Opioid Injection-Associated Bacterial Infections in England, 2002-2021: A Time Series Analysis of Seasonal Variation and the Impact of Coronavirus Disease 2019.

BACKGROUND: Bacterial infections cause substantial pain and disability among people who inject drugs. We described time trends in hospital admissions for injecting-related infections in England. METHODS: We analyzed hospital admissions in England between January 2002 and December 2021. We included patients with infections commonly caused by drug injection, including cutaneous abscesses, cellulitis, endocarditis, or osteomyelitis, and a diagnosis of opioid use disorder. We used Poisson regression to estimate seasonal variation and changes associated with coronavirus disease 2019 (COVID-19) response. RESULTS: There were 92 303 hospital admissions for injection-associated infections between 2002 and 2021. Eighty-seven percent were skin, soft-tissue, or vascular infections; 72% of patients were male; and the median age increased from 31 years in 2002 to 42 years in 2021. The rate of admissions reduced from 13.97 per day (95% confidence interval [CI], 13.59-14.36) in 2003 to 8.94 (95% CI, 8.64-9.25) in 2011, then increased to 18.91 (95% CI, 18.46-19.36) in 2019. At the introduction of COVID-19 response in March 2020, the rate of injection-associated infections reduced by 35.3% (95% CI, 32.1-38.4). Injection-associated infections were also seasonal; the rate was 1.21 (95% CI, 1.18-1.24) times higher in July than in February. CONCLUSIONS: This incidence of opioid injection-associated infections varies within years and reduced following COVID-19 response measures. This suggests that social and structural factors such as housing and the degree of social mixing may contribute to the risk of infection, supporting investment in improved social conditions for this population as a means to reduce the burden of injecting-related infections.

Guidance on take-home naloxone distribution and use by community overdose responders in Canada.

BACKGROUND: The increasing toxicity of opioids in the unregulated drug market has led to escalating numbers of overdoses in Canada and worldwide; takehome naloxone (THN) is an evidence-based intervention that distributes kits containing naloxone to people in the community who may witness an overdose. The purpose of this guidance is to provide policy recommendations for territorial, provincial and federal THN programs, using evidence from scientific and grey literature and community evidence that reflects 11 years of THN distribution in Canada. METHODS: The Naloxone Guidance Development Group - a multidisciplinary team including people with lived and living experience and expertise of drug use - used the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument to inform development of this guidance. We considered published evidence identified through systematic reviews of all literature types, along with community evidence and expertise, to generate recommendations between December 2021 and September 2022. We solicited feedback on preliminary recommendations through an External Review Committee and a public input process. The project was funded by the Canadian Institutes of Health Research through the Canadian Research Initiative in Substance Misuse. We used the Guideline International Network principles for managing competing interests. RECOMMENDATIONS: Existing evidence from the literature on THN was of low quality. We incorporated evidence from scientific and grey literature, and community expertise to develop our recommendations. These were in 3 areas: routes of naloxone administration, THN kit contents and overdose response. Take-home naloxone programs should offer the choice of both intramuscular and intranasal formulations of naloxone in THN kits. Recommended kit contents include naloxone, a naloxone delivery device, personal protective equipment, instructions and a carrying case. Trained community overdose responders should prioritize rescue breathing in the case of respiratory depression, and conventional cardiopulmonary resuscitation in the case of cardiac arrest, among other interventions. INTERPRETATION: This guidance development project provides direction for THN programs in Canada in the context of limited published evidence, with recommendations developed in collaboration with diverse stakeholders.

Opioid agonist treatment and risk of death or rehospitalization following injection drug use-associated bacterial and fungal infections: A cohort study in New South Wales, Australia.

BACKGROUND: Injecting-related bacterial and fungal infections are associated with significant morbidity and mortality among people who inject drugs (PWID), and they are increasing in incidence. Following hospitalization with an injecting-related infection, use of opioid agonist treatment (OAT; methadone or buprenorphine) may be associated with reduced risk of death or rehospitalization with an injecting-related infection. METHODS AND FINDINGS: Data came from the Opioid Agonist Treatment Safety (OATS) study, an administrative linkage cohort including all people in New South Wales, Australia, who accessed OAT between July 1, 2001 and June 28, 2018. Included participants survived a hospitalization with injecting-related infections (i.e., skin and soft-tissue infection, sepsis/bacteremia, endocarditis, osteomyelitis, septic arthritis, or epidural/brain abscess). Outcomes were all-cause death and rehospitalization for injecting-related infections. OAT exposure was classified as time varying by days on or off treatment, following hospital discharge. We used separate Cox proportional hazards models to assess associations between each outcome and OAT exposure. The study included 8,943 participants (mean age 39 years, standard deviation [SD] 11 years; 34% women). The most common infections during participants' index hospitalizations were skin and soft tissue (7,021; 79%), sepsis/bacteremia (1,207; 14%), and endocarditis (431; 5%). During median 6.56 years follow-up, 1,481 (17%) participants died; use of OAT was associated with lower hazard of death (adjusted hazard ratio [aHR] 0.63, 95% confidence interval [CI] 0.57 to 0.70). During median 3.41 years follow-up, 3,653 (41%) were rehospitalized for injecting-related infections; use of OAT was associated with lower hazard of these rehospitalizations (aHR 0.89, 95% CI 0.84 to 0.96). Study limitations include the use of routinely collected administrative data, which lacks information on other risk factors for injecting-related infections including injecting practices, injection stimulant use, housing status, and access to harm reduction services (e.g., needle exchange and supervised injecting sites); we also lacked information on OAT medication dosages. CONCLUSIONS: Following hospitalizations with injection drug use-associated bacterial and fungal infections, use of OAT is associated with lower risks of death and recurrent injecting-related infections among people with opioid use disorder.

