Issue 10, March 23, 2021

CDC Science Clips: Volume 13, Issue 10, March 23, 2021

This week, Science Clips is pleased to feature articles from the March 2021 Injury Prevention supplement on ICD-10-CM Injury Epidemiology and Surveillance Methodsexternal icon.

The following introduction is adapted from a blog postexternal icon by the CDC guest editors of the supplement (Renee L. Johnson, MSPH, RPT, Holly Hedegaard, MD, MSPH, Emilia Pasalic, MPH, and Pedro Martinez, MPH).

Injury epidemiologists live in a world of standard coding schemas, case definitions, and agreed-upon ways of grouping and categorizing injuries. But what happens when the basic foundation for this type of work undergoes a major change? For decades, injury epidemiologists in the United States and elsewhere relied on the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to identify and categorize injuries seen in hospitals and emergency departments. In 2015, a new coding rubric went into effect in the United States. The Department of Health and Human Services (HHS) required all hospitals and health care providers in the United States to use the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) to report electronic health care transactions beginning in October 2015. This change required an update to injury surveillance case definitions, analysis guidance, and standard tools that had been developed for use with ICD-9-CM-coded data to the new "language" of ICD-10-CM.

One might think this shouldn't be too difficult, but in reality, the transition required a huge effort involving multiple partnerships. The first phase began more than a decade ago when development for tools such as  proposed case definitionspdf icon and proposed groupings for categorizing injuries by external causepdf icon or by injury diagnosispdf icon began in the absence of any ICD-10-CM coded data. The approach used in these early efforts was to mirror or update the well-established ICD-9-CM-based tools that were already in place.

Beginning in 2016, injury epidemiologists began to have access to ICD-10-CM-coded hospital and emergency department discharge data. Analysis of these data provided the first opportunity to test the proposed tools and to learn what worked, what didn’t work, and what adjustments needed to be made. Collaborative partnerships among national, state, and local public health agencies; universities; and professional and non-profit organizations worked together to test and refine these tools.  The tools were adjusted based on the test findings and produced:

In addition to this collaborative work, individual researchers began to study and learn more about how to use ICD-10-CM coded hospital and emergency department discharge data for injury surveillance. Several of these studies have been recently published in a supplemental issue of Injury Prevention titled ICD-10-CM Injury Epidemiology and Surveillance Methodsexternal iconThese studies help clarify methodological considerations when using ICD-10-CM coded data and provide information to support decision-making for developing surveillance case definitions for subcategories of injuries.

The studies cover a broad range of injury topics, including general injury, drug overdose, unintentional falls, intentional self-harm, violence, child abuse and neglect, traumatic brain injury, and work-related injury, and encompass a variety of study methodologies. For example, several studies identified considerations for understanding injury trends and discontinuities across the transition, while other studies utilized medical chart review to estimate the positive predictive value of ICD-10-CM codes and new standardized case definitions. Each of the studies presented in the supplement provides a glimpse into the challenges and the potential of using ICD-10-CM-coded data for injury surveillance.

  1. Key Scientific Articles in Featured Topic Areas
    Subject matter experts decide what topic to feature, and articles are selected from the last 3 to 6 months of published literature. Key topic coincides monthly with other CDC products (e.g. Vital Signs). The names of CDC authors are indicated in bold text.
    • Injury and Violence - ICD-10-CM Injury Epidemiology and Surveillance Methods
      1. Use of ICD-10-CM coded hospitalisation and emergency department data for injury surveillanceexternal icon
        Johnson RL, Hedegaard H, Pasalic ES, Martinez PD.
        Inj Prev. 2021 Mar;27(S1):i1-i2.

      2. Health systems capture injuries using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification (ICD-10-CM) diagnostic codes and share data with public health to inform injury surveillance. This study analyses provider-assigned ICD-10-CM injury codes among self-reported injuries to determine the effectiveness of ICD-10-CM coding in capturing injury and assault. METHODS: Self-reported injury screen records from an urban, level 1 trauma centre collected between 20 November 2015 and 30 September 2019 were compared with corresponding provider-assigned ICD-10-CM codes discerning the frequency in which intentions are indicated among patients reporting (1) any injury and (2) assault. RESULTS: Of 380 922 patients screened, 32 788 (8.61%) reported any injury and 6763 (1.78%) reported assault. ICD-10-CM codes had a sensitivity of 67.40% (95% CI 66.89% to 67.91%) for any injury and specificity of 89.79% (95% CI 89.69% to 89.89%]). For assault, ICD-10-CM codes had sensitivity of 2.25% (95% CI 1.91% to 2.63%) and specificity of 99.97% (95% CI 99.97% 99.98%). DISCUSSION: This study found provider-assigned ICD-10-CM had limited sensitivity to identify injury and low sensitivity for assault. This study more fully characterises ICD-10-CM coding system effectiveness in identifying assaults.

      3. BACKGROUND: This study describes rates of non-fatal fall-injury emergency department (ED) visits and hospitalisations before and after the US 2015 transition from the 9th to 10th revision of the International Classification of Diseases, Clinical Modification (ICD-9-CM to ICD-10-CM). METHODS: ED visit and hospitalisation data for adults aged 65+ years were obtained from the 2010-2016 Healthcare Cost and Utilisation Project. Differences in fall injury rates between 2010 and 2014 (before transition), and 2014 and 2016 (before and after transition) were analysed using t-tests. RESULTS: For ED visits, rates did not differ significantly between 2014 and 2016 (4288 vs 4318 per 100 000, respectively). Hospitalisation rates were lower in 2014 (1232 per 100 000) compared with 2016 (1281 per 100 000). CONCLUSION: Increased rates of fall-related hospitalisations could be an artefact of the transition or may reflect an increase in the rate of fall-related hospitalisations. Analyses of fall-related hospitalisations across the transition should be interpreted cautiously.

      4. Multisite medical record review of emergency department visits for unspecified injury of head following the ICD-10-CM coding transitionexternal icon
        Peterson A, Gabella BA, Johnson J, Hume B, Liu A, Costich JF, Hathaway J, Slavova S, Johnson R, Breiding M.
        Inj Prev. 2021 Mar;27(S1):i13-i18.
        INTRODUCTION: In 2016, a proposed International Classification of Diseases, Tenth Edition, Clinical Modification surveillance definition for traumatic brain injury (TBI) morbidity was introduced that excluded the unspecified injury of head (S09.90) diagnosis code. This study assessed emergency department (ED) medical records containing S09.90 for evidence of TBI based on medical documentation. METHODS: State health department representatives in Maryland, Kentucky, Colorado and Massachusetts reviewed a target of 385 randomly sampled ED records uniquely assigned the S09.90 diagnosis code (without proposed TBI codes), which were initial medical encounters among state residents discharged home during October 2015-December 2018. Using standardised abstraction procedures, reviewers recorded signs and symptoms of TBI, and head imaging results. A tiered case confirmation strategy was applied that assigned a level of certainty (high, medium, low, none) to each record based on the number and type of symptoms and imaging results present in the record. Positive predictive value (PPV) of S09.90 by level of TBI certainty was calculated by state. RESULTS: Wide variation in PPV of sampled ED records assigned S09.90: 36%-52% had medium or high evidence of TBI, while 48%-64% contained low or no evidence of a TBI. Loss of consciousness was mentioned in 8%-24% of sampled medical records. DISCUSSION: Exclusion of the S09.90 code in surveillance estimates may result in many missed TBI cases; inclusion may result in counting many false positives. Further, missed TBI cases influenced by incidence estimates, based on the TBI surveillance definition, may lead to inadequate allocation of public health resources.

      5. Descriptive exploration of overdose codes in hospital and emergency department discharge data to inform development of drug overdose morbidity surveillance indicator definitions in ICD-10-CMexternal icon
        Tyndall Snow LM, Hall KE, Custis C, Rosenthal AL, Pasalic E, Nechuta S, Davis JW, Jacquemin BJ, Jagroep SR, Rock P, Contreras E, Gabella BA, James KA.
        Inj Prev. 2021 Mar;27(S1):i27-i34.
        BACKGROUND: In October 2015, discharge data coding in the USA shifted to the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), necessitating new indicator definitions for drug overdose morbidity. Amid the drug overdose crisis, characterising discharge records that have ICD-10-CM drug overdose codes can inform the development of standardised drug overdose morbidity indicator definitions for epidemiological surveillance. METHODS: Eight states submitted aggregated data involving hospital and emergency department (ED) discharge records with ICD-10-CM codes starting with T36-T50, for visits occurring from October 2015 to December 2016. Frequencies were calculated for (1) the position within the diagnosis billing fields where the drug overdose code occurred; (2) primary diagnosis code grouped by ICD-10-CM chapter; (3) encounter types; and (4) intents, underdosing and adverse effects. RESULTS: Among all records with a drug overdose code, the primary diagnosis field captured 70.6% of hospitalisations (median=69.5%, range=66.2%-76.8%) and 79.9% of ED visits (median=80.7%; range=69.8%-88.0%) on average across participating states. The most frequent primary diagnosis chapters included injury and mental disorder chapters. Among visits with codes for drug overdose initial encounters, subsequent encounters and sequelae, on average 94.6% of hospitalisation records (median=98.3%; range=68.8%-98.8%) and 95.5% of ED records (median=99.5%; range=79.2%-99.8%), represented initial encounters. Among records with drug overdose of any intent, adverse effect and underdosing codes, adverse effects comprised an average of 74.9% of hospitalisation records (median=76.3%; range=57.6%-81.1%) and 50.8% of ED records (median=48.9%; range=42.3%-66.8%), while unintentional intent comprised an average of 11.1% of hospitalisation records (median=11.0%; range=8.3%-14.5%) and 28.2% of ED records (median=25.6%; range=20.8%-40.7%). CONCLUSION: Results highlight considerations for adapting and standardising drug overdose indicator definitions in ICD-10-CM.

      6. Defining indicators for drug overdose emergency department visits and hospitalisations in ICD-10-CM coded discharge dataexternal icon
        Vivolo-Kantor A, Pasalic E, Liu S, Martinez PD, Gladden RM.
        Inj Prev. 2021 Mar;27(S1):i56-i61.
        INTRODUCTION: The drug overdose epidemic has worsened over the past decade; however, efforts have been made to better understand and track nonfatal overdoses using various data sources including emergency department and hospital admission data from billing and discharge files. METHODS AND FINDINGS: The Centers for Disease Control and Prevention (CDC) has developed surveillance case definition guidance using standardised discharge diagnosis codes for public health practitioners and epidemiologists using lessons learnt from CDC's funded recipients and the Council for State and Territorial Epidemiologists (CSTE) International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) Drug Poisoning Indicators Workgroup and General Injury ICD-10-CM Workgroup. CDC's guidance was informed by health departments and CSTE's workgroups and included several key aspects for assessing drug overdose in emergency department and hospitalisation discharge data. These include: (1) searching all diagnosis fields to identify drug overdose cases; (2) estimating drug overdose incidence using visits for initial encounter but excluding subsequent encounters and sequelae; (3) excluding underdosing and adverse effects from drug overdose incidence indicators; and (4) using codes T36-T50 for overdose surveillance. CDC's guidance also suggests analysing intent separately for ICD-10-CM coding. CONCLUSIONS: CDC's guidance provides health departments a key tool to better monitor drug overdoses in their community. The implementation and validation of this standardised guidance across all CDC-funded health departments will be key to ensuring consistent and accurate reporting across all entities.

      7. INTRODUCTION: On 1 October 2015, the USA transitioned from the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to the International Classification of Diseases, 10th Revision (ICD-10-CM). Considering the major changes to drug overdose coding, we examined how using different approaches to define all-drug overdose and opioid overdose morbidity indicators in ICD-9-CM impacts longitudinal analyses that span the transition, using emergency department (ED) and hospitalisation data from six states' hospital discharge data systems. METHODS: We calculated monthly all-drug and opioid overdose ED visit rates and hospitalisation rates (per 100 000 population) by state, starting in January 2010. We applied three ICD-9-CM indicator definitions that included identical all-drug or opioid-related codes but restricted the number of fields searched to varying degrees. Under ICD-10-CM, all fields were searched for relevant codes. Adjusting for seasonality and autocorrelation, we used interrupted time series models with level and slope change parameters in October 2015 to compare trend continuity when employing different ICD-9-CM definitions. RESULTS: Most states observed consistent or increased capture of all-drug and opioid overdose cases in ICD-10-CM coded hospital discharge data compared with ICD-9-CM. More inclusive ICD-9-CM indicator definitions reduced the magnitude of significant level changes, but the effect of the transition was not eliminated. DISCUSSION: The coding change appears to have introduced systematic differences in measurement of drug overdoses before and after 1 October 2015. When using hospital discharge data for drug overdose surveillance, researchers and decision makers should be aware that trends spanning the transition may not reflect actual changes in drug overdose rates.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. BACKGROUND: Stroke continues to be a leading cause of death and disability in the United States. Rates of intra-arterial reperfusion treatments (IAT) for acute ischemic stroke (AIS) are increasing, and these treatments are associated with more favorable outcomes. We sought to examine the effect of insurance status on outcomes for AIS patients receiving IAT within a multistate stroke registry. METHODS: We used data from the Paul Coverdell National Acute Stroke Program (PCNASP) from 2014 to 2019 to quantify rates of IAT (with or without intravenous thrombolysis) after AIS. We modeled outcomes based on insurance status: private, Medicare, Medicaid, or no insurance. Outcomes were defined as rates of discharge to home, in-hospital death, symptomatic intracranial hemorrhage (sICH), or life-threatening hemorrhage during hospitalization. RESULTS: During the study period, there were 486,180 patients with a clinical diagnosis of AIS (mean age 70.6 years, 50.3% male) from 674 participating hospitals in PCNASP. Only 4.3% of patients received any IAT. As compared to private insurance, uninsured patients receiving any IAT were more likely to experience in-hospital death (AOR 1.36 [95% CI 1.07-1.73]). Medicare (AOR 0.78 [95% CI 0.71-0.85]) and Medicaid (AOR 0.85 [95% CI 0.75-0.96]) beneficiaries were less likely but uninsured patients were more likely (AOR 1.90 [95% CI 1.61-2.24]) to be discharged home. Insurance status was not found to be independently associated with rates of sICH. CONCLUSIONS: Insurance status was independently associated with in-hospital death and discharge to home among AIS patients undergoing IAT.

      2. A longitudinal comparison of alternatives to CDC BMI z-scores for children with very high BMIsexternal icon
        Freedman DS, Goodwin Davies AJ, Kompaniyets L, Lange SJ, Goodman AB, Tam Phan TL, Cole FS, Dempsey A, Pajor N, Eneli I, Christakis DA, Forrest CB.
        J Pediatr. 2021 Mar 4.
        OBJECTIVE: The current CDC BMI z-scores are inaccurate for BMIs ≥ 97(th) percentile. We, therefore, considered 5 alternatives that can be used across the entire BMI distribution: modified BMIz, %CDC95th percentile, extended BMIz, %median, and %median adjusted for the dispersion of BMIs. STUDY DESIGN: We illustrate the behavior of the metrics among children of different ages and BMIs. We then compared the longitudinal tracking of the BMI metrics in electronic health record (EHR) data from 1.17 million children in PEDSnet using the intraclass correlation coefficient (ICC) to determine if one metric was superior. RESULTS: Our examples show that using CDC BMIz for high BMIs can result in nonsensical results. All alternative metrics showed higher tracking than CDC BMIz among children with obesity. Of the alternatives, modified BMIz performed poorly among children with severe obesity, and %median performed poorly among children who did not have obesity at their first visit. The highest ICCs were generally seen for extended BMIz, adjusted %median, and %CDC95(th) percentile. CONCLUSIONS: Based on the examples of differences in the BMI metrics, the longitudinal tracking results, and current familiarity BMI z-scores and percentiles, extended BMIz and extended BMI percentile may be suitable replacements for the current z-scores and percentiles. These metrics are identical to those in the CDC growth charts for BMIs < 95(th) percentile and are superior for very high BMIs. Researchers' familiarity with the current CDC z-scores and clinicians with the CDC percentiles may ease the transition to the extended BMI scale.

      3. Visualizing county-level data to target dental safety-net programs for childrenexternal icon
        Hamilton EK, Bernal J, Lin M, Thornton-Evans G, Griffin SO.
        Prev Chronic Dis. 2021 Mar 11;18:E21.

