Vital Signs: Drug Overdose Deaths, by Selected Sociodemographic and Social Determinants of Health Characteristics - 25 States and the District of Columbia, 2019-2020.

INTRODUCTION: Drug overdose deaths increased approximately 30% from 2019 to 2020 in the United States. Examining rates by demographic and social determinants of health characteristics can identify disproportionately affected populations and inform strategies to reduce drug overdose deaths. METHODS: Data from the State Unintentional Drug Overdose Reporting System (SUDORS) were used to analyze overdose death rates from 2019 to 2020 in 25 states and the District of Columbia. Rates were examined by race and ethnicity and county-level social determinants of health (e.g., income inequality and treatment provider availability). RESULTS: From 2019 to 2020, drug overdose death rates increased by 44% and 39% among non-Hispanic Black (Black) and non-Hispanic American Indian or Alaska Native (AI/AN) persons, respectively. Significant disparities were found across sex, age, and racial and ethnic subgroups. In particular, the rate in 2020 among Black males aged ≥65 years (52.6 per 100,000) was nearly seven times that of non-Hispanic White males aged ≥65 years (7.7). A history of substance use was frequently reported. Evidence of previous substance use treatment was lowest for Black persons (8.3%). Disparities in overdose deaths, particularly among Black persons, were larger in counties with greater income inequality. Opioid overdose rates in 2020 were higher in areas with more opioid treatment program availability compared with areas with lower opioid treatment availability, particularly among Black (34.3 versus 16.6) and AI/AN (33.4 versus 16.2) persons. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Health disparities in overdose rates continue to worsen, particularly among Black and AI/AN persons; social determinants of health, such as income inequality, exacerbate these inequities. Implementation of available, evidence-based, culturally responsive overdose prevention and response efforts that address health disparities impacting disproportionately affected populations are urgently needed.

Drug Overdose Deaths Among Persons Aged 10-19 Years - United States, July 2019-December 2021.

U.S. drug overdose deaths increased 30% from 2019 to 2020 and 15% in 2021, resulting in an estimated 108,000 deaths in 2021.* Among persons aged 14-18 years, overdose deaths increased 94% from 2019 to 2020 and 20% from 2020 to 2021 (1), although illicit drug use declined overall among surveyed middle and high school students during 2019-2020 (2). Widespread availability of illicitly manufactured fentanyls (IMFs),† proliferation of counterfeit pills resembling prescription drugs but containing IMFs or other illicit drugs,§ and ease of purchasing pills through social media¶ have increased fatal overdose risk among adolescents (1,3). Using CDC's State Unintentional Drug Overdose Reporting System (SUDORS), this report describes trends and characteristics of overdose deaths during July 2019-December 2021 among persons aged 10-19 years (hereafter referred to as adolescents). From July-December 2019 to July-December 2021, median monthly overdose deaths increased 109%, and deaths involving IMFs increased 182%. Approximately 90% of overdose deaths involved opioids, and 83.9% involved IMFs; however, only 35% of decedents had documented opioid use history. Counterfeit pill evidence was present in 24.5% of overdose deaths, and 40.9% of decedents had evidence of mental health conditions or treatment. To prevent overdose deaths among adolescents, urgent efforts are needed, including preventing substance use initiation, strengthening partnerships between public health and public safety to reduce availability of illicit drugs, expanding efforts focused on resilience and connectedness of adolescents to prevent substance misuse and related harms, increasing education regarding IMFs and counterfeit pills, expanding naloxone training and access, and ensuring access to treatment for substance use and mental health disorders.

Trends in and Characteristics of Drug Overdose Deaths Involving Illicitly Manufactured Fentanyls - United States, 2019-2020.

During May 2020-April 2021, the estimated number of drug overdose deaths in the United States exceeded 100,000 over a 12-month period for the first time, with 64.0% of deaths involving synthetic opioids other than methadone (mainly illicitly manufactured fentanyls [IMFs], which include both fentanyl and illicit fentanyl analogs).* Introduced primarily as adulterants in or replacements for white powder heroin east of the Mississippi River (1), IMFs are now widespread in white powder heroin markets, increasingly pressed into counterfeit pills resembling oxycodone, alprazolam, or other prescription drugs, and are expanding into new markets, including in the western United States† (2). This report describes trends in overdose deaths involving IMFs (IMF-involved deaths) during July 2019-December 2020 (29 states and the District of Columbia [DC]), and characteristics of IMF-involved deaths during 2020 (39 states and DC) using data from CDC's State Unintentional Drug Overdose Reporting System (SUDORS). During July 2019-December 2020, IMF-involved deaths increased sharply in midwestern (33.1%), southern (64.7%), and western (93.9%) jurisdictions participating in SUDORS. Approximately four in 10 IMF-involved deaths also involved a stimulant. Highlighting the need for timely overdose response, 56.1% of decedents had no pulse when first responders arrived. Injection drug use was the most frequently reported individual route of drug use (24.5%), but evidence of snorting, smoking, or ingestion, but not injection drug use was found among 27.1% of decedents. Adapting and expanding overdose prevention, harm reduction, and response efforts is urgently needed to address the high potency (3), and various routes of use for IMFs. Enhanced treatment for substance use disorders is also needed to address the increased risk for overdose (4) and treatment complications (5) associated with using IMFs with stimulants.

