eyede (based on WaveFront Phase Imaging Sensor). Approach: The measurements with this device were taken on healthy and keratoconic eyes at the Hospital Universitario Fundacion Jimenez Diaz (Madrid, Spain). The wavefront phase recovered is post-processed and displayed in different phase maps, using exclusively the high-pass filter map for this study. From this map, the Root Mean Square, the Peak-to-Valley, and the amplitude value of the predominant obtained from its Fourier Transform are the parameters to distinguish between healthy and keratoconic eyes. Furthermore, the banding pattern observed in most keratoconic eyes is quantitatively analyzed by means of its period and orientation calculated from the Fourier Transform. Results: The Control group was composed of 43 healthy eyes, and the Pathological group presented 43 keratoconic eyes. Regarding the first three parameters used to compare both groups, there were significant statistical differences between them in all parameters, where the values obtained with the keratoconic group were higher than those of the healthy group. Although the values cannot be statistically comparable between stages, they tended to increase according to the severity of the disease. On the other hand, analyzing the banding pattern, the mean value of the period was approximately 50 microns, and most orientations were obliquus, tending to be horizontal rather than vertical. Conclusions: The present study demonstrates that the objective analysis of the high frequencies detected by this wavefront sensor is a potential tool to reliably advise in the keratoconus diagnosis. Furthermore, combining this achievement with the quantitative assessment of the banding pattern would be used to objectively monitor the internal corneal status throughout the disease and its treatment optimization and surgery time.
Objectives: To examine the associations between catheter ablation treatment (CA) versus medical management and cognitive impairment among older adults with atrial fibrillation (AF). Methods: Ambulatory patients who had AF, were [≥] 65-years-old, and were eligible to receive oral anticoagulation could be enrolled into the SAGE (Systematic Assessment of Geriatric Elements)-AF study from internal medicine and cardiology clinics in Massachusetts and Georgia between 2016 and 2018. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) tool at baseline, one-, and two years. Cognitive impairment was defined as a MoCA score [≤] 23. Multivariate-adjusted logistic regression of longitudinal repeated measures was used to examine associations between treatment with CA vs. medical management and cognitive impairment. Results: 887 participants were included in this analysis. On average, participants were 75.2 +/- 6.7 years old, 48.6% women, and 87.4% white non-Hispanic. 193 (21.8%) participants received a CA before enrollment. Participants who had previously undergone CA were significantly less likely to be cognitively impaired during the two-year study period (aOR 0.70, 95% CI 0.50-0.97) than those medically managed (i.e., rate and/or rhythm control), even after adjusting with propensity score for CA. At the two-year follow-up a significantly greater number of individuals in the non-CA group were cognitively impaired (MoCA [≤] 23) compared to the CA-group (311 [44.8%] vs. 58 [30.1%], p=0.0002). Conclusions: In this two-year longitudinal prospective cohort study participants who underwent CA for AF before enrollment were less likely to have cognitive impairment than those who had not undergone CA.
Question: How good is the quality of systematic reviews on the effectiveness of physiotherapy for musculoskeletal conditions? Are there any factors associated with quality? Design: This is a meta-epidemiological study on systematic reviews with meta-analysis (SR-MA) of randomised controlled trials (RCT). Methods: MEDLINE, Cochrane Database of Systematic Reviews (CDSR), CINAHL, and PEDro were searched for SR-MA of RCT on physiotherapy in musculoskeletal disorders in the last ten years. Two independent researchers screened and extracted the records and analysed the full-texts. The quality of SR-MA was quantified with AMSTAR-2 tool on a sample of 100 studies, randomly selected from the records retrieved. Disagreements were solved by consensus. Results: The number of eligible publications increased over the past ten years. However, the methodological quality was critically low in as many as 90% of the studies retrieved and did not increase with time. The last author's H-index was the only quality predictor among the variables analysed. Conclusion: The methodological quality of the SR-MA of RCT is unacceptably low. Given the frequent application of physiotherapy in musculoskeletal disorders, there is an urgent need to improve secondary research by adopting more rigorous methods.
