The adaptive immune response to Trichuris in wild versus laboratory mice: An established model system in context.

Laboratory model organisms have provided a window into how the immune system functions. An increasing body of evidence, however, suggests that the immune responses of naive laboratory animals may differ substantially to those of their wild counterparts. Past exposure, environmental challenges and physiological condition may all impact on immune responsiveness. Chronic infections of soil-transmitted helminths, which we define as establishment of adult, fecund worms, impose significant health burdens on humans, livestock and wildlife, with limited treatment success. In laboratory mice, Th1 versus Th2 immune polarisation is the major determinant of helminth infection outcome. Here we compared antigen-specific immune responses to the soil-transmitted whipworm Trichuris muris between controlled laboratory and wild free-ranging populations of house mice (Mus musculus domesticus). Wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice. Wild mouse effector/memory CD4+ T cell phenotype reflected the antigen-specific cytokine response across the Th1/Th2 spectrum. Increasing egg shedding was associated with body condition loss. However, local Trichuris-specific Th1/Th2 balance was positively associated with worm burden only in older wild mice. Thus, although the fundamental relationships between the CD4+ T helper cell response and resistance to T. muris infection are similar in both laboratory and wild M. m. domesticus, there are quantitative differences and age-specific effects that are analogous to human immune responses. These context-dependent immune responses demonstrate the fundamental importance of understanding the differences between model and natural systems for translating mechanistic models to 'real world' immune function.

Overdose Risk and Brain Injury (Traumatic Brain Injury/Acquired Brain Injury), A Commentary.

OBJECTIVE: This commentary seeks to evaluate existing knowledge about the relationship between brain injury (BI) and overdose (OD), to unify distant bodies of literature, and to enhance prevention and treatment for opioid OD among individuals with BI. BACKGROUND: There is a hidden epidemic of undiagnosed BI in the United States. Due to lack of screening, the vast majority of BI sufferers do not know they have a BI. Not only are those with BI at elevated risk for opioid use, misuse, and opioid use disorder, but also they are at elevated risk for OD. Conversely, those with OUD and those who experienced an OD, are more likely to sustain BI. Key Findings/Conclusions: The existing literature suggests that primary strategies to reduce ABI (Acquired Brain Injury)/TBI (Traumatic Brain Injury) harms involve addressing: screening, stigma, racial disparities, and popular misconceptions about OD. The association between TBI and OD is an underexamined public health issue, exacerbated by the bidirectional nature of the relationship. Not only is TBI a risk factor for opioid OD; opioid OD was also found to be a major cause of ABI, which can have lifelong effects similar to Alzheimer's disease. Screening tools for BI were underutilized and inconsistently implemented across reviewed studies. Enhanced screening population wide is a promising intervention, complemented with expanded treatment and research. Black individuals face worse outcomes in BI and treatment outcomes. Anti-racist strategies must fight inequity while addressing social and structural drivers of overdose and BI within the opioid and opioid overdose crises.

Racial/ethnic disparities in opioid overdose prevention: comparison of the naloxone care cascade in White, Latinx, and Black people who use opioids in New York City.

