Harm reduction behaviors are associated with carrying naloxone among patients on methadone treatment.

BACKGROUND: Despite the widespread availability of naloxone, US opioid overdose rates continue to rise. The "Cascade of Care" (CoC) is a public health approach that identifies steps in achieving specific outcomes and has been used to identify gaps in naloxone carriage among individuals with opioid use disorder (OUD). We sought to apply this framework to a treatment-seeking population with OUD that may be more inclined to engage in harm reduction behaviors. METHODS: Patients were recruited from an urban methadone program to complete a survey. We assessed naloxone familiarity, availability, obtainability, training, and possession, as well as naloxone carriage rates, demographics, and harm reduction behaviors. A multivariable logistic regression examined associations between naloxone carriage and individual-level factors. RESULTS: Participants (n = 97) were majority male (59%), with a mean age of 48 (SD = 12), 27% had college education or higher, 64% indicated injection drug use, and 84% reported past naloxone training. All participants endorsed familiarity with naloxone, but only 42% regularly carried naloxone. The following variables were associated with carrying naloxone: White race (aOR = 2.94, 95% CI 1.02-8.52), college education (aOR = 8.11, 95% CI 1.76-37.47), and total number of self-reported harm reduction behaviors (aOR = 1.45, 95% CI 1.00-2.11). CONCLUSION: We found low rates of naloxone carriage among methadone-treated patients. Methadone programs provide opportunities for naloxone interventions and should target racial/ethnic minorities and individuals with lower education. The spectrum of harm reduction behaviors should be encouraged among these populations to enhance naloxone carriage.

The production of medicoethical misconduct: medical ethics and vivisection in Wilkie Collins's Heart and Science.

Even as Wilkie Collins's Heart and Science continues in the tradition of cautionary tales of medicine and science, it also integrates nineteenth-century discussions of medical ethics, vivisection and women, further building on earlier criticisms of scientific hubris. By indicting a fictional medical doctor and his methodology, Heart and Science depicts the extremes of good and bad, ethical and unethical medicine-whether the doctor can care, and not simply solve the medical enigma-in light of a changing medical field that prized objectivity and distance from the subject over the old holistic way of listening to a patient in order to understand her malady. In reading Collins within his historical context and against a changing environment within the medical sciences, literary critics discern a gendered doctor-patient relationship and observe a Victorian author's attempts to combat the fears of scientific advancement by using or aligning himself with a proto-feminist perspective.

Race-based differences in drug use prior to onset of opioid use disorder.

Rates of opioid use disorder (OUD) have increased dramatically over the past two decades, a rise that has been accompanied by changing demographics of those affected. Early exposure to drugs is a known risk factor for later development of opioid use disorder; but how and whether this risk factor may differ between racial groups is unknown. Our study seeks to identify race differences in self-report of current and past substance use in OUD-diagnosed treatment-seeking individuals. Patients (n = 157) presenting for methadone maintenance treatment at a racially diverse urban opioid treatment program were approached and consented for study involvement. Participants were administered substance use history questionnaires and urine drug screening at intake. Chi-square, t-tests, and rank-sum were used to assess race differences in demographic variables. Logistic and linear regressions assessed the relationship between race and substance use for binary and continuous variables, respectively. 61% of the population identified as Black and 39% as White. Black participants were significantly older; age was thus included as a covariate. Logistic regressions demonstrated that despite similar urine toxicology at intake, White participants were significantly more likely to report having used prescription opioids and psychedelic, stimulant, and sedative substance classes prior to their first use of non-pharmaceutical opioids. Compared to Black participants, White treatment-seeking OUD-diagnosed individuals reported using a wider range of substances ever and prior to first use of non-pharmaceutical opioids. There were no differences, however, in presentation for OUD treatment, suggesting different pathways to OUD, which may carry important clinical implications.

Non-native mangroves support carbon storage, sediment carbon burial, and accretion of coastal ecosystems.

Mangrove forests play an important role in climate change adaptation and mitigation by maintaining coastline elevations relative to sea level rise, protecting coastal infrastructure from storm damage, and storing substantial quantities of carbon (C) in live and detrital pools. Determining the efficacy of mangroves in achieving climate goals can be complicated by difficulty in quantifying C inputs (i.e., differentiating newer inputs from younger trees from older residual C pools), and mitigation assessments rarely consider potential offsets to CO2 storage by methane (CH4 ) production in mangrove sediments. The establishment of non-native Rhizophora mangle along Hawaiian coastlines over the last century offers an opportunity to examine the role mangroves play in climate mitigation and adaptation both globally and locally as novel ecosystems. We quantified total ecosystem C storage, sedimentation, accretion, sediment organic C burial and CH4 emissions from ~70 year old R. mangle stands and adjacent uninvaded mudflats. Ecosystem C stocks of mangrove stands exceeded mudflats by 434 ± 33 Mg C/ha, and mangrove establishment increased average coastal accretion by 460%. Sediment organic C burial increased 10-fold (to 4.5 Mg C ha-1  year-1 ), double the global mean for old growth mangrove forests, suggesting that C accumulation from younger trees may occur faster than previously thought, with implications for mangrove restoration. Simulations indicate that increased CH4 emissions from sediments offset ecosystem CO2 storage by only 2%-4%, equivalent to 30-60 Mg CO2 -eq/ha over mangrove lifetime (100 year sustained global warming potential). Results highlight the importance of mangroves as novel systems that can rapidly accumulate C, have a net positive atmospheric greenhouse gas removal effect, and support shoreline accretion rates that outpace current sea level rise. Sequestration potential of novel mangrove forests should be taken into account when considering their removal or management, especially in the context of climate mitigation goals.