Trends and Geographic Patterns in Drug and Synthetic Opioid Overdose Deaths - United States, 2013-2019.

Deaths involving synthetic opioids other than methadone (synthetic opioids), which largely consist of illicitly manufactured fentanyl; psychostimulants with abuse potential (e.g., methamphetamine); and cocaine have increased in recent years, particularly since 2013 (1,2). In 2019, a total of 70,630 drug overdose deaths occurred, corresponding to an age-adjusted rate of 21.6 per 100,000 population and a 4.3% increase from the 2018 rate (20.7) (3). CDC analyzed trends in age-adjusted overdose death rates involving synthetic opioids, psychostimulants, cocaine, heroin, and prescription opioids during 2013-2019, as well as geographic patterns in synthetic opioid- and psychostimulant-involved deaths during 2018-2019. From 2013 to 2019, the synthetic opioid-involved death rate increased 1,040%, from 1.0 to 11.4 per 100,000 age-adjusted (3,105 to 36,359). The psychostimulant-involved death rate increased 317%, from 1.2 (3,627) in 2013 to 5.0 (16,167) in 2019. In the presence of synthetic opioid coinvolvement, death rates for prescription opioids, heroin, psychostimulants, and cocaine increased. In the absence of synthetic opioid coinvolvement, death rates increased only for psychostimulants and cocaine. From 2018 to 2019, the largest relative increase in the synthetic opioid-involved death rate occurred in the West (67.9%), and the largest relative increase in the psychostimulant-involved death rate occurred in the Northeast (43.8%); these increases represent important changes in the geographic distribution of drug overdose deaths. Evidence-based prevention and response strategies including substance use disorder treatment and overdose prevention and response efforts focused on polysubstance use must be adapted to address the evolving drug overdose epidemic.

Pregnant? Validity of the pregnancy checkbox on death certificates in four states, and characteristics associated with pregnancy checkbox errors.

BACKGROUND: Maternal mortality rates in the United States appear to be increasing. One potential reason may be increased identification of maternal deaths after the addition of a pregnancy checkbox to the death certificate. In 2016, 4 state health departments (Georgia, Louisiana, Michigan, and Ohio) implemented a pregnancy checkbox quality assurance pilot, with technical assistance provided by the Centers for Disease Control and Prevention. The pilot aimed to improve accuracy of the pregnancy checkbox on death certificates and resultant state maternal mortality estimates. OBJECTIVE: To estimate the validity of the pregnancy checkbox on the death certificate, and to describe characteristics associated with errors using 2016 data from a 4-state quality assurance pilot. MATERIALS AND METHODS: Potential pregnancy-associated deaths were identified by linking death certificates with birth or fetal death certificates from within 1 year preceding death or by pregnancy checkbox status. Death certificates that indicated that the decedent was pregnant within 1 year of death via the pregnancy checkbox, but that did not link to a birth or fetal death certificate, were referred for active follow-up to confirm pregnancy status by either death certifier confirmation or medical record review. Descriptive statistics and 95% confidence intervals were used to examine the distributions of demographic characteristics by pregnancy confirmation category (confirmed pregnant, confirmed not pregnant, and unable to confirm). We compared the proportion confirmed pregnant and confirmed not pregnant within age, race/ethnicity, pregnancy checkbox category, and certifier type categories using a Wald test of proportions. Binomial and Poisson regression models were used to estimate prevalence ratios for having an incorrect pregnancy checkbox (false positive, false negative) by age group, race/ethnicity, pregnancy checkbox category, and certifier type. RESULTS: Among 467 potential pregnancy-associated deaths, 335 (72%) were confirmed pregnant via linkage to a birth or fetal death certificate, certifier confirmation, or review of medical records. A total of 97 women (21%) were confirmed not pregnant (false positives) and 35 (7%) were unable to be confirmed. Women confirmed pregnant were significantly younger than women confirmed not pregnant (P < .001). Deaths certified by coroners and medical examiners were more likely to be confirmed pregnant than confirmed not pregnant (P = .04). The association between decedent age category and false-positive status followed a dose-response relationship (P < .001), with increasing prevalence ratios for each increase in age category. Death certificates of non-Hispanic black women were more likely to be false positive, compared with non-Hispanic white women (prevalence ratio, 1.41; 95% confidence interval, 1.01, 1.96). The sensitivity of the pregnancy checkbox among these 4 states in 2016 was 62% and the positive predictive value was 68%. CONCLUSION: We provide a multi-state analysis of the validity of the pregnancy checkbox and highlight a need for more accurate reporting of pregnancy status on death certificates. States and other jurisdictions may increase the accuracy of their data used to calculate maternal mortality rates by implementing quality assurance processes.