BACKGROUND: Drug overdose mortality is rising precipitously among Black people who use drugs. In NYC, the overdose mortality rate is now highest in Black (38.2 per 100,000) followed by the Latinx (33.6 per 100,000) and white (32.7 per 100,000) residents. Improved understanding of access to harm reduction including naloxone across racial/ethnic groups is warranted. METHODS: Using data from an ongoing study of people who use illicit opioids in NYC (N = 575), we quantified racial/ethnic differences in the naloxone care cascade. RESULTS: We observed gaps across the cascade overall in the cohort, including in naloxone training (66%), current possession (53%) daily access during using and non-using days (21%), 100% access during opioid use (20%), and complete protection (having naloxone and someone who could administer it present during 100% of opioid use events; 12%). Naloxone coverage was greater in white (training: 79%, possession: 62%, daily access: 33%, access during use: 27%, and complete protection: 13%, respectively) and Latinx (training: 67%, possession: 54%, daily access: 22%, access during use: 24%, and complete protection: 16%, respectively) versus Black (training: 59%, possession: 48%, daily access:13%, access during use: 12%, and complete protection: 8%, respectively) participants. Black participants, versus white participants, had disproportionately low odds of naloxone training (OR 0.40, 95% CI 0.22-0.72). Among participants aged 51 years or older, Black race (versus white, the referent) was strongly associated with lower levels of being trained in naloxone use (OR 0.20, 95% CI 0.07-0.63) and having 100% naloxone access during use (OR 0.34, 95% CI 0.13-0.91). Compared to white women, Black women had 0.27 times the odds of being trained in naloxone use (95% CI 0.10-0.72). CONCLUSIONS: There is insufficient protection by naloxone during opioid use, with disproportionately low access among Black people who use drugs, and a heightened disparity among older Black people and Black women.

"As safe as possible": a qualitative study of opioid withdrawal and risk behavior among people who use illegal opioids.

BACKGROUND: Opioid withdrawal is a regular occurrence among many people who use illicit opioids (PWUIO) that has also been shown to increase their willingness to engage in risk-involved behavior. The proliferation of fentanyl in the illicit opioid market may have amplified this relationship, potentially putting PWUIO at greater risk of negative health outcomes. Understanding the relationship between withdrawal and risk-involved behavior may also have important implications for the ways that problematic drug use is conceptualized, particularly in disease models of addiction, which position risk behavior as evidence of pathology that helps to justify ontological distinctions between addicts and non-addicts. Examining withdrawal, and its role in PWUIO's willingness to engage in risk, may aid in the development of alternative theories of risk involvement and create discursive spaces for de-medicalizing and de-othering people who use illegal drugs. METHODS: This article is based on 32 semi-structured interviews with PWUIO in the New York City area who also reported recent withdrawal experience. Interviews were conducted remotely between April and August 2022 and recorded for later transcription. Data were then coded and analyzed based on a combination of inductive and deductive coding strategies and informed by the literature. RESULTS: Participants described a strong relationship between withdrawal and their willingness to engage in risk-involved behavior that was exacerbated by the proliferation of fentanyl. Yet, their descriptions did not align with narratives of risk as a product of bad decisions made by individuals. Rather, data demonstrated the substantial role of social and structural context, particularly drug policies like prohibition and criminalization, in the kinds of risks that PWUIO faced and their ability to respond to them. CONCLUSIONS: Withdrawal should be taken more seriously both from an ethical perspective and as an important catalyst of risk behavior. However, theories that position activities taken to avoid withdrawal as irrational and as evidence of pathology are poorly aligned with the complexity of PWUIO's actual lives. We recommend the use of less deterministic and less medicalized theories of risk that better account for differences between how people view the world, and for the role of socio-structural forces in the production of risk.

Provider Perspectives on Barriers to Routine HIV Testing of Adolescent and Young Adult Patients in Emergency Department Settings.

HIV testing rates among US youth aged 13-24 years are sub-optimal, with high rates of missed testing opportunities in emergency departments (EDs). We assessed barriers to routine HIV testing of youth in urban ED settings from the perspective of healthcare providers. Ten physicians and nurses were recruited from the pediatric and adult EDs at a high-volume hospital in New York City, USA to complete in-depth interviews to provide their perspectives on barriers to routine HIV testing of youth ages 13 to 24 in EDs. Interviews were conducted using a semi-structured interview guide with questions and probes. All interviews were conducted via Zoom due to the COVID-19 pandemic and were audio-recorded and transcribed verbatim. Transcripts were coded independently by two researchers using an inductive thematic analysis approach. Participants often offered HIV testing to youth in the ED based on their perceptions of patients' HIV risk, with pediatric providers sometimes discouraging adolescents they perceived to be at low HIV risk from testing. Participants cited other priorities, logistics of blood-based testing, and discomfort discussing HIV as other reasons for not offering HIV testing to all youth in the ED. Efforts are needed to encourage providers to offer HIV testing to all youth regardless of perceived risk, as the ED often serves as youths' only point of contact with the healthcare system. Emphasis on this and the importance of early detection, along with institutional change, clear guidance, and support for the testing process may help increase youth testing and avoid missed HIV diagnosis opportunities.