      4. Population measures of subjective cognitive decline: A means of advancing public health policy to address cognitive healthexternal icon
        Olivari BS, Baumgart M, Taylor CA, McGuire LC.
        Alzheimers Dement (N Y). 2021 ;7(1):e12142.
        Subjective cognitive decline (SCD) is receiving increasing attention as studies have suggested that SCD status is associated with risk of future cognitive decline and dementia. Population-based measures of SCD can be extremely useful to the public health community, health-care providers, researchers, and policymakers. A large population-based SCD measure now exists through the state-based Behavioral Risk Factor Surveillance System (BRFSS). All 50 states have included the cognitive decline module, which asks about SCD, to their BRFSS survey one or more times. Population measures of SCD can aid researchers in designing clinical studies by better estimating the populations that may be at risk for more severe cognitive decline based on their SCD status to ensure that the optimal groups are targeted. Population-level estimates of SCD can also help to inform health-care providers' decisions about initiating cognitive assessments, managing other conditions among those with memory problems, and identifying the needs of caregivers.

      5. The role and utility of population-based cancer registries in cervical cancer surveillance and controlexternal icon
        Piñeros M, Saraiya M, Baussano I, Bonjour M, Chao A, Bray F.
        Prev Med. 2021 Mar;144:106237.
        Population-based cancer registries (PBCR) are vital to the assessment of the cancer burden and in monitoring and evaluating national progress in cervical cancer surveillance and control. Yet the level of their development in countries exhibiting the highest cervical cancer incidence rates is suboptimal, and requires considerable investment if they are to document the impact of WHO global initiative to eliminate cervical cancer as a public health problem. As a starting point we propose a comprehensive cancer surveillance framework, positioning PBCR in relation to other health information systems that are required across the cancer control continuum. The key concepts of PBCR are revisited and their role in providing a situation analysis of the scale and profile of the cancer-specific incidence and survival, and their evolution over time is illustrated with specific examples. Linking cervical cancer data to screening and immunization information systems enables the development of a comprehensive set of measures capable of assessing the short- and long-term achievements and impact of the initiative. Such data form the basis of national and global estimates of the cancer burden and permit comparisons across countries, facilitating decision-making or triggering cancer control action. The initiation and sustainable development of PBCR must be an early step in the scale-up of cervical cancer control activities as a means to ensure progress is successfully monitored and appraised.

      6. Mammography use and breast cancer incidence among older U.S. womenexternal icon
        Turbow SD, White MC, Breslau ES, Sabatino SA.
        Breast Cancer Res Treat. 2021 Mar 5.
        PURPOSE: The death rate for female breast cancer increases progressively with age, but organizations differ in their mammography screening recommendations for older women. To understand current patterns of screening mammography use and breast cancer diagnoses among older women, we examined recent national data on mammography screening use and breast cancer incidence and stage at diagnosis among women aged ≥ 65 years. METHODS: We examined breast cancer incidence using the 2016 United States Cancer Statistics dataset and analyzed screening mammography use among women aged ≥ 65 years using the 2018 National Health Interview Survey. RESULTS: Women aged 70-74 years had the highest breast cancer incidence rate (458.3 cases per 100,000 women), and women aged ≥ 85 years had the lowest rate (295.2 per 100,000 women). The proportion of cancer diagnosed at distant stage or with unknown stage increased with age. Over half of women aged 80-84 years and 26.0% of women aged ≥ 85 years reported a screening mammogram within the last 2 years. Excellent/very good/good self-reported health status (p = .010) and no dependency in activities of daily living/instrumental activities of daily living (p < .001) were associated with recent mammography screening. CONCLUSION: Breast cancer incidence rates and stage at diagnosis vary by age. Many women aged ≥ 75 years receive screening mammograms. The results of this study point to areas for further investigation to promote optimal mammography screening among older women.

      7. A healthy start: National trends in child care regulations and uptake of obesity prevention standards (2010-2018)external icon
        Warnock AL, Dooyema C, Blanck HM, Lee SH, Hall K, Geary N, Galuska DA.
        Child Obes. 2021 Mar 10.
        Background: Obesity remains a significant public health issue in the United States. Each week, millions of infants and children are cared for in early care and education (ECE) programs, making it an important setting for building healthy habits. Since 2010, 39 states promulgated licensing regulations impacting infant feeding, nutrition, physical activity, or screen time practices. We assessed trends in ECE regulations across all 50 states and the District of Columbia (D.C.) and hypothesized that states included more obesity prevention standards over time. Methods: We analyzed published ratings of state licensing regulations (2010-2018) and describe trends in uptake of 47 high-impact standards derived from Caring for Our Children's, Preventing Childhood Obesity special collection. National trends are described by (1) care type (Centers, Large Care Homes, and Small Care Homes); (2) state and U.S. region; and (3) most and least supported standards. Results: Center regulations included the most obesity prevention standards (∼13% in 2010 vs. ∼29% in 2018) compared with other care types, and infant feeding and nutrition standards were most often included, while physical activity and screen time were least supported. Some states saw significant improvements in uptake, with six states and D.C. having a 30%-point increase 2010-2018. Conclusions: Nationally, there were consistent increases in the percentage of obesity prevention standards included in ECE licensing regulations. Future studies may examine facilitators and barriers to the uptake of obesity prevention standards and identify pathways by which public health and health care professionals can act as a resource and promote obesity prevention in ECE.

    • Communicable Diseases
      1. Severe acute respiratory syndrome coronavirus 2 seropositivity among healthcare personnel in hospitals and nursing homes, Rhode Island, USA, July-August 2020external icon
        Akinbami LJ, Chan PA, Vuong N, Sami S, Lewis D, Sheridan PE, Lukacs SL, Mackey L, Grohskopf LA, Patel A, Petersen LR.
        Emerg Infect Dis. 2021 Mar;27(3):823-834.
        Healthcare personnel are recognized to be at higher risk for infection with severe acute respiratory syndrome coronavirus 2. We conducted a serologic survey in 15 hospitals and 56 nursing homes across Rhode Island, USA, during July 17-August 28, 2020. Overall seropositivity among 9,863 healthcare personnel was 4.6% (95% CI 4.2%-5.0%) but varied 4-fold between hospital personnel (3.1%, 95% CI 2.7%-3.5%) and nursing home personnel (13.1%, 95% CI 11.5%-14.9%). Within nursing homes, prevalence was highest among personnel working in coronavirus disease units (24.1%; 95% CI 20.6%-27.8%). Adjusted analysis showed that in hospitals, nurses and receptionists/medical assistants had a higher likelihood of seropositivity than physicians. In nursing homes, nursing assistants and social workers/case managers had higher likelihoods of seropositivity than occupational/physical/speech therapists. Nursing home personnel in all occupations had elevated seropositivity compared with hospital counterparts. Additional mitigation strategies are needed to protect nursing home personnel from infection, regardless of occupation.

      2. Electronic dissemination of a web-based video promotes PrEP contemplation and conversation among US women engaged in care at Planned Parenthoodexternal icon
        Calabrese SK, Lane SB, Caldwell A, Kaplan C, Dovidio JF, Galvao RW, Ogburn DF, Safon CB, Tekeste M, Taggart T, Modrakovic D, Wilbourn BC, Blackstock O, Kershaw TS.
        AIDS Behav. 2021 Mar 11.
        We evaluated the acceptability and impact of a web-based PrEP educational video among women (n = 126) by comparing two Planned Parenthood centers: one assigned to a Web Video Condition and one to a Standard Condition. Most women reported the video helped them better understand what PrEP is (92%), how PrEP works (93%), and how to take PrEP (92%). One month post-intervention, more women in the Web Video Condition reported a high level of comfort discussing PrEP with a provider (82% vs. 48%) and commonly thinking about PrEP (36% vs. 4%). No women with linked medical records initiated PrEP during 1-year follow-up.

      3. Women's perspectives on relationship dynamics with their partners and their role in HIV acquisition, HIV disclosure, hormonal contraceptive uptake, and condom useexternal icon
        Chapola JC, Hatfield-Timajchy K, Bula AK, Hurst S, Chinula L, Kourtis AP, Tang JH.
        Afr J AIDS Res. 2021 Mar;20(1):61-69.
        Background: Limited information exists about relationship dynamics and their role in HIV acquisition, HIV disclosure, hormonal contraceptive uptake, and condom use among women in Malawi.Methods: Ninety-seven women aged 18-45 years were randomly assigned to initiate the depot medroxyprogesterone acetate injectable or levonorgestrel implant from May 2014 to April 2015 in Lilongwe, Malawi. Women were recruited after randomisation to participate in semi-structured interviews about HIV and family planning using purposive sampling. Interviews were thematically analysed using within and between group comparisons.Results: We conducted individual interviews and/or focus group discussions with 41 women: 30 (73%) women living with HIV and 11 (27%) women not living with HIV. Most women living with HIV who participated in in-depth interviews disclosed their status to their partners, and most partners agreed to get HIV tested only after disclosure. Nearly all women said their partners agreed to use condoms, but few used them consistently. Nearly all women believed their current and former partners had outside partners. Most women living with HIV who participated in in-depth interviews believed their current or other serious partners were the source of their infection. Some women thought their partner's infidelity was due to their partner's disinterest in sex with them during menstrual/ breakthrough bleeding. Some women included their partners in contraceptive decision-making when the partner was supportive.Discussion: Relationship dynamics affected decision-making for contraceptive and condom use, as well as serodisclosure for the women living with HIV in the study. All women reported challenges with consistent condom use with their male partners, although contraceptive use was generally more acceptable. Women included their partners in their decision-making concerning contraceptive use when they were supportive.

      4. First identified cases of SARS-CoV-2 variant p.1 in the United States - Minnesota, January 2021external icon
        Firestone MJ, Lorentz AJ, Meyer S, Wang X, Como-Sabetti K, Vetter S, Smith K, Holzbauer S, Beaudoin A, Garfin J, Ehresmann K, Danila R, Lynfield R.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 12;70(10):346-347.
        Since December 2020, the Minnesota Department of Health (MDH) Public Health Laboratory has been receiving 100 specimens per week (50 from each of two clinical partners) with low cycle threshold (Ct) values for routine surveillance for SARS-CoV-2, the virus that causes COVID-19. On January 25, 2021, MDH identified the SARS-CoV-2 variant P.1 in one specimen through this surveillance system using whole genome sequencing, representing the first identified case of this variant in the United States. The P.1 variant was first identified in travelers from Brazil during routine airport screening in Tokyo, Japan, in early January 2021 (1). This variant has been associated with increased transmissibility (2), and there are concerns that mutations in the spike protein receptor-binding domain might disrupt both vaccine-induced and natural immunity (3,4). As of February 28, 2021, a total of 10 P.1 cases had been identified in the United States, including the two cases described in this report, followed by one case each in Alaska, Florida, Maryland, and Oklahoma (5).

      5. Trends in prescribing of antibiotics and drugs investigated for COVID-19 treatment in U.S. nursing home residents during the COVID-19 pandemicexternal icon
        Gouin KA, Creasy S, Beckerson M, Wdowicki M, Hicks LA, Lind JN, Geller AI, Budnitz DS, Kabbani S.
        Clin Infect Dis. 2021 Mar 10.
        BACKGROUND: Trends in prescribing for nursing home (NH) residents, which may have been influenced by the COVID-19 pandemic, have not been characterized. METHODS: Long-term care pharmacy data from 1,944 U.S. NHs were used to evaluate trends in prescribing of antibiotics and drugs that were investigated for COVID-19 treatment, including hydroxychloroquine, famotidine, and dexamethasone. To account for seasonal variability in antibiotic prescribing and decreased NH occupancy during the pandemic, monthly prevalence of residents with a prescription dispensed per 1,000 residents serviced was calculated from January - October and compared as relative percent change from 2019 to 2020. RESULTS: In April 2020, prescribing was significantly higher in NHs for drugs investigated for COVID-19 treatment than 2019; including hydroxychloroquine (+563%, 95% confidence interval (CI) 5.87, 7.48) and azithromycin (+150%, 95% CI 2.37, 2.63). Ceftriaxone prescribing also increased (+43%, 95% CI 1.34, 1.54). Prescribing of dexamethasone was 36% lower in April (95% CI 0.55, 0.73) and 303% higher in July (95% CI 3.66, 4.45). Although azithromycin and ceftriaxone prescribing increased, total antibiotic prescribing among residents was lower from May (-5%, 95% CI 0.94, 0.97) through October (-4%, 95% CI 0.94, 0.97) in 2020 compared to 2019. CONCLUSIONS: During the pandemic, large numbers of residents were prescribed drugs investigated for COVID-19 treatment, and an increase in prescribing of antibiotics commonly used for respiratory infections was observed. Prescribing of these drugs may increase the risk of adverse events, without providing clear benefits. Surveillance of NH prescribing practices is critical to evaluate concordance with guideline-recommended therapy and improve resident safety.

      6. COVID-19 intra-action reviews: Potential for a sustained response planexternal icon
        Greiner AL, Nguyen L, Shamout M, Krishnan S, Stowell D.
        Lancet Glob Health. 2021 Mar 2.

      7. Association of state-issued mask mandates and allowing on-premises restaurant dining with county-level COVID-19 case and death growth rates - United States, March 1-December 31, 2020external icon
        Guy GP, Lee FC, Sunshine G, McCord R, Howard-Williams M, Kompaniyets L, Dunphy C, Gakh M, Weber R, Sauber-Schatz E, Omura JD, Massetti GM.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 12;70(10):350-354.
        CDC recommends a combination of evidence-based strategies to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Because the virus is transmitted predominantly by inhaling respiratory droplets from infected persons, universal mask use can help reduce transmission (1). Starting in April, 39 states and the District of Columbia (DC) issued mask mandates in 2020. Reducing person-to-person interactions by avoiding nonessential shared spaces, such as restaurants, where interactions are typically unmasked and physical distancing (≥6 ft) is difficult to maintain, can also decrease transmission (2). In March and April 2020, 49 states and DC prohibited any on-premises dining at restaurants, but by mid-June, all states and DC had lifted these restrictions. To examine the association of state-issued mask mandates and allowing on-premises restaurant dining with COVID-19 cases and deaths during March 1-December 31, 2020, county-level data on mask mandates and restaurant reopenings were compared with county-level changes in COVID-19 case and death growth rates relative to the mandate implementation and reopening dates. Mask mandates were associated with decreases in daily COVID-19 case and death growth rates 1-20, 21-40, 41-60, 61-80, and 81-100 days after implementation. Allowing any on-premises dining at restaurants was associated with increases in daily COVID-19 case growth rates 41-60, 61-80, and 81-100 days after reopening, and increases in daily COVID-19 death growth rates 61-80 and 81-100 days after reopening. Implementing mask mandates was associated with reduced SARS-CoV-2 transmission, whereas reopening restaurants for on-premises dining was associated with increased transmission. Policies that require universal mask use and restrict any on-premises restaurant dining are important components of a comprehensive strategy to reduce exposure to and transmission of SARS-CoV-2 (1). Such efforts are increasingly important given the emergence of highly transmissible SARS-CoV-2 variants in the United States (3,4).

