Predicting accidental drug overdose as the cause of fatality in near real-time using the Suspected Potential Overdose Tracker (SPOT): public health implications.

BACKGROUND: Effective responses to the worsening drug overdose epidemic require accurate and timely drug overdose surveillance data. The objectives of this paper are to describe the development, functionality, and accuracy of the Suspected Potential Overdose Tracker (SPOT) for predicting accidental drug overdose as the cause and manner of death in near real-time, and public health implications of adopting the tool. METHODS: SPOT was developed to rapidly identify overdose deaths through a simple and duplicable process using data collected by death investigators. The tool assigns each death a ranking of 1 through 3 based on the likelihood of it being an unintentional drug overdose, with 1 representing the highest likelihood that the death will be confirmed as an unintentional drug overdose and 3 representing the lowest. We measured the accuracy of the tool for predicting overdose deaths by comparing potential overdose deaths in New York City from 2018-2020 that were identified using SPOT to finalized death certificates. We also calculated the proportion of death certificate-confirmed overdoses that were missed by the SPOT tool and the proportion of type 1 errors. RESULTS: SPOT captured up to 77% of unintentional drug overdose deaths using data collected within 72 h of fatality. The tool predicted unintentional drug overdose from 2018 to 2020 with 93-97% accuracy for cases assigned a ranking of 1, 87-91% accuracy for cases assigned a ranking of 2, and 62-73% accuracy for cases assigned a ranking of 3. Among all unintentional overdose deaths in 2018, 2019, and 2020, 21%, 28%, and 33% were missed by the SPOT tool, respectively. During this timeframe, the proportion of type 1 errors ranged from 15%-23%. CONCLUSIONS: SPOT may be used by health departments, epidemiologists, public health programs, and others to monitor overdose fatalities before death certificate data becomes available. Improved monitoring of overdose fatalities allows for rapid data-driven decision making, identification of gaps in public health and public safety overdose response, and evaluation and response to overdose prevention interventions, programs, and policies.

Increasing Heroin-Methamphetamine (Goofball) Use and Related Morbidity Among Seattle Area People Who Inject Drugs.

BACKGROUND AND OBJECTIVES: Methamphetamine use is increasing in the United States, potentially including the simultaneous injection of methamphetamine with heroin (goofball). We compared demographic, behavioral, contextual, and health factors among people who inject drugs (PWID) in the Seattle area and who reported that their main drug was goofball, heroin, or methamphetamine. METHODS: We used data from 2017 and 2019 cross-sectional surveys of clients at Public Health-Seattle & King County's syringe services program (N = 792). RESULTS: Among PWID participants, 55.3% reported using goofball in the last 3 months, and the proportion reporting goofball as their main drug doubled between 2017 (10.3%) and 2019 (20.1%, P < .001). The goofball group had the highest proportions of people who were aged less than 30, women, homeless or unstably housed, and recently incarcerated. PWID whose main drug was goofball reported considerable health risks and morbidity. Witnessing an opioid overdose was most commonly reported by participants whose main drug was goofball. This group also reported naloxone possession and use in an overdose situation more than other participants. The majority of participants were interested in reducing or stopping their opioid and stimulant use. DISCUSSION AND CONCLUSIONS: Among PWID, using goofball as a main drug doubled over 2 years and was characterized by contextual and individual factors that increase the risk of morbidity and mortality. SCIENTIFIC SIGNIFICANCE: This is the first study to characterize goofball use as a main drug. Clinical and public health efforts to diminish morbidity associated with opioid use need to integrate interventions that address the co-use of methamphetamine. (Am J Addict 2020;00:00-00).

Discussing Drug Use With Health Care Providers Is Associated With Perceived Need and Receipt of Drug Treatment Among Adults in the United States: We Need to Talk.