Interlaboratory comparison of 25-hydroxyvitamin D assays: Vitamin D Standardization Program (VDSP) Intercomparison Study 2 - Part 2 ligand binding assays - impact of 25-hydroxyvitamin D2 and 24R,25-dihydroxyvitamin D3 on assay performance.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of ligand binding assays (Part 2) for the determination of serum total 25-hydroxyvitamin D [25(OH)D]. Fifty single-donor samples were assigned target values for concentrations of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3], and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] using isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 2 includes results from 17 laboratories using 32 ligand binding assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 50% of the ligand binding assays achieved the VDSP criterion of mean % bias ≤ |± 5%|. For the 13 unique ligand binding assays evaluated in this study, only 4 assays were consistently within ± 5% mean bias and 4 assays were consistently outside ± 5% mean bias regardless of the laboratory performing the assay. Based on multivariable regression analysis using the concentrations of individual vitamin D metabolites in the 50 single-donor samples, most assays underestimate 25(OH)D2 and several assays (Abbott, bioMérieux, DiaSorin, IDS-EIA, and IDS-iSYS) may have cross-reactivity from 24R,25(OH)2D3. The results of this interlaboratory study represent the most comprehensive comparison of 25(OH)D ligand binding assays published to date and is the only study to assess the impact of 24R,25(OH)2D3 content using results from a reference measurement procedure.

Naloxone protection, social support, network characteristics, and overdose experiences among a cohort of people who use illicit opioids in New York City.

BACKGROUND: Despite increased availability of take-home naloxone, many people who use opioids do so in unprotected contexts, with no other person who might administer naloxone present, increasing the likelihood that an overdose will result in death. Thus, there is a social nature to being "protected" from overdose mortality, which highlights the importance of identifying background factors that promote access to protective social networks among people who use opioids. METHODS: We used respondent-driven sampling to recruit adults residing in New York City who reported recent (past 3-day) nonmedical opioid use (n = 575). Participants completed a baseline assessment that included past 30-day measures of substance use, overdose experiences, and number of "protected" opioid use events, defined as involving naloxone and the presence of another person who could administer it, as well as measures of network characteristics and social support. We used modified Poisson regression with robust variance to estimate unadjusted and adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: 66% of participants had ever been trained to administer naloxone, 18% had used it in the past three months, and 32% had experienced a recent overdose (past 30 days). During recent opioid use events, 64% reported never having naloxone and a person to administer present. This was more common among those: aged ≥ 50 years (PR: 1.18 (CI 1.03, 1.34); who identified as non-Hispanic Black (PR: 1.27 (CI 1.05, 1.53); experienced higher levels of stigma consciousness (PR: 1.13 (CI 1.00, 1.28); and with small social networks (< 5 persons) (APR: 1.14 (CI 0.98, 1.31). Having a recent overdose experience was associated with severe opioid use disorder (PR: 2.45 (CI 1.49, 4.04), suicidality (PR: 1.72 (CI 1.19, 2.49), depression (PR: 1.54 (CI 1.20, 1.98) and positive urinalysis result for benzodiazepines (PR: 1.56 (CI 1.23, 1.96), but not with network size. CONCLUSIONS: Results show considerable gaps in naloxone protection among people who use opioids, with more vulnerable and historically disadvantaged subpopulations less likely to be protected. Larger social networks of people who use opioids may be an important resource to curtail overdose mortality, but more effort is needed to harness the protective aspects of social networks.