Drug and Opioid-Involved Overdose Deaths - United States, 2017-2018.

Of the 70,237 drug overdose deaths in the United States in 2017, approximately two thirds (47,600) involved an opioid (1). In recent years, increases in opioid-involved overdose deaths have been driven primarily by deaths involving synthetic opioids other than methadone (hereafter referred to as synthetic opioids) (1). CDC analyzed changes in age-adjusted death rates from 2017 to 2018 involving all opioids and opioid subcategories* by demographic characteristics, county urbanization levels, U.S. Census region, and state. During 2018, a total of 67,367 drug overdose deaths occurred in the United States, a 4.1% decline from 2017; 46,802 (69.5%) involved an opioid (2). From 2017 to 2018, deaths involving all opioids, prescription opioids, and heroin decreased 2%, 13.5%, and 4.1%, respectively. However, deaths involving synthetic opioids increased 10%, likely driven by illicitly manufactured fentanyl (IMF), including fentanyl analogs (1,3). Efforts related to all opioids, particularly deaths involving synthetic opioids, should be strengthened to sustain and accelerate declines in opioid-involved deaths. Comprehensive surveillance and prevention measures are critical to reducing opioid-involved deaths, including continued surveillance of evolving drug use and overdose, polysubstance use, and the changing illicit drug market; naloxone distribution and outreach to groups at risk for IMF exposure; linkage to evidence-based treatment for persons with substance use disorders; and continued partnerships with public safety.

Vital Signs: Characteristics of Drug Overdose Deaths Involving Opioids and Stimulants - 24 States and the District of Columbia, January-June 2019.

INTRODUCTION: Provisional estimates indicate that drug overdose deaths increased in 2019 after a slight decrease in 2018. In 2018, overdose deaths primarily involved opioids, with continued increases in deaths involving illicitly manufactured fentanyls (IMFs). Deaths involving stimulants such as cocaine and methamphetamine are also increasing, mainly in combination with opioids. METHODS: CDC analyzed data on drug overdose deaths during January-June 2019 from 24 states and the District of Columbia (DC) in the State Unintentional Drug Overdose Reporting System to describe characteristics and circumstances of opioid- and stimulant-involved overdose deaths. RESULTS: Among 16,236 drug overdose deaths in 24 states and DC, 7,936 (48.9%) involved opioids without stimulants, 5,301 (32.6%) involved opioids and stimulants, 2,056 (12.7%) involved stimulants without opioids, and 943 (5.8%) involved neither opioids nor stimulants. Approximately 80% of overdose deaths involved one or more opioid, and IMFs were involved in three of four opioid-involved overdose deaths. IMFs, heroin, cocaine, or methamphetamine (alone or in combination) were involved in 83.8% of overdose deaths. More than three in five (62.7%) overdose deaths had documentation of at least one potential opportunity for overdose prevention intervention. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Identifying opportunities to intervene before an overdose death and implementing evidence-based prevention policies, programs, and practices could save lives. Strategies should address characteristics of overdoses involving IMFs, such as rapid overdose progression, as well as opioid and stimulant co-involvement. These efforts should be complemented by efforts to prevent initiation of prescription opioid and stimulant misuse and illicit drug use.

Prescription of Antibacterial Drugs for HIV-Exposed, Uninfected Infants, Malawi, 2004-2010.