      8. Risk factors associated with SARS-CoV-2 seropositivity among US health care personnelexternal icon
        Jacob JT, Baker JM, Fridkin SK, Lopman BA, Steinberg JP, Christenson RH, King B, Leekha S, O'Hara LM, Rock P, Schrank GM, Hayden MK, Hota B, Lin MY, Stein BD, Caturegli P, Milstone AM, Rock C, Voskertchian A, Reddy SC, Harris AD.
        JAMA Netw Open. 2021 Mar 1;4(3):e211283.
        IMPORTANCE: Risks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care personnel (HCP) are unclear. OBJECTIVE: To evaluate the risk factors associated with SARS-CoV-2 seropositivity among HCP with the a priori hypothesis that community exposure but not health care exposure was associated with seropositivity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted among volunteer HCP at 4 large health care systems in 3 US states. Sites shared deidentified data sets, including previously collected serology results, questionnaire results on community and workplace exposures at the time of serology, and 3-digit residential zip code prefix of HCP. Site-specific responses were mapped to a common metadata set. Residential weekly coronavirus disease 2019 (COVID-19) cumulative incidence was calculated from state-based COVID-19 case and census data. EXPOSURES: Model variables included demographic (age, race, sex, ethnicity), community (known COVID-19 contact, COVID-19 cumulative incidence by 3-digit zip code prefix), and health care (workplace, job role, COVID-19 patient contact) factors. MAIN OUTCOME AND MEASURES: The main outcome was SARS-CoV-2 seropositivity. Risk factors for seropositivity were estimated using a mixed-effects logistic regression model with a random intercept to account for clustering by site. RESULTS: Among 24 749 HCP, most were younger than 50 years (17 233 [69.6%]), were women (19 361 [78.2%]), were White individuals (15 157 [61.2%]), and reported workplace contact with patients with COVID-19 (12 413 [50.2%]). Many HCP worked in the inpatient setting (8893 [35.9%]) and were nurses (7830 [31.6%]). Cumulative incidence of COVID-19 per 10 000 in the community up to 1 week prior to serology testing ranged from 8.2 to 275.6; 20 072 HCP (81.1%) reported no COVID-19 contact in the community. Seropositivity was 4.4% (95% CI, 4.1%-4.6%; 1080 HCP) overall. In multivariable analysis, community COVID-19 contact and community COVID-19 cumulative incidence were associated with seropositivity (community contact: adjusted odds ratio [aOR], 3.5; 95% CI, 2.9-4.1; community cumulative incidence: aOR, 1.8; 95% CI, 1.3-2.6). No assessed workplace factors were associated with seropositivity, including nurse job role (aOR, 1.1; 95% CI, 0.9-1.3), working in the emergency department (aOR, 1.0; 95% CI, 0.8-1.3), or workplace contact with patients with COVID-19 (aOR, 1.1; 95% CI, 0.9-1.3). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US HCP in 3 states, community exposures were associated with seropositivity to SARS-CoV-2, but workplace factors, including workplace role, environment, or contact with patients with known COVID-19, were not. These findings provide reassurance that current infection prevention practices in diverse health care settings are effective in preventing transmission of SARS-CoV-2 from patients to HCP.

      9. A fatal case of rhizopus azygosporus pneumonia following COVID-19external icon
        Kanwar A, Jordan A, Olewiler S, Wehberg K, Cortes M, Jackson BR.
        J Fungi (Basel). 2021 Feb 28;7(3).
        We report a fatal case of Rhizopus azygosporus pneumonia in a 56-year-old man hospitalized for COVID-19 who had received methylprednisolone and tocilizumab. Although COVID-associated pulmonary aspergillosis has been widely documented, mucormycosis has been rarely reported. In this patient, receipt of two commonly used immunosuppressants likely contributed to mucormycosis risk, suggesting the need for vigilance in hospitalized patients with COVID-19.

      10. Shedding of culturable virus, seroconversion, and 6-month follow-up antibody responses in the first 14 confirmed cases of COVID-19 in the United Statesexternal icon
        Killerby ME, Ata Ur Rasheed M, Tamin A, Harcourt JL, Abedi GR, Lu X, Kujawski S, Shah MM, Kirking HL, Gold JA, Salvatore PP, Coughlin MM, Whitaker B, Tate JE, Watson JT, Lindstrom S, Hall AJ, Fry AM, Gerber SI, Midgley CM, Thornburg NJ.
        J Infect Dis. 2021 Mar 7.
        We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to six months post-onset, among 14 early US COVID-19 patients. We isolated viable SARS-CoV-2 from rRT-PCR-positive respiratory specimens collected during days 0-8 post-onset, but not after. All 13 patients with two or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at six months post-onset; all retained detectable anti-spike IgG, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at six months.

      11. Body mass index and risk for COVID-19-related hospitalization, intensive care unit admission, invasive mechanical ventilation, and death - United States, March-December 2020external icon
        Kompaniyets L, Goodman AB, Belay B, Freedman DS, Sucosky MS, Lange SJ, Gundlapalli AV, Boehmer TK, Blanck HM.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 12;70(10):355-361.
        Obesity* is a recognized risk factor for severe COVID-19 (1,2), possibly related to chronic inflammation that disrupts immune and thrombogenic responses to pathogens (3) as well as to impaired lung function from excess weight (4). Obesity is a common metabolic disease, affecting 42.4% of U.S. adults (5), and is a risk factor for other chronic diseases, including type 2 diabetes, heart disease, and some cancers.(†) The Advisory Committee on Immunization Practices considers obesity to be a high-risk medical condition for COVID-19 vaccine prioritization (6). Using data from the Premier Healthcare Database Special COVID-19 Release (PHD-SR),(§) CDC assessed the association between body mass index (BMI) and risk for severe COVID-19 outcomes (i.e., hospitalization, intensive care unit [ICU] or stepdown unit admission, invasive mechanical ventilation, and death). Among 148,494 adults who received a COVID-19 diagnosis during an emergency department (ED) or inpatient visit at 238 U.S. hospitals during March-December 2020, 28.3% had overweight and 50.8% had obesity. Overweight and obesity were risk factors for invasive mechanical ventilation, and obesity was a risk factor for hospitalization and death, particularly among adults aged <65 years. Risks for hospitalization, ICU admission, and death were lowest among patients with BMIs of 24.2 kg/m(2), 25.9 kg/m(2), and 23.7 kg/m(2), respectively, and then increased sharply with higher BMIs. Risk for invasive mechanical ventilation increased over the full range of BMIs, from 15 kg/m(2) to 60 kg/m(2). As clinicians develop care plans for COVID-19 patients, they should consider the risk for severe outcomes in patients with higher BMIs, especially for those with severe obesity. These findings highlight the clinical and public health implications of higher BMIs, including the need for intensive COVID-19 illness management as obesity severity increases, promotion of COVID-19 prevention strategies including continued vaccine prioritization (6) and masking, and policies to ensure community access to nutrition and physical activities that promote and support a healthy BMI.

      12. Screening for HIV among patients at tuberculosis clinics - results from population-based HIV impact assessment surveys, Malawi, Zambia, and Zimbabwe, 2015-2016external icon
        Kothegal N, Wang A, Jonnalagadda S, MacNeil A, Radin E, Brown K, Mugurungi O, Choto R, Balachandra S, Rogers JH, Musuka G, Kalua T, Odo M, Auld A, Gunde L, Kim E, Payne D, Lungu P, Mulenga L, Hassani AS, Nkumbula T, Patel H, Parekh B, Voetsch AC.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 12;70(10):342-345.
        The World Health Organization and national guidelines recommend HIV testing and counseling at tuberculosis (TB) clinics for all patients, regardless of TB diagnosis (1). Population-based HIV Impact Assessment (PHIA) survey data for 2015-2016 in Malawi, Zambia, and Zimbabwe were analyzed to assess HIV screening at TB clinics among persons who had positive HIV test results in the survey. The analysis was stratified by history of TB diagnosis* (presumptive versus confirmed(†)), awareness(§) of HIV-positive status, antiretroviral therapy (ART)(¶) status, and viral load suppression among HIV-positive adults, by history of TB clinic visit. The percentage of adults who reported having ever visited a TB clinic ranged from 4.7% to 9.7%. Among all TB clinic attendees, the percentage who reported that they had received HIV testing during a TB clinic visit ranged from 48.0% to 62.1% across the three countries. Among adults who received a positive HIV test result during PHIA and who did not receive a test for HIV at a previous TB clinic visit, 29.4% (Malawi), 21.9% (Zambia), and 16.2% (Zimbabwe) reported that they did not know their HIV status at the time of the TB clinic visit. These findings represent missed opportunities for HIV screening and linkage to HIV care. In all three countries, viral load suppression rates were significantly higher among those who reported ever visiting a TB clinic than among those who had not (p<0.001). National programs could strengthen HIV screening at TB clinics and leverage them as entry points into the HIV diagnosis and treatment cascade (i.e., testing, initiation of treatment, and viral load suppression).

      13. Neurologic involvement in children and adolescents hospitalized in the United States for COVID-19 or multisystem inflammatory syndromeexternal icon
        LaRovere KL, Riggs BJ, Poussaint TY, Young CC, Newhams MM, Maamari M, Walker TC, Singh AR, Dapul H, Hobbs CV, McLaughlin GE, Son MB, Maddux AB, Clouser KN, Rowan CM, McGuire JK, Fitzgerald JC, Gertz SJ, Shein SL, Munoz AC, Thomas NJ, Irby K, Levy ER, Staat MA, Tenforde MW, Feldstein LR, Halasa NB, Giuliano JS, Hall MW, Kong M, Carroll CL, Schuster JE, Doymaz S, Loftis LL, Tarquinio KM, Babbitt CJ, Nofziger RA, Kleinman LC, Keenaghan MA, Cvijanovich NZ, Spinella PC, Hume JR, Wellnitz K, Mack EH, Michelson KN, Flori HR, Patel MM, Randolph AG.
        JAMA Neurol. 2021 Mar 5.
        IMPORTANCE: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. OBJECTIVE: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. SETTING, DESIGN, AND PARTICIPANTS: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. EXPOSURES: Severe acute respiratory syndrome coronavirus 2. MAIN OUTCOMES AND MEASURES: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. RESULTS: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. CONCLUSIONS AND RELEVANCE: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown.

      14. Declining chlamydia and gonorrhea diagnoses among pregnant women in South Carolina, 2008 to 2018external icon
        Lazenby GB, Savage AH, Horner G, Richmond J, Peterman TA.
        Sex Transm Dis. 2021 Mar 1;48(3):141-144.
        BACKGROUND: Reported US cases of chlamydia and gonorrhea have increased since 2000, whereas studies in select populations suggest that the prevalence of these diseases has decreased. We sought to determine if these diagnoses are increasing among pregnant women delivering at our center. METHODS: This is a retrospective study of women delivering at least 1 infant >18 weeks of gestation at the Medical University of South Carolina for 11 years (2008-2018). Using the perinatal information system, we collected maternal race, age, insurer, and chlamydia and gonorrhea screening results during the pregnancy of record. Cochran-Armitage trend analyses were performed to evaluate trends in these diagnoses by delivery year for all women and for age/race subgroups. RESULTS: During the study period, there were 24,807 deliveries. The median age of women was 28 years (interquartile range, 23-32 years). Five percent (5.0%) of women were diagnosed with chlamydia and 1.2% with gonorrhea. The percent of women diagnosed decreased for both chlamydia (9.6%-3.4%) and gonorrhea (2.5%-1.1%; P < 0.001, trend analyses for both). A higher percentage of Black women had chlamydia and gonorrhea, and both diagnoses declined over time: 17.4% to 6.9% (P < 0.0001) for chlamydia and 5.8% to 2.1% (P < 0.0001) for gonorrhea. In a subanalysis of race and age, Black women younger than 25 years experienced the most significant decline in chlamydia diagnoses (P < 0.0001). CONCLUSIONS: We observed declining diagnoses of chlamydia and gonorrhea among pregnant women in our center. Although Black women delivering were more likely to have either diagnoses, they experienced a significant decline in both chlamydia and gonorrhea over time.

      15. Endemic and other dimorphic mycoses in the Americasexternal icon
        Lockhart SR, Toda M, Benedict K, Caceres DH, Litvintseva AP.
        J Fungi (Basel). 2021 Feb 20;7(2).
        Endemic fungi are thermally dimorphic fungi that have a limited geographic range and can cause both primary disease and opportunistic infections. The Americas are home to more genera of endemic fungi than anywhere else on earth. These include Coccidioides, Histoplasma, Blastomyces, Paracoccidioides, and Sporothrix. Endemic fungi are found across the Americas and the Caribbean, from Blastomyces gilchristi, which extends into the northeast corners of North America, to Histoplasma capsulatum, which occurs all the way down in the southern regions of South America and into the Caribbean Islands. Symptoms of endemic fungal infection, when present, mimic those of many other diseases and are often diagnosed only after initial treatment for a bacterial or viral disease has failed. Endemic fungi place a significant medical burden on the populations they affect, especially in immunocompromised individuals and in resource-limited settings. This review summarizes the ecology, geographical range, epidemiology, and disease forms of the endemic fungi found in the Americas. An emphasis is placed on new and proposed taxonomic changes, including the assignment of new species names in Histoplasma, Blastomyces, and Paracoccidioides.

      16. Self-reported engagement in care among U.S. residents with latent tuberculosis infection - 2011-2012external icon
        Mancuso JD, Miramontes R, Winston CA, Horsburgh CR, Hill AN.
        Ann Am Thorac Soc. 2021 Mar 8.
        RATIONALE: A central strategy of tuberculosis (TB) control in the United States is reducing the burden of latent TB infection (LTBI) through targeted testing and treatment of persons with untreated LTBI. OBJECTIVES: The objective of the study was to provide estimates of and risk factors for engagement in LTBI care in the overall U.S. population and among specific risk groups. METHODS: We used nationally representative data from 7,080 participants in the 2011-2012 National Health and Nutrition Examination Survey. Engagement in LTBI care was assessed by estimating the proportion with a history of testing, diagnosis, treatment initiation and treatment completion. Weighted methods were used to account for the complex survey design and to derive national estimates. RESULTS: Only 1.4 million (10%) of an estimated 14.0 million individuals with LTBI had previously completed treatment. Of the 12.6 million who did not complete LTBI treatment, 3.7 million (29%) had never been tested and 7.2 million (57%) received testing but had no history of diagnosis. High-risk groups showed low levels of engagement, including TB contacts and persons born outside the United States. CONCLUSIONS: There is a reservoir of more than 12 million individuals in the U.S. who may be at risk for progression to TB disease and potential transmission. TB control programs and community providers should consider focused efforts to increase testing, diagnosis, and treatment for LTBI.

      17. Addressing reemergence of diphtheria among adolescents through program integration in Indiaexternal icon
        Maramraj KK, Latha ML, Reddy R, Sodha SV, Kaur S, Dikid T, Reddy S, Jain SK, Singh SK.
        Emerg Infect Dis. 2021 Mar;27(3):953-956.
        We report a diphtheria outbreak mostly among children (median 12 years; range 4-26 years) of a religious minority in urban India. Case-fatality rate (15%, 19/124) was higher among unimmunized patients (relative risk 4.1, 95% CI 1.5-11.7). We recommend mandating and integrating immunization into school health programs to prevent reemergence.

      18. Use of US public health travel restrictions during COVID-19 outbreak on Diamond Princess ship, Japan, February-April 2020external icon
        Medley AM, Marston BJ, Toda M, Kobayashi M, Weinberg M, Moriarty LF, Jungerman MR, Surpris AC, Knust B, Acosta AM, Shockey CE, Daigle D, Schneider ZD, Charles J, Ishizumi A, Stewart A, Vonnahme LA, Brown C, White S, Cohen NJ, Cetron M.
        Emerg Infect Dis. 2021 Mar;27(3):710-718.
        Public health travel restrictions (PHTR) are crucial measures during communicable disease outbreaks to prevent transmission during commercial airline travel and mitigate cross-border importation and spread. We evaluated PHTR implementation for US citizens on the Diamond Princess during its coronavirus disease (COVID-19) outbreak in Japan in February 2020 to explore how PHTR reduced importation of COVID-19 to the United States during the early phase of disease containment. Using PHTR required substantial collaboration among the US Centers for Disease Control and Prevention, other US government agencies, the cruise line, and public health authorities in Japan. Original US PHTR removal criteria were modified to reflect international testing protocols and enable removal of PHTR for persons who recovered from illness. The impact of PHTR on epidemic trajectory depends on the risk for transmission during travel and geographic spread of disease. Lessons learned from the Diamond Princess outbreak provide critical information for future PHTR use.

      19. COVID-19 case investigation and contact tracing in central Washington state, June-July 2020external icon
        Miller JS, Bonacci RA, Lash RR, Moonan PK, Houck P, Van Meter JJ, Butler M, Everson T, Morrison B, Sixberry M, Person A, Oeltmann JE.
        J Community Health. 2021 Mar 10:1-4.
        OBJECTIVE: To evaluate participation in COVID-19 case investigation and contact tracing in central Washington State between June 15 and July 12, 2020. METHODS: In this retrospective observational evaluation we combined SARS-CoV-2 RT-PCR and antigen test reports from the Washington Disease Reporting System with community case investigation and contact tracing data for 3 health districts (comprising 5 counties) in central Washington State. All 3 health districts have large Hispanic communities disproportionately affected by COVID-19. RESULTS: Investigators attempted to call all referred individuals with COVID-19 (n = 4,987); 71% were interviewed. Of those asked about close contacts (n = 3,572), 68% reported having no close contacts, with similar proportions across ethnicity, sex, and age group. The 968 individuals with COVID-19 who named specific contacts (27% of those asked) reported a total of 2,293 contacts (mean of 2.4 contacts per individual with COVID-19); 85% of listed contacts participated in an interview. CONCLUSIONS: Most individuals with COVID-19 reported having no close contacts. Increasing community engagement and public messaging, as well as understanding and addressing barriers to participation, are crucial for CICT to contribute meaningfully to controlling the SARS-CoV-2 pandemic.