"I Didn't Know What They're Gonna Do to Me: So That's Why I Said No": Why Youth Decline HIV Testing in Emergency Departments.

Youth between the ages of 13 and 24 account for over 20% of new HIV diagnoses in the United States but are the least likely age group to be HIV tested in healthcare settings including the emergency department. This is in part due to the fact that almost 50% of youth decline testing when offered. We elucidated youth patients' perspectives on barriers to and facilitators of routine HIV testing of youth in an urban emergency department setting. Thirty-seven patients aged 13-24 years were recruited from the pediatric and adult emergency departments at a high-volume hospital in New York City from August 2019 to March 2020. Semi-structured in-depth interviews were conducted with all participants. Interviews were audio-recorded and transcribed verbatim, and transcripts were coded using an inductive thematic analysis approach. Youths' main reasons for declining HIV testing when offered included low risk perception, privacy concerns, HIV-related stigma, and low levels of HIV-related knowledge. Participants' responses suggested that HIV educational materials provided when testing is offered may be insufficient. Participants recommended providing additional HIV education and better incorporating HIV testing into the emergency department routine to increase testing among youth. Efforts are needed to help youth recognize their own HIV risk and increase their HIV-related knowledge. This may be accomplished by providing youth with additional educational materials on HIV, possibly via tablet-based interventions or other methods that may enhance privacy, combined with discussions with healthcare providers. Such efforts may help increase HIV testing acceptance among youth seen in the emergency department.

A lesson from the wild: The natural state of eosinophils is Ly6Ghi.

With a long history of promoting pathological inflammation, eosinophils are now emerging as important regulatory cells. Yet, findings from controlled laboratory experiments so far lack translation to animals, including humans, in their natural environment. In order to appreciate the breadth of eosinophil phenotype under non-laboratory, uncontrolled conditions, we exploit a free-living population of the model organism Mus musculus domesticus. Eosinophils were present at significantly higher proportions in the spleen and bone marrow of wild mice compared with laboratory mice. Strikingly, the majority of eosinophils of wild mice exhibited a unique Ly6Ghi phenotype seldom described in laboratory literature. Ly6G expression correlated with activation status in spleen and bone marrow, but not peritoneal exudate cells, and is therefore likely not an activation marker per se. Intermediate Ly6G expression was transiently induced in a small proportion of eosinophils from C57BL/6 laboratory mice during acute infection with the whipworm Trichuris muris, but not during low-dose chronic infection, which better represents parasite exposure in the wild. We conclude that the natural state of the eosinophil is not adequately reflected in the standard laboratory mouse, which compromises our attempts to dissect their functional relevance. Our findings emphasize the importance of studying the immune system in its natural context - alongside more mechanistic laboratory experiments - in order to capture the entirety of immune phenotypes and functions.

Assessment of serum total 25-hydroxyvitamin D assay commutability of Standard Reference Materials and College of American Pathologists Accuracy-Based Vitamin D (ABVD) Scheme and Vitamin D External Quality Assessment Scheme (DEQAS) materials: Vitamin D Standardization Program (VDSP) Commutability Study 2.

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D2 and 25(OH)D3) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D3, was deemed non-commutable for 50% of the LC-MS/MS assays.

Toward a human-centered use of technology: a stakeholder analysis of harm reduction and CBO staff.

