INTRODUCTION: An error grid compares measured versus reference glucose concentrations to assign clinical risk values to observed errors. Widely used error grids for blood glucose monitors (BGMs) have limited value because they do not also reflect clinical accuracy of continuous glucose monitors (CGMs). METHODS: Diabetes Technology Society (DTS) convened 89 international experts in glucose monitoring to (1) smooth the borders of the Surveillance Error Grid (SEG) zones and create a user-friendly tool-the DTS Error Grid; (2) define five risk zones of clinical point accuracy (A-E) to be identical for BGMs and CGMs; (3) determine a relationship between DTS Error Grid percent in Zone A and mean absolute relative difference (MARD) from analyzing 22 BGM and nine CGM accuracy studies; and (4) create trend risk categories (1-5) for CGM trend accuracy. RESULTS: The DTS Error Grid for point accuracy contains five risk zones (A-E) with straight-line borders that can be applied to both BGM and CGM accuracy data. In a data set combining point accuracy data from 18 BGMs, 2.6% of total data pairs equally moved from Zones A to B and vice versa (SEG compared with DTS Error Grid). For every 1% increase in percent data in Zone A, the MARD decreased by approximately 0.33%. We also created a DTS Trend Accuracy Matrix with five trend risk categories (1-5) for CGM-reported trend indicators compared with reference trends calculated from reference glucose. CONCLUSION: The DTS Error Grid combines contemporary clinician input regarding clinical point accuracy for BGMs and CGMs. The DTS Trend Accuracy Matrix assesses accuracy of CGM trend indicators.

This report summarizes new recommendation and updates previous recommendations of the Advisory Committee on Immunization Practices (ACIP) for postexposure prophylaxis (PEP) to prevent human rabies (CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57[No. RR-3]). Previously, ACIP recommended a 5-dose rabies vaccination regimen with human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV). These new recommendations reduce the number of vaccine doses to four. The reduction in doses recommended for PEP was based in part on evidence from rabies virus pathogenesis data, experimental animal work, clinical studies, and epidemiologic surveillance. These studies indicated that 4 vaccine doses in combination with rabies immune globulin (RIG) elicited adequate immune responses and that a fifth dose of vaccine did not contribute to more favorable outcomes. For persons previously unvaccinated with rabies vaccine, the reduced regimen of 4 1-mL doses of HDCV or PCECV should be administered intramuscularly. The first dose of the 4-dose course should be administered as soon as possible after exposure (day 0). Additional doses then should be administered on days 3, 7, and 14 after the first vaccination. ACIP recommendations for the use of RIG remain unchanged. For persons who previously received a complete vaccination series (pre- or postexposure prophylaxis) with a cell-culture vaccine or who previously had a documented adequate rabies virus-neutralizing antibody titer following vaccination with noncell-culture vaccine, the recommendation for a 2-dose PEP vaccination series has not changed. Similarly, the number of doses recommended for persons with altered immunocompetence has not changed; for such persons, PEP should continue to comprise a 5-dose vaccination regimen with 1 dose of RIG. Recommendations for pre-exposure prophylaxis also remain unchanged, with 3 doses of vaccine administered on days 0, 7, and 21 or 28. Prompt rabies PEP combining wound care, infiltration of RIG into and around the wound, and multiple doses of rabies cell-culture vaccine continue to be highly effective in preventing human rabies.

Our ability to forecast epidemics far into the future is constrained by the many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify the future state of critical epidemic drivers. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make months ahead projections of SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a function of both scenario validity and model calibration. We show scenarios remained close to reality for 22 weeks on average before the arrival of unanticipated SARS-CoV-2 variants invalidated key assumptions. An ensemble of participating models that preserved variation between models (using the linear opinion pool method) was consistently more reliable than any single model in periods of valid scenario assumptions, while projection interval coverage was near target levels. SMH projections were used to guide pandemic response, illustrating the value of collaborative hubs for longer-term scenario projections.