      20. Decline of tuberculosis burden in Vietnam measured by consecutive national surveys, 2007-2017external icon
        Nguyen HV, Nguyen HB, Nguyen NV, Cobelens F, Finlay A, Dao CH, Mirtskhulava V, Glaziou P, Pham HT, de Haas P, Tiemersma E.
        Emerg Infect Dis. 2021 Mar;27(3):872-879.
        Vietnam, a high tuberculosis (TB) burden country, conducted national TB prevalence surveys in 2007 and 2017. In both surveys participants were screened by using a questionnaire and chest radiograph; sputum samples were then collected to test for Mycobacterium tuberculosis by smear microscopy and Löwenstein-Jensen culture. Culture-positive, smear-positive, and smear-negative TB cases were defined by laboratory results, and the prevalence of tuberculosis was compared between the 2 surveys. The results showed prevalence of culture-positive TB decreased by 37% (95% CI 11.5%-55.4%), from 199 (95% CI 160-248) cases/100,000 adults in 2007 to 125 (95% CI 98-159) cases/100,000 adults in 2017. Prevalence of smear-positive TB dropped by 53% (95% CI 27.0%-69.7%), from 99 (95% CI 78-125) cases/100,000 adults to 46 (95% CI 32-68) cases/100,000 adults; smear-negative TB showed no substantial decrease. Replacing microscopy with molecular methods for primary diagnostics might enhance diagnosis of pulmonary TB cases and further lower TB burden.

      21. Travel from the United Kingdom to the United States by a symptomatic patient infected with the SARS-CoV-2 B.1.1.7 variant - Texas, January 2021external icon
        Ojelade M, Rodriguez A, Gonzalez D, Otokunrin D, Ramachandruni S, Cuevas E, Moon K, Tyler CG, Freeland M, Anderson M, Haire K, Orozco Y, Scipio F, Springer Y, Prot E, Shuford JA.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 12;70(10):348-349.
        In December 2020, the B.1.1.7 genetic variant of SARS-CoV-2, the virus that causes COVID-19, was first reported after emergence and rapid circulation in the United Kingdom (1). Evidence suggests that the B.1.1.7 variant is more efficiently transmitted than are other SARS-CoV-2 variants, and widespread circulation could thereby increase SARS-CoV-2 infection and hospitalization rates (1,2). The first reported SARS-CoV-2 B.1.1.7 variant case in the United States was confirmed by sequencing in Colorado on December 29, 2020.* This report describes a person who traveled from the United Kingdom to the United States after experiencing COVID-19-compatible symptoms(†) and was eventually confirmed to be infected with the B.1.1.7 variant.

      22. Characteristics of adults aged 18-49 years without underlying conditions hospitalized with laboratory-confirmed coronavirus disease 2019 in the United States: COVID-NET-March-August 2020external icon
        Owusu D, Kim L, O'Halloran A, Whitaker M, Piasecki AM, Reingold A, Alden NB, Maslar A, Anderson EJ, Ryan PA, Kim S, Como-Sabetti K, Hancock EB, Muse A, Bennett NM, Billing LM, Sutton M, Talbot HK, Ortega J, Brammer L, Fry AM, Hall AJ, Garg S.
        Clin Infect Dis. 2021 Mar 1;72(5):e162-e166.
        Among 513 adults aged 18-49 years without underlying medical conditions hospitalized with coronavirus disease 2019 (COVID-19) during March 2020-August 2020, 22% were admitted to an intensive care unit, 10% required mechanical ventilation, and 3 patients died (0.6%). These data demonstrate that healthy younger adults can develop severe COVID-19.

      23. Summary of guidelines for managing histoplasmosis among people living with HIVexternal icon
        Perez F, Caceres DH, Ford N, Ravasi G, Gomez BL, Pasqualotto AC, Hine P, Adenis AA, Nacher M, Chiller T, Baddley J.
        J Fungi (Basel). 2021 Feb 12;7(2).
        Histoplasmosis is a frequent fungal opportunistic infection in people living with HIV (PLHIV), associated every year to a total of 5% to 15% of AIDS-related deaths among this population. In 2020, the first global guidelines for diagnosing and managing disseminated histoplasmosis among PLHIV was published. This document recommends (1) detection of circulating Histoplasma antigens as the recommended laboratory assay to diagnose histoplasmosis among PLHIV; (2) the use of liposomal amphotericin for induction therapy in severe or moderately severe disease, followed by a maintenance therapy with itraconazole for 12 months; a shorter maintenance therapy could be considered if the patient is clinically stable and if immune status has improved; (3) antiretroviral therapy initiation as soon as possible among patients with histoplasmosis without involvement of central nervous system; and (4) that for the treatment of co-infection with histoplasmosis and tuberculosis (TB), treatment of TB should be initiated according to the World Health Organization treatment guidelines. Appropriate health education of providers, supportive supervision, and policy guidance for the care of PLHIV are required.

      24. Prevalence of SARS-CoV-2 antibodies in first responders and public safety personnel, New York City, New York, USA, May-July 2020external icon
        Sami S, Akinbami LJ, Petersen LR, Crawley A, Lukacs SL, Weiss D, Henseler RA, Vuong N, Mackey L, Patel A, Grohskopf LA, Morgenthau BM, Daskalakis D, Pathela P.
        Emerg Infect Dis. 2021 Mar;27(3):796-804.
        We conducted a serologic survey in public service agencies in New York City, New York, USA, during May-July 2020 to determine prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among first responders. Of 22,647 participants, 22.5% tested positive for SARS-CoV-2-specific antibodies. Seroprevalence for police and firefighters was similar to overall seroprevalence; seroprevalence was highest in correctional staff (39.2%) and emergency medical technicians (38.3%) and lowest in laboratory technicians (10.1%) and medicolegal death investigators (10.8%). Adjusted analyses demonstrated association between seropositivity and exposure to SARS-CoV-2-positive household members (adjusted odds ratio [aOR] 3.52 [95% CI 3.19-3.87]), non-Hispanic Black race or ethnicity (aOR 1.50 [95% CI 1.33-1.68]), and severe obesity (aOR 1.31 [95% CI 1.05-1.65]). Consistent glove use (aOR 1.19 [95% CI 1.06-1.33]) increased likelihood of seropositivity; use of other personal protective equipment had no association. Infection control measures, including vaccination, should be prioritized for frontline workers.

      25. Rightsizing treatment for pneumonia in childrenexternal icon
        Tsay SV, Hersh AL, Fleming-Dutra KE.
        JAMA Pediatr. 2021 Mar 8.

      26. COVID-19 infections among students and staff in New York City public schoolsexternal icon
        Varma JK, Thamkittikasem J, Whittemore K, Alexander M, Stephens DH, Arslanian K, Bray J, Long TG.
        Pediatrics. 2021 Mar 9.

      27. Demographic trends in US HIV diagnoses, 2008-2017: Data moviesexternal icon
        Zalla LC, Edwards JK, Cole SR, Rudolph JE, Breger TL, Virkud A, Johnson AS, Hall HI.
        Am J Public Health. 2021 Apr;111(4):529-532.

      28. Population-based geospatial and molecular epidemiologic study of tuberculosis transmission dynamics, Botswana, 2012-2016external icon
        Zetola NM, Moonan PK, Click E, Oeltmann JE, Basotli J, Wen XJ, Boyd R, Tobias JL, Finlay A, Modongo C.
        Emerg Infect Dis. 2021 Mar;27(3):835-844.
        Tuberculosis (TB) elimination requires interrupting transmission of Mycobacterium tuberculosis. We used a multidisciplinary approach to describe TB transmission in 2 sociodemographically distinct districts in Botswana (Kopanyo Study). During August 2012-March 2016, all patients who had TB were enrolled, their sputum samples were cultured, and M. tuberculosis isolates were genotyped by using 24-locus mycobacterial interspersed repetitive units-variable number of tandem repeats. Of 5,515 TB patients, 4,331 (79%) were enrolled. Annualized TB incidence varied by geography (range 66-1,140 TB patients/100,000 persons). A total of 1,796 patient isolates had valid genotyping results and residential geocoordinates; 780 (41%) patients were involved in a localized TB transmission event. Residence in areas with a high burden of TB, age <24 years, being a current smoker, and unemployment were factors associated with localized transmission events. Patients with known HIV-positive status had lower odds of being involved in localized transmission.

    • Environmental Health
      1. Perchloroethylene and dry cleaning: It's time to move the industry to safer alternativesexternal icon
        Ceballos DM, Fellows KM, Evans AE, Janulewicz PA, Lee EG, Whittaker SG.
        Front Public Health. 2021 Mar;9:638082.
        Perchloroethylene (PERC) is the most common solvent used for dry cleaning in the United States. PERC is a reproductive toxicant, neurotoxicant, potential human carcinogen, and a persistent environmental pollutant. The Environmental Protection Agency is evaluating PERC under the Frank R. Lautenberg Chemical Safety for the 21st Century Act, which amended the Toxic Substances Control Act (amended TSCA), and has mandated that PERC dry cleaning machines be removed from residential buildings. Some local and state programs are also requiring or facilitating transitions to alternative cleaning technologies. However, the potential for these alternatives to harm human health and the environment is not well-understood. This review describes the issues surrounding the use of PERC and alternative solvents for dry cleaning while highlighting the lessons learned from a local government program that transitioned PERC dry cleaners to the safest current alternative: professional wet cleaning. Implications for future public health research and policy are discussed: (1) we must move away from PERC, (2) any transition must account for the economic instability and cultural aspects of the people who work in the industry, (3) legacy contamination must be addressed even after safer alternatives are adopted, and (4) evaluations of PERC alternatives are needed to determine their implications for the long-term health and sustainability of the people who work in the industry.

      2. Indoor wood combustion, carcinogenic exposure and esophageal cancer in southwest Kenyaexternal icon
        Mwachiro MM, Pritchett N, Calafat AM, Parker RK, Lando JO, Murphy G, Chepkwony R, Burgert SL, Abnet CC, Topazian MD, White RE, Dawsey SM, Etemadi A.
        Environ Int. 2021 Mar 6;152:106485.
        BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for esophageal squamous cell carcinoma (ESCC) in high-incidence areas of China, Iran and Brazil, but PAH assessments have not been conducted in East Africa, another ESCC hot spot. OBJECTIVE: To evaluate demographic or lifestyle factors associated with the PAH biomarker concentrations in the study population, and whether PAH metabolite concentrations showed any associations with esophageal precancerous lesions. METHODS: We recruited a community-based sample of 289 asymptomatic adults from a rural area of Kenya and performed Lugol's chromoendoscopy to detect esophageal squamous dysplasia (ESD); participants completed a questionnaire and provided a spot urine specimen. We analyzed urine for seven hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene at the U.S. National Center for Environmental Health, and compared creatinine-corrected PAH metabolite concentrations with questionnaire data and the presence of ESD. RESULTS: PAH metabolite concentrations among never tobacco users in these rural Kenya residents were 2.4-28.1 times higher than those reported from never tobacco users in Iran, Brazil and the USA. Female sex, cooking indoors, having no post-primary education, and age <50, but not tobacco use, were positively and significantly associated with PAH metabolite concentrations. Almost all participants used wood as cooking fuel. Nine participants had advanced ESD. Adjusted logistic regression showed a significant association between 2-hydroxynaphthalene (OR = 4.19, 95%CI: 1.01-17.47) and advanced ESD. All other PAH metabolites had positive but non-significant associations with advanced ESD. CONCLUSIONS: Urinary PAH metabolite concentrations among never tobacco users are markedly higher in this group from Kenya than in other populations and are associated with indoor cooking with wood on open, unvented stoves. These metabolite concentrations were also associated with the presence of advanced esophageal dysplasia. Our findings underline the importance of assessing alternative cooking conditions to reduce PAH exposure in this population.

      3. Dietary patterns and PFAS plasma concentrations in childhood: Project Viva, USAexternal icon
        Seshasayee SM, Rifas-Shiman SL, Chavarro JE, Carwile JL, Lin PD, Calafat AM, Sagiv SK, Oken E, Fleisch AF.
        Environ Int. 2021 Mar 8;151:106415.
        BACKGROUND: Diet is thought to account for most adult human exposure to per- and polyfluoroalkyl substances (PFAS). Children are particularly vulnerable to adverse health effects of PFAS and may have different eating habits than adults. However, studies of dietary patterns and PFAS in children are limited. METHODS: We studied 548 Boston-area children with food frequency questionnaire data (89 food items) in early childhood (median age 3.3 years) and plasma concentrations of 6 PFAS quantified in mid-childhood (median age 7.7 years). We used univariate linear regression to examine associations between each food item and PFAS, accounting for multiple comparisons. We next used reduced rank regression (RRR) to estimate overall percent variation in PFAS explained by diet and identify dietary patterns most correlated with PFAS. All models were adjusted for race/ethnicity, maternal education, and household income. RESULTS: In univariate analyses, 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA) plasma concentrations were 17.8% (95% CI: 7.2, 29.5) and 17.0% (95% CI: 6.4, 28.7) higher per SD increment in intake of ice cream and soda, respectively. RRR identified 6 dietary patterns that together explained 18% variation in the plasma concentrations of the 6 PFAS, of which 50% was explained by a dietary pattern consisting of primarily packaged foods (including ice cream and soda) and fish. Children with higher intake of the packaged foods and fish dietary pattern had higher plasma concentrations of all PFAS, particularly MeFOSAA and PFOS. CONCLUSIONS: Our analysis examined food intake in association with several PFAS in children and identified dietary determinants that may be sources of PFAS exposure or reflect correlated lifestyle or toxicokinetic factors. Further investigation may help inform measures to modify childhood PFAS exposure.

      4. Pyrethroid exposure among children residing in green versus non-green multi-family, low-income housingexternal icon
        Werthmann DW, Rabito FA, Stout DM, Tulve NS, Adamkiewicz G, Calafat AM, Ospina M, Chew GL.
        J Expo Sci Environ Epidemiol. 2021 Mar 6.
        BACKGROUND: There is growing concern about children's chronic low-level pesticide exposure and its impact on health. Green building practices (e.g., reducing leakage of the thermal and pressure barrier that surrounds the structure, integrated pest management, improved ventilation) have the potential to reduce pesticide exposure. However, the potential impact of living in green housing on children's pesticide exposure is unknown. OBJECTIVE: To address this question, a longitudinal study of pyrethroid metabolites (3-phenoxybenzoic acid [3-PBA], 4-fluoro-3-phenoxybenzoic acid [4-F-3-PBA], trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid [trans-DCCA]) in first morning void urine, collected from 68 children from New Orleans, Louisiana residing in green and non-green housing was conducted. METHODS: Children were followed for 1 year with three repeated measures of pesticide exposure. Generalized estimating equations examined associations between housing type (green vs. non-green) and urinary pyrethroid metabolite concentrations adjusting for demographic and household factors over the year. RESULTS: Ninety-five percent of samples had detectable concentrations of 3-PBA (limit of detection [LOD]: 0.1 μg/L); 8% of 4-F-3-PBA (LOD: 0.1 μg/L), and 12% of trans-DCCA (LOD: 0.6 μg/L). In adjusted models, green housing was not associated with statistically significant differences in children's 3-PBA urinary concentrations compared to non-green housing.

    • Food Safety
      1. Health care utilization and outcomes associated with accidental poisonous mushroom ingestions - United States, 2016-2018external icon
        Gold JA, Kiernan E, Yeh M, Jackson BR, Benedict K.
        MMWR Morb Mortal Wkly Rep. 2021 Mar 12;70(10):337-341.
        Accidental consumption of poisonous mushrooms can result in serious illness and death (1). Reports of severe poisonings from consumption of foraged mushrooms for food or hallucinogenic purposes increased during 1999-2016 (2), and approximately 7,500 poisonous mushroom ingestions were reported annually to poison control centers across the United States (1). To estimate the frequency of emergency department (ED) visits, hospitalizations, and severe adverse outcomes associated with accidental poisonous mushroom ingestion in the United States, CDC analyzed 2016 data from the Healthcare Cost and Utilization Project's* Nationwide Emergency Department Sample (HCUP-NEDS) and National Inpatient Sample (HCUP-NIS) databases as well as 2016-2018 data from three IBM MarketScan sources: Commercial Claims and Encounters (CCAE), Medicare Supplemental and Coordination of Benefits (Medicare), and Multi-State Medicaid databases. During 2016, 1,328 (standard error [SE] = 100) ED visits and 100 (SE = 22) hospitalizations (HCUP data) were associated with accidental poisonous mushroom ingestion. Among 556 patients with a diagnosis of accidental poisonous mushroom ingestion, 48 (8.6%) patients experienced a serious adverse outcome during 2016-2018 (MarketScan data). Serious adverse outcomes were more common among Medicaid-insured patients than among patients with commercial insurance or Medicare (11.5% versus 6.7%, p = 0.049). Because most mushroom poisonings are preventable, wild mushrooms should not be consumed unless they are identified by an expert; increased public health messaging about the potential dangers of mushroom poisoning is needed.

