Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD) characterized by hypoplasia of the left ventricle and aorta along with stenosis or atresia of the aortic and mitral valves. HLHS represents only ∼4%-8% of all CHDs but accounts for ∼25% of deaths. HLHS is an isolated defect (i.e., iHLHS) in 70% of families, the vast majority of which are simplex. Despite intense investigation, the genetic basis of iHLHS remains largely unknown. We performed exome sequencing on 331 families with iHLHS aggregated from four independent cohorts. A Mendelian-model-based analysis demonstrated that iHLHS was not due to single, large-effect alleles in genes previously reported to underlie iHLHS or CHD in >90% of families in this cohort. Gene-based association testing identified increased risk for iHLHS associated with variation in CAPN2 (p = 1.8 × 10(-5)), encoding a protein involved in functional adhesion. Functional validation studies in a vertebrate animal model (Xenopus laevis) confirmed CAPN2 is essential for cardiac ventricle morphogenesis and that in vivo loss of calpain function causes hypoplastic ventricle phenotypes and suggest that human CAPN2(707C>T) and CAPN2(1112C>T) variants, each found in multiple individuals with iHLHS, are hypomorphic alleles. Collectively, our findings show that iHLHS is typically not a Mendelian condition, demonstrate that CAPN2 variants increase risk of iHLHS, and identify a novel pathway involved in HLHS pathogenesis.

Using data from CDC's State Unintentional Drug Overdose Reporting System, this report describes trends in overdose deaths with evidence of counterfeit pill use during July 2019-December 2021 in 29 states and the District of Columbia (DC) and characteristics of deaths with and without evidence of counterfeit pill use during 2021 in 34 states and DC. The quarterly percentage of deaths with evidence of counterfeit pill use more than doubled from 2.0% during July-September 2019 to 4.7% during October-December 2021, and more than tripled in western jurisdictions (from 4.7% to 14.7%). Illicitly manufactured fentanyls were the only drugs involved (i.e., caused death) in 41.4% of deaths with evidence of counterfeit pill use and 19.5% of deaths without evidence. Decedents with evidence of counterfeit pill use, compared with those without evidence, were younger (57.1% versus 28.1% were aged <35 years), more often Hispanic or Latino (18.7% versus 9.4%), and more frequently had a history of prescription drug misuse (27.0% versus 9.4%). Smoking was the most common noningestion drug use route among deaths with evidence of counterfeit pill use (39.5%). Overdose prevention messaging that highlights the dangers of pills obtained illicitly or without a prescription (because they might be counterfeit), encourages drug product testing by persons using drugs, and is tailored to persons most at risk (e.g., younger persons) could help prevent overdose deaths.

BACKGROUND: Expanding access to medications to treat opioid use disorder (OUD), such as buprenorphine, is an evidence-based response to the mounting drug overdose crisis. However, concerns about buprenorphine diversion persist and contribute to limited access. METHODS: To inform decisions about expanding access, a scoping review was conducted on publications describing the scope of, motivations for, and outcomes associated with diverted buprenorphine in the U.S. RESULTS: In the 57 included studies, definitions for diversion were inconsistent. Most studied use of illicitly-obtained buprenorphine. Across studies, the scope of buprenorphine diversion ranged from 0% to 100%, varying by sample type and recall period. Among samples of people receiving buprenorphine for OUD treatment, diversion peaked at 4.8%. Motivations for using diverted buprenorphine were self-treatment, management of drug use, to get high, and when drug of choice was unavailable. Associated outcomes examined trended toward positive or neutral, including improved attitudes toward and retention in MOUD. CONCLUSIONS: Despite inconsistent definitions of diversion, studies reported a low scope of diversion among people receiving MOUD, with inability to access treatment as a motivating factor for using diverted buprenorphine, and increased retention in MOUD as an outcome associated with use of diverted buprenorphine. Future research should explore reasons for diverted buprenorphine use in the context of expanded treatment availability to address persistent barriers to evidence-based treatment for OUD.

In a report on the rise of emergency department visits for opioid overdoses, the US Centers for Disease Control and Prevention (CDC) described the importance of coordinated, informed efforts with public safety, including first responders and law enforcement.2 Since 2015, CDC has awarded millions in funding to support overdose prevention and surveillance efforts through Overdose Data to Action, the Overdose Response Strategy, and the Opioid Rapid Response Program.3,4 Improving partnerships between PH/PS to reduce drug overdose deaths is a core component of these signature CDC programs.5–7

