"It's Like A Partnership": Exploring the Primary Care Experiences and Patient-Defined Goals of People Who Use Drugs.

BACKGROUND: Primary care is an important yet underutilized resource in addressing the overdose crisis. Previous studies have identified important aspects of primary care for people who use drugs (PWUD) and have found patient involvement in healthcare decisions and goal-setting to be especially critical. However, there has been limited research describing the primary care goals of PWUD. In harm reduction settings, where it is imperative that PWUD set their own goals, this research gap becomes especially relevant. OBJECTIVE: To explore how PWUD navigate primary care with a focus on understanding their primary care goals. DESIGN: A qualitative study using semi-structured interviews. PARTICIPANTS: PWUD currently engaged in primary care at the Respectful and Equitable Access to Comprehensive Healthcare (REACH) Program, a harm reduction-based primary care program in New York City. APPROACH: Between June 2022 and August 2022, we conducted 17 semi-structured interviews. Informed by phenomenology, transcripts were coded using both inductive and deductive codes and themes were developed using thematic analysis approaches. KEY RESULTS: Phenomenological analysis identified four core components that, together, created an experience that participants described as "a partnership" between patient and provider: (1) patient-provider collaboration around patient-defined healthcare goals; (2) support provided by harm reduction-based approaches to primary care anchored in incrementalism and flexibility; (3) care teams' ability to address healthcare system fragmentation; and (4) the creation of social connections through primary care. This holistic partnership fostered positive primary care experiences and supported participants' self-defined care goals, thereby facilitating meaningful care outcomes. CONCLUSIONS: To best meet the primary care goals of PWUD, these findings underscore the importance of primary care providers and programs facilitating such partnerships through organizational-level support anchored in harm reduction. Future research should explore how these experiences in primary care affect patient health outcomes, ultimately shaping best practices in the provision of high-quality primary care for PWUD.

Applying a values-based decision process to facilitate comanagement of threatened species in Aotearoa New Zealand.

Ko koe ki tena, ko ahau ki tenai kiwai o te kete (you at that, and I at this handle of the basket). This Maori (New Zealanders of indigenous descent) saying conveys the principle of cooperation-we achieve more through working together, rather than separately. Despite decades of calls to rectify cultural imbalance in conservation, threatened species management still relies overwhelmingly on ideas from Western science and on top-down implementation. Values-based approaches to decision making can be used to integrate indigenous peoples' values into species conservation in a more meaningful way. We used such a values-based method, structured decision making, to develop comanagement of pekapeka (Mystacina tuberculata) (short-tailed bat) and tara iti (Sternula nereis davisae) (Fairy Tern) between Maori and Pakeha (New Zealanders of European descent). We implemented this framework in a series of workshops in which facilitated discussions were used to gather expert knowledge to predict outcomes and make management recommendations. For both species, stakeholders clearly stated their values as fundamental objectives from the start, which allowed alternative strategies to be devised that naturally addressed their diverse values, including matauranga Maori (Maori knowledge and perspectives). On this shared basis, all partners willingly engaged in the process, and decisions were largely agreed to by all. Most expectations of conflicts between values of Western science and Maori culture were unfounded. Where required, positive compromises were made by jointly developing alternative strategies. The values-based process successfully taha wairua taha tangata (brought both worlds together to achieve the objective) through codeveloped recovery strategies. This approach challenges the traditional model of scientists first preparing management plans focused on biological objectives, then consulting indigenous groups for approval. We recommend values-based approaches, such as structured decision making, as powerful methods for development of comanagement conservation plans between different peoples.

