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BACKGROUND: Acute gastroenteritis is an important reason for emergency department (ED) consultation in children. Ondansetron is reported to be effective in reducing vomiting in children with gastroenteritis, leading to less intravenous rehydration and hospital admission. OBJECTIVE(S): The aim of this study was to assess the effectiveness of triage nurse-initiated administration of ondansetron for children with suspected gastroenteritis in the paediatric ED to reduce the number of patients requiring observation following the first physician assessment. DESIGN/METHODS: This was a randomized controlled trial performed in a tertiary care paediatric ED. All children 6 months to 17 years old who presented to the ED with at least four episodes of non-billous, non-bloody vomiting in the previous 24 hours and the last vomiting occurring within the previous 2h were eligible. The intervention consisted of administration of a liquid formulation of an adapted to weight dose of ondansetron at triage compared to a color- and taste-matched placebo. The primary outcome was the number of patients requiring observation after the first physician's evaluation. Secondary outcomes were the number of episodes of vomiting after receiving the intervention, length of stay in the ED, comfort, and the proportion of children who returned for a medical visit within 48 hours. A sample size of 248 participants was initially identified to have a power of 90% to find a 20% difference in the proportion of children needing observation following physician evaluation. RESULT(S): Because of multiple external factors, including the COVID-19 pandemic, recruitment was stopped before the expected sample size was reached. A total of 91 patients were included and randomized to receive ondansetron (n= 44) or a placebo (n=47) just after triage. The baseline characteristics of the participants was similar between the two groups. A total of 40 (45%) participants were discharged immediately after the first evaluation by the treating physician. This was similar for both groups 44% vs. 45%;(95% CI for the difference -20 to 19%). There was no difference between the two groups for the total length of stay (median 232 vs. 227 minutes;p= 0.677) and for the length of stay after being seen by the physician (72 vs. 68 minutes;p=0.821). There was no statistical difference between the two groups in the number of vomiting episodes (difference of 15%;95% CI -2, 31), and proportion of participants needing a rescue medication (difference: 19%;95%CI:-0.6 to 36%) or an intravenous rehydration (difference: 8;95%CI:-6, 22). CONCLUSION(S): This study failed to demonstrate any benefit in using ondansetron at triage for children with presumed gastroenteritis.
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Background. mRNA vaccines for coronavirus disease 2019 (COVID-19) illicit strong humoral and cellular responses and have high efficacy for preventing and reducing the risk of severe illness from COVID-19. Since solid organ transplant (SOT) recipients were excluded from the phase 3 trials, the efficacy of the COVID-19 vaccine remains unknown. Understanding the serological responses to COVID vaccines among SOT recipients is essential to better understand vaccine protection for this vulnerable population. Methods. In this prospective cohort study, a subset of SOT recipients who were part of our center's larger antibody study were enrolled prior to receipt of two doses of the BNT162b2 (Pfizer, Inc) vaccine for high resolution immunophenotyping. To date, plasma has been collected for 10 participants on the day of their first dose (baseline), day of their second dose, and 28 days post second dose. 23 healthy participants planning to receive either BNT162b2 or mRNA-1273 (ModernaTX, Inc) were also enrolled, providing plasma at the same timepoints. Ultrasensitive single-molecule array (Simoa) assays were used to detect SARS-CoV-2 Spike (S), S1, receptor-binding domain (RBD) and Nucleocapsid (N) IgG antibodies. Results. Participant demographics and SOT recipient characteristics are summarized in Table 1. Low titers of anti-N IgG at all timepoints indicate no natural infection with COVID-19 during the study (Fig 1A). There were significantly lower magnitudes for anti-S (p< 0.0001), anti-S1 (p< 0.0001), and anti-RBD (p< 0.0001) IgG titers on the day of dose 2 and day 28 post second dose for SOT recipients compared to healthy controls (Fig 1B,C,D). Using the internally validated threshold of anti-S IgG >1.07 based on pre-pandemic controls, only 50% of the SOT sub-cohort responded to vaccine after series completion (Fig 2). There was a positive trend between months from transplant and anti-S IgG titer (Fig 3). Black error bars denote median and 95% CI. The dotted line on panel B denotes an internally validated cutoff of 1.07;anti-S IgG titers greater than 1.07 denote a positive response. SOT recipients further out from transplant tend to have a higher anti-S IgG response. The dotted line denotes an internally validated cutoff, with anti-S IgG titers greater than 1.07 indicating a positive response. Conclusion. SOT recipients had a significantly decreased humoral response to mRNA COVID-19 vaccines compared to the healthy cohort, with those further out from transplant more likely to respond. Further research is needed to evaluate T-cell responses and clinical efficacy to maximize the SARS-CoV-2 vaccine response among SOT recipients.
