Second Nationwide Tuberculosis Outbreak Caused by Bone Allografts Containing Live Cells - United States, 2023.

During July 7-11, 2023, CDC received reports of two patients in different states with a tuberculosis (TB) diagnosis following spinal surgical procedures that used bone allografts containing live cells from the same deceased donor. An outbreak associated with a similar product manufactured by the same tissue establishment (i.e., manufacturer) occurred in 2021. Because of concern that these cases represented a second outbreak, CDC and the Food and Drug Administration worked with the tissue establishment to determine that this product was obtained from a donor different from the one implicated in the 2021 outbreak and learned that the bone allograft product was distributed to 13 health care facilities in seven states. Notifications to all seven states occurred on July 12. As of December 20, 2023, five of 36 surgical bone allograft recipients received laboratory-confirmed TB disease diagnoses; two patients died of TB. Whole-genome sequencing demonstrated close genetic relatedness between positive Mycobacterium tuberculosis cultures from surgical recipients and unused product. Although the bone product had tested negative by nucleic acid amplification testing before distribution, M. tuberculosis culture of unused product was not performed until after the outbreak was recognized. The public health response prevented up to 53 additional surgical procedures using allografts from that donor; additional measures to protect patients from tissue-transmitted M. tuberculosis are urgently needed.

Patient brokering in for-profit substance use disorder treatment: a qualitative study with people with opioid use disorder and professionals in the field.

BACKGROUND: Opioid use and opioid overdose deaths are at an all-time high and evidence-based treatments for people with opioid use disorder (OUD) are underutilized. Therefore, we sought to understand experiences and perceptions of abuses in the for-profit substance use disorder treatment industry that could potentially put people with OUD at an increased risk for an overdose. METHODS: One-on-one semi-structured interviews were conducted from November 2018 to May 2019 in Southern California with 20 people with OUD and 20 professionals who work in the substance use disorder (SUD) treatment field. A grounded theory approach was conducted to discover emerging patterns from the data. RESULTS: Three major themes emerged:1) financial and material enticements, 2) encouraging substance use in the for-profit treatment sector, and 3) contributors to overdose risk. Participants reported that patient brokers would pay for plane tickets and offer financial incentives (e.g., money) to attract individuals to SUD treatment, capitalizing on insurance profits despite initial expenses. Participants reported being encouraged to use drugs before treatment to meet insurance conditions, thus jeopardizing genuine recovery efforts and adding to the temptation of drug use. Many participants linked patient brokering to increased overdose deaths, emphasizing the dangerous practices of brokers providing drugs, promoting relapse, and creating a revolving door of treatment, which compounds the overdose risk after periods of abstinence. CONCLUSIONS: Patient brokering and unethical abuses in the for-profit treatment industry have caused some people with OUD to seek treatment for money and housing instead of seeking treatment to stop opioid use. The harmful treatment environment was seen as a barrier to care and an unwanted obstacle to overcome on the path to recovery.

Optimizing naloxone distribution to prevent opioid overdose fatalities: results from piloting the Systems Analysis and Improvement Approach within syringe service programs.

BACKGROUND: Opioid overdose fatalities are preventable with timely administration of naloxone, an opioid antagonist, during an opioid overdose event. Syringe service programs have pioneered naloxone distribution for potential bystanders of opioid overdose. The objective of this study was to pilot test a multi-component implementation strategy-the systems analysis and improvement approach for naloxone (SAIA-Naloxone)-with the goal of improving naloxone distribution by syringe service programs. METHODS: Two syringe service programs participated in a 6-month pilot of SAIA-Naloxone, which included (1) analyzing program data to identify gaps in the naloxone delivery cascade, (2) flow mapping to identify causes of attrition and brainstorm programmatic changes for improvement, and (3) conducting continuous quality improvement to test and assess whether modifications improve the cascade. We conducted an interrupted time series analysis using 52 weeks of data before and 26 weeks of data after initiating SAIA-Naloxone. Poisson regression was used to evaluate the association between SAIA-Naloxone and the weekly number of participants receiving naloxone and number of naloxone doses distributed. RESULTS: Over the course of the study, 11,107 doses of naloxone were distributed to 6,071 participants. Through SAIA-Naloxone, syringe service programs prioritized testing programmatic modifications to improve data collection procedures, proactively screen and identify naloxone-naïve participants, streamline naloxone refill systems, and allow for secondary naloxone distribution. SAIA-Naloxone was associated with statistically significant increases in the average number of people receiving naloxone per week (37% more SPP participants; 95% CI, 12% to 67%) and average number of naloxone doses distributed per week (105% more naloxone doses; 95% CI, 79% to 136%) beyond the underlying pre-SAIA-Naloxone levels. These initial increases were extended by ongoing positive changes over time (1.6% more SSP participants received naloxone and 0.3% more naloxone doses were distributed in each subsequent week compared to the weekly trend in the pre-SAIA Naloxone period). CONCLUSIONS: SAIA-Naloxone has strong potential for improving naloxone distribution from syringe service programs. These findings are encouraging in the face of the worsening opioid overdose crisis in the United States and support testing SAIA-Naloxone in a large-scale randomized trial within syringe service programs.

