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In pretreatment isolates of M. tuberculosis with decrements of the minimum inhibitory concentration of isoniazid or rifampin below the standard resistance breakpoint, higher MIC values were associated with a greater risk of relapse than lower MIC values.

Hydroxychloroquine and chloroquine, primarily used to treat autoimmune diseases and to prevent and treat malaria, received national attention in early March 2020, as potential treatment and prophylaxis for coronavirus disease 2019 (COVID-19) (1). On March 20, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate in the Strategic National Stockpile to be used by licensed health care providers to treat patients hospitalized with COVID-19 when the providers determine the potential benefit outweighs the potential risk to the patient.* Following reports of cardiac and other adverse events in patients receiving hydroxychloroquine for COVID-19 (2), on April 24, 2020, FDA issued a caution against its use† and on June 15, rescinded its EUA for hydroxychloroquine from the Strategic National Stockpile.§ Following the FDA's issuance of caution and EUA rescindment, on May 12 and June 16, the federal COVID-19 Treatment Guidelines Panel issued recommendations against the use of hydroxychloroquine or chloroquine to treat COVID-19; the panel also noted that at that time no medication could be recommended for COVID-19 pre- or postexposure prophylaxis outside the setting of a clinical trial (3). However, public discussion concerning the effectiveness of these drugs on outcomes of COVID-19 (4,5), and clinical trials of hydroxychloroquine for prophylaxis of COVID-19 continue.¶ In response to recent reports of notable increases in prescriptions for hydroxychloroquine or chloroquine (6), CDC analyzed outpatient retail pharmacy transaction data to identify potential differences in prescriptions dispensed by provider type during January-June 2020 compared with the same period in 2019. Before 2020, primary care providers and specialists who routinely prescribed hydroxychloroquine, such as rheumatologists and dermatologists, accounted for approximately 97% of new prescriptions. New prescriptions by specialists who did not typically prescribe these medications (defined as specialties accounting for ≤2% of new prescriptions before 2020) increased from 1,143 prescriptions in February 2020 to 75,569 in March 2020, an 80-fold increase from March 2019. Although dispensing trends are returning to prepandemic levels, continued adherence to current clinical guidelines for the indicated use of these medications will ensure their availability and benefit to patients for whom their use is indicated (3,4), because current data on treatment and pre- or postexposure prophylaxis for COVID-19 indicate that the potential benefits of these drugs do not appear to outweigh their risks.Hydroxychloroquine and chloroquine, primarily used to treat autoimmune diseases and to prevent and treat malaria, received national attention in early March 2020, as potential treatment and prophylaxis for coronavirus disease 2019 (COVID-19) (1). On March 20, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate in the Strategic National Stockpile to be used by licensed health care providers to treat patients hospitalized with COVID-19 when the providers determine the potential benefit outweighs the potential risk to the patient.* Following reports of cardiac and other adverse events in patients receiving hydroxychloroquine for COVID-19 (2), on April 24, 2020, FDA issued a caution against its use† and on June 15, rescinded its EUA for hydroxychloroquine from the Strategic National Stockpile.§ Following the FDA's issuance of caution and EUA rescindment, on May 12 and June 16, the federal COVID-19 Treatment Guidelines Panel issued recommendations against the use of hydroxychloroquine or chloroquine to treat COVID-19; the panel also noted that at that time no medication could be recommended for COVID-19 pre- or postexposure prophylaxis outside the setting of a clinical trial (3). However, public discussion concerning the effectiveness of these drugs on outcomes of COVID-19 (4,5), and clinical trials of hydroxychloroquine for prophylaxis of COVID-19 continue.¶ In response to recent reports of notable increases in prescriptions for hydroxychloroquine or chloroquine (6), CDC analyzed outpatient retail pharmacy transaction data to identify potential differences in prescriptions dispensed by provider type during January-June 2020 compared with the same period in 2019. Before 2020, primary care providers and specialists who routinely prescribed hydroxychloroquine, such as rheumatologists and dermatologists, accounted for approximately 97% of new prescriptions. New prescriptions by specialists who did not typically prescribe these medications (defined as specialties accounting for ≤2% of new prescriptions before 2020) increased from 1,143 prescriptions in February 2020 to 75,569 in March 2020, an 80-fold increase from March 2019. Although dispensing trends are returning to prepandemic levels, continued adherence to current clinical guidelines for the indicated use of these medications will ensure their availability and benefit to patients for whom their use is indicated (3,4), because current data on treatment and pre- or postexposure prophylaxis for COVID-19 indicate that the potential benefits of these drugs do not appear to outweigh their risks.