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Background. Allogeneic stem cell transplant (SCT) recipients are at an increased risk of poor outcomes from COVID-19. While the mRNA-1273 (Moderna) and BNT162b2 (Pfizer) COVID-19 mRNA vaccines are highly immunogenic in the general population, the immune response in SCT recipients is poorly understood. We characterized the immunogenicity and reactogenicity of COVID-19 mRNA vaccines in a cohort of SCT patients. Methods. We performed a prospective cohort study of 16 allogeneic SCT patients and 23 healthy controls. Blood samples for both cohorts were collected prior to first vaccination (baseline), at the time of second vaccination, and approximately 28 days post-second vaccination. Anti-Spike (S), anti-S1, anti-receptor binding domain (RBD), and anti-Nucleocapsid (N) IgG levels were measured quantitatively from plasma using a multiplexed single molecule array (Simoa) immunoassay. Reactogenicity was captured for the SCT cohort via a self-reported post-vaccination diary for 7 days after each dose. Results. Demographics and SCT recipients' characteristics are shown in Table 1. In the SCT cohort, we observed a significantly lower anti-S (p< 0.0001), S1 (p< 0.0001), and RBD (p< 0.0001) IgG responses as compared to healthy controls, both at the time of dose 2 and 28 days post-vaccine series (Fig 1). Overall, 62.5% of SCT recipients were responders after vaccine series completion, as compared to 100% of healthy controls (Fig 2). While no patients had a reported history of COVID-19 diagnosis, 2 patients in the SCT cohort had elevated anti-S IgG levels and 1 showed elevated anti-N at baseline. 10/16 participants in the SCT cohort completed at least one post-vaccination diary. Local and systemic reactions were reported by 67% and 22% of participants, respectively, after dose 1, and 63% and 50% after dose 2 (Figure 3). All reported events were mild. Anti-Spike (A), anti-S1 (B), anti-RBD (C), and anti-nucleocapsid (D) IgG titers were measured at baseline, time of second dose, and approximately 28 days after second vaccination. IgG levels were measured quantitatively using multiplexed single molecule array (Simoa) immunoassays, and are reported as Normalized Average Enzymes per Bead (AEB). Allogeneic stem cell transplant recipients (mauve) showed significantly lower anti-S, S1, and RBD IgG responses as compared to healthy controls (mint). Low titers of anti-N IgG demonstrates no history of COVID-19 natural infection during the course of the study. 10 allogeneic stem cell transplant recipients completed at least one diary for 7 days after vaccination. Reactions after dose 1 are shown in light blue, and reactions after dose 2 are shown in dark blue. Local reactions (A) were reported by 67% (6/9) of participants after dose 1, and 63% (5/8) after dose 2. Systemic reactions (B) were reported by 22% (2/9) of participants after dose 1, and 50% (4/8) after dose 2. All reported events were mild (Grade 1). Conclusion. Among SCT recipients, mRNA COVID-19 vaccines were well-tolerated but less immunogenic than in healthy controls. Further study is warranted to better understand heterogeneous characteristics that may affect the immune response in order to optimize COVID-19 vaccination strategies for SCT recipients. Figure 2: Response Rate to COVID-19 Vaccination An internally validated threshold for responders was established using pre-pandemic sera from healthy adults. A positive antibody response was was defined as individuals with anti-Spike IgG levels above the 1.07 Normalized AEB threshold.
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Background. Patients with lymphoid malignancies are at high risk of severe COVID-19 disease and were not included in the phase 3 mRNA vaccine trials. Many patients with lymphoid malignancies receive immunosuppressive therapies, including B-cell depleting agents, that may negatively impact humoral response to vaccination. Methods. We recruited patients with lymphoid malignancies and healthy participants who planned to receive two doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). Blood was drawn at baseline, prior to second dose of vaccine, and 28 days after last vaccination. Disease characteristics and therapies were extracted from patients' electronic medical record. An ultrasensitive, single molecule array (Simoa) assay detected anti-Spike (S), anti-S1, anti-receptor binding domain (RBD), and anti-Nucleocapsid (N) IgG from plasma at each timepoint. Results. 23 healthy participants and 37 patients with lymphoid malignancies were enrolled (Table 1). Low titers of anti-N (Fig 1A) demonstrate no prior exposure or acquisition of COVID-19 before vaccination or during the study. 37.8% of the lymphoid malignancy cohort responded to the vaccine, using an internally validated AEB cutoff of 1.07. A significantly higher magnitude of anti-S (p< 0.0001), anti-S1 (p< 0.0001) and anti-RBD (p< 0.0001) are present in the healthy as compared to lymphoid malignancy cohort at the second dose and day 28 post-series (Fig 1B, Fig 1C and Fig 1D). Anti-S IgG titers were compared between the healthy cohort, treatment naI&Die;ve, and treatment experienced groups (Fig 2). The treatment naI&Die;ve cohort had high titers by series completion which were not significantly different from the healthy cohort (p=0.2259), although the treatment experienced group had significantly decreased titers (p< 0.0001). Of the 20 patients who had received CD20 therapy, there was no clear correlation of anti-S IgG response with time from CD20 therapy, although most patients who received CD20 therapies within 12 months from the vaccine had no response (Figure 3). Conclusion. The vaccine-induced immune response was poor among treatment-experienced patients with lymphoid malignancies, especially among those who received CD20 therapies within 12 months.