Reduced Emergency Department Visits and Hospitalisation with Use of an Unsanctioned Safe Consumption Site for Injection Drug Use in the United States.

BACKGROUND: Safe consumption sites (SCS) are an evidence-based intervention to prevent drug use-related harm. In late 2014, an organisation in an undisclosed location in the USA opened an unsanctioned SCS. OBJECTIVE: To evaluate whether use of the unsanctioned SCS affected medical outcomes. DESIGN: A prospective cohort study. SETTING: Neighbourhoods surrounding the SCS. PARTICIPANTS: People who injected drugs were recruited and interviewed at baseline and 6 and 12 months from 2018 to 2020. INTERVENTION: People using the SCS could bring pre-obtained drugs to consume via injection, which were monitored by trained staff with naloxone. MAIN MEASURES: Any overdose, number of non-fatal overdoses, skin and soft tissue infections, emergency department utilisation, number of emergency department visits, hospitalisation and number of nights spent in hospital. KEY RESULTS: A total of 494 participants enrolled in the study; 59 (12%) used the SCS at least once. We used propensity score weighting to analyse the association between SCS utilisation and measures. People using the SCS were 27% (95% CI: 12-46%) less likely to visit the emergency department, had 54% (95% CI: 33-71%) fewer emergency department visits, were 32% (95% CI: 4-57%) less likely to be hospitalised, and spent 50% (95% CI: 1-85%) fewer nights in hospital. Though not significant, people using the SCS had a lower likelihood of overdosing and slightly higher likelihood of skin and soft tissue infections. CONCLUSIONS: Our findings support the use of SCS in the USA to reduce the growing burden of acute care service utilisation related to injection drug use.

Establishment and Enforcement of Operational Rules at an Unsanctioned Safe Drug Consumption Site in the United States, 2014-2020.

Objectives. To examine how operational rules are established and enforced at an unsanctioned safe consumption site (SCS) operating in the United States. Methods. We conducted 44 qualitative interviews with people who use drugs, staff members, and volunteers at an unsanctioned SCS and analyzed them using an inductive thematic approach. Results. Rule-making processes were largely driven by concerns raised by service users rather than driven by external pressures, and iterated rapidly in response to changing needs. The unsanctioned nature of the site produced an environment where bottom-up rule-making was critical to generating a shared sense of ownership of the site and where enforcement was necessarily fluid. Conclusions. Removing external restrictions on operational rules for SCSs results in a flexible set of rules that are highly responsive to the social and public health needs of people who use drugs. Legislation and regulations of SCSs should aim to place as few hard limits on operating conditions as possible to maximize involvement of and responsiveness to people who use drugs. (Am J Public Health. 2022;112(S2):S166-S172. https://doi.org/10.2105/AJPH.2022.306714).

"We're already doing this work": ethical research with community-based organizations.