Antimicrobial drug resistance is a serious health hazard driven by overuse. Administration of antimicrobial drugs to HIV-exposed, uninfected infants, a population that is growing and at high risk for infection, is poorly studied. We therefore analyzed factors associated with antibacterial drug administration to HIV-exposed, uninfected infants during their first year of life. Our study population was 2,152 HIV-exposed, uninfected infants enrolled in the Breastfeeding, Antiretrovirals and Nutrition study in Lilongwe, Malawi, during 2004-2010. All infants were breastfed through 28 weeks of age. Antibacterial drugs were prescribed frequently (to 80% of infants), and most (67%) of the 5,329 prescriptions were for respiratory indications. Most commonly prescribed were penicillins (43%) and sulfonamides (23%). Factors associated with lower hazard for antibacterial drug prescription included receipt of cotrimoxazole preventive therapy, receipt of antiretroviral drugs, and increased age. Thus, cotrimoxazole preventive therapy may lead to fewer prescriptions for antibacterial drugs for these infants.

Changing the conversation: applying a health equity framework to maternal mortality reviews.

The risk of maternal death in the United States is higher than peer nations and is rising and varies dramatically by the race and place of residence of the woman. Critical efforts to reduce maternal mortality include patient risk stratification and system-level quality improvement efforts targeting specific aspects of clinical care. These efforts are important for addressing the causes of an individual's risk, but research to date suggests that individual risk factors alone do not adequately explain between-group disparities in pregnancy-related death by race, ethnicity, or geography. The holistic review and multidisciplinary makeup of maternal mortality review committees make them well positioned to fill knowledge gaps about the drivers of racial and geographic inequity in maternal death. However, committees may lack the conceptual framework, contextual data, and evidence base needed to identify community-based contributing factors to death and, when appropriate, to make recommendations for future action. By incorporating a multileveled, theory-grounded framework for causes of health inequity, along with indicators of the community vital signs, the social and community context in which women live, work, and seek health care, maternal mortality review committees may identify novel underlying factors at the community level that enhance understanding of racial and geographic inequity in maternal mortality. By considering evidence-informed community and regional resources and policies for addressing these factors, novel prevention recommendations, including recommendations that extend outside the realm of the formal health care system, may emerge.

Racial/Ethnic Disparities in Pregnancy-Related Deaths - United States, 2007-2016.

Approximately 700 women die in the United States each year as a result of pregnancy or its complications, and significant racial/ethnic disparities in pregnancy-related mortality exist (1). Data from CDC's Pregnancy Mortality Surveillance System (PMSS) for 2007-2016 were analyzed. Pregnancy-related mortality ratios (PRMRs) (i.e., pregnancy-related deaths per 100,000 live births) were analyzed by demographic characteristics and state PRMR tertiles (i.e., states with lowest, middle, and highest PRMR); cause-specific proportionate mortality by race/ethnicity also was calculated. Over the period analyzed, the U.S. overall PRMR was 16.7 pregnancy-related deaths per 100,000 births. Non-Hispanic black (black) and non-Hispanic American Indian/Alaska Native (AI/AN) women experienced higher PRMRs (40.8 and 29.7, respectively) than did all other racial/ethnic groups. This disparity persisted over time and across age groups. The PRMR for black and AI/AN women aged ≥30 years was approximately four to five times that for their white counterparts. PRMRs for black and AI/AN women with at least some college education were higher than those for all other racial/ethnic groups with less than a high school diploma. Among state PRMR tertiles, the PRMRs for black and AI/AN women were 2.8-3.3 and 1.7-3.3 times as high, respectively, as those for non-Hispanic white (white) women. Significant differences in cause-specific proportionate mortality were observed among racial/ethnic populations. Strategies to address racial/ethnic disparities in pregnancy-related deaths, including improving women's health and access to quality care in the preconception, pregnancy, and postpartum periods, can be implemented through coordination at the community, health facility, patient, provider, and system levels.

Vital Signs: Pregnancy-Related Deaths, United States, 2011-2015, and Strategies for Prevention, 13 States, 2013-2017.