This study aimed to estimate dietary sodium and potassium consumption among Jamaicans and evaluate associations with sociodemographic and clinical characteristics. A cross-sectional study was conducted using data from the Jamaica Health and Lifestyle Survey 2016-2017. Participants were noninstitutionalized Jamaicans aged ≥15 years. Trained staff collected sociodemographic and health data via interviewer-administered questionnaires and spot urine samples. The Pan American Health Organization formula was used to estimate 24-hour urine sodium and potassium excretion. High sodium level was defined as ≥2000 mg/day, and low potassium levels as <3510 mg/day (World Health Organization criteria). Associations between these outcomes and sociodemographic and clinical characteristics were explored using multivariable ANOVA models using log-transformed 24-hour urine sodium and potassium as outcome variables. Analyses included 1009 participants (368 males, 641 females; mean age 48.5 years). The mean sodium excretion was 3582 mg/day (males 3943 mg/day, females 3245 mg/day, P < .001). The mean potassium excretion was 2052 mg/day (males, 2210 mg/day; females, 1904 mg/day; P = .001). The prevalence of high sodium consumption was 66.6% (males 72.8%, females 60.7%, P < .001) and that of low potassium intake was 88.8% (85.1% males, 92.3% females, P < .001). Sodium consumption was inversely associated with older age, higher education, and low glomerular filtration rate but was directly associated with being male, current smoking, and obesity. Overall, males had higher sodium consumption than women, with the effect being larger among hypertensive men. Women with hypertension had lower sodium consumption than nonhypertensive women; however, hypertensive men had higher sodium consumption than nonhypertensive men. Potassium consumption was higher among men, persons with obesity, and those with high total cholesterol but was lower among men with "more than high school" education compared to men with "less than high school" education. We conclude that most Jamaican adults have diets high in sodium and low in potassium. In this study, sodium consumption was directly associated with male sex, obesity, and current smoking but was inversely associated with older age and higher education. High potassium consumption was associated with obesity and high cholesterol levels. These associations should be further explored in longitudinal studies and population-based strategies should be developed to address these cardiovascular risk factors.

Eight cases of locally acquired, mosquito-transmitted (i.e., autochthonous) Plasmodium vivax malaria, which has not been reported in the United States since 2003, were reported to CDC from state health departments in Florida and Texas during May 18-July 17, 2023. As of August 4, 2023, case surveillance, mosquito surveillance and control activities, and public outreach and education activities continue in both states. U.S. clinicians need to consider a malaria diagnosis in patients with unexplained fever, especially in areas where autochthonous malaria has been recently reported, although the risk for autochthonous malaria in the United States remains very low. Prompt diagnosis and treatment of malaria can prevent severe disease or death and limit ongoing transmission to local Anopheles mosquitoes and other persons. Preventing mosquito bites and controlling mosquitoes at home can prevent mosquitoborne diseases, including malaria. Before traveling internationally to areas with endemic malaria, travelers should consult with a health care provider regarding recommended malaria prevention measures, including potentially taking malaria prophylaxis. Malaria is a nationally notifiable disease; continued reporting of malaria cases to jurisdictional health departments and CDC will also help ensure robust surveillance to detect and prevent autochthonous malaria in the United States.

We report a dengue outbreak in Key Largo, Florida, USA, from February through August 2020, during the COVID-19 pandemic. Successful community engagement resulted in 61% of case-patients self-reporting. We also describe COVID-19 pandemic effects on the dengue outbreak investigation and the need to increase clinician awareness of dengue testing recommendations.

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

Objective: To estimate dietary sodium and potassium consumption among Jamaicans and evaluate associations with sociodemographic and clinical characteristics. Method(s): We conducted a cross-sectional analysis of data from the Jamaica Health and Lifestyle Survey 2016-2017. Participants were non-institutionalized Jamaicans, >=15 years. Trained staff collected sociodemographic and health data via interviewer administered questionnaires and collected spot urine samples. The Pan American Health Organization Formulae were used to estimate 24-hour urine sodium and potassium excretion. High sodium was defined as >=2000 mg/day and low potassium as <3510 mg/day (World Health Organization criteria). Associations of these outcomes with sociodemographic and clinical characteristics were explored in sex specific multivariable ANOVA models. Result(s): Analyses included 1009 participants (368 males, 641 females; mean age 48.5 years). Mean sodium excretion was 3582 mg/day (males 3943 mg/day, females 3245 mg/day, p<0.001). Mean potassium excretion was 2052 mg/day (males 2210 mg/day, females 1904 mg/day, p=0.001). The prevalence of high sodium consumption was 66.6% (males 72.8%, female 60.7%, p<0.001) and low potassium intake was 88.8% (85.1% males, 92.3% females, p<0.001). Among males, sodium consumption was inversely associated with older age and prehypertension, but directly associated with current smoking and obesity. Among females, sodium consumption was inversely associated with hypertension, impaired fasting glucose, low GFR and high physical activity, but was directly associated with obesity. Conclusion(s): Most Jamaican adults have diets high in sodium and low in potassium. Sodium consumption was directly associated with obesity in both men and women. Population based strategies are therefore required to address these cardiovascular risk factors. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Background SARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains. Methods Nine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches. Findings Absent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid-March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts. Conclusions Results from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

