Urinary bother, Urinalysis, and Two-Year Efficacy Follow-Up Results of Phase I Trial of Intravesical Bacillus Calmette-Guérin Combined with Intravenous Pembrolizumab in Recurrent or Persistent High-Grade Non-Muscle-Invasive Bladder Cancer after Previous Bacillus Calmette-Guérin Treatment.

OBJECTIVE: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).

Untrained Bystanders Administering Drone-Delivered Naloxone: An Exploratory Study.

Introduction: Opioid overdose deaths continue to climb in the United States. Administering naloxone to an overdose victim can save their life, but rapid access to naloxone remains a barrier. Delivering naloxone to a bystander using a drone has potential to increase naloxone availability but there are still many uncertainties about this mode of delivery. Can an untrained bystander to an opioid overdose successfully administer drone delivered naloxone after viewing video instructions on the drone and how long does it take? Methods: This mixed-methods observational study, conducted in a controlled outdoor environment, simulated an opioid overdose using a mannequin (overdose victim) and panicked bystander. Untrained and medically naïve participants were instructed to call for help, move the drone from the landing spot to the mannequin, and follow the instructions provided by the drone to administer naloxone. Data was collected using video recordings, interviews, and an online survey. Time stamp data was extracted from the video for 2 time points: time for removing the naloxone from the drone and time to administer the naloxone. Interviews were audio recorded and analyzed using an inductive concept analysis approach. One interview question was coded as a binary response of anxiety/no anxiety and added to the demographic data. Results: The average time to remove and administer naloxone was 62 seconds. Anxiety during the activity was reported by 59% of the participants but there was no correlation between anxiety and time. The design of our drone and instructional video can be improved. Conclusions: We have established baseline times for completing steps in administering naloxone delivered by drone. We were able to successfully induce anxiety and have a baseline measure for what percentage of untrained bystanders may experience anxiety when involved with an emergency situation. Design of instructional materials and drone construction can contribute to anxiety and successful administration of naloxone.

Tolfenpyrad displays Francisella-targeted antibiotic activity that requires an oxidative stress response regulator for sensitivity.

IMPORTANCE: Francisella species are highly pathogenic bacteria that pose a threat to global health security. These bacteria can be made resistant to antibiotics through facile methods, and we lack a safe and protective vaccine. Given their history of development as bioweapons, new treatment options must be developed to bolster public health preparedness. Here, we report that tolfenpyrad, a pesticide that is currently in use worldwide, effectively inhibits the growth of Francisella. This drug has an extensive history of use and a plethora of safety and toxicity data, making it a good candidate for development as an antibiotic. We identified mutations in Francisella novicida that confer resistance to tolfenpyrad and characterized a transcriptional regulator that is required for sensitivity to both tolfenpyrad and reactive oxygen species.

Learning in a crisis moment: a randomized controlled trial in emergency bystander intervention.

BACKGROUND: Opioid overdose is the leading cause of injury-related death in the United States. Individuals who overdose outside of clinical settings have more positive clinical outcomes when they receive naloxone, an opioid antagonist, from a bystander as an early intervention before emergency personnel arrive. However, there is a gap in knowledge about successful instantaneous learning and intervention in a real-life stressful environment. The objective of this study is to explore the efficacy of different instructional delivery methods for bystanders in a stressful environment. We aim to evaluate which methods are most effective for instantaneous learning, successful intervention, and improved clinical outcomes. METHODS: To explore instantaneous learning in a stressful environment, we conducted a quantitative randomized controlled trial to measure how accurately individuals responded to memory-based survey questions guided by different instructional methods. Students from a large university in the Midwest (n = 157) were recruited in a public space on campus and accessed the six-question survey on their mobile devices. The intervention group competed the survey immediately while the research team created a distracting environment. The control group was asked to complete the survey later in a quiet environment. RESULTS: The intervention group correctly answered 0.72 questions fewer than the control group (p = .000, CI [0.337, 1.103]). Questions Q1 and Q5 contained direct instructions with a verbal component and showed the greatest accuracy with over 90% correct for both stressful and controlled environments. CONCLUSIONS: The variability in the responses suggests that there are environmental factors as well as instructional design features which influence instantaneous learning. The findings of this study begin to address the gap in knowledge about the effects of stress on instantaneous learning and the most effective types of instruction for untrained bystanders in emergency situations.