BACKGROUND: Drug treatment utilization is low despite a high public health burden of drug use disorders (DUDs). Engaging people at risk for DUDs across a broader range of health care settings may improve uptake of drug treatment. OBJECTIVES: To estimate the prevalence of drug use screening/discussions between health care providers and individuals with past-year drug use, and to assess the associations between drug use screening/discussions and perceived need and use of drug treatment. METHODS: We analyzed representative cross-sectional data from the 2015 to 2017 National Surveys on Drug Use and Health. The sample included adults aged 18 years and above reporting past-year drug use and ≥1 health care visit. We measured correlates of drug use screening/discussions using multinomial logistic regression. Overall and among adults meeting DUD criteria, we used logistic regression to estimate associations between drug use screening/discussions and (1) past-year drug treatment and (2) perceived need for treatment. RESULTS: In the full sample (n=21,505), 34.50% reported no screening/discussions, 44.50% reported screening only, and 21.00% reported discussions with providers. Discussions were associated with significantly higher odds of receiving any drug treatment [adjusted odds ratio (aOR)=3.52 (2.66-4.65)], specialty drug treatment [aOR=4.13 (2.92-5.82)], and perceived treatment need [aOR=2.08 (1.21-3.59)]. Among people with DUD (n=3,834; 15.69%), discussions were associated with treatment use, but not with perceived need. CONCLUSIONS: Discussing drug use with providers may impact people's perceptions of drug treatment need and use, indicating potential opportunities to engage people in addiction treatment. Addressing barriers to discussing drug use across care settings could increase treatment use, particularly among people with DUD.

Cirrhosis-related coagulopathy resulting in disseminated intravascular coagulation and spontaneous orbital hemorrhages.

A 33-year-old patient presented to our Emergency Department (ED) with left-sided eyelid ecchymoses and edema. A CT scan of the orbits demonstrated a left retrobulbar hemorrhage, prompting an ophthalmology consultation. Upon examination, the patient reported worsening eye pain and decreasing vision in the left eye. Despite aggressive management with superior and inferior lateral canthotomy/cantholysis with placement of an orbital drain, visual loss occurred, and the patient ultimately expired from her systemic condition. Coagulopathy from liver disease resulting in systemic hemorrhage is commonly seen. Orbital hemorrhage in this setting requires emergent diagnosis and management to prevent irreversible compressive optic neuropathy.

Barriers Faced by American Indian Women in Urban Wisconsin in Seeking Help Following an Experience of Intimate Partner Violence.

American Indian1 (AI) women experience high rates of intimate partner violence (IPV) and face many barriers when help-seeking. This study aims to understand better the context of IPV and help-seeking behaviors for urban AI women after experiences with IPV. Postcolonial and Indigenous feminist frameworks framed this critical ethnography study. Semistructured interviews with 34 AI IPV survivors2 living in Wisconsin urban areas were conducted. Our findings highlight context-specific structural barriers to help-seeking after experiences of IPV heightened by the COVID-19 pandemic. Context-specific and survivor-led interventions are necessary to address and reduce barriers that urban AI women face.

A transposon site hybridization screen identifies galU and wecBC as important for survival of Yersinia pestis in murine macrophages.

Yersinia pestis is able to survive and replicate within murine macrophages. However, the mechanism by which Y. pestis promotes its intracellular survival is not well understood. To identify genes that are important for Y. pestis survival in macrophages, a library comprised of ∼31,500 Y. pestis KIM6+ transposon insertion mutants (input pool) was subjected to negative selection in primary murine macrophages. Genes underrepresented in the output pool of surviving bacteria were identified by transposon site hybridization to DNA oligonucleotide microarrays. The screen identified several genes known to be important for survival of Y. pestis in macrophages, including phoPQ and members of the PhoPQ regulon (e.g., pmrF). In addition, genes predicated to encode a glucose-1-phosphate uridylyltransferase (galU), a UDP-N-acetylglucosamine 2-epimerase (wecB) and a UDP-N-acetyl-d-mannosamine dehydrogenase (wecC) were identified in the screen. Viable-count assays demonstrated that a KIM6+ galU mutant and a KIM6+ wecBC mutant were defective for survival in murine macrophages. The galU mutant was studied further because of its strong phenotype. The KIM6+ galU mutant exhibited increased susceptibility to the antimicrobial peptides polymyxin B and cathelicidin-related antimicrobial peptide (CRAMP). Polyacrylamide gel electrophoresis demonstrated that the lipooligosaccharide (LOS) of the galU mutant migrated faster than the LOS of the parent KIM6+, suggesting the core was truncated. In addition, the analysis of LOS isolated from the galU mutant by mass spectrometry showed that aminoarabinose modification of lipid A is absent. Therefore, addition of aminoarabinose to lipid A and complete LOS core (galU), as well as enterobacterial common antigen (wecB and wecC), is important for survival of Y. pestis in macrophages.