BACKGROUND: Technology can enable syringe service programs (SSPs) and other community-based organizations (CBOs) operating under a harm reduction framework to work with an increased number of clients and can also enable organizations to offer services more effectively (e.g., offering HIV testing in ways participants may be more likely to accept). In the current time of COVID-19 social distancing, technology can also help organizations more safely provide services to people with compromised immune systems and to clients who might otherwise not be reached. However, technology projects implemented in harm reduction settings are frequently conceptualized and developed by researchers or technology specialists rather than by SSP staff or clients. METHODS: To more effectively meet the needs of SSPs and other CBOs across the USA, our team conducted qualitative interviews with 16 individuals who have extensive backgrounds working in the field of harm reduction. Interviews were digitally recorded and professionally transcribed, and the transcripts were checked for accuracy by the interviewers. The resulting transcripts were coded and analyzed to determine emerging themes. RESULTS: Interviewees mentioned the ability of technology to deliver consistent quality messaging to multiple clients at the same time and the potential to customize or tailor technology-based messaging to specific client populations as positive benefits. Clear barriers to technology use also emerged, in particular regarding privacy, data security, and the need to maintain client trust when discussing sensitive issues (e.g., illicit drug use). CONCLUSIONS: Technology offers the potential to deliver consistently high-quality health communication and maintain contact with clients who may have no other access to care. If designed and managed effectively, technology can also address issues related to providing services during times when physical contact is limited due to COVID-19 social distancing measures.

Amount of naloxone used to reverse opioid overdoses outside of medical practice in a city with increasing illicitly manufactured fentanyl in illicit drug supply.

Background: Illicitly manufactured fentanyl (IMF) prevalence has increased. However, there is uncertainty about naloxone dose(s) used by nonmedical bystanders to reverse opioid overdoses in the context of increasing IMF. Methods: We used community naloxone distribution program data about naloxone doses and fatal opioid overdoses from the Allegheny County Medical Examiner. From January 2013 to December 2016, staff interviewed participants who administered naloxone in response to 1072 overdoses. We calculated frequencies, percentages, and conducted a 1-way analysis of variance (ANOVA). Results: Despite increases in fentanyl-contributed deaths, there were no statistically significant differences between any of the 4 years (2013-2016) on average number of naloxone doses used by participants to reverse an overdose (F = 0.88; P = .449). Conclusion: Even though IMF is more potent than heroin and is a rapidly increasing contributor to drug overdose deaths in Allegheny County, the average dose of naloxone administered has not changed. Our findings differ from studies in different areas also experiencing increasing IMF prevalence. Additional investigations are needed to clarify the amount of naloxone needed to reverse opioid overdoses in the community caused by new synthetic opioids.

Central neurological complications following obstetric neuraxial blockade.

PURPOSE OF REVIEW: Central neuraxial blockade is increasingly the anaesthetic management of choice for parturients, including in higher risk pregnancies. Although they are usually effective and safe, there are potentially devastating neurological complications that may present either overtly or insidiously. A thorough understanding of the variety of potential neurological complications is essential to adequately consent patients in addition to diagnosing and managing complications following neuraxial anaesthesia. This review aims to describe a number of potential neurological injuries that may occur and suggested management based on available evidence. RECENT FINDINGS: Current evidence supports neuraxial anaesthesia as a safe management strategy in low and many higher risk pregnancies, with a low overall incidence of neurological complications. Neuraxial blockade is safe in patients with platelet counts greater than 70 000/µl and the risk of infective complications secondary to epidural catheterization remains low until day five post procedure. There is also some early evidence supporting the use of transnasal local anaesthetic as a strategy for managing postdural puncture headache. SUMMARY: Difficulty remains in establishing absolute risk of complications and optimal management strategies given the low overall number of patients affected and heterogeneity of therapy. There may be a role for centralized registration of postneuraxial complications in obstetric patients to further develop our collective understanding of these conditions.

Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review.

BACKGROUND: Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. METHODS: We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill-a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. FINDINGS: Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14-23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen. INTERPRETATION: The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability. FUNDING: National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.

Temporal Spatial and Metabolic Measures of Walking in Highly Functional Individuals With Lower Limb Amputations.