    • Genetics and Genomics
      1. Complete and circularized bacterial genome sequence of Gordonia sp. strain x0973external icon
        Gulvik CA, Batra D, Rowe LA, Sheth M, Nobles S, Lee JS, McQuiston JR, Lasker BA.
        Microbiol Resour Announc. 2021 Mar 4;10(9).
        Gordonia sp. strain X0973 is a Gram-positive, weakly acid-fast, aerobic actinomycete obtained from a human abscess with Gordonia araii NBRC 100433(T) as its closest phylogenetic neighbor. Here, we report using Illumina MiSeq and PacBio reads to assemble the complete and circular genome sequence of 3.75 Mbp with 3,601 predicted coding sequences.

      2. Paternal genetic variants and risk of obstructive heart defects: A parent-of-origin approachexternal icon
        Patel J, Bircan E, Tang X, Orloff M, Hobbs CA, Browne ML, Botto LD, Finnell RH, Jenkins MM, Olshan A, Romitti PA, Shaw GM, Werler MM, Li J, Nembhard WN.
        PLoS Genet. 2021 Mar 8;17(3):e1009413.
        Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways.

    • Health Economics
      1. State-level health care expenditures associated with disabilityexternal icon
        Khavjou OA, Anderson WL, Honeycutt AA, Bates LG, Hollis ND, Grosse SD, Razzaghi H.
        Public Health Rep. 2021 Mar 5:33354920979807.
        OBJECTIVE: Given the growth in national disability-associated health care expenditures (DAHE) and the changes in health insurance-specific DAHE distribution, updated estimates of state-level DAHE are needed. The objective of this study was to update state-level estimates of DAHE. METHODS: We combined data from the 2013-2015 Medical Expenditure Panel Survey, 2013-2015 Behavioral Risk Factor Surveillance System, and 2014 National Health Expenditure Accounts to calculate state-level DAHE for US adults in total, per adult, and per (adult) person with disability (PWD). We adjusted expenditures to 2017 prices and assessed changes in DAHE from 2003 to 2015. RESULTS: In 2015, DAHE were $868 billion nationally (range, $1.4 billion in Wyoming to $102.8 billion in California) accounting for 36% of total health care expenditures (range, 29%-41%). From 2003 to 2015, total DAHE increased by 65% (range, 35%-125%). In 2015, DAHE per PWD were highest in the District of Columbia ($27 839) and lowest in Alabama ($12 603). From 2003 to 2015, per-PWD DAHE increased by 13% (range, -20% to 61%) and per-capita DAHE increased by 28% (range, 7%-84%). In 2015, Medicare DAHE per PWD ranged from $10 067 in Alaska to $18 768 in New Jersey. Medicaid DAHE per PWD ranged from $9825 in Nevada to $43 365 in the District of Columbia. Nonpublic-health insurer per-PWD DAHE ranged from $7641 in Arkansas to $18 796 in Alaska. CONCLUSION: DAHE are substantial and vary by state. The public sector largely supports the health care costs of people with disabilities. State policy makers and other stakeholders can use these results to inform the development of public health programs that support and provide ongoing health care to people with disabilities.

      2. Assessment of annual cost of substance use disorder in US hospitalsexternal icon
        Peterson C, Li M, Xu L, Mikosz CA, Luo F.
        JAMA Netw Open. 2021 Mar 1;4(3):e210242.
        IMPORTANCE: A persistently high US drug overdose death toll and increasing health care use associated with substance use disorder (SUD) create urgency for comprehensive estimates of attributable direct costs, which can assist in identifying cost-effective ways to prevent SUD and help people to receive effective treatment. OBJECTIVE: To estimate the annual attributable medical cost of SUD in US hospitals from the health care payer perspective. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation of observational data used multivariable regression analysis and mathematical modeling of hospital encounter costs, controlling for patient demographic, clinical, and insurance characteristics, and compared encounters with and without secondary SUD diagnosis to statistically identify the total attributable cost of SUD. Nationally representative hospital emergency department (ED) and inpatient encounters from the 2017 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample and National Inpatient Sample were studied. Statistical analysis was performed from March to June 2020. EXPOSURES: International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) principal or secondary SUD diagnosis on the hospital discharge record according to the Clinical Classifications Software categories (disorders related to alcohol, cannabis, hallucinogens, inhalants, opioids, sedatives, stimulants, and other substances). MAIN OUTCOMES AND MEASURES: Annual attributable SUD medical cost in hospitals overall and by substance type (eg, alcohol). The number of encounters (ED and inpatient) with SUD diagnosis (principal or secondary) and the mean cost attributable to SUD per encounter by substance type are also reported. RESULTS: This study examined a total of 124 573 175 hospital ED encounters and 33 648 910 hospital inpatient encounters from the 2017 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample and National Inpatient Sample. Total annual estimated attributable SUD medical cost in hospitals was $13.2 billion. By substance type, the cost ranged from $4 million for inhalant-related disorders to $7.6 billion for alcohol-related disorders. CONCLUSIONS AND RELEVANCE: This study's results suggest that the cost of effective prevention and treatment may be substantially offset by a reduction in the high direct medical cost of SUD hospital care. The findings of this study may inform the treatment of patients with SUD during hospitalization, which presents a critical opportunity to engage patients who are at high risk for overdose. Aligning incentives such that prevention cost savings accrue to payers and practitioners that are otherwise responsible for SUD-related medical costs in hospitals and other health care settings may encourage prevention investment.

    • Healthcare Associated Infections
      1. Suggestions for the prevention of Clostridioides difficile spread within outpatient hemodialysis facilitiesexternal icon
        D'Agata EM, Apata IW, Booth S, Boyce JM, Deaver K, Gualandi N, Neu A, Nguyen D, Novosad S, Palevsky PM, Rodgers D.
        Kidney Int. 2021 Mar 2.
        Clostridioides difficile infections (CDI) cause substantial morbidity and mortality. Patients on maintenance hemodialysis (MHD) are 2-2.5 times more likely to develop CDI with mortality rates 2-fold higher than the general population. Hospitalizations due to CDI among the MHD population are high and the frequency of antibiotic exposures and hospitalizations may contribute to CDI risk. In this report, a panel of experts in clinical nephrology, infectious diseases, and infection prevention provide guidance, based on expert opinion and published literature, aimed at preventing the spread of CDI in outpatient hemodialysis facilities.

      2. The state of microbiome science at the intersection of infectious diseases and antimicrobial resistanceexternal icon
        Ranallo RT, McDonald LC, Halpin AL, Hiltke T, Young VB.
        J Infect Dis. 2021 Mar 1.
        Along with the rise in modern chronic diseases, ranging from diabetes to asthma, lay the challenges posed by increasing antibiotic resistance resulting in difficult to treat infections, as well as sepsis. An emerging and unifying theme in the pathogenesis of these diverse public health threats is changes in the microbial communities that inhabit multiple body sites. Although there is great promise in exploring the role of these microbial communities in chronic disease pathogenesis, the shorter timeframe of most infectious disease pathogenesis may allow early translation of our basic scientific understanding of microbial ecology and host-microbiota-pathogen interactions. Likely translation avenues include development of preventive strategies, diagnostics, and therapeutics. For example, as basic research related to microbial pathogenesis continues to progress, Clostridioides difficile infection (CDI) is already being addressed clinically through at least two of these three avenues: targeted antibiotic stewardship and treatment of recurrent disease through fecal microbiota transplantation (FMT).

    • Immunity and Immunization
      1. Changes in strength of recommendation and perceived barriers to HPV vaccination: Longitudinal analysis of primary care physicians, 2008-2018external icon
        Cataldi JR, O'Leary ST, Markowitz LE, Allison MA, Crane LA, Hurley LP, Brtnikova M, Beaty BL, Gorman C, Meites E, Lindley MC, Kempe A.
        J Pediatr. 2021 Mar 6.
        OBJECTIVES: To evaluate among pediatricians and family physicians how human papillomavirus (HPV) vaccination recommendation practices for 11-12 year-old youth; report parental refusal/ deferral of HPV vaccination; and report barriers to HPV vaccination changed over time. STUDY DESIGN: We surveyed nationally representative networks of pediatricians and family physicians in 2008, 2010, 2013-2014 and 2018. Male vaccination questions were not asked in 2008; barriers and parental vaccine refusal questions were not asked in 2010. RESULTS: Response rates were 80% in 2008 (680/848), 72% in 2010 (609/842), 70% in 2013-2014 (582/829), and 65% in 2018 (588/908). The proportion of physicians strongly recommending HPV vaccination for 11-12 year-old patients increased from 53% in 2008 to 79% in 2018 for female patients, and from 48% in 2014 to 76% in 2018 for male patients (both p<0.0001). The proportion of physicians indicating ≥50% of parents refused/deferred HPV vaccination remained steady for female patients (24% in 2008 vs. 22% in 2018, p=0.40) and decreased for male patients (42% in 2014 vs, 28% in 2018, p<0.001). Physician barriers to providing HPV vaccination were rare and decreased over time. Increasing numbers of physicians reported perceived parental barriers of vaccine safety concerns (5% 'major barrier' in 2008 vs 35% in 2018, p<0.0001) and moral/religious concerns (5% in 2008 vs. 25% in 2018, P < .0001). CONCLUSIONS: Between 2008 and 2018, more primary care physicians reported recommending HPV vaccination for adolescents, fewer reported barriers, and more physicians reported parents had vaccine safety or moral/religious concerns.

      2. Differential miRNA profiles correlate with disparate immunity outcomes associated with vaccine immunization and Chlamydial infectionexternal icon
        Howard S, Richardson S, Benyeogor I, Omosun Y, Dye K, Medhavi F, Lundy S, Adebayo O, Igietseme JU, Eko FO.
        Front Immunol. 2021 ;12:625318.
        Vaccine-induced immune responses following immunization with promising Chlamydia vaccines protected experimental animals from Chlamydia-induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live Chlamydia does not protect against these pathologies. We hypothesized that differential miRNA profiles induced in the upper genital tracts (UGT) of mice correlate with the disparate immunity vs. pathologic outcomes associated with vaccine immunization and chlamydial infection. Thus, miRNA expression profiles in the UGT of mice after Chlamydia infection (Live EB) and immunization with dendritic cell (DC)-based vaccine (DC vaccine) or VCG-based vaccine (VCG vaccine) were compared using the NanoString nCounter Mouse miRNA assay. Of the 602 miRNAs differentially expressed (DE) in the UGT of immunized and infected mice, we selected 58 with counts >100 and p-values < 0.05 for further analysis. Interestingly, vaccine immunization and Chlamydia infection induced the expression of distinct miRNA profiles with a higher proportion in vaccine-immunized compared to Chlamydia infected mice; DC vaccine (41), VCG vaccine (23), and Live EB (15). Hierarchical clustering analysis showed notable differences in the uniquely DE miRNAs for each experimental group, with DC vaccine showing the highest number (21 up-regulated, five down-regulated), VCG vaccine (two up-regulated, five down-regulated), and live EB (two up-regulated, four down-regulated). The DC vaccine-immunized group showed the highest number (21 up-regulated and five down-regulated compared to two up-regulated and four down-regulated in the live Chlamydia infected group). Pathway analysis showed that the DE miRNAs target genes that regulate several biological processes and functions associated with immune response and inflammation. These results suggest that the induction of differential miRNA expression plays a significant role in the disparate immunity outcomes associated with Chlamydia infection and vaccination.

      3. Age-specific effects of vaccine egg-adaptation and immune priming on A(H3N2) antibody responses following influenza vaccinationexternal icon
        Liu F, Gross FL, Jefferson SN, Holiday C, Bai Y, Wang L, Zhou B, Levine MZ.
        J Clin Invest. 2021 Mar 9.
        A(H3N2) Influenza vaccine effectiveness (VE) were low during 2016-2019 seasons and varied by age. We analyzed neutralizing antibody responses to egg- and cell-propagated vaccine and circulating viruses following vaccination in 375 individuals (aged 7 months to 82 years) across all vaccine eligible age groups in 3 influenza seasons. Antibody responses to cell- compared to egg-propagated vaccine viruses were significantly reduced due to egg-adapted changes T160K, D225G, and L194P in the vaccine hemagglutinins. Vaccine egg-adaptation had differential impact on antibody responses across different age groups. Immunologically naive children immunized with egg-adapted vaccines mostly mounted antibodies targeting egg-adapted epitopes, whereas those previously primed with infection produced broader responses even when vaccinated with egg-based vaccines. In elderly, repeated boost of vaccine egg-adapted epitopes significantly reduced antibody responses to the wild type cell-grown viruses. Analysis with reverse genetics viruses suggested that the response to each egg-adapted substitution varied by age. Antibody responses did not differ in male versus female vaccinees. Here, the combination of age-specific responses to vaccine egg-adapted substitutions, diverse host immune priming histories and virus antigenic drift impacted antibody responses following vaccination and may have led to the low and variable VE against A(H3N2) viruses across different age groups.

      4. On October 7, 2016, the Food and Drug Administration approved recombinant hemagglutinin quadrivalent influenza vaccine (RIV4) (Spodoptera frugiperda cell line; Flublok Quadrivalent) for active immunization for the prevention of influenza disease in individuals 18 years of age and older. Clinical trials did not reveal any major differences in adverse events or serious adverse events following Flublok Quadrivalent versus standard-dose quadrivalent inactivated influenza vaccine. To improve our understanding of the safety profile of this vaccine, we reviewed and summarized adverse event reports after Flublok Quadrivalent administration to the Vaccine Adverse Event Reporting System (VAERS). Through June 30, 2020, VAERS received 849 reports after RIV4 vaccination. The vast majority (810; 95%) were non-serious. Among serious events, there were 10 cases of Guillain-Barré syndrome, including 5 people who required mechanical ventilation and 2 people who died. Many allergic reactions were reported as non-serious, but required interventions to treat a life-threatening event, e.g., epinephrine, nebulizers, albuterol, glucocorticoids, and supplemental oxygen. Two people experienced a positive rechallenge (i.e., allergic reactions after repeated vaccination with RIV4), including a person who-despite premedication with antihistamines-developed respiratory difficulties, required epinephrine, and was transported to the emergency department. The occurrence of anaphylaxis and other allergic reactions in some individuals may reflect an underlying predisposition to atopy that may manifest itself after an exposure to any drug or vaccine, and does not necessarily suggest that Flublok Quadrivalent is particularly allergenic. Postmarketing safety surveillance will continue to be vital for understanding the benefits and risks of quadrivalent recombinant influenza vaccine.

    • Informatics
      1. Using synthetic data to replace linkage derived elements: A case studyexternal icon
        Resnick DM, Cox CS, Mirel LB.
        Health Serv Outcomes Res Methodol. 2021 .
        While record linkage can expand analyses performable from survey microdata, it also incurs greater risk of privacy-encroaching disclosure. One way to mitigate this risk is to replace some of the information added through linkage with synthetic data elements. This paper describes a case study using the National Hospital Care Survey (NHCS), which collects patient records under a pledge of protecting patient privacy from a sample of U.S. hospitals for statistical analysis purposes. The NHCS data were linked to the National Death Index (NDI) to enhance the survey with mortality information. The added information from NDI linkage enables survival analyses related to hospitalization, but as the death information includes dates of death and detailed causes of death, having it joined with the patient records increases the risk of patient re-identification (albeit only for deceased persons). For this reason, an approach was tested to develop synthetic data that uses models from survival analysis to replace vital status and actual dates-of-death with synthetic values and uses classification tree analysis to replace actual causes of death with synthesized causes of death. The degree to which analyses performed on the synthetic data replicate results from analysis on the actual data is measured by comparing survival analysis parameter estimates from both data files. Because synthetic data only have value to the degree that they can be used to produce statistical estimates that are like those based on the actual data, this evaluation is an essential first step in assessing the potential utility of synthetic mortality data.