BACKGROUND: Approximately 700 women die from pregnancy-related complications in the United States every year. METHODS: Data from CDC's national Pregnancy Mortality Surveillance System (PMSS) for 2011-2015 were analyzed. Pregnancy-related mortality ratios (pregnancy-related deaths per 100,000 live births; PRMRs) were calculated overall and by sociodemographic characteristics. The distribution of pregnancy-related deaths by timing relative to the end of pregnancy and leading causes of death were calculated. Detailed data on pregnancy-related deaths during 2013-2017 from 13 state maternal mortality review committees (MMRCs) were analyzed for preventability, factors that contributed to pregnancy-related deaths, and MMRC-identified prevention strategies to address contributing factors. RESULTS: For 2011-2015, the national PRMR was 17.2 per 100,000 live births. Non-Hispanic black (black) women and American Indian/Alaska Native women had the highest PRMRs (42.8 and 32.5, respectively), 3.3 and 2.5 times as high, respectively, as the PRMR for non-Hispanic white (white) women (13.0). Timing of death was known for 87.7% (2,990) of pregnancy-related deaths. Among these deaths, 31.3% occurred during pregnancy, 16.9% on the day of delivery, 18.6% 1-6 days postpartum, 21.4% 7-42 days postpartum, and 11.7% 43-365 days postpartum. Leading causes of death included cardiovascular conditions, infection, and hemorrhage, and varied by timing. Approximately sixty percent of pregnancy-related deaths from state MMRCs were determined to be preventable and did not differ significantly by race/ethnicity or timing of death. MMRC data indicated that multiple factors contributed to pregnancy-related deaths. Contributing factors and prevention strategies can be categorized at the community, health facility, patient, provider, and system levels and include improving access to, and coordination and delivery of, quality care. CONCLUSIONS: Pregnancy-related deaths occurred during pregnancy, around the time of delivery, and up to 1 year postpartum; leading causes varied by timing of death. Approximately three in five pregnancy-related deaths were preventable. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Strategies to address contributing factors to pregnancy-related deaths can be enacted at the community, health facility, patient, provider, and system levels.

Prevalence, Magnitude, and Correlates of HIV-1 Genital Shedding in Women on Antiretroviral Therapy.

Background: Genital human immunodeficiency virus (HIV) RNA shedding can continue despite HIV being undetectable in blood, and can be associated with transmission. Methods: We included African women on antiretroviral therapy (ART). Linear and generalized linear mixed models were used to compare the magnitude and prevalence of genital shedding, respectively, by time since ART initiation. Multivariable logistic regression with generalized estimating equations was used to assess predictors of genital shedding among women with undetectable plasma viral load (VL). Results: Among 1114 women, 5.8% of visits with undetectable plasma VL and 23.6% of visits with detectable VL had genital shedding. The proportion of visits with genital shedding decreased with time since ART initiation but the magnitude of shedding remained unchanged when plasma VL was undetectable (P = .032). Prevalence of shedding did not vary by time since ART initiation when plasma VL was detectable (P = .195), though the magnitude of shedding significantly increased (P = .04). Predictors of genital shedding were HIV disease stage, antiretroviral regimen, and genital ulcers or cervical tenderness. Discussion: In addition to ART, reducing immune activation through prevention and treatment of HIV-related conditions and genital tract infections may decrease the risk of HIV-1 shedding and potential transmission.

Co-trimoxazole Prophylaxis, Asymptomatic Malaria Parasitemia, and Infectious Morbidity in Human Immunodeficiency Virus-Exposed, Uninfected Infants in Malawi: The BAN Study.

Background: Human immunodeficiency virus (HIV)-exposed infants are disproportionately at risk of morbidity and mortality compared with their HIV-unexposed counterparts. The role of co-trimoxazole preventive therapy (CPT) in reducing leading causes of infectious morbidity is unclear. Methods: We used data from the Breastfeeding, Antiretrovirals and Nutrition (BAN) clinical trial (conducted 2004-2010, Malawi) to assess the association of (1) CPT and (2) asymptomatic malaria parasitemia with respiratory and diarrheal morbidity in infants. In June 2006, all HIV-exposed infants in BAN began receiving CPT (240 mg) from 6 to 36 weeks of age, or until weaning occurred and HIV infection was ruled out. All HIV-exposed, uninfected infants (HEIs) at 8 weeks of age (n = 1984) were included when CPT was the exposure. A subset of HEIs (n = 471) were tested for malarial parasitemia using dried blood spots from 12, 24, and 36 weeks of age. Cox proportional hazards models for recurrent gap-time data were used to examine the association of time-varying exposures on morbidity. Results: CPT was associated with a 36% reduction in respiratory morbidity (hazard ratio [HR], 0.64 [95% confidence interval {CI}, .60-.69]) and a 41% reduction in diarrheal morbidity (HR, 0.59 [95% CI, .54-.65]). Having asymptomatic malaria parasitemia was associated with a 40% increase in respiratory morbidity (HR, 1.40 [95% CI, 1.13-1.74]) and a 50% increase in diarrheal morbidity (HR, 1.50 [95% CI, 1.09-2.06]), after adjusting for CPT. Conclusions: CPT may have an important role to play in reducing the leading global causes of morbidity and mortality in the growing population of HEIs in malaria-endemic resource-limited settings.