BACKGROUND: Public health research frequently relies on collaborations with community-based organizations, and these partnerships can be essential to the success of a project. However, while public health ethics and oversight policies have historically focused on ensuring that individual subjects are protected from unethical or unfair practices, there are few guidelines to protect the organizations which facilitate relationships with - and are frequently composed of - these same vulnerable populations. As universities, governments, and donors place a renewed emphasis on the need for community engaged research to address systematic drivers of health inequity, it is vital that the ways in which research is conducted does not uphold the same intersecting systems of gender, race, and class oppression which led to the very same health inequities of interest. METHODS: To understand how traditional notions of public health research ethics might be expanded to encompass partnerships with organizations as well as individuals, we conducted qualitative interviews with 39 staff members (executive directors and frontline) at community-based organizations that primarily serve people who use drugs, Black men who have sex with men, and sex workers across the United States from January 2016 - August 2017. We also conducted 11 in-depth interviews with professional academic researchers with experience partnering with CBOs that serve similar populations. Transcripts were analyzed thematically using emergent codes and a priori codes derived from the Belmont Report. RESULTS: The concepts of respect, beneficence, and justice are a starting point for collaboration with CBOs, but participants deepened them beyond traditional regulatory concepts to consider the ethics of relationships, care, and solidarity. These concepts could and should apply to the treatment of organizations that participate in research just as they apply to individual human subjects, although their implementation will differ when applied to CBOs vs individual human subjects. CONCLUSIONS: Academic-CBO partnerships are likely to be more successful for both academics and CBOs if academic researchers work to center individual-level relationship building that is mutually respectful and grounded in cultural humility. More support from academic institutions and ethical oversight entities can enable more ethically grounded relationships between academic researchers, academic institutions, and community based organizations.

Identification of Non-Fatal Opioid Overdose Cases Using 9-1-1 Computer Assisted Dispatch and Prehospital Patient Clinical Record Variables.

Background: The current epidemic of opioid overdoses in the United States necessitates a robust public health and clinical response. We described patterns of non-fatal opioid overdoses (NFOODs) in a small western region using data from the 9-1-1 Computer Assisted Dispatch (CAD) record and electronic Patient Clinical Records (ePCR) completed by EMS responders. We determined whether CAD and ePCR variables could identify NFOOD cases in 9-1-1 data for intervention and surveillance efforts. Methods: We conducted a retrospective analysis of 1 year of 9-1-1 emergency medical CAD and ePCR (including naloxone administration) data from the sole EMS provider in the response area. Cases were identified based on clinician review of the ePCR, and categorized as definitive NFOOD, probable NFOOD, or non-OOD. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the most prevalent CAD and ePCR variables were calculated. We used a machine learning technique-Random-Forests (RF) modeling-to optimize our ability to accurately predict NFOOD cases within census blocks. Results: Of 37,960 9-1-1 calls, clinical review identified 158 NFOOD cases (0.4%), of which 123 (77.8%) were definitive and 35 (22.2%) were probable cases. Overall, 106 (67.1%) received naloxone from the EMS responder at the scene. As a predictor of NFOOD, naloxone administration by paramedics had 67.1% sensitivity, 99.6% specificity, 44% PPV, and 99.9% NPV. Using CAD variables alone achieved a sensitivity of 36.7% and specificity of 99.7%. Combining ePCR variables with CAD variables increased the diagnostic accuracy with the best RF model yielding 75.9% sensitivity, 99.9% specificity, 71.4% PPV, and 99.9% NPV. Conclusion: CAD problem type variables and naloxone administration, used alone or in combination, had sub-optimal predictive accuracy. However, a Random Forests modeling approach improved accuracy of identification, which could foster improved surveillance and intervention efforts. We identified the set of NFOODs that EMS encountered in a year and may be useful for future surveillance efforts.

Factors Associated With Calling 911 for an Overdose: An Ethnographic Decision Tree Modeling Approach.

Objectives. To identify factors that influence when people who use drugs (PWUDs) call 911 for an overdose. Methods. We conducted 45 qualitative interviews and 180 surveys with PWUDs who had recently witnessed overdoses in Southern California from 2017 to 2019. We used conditional inference tree and random forest models to generate and validate a model to predict whether 911 would be called. Results. Our model had good in- (83%) and out-of-sample (84%) predictive accuracy. Three aspects of the social and policy environment influenced calling 911 for an overdose: the effectiveness of response strategies employed, the behavior of other bystanders, and whether the responder believes it is their responsibility to call. Conclusions. Even in the presence of policies that provide some protections, PWUDs are faced with difficult decisions about calling 911 and must weigh their own safety against that of an overdose victim. Potential interventions include strengthening training and safety planning for PWUDs, bolstering protections for PWUDs when they call 911, and separating law enforcement response from emergency medical response to overdoses.

Overdose Prevention Site Acceptability among Residents and Businesses Surrounding a Proposed Site in Philadelphia, USA.