No Country for Old Men: Four Challenges for Men Facing the Fourth Age.

This essay reads the protagonist of Cormac McCarthy's No Country for Old Men (2005), Sheriff Ed Tom Bell, as an exemplar of problems that contemporary aging men face when they look to ahead to the so-called Fourth Age. As the plot unfolds, Bell is an aging, increasingly ineffectual cowboy lawman who retires, renounces the violence that sustained his male dominance, and loses the moral certainty that ensured his identity. Like Bell, most old men struggle with four interrelated challenges as they move along the ever-lengthening journey of life: relevance, masculinity, love, and meaning.

Practical Aspects of Designing and Conducting Validation Studies Involving Multi-study Trials.

This chapter focuses on practical aspects of conducting prospective in vitro validation studies, and in particular, by laboratories that are members of the European Union Network of Laboratories for the Validation of Alternative Methods (EU-NETVAL) that is coordinated by the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM). Prospective validation studies involving EU-NETVAL, comprising a multi-study trial involving several laboratories or "test facilities", typically consist of two main steps: (1) the design of the validation study by EURL ECVAM and (2) the execution of the multi-study trial by a number of qualified laboratories within EU-NETVAL, coordinated and supported by EURL ECVAM. The approach adopted in the conduct of these validation studies adheres to the principles described in the OECD Guidance Document on the Validation and International Acceptance of new or updated test methods for Hazard Assessment No. 34 (OECD 2005). The context and scope of conducting prospective in vitro validation studies is dealt with in Chap. 4 . Here we focus mainly on the processes followed to carry out a prospective validation of in vitro methods involving different laboratories with the ultimate aim of generating a dataset that can support a decision in relation to the possible development of an international test guideline (e.g. by the OECD) or the establishment of performance standards.

Femoral neck shaft angles: A radiological anthropometry study.

BACKGROUND: Most of the available orthopaedic implants were designed and manufactured based on data from Western population whose skeletal dimensions are different from those of Africans. OBJECTIVES: This study was conducted to determine the value of the neck-shaft angle (NSA) of Nigerians living in Lagos for the purpose of adequate planning, preparation, and pre-operative selection of orthopaedic implants for surgeries involving the femoral neck and stocking of orthopaedic implants in hospitals located in resource poor countries like Nigeria. MATERIALS AND METHODS: This was a retrospective study which involved measuring the NSAs of anterior-posterior views of pelvic radiographs of adult patients reported "normal study" by the radiologist. RESULTS: A total of 264 femoral necks were analysed from 132 patients' radiographs comprising of 68 males and 64 females. The average NSA for an adult Nigerian living in Lagos is 130.77° ± 6.03° with mean NSA value of 131.28° ± 6.56° for the right and 130.22° ± 5.18° for the left. The mean value of NSA for an adult male is 131.57° ± 5.66° whereas the mean value for an adult female is 129.97° ± 6.33°. CONCLUSION: The value of NSA obtained from this study should be considered during the surgical fixation of the neck of femur fractures or osteotomies around the neck of the femur of adult Nigerians. It should also be noted during designing and bioengineering construction of orthopaedic implants and hip prosthesis for Nigerians.

Risk factors for suicide among older adults with cancer.

OBJECTIVE: To determine whether the increased risk of suicide for individuals with cancer may be explained by functional limitations, lack of social support, or other factors. METHOD: In this population-based case-control study, interviews of primary informants for suicides in the state of North Carolina were compared to interviews with participants in the Piedmont Health Study of the Elderly to estimate adjusted odds ratios for suicide and self-reported, physician diagnosed cancer, heart attack, stroke, and hip fracture. RESULTS: Adjusting for all other factors, there was a statistically significant association of suicide and cancer (odds ratio [OR] 2.62, 95% confidence interval [CI] CI 1.84-3.73), but not heart attack, hip fracture, or stroke. The risk of suicide was also elevated for men vs. women (OR 17.15, CI 10.88-27.02), whites vs. blacks (OR 9.70, CI 6.07-15.50), and individuals with stressful life events (OR 2.75, CI 1.97-3.86) or limitations of instrumental (OR 2.93, CI 2.03-4.22) but not physical activities of daily living. Suicide cases were not more likely to be short of breath or poor sleep quality. Suicide was statistically significantly less likely for study participants who were married with spouse living vs. other (OR 0.61, CI 0.43-0.88) or who had one or more indicators of social support (OR 0.27, CI 0.19-0.39). CONCLUSION: After adjustment for other risk factors, suicide was strongly associated with cancer but not with other disabling, potentially fatal conditions.