Assessing the Impact of Indiana Public Law 194 on Curbing the Concurrent Opioid Prescribing for Indiana Medicaid Enrollees.

Background: Several US states have introduced legislation to support the legitimate medical use of opioids while limiting misuse and diversion. One concern which has been addressed through legislation is preventing individuals from seeking opioid prescriptions concurrently from multiple providers. However, the impact of this legislation on the incidence of patients receiving concurrent prescriptions remains relatively unexplored. This study examines this phenomenon based on claims data from Medicaid enrollees and the enactment of legislation in Indiana. Methods: Indiana Medicaid claims data over the period of January 2014 to December 2019 were used to determine the changes in the percentage of individuals receiving opioid prescriptions from multiple providers within a 30-day period, that is, concurrent opioid prescription (COP) individuals. Indiana Medicaid enrollees with a diagnosis of opioid use disorder (OUD) receiving opioid prescriptions, that is, the OUD-group, were identified and separated from the enrollees without a diagnosis but receiving opioid prescriptions, that is, the non-OUD group. The mean percentages of COP individuals (with or without an OUD diagnosis) within the subset of individuals that received opioid prescriptions were compared before and after the passage of Indiana Public Law 194. Results: There were 5336 who met the criteria of COP individuals, and 2050 of those were in the OUD-group. In either group, there was a significant difference in the change in percentages (slope) before and after Indiana Public Law 194 passed. In addition, there was a significant decrease in the mean percentage of COP individuals in the non-OUD group, while the difference was not significant in the OUD group. Conclusion: Our study suggests that Indiana Public Law 194 had a positive impact on curbing COP. This study is limited by the level of details available from claims data and suggests additional studies to evaluate prescription use and prescribing practices are warranted.

Genomic recovery lags behind demographic recovery in bottlenecked populations of the Channel Island fox, Urocyon littoralis.

With continued global change, recovery of species listed under the Endangered Species Act is increasingly challenging. One rare success was the recovery and delisting of the Channel Island fox (Urocyon littoralis) after 90%-99% population declines in the 1990s. While their demographic recovery was marked, less is known about their genetic recovery. To address genetic changes, we conducted the first multi-individual and population-level direct genetic comparison of samples collected before and after the recent bottlenecks. Using whole-exome sequencing, we found that already genetically depauperate populations were further degraded by the 1990s declines and remain low, particularly on San Miguel and Santa Rosa Islands, which underwent the most severe bottlenecks. The two other islands that experienced recent bottlenecks (Santa Cruz, and Santa Catalina islands) showed mixed results based on multiple metrics of genetic diversity. Previous island fox genomics studies showed low genetic diversity before the declines and no change after the demographic recovery, thus this is the first study to show a decrease in genetic diversity over time in U. littoralis. Additionally, we found that divergence between populations consistently increased over time, complicating prospects for using inter-island translocation as a conservation tool. The Santa Catalina subspecies is now federally listed as threatened, yet other de-listed subspecies are still recovering genetic variation which may limit their ability to adapt to changing environmental conditions. This study further demonstrates that species conservation is more complex than population size and that some island fox populations are not yet 'out of the woods'.

Opioid-Related Treatment Disparities Among Medicaid Enrollees in Indiana.

Introduction: Health care disparities based on race/ethnicity and sex can be found in a variety of settings. Our aim is to determine if there are disparities in treatment provided to Indiana Medicaid enrollees who have medically documented opioid use. Study Data and Methods: We used Medicaid reimbursement claims data to extract patients who were diagnosed with opioid use disorder (OUD) or had other medical event related to opioid use between January 2018 and March 2019. We used a two-proportion Z-test to verify the difference in the proportion of treatment provided between population subgroups. The study was approved by the Purdue University Institutional Review Board (2019-118). Study Results: Over the study period, there were 52,994 Indiana Medicaid enrollees diagnosed with OUD or documentation of another opioid related event. Only 5.41% of them received at least one type of treatment service (detoxification, psychosocial, medication assisted treatment, or comprehensive). Discussion: Although Medicaid began covering treatment services for enrollees with an OUD in Indiana at the start of 2018, very few received evidence-based services. Men and White enrollees with an OUD were in general more likely to receive services compared to women and non-White enrollees.