The objective of this analysis was to describe patterns of prescription medication use during pregnancy, including secular trends, with consideration of indication, and distributions of use within demographic subgroups. We conducted a descriptive secondary analysis using data from 9,755 women whose infants served as controls in two large United States case-control studies from 1997-2011 and 2014-2018. After excluding vitamin, herbal, mineral, vaccine, IV fluid, and topical products and over-the-counter medications, the proportion of women that reported taking at least one prescription medication in the first trimester increased over the study years, from 37% to 50% of women. The corresponding proportions increased with increasing maternal age and years of education, were highest for non-Hispanic White women (47%) and lowest for Hispanic women (24%). The most common indication for first trimester use of a medication was infection (12-15%). Increases were observed across the years for medications used for indications related to nausea/vomiting, depression/anxiety, infertility, thyroid disease, diabetes, and epilepsy. The largest relative increase in use among women was observed for medications to treat nausea/vomiting, which increased from 3.8% in the earliest years of the study (1997-2001) to 14.8% in 2014-2018, driven in large part by ondansetron use. Prescription medication use in the first trimester of pregnancy is common and increasing. Many medical conditions require treatments among pregnant women, often involving pharmacotherapy, which necessitates consideration of the risk and safety profiles for both mother and fetus.

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

BACKGROUND: The COVID-19 Scenario Modeling Hub convened nine modeling teams to project the impact of expanding SARS-CoV-2 vaccination to children aged 5-11 years on COVID-19 burden and resilience against variant strains. METHODS: Teams contributed state- and national-level weekly projections of cases, hospitalizations, and deaths in the United States from September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of 1) vaccination (or not) of children aged 5-11 years (starting November 1, 2021), and 2) emergence (or not) of a variant more transmissible than the Delta variant (emerging November 15, 2021). Individual team projections were linearly pooled. The effect of childhood vaccination on overall and age-specific outcomes was estimated using meta-analyses. FINDINGS: Assuming that a new variant would not emerge, all-age COVID-19 outcomes were projected to decrease nationally through mid-March 2022. In this setting, vaccination of children 5-11 years old was associated with reductions in projections for all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios without childhood vaccination. Vaccine benefits increased for scenarios including a hypothesized more transmissible variant, assuming similar vaccine effectiveness. Projected relative reductions in cumulative outcomes were larger for children than for the entire population. State-level variation was observed. INTERPRETATION: Given the scenario assumptions (defined before the emergence of Omicron), expanding vaccination to children 5-11 years old would provide measurable direct benefits, as well as indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. FUNDING: Various (see acknowledgments).

BACKGROUND: Although results from studies of first-trimester influenza vaccination and congenital heart defects (CHDs) have been reassuring, data are limited for specific CHDs. METHODS: We assessed associations between reported maternal influenza vaccination, 1 month before pregnancy (B1) through end of third pregnancy month (P3), and specific CHDs using data from a multisite, population-based case-control study. Analysis included 2,982 case children diagnosed with a simple CHD (no other cardiac involvement with or without extracardiac defects) and 4,937 control children without a birth defect with estimated delivery dates during 2006-2011. For defects with ≥5 exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; and maternal age at delivery, race/ethnicity, low folate intake, and smoking and alcohol use during B1P3. RESULTS: Overall, 124 (4.2%) simple CHD case mothers and 197 (4.0%) control mothers reported influenza vaccination from 1 month before through the third pregnancy month. The aOR for any simple CHD was 0.97 (95% CI: 0.76-1.23). Adjusted ORs for specific simple CHDs ranged from 0.62 for hypoplastic left heart syndrome to 2.34 for total anomalous pulmonary venous return (TAPVR). All adjusted CIs included the null except for TAPVR. CONCLUSIONS: Although we cannot fully exclude that exposure misclassification may have masked risks for some CHDs, findings add to existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. The TAPVR result may be due to chance, but it may help inform future studies.