Aplicación de un Proceso de Decisiones Basadas en Valores para Facilitar el Comanejo de Especies Amenazadas en Aotearoa Nueva Zelanda Resumen Ko koe ki tena, ko ahau ki tenai kiwai o te kete (tú en ésa y yo en esta asa de la cesta). Este dicho Maori (neozelandeses con ascendencia indígena) expresa el principio de la cooperación - logramos más trabajando juntos que por separado. A pesar de las décadas de peticiones para rectificar el desbalance ambiental que existe en la conservación, el manejo de especies amenazadas todavía depende abrumadoramente de ideas tomadas de la ciencia occidental y en la implementación de arriba-abajo. Los enfoques para la toma de decisiones basados en valores pueden usarse para integrar de manera más significativa los valores de los pueblos indígenas dentro de la conservación de especies. Usamos un método basado en valores, la toma estructurada de decisiones, para desarrollar una estrategia de comanejo del pekapeka (Mystacina tuberculata) (murciélago de cola corta) y el tara iti (Sternula nereis davisae) (charrancito australiano) entre los Maori y los Pakeha (neozelandeses de ascendencia europea). Implementamos este marco de trabajo en una serie de talleres en los cuales se usaron discusiones facilitadas para recabar el conocimiento de los expertos para pronosticar los resultados y realizar recomendaciones de manejo. Para ambas especies, los actores sociales mencionaron claramente a sus valores como objetivos fundamentales desde el inicio, lo que permitió el diseño de estrategias alternativas que consideraran naturalmente estos diferentes valores, incluyendo el matauranga Maori (conocimiento y perspectivas Maori). Sobre esta base compartida, todos los colaboradores participaron voluntariamente en el proceso y la mayoría estuvo de acuerdo con las decisiones. La mayoría de los conflictos esperados entre la ciencia occidental y la cultura Maori no tuvieron fundamentos. En donde fueron requeridos, se realizaron concesiones positivas mediante el desarrollo conjunto de estrategias alternativas. El proceso basado en valores logró exitosamente taha wairua taha tangata (juntó a ambos mundos para conseguir el objetivo) por medio de estrategias de recuperación desarrolladas en conjunto. Esta estrategia desafía el modelo tradicional de los científicos preparando primero los planes de manejo enfocados en objetivos biológicos para después consultar a los grupos indígenas para que los aprueben. Recomendamos estos enfoques basados en valores, como la toma estructurada de decisiones, como métodos poderosos para el desarrollo de planes de conservación que incluyan el comanejo entre diferentes pueblos y personas.

U.S. Survey of Shared Decision Making Use for Treating Pregnant Women Presenting with Opioid Use Disorder.

Background: The incidence of pregnant women with an opioid use disorder (PWOUD) at delivery has quadrupled since 1999. State-specific statutes regarding PWOUD often pose punitive measures to the mother-infant dyad, involving the child welfare and criminal justice systems. Shared decision making (SDM) assists individuals through complex health and recovery processes. Objectives: To determine use of SDM in treating PWOUD and associated factors and to quantify physicians' review and discussion of child welfare statutes. Methods: The American College of Obstetricians and Gynecologists (ACOG) e-mailed the survey to a random sample of members, with 568 responding. Bivariate analyses to identify factors associated with each outcome were performed using Wilcoxon Rank Sum tests or Fisher's Exact tests. Variables yielding p values < .20 were included in initial logistic regression models; the final model included only significant (<.05) variables. Results: Sixty-one percent used SDM most of the time. Logistic regression indicated that those using SDM were more likely to have had training in substance use disorder and felt prepared for caring for PWOUD; 39% reviewed statutes, and 54% discussed them with PWOUDs. Conclusion: Survey results provide evidence for patient-centered care approaches that support PWOUD involvement in treatment decision making. The SDM model provides an empowerment framework for women to be involved in the process during their pregnancies and opioid use disorder treatments. Future studies might assess the effectiveness of SDM dialogs with PWOUD and evaluate CME training and medical curricula regarding the SDM model.

The impact on hospital resource utilisation of treatment of hepatic encephalopathy with rifaximin-α.