OBJECTIVE: To record the temporal spatial parameters and metabolic energy expenditure during walking of individuals with amputation, walking with advanced prostheses, and after completion of comprehensive rehabilitation compared with able-bodied persons. DESIGN: Cross-sectional. SETTING: Multidisciplinary comprehensive rehabilitation center. PARTICIPANTS: Severely injured UK military personnel with amputation and subsequent completion of their rehabilitation program (n=30; unilateral transtibial: n=10, unilateral transfemoral: n=10, and bilateral transfemoral: n=10) were compared with able-bodied persons (n=10) with similar age, height, and mass (P>.537). Total number of participants (N = 40). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Temporal spatial and metabolic energy expenditure data were captured during walking on level ground at a self-selected speed. RESULTS: The individuals with amputation were all men, with a mean age of 29±4 years and a mean New Injury Severity Score of 31±16. Walking speed, stride length, step length, and cadence of individuals with a unilateral transtibial or transfemoral amputation were comparable with able-bodied persons, and only individuals with a bilateral transfemoral amputation had a significantly slower walking speed (1.12m/s, P=.025) and reduced cadence (96 steps per minute, P=.026). Oxygen cost for individuals with a unilateral transtibial amputation (0.15mL/kg/m) was the same as for able-bodied persons (0.15mL/kg/m) and significantly increased by 20% (0.18mL/kg/m, P=.023) for unilateral transfemoral amputation and by 60% (0.24mL/kg/m, P<.001) for bilateral transfemoral individuals with amputation. CONCLUSIONS: The scientific literature reports a wide range of gait and metabolic energy expenditure across individuals with amputation. The results of this study indicate that individuals with amputation have a gait pattern which is highly functional and efficient. This is comparable with a small number of studies reporting similar outcomes for individuals with a unilateral transtibial amputation, but the results from this study are better than those on individuals with transfemoral amputations reported elsewhere, despite comparison with populations wearing similar prosthetic componentry. Those studies that do report similar outcomes have included individuals who have been provided with a comprehensive rehabilitation program. This suggests that such a program may be as important as, or even more important than, prosthetic component selection in improving metabolic energy expenditure. The data are made available as a benchmark for what is achievable in the rehabilitation of some individuals with amputations, but agreeably may not be possible for all amputees to achieve.

Opioid-Involved Overdose Among Male Afghanistan/Iraq-Era U.S. Military Veterans: A Multidimensional Perspective.

BACKGROUND: Mirroring nationwide trends in a broad range of U.S. populations, an alarming number of Afghanistan/Iraq-era U.S. Military veterans have experienced opioid-related overdoses. A growing body of research has examined the proximal behaviors that can precipitate an overdose; considerably less is known about more distal physiological, psychosocial and structural influences on these risk behaviors. OBJECTIVES: This study adopts a multidimensional approach to better understand opioid-related overdose among U.S. Military veterans, and seeks to explore not only the proximal behavioral precipitants of overdose events, but also the complex nexus of physiological, psychological, and sociological influences that undergird overdose events. METHODS: This qualitative examination is based on interview data from 36 male veterans who were discharged from the military after September 2001 and experienced at least one opioid-related overdose during or after military service. Participants were recruited in New York City during 2014 to share narrative accounts of their overdoses. RESULTS: Veterans' accounts indicate that background experiences, such as self-medication for social and psychological pain, trauma, social alienation and isolation, and histories of illicit drug use, precondition the more immediate factors and behaviors that precipitate overdose (including bingeing on drugs, mixing drugs, naiveté about dosage, and ambivalence about life/death). CONCLUSIONS: Findings suggest the need for comprehensive drug safety and overdose education that is sensitive to veterans' physiological, psychological, and sociological conditions. A multidimensional understanding of the distal and proximal overdose risks faced by veterans and other vulnerable groups may help lay a foundation for more inclusive/holistic approaches to overdose prevention and education.

Development of an opioid-related Overdose Risk Behavior Scale (ORBS).