Rates of drug overdose deaths are high and growing. Innovative strategies, such as partnerships between public health and public safety (PH/PS) agencies, are needed to curb these trends. Support for PH/PS partnerships as an overdose prevention strategy is growing; however, little information exists on the makeup of activities within this strategy. The US Centers for Disease Control and Prevention's (CDC's) Overdose Data to Action (OD2A) cooperative agreement supports innovative and comprehensive overdose surveillance and prevention activities across the United States. Within OD2A, funded states, counties/cities, and territories may implement PH/PS partnerships to reduce overdose deaths. An inventory of PH/PS activities described in OD2A recipients' year 2 annual progress reports was conducted. These activities were abstracted for PH/PS partners' roles, intended audience, deliverables, objectives, stage of overdose risk addressed, and type of strategy implemented. The inventory revealed that 49 of the 66 funded jurisdictions planned 109 PH/PS activities. Most aimed to bridge knowledge, data, and service gaps and intervened at higher levels of overdose risk. This analysis highlights opportunities to adapt and expand cross-sector overdose prevention efforts across the overdose risk continuum.

CONTEXT: Public health and public safety collaborations can strengthen and improve efforts to address the worsening drug overdose crisis. PROGRAM: The Overdose Response Strategy is addressing this need through a national public health and public safety program designed to foster the cross-sector sharing of timely data, pertinent intelligence, and evidence-based and innovative strategies to prevent and respond to drug overdose. IMPLEMENTATION: Since 2015, the Overdose Response Strategy has been implemented by state-based public health and public safety teams who work together to prevent and respond to drug overdoses within and across sectors, states, and territories. The public health and public safety teams share data systems to inform rapid and effective community overdose prevention efforts; support immediate, evidence-based response efforts that can directly reduce overdose deaths; design and use promising strategies at the intersection of public health and public safety; and use effective and efficient primary prevention strategies that can reduce substance use and overdose long term. Implementation of the Overdose Response Strategy aligns with the US Centers for Disease Control and Prevention's Strategic Partnering Framework. EVALUATION: The evaluation of the Overdose Response Strategy, which is currently underway, is based on 2 evaluation approaches: Collective Impact and Organizational Network Analysis. These approaches provide a way to look at the strength of the relationship between public health and public safety and the way the relationship is leveraged to advance program goals and objectives. DISCUSSION: The Overdose Response Strategy serves as a strategic partnership model that can potentially be applied to other issues, such as gun violence, that may benefit from public health and public safety collaboration.

CONTEXT: In response to the drug overdose crisis, first responders, in partnership with public health, provide new pathways to substance use disorder (SUD) treatment and other services for individuals they encounter in their day-to-day work. OBJECTIVE: This scoping review synthesizes available evidence on first responder programs that take an assertive approach to making linkages to care. RESULTS: Seven databases were searched for studies published in English in peer-reviewed journals between January 2000 and December 2019. Additional articles were identified through reference-checking and subject matter experts. Studies were selected for inclusion if they sufficiently described interventions that (1) focus on adults who use drugs; (2) are in the United States; (3) involve police, fire, or emergency medical services; and (4) assertively link individuals to SUD treatment. Twenty-two studies met inclusion criteria and described 34 unique programs, implementation barriers and facilitators, assertive linkage strategies, and linkage outcomes, including unintended consequences. CONCLUSIONS: Findings highlight the range of linkage strategies concurrently implemented and areas for improving practice and research, such as the need for more linkages to evidence-based strategies, namely, medications for opioid use disorder, harm reduction, and wraparound services.

Key populations, ie, female sex workers, men who have sex with men, transgender people, people who inject drugs, and people in prisons and other closed settings, experience stigma, discrimination, and structural barriers when accessing HIV prevention and care. Public health facilities in Myanmar became increasingly involved in HIV service delivery, leading to an urgent need for healthcare workers to provide client-centred, key population-friendly services. Between July 2017-June 2018, the Myanmar Ministry of Health and Sports and National AIDS Programme collaborated with ICAP at Columbia University and the US Centers for Disease Control and Prevention to implement a quasi-experimental, multicomponent intervention including healthcare worker sensitization training with pre- and post- knowledge assessments, healthcare worker and client satisfaction surveys, and structural changes. We observed modest improvements among healthcare workers (n = 50) in knowledge assessments. Classification of clients into key population groups increased and fewer clients were classified as low risk. Key population clients reported favourable perceptions of the quality and confidentiality of care through self-administered surveys. Our findings suggest public health facilities can deliver HIV services that are valued by key population clients.