BACKGROUND & AIMS: Rifaximin-α reduces the risk of recurrence of overt hepatic encephalopathy. However, there remain concerns regarding the financial cost of the drug. We aimed to study the impact of treatment with rifaximin-α on healthcare resource utilisation using data from seven UK liver treatment centres. METHODS: All seven centres agreed a standardised data set and data characterising clinical, demographic and emergency hospital admissions were collected retrospectively for the time periods 3, 6 and 12 months before and following initiation of rifaximin-α. Admission rates and hospital length of stay before and during therapy were compared. Costs of admissions and drug acquisition were estimated using published sources. Multivariate analyses were carried out to assess the relative impact of various factors on hospital length of stay. RESULTS: Data were available from 326 patients. Following the commencement of rifaximin, the total hospital length of stay reduced by an estimated 31-53%, equating to a reduction in inpatient costs of between £4858 and £6607 per year. Taking into account drug costs of £3379 for 1-year treatment with rifaximin-α, there was an estimated annual mean saving of £1480-£3228 per patient. CONCLUSIONS: Initiation of treatment with rifaximin-α was associated with a marked reduction in the number of hospital admissions and hospital length of stay. These data suggest that treatment of patients with rifaximin-α for hepatic encephalopathy was generally cost saving.

Mechanically modulating the photophysical properties of fluorescent protein biocomposites for ratio- and intensiometric sensors.

Mechanically sensitive biocomposites comprised of fluorescent proteins report stress through distinct pathways. Whereas a composite containing an enhanced yellow fluorescent protein (eYFP) exhibited hypsochromic shifts in its fluorescence emission maxima following compression, a composite containing a modified green fluorescent protein (GFPuv) exhibited fluorescence quenching under the action of mechanical force. These ratio- and intensiometric sensors demonstrate that insights garnered from disparate fields (that is, polymer mechanochemistry and biophysics) can be harnessed to guide the rational design of new classes of biomechanophore-containing materials.

The shared decision-making tool for caregivers of children with prenatal opioid exposure: A pilot and acceptability study.

This pilot and acceptability study sought to report provider acceptability and developmental concerns expressed by caregivers of children with prenatal opioid exposure using the Shared Decision-Making Tool (SDMT), an instrument created by study authors. Data were collected from five health care and early intervention providers and 83 caregivers from a medical clinic and early intervention service center. Descriptive statistics were used to identify frequency, mean level, and prioritization of developmental concerns using the SDMT, and to summarize provider acceptability about integrating the SDMT into their workflow. Communication was the most frequently cited concern in four consecutive age categories, followed by Inattention/impulsivity and Problem behavior. All providers "strongly agreed" or "agreed" with all statements on the provider feedback survey, except two instances. Results of this study support the SDMT as a potential tool to help engage caregivers and providers of children with prenatal opioid exposure in the shared decision-making process by standardizing communication related to areas of developmental concern and caregivers' priority needs. Findings from this pilot study will inform modifications to the SDMT and administration instructions before our next study, which will examine psychometric properties and caregiver acceptability of the scale.

Preparing Physicians to Treat Addiction: Inclusion of Dedicated Addiction Training During Internal Medicine Residency.

BACKGROUND: Physicians in internal medicine lack comfort and skills required to diagnose and treat substance use disorder (SUD). Formal training in substance use treatment within primary care training has traditionally been inconsistent and sparse. The purpose of this study is to assess the impact of a longitudinal experiential addiction curriculum on the attitudes and experiences of graduates from a primary care/internal medicine residency program that included formal addiction didactics, rotations in an outpatient addiction clinic embedded within the resident primary care clinic, and exposure to addiction medicine faculty across treatment settings. METHODS: A survey was emailed to all graduates from a single academic primary care residency program who graduated between 2016 and 2018 (n = 53). The survey assessed pharmacotherapy for SUD prescribing patterns, comfort with SUD pharmacotherapy, overall comfort treating SUD, experience correcting stigmatizing language, and providing guidance to colleagues on the care of patients with SUD. A subset of respondents (n = 14) were interviewed regarding their experience with the residency program's addiction medicine curriculum and its impact on their current clinical practice. RESULTS: Sixty percent (n = 28) of graduates responded to the survey. All respondents felt comfortable using medications to treat SUD. Eighty-four percent perceived themselves as more comfortable using pharmacotherapy to treat SUD than their colleagues. Qualitative interviews revealed that this addiction medicine training shaped participants' attitudes toward patients with SUD and imparted them with the skills to address stigmatizing language. Participants described how they have become ambassadors of addiction medicine in their workplace and a resource to colleagues with less comfort in the management of SUD. CONCLUSION: Graduates of a primary care/internal medicine residency with a dedicated addiction medicine curriculum are comfortable prescribing pharmacotherapy for SUD, taking an active role in reducing SUD-related stigma, and serving as a resource for colleagues.