OBJECTIVE: In 2020, the COVID-19 pandemic overburdened the US health care system because of extended and unprecedented patient surges and supply shortages in hospitals. We investigated the extent to which several US hospitals experienced emergency department (ED) and intensive care unit (ICU) overcrowding and ventilator shortages during the COVID-19 pandemic. METHODS: We analyzed Health Pulse data to assess the extent to which US hospitals reported alerts when experiencing ED overcrowding, ICU overcrowding, and ventilator shortages from March 7, 2020, through April 30, 2021. RESULTS: Of 625 participating hospitals in 29 states, 393 (63%) reported at least 1 hospital alert during the study period: 246 (63%) reported ED overcrowding, 239 (61%) reported ICU overcrowding, and 48 (12%) reported ventilator shortages. The number of alerts for overcrowding in EDs and ICUs increased as the number of COVID-19 cases surged. CONCLUSIONS: Timely assessment and communication about critical factors such as ED and ICU overcrowding and ventilator shortages during public health emergencies can guide public health response efforts in supporting federal, state, and local public health agencies.

PURPOSE: To assess associations between influenza vaccination during etiologically-relevant windows and selected major structural non-cardiac birth defects. STUDY DESIGN: We analyzed data from the National Birth Defects Prevention Study, a multisite, population-based case-control study, for 8233 case children diagnosed with a birth defect and 4937 control children without a birth defect with delivery dates during 2006-2011. For all analyses except for neural tube defects (NTDs), we classified mothers who reported influenza vaccination one month before through the third pregnancy month as exposed; the exposure window for NTDs was one month before through the first pregnancy month. For defects with five or more exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; maternal age; race/ethnicity; plurality; smoking and alcohol use; low folate intake; and, for NTDs, folate antagonist medications. RESULTS: There were 334 (4.1%) case and 197 (4.0%) control mothers who reported influenza vaccination from one month before through the third pregnancy month. Adjusted ORs ranged from 0.53 for omphalocele to 1.74 for duodenal atresia/stenosis. Most aORs (11 of 19) were ≤1 and all adjusted CIs included the null. The unadjusted CIs for two defects, hypospadias and craniosynostosis, excluded the null. These estimates were attenuated upon covariate adjustment (hypospadias aOR: 1.25 (95% CI 0.89, 1.76); craniosynostosis aOR: 1.23 (95% CI: 0.88, 1.74)). CONCLUSIONS: Results for several non-cardiac major birth defects add to the existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. Under-reporting of vaccination may have biased estimates downward. This article is protected by copyright. All rights reserved.

BACKGROUND: Understanding parents' concussion-related knowledge and attitudes will contribute to the development of strategies that aim to improve concussion prevention and sport safety for elementary school children. This study investigated the association between parent- and child-related factors and concussion symptom knowledge and care-seeking attitudes among parents of elementary school children (aged 5-10 years). METHODS: Four hundred parents of elementary school children completed an online questionnaire capturing parental and child characteristics; concussion symptom knowledge (25 items, range = 0-50; higher = better knowledge); and concussion care-seeking attitudes (five 7-point scale items, range = 5-35; higher = more positive attitudes). Multivariable ordinal logistic regression models identified predictors of higher score levels. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) excluding 1.00 were deemed statistically significant. RESULTS: Select parent and child characteristics were associated with higher score levels for both outcomes. For example, odds of better knowledge level in parents were higher with increased age (10-year increase aOR = 1.59; 95% CI = 1.10-2.28), among females (aOR = 3.90; 95% CI = 2.27-6.70), and among white/non-Hispanics (aOR = 1.79; 95%CI = 1.07-2.99). Odds of more positive concussion care-seeking attitude levels were higher among parents with a college degree (aOR = 1.98; 95%CI = 1.09-3.60). Child sports participation was not associated with higher score levels for either outcome. CONCLUSIONS: Certain elementary school parent characteristics were associated with parents' concussion symptom knowledge and care-seeking attitudes. While the findings suggest providing parents with culturally and demographically relevant concussion education might be helpful, they also emphasize the importance of ensuring education/prevention regardless of their children's sports participation. Practical Applications: Pediatric healthcare providers and elementary schools offer an optimal community-centered location to reach parents with this information within various communities.