Widespread gene flow following range expansion in Anna's Hummingbird.

Anthropogenic changes have altered the historical distributions of many North American taxa. As environments shift, ecological and evolutionary processes can combine in complex ways to either stimulate or inhibit range expansion. Here, we examined the role of evolution in a rapid range expansion whose ecological context has been well-documented, Anna's Hummingbird (Calypte anna). Previous studies have suggested that the C. anna range expansion is the result of an ecological release facilitated by human-mediated environmental changes, where access to new food sources have allowed further filling of the abiotic niche. We examined the role of gene flow and adaptation during range expansion from their native California breeding range, north into Canada and east into New Mexico and Texas, USA. Using low coverage whole genome sequencing we found high genetic diversity, low divergence, and little evidence of selection on the northern and eastern expansion fronts. Additionally, there are no clear barriers to gene flow across the native and expanded range. The lack of selective signals between core and expanded ranges could reflect (i) an absence of novel selection pressure in the expanded range (supporting the ecological release hypothesis), (ii) swamping of adaptive variation due to high gene flow, or (iii) limitations of genome scans for detecting small shifts in allele frequencies across many loci. Nevertheless, our results provide an example where strong selection is not apparent during a rapid, contemporary range shift.

Substance Use Disorder Education: A Statewide Assessment of Core Content in Nursing Schools.

Of individuals who need treatment for substance use disorder (SUD), 12.6% do not receive it. One reason for this failure to treat is an inadequately prepared health care workforce, including nurses. To establish a state-wide baseline of SUD curricular content, we collected information about topics taught and barriers to teaching important topics using an anonymous survey sent to all 55 nursing programs in Indiana. Topics deemed important were taught more frequently, such as opioid withdrawal (60.6%). Lack of expertise was more commonly reported as a barrier than lack of time (25.3% vs. 7.1%). Findings suggest that nursing students in Indiana are not taught requisite content related to SUD. We have provided pragmatic recommendations to enhance content in schools of nursing and address lack of expertise among faculty. Leaders need to actively evaluate and augment the content of their curriculums to include SUD. [Journal of Psychosocial Nursing and Mental Health Services, 61(9), 15-23.].

Trends of repeated emergency department visits among adolescents and young adults for substance use: A repeated cross-sectional study.

Emergency Department (ED) visits for substance-related concerns among young people have been increasing in recent years. Understanding the factors related to repeated ED visits (two or more ED visits per year) for substance use concerns among young people is critical to developing a more efficient mental healthcare system that does not overburden ED and that provides efficient care for substance use patients. This study examined trends of substance use-related ED visits and factors related to repeated ED visits (two or more ED visits per year, in comparison to one ED visit per year) among adolescents and young adults (aged 13 to 25 years) in the province of Ontario, Canada. Binary logistic regression models were conducted to examine associations between hospital-related factors (hospital size, urbanicity, triage level, ED wait time) and visit status (2+ vs 1 ED visit/year), controlling for patient characteristics (age/sex). A population-based, repeated cross-sectional data over a 10-year period (2008, 2013, and 2018) was used. The proportion of substance use-related repeated ED visits significantly and consistently increased in the year 2013 and 2018 compared to 2008 (2008 = 12.52%, 2013 = 19.47%, 2018 = 20.19%). Young adult, male, medium-sized hospital, urban location, wait times longer than 6 hours, and symptom severity was associated with increased numbers of repeated ED visits. Furthermore, polysubstance use, opioid use, cocaine use, and stimulant use were strongly associated with repeated ED visits compared with the use of substances such as cannabis, alcohol and sedatives. Current findings suggest that repeated ED visits for substance use concerns could be reduced by policies that reinforce evenly distributed mental health and addiction treatment services across the provinces in rural areas and small hospitals. These services should put special efforts into developing specific (e.g., withdrawal/treatment) programming for substance-related repeated ED patients. The services should target young people using multiple psychoactive substances, stimulants and cocaine.

Child developmental and special education service receipt: The intersection of health and poverty.