Increasing Chlamydia and Gonorrhea Testing for Adolescents in the Pediatric Emergency Department.

OBJECTIVE: Adolescents who use the emergency department are more likely to engage in high-risk sexual activity and are at an increased risk of sexually transmitted infections. We aimed to increase testing for Chlamydia and gonorrhea from 12% to 50% among adolescents presenting to our pediatric emergency department with at-risk chief complaints over 12 months. METHODS: Plan-Do-Study-Act cycles were initiated in July 2020. A multidisciplinary team reviewed preexisting data and developed interventions to increase Chlamydia and gonorrhea testing in teens with at-risk complaints, including genitourinary and behavioral health complaints, and females with abdominal pain. Two categories of interventions were implemented: education and electronic medical record optimization. Process measures were the proportion of patients with a documented sexual history and the proportion of patients tested with a documented confidential phone number. Secondary outcome measures included the weekly number of positive test results and the proportion of patients testing positive who were contacted to arrange treatment. Statistical process control charts were used to examine changes in measures over time. RESULTS: Within 14 months of project initiation, the proportion of at-risk patients tested increased from 12% to 59%. Teen phone number documentation remained unchanged from 23%. Sexual history documentation remained unchanged from 46%. The number of positive test results increased from 1.8 to 3.4 per month, and the proportion of patients testing positive who were contacted to arrange treatment remained unchanged at 83%. CONCLUSIONS: We surpassed our goal and increased the proportion of at-risk patients tested for Chlamydia and gonorrhea to 59%, sustained for 4 months from the last intervention.

Overexpression of NF-κB p65 in macrophages ameliorates atherosclerosis in apoE-knockout mice.

The transcription factor NF-κB p65 is a key regulator in the regulation of an inflammatory response and in the pathology of atherosclerosis. However, there is no direct evidence for the role of NF-κB in macrophages in the development of atherosclerosis. We investigated whether macrophage overexpression of p65 in apoE-knockout mice could improve atherosclerosis. Transgenic (Tg) mice overexpressing p65 in macrophages were generated by crossing fatty acid-binding protein 4 (aP2) promoter-controlled p65 mice with apoE-knockout (KO) mice. Tg mice exhibited functional activation of NF-κB signaling in macrophages and fat tissues. We observed that the atherosclerotic lesion was 40% less in the Tg mice compared with the apoE-KO controls fed a standard atherogenic diet for 16 wk (n = 12). The Tg mice were leaner from reduced fat mass by increased energy expenditure. Moreover, the overexpression of p65 in macrophages suppressed foam cell formation. Our results show that there is 1) an increased fatty acid oxidation in macrophages, 2) a reduced scavenger receptor CD36 expression and lipid accumulation in microphages, 3) reduced-inflammation cytokines in serum, and 4) enhanced energy expenditure in Tg mice. Our data suggest that activation of NF-κB in macrophages has atheroprotective effects in mice by enhancing lipid metabolism and energy expenditure.

Changes in seasonal expression patterns of ecdysone receptor, retinoid X receptor and an A-type allatostatin in the copepod, Calanus finmarchicus, in a sea loch environment: an investigation of possible mediators of diapause.