Disasters can adversely affect population health, resulting in increased need for health services. Hurricane Irma made landfall in the Florida Keys (Monroe County) as a Category 4 hurricane on September 10, 2017. The hurricane caused substantial damage to 65% of homes and resulted in 40 persons injured and 17 deaths from hurricane-related causes.* During 2018, the county suicide rate increased to 34.9 per 100,000 population from the 5-year (2013-2017) average of 25.2 per 100,000 population (1). In May 2019, 20 months after the hurricane, the Florida Department of Health (FDOH) conducted a modified Community Assessment for Public Health Emergency Response (CASPER) to assess the community's mental, physical, and economic health and develop public health interventions to decrease the suicide rate. A consenting adult member from 231 households was interviewed, and a weighted cluster analysis was conducted to estimate the number and percentage of households throughout the Florida Keys with a particular response, as well as the number and percentage of persons at risk for suicide. During the 20 months since Hurricane Irma, 17% of households reported a need for a mental health care provider; 37.9% of these did not receive those services. A modified CASPER was used to calculate population estimates of suicide risk in an area of high landfall for hurricanes; estimated population suicide risk was 7.3%. Respondents reported worsening of respiratory conditions (17.7%), anxiety (17.0%), and depression (11.3%). Emergency preparedness plans should consider strengthening mental health service delivery after a hurricane, particularly during the long-term recovery phase.

OBJECTIVE: To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION: This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.

For years, experts have warned that a global pandemic was only a matter of time. Indeed, over the past two decades, several outbreaks and pandemics, from SARS to Ebola, have tested our ability to respond to a disease threat and provided the opportunity to refine our preparedness systems. However, when a novel coronavirus with human-to-human transmissibility emerged in China in 2019, many of these systems were found lacking. From international disputes over data and resources to individual disagreements over the effectiveness of facemasks, the COVID-19 pandemic has revealed several vulnerabilities. As of early November 2020, the WHO has confirmed over 46 million cases and 1.2 million deaths worldwide. While the world will likely be reeling from the effects of COVID-19 for months, and perhaps years, to come, one key question must be asked, How can we do better next time? This report summarizes views of experts from around the world on how lessons from past pandemics have shaped our current disease preparedness and response efforts, and how the COVID-19 pandemic may offer an opportunity to reinvent public health and healthcare systems to be more robust the next time a major challenge appears.

During an influenza pandemic, healthcare facilities are likely to be filled to capacity, leading to delays in seeing a provider and obtaining treatment. Flu on Call is a collaborative effort between the US Centers for Disease Control and Prevention and partners to develop a toll-free telephone helpline to reduce the burden on healthcare facilities and improve access to antivirals for people who are ill during an influenza pandemic. This study tested the feasibility of Flu on Call during a 1-day simulation using a severe pandemic scenario. Trained volunteer actors placed calls to the helpline using prepared scripts that were precoded for an expected outcome ("disposition") of the call. Scripts represented callers who were ill, those calling for someone else who was ill, and callers who were only seeking information. Information specialists and medical professionals managed the calls. Results demonstrated that Flu on Call may effectively assist callers during a pandemic, increase access to antiviral prescriptions, and direct patients to the appropriate level of care. Overall, 84% of calls exactly matched the expected call disposition; few calls (2%) were undermanaged (eg, the caller was ill but not transferred to a medical professional or received advice from the medical professional that was less intensive than what was warranted). Callers indicated a high level of satisfaction (83% reported their needs were met). Because of the high volume of calls that may be received during a severe pandemic, the Flu on Call platform should evolve to include additional triage channels (eg, through internet, chat, and/or text access).