    • Injury and Violence
      1. Child corporal punishment is a prevalent public health problem in the US. Although corporal punishment is sustained through parents' perceptions of social norms supporting this discipline behavior, little research has investigated where these normative perceptions come from. To fill this gap, we conducted 13 focus groups including 75 low-income Black, Latino, and White parents across five states in the US. Results revealed that one influential source of Black and White parents' perceived norms was their positive framing of corporal punishment experiences during childhood. Furthermore, Black parents formed normative perceptions based on identification with parents in their racial/ethnic group, while White parents did so with parents sharing the same generation. Results are interpreted in light of the false consensus effect and self-categorization theory. In contrast, Latino parents viewed their childhood experience of corporal punishment as negative and distanced their parenting practices from those practiced in their countries of origin, suggesting an influence of acculturation. Their perceived norms were likely transmitted through interpersonal communication within their social networks. These findings shed light on how social norms are formed and in turn guide parents' use of corporal punishment as a tool to discipline children.

    • Laboratory Sciences
      1. Antifungal activity of nikkomycin Z against Candida aurisexternal icon
        Bentz ML, Nunnally N, Lockhart SR, Sexton DJ, Berkow EL.
        J Antimicrob Chemother. 2021 Mar 3.
        BACKGROUND: Nikkomycin Z is a competitive inhibitor of chitin synthase-an enzyme needed for synthesis of the fungal cell wall. Nikkomycin Z shows promise as a treatment for coccidioidomycoses and mixed activity has been described against other fungi and yeast. To our knowledge, it has not previously been tested against the emerging fungal pathogen Candida auris. OBJECTIVES: To determine the in vitro activity of nikkomycin Z against C. auris. METHODS: Nikkomycin Z was tested by broth microdilution against a panel of 100 isolates of genetically diverse C. auris from around the world. RESULTS: Nikkomycin Z showed mixed activity against the tested isolates, with an MIC range of 0.125 to >64 mg/L. The MIC50 and MIC90 were 2 and 32 mg/L, respectively. CONCLUSIONS: These findings suggest nikkomycin Z has in vitro activity against some, but not all isolates of C. auris.

      2. Diagnostic testing for galactose-alpha-1,3-galactose, United States, 2010 to 2018external icon
        Binder AM, Commins SP, Altrich ML, Wachs T, Biggerstaff BJ, Beard CB, Petersen LR, Kersh GJ, Armstrong PA.
        Ann Allergy Asthma Immunol. 2021 Jan 7.
        BACKGROUND: Alpha-gal syndrome (AGS) is an emerging immunoglobulin E (IgE)-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal). The geographic distribution and burden of AGS in the United States are unknown. OBJECTIVE: To characterize alpha-gal IgE testing patterns and describe the trends and distribution from 2010 to 2018 in the United States. METHODS: This retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee's Summit, Missouri), the primary site of testing in the United States. Data included age and sex of person tested, specimen state of origin, collection date, and result value; persons with at least 1 positive test result (≥0.1 kU/L) were compared with negatives. Proportions tested and with positive test results were calculated using the US Census population estimates. RESULTS: Overall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010, to December 31, 2018. Nearly one-third (34,256, 32.4%) had at least 1 positive result. The number of persons receiving positive test results increased 6-fold from 1110 in 2011 to 7798 in 2018. Of those receiving positive test results, mean [SD] age was 46.9 (19.8) years; men were more likely to test positive than women (43.3% vs 26.0%). Arkansas, Virginia, Kentucky, Oklahoma, and Missouri had the highest number of persons who were tested and had a positive result per 100,000 population. CONCLUSION: More than 34,000 persons, most presumably symptomatic, have received positive test results for IgE antibodies to alpha-gal, suggesting AGS is an increasingly recognized public health problem. The geographic distribution of persons who tested positive is consistent with exposure to Amblyomma americanum ticks.

      3. Systematic review of pooling sputum as an efficient method for Xpert MTB/RIF tuberculosis testing during the COVID-19 pandemicexternal icon
        Cuevas LE, Santos VS, Lima S, Kontogianni K, Bimba JS, Iem V, Dominguez J, Adams E, Atienzar AC, Edwards T, Squire SB, Hall PJ, Creswell J.
        Emerg Infect Dis. 2021 Mar;27(3):719-727.
        GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%-98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%-100% specificity and 27%-31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.

      4. Redox epiphospholipidome in programmed cell death signaling: Catalytic mechanisms and regulationexternal icon
        Kagan VE, Tyurina YY, Vlasova , Kapralov AA, Amoscato AA, Anthonymuthu TS, Tyurin VA, Shrivastava IH, Cinemre FB, Lamade A, Epperly MW, Greenberger JS, Beezhold DH, Mallampalli RK, Srivastava AK, Bayir H, Shvedova AA.
        Front Endocrinol (Lausanne). 2020 ;11:628079.
        A huge diversification of phospholipids, forming the aqueous interfaces of all biomembranes, cannot be accommodated within a simple concept of their role as membrane building blocks. Indeed, a number of signaling functions of (phospho)lipid molecules has been discovered. Among these signaling lipids, a particular group of oxygenated polyunsaturated fatty acids (PUFA), so called lipid mediators, has been thoroughly investigated over several decades. This group includes oxygenated octadecanoids, eicosanoids, and docosanoids and includes several hundreds of individual species. Oxygenation of PUFA can occur when they are esterified into major classes of phospholipids. Initially, these events have been associated with non-specific oxidative injury of biomembranes. An alternative concept is that these post-synthetically oxidatively modified phospholipids and their adducts with proteins are a part of a redox epiphospholipidome that represents a rich and versatile language for intra- and inter-cellular communications. The redox epiphospholipidome may include hundreds of thousands of individual molecular species acting as meaningful biological signals. This review describes the signaling role of oxygenated phospholipids in programs of regulated cell death. Although phospholipid peroxidation has been associated with almost all known cell death programs, we chose to discuss enzymatic pathways activated during apoptosis and ferroptosis and leading to peroxidation of two phospholipid classes, cardiolipins (CLs) and phosphatidylethanolamines (PEs). This is based on the available LC-MS identification and quantitative information on the respective peroxidation products of CLs and PEs. We focused on molecular mechanisms through which two proteins, a mitochondrial hemoprotein cytochrome c (cyt c), and non-heme Fe lipoxygenase (LOX), change their catalytic properties to fulfill new functions of generating oxygenated CL and PE species. Given the high selectivity and specificity of CL and PE peroxidation we argue that enzymatic reactions catalyzed by cyt c/CL complexes and 15-lipoxygenase/phosphatidylethanolamine binding protein 1 (15LOX/PEBP1) complexes dominate, at least during the initiation stage of peroxidation, in apoptosis and ferroptosis. We contrast cell-autonomous nature of CLox signaling in apoptosis correlating with its anti-inflammatory functions vs. non-cell-autonomous ferroptotic signaling facilitating pro-inflammatory (necro-inflammatory) responses. Finally, we propose that small molecule mechanism-based regulators of enzymatic phospholipid peroxidation may lead to highly specific anti-apoptotic and anti-ferroptotic therapeutic modalities.

      5. Rickettsia are significant sources of tick-borne diseases in humans worldwide. In North America, two species in the spotted fever group of Rickettsia have been conclusively associated with disease of humans: Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, and Rickettsia parkeri, the cause of R. parkeri rickettsiosis. Previous work in our lab demonstrated non-endothelial parasitism by another pathogenic SFG Rickettsia species, Rickettsia conorii, within THP-1-derived macrophages, and we have hypothesized that this growth characteristic may be an underappreciated aspect of rickettsial pathogenesis in mammalian hosts. In this work, we demonstrated that multiple other recognized human pathogenic species of Rickettsia, including R. rickettsii, R. parkeri, Rickettsia africae, and Rickettsiaakari can grow within target endothelial cells as well as within PMA-differentiated THP-1 cells. In contrast, Rickettsia bellii, a Rickettsia species not associated with disease of humans, and R. rickettsii strain Iowa, an avirulent derivative of pathogenic R. rickettsii, could invade both cell types but proliferate only within endothelial cells. Further analysis revealed that similar to previous studies on R. conorii, other recognized pathogenic Rickettsia species could grow within the cytosol of THP-1-derived macrophages and avoided localization with two different markers of lysosomal compartments; LAMP-2 and cathepsin D. R. bellii, on the other hand, demonstrated significant co-localization with lysosomal compartments. Collectively, these findings suggest that the ability of pathogenic rickettsial species to establish a niche within macrophage-like cells could be an important factor in their ability to cause disease in mammals. These findings also suggest that analysis of growth within mammalian phagocytic cells may be useful to predict the pathogenic potential of newly isolated and identified Rickettsia species.

      6. Chemical characterization and quantification of circulating intact PTH and PTH fragments by high-resolution mass spectrometry in chronic renal failureexternal icon
        Kritmetapak K, Losbanos LA, Hines JM, O'Grady KL, Ulmer CZ, Vesper HW, Enders FT, Singh RJ, Kumar R.
        Clin Chem. 2021 Mar 6.
        BACKGROUND: The precise concentrations of full-length parathyroid hormone (PTH1-84) and the identity and concentrations of PTH fragments in patients with various stages of chronic renal failure are unknown. METHODS: We developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method to characterize and quantify PTH1-84 and PTH fragments in serum of 221 patients with progressive renal dysfunction. Following capture by matrix-bound amino-terminal or carboxyl-terminal region-specific antibodies and elution from matrix, PTH1-84 and PTH fragments were identified and quantitated using LC-HRMS. PTH was simultaneously measured using an intact PTH (iPTH) immunoassay. RESULTS: Full-length PTH1-84 and 8 PTH fragments (PTH28-84, 34-77, 34-84, 37-77, 37-84, 38-77, 38-84, and 45-84) were unequivocally identified and were shown to increase significantly when an eGFR declined to ≤17-23 mL/min/1.73m2. Serum concentrations of PTH1-84 were similar when measured by LC-HRMS following capture by amino-terminal or carboxyl-terminal immunocapture methods. In patients with an eGFR of <30 mL/min/1.73 m2, serum PTH concentrations measured using LC-HRMS were significantly lower than PTH measured using an iPTH immunoassay. PTH7-84 and oxidized forms of PTH1-84 were below the limit of detection (30 and 50 pg/mL, respectively). CONCLUSIONS: LC-HRMS identifies circulating PTH1-84, carboxyl-terminal PTH fragments, and mid-region PTH fragments, in patients with progressive renal failure. Serum PTH1-84 and its fragments markedly rise when an eGFR decreases to ≤17-23 mL/min/1.73 m2. PTH concentrations measured using LC-HRMS tend to be lower than those measured using an iPTH immunoassay, particularly in severe chronic renal failure. Our data do not support the existence of circulating PTH7-84 and oxidized PTH1-84.

      7. Rat bite fever and Haverhill fever are often difficult to diagnose in a clinical setting. This difficulty results in part from clinicians and laboratory professionals not being able to reliably recover the causative agent Streptobacillus moniliformis using culture-based methods. After utilizing an automated continuous-monitoring blood culture bottle system, we showed that the organism can be reliably cultured when a blood volume inoculum of 10 mL is used. Further, we showed that when the above recommendation is followed, sodium polyanethole sulfonate (up to a concentration of 0.05% w/v) in commercially purchased blood culture bottle formulations seems to be inactivated, allowing for the growth and detection of S. moniliformis. Herein, we offer data and methods used to overcome these clinical limitations. This is a comprehensive study of the historical collection of S. moniliformis isolates maintained by our facility and believed to be the largest of its kind to date.

      8. Here we report a new procedure to determine 239Pu in urine using a custom-made automated pre-analytical processing system (single probe) with 242Pu as a tracer followed by analysis by SF-ICP-MS. An average 242Pu recovery rate of 88% was obtained with CF-ThU-1000 columns reused &gt; 100 times. Analytical results agree with measurements obtained using the CDC manual method with a R2 of 0.9994. Results for Oak Ridge National Laboratory reference materials align with target values with a bias range of − 3.44 to 3.05%. The limit of detection for this method is 0.63 pg/L, which is comparable to previous manual methods.

    • Maternal and Child Health
      1. Ffg healthy and ready to learn: Prevalence and correlates of school readiness among US preschoolersexternal icon
        Ghandour RM, Hirai AH, Moore KA, Robinson LR, Kaminski JW, Murphy K, Lu MC, Kogan MD.
        Acad Pediatr. 2021 Mar 2.
        OBJECTIVE: To assess the national and state prevalence of being "Healthy and Ready to Learn" (HRL) and associated sociodemographic, health, family and neighborhood factors. METHODS: Cross-sectional analysis of the 2016 National Survey of Children's Health, a nationally representative parent-reported survey administered by web and paper June 2016-February 2017. Four domains were constructed from 18 items through confirmatory factor analyses: "Early Learning Skills", "Social-Emotional Development", "Self-Regulation", and "Physical Well-being and Motor Development." Each item and domain were scored according to age-specific standards as "On-Track", "Needs Support", and "At Risk" with overall HRL defined as "On-Track" in all domains for 7,565 randomly selected children ages 3-5 years. RESULTS: In 2016, 42.2% of children ages 3-5 years were considered HRL with the proportion considered "On-Track" ranging from 58.4% for Early Learning Skills to 85.5% for Physical Well-being and Motor Development"; approximately 80% of children were considered "On-Track" in Social-Emotional Development and Self-Regulation, respectively. Sociodemographic differences were mostly non-significant in multivariable analyses. Health, family, and neighborhood factors (i.e., special health care needs status/type, parental mental health, reading, singing and storytelling, screen time, adverse childhood experiences, and neighborhood amenities) were associated with HRL. HRL prevalence ranged from 25.5% (NV) to 58.7% (NY), but only four states were significantly different from the U.S. overall. CONCLUSIONS: Based on this pilot measure, only about four in ten US children ages 3-5 years may be considered "Healthy and Ready to Learn." Improvement opportunities exist for multiple, modifiable factors to affect young children's readiness to start school.

      2. A One Health approach to child stunting: Evidence and research agendaexternal icon
        Gharpure R, Mor S, Viney M, Hodobo T, Lello J, Siwila J, Dube K, Robertson RC, Mutasa K, Berger CN, Hirai M, Brown T, Ntozini R, Evans C, Hoto P, Smith LE, Tavengwa NV, Joyeux M, Humphrey JH, Berendes D, Prendergast AJ.
        Am J Trop Med Hyg. 2021 Mar 8.
        Stunting (low height for age) affects approximately one-quarter of children aged < 5 years worldwide. Given the limited impact of current interventions for stunting, new multisectoral evidence-based approaches are needed to decrease the burden of stunting in low- and middle-income countries (LMICs). Recognizing that the health of people, animals, and the environment are connected, we present the rationale and research agenda for considering a One Health approach to child stunting. We contend that a One Health strategy may uncover new approaches to tackling child stunting by addressing several interdependent factors that prevent children from thriving in LMICs, and that coordinated interventions among humans, animals, and environmental health sectors may have a synergistic effect in stunting reduction.