Overdose prevention sites (OPS) are places where people use previously obtained drugs under the supervision of a health professional. They have been proposed in six United States (US) cities, including Philadelphia, to help reduce opioid-related overdose deaths and public injection. Philadelphia has the highest overdose rate among large cities in the US, which has led a local community-based organization to plan the implementation of OPS. Kensington, a neighborhood with the highest drug mortality overdose rates in the city, is a likely site for the proposed OPS. Given the dearth of research systematically assessing public opinion towards OPS prior to implementation, we enrolled 360 residents and 79 business owners/staff in the Kensington neighborhood in a cross-sectional acceptability study. Face-to-face surveys assessed participant characteristics, experiences with drug-related social problems, and OPS acceptability. Using descriptive statistics, we estimated factors associated with favorability towards opening an OPS in the Kensington neighborhood. Ninety percent of residents were in favor of an OPS opening in Kensington. Support was significantly higher among unstably housed individuals and persons who currently use opioids. In the business sample, 63% of owners/staff were in favor of opening an OPS in Kensington. A greater proportion of Asian/Pacific Islanders, Hispanic/Latinx respondents, and non-Hispanic/Latinx Black respondents were in favor of an OPS opening in Kensington compared with white respondents (p < 0.04). While details about implementation are still being considered, results indicate general acceptability among Kensington residents and businesses for an OPS, especially if it can deliver benefits that curb drug-related social problems. Should an OPS be implemented in Philadelphia, it would be important to monitor changes in drug-related social problems and acceptability post implementation.

"Another Person Was Going to Do It": The Provision of Injection Drug Use Initiation Assistance in a High-Risk U.S.-Mexico Border Region.

Background: Persons who inject drugs (PWID) play a key role in assisting others' initiation into injection drug use (IDU). We aimed to explore the pathways and socio-structural contexts for this phenomenon in Tijuana, Mexico, a border setting marked by a large PWID population with limited access to health and social services. Methods: Preventing Injecting by Modifying Existing Responses (PRIMER) is a multi-cohort study assessing socio-structural factors associated with PWID assisting others into initiating IDU. Semi-structured qualitative interviews in Tijuana included participants ≥18 years old, who reported IDU within the month prior to cohort enrollment and ever initiating others into IDU. Purposive sampling ensured a range of drug use experiences and behaviors related to injection initiation assistance. Thematic analysis was used to develop recurring and significant data categories. Results: Twenty-one participants were interviewed (8 women, 13 men). Broadly, participants considered public injection to increase curiosity about IDU. Many considered transitioning into IDU as inevitable. Emergent themes included providing assistance to mitigate overdose risk and to protect initiates from being taken advantage of by others. Participants described reluctance in engaging in this process. For some, access to resources (e.g., shared drugs or a monetary fee) was a motivator to initiate others. Conclusion: In Tijuana, public injection and a lack of harm reduction services are perceived to fuel the incidence of IDU initiation and to incentivize PWID to assist in injection initiation. IDU prevention efforts should address structural factors driving PWID participation in IDU initiation while including PWID in their development and implementation.

Race and nativity are major determinants of tuberculosis in the U.S.: evidence of health disparities in tuberculosis incidence in Michigan, 2004-2012.

BACKGROUND: The incidence of TB in Michigan was 1.5 per 100,000 people in 2012, roughly half the U.S. incidence. Despite successes in TB control, disparities in TB still exist in Michigan, particularly by race, age, and nativity. A major challenge in understanding disparities in TB burden is distinguishing between TB cases resulting from recent transmission and those resulting from reactivation of latent TB infection, information critical to tailoring control strategies. We examined nine-year trends in tuberculosis (TB) incidence patterns for the entire population of Michigan, and within demographic subgroups. METHODS: Using a cross-sectional study of TB surveillance data, we analyzed 1254 TB cases reported in Michigan during 2004-2012. Cases included were those for whom both spoligotyping and 12-locus-MIRU-VNTR results were available. Using a combination of the genotyping information and time of diagnosis, we then classified cases as resulting from either recent transmission or reactivation of latent TB infection. We used multivariable negative binomial regression models to study trends in the TB incidence rate for the entire population and by race, nativity, gender, and age. RESULTS: Overall, the incidence rate of TB declined by an average of 8% per year-11% among recently transmitted cases, and 9% among reactivation cases. For recently transmitted disease, Blacks had an average incidence rate 25 times greater than Whites, after controlling for nativity, gender, and age. For disease resulting from latent TB infection Asians had an average incidence rate 24 times greater than Whites, after controlling for nativity, gender, and age. CONCLUSIONS: Disparities in incidence persist despite ongoing TB control efforts. Greater disparities were observed by race and nativity demonstrating some of the ways that TB incidence is socially patterned. Reducing these disparities will require a multi-faceted approach encompassing the social and environmental contexts of high-risk populations.