OBJECTIVE: Developing appropriate concussion prevention and management paradigms in middle school (MS) settings requires understanding parents' general levels of concussion-related knowledge and attitudes. This study examined factors associated with concussion symptom knowledge and care-seeking attitudes among parents of MS children (aged ∼10-15 years). METHODS: A panel of 1224 randomly selected US residents, aged ≥18 years and identifying as parents of MS children, completed an online questionnaire capturing parental and child characteristics. The parents' concussion symptom knowledge was measured using 25 questions, with possible answers being "yes", "maybe", and "no". Correct answers earned 2 points, "maybe" answers earned 1 point, and incorrect answers earned 0 points (range = 0-50; higher scores = better knowledge). Concussion care-seeking attitudes were also collected using five 7-point scale items (range = 5-35; higher scores = more positive attitudes). Multivariable ordinal logistic regression models identified predictors of higher scores. Models met proportional odds assumptions. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) (excluding 1.00) were deemed statistically significant. RESULTS: Median scores were 39 (interquartile range (IQR) = 32-44) for symptom knowledge and 32 (IQR = 28-35) for care-seeking attitude. In multivariable models, odds of better symptom knowledge were higher in women vs. men (aOR = 2.28; 95%CI: 1.71-3.05), white/non-Hispanics vs. other racial or ethnic groups (aOR = 1.88; 95%CI: 1.42-2.49), higher parental age (10-year-increase aOR = 1.47; 95%CI: 1.26-1.71) and greater competitiveness (10%-scale-increase aOR = 1.24; 95%CI: 1.13-1.36). Odds of more positive care-seeking attitudes were higher in white/non-Hispanics versus other racial or ethnic groups (aOR = 1.45; 95%CI: 1.06-1.99), and higher parental age (10-year-increase aOR = 1.24; 95%CI: 1.05-1.47). CONCLUSION: Characteristics of middle school children's parents (e.g., sex, race or ethnicity, age) are associated with their concussion symptom knowledge and care-seeking attitudes. Parents' variations in concussion knowledge and attitudes warrant tailored concussion education and prevention.

BACKGROUND: Maternal folic acid (FA) intake before and during early pregnancy reduces the risk for neural tube defects (NTDs); evidence suggests it may also reduce the risk for oral clefts, urinary defects, and cardiac defects. We sought to re-examine the use of drugs, which affect folate metabolism, dihydrofolate reductase inhibiting (DHFRI) medications, and anti-epileptic drugs (AEDs), in data collected in the post-FA fortification era (1998+) in the Slone Birth Defects Study. METHODS: We assessed maternal DHFRI and AED use and risk for NTDs, oral clefts, and urinary and cardiac defects. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. We assessed daily average FA intake of ≥400 mcg as a potential effect modifier. RESULTS: We analyzed data from 10,209 control and 9,625 case mothers. Among controls, the prevalence of exposure to DHFRI medications was 0.3% and to AEDs was 0.5%. Maternal use of AEDs was associated with increased risks for NTDs (OR: 3.4; 95% CI: 1.5, 7.5), oral clefts (OR: 2.3; 95% CI: 1.3, 4.0), urinary defects (OR: 1.6; 95% CI: 1.0, 2.7), and cardiac defects (OR: 1.6; 95% CI: 1.1, 2.3); similar or further increased risks were found among those with FA intake ≥400 mcg per day. DHFRI use was rare and relative risk estimates were imprecise and consistent with the null. CONCLUSIONS: Similar to our previous analyses, we observed associations between AED use and these defects. For DHFRI exposure, we found no evidence for increased risk of these defects. Though statistical power to examine FA effect modification was low, we found no evidence of further protection among those with FA intake ≥400 mcg, with some associations somewhat stronger in this group.

OBJECTIVES: Tuberculosis (TB) outbreaks disproportionately affect persons experiencing homelessness (PEH) in the United States. During 2014-2016, a resurgent TB outbreak occurred among PEH in Atlanta, Georgia. To control the outbreak, citywide policies and educational interventions were implemented in January 2015. Policy changes standardized and enforced TB screening requirements for PEH in homeless shelters. Educational campaigns informed PEH of the outbreak and encouraged TB screening. We evaluated factors associated with, and the effect policy changes and educational interventions had on, TB screening and awareness among PEH in Atlanta. METHODS: Questions related to TB screening and awareness of the outbreak were added to an annual US Department of Housing and Urban Development survey of PEH in Atlanta in 2015 (n = 296 respondents) and 2016 (n = 1325 respondents). We analyzed the 2016 survey data to determine characteristics associated with outcomes. RESULTS: From 2015 to 2016, reported TB screening increased from 81% to 86%, and awareness of the TB outbreak increased from 68% to 75%. In 2016, sheltered PEH were significantly more likely than unsheltered PEH to report being evaluated for TB in the previous 6 months (prevalence odds ratio [pOR] = 3.18; 95% confidence interval [CI], 2.28-4.47) and to report being aware of the TB outbreak (pOR = 4.00; 95% CI, 2.89-5.55). CONCLUSIONS: Implementation of required TB screening and educational interventions may reduce the incidence and severity of TB outbreaks among PEH in other communities. Furthermore, the annual survey of PEH offers an opportunity to collect data to better inform practices and policies.