The marine copepod, Calanus finmarchicus, is a crucial component of the pelagic food web in the North Atlantic and peripheral seas where it is a major player in biogeochemical cycles and the productivity of commercially important fisheries. A key stage in its life cycle is the emergence of the pre-adult, copepodite developmental stage five (CV) from a period of overwintering dormancy, known as diapause. As is the case in many insect species, diapause is also likely to be under endocrine control in C. finmarchicus. To investigate the hormonal regulation of diapause behaviour of stage CV C. finmarchicus, the expression of three key genes: ecdysone receptor (EcR), retinoid X receptor (RXR) and an A-type allatostatin (A-type AST), were measured in specimens collected at monthly intervals from Loch Etive, a ca. 150m deep sea loch on the west coast of Scotland, between June 2006 and May 2007. The full length RXR gene was cloned and sequenced from C. finmarchicus, and was found to share 49-53% total identity with equivalent genes encoding proteins from other crustaceans, and >80% identity in the DNA binding domain with other crustaceans, insects and vertebrates. EcR expression was least in December when the animals are expected to be in diapause, but began to increase in January, when the animals were terminating diapause. Concomittant with the rise in EcR in January was low expression of A-type AST and high expression of RXR.

The sensory and affective components of pain differentially shape pupillary dilatation during cold pressor tests.

Nociceptive and affective stimuli increase reflex sympathetic outflow to the pupils. To investigate effects of stimulus intensity, unpleasantness and distress on these pupillary reflexes, and to assess their stability, healthy participants immersed their hand in ice-water three times (for 20, 40 and 60 s; or 60, 40 and 20 s; or three times for 60 s) (N = 21 in each condition). Each ice-water immersion was preceded by a 90 s warm water immersion. To evaluate phasic sympathetic influences on pupil diameter, pupillary re-dilatation after 1 s of bright light was assessed during the last 10 s of each immersion. By-and-large, pain ratings and pupil diameter were greater during longer than shorter ice-water immersions, and ice-water immersions facilitated pupillary re-dilatation after the flash stimulus. However, mean pupil diameter during ice- and warm water immersions, minor ipsilateral amplification of the pupillary response, and ratings of pain unpleasantness and distress decreased across the experiment. Together, these findings suggest that nociceptive input increased sympathetic pupillary tone and amplified phasic increases in sympathetic activity after exposure to light. However, tonic sympathetic influences on pupil diameter and lateralization decreased across repeated immersions, possibly as novel or threatening aspects of the experience declined. Pupillary nociceptive and affective reflexes involve the locus coeruleus, an integral component of neural circuits that heighten cortical arousal and regulate pain. As these reflexes appear to reflect different aspects of sensory and affective processing, their combined assessment might increase the sensitivity and specificity of tests of locus coeruleus function in patients with suspected deficits.

Xylazine in the drug supply: Emerging threats and lessons learned in areas with high levels of adulteration.

BACKGROUND: Xylazine, a sedative analgesic drug approved as an animal tranquilizer but not for human use, has become an adulterant in the illicit opioid marketplace in North America. Recently declared an emerging health threat in the U.S., the prevalence of xylazine in overdose deaths increased 5.5-fold between 2019 and 2021. More information is needed about the impact of xylazine on opioid users and harm reduction service providers. METHODS: The impact of xylazine adulteration was triangulated through examination of (1) opioid overdose fatalities in Connecticut between 2017 and 2021 reported by the Office of the Chief Medical Examiner data, (2) a convenience survey of people in Connecticut who use drugs (PWUD) regarding their knowledge of and attitude about the local illicit drug supply, and (3) semi-structured interviews of harm reduction service providers in Connecticut and Philadelphia in response to prompts on the impacts of and responses to xylazine adulteration. RESULTS: The presence of fentanyl or its analogues in fatal opioid overdoses was a statistically significant predictor of xylazine presence [OR = 25.0, 95%CI (10.7,81.1)] as was being Hispanic [OR = 1.36, 95%CI (1.03,1.77)]. A survey of people who used drugs revealed that 43% (n = 286) were concerned that the drug supply was always unpredictable. Three-quarters of respondents were aware of xylazine and two-thirds would use a xylazine test strip if one was available. Respondents who identified as White, Hispanic were most likely to be aware of xylazine, to have used a fentanyl test strip, and to be interested in a xylazine test strip. Respondents who injected drugs were 3.6-fold more likely than those who did not inject to endorse an interest in a xylazine test strip. Harm reduction service providers were cognizant of a range of problems surrounding the use and injection of xylazine. Although they reported implementing practices to better respond to xylazine harms, they recognized the absence of solutions to many of the problems encountered. CONCLUSION: The prevalence of xylazine has expanded, especially in combination with fentanyl. Harm reduction education efforts with fidelity to best practices have emerged, but the harms persist and community prevention needs are largely unmet.