BACKGROUND AND PURPOSE: Characterization of emergency department (ED) visits for acute harms related to use of over-the-counter cough and cold medications (CCMs) by patient demographics, intent of CCM use, concurrent substance use, and clinical manifestations can help guide prevention of medication harms. METHODS: Public health surveillance data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project were used to estimate numbers and population rates of ED visits from 2017-2019. RESULTS: Based on 1,396 surveillance cases, there were an estimated 26,735 (95% CI, 21,679-31,791) US ED visits for CCM-related harms annually, accounting for 1.3% (95% CI, 1.2%-1.5%) of all ED visits for medication adverse events. Three fifths (61.4%, 95% CI, 55.6%-67.2%) of these visits were attributed to non-therapeutic CCM use (nonmedical use, self-harm, unsupervised pediatric exposures). Most visits by children aged <4 years (74.0%, 95% CI, 59.7%-88.3%) were for unsupervised CCM exposures. Proportion hospitalized was higher for visits for self-harm (76.5%, 95% CI, 68.9%-84.2%) than for visits for nonmedical use (30.3%, 95% CI, 21.1%-39.6%) and therapeutic use (8.8%, 95% CI, 5.9%-11.8%). Overall, estimated population rates of ED visits for CCM-related harms were higher for patients aged 12-34 years (16.5 per 100,000, 95% CI, 13.0-20.0) compared with patients aged <12 years (5.1 per 100,000, 95% CI, 3.6-6.5) and ≥35 years (4.3 per 100,000, 95% CI, 3.4-5.1). Concurrent use of other medications, illicit drugs, or alcohol was frequent in ED visits for nonmedical use (61.3%) and self-harm (75.9%). CONCLUSIONS: Continued national surveillance of CCM-related harms can assess progress toward safer use.

BACKGROUND: Rates of fatal overdose (OD) from synthetic opioids rose nearly 60 % from 2016 to 2018. 911 Good Samaritan Laws (GSLs) are an evidenced-based strategy for preventing OD fatality. This study describes patrol officers' knowledge of their state's GSL, experience with OD response, and their perspectives on strategies to prevent and respond to opioid OD. METHODS: An electronic survey assessed officers' knowledge of state GSLs and experiences responding to OD. Descriptive statistics and hierarchical linear modeling were generated to examine differences in knowledge, preparedness, and endorsement of OD response efforts by experience with OD response. RESULTS: 2,829 officers responded to the survey. Among those who had responded to an OD call in the past six months (n = 1,946), 37 % reported administering naloxone on scene and 36 % reported making an arrest. Most (91 %) correctly reported whether their state had a GSL in effect. Only 26 % correctly reported whether that law provides limited immunity from arrest. Fifteen percent of officers who had responded to an OD work in departments that do not carry naloxone. Compared with officers who had not responded to any OD calls, those who reported responding OD calls at least monthly and at least weekly, were significantly less likely to endorse OD response efforts. CONCLUSION: Officers who respond to OD calls are generally receiving training and naloxone supplies to respond, but knowledge gaps and additional training needs persist. Additional training and strategies to relieve compassion fatigue among those who have more experience with OD response efforts may be indicated.

INTRODUCTION: Rates of opioid overdose (OD) have risen to unprecedented numbers and more than half of incarcerated individuals meet the criteria for substance use disorder, placing them at high risk. This review describes the relationship between incarceration history and OD. METHODS: A scoping review was conducted and criteria for inclusion were: set in North America, published in English, and non-experimental study of formerly incarcerated individuals. Due to inconsistent definitions of opioid OD, we included all studies examining OD where opioids were mentioned. RESULTS: The 18 included studies were all published in 2001 or later. Four associations between incarceration history and OD were identified: (1) six studies assessed incarceration history as a risk factor for OD and four found a significantly higher risk of OD among individuals with a history of incarceration compared to those without; (2) nine studies examined the rate of OD compared to the general population: eight found a significantly higher risk of fatal OD among those with a history of incarceration and three documented the highest risk of death immediately following release; (3) six studies found demographic, substance use and mental health, and incarceration-related risk factors for OD among formerly incarcerated individuals; and (4) four studies assessed the proportion of deaths due to OD and found a range from 5 % to 57 % among formerly incarcerated individuals. DISCUSSION: Findings support the growing call for large-scale implementation of evidence-based OD prevention interventions in correctional settings and among justice-involved populations to reduce OD burden in this high-risk population.

The U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the largest bilateral funder of human immunodeficiency virus (HIV) prevention and control programs worldwide, currently supports implementation of preexposure prophylaxis (PrEP) to reduce HIV incidence among persons at substantial risk for infection, including female sex workers, men who have sex with men (MSM), and transgender women (hereafter referred to as key populations). Recent estimates suggest that 54% of all global new HIV infections in 2018 occurred among key populations and their sexual partners (1). In 2016, PEPFAR began tracking initiation of PrEP by key populations and other groups at high risk (2). The implementation and scale-up of PrEP programs across 35 PEPFAR-supported country or regional programs* was assessed by determining the number of programs reporting any new PrEP clients during each quarter from October 2016 to September 2018. As of September 2018, only 15 (43%) PEPFAR-supported country or regional programs had implemented PrEP programs; however, client volume increased by 3,351% over the assessment period in 15 country or regional programs. Scale-up of PrEP among general population clients (5,255%) was nearly three times that of key population clients (1,880%). Among key populations, the largest increase (3,518%) occurred among MSM. Factors that helped drive the success of these PrEP early adopter programs included initiation of national, regional, and multilateral stakeholder meetings; engagement of ministries of health and community advocates; revision of HIV treatment guidelines to include PrEP; training for HIV service providers; and establishment of drug procurement policies. These best practices can help facilitate PrEP implementation, particularly among key populations, in other country or regional programs to reduce global incidence of HIV infection.