Priority setting for Canadian Take-Home Naloxone best practice guideline development: an adapted online Delphi method.

BACKGROUND: Take-Home Naloxone (THN) is a core intervention aimed at addressing the toxic illicit opioid drug supply crisis. Although THN programs are available in all provinces and territories throughout Canada, there are currently no standardized guidelines for THN programs. The Delphi method is a tool for consensus building often used in policy development that allows for engagement of stakeholders. METHODS: We used an adapted anonymous online Delphi method to elicit priorities for a Canadian guideline on THN as a means of facilitating meaningful stakeholder engagement. A guideline development group generated a series of key questions that were then brought to a 15-member voting panel. The voting panel was comprised of people with lived and living experience of substance use, academics specializing in harm reduction, and clinicians and public health professionals from across Canada. Two rounds of voting were undertaken to score questions on importance for inclusion in the guideline. RESULTS: Nine questions that were identified as most important include what equipment should be in THN kits, whether there are important differences between intramuscular and intranasal naloxone administration, how stigma impacts access to distribution programs, how effective THN programs are at saving lives, what distribution models are most effective and equitable, storage considerations for naloxone in a community setting, the role of CPR and rescue breathing in overdose response, client preference of naloxone distribution program type, and what aftercare should be provided for people who respond to overdoses. CONCLUSIONS: The Delphi method is an equitable consensus building process that generated priorities to guide guideline development.

Fatal opioid overdoses during and shortly after hospital admissions in England: A case-crossover study.

BACKGROUND: Hospital patients who use illicit opioids such as heroin may use drugs during an admission or leave the hospital in order to use drugs. There have been reports of patients found dead from drug poisoning on the hospital premises or shortly after leaving the hospital. This study examines whether hospital admission and discharge are associated with increased risk of opioid-related death. METHODS AND FINDINGS: We conducted a case-crossover study of opioid-related deaths in England. Our study included 13,609 deaths between January 1, 2010 and December 31, 2019 among individuals aged 18 to 64. For each death, we sampled 5 control days from the period 730 to 28 days before death. We used data from the national Hospital Episode Statistics database to determine the time proximity of deaths and control days to hospital admissions. We estimated the association between hospital admission and opioid-related death using conditional logistic regression, with a reference category of time neither admitted to the hospital nor within 14 days of discharge. A total of 236/13,609 deaths (1.7%) occurred following drug use while admitted to the hospital. The risk during hospital admissions was similar or lower than periods neither admitted to the hospital nor recently discharged, with odds ratios 1.03 (95% CI 0.87 to 1.21; p = 0.75) for the first 14 days of an admission and 0.41 (95% CI 0.30 to 0.56; p < 0.001) for days 15 onwards. 1,088/13,609 deaths (8.0%) occurred in the 14 days after discharge. The risk of opioid-related death increased in this period, with odds ratios of 4.39 (95% CI 3.75 to 5.14; p < 0.001) on days 1 to 2 after discharge and 2.09 (95% CI 1.92 to 2.28; p < 0.001) on days 3 to 14. 11,629/13,609 deaths (85.5%) did not occur close to a hospital admission, and the remaining 656/13,609 deaths (4.8%) occurred in hospital following admission due to drug poisoning. Risk was greater for patients discharged from psychiatric admissions, those who left the hospital against medical advice, and those leaving the hospital after admissions of 7 days or more. The main limitation of the method is that it does not control for time-varying health or drug use within individuals; therefore, hospital admissions coinciding with high-risk periods may in part explain the results. CONCLUSIONS: Discharge from the hospital is associated with an acute increase in the risk of opioid-related death, and 1 in 14 opioid-related deaths in England happens in the 2 weeks after the hospital discharge. This supports interventions that prevent early discharge and improve linkage with community drug treatment and harm reduction services.