Although the tuberculin skin test (TST) is frequently used to aid in the diagnosis of tuberculosis (TB) disease and to identify persons with latent TB infection, it is an imperfect test and approximately 10-25% of persons with microbiologically confirmed TB disease have a negative TST. Previous studies have suggested that persons with a negative TST are more likely to present with severe TB disease and have an increased rate of TB-related death. We analyzed culture-confirmed TB cases captured in US TB surveillance data from 1993 to 2008 and performed multivariate logistic regression analysis to determine the association between TST result and death. Of 284,866 cases of TB reported in the US, 58,180 persons were eligible for inclusion in the analysis and 3,270 of those persons died after initiating TB treatment. Persons with a negative TST accounted for only 14% of the eligible cases but accounted for 42% of the deaths. Persons with a TST≥15 mm had 67% lower odds of death than persons with a negative TST (adjusted odds ratio 0.33, 95% confidence interval 0.30-0.36). A negative TST is associated with an increased risk of death among persons with culture-confirmed TB disease, even after adjustment for HIV status, site of TB disease, sputum smear AFB status, drug susceptibility, age, sex, and origin of birth. In addition to indicating risk of developing disease, the TST may also be a marker for increased risk of death.

Coronavirus disease 2019 (COVID-19) is a complex clinical illness with potential complications that might require ongoing clinical care (1-3). Few studies have investigated discharge patterns and hospital readmissions among large groups of patients after an initial COVID-19 hospitalization (4-7). Using electronic health record and administrative data from the Premier Healthcare Database,* CDC assessed patterns of hospital discharge, readmission, and demographic and clinical characteristics associated with hospital readmission after a patient's initial COVID-19 hospitalization (index hospitalization). Among 126,137 unique patients with an index COVID-19 admission during March-July 2020, 15% died during the index hospitalization. Among the 106,543 (85%) surviving patients, 9% (9,504) were readmitted to the same hospital within 2 months of discharge through August 2020. More than a single readmission occurred among 1.6% of patients discharged after the index hospitalization. Readmissions occurred more often among patients discharged to a skilled nursing facility (SNF) (15%) or those needing home health care (12%) than among patients discharged to home or self-care (7%). The odds of hospital readmission increased with age among persons aged ≥65 years, presence of certain chronic conditions, hospitalization within the 3 months preceding the index hospitalization, and if discharge from the index hospitalization was to a SNF or to home with health care assistance. These results support recent analyses that found chronic conditions to be significantly associated with hospital readmission (6,7) and could be explained by the complications of underlying conditions in the presence of COVID-19 (8), COVID-19 sequelae (3), or indirect effects of the COVID-19 pandemic (9). Understanding the frequency of, and risk factors for, readmission can inform clinical practice, discharge disposition decisions, and public health priorities such as health care planning to ensure availability of resources needed for acute and follow-up care of COVID-19 patients. With the recent increases in cases nationwide, hospital planning can account for these increasing numbers along with the potential for at least 9% of patients to be readmitted, requiring additional beds and resources.