Stakeholder-driven development and implementation of CRICIT: an app to support high-quality data capture and protocol monitoring for outpatient clinical trials with vulnerable populations.

Introduction: Choosing an appropriate electronic data capture system (EDC) is a critical decision for all randomized controlled trials (RCT). In this paper, we document our process for developing and implementing an EDC for a multisite RCT evaluating the efficacy and implementation of an enhanced primary care model for individuals with opioid use disorder who are returning to the community from incarceration. Methods: Informed by the Knowledge-to-Action conceptual framework and user-centered design principles, we used Claris Filemaker software to design and implement CRICIT, a novel EDC that could meet the varied needs of the many stakeholders involved in our study. Results: CRICIT was deployed in May 2021 and has been continuously iterated and adapted since. CRICIT's features include extensive participant tracking capabilities, site-specific adaptability, integrated randomization protocols, and the ability to generate both site-specific and study-wide summary reports. Conclusions: CRICIT is highly customizable, adaptable, and secure. Its implementation has enhanced the quality of the study's data, increased fidelity to a complicated research protocol, and reduced research staff's administrative burden. CRICIT and similar systems have the potential to streamline research activities and contribute to the efficient collection and utilization of clinical research data.

Sexual History Documentation and Screening in Adolescent Females with Suicidal Ideation in the Emergency Department.

Adolescents with mental illness often seek care in the emergency department (ED) and are more likely to engage in risky behaviors such as substance abuse and unprotected sex, increasing their risk of sexually transmitted infections (STI), unintended pregnancy, and non-consensual sex. This was a retrospective study of 312 females, aged 13-17 years, presenting to the pediatric ED with the chief complaint of suicidal ideation from February to May 2018. Electronic medical records were reviewed for demographics, psychiatric history, sexual history, and testing for pregnancy or STI. The primary outcome was the documentation of the presence or absence of prior sexual activity. Secondary outcomes included documented aspects of sexual history and pregnancy or STI testing performed in the ED. Of the 312 eligible patients, 144 (46.2%) had a documented sexual history, and of those 50 (34.7%) reported being sexually active. Sexual history documentation was not associated with patient age, race, ethnicity, insurance, or the gender of the ED provider. A history of anxiety and a recent suicide attempt were associated with a lack of sexual history documentation (p = 0.03). Of the sexually active patients, 28 (56%) had documentation of contraception use. Pregnancy testing was performed in 67.3% of all patients and 80% of sexually active patients. Only 10 patients had STI testing in the ED, with most testing occurring in those with sexual history documentation (p = 0.007). In conclusion, more than half of females with suicidal ideation in our ED had no documentation of sexual history, and when documentation was completed, it was often missing important elements, including screening for pregnancy, STI, non-consensual sex, and contraception use. Since the ED visit provides an important opportunity to address the reproductive health needs of this high-risk population, further work is needed to determine ways to improve provider documentation and sexual health screening.

Chromosomal translocations are a common phenomenon in Arabidopsis thaliana T-DNA insertion lines.