Human rhinovirus 2 induces the autophagic pathway and replicates more efficiently in autophagic cells.

Picornaviruses rearrange cellular membranes to form cytosolic replication sites. In the case of poliovirus and several other picornaviruses, these membranes are derived from subversion of the cellular autophagy pathway. We also reported observation of autophagosome-like structures during infection by two human rhinoviruses (HRVs), HRV-2 and HRV-14 (W. T. Jackson et al., PLoS Biol. 3:e156, 2005). Another group reported that HRV-2 does not induce autophagosomes or respond to changes in cellular autophagy (M. Brabec-Zaruba, U. Berka, D. Blaas, and R. Fuchs, J. Virol. 81:10815-10817, 2007). In this study, we tested HRV-2-infected cells for activation of autophagic signaling and changes in virus growth in response to changes in autophagy levels. Our data indicate that HRV-2 induces and subverts the autophagic machinery to promote its own replication.

A Historical Analysis of the Impact of Hegemonic Masculinities on Sexual Assault in the Lives of Ethnic Minority Women: Informing Nursing Interventions and Health Policy.

Women's experiences of sexual assault are rooted in and informed by a history that nurses need to understand in order to provide meaningful and effective care. In this article, we present a comprehensive literature review guided by intersectionality theory to deepen our understanding of the historical role that hegemonic masculinity plays in shaping ethnic minority women's experiences of sexual assault. Final sources included were analyzed using thematic analysis. On the basis of our analyses, we identified 4 themes: social order hierarchies, "othering" dynamics, economic labor divisions, and negative media/mass communication depiction. Our findings contribute to our understanding of these important histories that speak to the trauma of sexual violence inflicted upon the bodies of ethnic minority women, which we can incorporate into nursing education curricula. Incorporating this knowledge would equip nurses and allied health professionals with the necessary knowledge and skills that would enable them to help patients navigate multiple systems of oppression as they engage in help seeking following a sexual assault experience. This knowledge also acknowledges rather than dismisses the historically acceptable use of sexual violence against ethnic minority women. In addition, acknowledging these histories enables us to move forward as a society in engaging in an urgently needed cultural shift to address the hegemonic masculinities that perpetuate violence against women in the United States.

The Utility of Postcolonial and Indigenous Feminist Frameworks in Guiding Nursing Research and Practice About Intimate Partner Violence in the Lives of American Indian Women.

The purpose of this theoretical article is to analyze the utility of postcolonial and Indigenous feminist frameworks in informing nursing research and practice specific to addressing intimate partner violence (IPV) in the lives of Indigenous women. Prevailing feminist narratives of the 20th century focused overwhelmingly on patriarchy as the sole source of oppression against women and root cause of IPV. These narratives failed to consider the complex historical ways in which patriarchy intersected with colonialism and racism to produce violence, affecting the contemporary realities of Indigenous women. In contrast, postcolonial and Indigenous feminist frameworks consider the colonial history that has disempowered Indigenous women and their nations over centuries of settler occupation. Situating IPV within historical, legal, social, and political contexts can unmask how current research and health care discourses may continue to constrain, rather than improve, access, care, and services for Indigenous victims of IPV.

Anticipated use of a supervised drug consumption site among syringe services program clients in King County, Washington: Assessing the role of opioid overdose and injection behavior.