BACKGROUND: Children born of low birth weight (LBW) and/or premature may have developmental delays and difficulties. The vulnerability, without early intervention, would have detrimental lifelong effects. OBJECTIVES: This study examined 1) the relationship between LBW and prematurity and the occurrence and timing of children's receipt of developmental and special education services; and 2) whether poverty intersects with LBW and prematurity affecting service receipt. METHODS: This population-based study used cross-sectional data from the National Survey of Children's Health which consisted of approximately 52,000 participants aged 1-17 between 2017 and 2018 in the United States. We conducted logistic regression to analyze the predictive relationship of LBW/prematurity and the occurrence of receiving developmental and special education services. We then conducted ordered logistic regression to examine whether LBW and prematurity predicted the timing of receiving developmental and special education services. Further, we conducted moderating analyses to examine whether the predictive relationships above varied with poverty. The analyses listed above were weighted to reflect the population drawn. RESULTS: Children born with LBW and prematurity were more likely to receive developmental and special education services and they tended to receive services earlier than those born at normal weight and term. Educational disparities were evident among children in low-income families. Children of LBW in low-income families were less likely to receive earlier services than those in affluent families. CONCLUSIONS: This study indicates developmental and special education needs of children born LBW and/or premature. With restrained assets, low-income families may need more assistance to promote optimal development for their children.

Establishment and maintenance of DNA methylation in nematode feeding sites.

A growing body of evidence indicates that epigenetic mechanisms, particularly DNA methylation, play key regulatory roles in plant-nematode interactions. Nevertheless, the transcriptional activity of key genes mediating DNA methylation and active demethylation in the nematode feeding sites remains largely unknown. Here, we profiled the promoter activity of 12 genes involved in maintenance and de novo establishment of DNA methylation and active demethylation in the syncytia and galls induced respectively by the cyst nematode Heterodera schachtii and the root-knot nematode Meloidogyne incognita in Arabidopsis roots. The promoter activity assays revealed that expression of the CG-context methyltransferases is restricted to feeding site formation and development stages. Chromomethylase1 (CMT1), CMT2, and CMT3 and Domains Rearranged Methyltransferase2 (DRM2) and DRM3, which mediate non-CG methylation, showed similar and distinct expression patterns in the syncytia and galls at various time points. Notably, the promoters of various DNA demethylases were more active in galls as compared with the syncytia, particularly during the early stage of infection. Mutants impaired in CG or CHH methylation similarly enhanced plant susceptibility to H. schachtii and M. incognita, whereas mutants impaired in CHG methylation reduced plant susceptibility only to M. incognita. Interestingly, hypermethylated mutants defective in active DNA demethylation exhibited contrasting responses to infection by H. schachtii and M. incognita, a finding most likely associated with differential regulation of defense-related genes in these mutants upon nematode infection. Our results point to methylation-dependent mechanisms regulating plant responses to infection by cyst and root-knot nematodes.

Effect of Geography and Captivity on Scat Bacterial Communities in the Imperiled Channel Island Fox.

With developing understanding that host-associated microbiota play significant roles in individual health and fitness, taking an interdisciplinary approach combining microbiome research with conservation science is increasingly favored. Here we establish the scat microbiome of the imperiled Channel Island fox (Urocyon littoralis) and examine the effects of geography and captivity on the variation in bacterial communities. Using high throughput 16S rRNA gene amplicon sequencing, we discovered distinct bacterial communities in each island fox subspecies. Weight, timing of the sample collection, and sex contributed to the geographic patterns. We uncovered significant taxonomic differences and an overall decrease in bacterial diversity in captive versus wild foxes. Understanding the drivers of microbial variation in this system provides a valuable lens through which to evaluate the health and conservation of these genetically depauperate foxes. The island-specific bacterial community baselines established in this study can make monitoring island fox health easier and understanding the implications of inter-island translocation clearer. The decrease in bacterial diversity within captive foxes could lead to losses in the functional services normally provided by commensal microbes and suggests that zoos and captive breeding programs would benefit from maintaining microbial diversity.

Neurogenic Stunned Myocardium Following an Attempt to Pass a Drug Test.