Abstract BackgroundOlder adults and people from certain racial and ethnic groups are disproportionately represented in coronavirus disease 2019 (COVID-19) hospitalizations and deaths. MethodsUsing data from the Premier Healthcare Database on 181 813 hospitalized adults diagnosed with COVID-19 during March–September 2020, we applied multivariable log-binomial regression to assess the associations between age and race/ethnicity and COVID-19 clinical severity (intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], and death) and to determine whether the impact of age on clinical severity differs by race/ethnicity. ResultsOverall, 84 497 (47%) patients were admitted to the ICU, 29 078 (16%) received IMV, and 27 864 (15%) died in the hospital. Increased age was strongly associated with clinical severity when controlling for underlying medical conditions and other covariates; the strength of this association differed by race/ethnicity. Compared with non-Hispanic White patients, risk of death was lower among non-Hispanic Black patients (adjusted risk ratio, 0.96; 95% CI, 0.92–0.99) and higher among Hispanic/Latino patients (risk ratio [RR], 1.15; 95% CI, 1.09–1.20), non-Hispanic Asian patients (RR, 1.16; 95% CI, 1.09–1.23), and patients of other racial and ethnic groups (RR, 1.13; 95% CI, 1.06–1.21). Risk of ICU admission and risk of IMV were elevated among some racial and ethnic groups. ConclusionsThese results indicate that age is a driver of poor outcomes among hospitalized persons with COVID-19. Additionally, clinical severity may be elevated among patients of some racial and ethnic minority groups. Public health strategies to reduce severe acute respiratory syndrome coronavirus 2 infection rates among older adults and racial and ethnic minorities are essential to reduce poor outcomes.

The future of surveillance is electronic case reporting (eCR), by which cases of reportable conditions are automatically generated from electronic health record systems and transmitted to public health agencies for review and action. eCR holds promise for enhancing the quality and effectiveness of public health surveillance. Greater use of eCR could result in more complete and accurate case data in near real time for public health action; earlier detection of cases, permitting earlier intervention and lowered transmission of disease; improved detection of outbreaks to allow earlier investigation and, potentially, earlier identification of risk factors for the spread of disease; and creation of a new infrastructure to support rapid reporting of newly recognized and emerging conditions. Here, Mac Kenzie et al examine the promise of eCR and present their vision for a nationally interoperable eCR system that allows for timely reporting to public health and information sharing among jurisdictions.

Introduction Severe COVID-19 illness in adults has been linked to underlying medical conditions. This study identified frequent underlying conditions and their attributable risk of severe COVID-19 illness. Methods We used data from more than 800 US hospitals in the Premier Healthcare Database Special COVID-19 Release (PHD-SR) to describe hospitalized patients aged 18 years or older with COVID-19 from March 2020 through March 2021. We used multivariable generalized linear models to estimate adjusted risk of intensive care unit admission, invasive mechanical ventilation, and death associated with frequent conditions and total number of conditions. Results Among 4,899,447 hospitalized adults in PHD-SR, 540,667 (11.0%) were patients with COVID-19, of whom 94.9% had at least 1 underlying medical condition. Essential hypertension (50.4%), disorders of lipid metabolism (49.4%), and obesity (33.0%) were the most common. The strongest risk factors for death were obesity (adjusted risk ratio [aRR] = 1.30; 95% CI, 1.27–1.33), anxiety and fear-related disorders (aRR = 1.28; 95% CI, 1.25–1.31), and diabetes with complication (aRR = 1.26; 95% CI, 1.24–1.28), as well as the total number of conditions, with aRRs of death ranging from 1.53 (95% CI, 1.41–1.67) for patients with 1 condition to 3.82 (95% CI, 3.45–4.23) for patients with more than 10 conditions (compared with patients with no conditions). Conclusion Certain underlying conditions and the number of conditions were associated with severe COVID-19 illness. Hypertension and disorders of lipid metabolism were the most frequent, whereas obesity, diabetes with complication, and anxiety disorders were the strongest risk factors for severe COVID-19 illness. Careful evaluation and management of underlying conditions among patients with COVID-19 can help stratify risk for severe illness.