      3. Comparative analysis of perinatal outcomes and birth defects amongst adolescent and older Ugandan mothers: Evidence from a hospital-based surveillance databaseexternal icon
        Serunjogi R, Barlow-Mosha L, Mumpe-Mwanja D, Williamson D, Valencia D, Tinker SC, Adler MR, Namale-Matovu J, Kalibbala D, Nankunda J, Nabunya E, Birabwa-Male D, Byamugisha J, Musoke P.
        Reprod Health. 2021 Mar 4;18(1):56.
        BACKGROUND: Uganda has one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes between adolescents (age 12-19 years) and mothers (age 20-34 years) in four urban hospitals. METHODS: Maternal demographics, HIV status, and birth outcomes of all live births, stillbirths, and spontaneous abortions delivered from August 2015 to December 2018 were extracted from a hospital-based birth defects surveillance database. Differences in the distributions of maternal and infant characteristics by maternal age groups were tested with Pearson's chi-square. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated using logistic regression to compare the prevalence of adverse birth outcomes among adolescents to mothers 20-34 years. RESULTS: A total of 100,189 births were analyzed, with 11.1% among adolescent mothers and 89.0% among older mothers. Adolescent mothers had an increased risk of preterm delivery (aOR: 1.14; CI 1.06-1.23), low birth weight (aOR: 1.46; CI 1.34-1.59), and early neonatal deaths (aOR: 1.58; CI 1.23-2.02). Newborns of adolescent mothers had an increased risk of major external birth defects (aOR: 1.33; CI 1.02-1.76), specifically, gastroschisis (aOR: 3.20; CI 1.12-9.13) compared to mothers 20-34 years. The difference between the prevalence of gastroschisis among adolescent mothers (7.3 per 10,000 births; 95% CI 3.7-14.3) was statistically significant when compared to mothers 20-34 years (1.6 per 10,000 births; 95% CI 0.9-2.6). CONCLUSIONS: This study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20-34 years, similar to findings in the region and globally. Interventions are needed to improve birth outcomes in this vulnerable population. Adolescent pregnancies are a global problem occurring in high-, middle-, and low-income countries with Uganda having one of the highest adolescent pregnancy rates in sub-Saharan Africa. We compared the risk of adverse birth outcomes, including major external birth defects, between adolescents, (age 12–19 years) and mothers (age 20–34 years) in four urban hospitals.All informative births, including live births, stillbirths, and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2018 were examined. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes.Of the 100,189 births, 11.0% were among adolescent mothers and 89.0% among mothers (20–34 years). Adolescent mothers were more likely than mothers (20–34 years) to have an infant with preterm delivery, low birth weight, early neonatal death, and major external birth defects. Adolescent pregnancies were also associated with an increased risk of gastroschisis when compared to mothers (20–34 years).In conclusion, this study found that adolescent mothers had an increased risk for several adverse birth outcomes compared to mothers 20–34 years. Research on the potential underlying causes or mechanisms for these adverse outcomes among adolescent births is necessary to identify possible interventions. eng

      4. Incidence of urinary tract infections in newborns with spina bifida: Is antibiotic prophylaxis necessary?external icon
        Wallis MC, Paramsothy P, Newsome K, Williams T, Routh JC, Joseph DB, Cheng E, Tu D, Austin JC, Tanaka ST, Walker WO, Smith KA, Baum MA, Wiener JS.
        J Urol. 2021 Mar 8:101097ju0000000000001690.
        PURPOSE: Urinary tract infections (UTI) commonly occur in patients with spina bifida (SB) and pose a risk for renal scarring. Routine antibiotic prophylaxis has been utilized in newborns with SB to prevent UTI. We hypothesized that prophylaxis can safely be withheld in newborns with SB until clinical assessment allows for risk stratification. MATERIALS AND METHODS: Newborns with myelomeningocele at nine institutions were prospectively enrolled in the UMPIRE study and managed by a standardized protocol with a strict definition for UTI. Patient data were collected regarding details of reported UTI, baseline renal ultrasound findings, vesicoureteral reflux, use of clean intermittent catheterization (CIC), and circumcision status in boys. Risk Ratios (RRs) and corresponding 95% confidence intervals (CIs) were calculated using log-binomial models. RESULTS: From 2/2015 through 8/2019, data were available on 299 newborns (50.5% male). During the first four months of life, 48 (16.1%) newborns were treated for UTI with 23 (7.7%) having positive cultures; however, only 12 (4.0%) met the strict UTI definition. Infants with grade 3-4 hydronephrosis had an increased risk of UTI compared to infants with no hydronephrosis (RR=10.1; 95%CI=2.8, 36.3). Infants on CIC also had an increased risk of UTI (RR=3.3; 95%CI=1.0, 10.5). CONCLUSIONS: The incidence of a culture-positive, symptomatic UTI among newborns with SB in the first 4 months of life was low. Patients with high grades of hydronephrosis or those on CIC had a significantly greater incidence of UTI. Our findings suggest that routine antibiotic prophylaxis may not be necessary for most newborns with SB.

    • Nutritional Sciences
      1. Associations between zinc and hemoglobin concentrations in preschool children and women of reproductive age: An analysis of representative survey data from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) projectexternal icon
        Greffeuille V, Fortin S, Gibson R, Rohner F, Williams A, Young MF, Houghton L, Ou J, Dijkhuizen MA, Wirth JP, Lander RL, McDonald CM, Suchdev PS, Berger J, Wieringa FT.
        J Nutr. 2021 Mar 9.
        BACKGROUND: Anemia is a worldwide concern. Nutritional deficiencies and inflammation are considered main contributors, but zinc deficiency has only recently been associated with anemia. OBJECTIVES: In this study we assessed associations between zinc status and hemoglobin (Hb) concentrations and anemia in preschool children 6-59 mo old (PSC) and nonpregnant women of reproductive age 15-49 y old (WRA) in population-based nutrition surveys. METHODS: Cross-sectional data from 13 (PSC) and 12 (WRA) countries within the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were used. Multivariable linear models were constructed that included zinc status (plasma/serum zinc concentrations), Hb concentrations and anemia, iron status, age, sex, and inflammation (C-reactive protein and α-1-acid glycoprotein). Zinc was adjusted for inflammation in PSC according to the BRINDA algorithm. RESULTS: Data were available for 18,658 PSC and 22,633 WRA. Prevalence of anemia ranged from 7.5% to 73.7% and from 11.5% to 94.7% in PSC and WRA, respectively. Prevalence of zinc deficiency ranged from 9.2% to 78.4% in PSC and from 9.8% to 84.7% in WRA, with prevalence of zinc deficiency >20% in all countries except Azerbaijan (PSC), Ecuador (PSC), and the United Kingdom (WRA). Multivariable linear regression models showed that zinc concentrations were independently and positively associated with Hb concentrations in 7 of 13 countries for PSC and 5 of 12 countries for WRA. In the same models, ferritin concentration was also significantly associated with Hb among PSC and WRA in 9 and 10 countries, respectively. Zinc deficiency was significantly associated with anemia in PSC and WRA in 5 and 4 countries respectively. CONCLUSIONS: Zinc deficiency was prevalent in most countries and associations between zinc and Hb in roughly half of the countries examined suggesting that strategies to combat zinc deficiency may help reduce anemia prevalence. More research on mechanisms by which zinc deficiency is associated with anemia and the reasons for the heterogeneity among countries is warranted.

    • Occupational Safety and Health
      1. Impact of a crime prevention ordinance for small retail establishmentsexternal icon
        Davis J, Casteel C, Menéndez CC.
        Am J Ind Med. 2021 Mar 8.
        BACKGROUND: Ordinances requiring the implementation of robbery prevention measures have been enacted at the city level in many jurisdictions. We evaluated the impact of an ordinance requiring crime prevention measures on subsequent crime rates. METHODS: Crime reports for robbery and aggravated assault from January 2006 through December 2015 were linked to randomly-selected convenience stores and small retail grocers in Houston (n = 293). Store characteristics and compliance with a list of safety measures were collected by surveyors in 2011. Generalized linear mixed models were used to compare rates of crime before and after the implementation of the ordinance. RESULTS: Robberies decreased significantly after the ordinance went into effect (rate ratio = 0.38; 95% confidence interval 0.29-0.51). No individual safety measure was associated with decreased robbery rates. No similar decrease was observed for aggravated assault. CONCLUSIONS: City ordinances mandating crime prevention measures can be effective. We could not parse out the effectiveness of individual elements, suggesting a comprehensive approach may be more effective.

    • Occupational Safety and Health - Mining
      1. The drilling operation in the roof bolting process, especially in hard rock, generates excessive respirable coal and quartz dusts, which could expose the roof bolting operator to continued health risks. Previous research has shown that the amount of respirable dust produced is dependent on the main drilling parameters, specifically the drilling rotational and penetration rate. In this paper, a roof bolter drilling control process was proposed to reduce the generation of respirable dust. Based on the analysis of laboratory drilling test results, a rational drilling control process (adjusting rotational and penetration rates) to achieve the optimal drilling parameter for different rock types was proposed. In this process, the ratio between specific energy and rock uniaxial compressive strength was used as the index to determine the optimal operation point. The recommended drilling operation range for the rock type used in the experiment was provided, and the reduction in respirable dust generation was demonstrated. By following this control process, the drilling efficiency can be monitored in real time, so the system can stay in a relatively high-energy efficiency with less respirable dust production from the drilling source. This algorithm is targeted to be incorporated into the current roof bolter drilling control system for drilling automation so that a safe and productive drilling operation can be conducted in a healthy working environment.

    • Parasitic Diseases
      1. Cost and cost-effectiveness of indoor residual spraying with pirimiphos-methyl in a high malaria transmission district of Mozambique with high access to standard insecticide-treated netsexternal icon
        Alonso S, Chaccour CJ, Wagman J, Candrinho B, Muthoni R, Saifodine A, Saute F, Robertson M, Zulliger R.
        Malar J. 2021 Mar 10;20(1):143.
        BACKGROUND: As malaria cases increase in some of the highest burden countries, more strategic deployment of new and proven interventions must be evaluated to meet global malaria reduction goals. METHODS: The cost and cost-effectiveness of indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS) were assessed in a high transmission district (Mopeia) with high access to pyrethroid insecticide-treated nets (ITNs), compared to ITNs alone. The major mosquito vectors in the area were susceptible to primiphos-methyl, but resistant to pyrethoids. A decision analysis approach was followed to conduct deterministic and probabilistic sensitivity analyses in a theoretical cohort of 10,000 children under five years of age (U5) and 10,000 individuals of all ages, separately. Model parameters and distributions were based on prospectively collected cost and epidemiological data from a cluster-randomized control trial and a literature review. The primary analysis used health facility-malaria incidence, while community cohort incidence and cross-sectional prevalence rates were used in sensitivity analyses. Lifetime costs, malaria cases, deaths and disability-adjusted life-years (DALYs) were calculated to determine the incremental costs per DALY averted through IRS. RESULTS: The average IRS cost per person protected was US$8.26 and 51% of the cost was insecticide. IRS averted 46,609 (95% CI 46,570-46,646) uncomplicated and 242 (95% CI 241-243) severe lifetime cases in a theoretical children U5 cohort, yielding an incremental cost-effectiveness ratio (ICER) of US$400 (95% CI 399-402) per DALY averted. In the all-age cohort, the ICER was higher: US$1,860 (95% CI 1,852-1,868) per DALY averted. Deterministic and probabilistic results were consistent. When adding the community protective effect of IRS, the cost per person protected decreased (US$7.06) and IRS was highly cost-effective in children U5 (ICER = US$312) and cost-effective in individuals of all ages (ICER = US$1,431), compared to ITNs alone. CONCLUSION: This study provides robust evidence that IRS with pirimiphos-methyl can be cost-effective in high transmission regions with high pyrethroid ITN coverage where the major vector is susceptible to pirimiphos-methyl but resistant to pyrethroids. The finding that insecticide cost is the main driver of IRS costs highlights the need to reduce the insecticide price without jeopardizing effectiveness. TRIAL REGISTRATION: identifier NCT02910934 (Registered 22 September 2016).

      2. Cost-effectiveness of district-wide seasonal malaria chemoprevention when implemented through routine malaria control programme in Kita, Mali using fixed point distributionexternal icon
        Diawara H, Walker P, Cairns M, Steinhardt LC, Diawara F, Kamate B, Duval L, Sicuri E, Sagara I, Sadou A, Mihigo J, Eckert E, Dicko A, Conteh L.
        Malar J. 2021 Mar 4;20(1):128.
        BACKGROUND: Seasonal malaria chemoprevention (SMC) is a strategy for malaria control recommended by the World Health Organization (WHO) since 2012 for Sahelian countries. The Mali National Malaria Control Programme adopted a plan for pilot implementation and nationwide scale-up by 2016. Given that SMC is a relatively new approach, there is an urgent need to assess the costs and cost effectiveness of SMC when implemented through the routine health system to inform decisions on resource allocation. METHODS: Cost data were collected from pilot implementation of SMC in Kita district, which targeted 77,497 children aged 3-59 months. Starting in August 2014, SMC was delivered by fixed point distribution in villages with the first dose observed each month. Treatment consisted of sulfadoxine-pyrimethamine and amodiaquine once a month for four consecutive months, or rounds. Economic and financial costs were collected from the provider perspective using an ingredients approach. Effectiveness estimates were based upon a published mathematical transmission model calibrated to local epidemiology, rainfall patterns and scale-up of interventions. Incremental cost effectiveness ratios were calculated for the cost per malaria episode averted, cost per disability adjusted life years (DALYs) averted, and cost per death averted. RESULTS: The total economic cost of the intervention in the district of Kita was US $357,494. Drug costs and personnel costs accounted for 34% and 31%, respectively. Incentives (payment other than salary for efforts beyond routine activities) accounted for 25% of total implementation costs. Average financial and economic unit costs per child per round were US $0.73 and US $0.86, respectively; total annual financial and economic costs per child receiving SMC were US $2.92 and US $3.43, respectively. Accounting for coverage, the economic cost per child fully adherent (receiving all four rounds) was US $6.38 and US $4.69, if weighted highly adherent, (receiving 3 or 4 rounds of SMC). When costs were combined with modelled effects, the economic cost per malaria episode averted in children was US $4.26 (uncertainty bound 2.83-7.17), US $144 (135-153) per DALY averted and US $ 14,503 (13,604-15,402) per death averted. CONCLUSIONS: When implemented at fixed point distribution through the routine health system in Mali, SMC was highly cost-effective. As in previous SMC implementation studies, financial incentives were a large cost component.

      3. The effect of drug pricing on outpatient payments and treatment for three soil-transmitted helminth infections in the United States, 2010-2017external icon
        Joo H, Lee J, Maskery BA, Park C, Alpern JD, Phares CR, Weinberg M, Stauffer WM.
        Am J Trop Med Hyg. 2021 Mar 8.
        The price of certain antiparasitic drugs (e.g., albendazole and mebendazole) has dramatically increased since 2010. The effect of these rising prices on treatment costs and use of standard of care (SOC) drugs is unknown. To measure the impact of drug prices on overall outpatient cost and quality of care, we identified outpatient visits associated with ascariasis, hookworm, and trichuriasis infections from the 2010 to 2017 MarketScan Commercial Claims and Encounters and Multi-state Medicaid databases using Truven Health MarketScan Treatment Pathways. Evaluation was limited to members with continuous enrollment in non-capitated plans 30 days prior, and 90 days following, the first diagnosis. The utilization of SOC prescriptions was considered a marker for quality of care. The impact of drug price on the outpatient expenses was measured by comparing the changes in drug and nondrug outpatient payments per patient through Welch's two sample t-tests. The total outpatient payments per patient (drug and nondrug), for the three parasitic infections, increased between 2010 and 2017. The increase was driven primarily by prescription drug payments, which increased 20.6-137.0 times, as compared with nondrug outpatient payments, which increased 0.3-2.2 times. As prices of mebendazole and albendazole increased, a shift to alternative SOC and non-SOC drug utilization was observed. Using parasitic infection treatment as a model, increases in prescription drug prices can act as the primary driver of increasing outpatient care costs. Simultaneously, there was a shift to alternative SOC, but also to non-SOC drug treatment, suggesting a decrease in quality of care.

    • Reproductive Health
      1. Design and methodology of the Study of Associated Risks of Stillbirth (SOARS) in Utahexternal icon
        DeSisto CL, Stone N, Algarin B, Baksh L, Dieke A, D'Angelo DV, Harrison L, Warner L, Shulman HB.
        Public Health Rep. 2021 Mar 5:33354921994895.
        OBJECTIVES: The Utah Study of Associated Risks of Stillbirth (SOARS) collects data about stillbirths that are not included in medical records or on fetal death certificates. We describe the design, methods, and survey response rate from the first year of SOARS. METHODS: The Utah Department of Health identified all Utah women who experienced a stillbirth from June 1, 2018, through May 31, 2019, via fetal death certificates and invited them to participate in SOARS. The research team based the study protocol on the Pregnancy Risk Assessment Monitoring System surveillance of women with live births and modified it to be sensitive to women's recent experience of a stillbirth. We used fetal death certificates to examine survey response rates overall and by maternal characteristics, gestational age of the fetus, and month in which the loss occurred. RESULTS: Of 288 women invited to participate in the study, 167 (58.0%) completed the survey; 149 (89.2%) responded by mail and 18 (10.8%) by telephone. A higher proportion of women who were non-Hispanic White (vs other races/ethnicities), were married (vs unmarried), and had ≥high school education (vs <high school education) responded to the survey. Differences between responders and nonresponders by maternal age, gestational age of the fetus, or month of delivery were not significant. Among responders, item nonresponse rates were low (range, 0.6%-5.4%). The question about income (4.8%) and the questions about tests offered and performed during the hospital stay had the highest item nonresponse rates. CONCLUSIONS: The response rate suggests that a mail- and telephone-based survey can be successful in collecting self-reported information about risk factors for stillbirths not currently included in medical records or fetal death certificates.