BACKGROUND: US jurisdictions are considering implementing supervised drug consumption sites (SCSs) to combat the overdose epidemic. No sanctioned SCS exists in the US, but King County, Washington has proposed Community Health Engagement Locations (CHELs), which would include supervised drug consumption. We assessed characteristics of people engaged in syringe services programs (SSPs) who anticipated SCS use. METHODS: We estimated prevalence of anticipated SCS use in a 2017 cross-sectional sample of King County SSP participants (N = 377). We used Poisson regression with robust standard errors to estimate likelihood of anticipated SCS use by overdose history (experienced, witnessed only, neither), public injection frequency (always, some/most times, never), drug use behaviors, and sociodemographic characteristics. RESULTS: The sample was primarily male (66.8 %), white (69.5 %), and averaged 37 years old. Almost two-thirds of participants witnessed or experienced an overdose in the past year (43.2 % witnessed only; 19.6 % experienced overdose). Four in five SSP participants (83.0 %) anticipated any SCS use. Anticipated SCS use was higher among participants who experienced an overdose (risk ratio [RR] = 1.14, 95 % CI = 1.04, 1.24) than those with no overdose experience. In multivariable analyses, anticipated SCS use was higher among people reporting injecting publicly (e.g., always vs. never: aRR = 1.26, 95 % CI = 1.11, 1.43), and lower among people primarily using methamphetamine (aRR = 0.80, 95 % CI = 0.67, 0.96) compared to people primarily using opioids. CONCLUSIONS: In King County, SCS services would be used by people at high risk of overdose, including SSP participants reporting injecting in public. SCSs could be an important step to promote health and safety across communities.

Yersinia pestis can reside in autophagosomes and avoid xenophagy in murine macrophages by preventing vacuole acidification.

Yersinia pestis survives and replicates in phagosomes of murine macrophages. Previous studies demonstrated that Y. pestis-containing vacuoles (YCVs) acquire markers of late endosomes or lysosomes in naïve macrophages and that this bacterium can survive in macrophages activated with the cytokine gamma interferon. An autophagic process known as xenophagy, which destroys pathogens in acidic autophagolysosomes, can occur in naïve macrophages and is upregulated in activated macrophages. Studies were undertaken here to investigate the mechanism of Y. pestis survival in phagosomes of naïve and activated macrophages and to determine if the pathogen avoids or co-opts autophagy. Colocalization of the YCV with markers of autophagosomes or acidic lysosomes and the pH of the YCV were determined by microscopic imaging of infected macrophages. Some YCVs contained double membranes characteristic of autophagosomes, as determined by electron microscopy. Fluorescence microscopy showed that approximately 40% of YCVs colocalized with green fluorescent protein (GFP)-LC3, a marker of autophagic membranes, and that YCVs failed to acidify below pH 7 in naïve macrophages. Replication of Y. pestis in naïve macrophages caused accumulation of LC3-II, as determined by immunoblotting. While activation of infected macrophages increased LC3-II accumulation, it decreased the percentage of GFP-LC3-positive YCVs (approximately 30%). A viable count assay showed that Y. pestis survived equally well in macrophages proficient for autophagy and macrophages rendered deficient for this process by Cre-mediated deletion of ATG5, revealing that this pathogen does not require autophagy for intracellular replication. We conclude that although YCVs can acquire an autophagic membrane and accumulate LC3-II, the pathogen avoids xenophagy by preventing vacuole acidification.

Poliovirus induces autophagic signaling independent of the ULK1 complex.