Contribution of maternal age and pregnancy checkbox on maternal mortality ratios in the United States, 1978-2012.

BACKGROUND: Maternal mortality ratios (MMR) appear to have increased in the United States over the last decade. Three potential contributing factors are (1) a shifting maternal age distribution, (2) changes in age-specific MMR, and (3) the addition of a checkbox indicating recent pregnancy on the death certificate. OBJECTIVE: To determine the contribution of increasing maternal age on changes in MMR from 1978 to 2012 and estimate the contribution of the pregnancy checkbox on increases in MMR over the last decade. STUDY DESIGN: Kitagawa decomposition analyses were conducted to partition the maternal age contribution to the MMR increase into 2 components: changes due to a shifting maternal age distribution and changes due to greater age-specific mortality ratios. We used National Vital Statistics System natality and mortality data. The following 5-year groupings were used: 1978-1982, 1988-1992, 1998-2002, and 2008-2012. Changes in age-specific MMRs among states that adopted the standard pregnancy checkbox onto their death certificate before 2008 (n = 23) were compared with states that had not adopted the standard pregnancy checkbox on their death certificate by the end of 2012 (n = 11) to estimate the percentage increase in the MMR due to the pregnancy checkbox. RESULTS: Overall US MMRs for 1978-1982, 1988-1992, and 1998-2002 were 9.0, 8.1, and 9.1 deaths per 100,000 live births, respectively. There was a modest increase in the MMR between 1998-2002 and 2008-2012 in the 11 states that had not adopted the standard pregnancy checkbox on their death certificate by the end of 2012 (8.6 and 9.9 deaths per 100,000, respectively). However, the MMR more than doubled between 1998-2002 and 2008-2012 in the 23 states that adopted the standard pregnancy checkbox (9.0-22.4); this dramatic increase was almost entirely attributable to increases in age-specific MMRs (94.9%) as opposed to increases in maternal age (5.1%), with an estimated 90% of the observed change reflecting the change in maternal death identification rather than a real change in age-specific rates alone. Of all age categories, women ages 40 and older in states that adopted the standard pregnancy checkbox had the largest increase in MMR-from 31.9 to 200.5-a relative increase of 528%, which accounted for nearly one third of the overall increase. An estimated 28.8% of the observed change was potentially due to maternal death misclassification among women ≥40 years. CONCLUSION: Increasing age-specific maternal mortality seems to be contributing more heavily than a changing maternal age distribution to recent increases in MMR. In states with the standard pregnancy checkbox, the vast majority of the observed change in MMR over the last decade was estimated to be due to the pregnancy checkbox, with the greatest change in MMR occurring in women ages ≥40 years. The addition of a pregnancy checkbox on state death certificates appears to be increasing case identification but also may be leading to maternal death misclassification, particularly for women ages ≥40 years.

Perinatal regionalization: a geospatial view of perinatal critical care, United States, 2010-2013.

BACKGROUND: Perinatal services exist today as a dyad of maternal and neonatal care. When perinatal care is fragmented or unavailable, excess morbidity and mortality may occur in pregnant women and newborns. OBJECTIVE: The objective of the study was to describe spatial relationships between women of reproductive age, individual perinatal subspecialists (maternal-fetal medicine and neonatology), and obstetric and neonatal critical care facilities in the United States to identify gaps in health care access. STUDY DESIGN: We used geographic visualization and conducted surface interpolation, nearest neighbor, and proximity analyses. Source data included 2010 US Census, October 2013 National Provider Index, 2012 American Hospital Association, 2012 National Center for Health Statistics Natality File, and the 2011 American Academy of Pediatrics directory. RESULTS: In October 2013, there were 2.5 neonatologists for every maternal-fetal medicine specialist in the United States. In 2012 there were 1.4 level III or higher neonatal intensive care units for every level III obstetric unit (hereafter, obstetric critical care unit). Nationally, 87% of women of reproductive age live within 50 miles of both an obstetric critical care unit and a neonatal intensive care unit. However, 18% of obstetric critical care units had no neonatal intensive care unit, and 20% of neonatal intensive care units had no obstetric critical care unit within a 10 mile radius. Additionally, 26% of obstetric critical care units had no maternal-fetal medicine specialist practicing within 10 miles of the facility, and 4% of neonatal intensive care units had no neonatologist practicing within 10 miles. CONCLUSION: Gaps in access and discordance between the availability of level III or higher obstetric and neonatal care may affect the delivery of risk-appropriate care for high-risk maternal fetal dyads. Further study is needed to understand the importance of these gaps and discordance on maternal and neonatal outcomes.