Ingestion of a large volume of free water or other hypotonic solution can cause acute hyponatremia, leading to multiorgan dysfunction. Individuals may attempt to generate a false-negative urine drug screen through increased free water consumption leading to acute hyponatremia requiring emergency medical care. We present the case of a 19-year-old male who presented to a community emergency department for altered mental status after an attempt to generate a false-negative urine drug screen. He ingested a large volume of free water and multiple detoxification solutions, causing acute hyponatremia with resultant cerebral edema and neurogenic stunned myocardium. He required extracorporeal membrane oxygenation therapy with complete recovery of neurologic and cardiac function. Acute hyponatremia from excess free water consumption is a well-documented phenomenon that all emergency providers should be aware of. Prompt identification and management of acute hyponatremia are essential to prevent potentially severe, devastating sequelae, including cerebral edema and cardiopulmonary failure.In addition, extracorporeal membrane oxygenation may be considered in patients with cardiopulmonary failure in the setting of reversible cardiomyopathy, as evidenced in our case.

HIV-1 Transmission linkages among persons with incident infection to inform public health surveillance.

BACKGROUND: We evaluated features of HIV transmission networks involving persons diagnosed during incident HIV infection (IHI) to assess network-based opportunities to curtail onward transmission. METHODS: Transmission networks were constructed using partial pol sequences reported to North Carolina surveillance among persons with recent (2014-2018) and past (<2014) HIV diagnoses. IHI were defined as documented acute infections or seroconversion. Demographic and virologic features of HIV genetic clusters (<1.5% pairwise genetic distance) involving ≥ 1 IHI were assessed. Persons with viral genetic links and who had diagnoses >90 days prior to an IHI were further characterized. We assessed named partner outcomes among IHI index persons using contact tracing data. FINDINGS: Of 4,405 HIV diagnoses 2014-2018 with sequences, there were 323 (7%) IHI index persons; most were male (88%), Black (65%), young (68% <30 years), and reported sex with men (MSM) risk (79%). Index persons were more likely to be cluster members compared to non-index persons diagnosed during the same period (72% vs. 49%). In total, 162 clusters were identified involving 233 IHI, 577 recent diagnoses, and 163 past diagnoses. Most IHI cases (53%) had viral linkages to ≥1 previously diagnosed person without evidence of HIV viral suppression in the year prior to the diagnosis of the IHI index. In contact tracing, only 53% IHI cases named an HIV-positive contact, resulting in 0.5 previously diagnosed persons detected per IHI investigated. When combined with viral analyses, the detection rate of viremic previously diagnosed persons increased to 1.3. INTERPRETATION: Integrating public health with molecular epidemiology, revealed that more than half of IHI have viral links to persons with previously diagnosed unsuppressed HIV infection which was largely unrecognized by traditional contact tracing. Enhanced partner services to support engagement and retention in HIV care and improved case finding supported by rapid phylogenetic analysis are tools to substantially reduce onward HIV transmission.

Phase I trial of intravesical Bacillus Calmette-Guérin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin treatment.

OBJECTIVES: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment. METHODS: Eighteen patients were consented for the study, five of which were screen failures. Six doses of pembrolizumab were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated from the time of consent through 30 days following pembrolizumab treatment. Clinical activity was determined using cystoscopy and biopsy of suspicious lesions. RESULTS: Treatment-related adverse events included one grade 4 adverse event (AEs) (adrenal insufficiency). There were nine grade 3 AEs (chest discomfort, pulmonary embolism, arthritis, wrist edema, injection site reaction, bilateral wrist pain, cardiomyopathy, hypokalemia, urinary tract infection). There were 49 grade 1 and 30 grade 2 AEs (88% of AEs). Eleven patients finished the treatment, and two patients died during the study. Of 13 patients treated, nine patients (69%) had no evidence of disease at 3 months following BCG treatment. CONCLUSIONS: We report for the first time that combining BCG and pembrolizumab in treating HGNMIBC is safe allowing complete treatment of most patients. A phase III trial has opened to test the efficacy of this combination in HGNMIBC (KEYNOTE-676).

Assessing the impact of Indiana legislation on opioid-based doctor shopping among Medicaid-enrolled pregnant women: a regression analysis.