Poliovirus (PV), like many positive-strand RNA viruses, subverts the macroautophagy/autophagy pathway to promote its own replication. Here, we investigate whether the virus uses the canonical autophagic signaling complex, consisting of the ULK1/2 kinases, ATG13, RB1CC1, and ATG101, to activate autophagy. We find that the virus sends autophagic signals independent of the ULK1 complex, and that the members of the autophagic complex are not required for normal levels of viral replication. We also show that the SQSTM1/p62 receptor protein is not degraded in a conventional manner during infection, but is likely cleaved in a manner similar to that shown for coxsackievirus B3. This means that SQSTM1, normally used to monitor autophagic degradation, cannot be used to accurately monitor degradation during poliovirus infection. In fact, autophagic degradation may be affected by the loss of SQSTM1 at the same time as autophagic signals are being sent. Finally, we demonstrate that ULK1 and ULK2 protein levels are greatly reduced during PV infection, and ATG13, RB1CC1, and ATG101 protein levels are reduced as well. Surprisingly, autophagic signaling appears to increase as ULK1 levels decrease. Overexpression of wild-type or dominant-negative ULK1 constructs does not affect virus replication, indicating that ULK1 degradation may be a side effect of the ULK1-independent signaling mechanism used by PV, inducing complex instability. This demonstration of ULK1-independent autophagic signaling is novel and leads to a model by which the virus is signaling to generate autophagosomes downstream of ULK1, while at the same time, cleaving cargo receptors, which may affect cargo loading and autophagic degradative flux. Our data suggest that PV has a finely-tuned relationship with the autophagic machinery, generating autophagosomes without using the primary autophagy signaling pathway. ABBREVIATIONS: ACTB - actin beta; ATG13 - autophagy related 13; ATG14 - autophagy related 14; ATG101 - autophagy related 101; BECN1 - beclin 1; CVB3 - coxsackievirus B3; DMV - double-membraned vesicles; EM - electron microscopy; EMCV - encephalomyocarditis virus; EV-71 - enterovirus 71; FMDV - foot and mouth disease virus; GFP - green fluorescent protein; MAP1LC3B/LC3B - microtubule associated protein 1 light chain 3 beta; MOI - multiplicity of infection; MTOR - mechanistic target of rapamycin kinase; PIK3C3 - phosphatidylinositol 3-kinase catalytic subunit type 3; PRKAA2 - protein kinase AMP-activated catalytic subunit alpha 2; PSMG1 - proteasome assembly chaperone 1; PSMG2 - proteasome assembly chaperone 2PV - poliovirus; RB1CC1 - RB1 inducible coiled-coil 1; SQSTM1 - sequestosome 1; ULK1 - unc-51 like autophagy activating kinase 1; ULK2 - unc-51 like autophagy activating kinase 2; WIPI1 - WD repeat domain, phosphoinositide interacting 1.

Zebrafish short fin mutations in connexin43 lead to aberrant gap junctional intercellular communication.

Mutations in the zebrafish connexin43 (cx43) gene cause the short fin phenotype, indicating that direct cell-cell communication contributes to bone length. Three independently generated cx43 alleles exhibit short segments of variable sizes, suggesting that gap junctional intercellular communication may regulate bone growth. Dye coupling assays showed that all alleles are capable of forming gap junction channels. However, ionic coupling assays revealed allele-specific differences in coupling efficiency and gating. For instance, oocyte pairs expressing the weakest allele exhibited much higher levels of coupling than either of the strong alleles. Therefore, measurable differences in Cx43 function may be correlated with the severity of defects in bone length.

Grand rounds: nephrotoxicity in a young child exposed to uranium from contaminated well water.

CONTEXT: Private wells that tap groundwater are largely exempt from federal drinking-water regulations, and in most states well water is not subject to much of the mandatory testing required of public water systems. Families that rely on private wells are thus at risk of exposure to a variety of unmeasured contaminants. CASE PRESENTATION: A family of seven--two adults and five children--residing in rural northwestern Connecticut discovered elevated concentrations of uranium in their drinking water, with levels measured at 866 and 1,160 microg/L, values well above the U.S. Environmental Protection Agency maximum contaminant level for uranium in public water supplies of 30 microg/L. The uranium was of natural origin, and the source of exposure was found to be a 500-foot well that tapped groundwater from the Brookfield Gneiss, a geologic formation known to contain uranium. Other nearby wells also had elevated uranium, arsenic, and radon levels, though concentrations varied widely. At least one 24-hr urine uranium level was elevated (> 1 microg/24 hr) in six of seven family members (range, 1.1-2.5 microg/24 hr). To assess possible renal injury, we measured urinary beta-2-microglobulin. Levels were elevated (> 120 microg/L) in five of seven family members, but after correction for creatine excretion, the beta-2-microglobulin excretion rate remained elevated (> 40 microg/mmol creatinine) only in the youngest child, a 3-year-old with a corrected level of 90 microg/mmol creatinine. Three months after cessation of well water consumption, this child's corrected beta-2-microglobulin level had fallen to 52 microg/mmol creatinine. SIGNIFICANCE: This case underscores the hazards of consuming groundwater from private wells. It documents the potential for significant residential exposure to naturally occurring uranium in well water. It highlights the special sensitivity of young children to residential environmental exposures, a reflection of the large amount of time they spend in their homes, the developmental immaturity of their kidneys and other organ systems, and the large volume of water they consume relative to body mass.