Ordered collections of Arabidopsis thaliana lines containing mapped T-DNA insertions have become an important resource for plant scientists performing genetic studies. Previous reports have indicated that T-DNA insertion lines can have chromosomal translocations associated with the T-DNA insertion site, but the prevalence of these rearrangements has not been well documented. To determine the frequency with which translocations are present in a widely-used collection of T-DNA insertion lines, we analyzed 64 independent lines from the Salk T-DNA mutant collection. Chromosomal translocations were detected in 12 of the 64 lines surveyed (19%). Two assays were used to screen the T-DNA lines for translocations: pollen viability and genome-wide genetic mapping. Although the measurement of pollen viability is an indirect screen for the presence of a translocation, all 11 of the T-DNA lines showing an abnormal pollen phenotype were found to contain a translocation when analyzed using genetic mapping. A normal pollen phenotype does not, however, guarantee the absence of a translocation. We observed one T-DNA line with normal pollen that nevertheless had a translocation based on genetic mapping results. One additional phenomenon that we observed through our genetic mapping experiments was that the T-DNA junctions on the 5'- and 3'-sides of a targeted gene can genetically separate from each other in some cases. Two of the lines in our survey displayed this 'T-DNA borders separate' phenomenon. Experimental procedures for efficiently screening T-DNA lines for the presence of chromosomal abnormalities are presented and discussed.

IRB Decision-Making about Minimal Risk Research with Pregnant Participants.

Pregnant individuals are often excluded from research without clear justification, even when the research poses minimal risk of harm to the fetus. Little is known about institutional review board (IRB) decision-making practices when reviewing such research. We conducted a survey of current and former IRB personnel in the United States to elicit their interpretations of "minimal risk"-a formal regulatory category-and to identify factors that may influence IRB decisions to approve or disapprove research involving pregnant participants. Study results revealed some consensus among IRB members about the risk level of individual research procedures and hypothetical study vignettes. However, we uncovered important variations not only in the assessment of risk but also in the willingness of IRB members to approve minimal risk research that includes pregnant women. Based on our findings, guidance is needed to assist IRB members in characterizing risk, applying federal regulations, and appropriately ensuring the inclusion or justified exclusion of pregnant people in research.

Potential Therapeutic Targets for Combination Antibody Therapy against Pseudomonas aeruginosa Infections.

Despite advances in antimicrobial therapy and even the advent of some effective vaccines, Pseudomonas aeruginosa (P. aeruginosa) remains a significant cause of infectious disease, primarily due to antibiotic resistance. Although P. aeruginosa is commonly treatable with readily available therapeutics, these therapies are not always efficacious, particularly for certain classes of patients (e.g., cystic fibrosis (CF)) and for drug-resistant strains. Multi-drug resistant P. aeruginosa infections are listed on both the CDC's and WHO's list of serious worldwide threats. This increasing emergence of drug resistance and prevalence of P. aeruginosa highlights the need to identify new therapeutic strategies. Combinations of monoclonal antibodies against different targets and epitopes have demonstrated synergistic efficacy with each other as well as in combination with antimicrobial agents typically used to treat these infections. Such a strategy has reduced the ability of infectious agents to develop resistance. This manuscript details the development of potential therapeutic targets for polyclonal antibody therapies to combat the emergence of multidrug-resistant P. aeruginosa infections. In particular, potential drug targets for combinational immunotherapy against P. aeruginosa are identified to combat current and future drug resistance.

Implementation of a volunteer contact tracing program for COVID-19 in the United States: A qualitative focus group study.