BACKGROUND: States have passed various legislative acts in an attempt to reduce opioid prescribing and corresponding doctor shopping, including prescription drug monitoring programs. This study seeks to determine the association between two state-based interventions enacted in Indiana and the level of doctor shopping among Medicaid-enrolled pregnant women. METHODS: Indiana Medicaid claims data over the period of January 2014 to March 2019 were used in a regression model to determine the longitudinal change in percentage of pregnant women engaged in doctor shopping based on passage of Indiana Administrative Code Title 884 in 2014 and Public Law 194 in 2018. The primary reasons for prescribing were also identified. RESULTS: There were 37,451 women that had both pregnancy and prescription opioid claims over the time horizon. Of these, 2130 women met the criteria for doctor shopping. Doctor shopping continued to increase over the time between the passage of the two interventions but decreased after passage of Public Law 194. CONCLUSION: The decrease in doctor shopping among Medicaid-enrolled pregnant women after passage of Public Law 194 points to the importance of addressing this issue across a broad set of healthcare professionals including nurse practitioners and physician assistants. It is also possible that the potential punitive component in the Law for non-compliance played a role.

Australia's persistently high rate of early-term prelabour Caesarean delivery.

Objective To compare the incidence of prelabour Caesarean delivery (PCD) at early term (37 weeks and 0 days (370) to 38 weeks and 6 days (386) of gestation) between Australian states and hospital sectors over time and to compare these rates with those of England and the United States of America (USA). Method A population-based descriptive study of 556040 singleton PCDs at term (370-406 weeks) in all public and private hospitals in Australian states, 2005-16, was performed. The primary outcome was the early-term PCD rate, defined as early-term PCDs as a percentage of all term PCDs. Results Across Australian states, the early-term PCD rate fell from 56.4% in 2005 to 52.0% in 2016. Over a similar period, England's rate fell from 48.2% in 2006-07 to 35.2% in 2016-17, while the USA's rate fell from 47.4% in 2006 to 34.2% in 2016. Australian public hospitals reduced their rate from 54.2% in 2005 to 44.7% in 2016, but the rate increased in private hospitals from 59.1% in 2005 to 62.5% in 2016. There was considerable variation between states and hospital sectors. Conclusions The early-term PCD rate increased in Australian private hospitals from 2005 to 2016. The public hospital rate fell by nearly 10% over the period but remained ~10% above the English and USA national rates. What is known about the topic? Babies born at early term (370-386 weeks) are at greater risk of morbidity than babies born at full term (390-406 weeks). Australia has a persistently high rate of early-term prelabour Caesarean delivery (PCD). What does this paper add? This paper reveals concerning differences in the early-term PCD rate between Australian states and hospital sectors. Further, the paper highlights that both Australian hospital sectors (public and private) have not reduced their rates to levels achieved in England and the USA. What are the implications for practitioners? These results should inform efforts to reduce Australia's early-term PCD rate to prevent harm to babies.

An Analysis of State-Level Policies and Opioid Overdose Deaths.

Many legislative and regulatory changes have occurred at the state level in response to the opioid crisis in an attempt to decrease overdose deaths. We conducted a negative binomial, regression-based, interrupted time series analysis to evaluate the effects of policies on opioid overdose death counts for 2008-2017 in five Midwestern states: Illinois, Indiana, Kentucky, Michigan, and Ohio. Except for the Good Samaritan laws in Illinois, no single policy change was statistically significant in decreasing overdose deaths. Governmental involvement as a whole was significantly associated with an increase in overdose deaths in Indiana. Policies created to address opioid overdose mortality have had minimal impact in these five Midwestern states. Most of the legislation and regulation that have been created lack educational components for prescribers and community members, which may explain why these policies have not had the intended effect.

Using Community Engagement to Map Pathways of Opioid Use and Recovery.

We created a tool for use by the community of Tippecanoe County Indiana and their Opioid Task Force to guide their collaborative efforts in addressing the opioid crisis. A community-engaged research strategy led to the creation of a map of opioid pathways based in a systems thinking approach that considers key stakeholders and community members as system components and reflects local resources, supply, and demand for services, and the social ecology unique to this community. Organizations are able to visualize the importance of their interactions with other organizations within the community as they work together to address the crisis. This approach could be replicated in other communities and used to address other public health issues.