Impact of daily cotrimoxazole on clinical malaria and asymptomatic parasitemias in HIV-exposed, uninfected infants.

BACKGROUND: Cotrimoxazole preventive therapy (CPT) is recommended for all human immunodeficiency virus (HIV)-exposed infants to avoid opportunistic infections. Cotrimoxazole has antimalarial effects and appears to reduce clinical malaria infections, but the impact on asymptomatic malaria infections is unknown. METHODS: We conducted an observational cohort study using data and dried blood spots (DBSs) from the Breastfeeding, Antiretrovirals and Nutrition study to evaluate the impact of CPT on malaria infection during peak malaria season in Lilongwe, Malawi. We compared malaria incidence 1 year before and after CPT implementation (292 and 682 CPT-unexposed and CPT-exposed infants, respectively), including only infants who remained HIV negative by 36 weeks of age. Malaria was defined as clinical, asymptomatic (using DBSs at 12, 24, and 36 weeks), or a composite outcome of clinical or asymptomatic. Linear and binomial regression with generalized estimating equations were used to estimate the association between CPT and malaria. Differences in characteristics of parasitemias and drug resistance polymorphisms by CPT status were also assessed in the asymptomatic infections. RESULTS: CPT was associated with a 70% (95% confidence interval, 53%-81%) relative reduction in the risk of asymptomatic infection between 6 and 36 weeks of age. CPT appeared to provide temporary protection against clinical malaria and more sustained protection against asymptomatic infections, with no difference in parasitemia characteristics. CONCLUSIONS: CPT appears to reduce overall malaria infections, with more prolonged impacts on asymptomatic infections. Asymptomatic infections are potentially important reservoirs for malaria transmission. Therefore, CPT prophylaxis may have important individual and public health benefits.

Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women.

BACKGROUND: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. OBJECTIVE: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. METHODS: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor-based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. RESULTS: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. CONCLUSION: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736.

Development of a severity of illness scoring system (inpatient triage, assessment and treatment) for resource-constrained hospitals in developing countries.

OBJECTIVE: To develop a new paediatric illness severity score, called inpatient triage, assessment and treatment (ITAT), for resource-limited settings to identify hospitalised patients at highest risk of death and facilitate urgent clinical re-evaluation. METHODS: We performed a nested case-control study at a Malawian referral hospital. The ITAT score was derived from four equally weighted variables, yielding a cumulative score between 0 and 8. Variables included oxygen saturation, temperature, and age-adjusted heart and respiratory rates. We compared the ITAT score between cases (deaths) and controls (discharges) in predicting death within 2 days. Our analysis includes predictive statistics, bivariable and multivariable logistic regression, and calculation of data-driven scores. RESULTS: A total of 54 cases and 161 controls were included in the analysis. The area under the receiver operating characteristic curve was 0.76. At an ITAT cut-off of 4, the sensitivity, specificity and likelihood ratio were 0.44, 0.86 and 1.70, respectively. A cumulative ITAT score of 4 or higher was associated with increased odds of death (OR 4.80; 95% CI 2.39-9.64). A score of 2 for all individual vital signs was a statistically significant independent predictor of death. CONCLUSIONS: We developed an inpatient triage tool (ITAT) appropriate for resource-constrained hospitals that identifies high-risk children after hospital admission. Further research is needed to study how best to operationalise ITAT in developing countries.

Trends and Characteristics of Buprenorphine-Involved Overdose Deaths Prior to and During the COVID-19 Pandemic.