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[Figure: see text].
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Mapping the prevalence and spread of infectious diseases has never been more critical than during the COVID-19 pandemic. A plethora of Web-based GIS dashboards have been created that incorporate basic GIS functionality;these dashboards have served as platforms for rapid data sharing and real-time information, ultimately facilitating decision making. However, many of them have merely focused on presenting and monitoring cumulative or daily incidence of COVID-19 data, disregarding the temporal dimension. In this paper, we review the usefulness of GIS-based dashboards for mapping the prevalence of COVID-19, but also missed opportunities to emphasize the temporal component of the disease (cyclicity, seasonality). We suggest that advanced geovisualization techniques can be used to integrate the temporal component in interactive animated maps illustrating (a) the daily relative risk and the number of days a geographic region has been in a disease cluster, (b) the ratio between the observed and expected number of cases over time, and (c) mortality count dynamics in a space-time cube. We illustrate these approaches by using COVID-19 cases and death counts across the U.S. at the county level from 25 January 2020 to 1 October 2020. We discuss how each of these visualization approaches can promote the understanding of important public health concepts applied to the pandemic such as risk, spread, and mortality. Finally, we suggest future avenues to promote research at the intersection of space-time visualization and infectious diseases.
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The first case of COVID-19 in South America occurred in Brazil on February 25, 2020. By July 20, 2020, there were 2,118,646 confirmed cases and 80,120 confirmed deaths. To assist with the development of preventive measures and targeted interventions to combat the pandemic in Brazil, we present a geographic study to detect "active" and "emerging" space-time clusters of COVID-19. We document the relationship between relative risk of COVID-19 and mortality, inequality, socioeconomic vulnerability variables. We used the prospective space-time scan statistic to detect daily COVID-19 clusters and examine the relative risk between February 25-June 7, 2020, and February 25-July 20, 2020, in 5570 Brazilian municipalities. We apply a Generalized Linear Model (GLM) to assess whether mortality rate, GINI index, and social inequality are predictors for the relative risk of each cluster. We detected 7 "active" clusters in the first time period, being one in the north, two in the northeast, two in the southeast, one in the south, and one in the capital of Brazil. In the second period, we found 9 clusters with RR > 1 located in all Brazilian regions. The results obtained through the GLM showed that there is a significant positive correlation between the predictor variables in relation to the relative risk of COVID-19. Given the presence of spatial autocorrelation in the GLM residuals, a spatial lag model was conducted that revealed that spatial effects, and both GINI index and mortality rate were strong predictors in the increase in COVID-19 relative risk in Brazil. Our research can be utilized to improve COVID-19 response and planning in all Brazilian states. The results from this study are particularly salient to public health, as they can guide targeted intervention measures, lowering the magnitude and spread of COVID-19. They can also improve resource allocation such as tests and vaccines (when available) by informing key public health officials about the highest risk areas of COVID-19.
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Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China in December 2019, and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is a pandemic with an estimated death rate between 1% and 5%; and an estimated R 0 between 2.2 and 6.7 according to various sources. As of March 28th, 2020, there were over 649,000 confirmed cases and 30,249 total deaths, globally. In the United States, there were over 115,500 cases and 1891 deaths and this number is likely to increase rapidly. It is critical to detect clusters of COVID-19 to better allocate resources and improve decision-making as the outbreaks continue to grow. Using daily case data at the county level provided by Johns Hopkins University, we conducted a prospective spatial-temporal analysis with SaTScan. We detect statistically significant space-time clusters of COVID-19 at the county level in the U.S. between January 22nd-March 9th, 2020, and January 22nd-March 27th, 2020. The space-time prospective scan statistic detected "active" and emerging clusters that are present at the end of our study periods - notably, 18 more clusters were detected when adding the updated case data. These timely results can inform public health officials and decision makers about where to improve the allocation of resources, testing sites; also, where to implement stricter quarantines and travel bans. As more data becomes available, the statistic can be rerun to support timely surveillance of COVID-19, demonstrated here. Our research is the first geographic study that utilizes space-time statistics to monitor COVID-19 in the U.S.