BACKGROUND: Drug overdose has emerged as the leading cause of injury-related death in the United States, driven by prescription opioid (PO) misuse, polysubstance use, and use of heroin. To better understand opioid-related overdose risks that may change over time and across populations, there is a need for a more comprehensive assessment of related risk behaviors. Drawing on existing research, formative interviews, and discussions with community and scientific advisors an opioid-related Overdose Risk Behavior Scale (ORBS) was developed. METHODS: Military veterans reporting any use of heroin or POs in the past month were enrolled using venue-based and chain referral recruitment. The final scale consisted of 25 items grouped into 5 subscales eliciting the number of days in the past 30 during which the participant engaged in each behavior. Internal reliability, test-retest reliability and criterion validity were assessed using Cronbach's alpha, intraclass correlations (ICC) and Pearson's correlations with indicators of having overdosed during the past 30 days, respectivelyInternal reliability, test-retest reliability and criterion validity were assessed using Cronbach's alpha, intraclass correlations (ICC) and Pearson's correlations with indicators of having overdosed during the past 30 days, respectively. RESULTS: Data for 220 veterans were analyzed. The 5 subscales-(A) Adherence to Opioid Dosage and Therapeutic Purposes; (B) Alternative Methods of Opioid Administration; (C) Solitary Opioid Use; (D) Use of Nonprescribed Overdose-associated Drugs; and (E) Concurrent Use of POs, Other Psychoactive Drugs and Alcohol-generally showed good internal reliability (alpha range = 0.61 to 0.88), test-retest reliability (ICC range = 0.81 to 0.90), and criterion validity (r range = 0.22 to 0.66). The subscales were internally consistent with each other (alpha = 0.84). The scale mean had an ICC value of 0.99, and correlations with validators ranged from 0.44 to 0.56. CONCLUSIONS: These results constitute preliminary evidence for the reliability and validity of the new scale. If further validated, it could help improve overdose prevention and response research and could help improve the precision of overdose education and prevention efforts.

Recent Overdose Experiences in a Community Sample of Military Veterans Who Use Opioids.

Rising rates of overdose mortality underscore the importance of understanding and preventing overdose. We developed a seven-item scale for the assessment of nonfatal opioid-related overdose experiences, adding items on others' perceptions of whether the participant had overdosed and whether an intervention was attempted to frequently used criteria. We administered the scale to 240 primarily male and minority veterans, recruited using venue-based and chain-referral sampling, who separated from the military post-9/11 and reported current opioid use. The items were internally consistent, and correlated well with overdose risk behaviors (r = .13-.45). The new scale detected overdose events in a significantly higher proportion of participants (36.5%) than that using either self-report criterion (18.2%) or difficulty breathing and losing consciousness criteria (23.8%). These experiences or perceptions should be investigated to inform and better tailor the development of more effective overdose prevention and response programs.

Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group.

OBJECTIVES: To review and update the existing definition of a positive MRI for classification of axial spondyloarthritis (SpA). METHODS: The Assessment in SpondyloArthritis International Society (ASAS) MRI working group conducted a consensus exercise to review the definition of a positive MRI for inclusion in the ASAS classification criteria of axial SpA. Existing definitions and new data relevant to the MRI diagnosis and classification of sacroiliitis and spondylitis in axial SpA, published since the ASAS definition first appeared in print in 2009, were reviewed and discussed. The precise wording of the existing definition was examined in detail and the data and a draft proposal were presented to and voted on by the ASAS membership. RESULTS: The clear presence of bone marrow oedema on MRI in subchondral bone is still considered to be the defining observation that determines the presence of active sacroiliitis. Structural damage lesions seen on MRI may contribute to a decision by the observer that inflammatory lesions are genuinely due to SpA but are not required to meet the definition. The existing definition was clarified adding guidelines and images to assist in the application of the definition. CONCLUSION: The definition of a positive MRI for classification of axial SpA should continue to primarily depend on the imaging features of 'active sacroiliitis' until more data are available regarding MRI features of structural damage in the sacroiliac joint and MRI features in the spine and their utility when used for classification purposes.