INTRODUCTION: While relatively rare events, abrupt disruptions in heroin availability have a significant impact on morbidity and mortality risk among those who are heroin dependent. A heroin shortage occurred in Coast Province, Kenya from December 2010 to March 2011. This qualitative analysis describes the shortage events and consequences from the perspective of heroin users, along with implications for health and other public sectors. METHODS: As part of a rapid assessment, 66 key informant interviews and 15 focus groups among heroin users in Coast Province, Kenya were conducted. A qualitative thematic analysis was undertaken in Atlas.ti. to identify salient themes related to the shortage. RESULTS: Overall, participant accounts were rooted in a theme of desperation and uncertainty, with emphasis on six sub-themes: (1) withdrawal and strategies for alleviating withdrawal, including use of medical intervention and other detoxification attempts; (2) challenges of dealing with unpredictable drug availability, cost, and purity; (3) changes in drug use patterns, and actions taken to procure heroin and other drugs; (4) modifications in drug user relationship dynamics and networks, including introduction of risky group-level injection practices; (5) family and community response; and (6) new challenges with the heroin market resurgence. CONCLUSIONS: The heroin shortage led to a series of consequences for drug users, including increased risk of morbidity, mortality and disenfranchisement at social and structural levels. Availability of evidence-based services for drug users and emergency preparedness plans could have mitigated this impact.

We utilized data from the 2012 Crane Survey in Kampala, Uganda to estimate prevalence of rape among female sex workers (FSWs) and to identify risk factors for and prevalence of client-initiated gender-based violence (GBV) among FSWs. Participants were recruited using respondent-driven sampling. Analyses were weighted using RDSAT-generated individualized weights for each of the five dependent GBV outcomes. Analyses were conducted utilizing SAS 9.3. Among 1,467 FSWs who were interviewed, 82 % (95 % CI: 79-84) experienced client-initiated GBV and 49 % (95 % CI: 47-53) had been raped at least once in their lifetime. GBV risk increased with increasing frequency of client demands for unprotected sex, length of time engaged in sex work, and FSW alcohol consumption. Risk decreased when sex with clients occurred at the FSW's or client's house or a hotel compared to when sex occurred in open spaces. Our findings demonstrate a high prevalence of GBV among FSWs. This research reinforces the urgent need for GBV prevention and response strategies to be integrated into FSW programming and the continuing need for GBV research among key populations.

This report summarizes current (as of 2011) guidelines or recommendations published by multiple agencies of the U.S. Department of Health and Human Services (DHHS) for prevention and control of human immunodeficiency virus (HIV) infection, viral hepatitis, sexually transmitted diseases (STDs), and tuberculosis (TB) for persons who use drugs illicitly. It also summarizes existing evidence of effectiveness for practices to support delivery of integrated prevention services. Implementing integrated services for prevention of HIV infection, viral hepatitis, STDs, and TB is intended to provide persons who use drugs illicitly with increased access to services, to improve timeliness of service delivery, and to increase effectiveness of efforts to prevent infectious diseases that share common risk factors, behaviors, and social determinants. This guidance is intended for use by decision makers (e.g., local and federal agencies and leaders and managers of prevention and treatment services), health-care providers, social service providers, and prevention and treatment support groups. Consolidated guidance can strengthen efforts of health-care providers and public health providers to prevent and treat infectious diseases and substance use and mental disorders, use resources efficiently, and improve health-care services and outcomes in persons who use drugs illicitly. An integrated approach to service delivery for persons who use drugs incorporates recommended science-based public health strategies, including 1) prevention and treatment of substance use and mental disorders; 2) outreach programs; 3) risk assessment for illicit use of drugs; 4) risk assessment for infectious diseases; 5) screening, diagnosis, and counseling for infectious diseases; 6) vaccination; 7) prevention of mother-to-child transmission of infectious diseases; 8) interventions for reduction of risk behaviors; 9) partner services and contact follow-up; 10) referrals and linkage to care; 11) medical treatment for infectious diseases; and 12) delivery of integrated prevention services. These strategies are science-based, public health strategies to prevent and treat infectious diseases, substance use disorders, and mental disorders. Treatment of infectious diseases and treatment of substance use and mental disorders contribute to prevention of transmission of infectious diseases. Integrating prevention services can increase access to and timeliness of prevention and treatment.