A Longitudinal Study of Multiple Drug Use and Overdose Among Young People Who Inject Drugs.

OBJECTIVES: To determine the association between multiple drug use and nonfatal overdose among young people (younger than 30 years) who inject drugs. METHODS: We completed a longitudinal study of 173 injection drug users younger than 30 years living in San Francisco, California, between April 2012 and February 2014. RESULTS: The odds of nonfatal overdose increased significantly as heroin and benzodiazepine pill-taking days increased and when alcohol consumption exceeded 10 drinks per day compared with 0 drinks per day. CONCLUSIONS: Heroin, benzodiazepine, and alcohol use were independently associated with nonfatal overdose over time among young people who inject drugs. Efforts to address multiple central nervous system depressant use remain an important component of a comprehensive approach to overdose, particularly among young people.

Tuberculosis Among Temporary Visa Holders Working in the Tourism Industry - United States, 2012-2014.

Tuberculosis (TB) is a contagious bacterial disease of global concern. During 2013, an estimated nine million incident TB cases occurred worldwide (1). The majority (82%) were diagnosed in 22 countries, including South Africa and the Philippines, where annual incidence was 860 TB cases per 100,000 persons and 292 TB cases per 100,000 persons, respectively (1). The 2013 TB incidence in the United States was three cases per 100,000 persons (2). Under the Immigration and Nationality Act, TB screening is required for persons seeking permanent residence in the United States (i.e., immigrants and refugees), but it is not routinely required for nonimmigrants who are issued temporary visas for school or work (3). A portion of the U.S. tourism industry relies on temporary visa holders to accommodate seasonal and fluctuating demand for service personnel (4). This report describes three foreign-born persons holding temporary visas who had infectious TB while working at tourist destinations in the United States during 2012-2014. Multiple factors, including dormitory-style housing, transient work patterns, and diagnostic delays might have contributed to increased opportunity for TB transmission. Clinicians in seasonally driven tourist destinations should be aware of the potential for imported TB disease in foreign-born seasonal workers and promptly report suspected cases to health officials.

Neighborhood-Level and Spatial Characteristics Associated with Lay Naloxone Reversal Events and Opioid Overdose Deaths.

There were over 23,000 opioid overdose deaths in the USA in 2013, and opioid-related mortality is increasing. Increased access to naloxone, particularly through community-based lay naloxone distribution, is a widely supported strategy to reduce opioid overdose mortality; however, little is known about the ecological and spatial patterns of the distribution and utilization of lay naloxone. This study aims to investigate the neighborhood-level correlates and spatial relationships of lay naloxone distribution and utilization and opioid overdose deaths. We determined the locations of lay naloxone distribution sites and the number of unintentional opioid overdose deaths and reported reversal events in San Francisco census tracts (n = 195) from 2010 to 2012. We used Wilcoxon rank-sum tests to compare census tract characteristics across tracts adjacent and not adjacent to distribution sites and multivariable negative binomial regression models to assess the association between census tract characteristics, including distance to the nearest site, and counts of opioid overdose deaths and naloxone reversal events. Three hundred forty-two opioid overdose deaths and 316 overdose reversals with valid location data were included in our analysis. Census tracts including or adjacent to a distribution site had higher income inequality, lower percentage black or African American residents, more drug arrests, higher population density, more overdose deaths, and more reversal events (all p < 0.05). In multivariable analysis, greater distance to the nearest distribution site (up to a distance of 4000 m) was associated with a lower count of Naloxone reversals [incidence rate ratio (IRR) = 0.51 per 500 m increase, 95% CI 0.39-0.67, p < 0.001] but was not significantly associated with opioid overdose deaths. These findings affirm that locating lay naloxone distribution sites in areas with high levels of substance use and overdose risk facilitates reversals of opioid overdoses in those immediate areas but suggests that alternative delivery methods may be necessary to reach individuals in other areas with less concentrated risk.

A socio-structural approach to preventing injection drug use initiation: rationale for the PRIMER study.