BACKGROUND: The main advantage of GeneXpert MTB/RIF® (Xpert) molecular diagnostic technology is the rapid detection of M.tuberculosis DNA and mutations associated with rifampicin (RIF) resistance for timely initiation of appropriate treatment and, consequently, preventing further transmission of the disease. We assessed time to treatment initiation and treatment outcomes of RIF-resistant and RIF-susceptible TB patients diagnosed and treated in Vladimir TB Dispensary, Russia in 2012, before and after implementation of GeneXpert MTB/RIF® diagnostic technology. METHODS: All adult patients suspected of having TB during February-December 2012 underwent a clinical examination, chest x-ray, microscopy, culture, and phenotypic drug susceptibility testing (DST). Starting August 2012 Xpert diagnostic technology became available in the facility. We used logistic regression to compare treatment outcomes in pre-Xpert and post-Xpert periods. Kaplan-Meier curves and log-rank test were used to compare the time to treatment initiation between the groups. RESULTS: Of 402 patients screened for TB during February-December 2012, 338 were diagnosed with TB (280 RIF-susceptible, 58 RIF-resistant). RIF-resistant patients in the post-Xpert group started treatment with second-line drugs (SLD) earlier than those in pre-Xpert group (median 11 vs. 37 days, Log-rank p = 0.02). The hazard ratio for time to SLD treatment initiation was significantly higher in post-Xpert group (HR:2.06; 95%CI:1.09,3.89) compared to pre-Xpert group. Among the 53/58 RIF-resistant TB patients with available treatment outcome, 28 (53%) had successful outcomes (cured/completed treatment) including 15/26 (58%) in post-Xpert group versus 13/27 (48%) in pre-Xpert group. The observed difference, however, was not statistically significant (OR:0.69; 95%CI:0.23,2.06). Among RIF-susceptible TB cases time to treatment initiation was not significantly different between the groups (2 vs. 3 days, Log-rank p = 0.73). Of 252/280 RIF-susceptible TB cases with treatment outcome, 199 (79%) cases had successful outcome including 94/114 (82%) in post-Xpert group versus 105/138 (76%) in pre-Xpert group (OR:0.68; 95%CI:0.36,1.26). CONCLUSION: We observed that availability of Xpert for initial diagnosis significantly reduced the time to SLD treatment for RIF-resistant patients in the Vladimir TB Dispensary. Although implementation of rapid diagnostics did not improve treatment outcomes, early diagnosis of MDR-TB is important for selection of appropriate treatment regimen and prevention of transmission of drug-resistant strains of TB.

OBJECTIVE: Parents may use various information sources to obtain information about sport-related concussions (SRC). This study examined SRC-related information sources used by parents of United States middle school (MS) children (aged approximately 10-15 years). METHODS: A panel of 1083 randomly selected U.S. residents, aged >/=18 years and identifying as parents of MS children, completed an online questionnaire capturing parental and child characteristics, and utilization and perceived trustworthiness of various sources of SRC-related information. Multivariable logistic regression models identified factors associated with utilizing each source. Adjusted odds ratios (OR) with 95% confidence intervals (CIs) excluding 1.00 were deemed significant. RESULTS: Doctors/healthcare providers (49.9%) and other healthcare-related resources (e.g., Centers for Disease Control and Prevention, WebMD) (37.8%) were common SRC-related information sources; 64.0% of parents utilized at least one of these sources. Both sources were considered "very" or "extremely" trustworthy for SRC-related information among parents using these sources (doctors/healthcare providers: 89.8%; other healthcare-related resources: 70.9%). A 10-year increase in parental age was associated with higher odds of utilizing doctors/healthcare providers (adjusted odd ratio (ORadjusted)=1.09, 95%CI: 1.02-1.16) and other healthcare-related resources (ORadjusted=1.11, 95%CI: 1.03-1.19). The odds of utilizing doctors/healthcare providers (ORadjusted=0.58, 95%CI: 0.40-0.84) and other healthcare-related resources (ORadjusted=0.64, 95%CI: 0.44-0.93) were lower among parents whose MS children had concussion histories versus the parents of children who did not have concussion histories. CONCLUSIONS: One-third of parents did not report using doctors/healthcare providers or other healthcare-related resources for SRC-related information. Factors associated with under-utilization of these sources may be targets for future intervention. Continuing education for healthcare providers and educational opportunities for parents should highlight accurate and up-to-date SRC-related information.