Entrances and exits: health insurance churning, 1998-2000.

Analysis of 1998-2000 health insurance data from the Medical Expenditure Panel Survey shows large numbers of people with unstable health insurance coverage. Young adults, Hispanics, people with low levels of education, those who transition into and out of poverty, and those with private non-group insurance are most likely to have unstable coverage. In addition, demographic factors and type of insurance interact to determine stability of coverage. Young adults and Hispanics with Medicaid or private insurance, for example, were relatively likely to lose their coverage. And less than half of people who transitioned into and out of low income and were initially uninsured were able to obtain coverage. Policies must target these high-risk groups in order to provide them with stable health insurance coverage.

Anesthetic and airway management during laser treatment for retinopathy of prematurity: a survey of US ophthalmologists and neonatologists.

Ophthalmologists and neonatologists were surveyed to assess current practices for anesthetic and airway management techniques used during laser treatment for retinopathy of prematurity. Of the 351 practitioners who completed the survey, most perform fewer than 10 treatments annually. Intravenous sedation, rather than general anesthesia, is used by 60% of respondents. Routine intubation is used by 58%, whereas 36% monitor infants at their current level of respiratory support.

Nonarteritic anterior ischemic optic neuropathy in a child with optic disk drusen.

Optic disk drusen are calcific deposits that form in the optic nerve head secondary to abnormalities in axonal metabolism and degeneration. The clinical course is variable, ranging from stable vision to acute or progressive visual loss. We evaluated a healthy 12-year-old boy with a history of asymptomatic bilateral disk drusen who presented with acute painless unilateral visual loss after hiking to an altitude of 11,000 feet. Findings were consistent with nonarteritic anterior ischemic optic neuropathy.

Picornavirus subversion of the autophagy pathway.

While autophagy has been shown to act as an anti-viral defense, the Picornaviridae avoid and, in many cases, subvert this pathway to promote their own replication. Evidence indicates that some picornaviruses hijack autophagy in order to induce autophagosome-like membrane structures for genomic RNA replication. Expression of picornavirus proteins can specifically induce the machinery of autophagy, although the mechanisms by which the viruses employ autophagy appear to differ. Many picornaviruses up-regulate autophagy in order to promote viral replication while some members of the family also inhibit degradation by autolysosomes. Here we explore the unusual relationship of this medically important family of viruses with a degradative mechanism of innate immunity.

Mycobacterium marinum Erp is a virulence determinant required for cell wall integrity and intracellular survival.

The Mycobacterium tuberculosis exported repetitive protein (Erp) is a virulence determinant required for growth in cultured macrophages and in vivo. To better understand the role of Erp in Mycobacterium pathogenesis, we generated a mutation in the erp homologue of Mycobacterium marinum, a close genetic relative of M. tuberculosis. erp-deficient M. marinum was growth attenuated in cultured macrophage monolayers and during chronic granulomatous infection of leopard frogs, suggesting that Erp function is similarly required for the virulence of both M. tuberculosis and M. marinum. To pinpoint the step in infection at which Erp is required, we utilized a zebrafish embryo infection model that allows M. marinum infections to be visualized in real-time, comparing the erp-deficient strain to a DeltaRD1 mutant whose stage of attenuation was previously characterized in zebrafish embryos. A detailed microscopic examination of infected embryos revealed that bacteria lacking Erp were compromised very early in infection, failing to grow and/or survive upon phagocytosis by host macrophages. In contrast, DeltaRD1 mutant bacteria grow normally in macrophages but fail to induce host macrophage aggregation and subsequent cell-to-cell spread. Consistent with these in vivo findings, erp-deficient but not RD1-deficient bacteria exhibited permeability defects in vitro, which may be responsible for their specific failure to survive in host macrophages.