BACKGROUND: Contact tracing is an important tool for suppressing COVID-19 but has been difficult to adapt to the conditions of a public health emergency. This study explored the experiences and perspectives of volunteer contact tracers in order to identify facilitators, challenges, and novel solutions for implementing COVID-19 contact tracing. METHODS: As part of a study to evaluate an emergently established volunteer contact tracing program for COVID-19 in New Haven, Connecticut, April-June 2020, we conducted focus groups with 36 volunteer contact tracers, thematically analyzed the data, and synthesized the findings using the RE-AIM implementation framework. RESULTS: To successfully reach cases and contacts, participants recommended identifying clients' outreach preferences, engaging clients authentically, and addressing sources of mistrust. Participants felt that the effectiveness of successful isolation and quarantine was contingent on minimizing delays in reaching clients and on systematically assessing and addressing their nutritional, financial, and housing needs. They felt that successful adoption of a volunteer-driven contact tracing model depended on the ability to recruit self-motivated contact tracers and provide rapid training and consistent, supportive supervision. Participants noted that implementation could be enhanced with better management tools, such as more engaging interview scripts, user-friendly data management software, and protocols for special situations and populations. They also emphasized the value of coordinating outreach efforts with other involved providers and agencies. Finally, they believed that long-term maintenance of a volunteer-driven program requires monetary or educational incentives to sustain participation. CONCLUSIONS: This is one of the first studies to qualitatively examine implementation of a volunteer-run COVID-19 contact tracing program. Participants identified facilitators, barriers, and potential solutions for improving implementation of COVID-19 contact tracing in this context. These included standardized communication skills training, supportive supervision, and peer networking to improve implementation, as well as greater cooperation with outside agencies, flexible scheduling, and volunteer incentives to promote sustainability.

Chronic Systemic Inflammatory Skin Disease as a Risk Factor for Cardiovascular Disease.

Chronic systemic skin disease and cardiovascular disease are multisystem disorders which have been associated with each other for centuries. Recent research has strengthened this association, particularly in systemic inflammatory disease. Here we explore the current literature on psoriasis, hidradenitis suppurativa, lupus erythematosus, acanthosis nigricans, atopic dermatitis, and bullous pemphigoid. Psoriasis is a chronic inflammatory disorder that has been labeled as a risk-modifier for hyperlipidemia and coronary artery disease by the American College of Cardiology ACC lipid guidelines. Cardiovascular disease is also found at a significantly higher rate in patients with hidradenitis suppurativa and lupus erythematosus. Some associations have even been noted between cardiovascular disease and acanthosis nigricans, atopic dermatitis, and bullous pemphigoid. While many of these associations have been attributed to a shared underlying disease process such as chronic systemic inflammation and shared underlying risk factors, these dermatologic manifestations can help to identify patients at higher risk for cardiovascular disease.

The geography of emergency department-based HIV testing in South Africa: Can patients link to care?

BACKGROUND: Emergency Departments (EDs) can serve as clinical sites for identification of new HIV infections and their entry into care. We examined if HIV-positive patients who present to EDs in South Africa are able to successfully link to care. METHODS: We conducted a one-year longitudinal prospective cohort study in four hospitals across the Eastern Cape, South Africa, with participants followed between July 2016 and July 2018. All adult, non-critical patients presenting to the ED were systematically approached, asked about their HIV status, and, if unknown, offered a point-of-care (POC) HIV test. All HIV-positive patients were further consented to participate in a follow-up study to assess subsequent linkage to care and distance from "home" to ED. Linkage to care was defined as self-reported linkage (telephonic) or evidence of repeated CD4/viral load testing in the National Health Laboratory System (NHLS) at either the 6- or 12-months post index ED visit. FINDINGS: A total of 983 HIV-positive patients consented to participate in the study. In the 12 months following their ED visit, 34·1% of patients demonstrated linkage to care (335/983), 23·8% did not link to care (234/983), and 42·1% (414/983) were lost to follow-up. Though not statistically significant, a high percentage of young men (27/50, 54%) and those presenting with a trauma-related complaints (100/205, 48.8%) did not link to care. A considerable proportion of patients (105/454, 23·2%,) resided 50 or more kilometers from their index ED sites, though there was not a significant difference in linkage to care rate between those who lived closer or further from the ED. INTERPRETATION: We have shown that strategies to improve linkage to care from the ED should consider the high rates of poor linkage among young men and those presenting to the ED with trauma. Furthermore, innovative linkage to care solutions will need to account for the unique geographical consideration of this population, given that many ED patients will need to continue care at a site distant from the diagnosis site. FUNDING: This research was supported by the South African Medical Research Council, the Division of Intramural Research, the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Johns Hopkins Center for Global Health.