This is a summary report of the most important aspects discussed during the YSI 2300 Analyzer Replacement Meeting. The aim is to provide the interested reader with an overview of the complex topic and propose solutions for the current issue. This solution should not only be adequate for the United States or Europe markets but also for all other countries. The meeting addendum presents three outcomes of the meeting.

INTRODUCTION: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost-effective. To guide their HIV testing programmes, countries require appropriate metrics that can be measured. The cost-per-diagnosis is potentially a useful metric. METHODS: We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of "core" testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) core-testing as above plus additional testing beyond this ("additional-testing"), for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than those without HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosis and the incremental cost-effectiveness ratio (ICER) of the additional-testing policy. The discount rate used in the base case was 3% per annum (costs in 2018 U.S. dollars). RESULTS: There was a strong graded relationship between the cost-per-diagnosis and the ICER. Overall, the ICER was below $500 per-DALY-averted (the cost-effectiveness threshold used in primary analysis) so long as the cost-per-diagnosis was below $315. This threshold cost-per-diagnosis was similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restricting to women, additional-testing did not appear cost-effective even at a cost-per-diagnosis of below $50, while restricting to men additional-testing was cost-effective up to a cost-per-diagnosis of $585. The threshold cost per diagnosis for testing in men to be cost-effective fell to $256 when the cost-effectiveness threshold was $300 instead of $500, and to $81 when considering a discount rate of 10% per annum. CONCLUSIONS: For testing programmes in low-income settings in southern African there is an extremely strong relationship between the cost-per-diagnosis and the cost-per-DALY averted, indicating that the cost-per-diagnosis can be used to monitor the cost-effectiveness of testing programmes.

Rapidly evolving RNA viruses, such as the GII.4 strain of human norovirus (HuNoV), and their vaccines elicit complex serological responses associated with previous exposure. Specific correlates of protection, moreover, remain poorly understood. Here, we report the GII.4-serological antibody repertoire-pre- and post-vaccination-and select several antibody clonotypes for epitope and structural analysis. The humoral response was dominated by GII.4-specific antibodies that blocked ancestral strains or by antibodies that bound to divergent genotypes and did not block viral-entry-ligand interactions. However, one antibody, A1431, showed broad blockade toward tested GII.4 strains and neutralized the pandemic GII.P16-GII.4 Sydney strain. Structural mapping revealed conserved epitopes, which were occluded on the virion or partially exposed, allowing for broad blockade with neutralizing activity. Overall, our results provide high-resolution molecular information on humoral immune responses after HuNoV vaccination and demonstrate that infection-derived and vaccine-elicited antibodies can exhibit broad blockade and neutralization against this prevalent human pathogen.

Behavioral interventions to increase disclosure and proper management of concussion in youth sports have unrealized potential when it comes to preventing concussion. Interventions have focused on changing individual athlete behavior and have fallen short of the potential for sustained systemic behavioral change. One potentially critical reason for this shortfall is that other key determinants of risk behaviors at all levels of the socio-ecological model (e.g. interpersonal, community, policy) are not addressed in extant programming. There is a critical need for theory-driven interventions that address concussion prevention and education at the community level and target sustainable culture change. The Popular Opinion Leader (POL) intervention, a multi-level intervention model previously successfully employed in multiple public health contexts, is theoretically well positioned to affect such change. POL is based on the Diffusion of Innovations framework and involves identifying, recruiting, and training well-respected and trusted individuals to personally endorse prevention and risk-reduction within their social networks. Critical behavioral changes related to concussion disclosure and management have been shown to diffuse to others if enough opinion leaders endorse and support the behaviors. This article summarizes the concepts and principles of POL and describes how it could be adapted for and implemented in youth sport settings. For optimal impact, POL needs to adapt to several factors unique to youth sports settings and culture. First, adult involvement may be important, given their direct involvement in the athlete's medical care. However, parents and coaches' opinions on injury care-seeking, competition, and safety may affect their perceptions of POL. Second, youth sports are structured settings both physically and socioculturally. Games and practices may provide opportunities for the informal interactions that are critical to the success of POL. However, youth sport setting membership is transient as players get older and move to other sport settings; POL approaches need to be self-sustaining despite this turnover. Moreover, stakeholder value placed on athlete development and competition, alongside safety, must be considered. Formative research is needed to ensure that POL principles are translated into the youth sport setting while maintaining fidelity to the concepts and principles that have made POL successful for other health outcomes.