BACKGROUND: Injection drug use remains a primary driver of HIV and HCV-related harms globally. However, there is a gap in efforts to prevent individuals from transitioning into injecting. People who inject drugs (PWID) play a key role in the transition of others into injecting, and while behavioral interventions have been developed to address this phenomenon, socio-structural approaches remain unexplored. To that end, we hypothesize that certain interventions designed to reduce injecting-related risk behaviors may also reduce the risk that PWID expose and introduce others into injecting. Identifying the preventive potential of existing interventions will inform broader efforts to prevent injecting and related harms. METHODS: The Preventing Injecting by Modifying Existing Responses (PRIMER) study is a multi-country mixed methods study with an aim to investigate whether specific interventions (e.g., opioid substitution therapy, supervised injection facilities, stable housing, incarceration environments) and related factors (e.g., public injecting and gender) influence the likelihood that PWID initiate others into injecting. This study will (1) investigate the PWID participation in injection initiation; (2) identify factors influencing the risk that PWID expose others to or facilitate injection initiation; (3) describe drug scene roles that increase the risk of PWID facilitating injection initiation; and (4) evaluate the impact of structural, social, or biomedical interventions on the risk that PWID facilitate injection initiation. It does so by pooling observational data from cohort studies of PWID in six cities: Vancouver, Canada; San Diego, USA; Tijuana, Mexico; Paris, Marseille, and Bordeaux, France. RESULTS: Team members are conducting a prospective, multi-site study of PWID (n = 3050) in North America and France that includes quantitative and qualitative data collection through four separate cohort studies of PWID (San Diego, STAHR II; Tijuana, El Cuete IV; Vancouver, V-DUS; Bordeaux, Marseille, Paris and Strasbourg, COSINUS). CONCLUSIONS: PRIMER is the largest study of injection initiation to date and the first to investigate structural approaches to preventing injection drug use initiation. Findings have the potential to inform the development and scale up of new and existing interventions to prevent transitions into injecting. TRIAL REGISTRATION: Preventing Injecting by Modifying Existing Responses (PRIMER), NIDA DP2-DA040256-01 .

Hsp90 and hepatobiliary transformation during sea lamprey metamorphosis.

BACKGROUND: Biliary atresia (BA) is a human infant disease with inflammatory fibrous obstructions in the bile ducts and is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult. Therefore, sea lamprey liver metamorphosis may serve as an etiological model for human BA and provide pivotal information for hepatobiliary transformation and possible therapeutics. RESULTS: We hypothesized that liver metamorphosis in sea lamprey is due to transcriptional reprogramming that dictates cellular remodeling during metamorphosis. We determined global gene expressions in liver at several metamorphic landmark stages by integrating mRNA-Seq and gene ontology analyses, and validated the results with real-time quantitative PCR, histological and immunohistochemical staining. These analyses revealed that gene expressions of protein folding chaperones, membrane transporters and extracellular matrices were altered and shifted during liver metamorphosis. HSP90, important in protein folding and invertebrate metamorphosis, was identified as a candidate key factor during liver metamorphosis in sea lamprey. Blocking HSP90 with geldanamycin facilitated liver metamorphosis and decreased the gene expressions of the rate limiting enzyme for cholesterol biosynthesis, HMGCoA reductase (hmgcr), and bile acid biosynthesis, cyp7a1. Injection of hsp90 siRNA for 4 days altered gene expressions of met, hmgcr, cyp27a1, and slc10a1. Bile acid concentrations were increased while bile duct and gall bladder degeneration was facilitated and synchronized after hsp90 siRNA injection. CONCLUSIONS: HSP90 appears to play crucial roles in hepatobiliary transformation during sea lamprey metamorphosis. Sea lamprey is a useful animal model to study postembryonic development and mechanisms for hsp90-induced hepatobiliary transformation.

Opioid Overdose Prevention Programs Providing Naloxone to Laypersons - United States, 2014.