Importance: Buprenorphine remains underused in treating opioid use disorder, despite its effectiveness. During the onset of the COVID-19 pandemic, the US government implemented prescribing flexibilities to support continued access. Objective: To determine whether buprenorphine-involved overdose deaths changed after implementing these policy changes and highlight characteristics and circumstances of these deaths. Design, Setting, and Participants: This cross-sectional study used data from the State Unintentional Drug Overdose Reporting System (SUDORS) to assess overdose deaths in 46 states and the District of Columbia occurring July 2019 to June 2021. Data were analyzed from March 7, 2022, to June 30, 2022. Main Outcomes and Measures: Buprenorphine-involved and other opioid-involved overdose deaths were examined. Monthly opioid-involved overdose deaths and the percentage involving buprenorphine were computed to assess trends. Proportions and exact 95% CIs of drug coinvolvement, demographics, and circumstances were calculated by group. Results: During July 2019 to June 2021, 32 jurisdictions reported 89 111 total overdose deaths and 74 474 opioid-involved overdose deaths, including 1955 buprenorphine-involved overdose deaths, accounting for 2.2% of all drug overdose deaths and 2.6% of opioid-involved overdose deaths. Median (IQR) age was similar for buprenorphine-involved overdose deaths (41 [34-55] years) and other opioid-involved overdose deaths (40 [31-52] years). A higher proportion of buprenorphine-involved overdose decedents, compared with other opioid-involved decedents, were female (36.1% [95% CI, 34.2%-38.2%] vs 29.1% [95% CI, 28.8%-29.4%]), non-Hispanic White (86.1% [95% CI, 84.6%-87.6%] vs 69.4% [95% CI, 69.1%-69.7%]), and residing in rural areas (20.8% [95% CI, 19.1%-22.5%] vs 11.4% [95% CI, 11.2%-11.7%]). Although monthly opioid-involved overdose deaths increased, the proportion involving buprenorphine fluctuated but did not increase during July 2019 to June 2021. Nearly all (92.7% [95% CI, 91.5%-93.7%]) buprenorphine-involved overdose deaths involved at least 1 other drug; higher proportions involved other prescription medications compared with other opioid-involved overdose deaths (eg, anticonvulsants: 18.6% [95% CI, 17.0%-20.3%] vs 5.4% [95% CI, 5.2%-5.5%]) and a lower proportion involved illicitly manufactured fentanyls (50.2% [95% CI, 48.1%-52.3%] vs 85.3% [95% CI, 85.1%-85.5%]). Buprenorphine decedents were more likely to be receiving mental health treatment than other opioid-involved overdose decedents (31.4% [95% CI, 29.3%-33.5%] vs 13.3% [95% CI, 13.1%-13.6%]). Conclusions and Relevance: The findings of this cross-sectional study suggest that actions to facilitate access to buprenorphine-based treatment for opioid use disorder during the COVID-19 pandemic were not associated with an increased proportion of overdose deaths involving buprenorphine. Efforts are needed to expand more equitable and culturally competent access to and provision of buprenorphine-based treatment.

Influence of Hormonal Contraceptive Use and HIV on Cervicovaginal Cytokines and Microbiota in Malawi.

Important questions remain on how hormonal contraceptives alter the local immune environment and the microbiota in the female genital tract and how such effects may impact susceptibility to HIV infection. We leveraged samples from a previously conducted clinical trial of Malawian women with (n = 73) and without (n = 24) HIV infection randomized to depot medroxyprogesterone acetate (DMPA) or the levonogestrel implant in equal numbers within each group and determined the effects of these hormonal contraceptives (HCs) on the vaginal immune milieu and the composition of the vaginal microbiota. Longitudinal data for soluble immune mediators, measured by multiplex bead arrays and enzyme-linked immunosorbent assays (ELISAs), and vaginal microbiota, assessed by 16S rRNA gene amplicon, were collected prior to and over a period of 180 days post-HC initiation. DMPA and levonogestrel had only minimal effects on the vaginal immune milieu and microbiota. In women with HIV, with the caveat of a small sample size, there was an association between the median log10 change in the interleukin-12 (IL-12)/IL-10 ratio in vaginal fluid at day 180 post-HC compared to baseline when these women were classified as having a community state type (CST) IV vaginal microbiota and were randomized to DMPA. Long-lasting alterations in soluble immune markers or shifts in microbiota composition were not observed. Furthermore, women with HIV did not exhibit increased viral shedding in the genital tract after HC initiation. Consistent with the results of the ECHO (Evidence for Contraceptive Options and HIV Outcomes) trial, our data imply that the progestin-based HC DMPA and levonorgestrel are associated with minimal risk for women with HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT02103660). IMPORTANCE The results of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, the first large randomized controlled clinical trial comparing the HIV acquisition risk of women receiving DMPA, the levonorgestrel (LNG) implant, or the copper intrauterine device (IUD), did not reveal an increased risk of HIV acquisition for women on any of these three contraceptives. Our study results confirm that the two different progestin-based hormonal contraceptives DMPA and levonogestrel will not increase the risk for HIV infection. Furthermore, DMPA and levonogestrel have only minimal effects on the immune milieu and the microbiota in the vaginal tract, attesting to the safety of these hormonal contraceptives.