Correlates of Staff Acceptability of a Novel Telemedicine-Delivered Medications for Opioid Use Disorder Program in a Rural Detention Center.

Opioid overdose death is significantly increased immediately following incarceration. Evidence-based medications are underutilized in rural jails and detention centers. We have reported our efforts to address this gap through telemedicine-based medications for opioid use disorder treatment (tele-MOUD) for incarcerated patients. Staff acceptance and perceptions are critically important factors in the assurance of program validation. We assessed tele-MOUD acceptability and perceptions of effectiveness and stigma in one detention center. Overall, we found that jail staff's general acceptability of the program was rather low, as was perceived effectiveness of MOUD, while stigmatizing beliefs were present. Furthermore, tele-MOUD acceptability was positively correlated with perceptions of MOUD effectiveness and negatively correlated with stigmatizing notions of MOUD (p's < 0.001). Findings suggest the need for educational interventions. Future research investigating the potential moderating effects of training on staff acceptability of jail-based tele-MOUD will support the implementation and sustainability of these life-saving programs.

Association of apolipoprotein B and nuclear magnetic resonance spectroscopy-derived LDL particle number with outcomes in 25 clinical studies: assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices.

BACKGROUND: The number of circulating LDL particles is a strong indicator of future cardiovascular disease (CVD) events, even superior to the concentration of LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum to obtain NMR-derived LDL particle number (LDL-P). CONTENT: To assess the comparability of apo B and LDL-P, we reviewed 25 clinical studies containing 85 outcomes for which both biomarkers were determined. In 21 of 25 (84.0%) studies, both apo B and LDL-P were significant for at least 1 outcome. Neither was significant for any outcome in only 1 study (4.0%). In 50 of 85 comparisons (58.8%), both apo B and LDL-P had statistically significant associations with the clinical outcome, whereas in 17 comparisons (20.0%) neither was significantly associated with the outcome. In 18 comparisons (21.1%) there was discordance between apo B and LDL-P. CONCLUSIONS: In most studies, both apo B and LDL-P were comparable in association with clinical outcomes. The biomarkers were nearly equivalent in their ability to assess risk for CVD and both have consistently been shown to be stronger risk factors than LDL-C. We support the adoption of apo B and/or LDL-P as indicators of atherogenic particle numbers into CVD risk screening and treatment guidelines. Currently, in the opinion of this Working Group on Best Practices, apo B appears to be the preferable biomarker for guideline adoption because of its availability, scalability, standardization, and relatively low cost.

Assessment of the predictive capacity of the 3T3 Neutral Red Uptake cytotoxicity test method to identify substances not classified for acute oral toxicity (LD50>2000 mg/kg): results of an ECVAM validation study.

Assessing chemicals for acute oral toxicity is a standard information requirement of regulatory testing. However, animal testing is now prohibited in the cosmetics sector in Europe, and strongly discouraged for industrial chemicals. Building on the results of a previous international validation study, a follow up study was organised to assess if the 3T3 Neutral Red Uptake cytotoxicity assay could identify substances not requiring classification as acute oral toxicants under the EU regulations. Fifty-six coded industrial chemicals were tested in three laboratories, each using one of the following protocols: the previously validated protocol, an abbreviated version of the protocol and the protocol adapted for an automation platform. Predictions were very similar among the three laboratories. The assay exhibited high sensitivity (92-96%) but relatively low specificity (40-44%). Three chemicals were under predicted. Assuming that most industrial chemicals are not likely to be acutely toxic, this test method could prove a valuable component of an integrated testing strategy, a read-across argument, or weight-of-evidence approach to identify non toxic chemicals (LD50>2000 mg/kg). However, it is likely to under predict chemicals acting via specific mechanisms of action not captured by the 3T3 test system, or which first require biotransformation in vivo.

Gastroblastoma of the Pylorus: A Case Report and Review of the Literature.

Gastroblastoma is an extremely rare biphasic tumor that typically occurs in the stomach in patients between the ages of 10 and 30. Only 16 cases have been reported previously. These tumors are important to diagnose and distinguish from more aggressive neoplasms; although numbers are small, prognosis appears excellent overall with complete excision, with only occasional metastasis and/or local recurrence. We report a case of gastroblastoma in a 26-year-old male arising from the pylorus and extending through the first and second portions of the duodenum. This is the first case to be reported from this specific location.