Drug overdose deaths in the United States have more than doubled since 1999. During 2013, 43,982 drug overdose deaths (unintentional, intentional [suicide or homicide], or undetermined intent) were reported. Among these, 16,235 (37%) were associated with prescription opioid analgesics (e.g., oxycodone and hydrocodone) and 8,257 (19%) with heroin. For many years, community-based programs have offered opioid overdose prevention services to laypersons who might witness an overdose, including persons who use drugs, their families and friends, and service providers. Since 1996, an increasing number of programs provide laypersons with training and kits containing the opioid antagonist naloxone hydrochloride (naloxone) to reverse the potentially fatal respiratory depression caused by heroin and other opioids. In July 2014, the Harm Reduction Coalition (HRC), a national advocacy and capacity-building organization, surveyed 140 managers of organizations in the United States known to provide naloxone kits to laypersons. Managers at 136 organizations completed the survey, reporting on the amount of naloxone distributed, overdose reversals by bystanders, and other program data for 644 sites that were providing naloxone kits to laypersons as of June 2014. From 1996 through June 2014, surveyed organizations provided naloxone kits to 152,283 laypersons and received reports of 26,463 overdose reversals. Providing opioid overdose training and naloxone kits to laypersons who might witness an opioid overdose can help reduce opioid overdose mortality.

Assessing ecological correlates of marine bird declines to inform marine conservation.

Identifying drivers of ecosystem change in large marine ecosystems is central for their effective management and conservation. This is a sizable challenge, particularly in ecosystems transcending international borders, where monitoring and conservation of long-range migratory species and their habitats are logistically and financially problematic. Here, using tools borrowed from epidemiology, we elucidated common drivers underlying species declines within a marine ecosystem, much in the way epidemiological analyses evaluate risk factors for negative health outcomes to better inform decisions. Thus, we identified ecological traits and dietary specializations associated with species declines in a community of marine predators that could be reflective of ecosystem change. To do so, we integrated count data from winter surveys collected in long-term marine bird monitoring programs conducted throughout the Salish Sea--a transboundary large marine ecosystem in North America's Pacific Northwest. We found that decadal declines in winter counts were most prevalent among pursuit divers such as alcids (Alcidae) and grebes (Podicipedidae) that have specialized diets based on forage fish, and that wide-ranging species without local breeding colonies were more prone to these declines. Although a combination of factors is most likely driving declines of diving forage fish specialists, we propose that changes in the availability of low-trophic prey may be forcing wintering range shifts of diving birds in the Salish Sea. Such a synthesis of long-term trends in a marine predator community not only provides unique insights into the types of species that are at risk of extirpation and why, but may also inform proactive conservation measures to counteract threats--information that is paramount for species-specific and ecosystem-wide conservation.

The impact of registration of clinical trials units: the UK experience.

BACKGROUND: Over the last decade, the United Kingdom has invested significant resources in its clinical trial infrastructure. Clinical research networks have been formed, and some general oversight functions for clinical research have been centralised. One of the initiatives is a registration programme for Clinical Trials Units involved in the coordination of clinical trials. An international review panel of experts in clinical trials has been convened for three reviews over time, reviewing applications from Clinical Trials Units in the United Kingdom. The process benefited from earlier work by the National Cancer Research Institute that developed accreditation procedures for trials units involved in cancer trials. This article describes the experience with the three reviews of UK Clinical Trials Units which submitted applications. PURPOSE: This article describes the evolution and impact of this registration process from the perspective of the current international review panel members, some of whom have served on all reviews, including two done by the National Cancer Research Institute. PROCESS: Applications for registration were invited from all active, non-commercial Clinical Trials Units in the United Kingdom. The invitations were issued in 2007, 2009 and 2012, and applicants were asked to describe their expertise and staffing levels in specific areas. To ensure that the reviews were as objective as possible, a description of expected core competencies was developed and applicants were asked to document their compliance with meeting these. The review panel assessed each Clinical Trials Unit against the competencies. The Clinical Trials Unit registration process has evolved over time with each successive review benefiting from what was learned in earlier ones. RESULTS: The review panel has seen positive changes over time, including an increase in the number of units applying, a greater awareness on the part of host institutions about the trials activity within their organisations, more widespread development of Standard Operating Procedures in key areas and improvements in information technology systems used to host clinical trials databases. Key funders are awarding funds only to registered units, and host institutions are implementing procedures and structures to ensure improved communication between all parties involved in trials within their organisation. CONCLUSION: The registration process developed in the United Kingdom has helped to ensure that trials units in the United Kingdom are compliant with regulatory standards and can meet acceptable standards of quality in their conduct of clinical trials. There is an increased awareness among funders, host institutions and Clinical Trials Units themselves of the required competencies, and communication between all those involved in trials has increased. The registration process is an effective and financially viable way of ensuring that objective standards are met at a national level.