      2. Persistent racial/ethnic disparities in supine sleep positioning among U.S.-born preterm infants, 2000-2015external icon
        Hwang SS, Tong S, Smith RA, Barfield WD, Pyle L, Battaglia C, McManus B, Niermeyer S, Sauaia A.
        J Pediatr. 2021 Mar 4.
        OBJECTIVE: To assess trends in racial disparity in supine sleep positioning across racial/ethnic groups of early preterm (EPT;<34 weeks) and late preterm (LPT;34-36 weeks) infants from 2000-2015. STUDY DESIGN: We analyzed Pregnancy Risk Assessment Monitoring System (PRAMS) data (a population-based perinatal surveillance system) from 16 U.S. states from 2000 to 2015 (Weighted N=1,020,986). Marginal prevalence of SSP by year was estimated for EPT and LPT infants, adjusting for maternal and infant characteristics. After stratifying EPT and LPT infants, adjusted odds of SSP trends were compared across racial/ethnic groups by testing the time-race interaction. RESULTS: From 2000 to 2015, Non-Hispanic Black infants had lower odds of SSP compared with Non-Hispanic White infants for EPT (AOR:0.61;95% CI 0.47-0.78) and LPT (AOR:0.44;95% CI:0.34-0.56) groups. For Hispanic infants, there was no statistically significant difference for either preterm group when compared with Non-Hispanic White infants. Adjusted odds of supine sleep positioning increased (on average) annually by 10.0%,7.3% and 7.7% respectively in Non-Hispanic White, Non-Hispanic Black, and Hispanic EPT infants and by 5.8%,5.9%, and 4.8% among Non-Hispanic White, Non-Hispanic Black, and Hispanic LPT infants. However, there were no significant between-group differences in annual changes (EPT:p=0.11; LPT:p=0.25). CONCLUSIONS: Supine sleep positioning increased for all racial/ethnic preterm groups from 2000 to 2015. However, the racial/ethnic disparity in supine sleep positioning among EPT and LPT groups persists.

      3. Impact of the COVID-19 pandemic on mental health, access to care, and health disparities in the perinatal periodexternal icon
        Masters GA, Asipenko E, Bergman AL, Person SD, Brenckle L, Moore Simas TA, Ko JY, Robbins CL, Byatt N.
        J Psychiatr Res. 2021 Mar 1;137:126-130.
        BACKGROUND: The COVID-19 pandemic has affected mental health and created barriers to healthcare. In this study, we sought to elucidate the pandemic's effects on mental health and access to care for perinatal individuals. METHODS: This cross-sectional study of individuals in Massachusetts who were pregnant or up to three months postpartum with a history of depressive symptoms examined associations between demographics and psychiatric symptoms (via validated mental health screening instruments) and the COVID-19 pandemic's effects on mental health and access to care. Chi-square associations and multivariate regression models were used. RESULTS: Of 163 participants, 80.8% perceived increased symptoms of depression and 88.8% of anxiety due to the pandemic. Positive screens for depression, anxiety, and/or PTSD at time of interview, higher education, and income were associated with increased symptoms of depression and anxiety due to the pandemic. Positive screens for depression, anxiety, and/or PTSD were also associated with perceived changes in access to mental healthcare. Compared to non-Hispanic White participants, participants of color (Black, Asian, Multiracial, and/or Hispanic/Latinx) were more likely to report that the pandemic changed their mental healthcare access (aOR:3.25, 95%CI:1.23, 8.59). LIMITATIONS: Limitations included study generalizability, given that participants have a history of depressive symptoms, and cross-sectional design. CONCLUSIONS: The pandemic has increased symptoms of perinatal depression and anxiety and impacted perceived access to care. Self-reported increases in depression and anxiety and changes to healthcare access varied by education, race/ethnicity, income, and positive screens. Understanding these differences is important to address perinatal mental health and provide equitable care.

    • Substance Use and Abuse
      1. Initiation of nonmedical use of prescription opioids among high school studentsexternal icon
        Deputy NP, Lowry R, Clayton HB, Demissie Z, Bohm MK, Conklin S.
        Subst Abus. 2021 Mar 8:1-6.
        Nonmedical use of prescription opioids (NUPO) is associated with heroin use and other adverse outcomes among adolescents. To inform the timing of substance use prevention activities and which substances to target, we examined age at NUPO initiation, associations between substance use initiation and current (past 30-day) NUPO, and order of NUPO initiation relative to other substances. Methods: Data from 2,834 students aged 15 or older participating in the 2017 Virginia Youth Survey, the first Youth Risk Behavior Surveillance System survey to assess age at NUPO initiation and current NUPO, were analyzed in 2019. Students reported current NUPO and ages at initiation for cigarettes, alcohol, marijuana, and NUPO (categorized as 12 or younger, 13 or 14, 15 or older, or never). Associations between age at substance use initiation and current NUPO were examined using adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs). Results: Overall, 12% of students reported lifetime NUPO, with 2.4%, 4.0%, and 5.6% initiating at 12 or younger, 13 or 14, and 15 or older, respectively; 5.3% reported current NUPO. Initiating cigarettes, alcohol, and marijuana at each age category (compared with never) was associated with an increased prevalence of current NUPO after adjusting for demographics and initiation of other substances. Among students initiating NUPO, initiating NUPO at 12 or younger (compared with 15 or older) was associated with an increased prevalence of current NUPO after adjusting for demographics (aPR = 1.54, 95% CI: 1.10-2.16), but not after further adjustment for initiation of other substances (aPR = 1.38, 95% CI = 0.97-1.97). Among students initiating NUPO, 45.4% initiated NUPO before or during the same age as other substances. Conclusions: More than 6% of students initiated NUPO at 14 or younger. Younger substance use initiation was associated with current NUPO, suggesting that some students may benefit from prevention activities during early adolescence that address multiple substances.

      2. Tobacco-specific nitrosamines in the tobacco and mainstream smoke of commercial little cigarsexternal icon
        Edwards SH, Hassink MD, Taylor KM, Watson CH, Kuklenyik P, Kimbrell B, Wang L, Chen P, Valentín-Blasini L.
        Chem Res Toxicol. 2021 Mar 5.
        Cigars are among the broad variety of tobacco products that have not been as extensively studied and characterized as cigarettes. Small cigars wrapped in a tobacco-containing sheet, commonly referred to as little cigars, are a subcategory that are similar to conventional cigarettes with respect to dimensions, filters, and overall appearance. Tobacco-specific nitrosamines (TSNAs) are carcinogens in the tobacco used in both little cigars and cigarettes. This study uses a validated high-performance liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS) method to measure the TSNAs 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) in the tobacco filler and the nonintense International Organization for Standardization smoking regimen, ISO 3308, and the newer ISO 20778 Cigarette Intensive (CI) smoking regimen mainstream smoke of 60 commercial little cigars. Tobacco filler NNK and NNN quantities ranged from 26 to 2950 and 1440 to 12 100 ng/g tobacco, respectively. NNK and NNN by the ISO nonintense smoking regimen ranged from 89 to 879 and 200 to 1540 ng/cigar, respectively; by the CI regimen, NNK and NNN ranged from 138 to 1570 and 445 to 2780 ng/cigar, respectively. The average transfer (%) for NNK and NNN from tobacco filler to mainstream smoke was 24% and 36% by the ISO nonintense and CI smoking regimens, respectively. By the ISO nonintense and CI smoking regimens, mainstream smoke NNK and NNN yields showed a moderate to strong correlation (ISO nonintense, R(2) = 0.60-0.68, p < 0.0001; CI, R(2) = 0.78-0.81, p < 0.0001) with tobacco filler NNK and NNN quantities. In addition, the mainstream smoke NNK and NNN yields of little cigars were determined to be 3- to 5-fold higher compared to previously tested commercial cigarettes. The mainstream smoke NNK and NNN yields have wide variation among commercial little cigars and suggest that, despite design similarities to cigarettes, machine-smoke yields of carcinogenic TSNAs are higher in little cigars.

      3. A rapid-cycle assessment strategy for understanding the opioid overdose epidemic in local communitiesexternal icon
        Taubenberger S, Spencer N, Chang JC, Paul N, Fabre S, Jagessar B, Trimble D, Roberto R, Gill P, Hulsey E, Arnold A, Hacker K.
        Subst Abus. 2021 Mar 9:1-15.
        Certain communities in the United States experience greater opioid-involved overdose mortality than others. Interventions to stem overdose benefit from contextual understandings of communities' needs and strengths in addressing the opioid crisis. This project aims to understand multiple stakeholder perspectives on the opioid epidemic in communities disproportionately affected by opioid-involved overdose mortality. Methods: We performed a rapid-cycle qualitative assessment study utilizing in-depth interviews with community stakeholders and observations of community meetings in eight communities in Allegheny County, Pennsylvania, USA, disproportionately impacted by opioid-involved overdose mortality. Stakeholder categories included: current and past illicit users of opioids; medical and social service providers; emergency medical services; law enforcement; spouse or other family members of illicit users/former users of opioids; government officials; school officials; community members. Content analysis was utilized to identify themes and answer study questions. Regular feedback to stakeholders was provided to support targeted interventions. Results: We performed semi-structured, in-depth interviews with 130 community stakeholders and 29 community meeting observations in 2018-2019. Participants perceived similar economic and social determinants as origins of the opioid overdose epidemic including lack of economic resources, loss of jobs, transient populations and dilapidated housing. However, they differed in their awareness of and attention to the epidemic. Awareness was dependent on the visibility of opioid use (presence of paraphernalia litter, location of drug users, media coverage, and relationship to users). Overall, there was good knowledge of naloxone for opioid overdose reversal but less knowledge about local syringe services programs. Perceptions of harm reduction efforts were ambivalent. Conclusions: Members of communities impacted by the opioid epidemic perceived that economic downturn was a major factor in the opioid overdose epidemic. However, the varied beliefs within and between communities suggest that interventions need to be tailored according to the cultural norms of place.

      4. Cumulative protective factors are associated with decreased risk for prescription opioid misuse among high school studentsexternal icon
        Timpe Z, Clayton HB, Andrzejewski J, Phillips C, Conklin S, Bohm MK.
        J Epidemiol Community Health. 2021 Mar 8.
        BACKGROUND: Multiple protective factors at the individual and environmental levels have been associated with prescription opioid misuse (POM) among adolescents. The literature may benefit by extending this research to consider the association between cumulative protective factors and current (ie, within the past 30 days) POM. METHODS: The 2017 Virginia Youth Survey (part of the Youth Risk Behaviour Surveillance System) (N=3697) was used to investigate recent POM and the presence of individual and cumulative protective factors among high school students. Youth were asked to indicate whether they had engaged POM within the past 30 days. A set of protective factors representing youths' internal assets (eg, aspirational plans for education) and external resources (eg, family meals, safe school environment) were investigated as predictors of current POM, followed by testing of a cumulative protective factor score. Logistic regression models estimated ORs and 95% CIs. RESULTS: When including demographics and risk factors in the model, none of the individual protective factors were significantly associated with current POM. Alternatively, the cumulative protective factor score was significantly associated with a decrease in the odds of current POM. CONCLUSIONS: The cumulative protective factor score was significantly associated with a decrease in the odds of current POM among high school students in Virginia. Programmes designed to provide multiple forms of support may be effective strategies for preventing current POM.

    • Zoonotic and Vectorborne Diseases
      1. Sporadic outbreaks of Crimean-Congo haemorrhagic fever in Uganda, July 2018-January 2019external icon
        Mirembe BB, Musewa A, Kadobera D, Kisaakye E, Birungi D, Eurien D, Nyakarahuka L, Balinandi S, Tumusiime A, Kyondo J, Mulei SM, Baluku J, Kwesiga B, Kabwama SN, Zhu BP, Harris JR, Lutwama JJ, Ario AR.
        PLoS Negl Trop Dis. 2021 Mar 8;15(3):e0009213.
        INTRODUCTION: Crimean-Congo haemorrhagic fever (CCHF) is a tick-borne, zoonotic viral disease that causes haemorrhagic symptoms. Despite having eight confirmed outbreaks between 2013 and 2017, all within Uganda's 'cattle corridor', no targeted tick control programs exist in Uganda to prevent disease. During a seven-month-period from July 2018-January 2019, the Ministry of Health confirmed multiple independent CCHF outbreaks. We investigated to identify risk factors and recommend interventions to prevent future outbreaks. METHODS: We defined a confirmed case as sudden onset of fever (≥37.5°C) with ≥4 of the following signs and symptoms: anorexia, vomiting, diarrhoea, headache, abdominal pain, joint pain, or sudden unexplained bleeding in a resident of the affected districts who tested positive for Crimean-Congo haemorrhagic fever virus (CCHFv) by RT-PCR from 1 July 2018-30 January 2019. We reviewed medical records and performed active case-finding. We conducted a case-control study and compared exposures of case-patients with age-, sex-, and sub-county-matched control-persons (1:4). RESULTS: We identified 14 confirmed cases (64% males) with five deaths (case-fatality rate: 36%) from 11 districts in western and central region. Of these, eight (73%) case-patients resided in Uganda's 'cattle corridor'. One outbreak involved two case-patients and the remainder involved one. All case-patients had fever and 93% had unexplained bleeding. Case-patients were aged 6-36 years, with persons aged 20-44 years more affected (AR: 7.2/1,000,000) than persons ≤19 years (2.0/1,000,000), p = 0.015. Most (93%) case-patients had contact with livestock ≤2 weeks before symptom onset. Twelve (86%) lived <1 km from grazing fields compared with 27 (48%) controls (ORM-H = 18, 95% CI = 3.2-∞) and 10 (71%) of 14 case-patients found ticks attached to their bodies ≤2 weeks before symptom onset, compared to 15 (27%) of 56 control-persons (ORM-H = 9.3, 95%CI = 1.9-46). CONCLUSIONS: CCHF outbreaks occurred sporadically during 2018-2019, both within and outside 'cattle corridor' districts of Uganda. Most cases were associated with tick exposure. The Ministry of Health should partner with the Ministry of Agriculture, Animal Industry and Fisheries to develop joint nationwide tick control programs and strategies with shared responsibilities through a One Health approach.

      2. Traveller exposures to animals: A GeoSentinel analysisexternal icon
        Muehlenbein MP, Angelo KM, Schlagenhauf P, Chen L, Grobusch MP, Gautret P, Duvignaud A, Chappuis F, Kain KC, Bottieau E, Epelboin L, Shaw M, Hynes N, Hamer DH.
        J Travel Med. 2020 Nov 9;27(7).
        BACKGROUND: Human coexistence with other animals can result in both intentional and unintentional contact with a variety of mammalian and non-mammalian species. International travellers are at risk for such encounters; travellers risk injury, infection and possibly death from domestic and wild animal bites, scratches, licks and other exposures. The aim of the present analysis was to understand the diversity and distribution of animal-related exposures among international travellers. METHODS: Data from January 2007 through December 2018 from the GeoSentinel Surveillance Network were reviewed. Records were included if the exposure was non-migration travel with a diagnosis of an animal (dog, cat, monkey, snake or other) bite or other exposure (non-bite); records were excluded if the region of exposure was not ascertainable or if another, unrelated acute diagnosis was reported. RESULTS: A total of 6470 animal exposures (bite or non-bite) were included. The majority (71%) occurred in Asia. Travellers to 167 countries had at least one report of an animal bite or non-bite exposure. The majority (76%) involved dogs, monkeys and cats, although a wide range of wild and domestic species were involved. Almost two-thirds (62.6%) of 4395 travellers with information available did not report a pretravel consultation with a healthcare provider. CONCLUSIONS: Minimizing bites and other animal exposures requires education (particularly during pretravel consultations) and behavioral modification. These should be supplemented by the use of pre-exposure rabies vaccination for travellers to high-risk countries (especially to those with limited access to rabies immunoglobulin), as well as encouragement of timely (in-country) post-exposure prophylaxis for rabies and Macacine alphaherpesvirus 1 (herpesvirus B) when warranted.

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DISCLAIMER: Articles listed in the CDC Science Clips are selected by the Stephen B. Thacker CDC Library to provide current awareness of the public health literature. An article's inclusion does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.

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