Purpose or Learning Objective Artificial intelligence (AI) with convolutional neural network allows fully automated detection and segmentation of bronchial changes on CT-scans of cystic fibrosis (CF). However, the superiority of two-dimensional (2D) versus three-dimensional (3D) architectures remains to be explored. Method or Background CT-scans from fifty CF patients were retrospectively included at two CF reference centers. The nnUnet model was implemented in both 2D and 3D, and trained to segment five structural alterations: bronchiectasis, wall thickening, mucus plugs, bronchiolar impactions and consolidations. A semantic validation was done by using fifty CTs with a five-fold cross validation strategy, by comparing normalized Dice-Sorensen coefficient (DSC) between 2D and 3D architectures, with manual segmentations as Gold Standard. Results or Findings The 3D nnUnet was found able to segment the five CF main hallmarks such as bronchiectasis, wall thickening, mucus plugs, bronchiolar impactions and consolidations. Metrics obtained with the 3D architecture were superior for mucus plugs, bronchiolar impactions and consolidations (p<0.001) but not significantly different for bronchiectasis and wall thickening (p>0.05). Conclusion AI with the 3D-nnUnet model can perform fully automated segmentation of CF-related structural hallmarks on CT scans, and overcome 2D implementation. Non-invasive, holistic 3D quantifications are allowed for promising next clinical applications.
Pneumonia is one of the most common causes of hospital admission in the United States. Worldwide, the majority of antibiotics are prescribed for upper respiratory infections, much of which could be avoided with highly accurate methods of diagnosing or excluding pneumonia at the bedside. Despite the high prevalence of infectious pneumonia and decades of medical progress, accurately diagnosing or ruling out pneumonia without the use of computed tomography (CT) scanners and distinguishing between viral or bacterial etiologies remains challenging. We enrolled 61 patients in a prospective, blinded study to determine the sensitivity of lung ultrasound (LUS) using a handheld ultrasound probe in patients who had a computed tomography (CT) scan of their chest for any reason. The sensitivity of lung ultrasound to detect patients with evidence of pneumonia as compared to a CT scan was 94.4% (72.7 - 99.9) with a negative predictive value of 96.2% (80.4 - 99.9) when the scan was normal. Due to our broad inclusion criteria and the high prevalence of of non-infectious lung disease at the site of this study, the specificity was 61% (44.5 - 75.8) and positive predictive value was 51.5% (33.5 - 69.2). This simple lung ultrasound scan can be incorporated into the physical exam, has very high sensitivity to detect patients with pneumonia, and can be effectively used to rule out pneumonia if the lung exam is normal.
Whilst healthcare workers (HCWs) are at high risk of contracting COVID-19, measures can be put in place to reduce the spread of COVID-19 and other respiratory infections in healthcare settings. These currently include the use of masks: fluid-resistant surgical masks and respiratory protective equipment. However, for mask policies to be effective, compliance with their use must be high. This study interviewed 12 HCWs from a variety of backgrounds to understand their experiences of mask use. We explored factors associated with compliance with mask use and potential impacts on HCW wellbeing. Overall, participants reported good understanding of the benefits of masks and high compliance levels with policy. However, factors that reduced their compliance with mask policy and impacted their ability to carry out their role were highlighted. These included wearing masks for longer durations, policy being perceived as out of proportion with risk, communication challenges, and discomfort. This study highlights the importance of clear communication of guidance, particularly when it has changed, ensuring staff are familiar with up-to-date research on efficacy of masks, and ensuring guidance aligns with risk. Furthermore, this study highlights the importance of masks being required for an appropriate duration (based on risk).
Exposure in vivo is a highly effective treatment for anxiety disorders and acrophobia in particular. Nevertheless, it is rarely implemented in outpatient treatment. Exposure in virtual reality (VR) might be an alternative but its effect on subjective symptom burden and physiological parameters is questionable. Therefore, in this study, N = 33 participants with fear of heights received both in vivo and VR exposure in a randomized order. Subjective symptom burden before and after each exposure as well as heart rate and heart rate variability (SDNN, LF/HF ratio) during exposure sessions were assessed. Linear mixed models were calculated with the effect of condition (VR vs. in vivo) and scenario on HR, SDNN and LF/HF ratio. Subjective symptom burden was significantly reduced after both exposure sessions (p = .002; p < .001). Heart rate was significantly higher during exposure scenarios than baseline (p < .001). SDNN and LF/HF ratio reflected a significantly higher general power of HRV and a significantly higher activation of the sympathetic nervous system during exposure sessions compared to baseline and during VR exposure compared to in vivo. All in all, VR exposure shows comparable or superior effects compared to in vivo exposure regarding acrophobic fears and physiological parameters.