Patient experiences of COVID-19-induced changes to methadone treatment in a large community-based opioid treatment program in Baltimore.

INTRODUCTION: Following the March 2020 federal declaration of a COVID-19 public health emergency, in line with recommendations for social distancing and decreased congregation, federal agencies issued sweeping regulation changes to facilitate access to medications for opioid use disorder (MOUD) treatment. These changes allowed patients new to treatment to receive multiple days of take-home medications (THM) and to use remote technology for treatment encounters-allowances that previously had been reserved exclusively for "stable" patients who met minimum adherence and time-in-treatment criteria. The impact of these changes on low-income, minoritized patients (frequently the largest recipients of opioid treatment program [OTP]-based addiction care), however, is not well characterized. We aimed to explore the experiences of patients who were enrolled in treatment prior to COVID-19 OTP regulation changes, with the goal of understanding patients' perceptions of the impact of these changes on treatment. METHODS: This study included semistructured, qualitative interviews with 28 patients. We used a purposeful sampling method to recruit individuals who were active in treatment just before COVID-19-related policy changes went into effect, and who were still in treatment several months later. To ensure a diverse array of perspectives, we interviewed individuals who either had or had not experienced challenges with methadone medication adherence from 3/24/21 to 6/8/21, approximately 12-15 months following the onset of COVID-19. Interviews were transcribed and coded using thematic analysis. RESULTS: Participants were majority male (57 %), Black/African American (57 %), with a mean age of 50.1 (SD = 9.3). Fifty percent received THM prior to COVID-19, which increased to 93 % during the pandemic. COVID-19 program changes had mixed effects on treatment and recovery experiences. Themes identified convenience, safety, and employment as reasons for preferring THM. Challenges included difficulty with managing/storing medications, experiencing isolation, and concern about relapse. Furthermore, some participants reported that telebehavioral health encounters felt less personal. CONCLUSIONS: Policymakers should consider patients' perspectives to foster a more patient-centered approach to methadone dosing that is safe, flexible, and accommodating to a diverse array of patients' needs. Additionally, technical support should be provided to OTPs to ensure interpersonal connections are maintained in the patient-provider relationship beyond the pandemic.

Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial.

Importance: Methadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects. Objective: To determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep. Design, Setting, and Participants: This 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment. Interventions: Participants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups. Main Outcomes and Measures: Outcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat. Results: Of the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality. Conclusions and Relevance: In this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP. Trial Registration: ClinicalTrials.gov Identifier: NCT02941809.

p38MAPKα Stromal Reprogramming Sensitizes Metastatic Breast Cancer to Immunotherapy.

Metastatic breast cancer is an intractable disease that responds poorly to immunotherapy. We show that p38MAPKα inhibition (p38i) limits tumor growth by reprogramming the metastatic tumor microenvironment in a CD4+ T cell-, IFNγ-, and macrophage-dependent manner. To identify targets that further increased p38i efficacy, we utilized a stromal labeling approach and single-cell RNA sequencing. Thus, we combined p38i and an OX40 agonist that synergistically reduced metastatic growth and increased overall survival. Intriguingly, patients with a p38i metastatic stromal signature had better overall survival that was further improved by the presence of an increased mutational load, leading us to ask if our approach would be effective in antigenic breast cancer. The combination of p38i, anti-OX40, and cytotoxic T-cell engagement cured mice of metastatic disease and produced long-term immunologic memory. Our findings demonstrate that a detailed understanding of the stromal compartment can be used to design effective antimetastatic therapies. SIGNIFICANCE: Immunotherapy is rarely effective in breast cancer. We dissected the metastatic tumor stroma, which revealed a novel therapeutic approach that targets the stromal p38MAPK pathway and creates an opportunity to unleash an immunologic response. Our work underscores the importance of understanding the tumor stromal compartment in therapeutic design. This article is highlighted in the In This Issue feature, p. 1275.

Inside aging masculinities and gerontological careers.

This roundtable discussion is a creative contribution to this special issue on 'aging masculinities' based on questions posed by editor Stephen Katz to three leading senior scholars in the critical gerontological field in the United States. W. Andrew Achenbaum is a renowned historian who has devoted his career to writing about the relevance of past politics, cultures, and knowledges of aging to comprehending our current dilemmas. Thomas R. Cole is an acclaimed historical scholar and mentor to generations of Humanities researchers across the globe. His work also includes film, literature, ethics, and spirituality. Brian de Vries is a social gerontologist whose bold research on LGBTQ aging is a powerful voice in critiquing the multiple forms of discrimination, violence and hardships, and denied rights and life-chances imposed by hetero-patriarchal regimes in later life. That these men have shaped and been shaped by their work and advocacy is the key theme that inspires our conversation.