Objectives. We examined trends in tuberculosis (TB) cases and case rates among US- and foreign-born children and adolescents and analyzed the potential effect of changes to overseas screening of applicants for immigration to the United States. Methods. We analyzed TB case data from the National Tuberculosis Surveillance System for 1994 to 2007. Results. Foreign-born children and adolescents accounted for 31% of 18 659 reported TB cases in persons younger than age 18 years from 1994 to 2007. TB rates declined 44% among foreign-born children and adolescents (20.3 per 100 00 to 11.4 per 100 000 population) and 48% (2.1 per 100 000 to 1.1 per 100 000) among those who were born in the United States. Rates were nearly 20 times as high among foreign-born as among US-born adolescents. Among foreign-born children and adolescents with known month of US entry (88%), more than 20% were diagnosed with TB within 3 months of entry. Conclusions. Marked disparities in TB morbidity persist between foreign- and US-born children and adolescents. These disparities and the high proportion of TB cases diagnosed shortly after US entry suggest a need for enhanced pre- and postimmigration screening.

The Centers for Disease Control and Prevention and National Institutes of Health convened a multidisciplinary meeting to discuss surrogate markers of treatment response in tuberculosis. The goals were to assess recent surrogate marker research and to provide specific recommendations for (1) the qualification and validation of biomarkers of treatment outcome; (2) the standardization of specimen and data collection for future clinical trials, including a minimum set of samples and collection time points; and (3) the creation ofa specimen repository to support biomarker testing. This article summarizes these recommendations and provides a roadmap for their implementation.

Importance Information on underlying conditions and severe COVID-19 illness among children is limited. Objective To examine the risk of severe COVID-19 illness among children associated with underlying medical conditions and medical complexity. Design, Setting, and Participants This cross-sectional study included patients aged 18 years and younger withInternational Statistical Classification of Diseases, Tenth Revision, Clinical Modification code U07.1 (COVID-19) or B97.29 (other coronavirus) during an emergency department or inpatient encounter from March 2020 through January 2021. Data were collected from the Premier Healthcare Database Special COVID-19 Release, which included data from more than 800 US hospitals. Multivariable generalized linear models, controlling for patient and hospital characteristics, were used to estimate adjusted risk of severe COVID-19 illness associated with underlying medical conditions and medical complexity. Exposures Underlying medical conditions and medical complexity (ie, presence of complex or noncomplex chronic disease). Main Outcomes and Measures Hospitalization and severe illness when hospitalized (ie, combined outcome of intensive care unit admission, invasive mechanical ventilation, or death). Results Among 43 465 patients with COVID-19 aged 18 years or younger, the median (interquartile range) age was 12 (4-16) years, 22 943 (52.8%) were female patients, and 12 491 (28.7%) had underlying medical conditions. The most common diagnosed conditions were asthma (4416 [10.2%]), neurodevelopmental disorders (1690 [3.9%]), anxiety and fear-related disorders (1374 [3.2%]), depressive disorders (1209 [2.8%]), and obesity (1071 [2.5%]). The strongest risk factors for hospitalization were type 1 diabetes (adjusted risk ratio [aRR], 4.60; 95% CI, 3.91-5.42) and obesity (aRR, 3.07; 95% CI, 2.66-3.54), and the strongest risk factors for severe COVID-19 illness were type 1 diabetes (aRR, 2.38; 95% CI, 2.06-2.76) and cardiac and circulatory congenital anomalies (aRR, 1.72; 95% CI, 1.48-1.99). Prematurity was a risk factor for severe COVID-19 illness among children younger than 2 years (aRR, 1.83; 95% CI, 1.47-2.29). Chronic and complex chronic disease were risk factors for hospitalization, with aRRs of 2.91 (95% CI, 2.63-3.23) and 7.86 (95% CI, 6.91-8.95), respectively, as well as for severe COVID-19 illness, with aRRs of 1.95 (95% CI, 1.69-2.26) and 2.86 (95% CI, 2.47-3.32), respectively. Conclusions and Relevance This cross-sectional study found a higher risk of severe COVID-19 illness among children with medical complexity and certain underlying conditions, such as type 1 diabetes, cardiac and circulatory congenital anomalies, and obesity. Health care practitioners could consider the potential need for close observation and cautious clinical management of children with these conditions and COVID-19.