Background and objectives: Public health measures, parental fear of infection, and redeployment of medical resources in response to the COVID-19 pandemic might have led to a decrease in pediatric healthcare access. As a result, a delay in type 1 diabetes diagnosis might have occurred, leading to the worsening of its clinical presentation in the pediatric population. This study aimed to examine the clinical and biochemical features of new-onset DM1 in children and adolescents during the COVID-19 pandemic, comparing it to the pre-pandemic period. Materials and methods: The clinical and biochemical features of diabetes observed during the COVID-19 period from April 1, 2020, until December 31, 2022, were compared with the period from April 1, 2017, until December 31, 2019. In the COVID-19 pandemic group, the clinical and biochemical features were compared between children with and without SARS-CoV-2 infection at diagnosis or before the diagnosis of DM1. Results: During the COVID-19 pandemic, observed frequencies of DKA and severe DKA at diagnosis were 47.6% and 20.7%, both significantly higher than during the pre-pandemic period (an absolute increase of 15% and 11.3%, respectively). In the COVID-19 group, blood pH levels were significantly lower than in the pre-pandemic group, while HbA1c levels were higher. Clinical and biochemical features of diabetes in children with SARS-CoV-2 infection at or before the diagnosis were not significantly different compared to children without an infection. Conclusion: We report a significant worsening of the clinical presentation of new-onset type 1 diabetes and an increase in the frequency of DKA and severe DKA at diagnosis during the COVID-19 pandemic. Further studies are necessary to gain quantitative insight into pediatric healthcare availability in Serbia.
Seroprevalence studies are the gold standard for disease surveillance, and serology was used to determine eligibility for the first licensed dengue vaccine. However, expanding flavivirus endemicity, co-circulation, and vaccination complicate serology results. Among 713 healthy Cambodian children, a commonly used indirect dengue virus IgG ELISA (PanBio) had a lower specificity than previously reported (94% vs. 100%). Of those with false positive PanBio results, 46% had detectable neutralizing antibodies against other flaviviruses, with the highest frequency against West Nile virus (WNV). Immunity to non-dengue flaviviruses can impact dengue surveillance and potentially pre-vaccine screening efforts.
INTRODUCTION: We evaluated the impact of a real-time locating system on emergency department efficiency and frustration locating mobile otoscope/ophthalmoscope carts. DATA AND METHODS: Thirty ED providers were selected on-shift, each serving as their own control. Investigators hid two mobile otoscope/ophthalmoscopes carts (with and without the RTLS device) equidistant from the center of a provider's work area. Providers were timed finding both devices and were queried regarding feelings about the search experience. RESULTS: RTLS was associated with statistically-significantly less time locating equipment (average of 25 vs. 92 seconds) and percent of providers requiring 30, 60, 90, and 120 seconds to find the device. Providers felt finding the mobile cart with RTLS was easier; all rated finding the RTLS-tagged cart as easy. Without RTLS, two-thirds of subjects reported either frustration or extreme frustration vs. 3% with RTLS. All differences in comparisons of subjective experience were statistically-significant. Annual time and cost saving with RTLS would be 116.4 hours ($9,135.66). CONCLUSION: RTLS in EDs can decrease time and frustration associated with finding equipment and is cost-effective. Frustration is a common driver behind burnout in Emergency Medicine. Use of RTLS technology might improve the provider experience and, thereby, reduce burnout levels.
Introduction: Fractures over venous sinuses (FOVS) are associated with difficulties in diagnosis, and treatment resulting in a high level of morbidity, and mortality. Despite its importance, there is limited aggregate data to guide the management of these fractures ultimately inflicting a major challenge to neurosurgeons. This protocol describes the methodology of a scoping review that aims to synthesise contemporary evidence on the management and outcomes of FOVS. Methods and analysis: The proposed study will be conducted in accordance with the Arksey and O Malleys framework for scoping reviews. The research question, eligibility criteria and search strategy were developed based on the Population, Intervention, Comparator, Outcome strategy. The following electronic bibliographic databases will be searched without restrictions on language, and date of publication: PubMed, WHO Global Index Medicus, African Journals Online, SCOPUS, Embase. All peer-reviewed studies of primary data reporting on the management and outcomes of FOVS will be included. The data extracted from included articles will be presented through descriptive statistics, pooled statistics, and a narrative description. Ethics and dissemination: Because this study did not directly involve human individuals, ethical approval was not necessary. Dissemination strategies will include publication in a peer-reviewed journal, oral and poster presentations at local, regional, national and international conferences and promotion over social media.