Implementation and evaluation of a novel, unofficial, trainee-organized hospital addiction medicine consultation service.

Background: To evaluate a novel, unofficial, trainee-organized, hospital addiction medicine consultation service (AMCS), we aimed to assess whether it was (1) acceptable to hospital providers and patients, (2) feasible to organize and deliver, and (3) impacted patient care. Methods: We performed a retrospective descriptive study of all AMCS consultations over the first 16 months. We determined acceptability via the number of referrals received from admitting services, and the proportion of referred patients who consented to consultation. We evaluated feasibility via continuation/growth of the service over time, and the proportion of referrals successfully completed before hospital discharge. As most referrals related to opioid use disorder, we determined impact through the proportion of eligible patients offered and initiated on opioid agonist therapy (OAT) in hospital, and the proportion of patients who filled their outpatient prescription or attended their first visit with their outpatient OAT prescriber. Results: The unofficial AMCS grew to involve six hospital-based residents and five supervising community-based addiction physicians. The service received 59 referrals, primarily related to injection opioid use, for 50 unique patients from 12 different admitting services. 90% of patients were seen before discharge, and 98% agreed to addiction medicine consultation. Among 34 patients with active moderate-severe opioid use disorder who were not already on OAT, 82% initiated OAT in hospital and 89% of these patients continued after discharge. Conclusions: Established in response to identified gaps in patient care and learning opportunities, a novel, unofficial, trainee-organized AMCS was acceptable, feasible, and positively impacted patient care over the first 16 months. This trainee-organized, unofficial AMCS could be used as a model for other hospitals that do not yet have an official AMCS.

Case Series: Limited Opioid Withdrawal With Use of Transdermal Buprenorphine to Bridge to Sublingual Buprenorphine in Hospitalized Patients.

BACKGROUND: Prerequisite opioid withdrawal symptoms prior to buprenorphine induction are unacceptable to many patients. We assessed whether transdermal buprenorphine minimized withdrawal while bridging to sublingual therapy among hospital inpatients. METHODS: Retrospective chart review of (n = 23) inpatients with opioid use disorder or opioid dependence due to chronic pain. RESULTS: Of 23 inpatients, 65% transitioned without symptoms, while 35% experienced mild withdrawal. Ninety-six percent completed planned hospitalizations, with 83% engaged in treatment 4 weeks post-discharge. DISCUSSION AND CONCLUSIONS: Bridging to sublingual therapy with transdermal buprenorphine patches was feasible without withdrawal symptoms. SCIENTIFIC SIGNIFICANCE: This strategy may facilitate buprenorphine therapy in hospital inpatients. (Am J Addict 2019;00:1-4).

Document d'orientation sur la distribution et l'utilisation de trousses de naloxone à emporter par les intervenants et intervenantes communautaires en cas de surdose au Canada.

CONTEXTE: La toxicité croissante des opioïdes dans le marché illicite des drogues a fait exploser le nombre de surdoses au Canada et ailleurs dans le monde; le programme de naloxone à emporter (NàE) est une intervention fondée sur des données probantes qui consiste à distribuer des trousses contenant de la naloxone aux membres de la communauté susceptibles d'être témoins d'une surdose. L'objectif du présent document d'orientation est de formuler des recommandations stratégiques à l'intention des programmes fédéraux, provinciaux et territoriaux de NàE, en s'appuyant sur des données probantes issues de la documentation scientifique, de la littérature grise et des communautés, à la lumière de 11 années de distribution de NàE au Canada. MÉTHODES : Le groupe d'élaboration des documents d'orientation sur la naloxone, une équipe multidisciplinaire composée de personnes ayant une expertise et une expérience vécue en matière de toxicomanie, a appliqué l'outil AGREE II (Appraisal of Guidelines for Research & Evaluation) afin d'éclairer l'élaboration du présent document d'orientation. En vue de l'élaboration de nos recommandations, nous avons procédé entre décembre 2021 et septembre 2022 à une revue systématique de tous les types d'ouvrages dans le but de recueillir les données probantes publiées, ainsi que les données probantes et l'expertise issues de la communauté. Nous avons sollicité des commentaires sur nos recommandations préliminaires par le biais d'un comité de révision externe et d'un processus de participation du public. Le projet a été financé par les Instituts de recherche en santé du Canada dans le cadre de l'Initiative canadienne de recherche sur l'abus de substances (ICRAS). Nous avons appliqué les principes du Réseau international en matière de lignes directrices (Guidelines International Network) pour gérer les intérêts concurrents. RECOMMANDATIONS: Les données probantes existantes issues de la documentation sur la NàE étaient de faible qualité. Pour élaborer nos recommandations, nous avons incorporé des données probantes tirées de la documentation scientifique et de la littérature grise, ainsi que l'expertise de la communauté. Nos recommandations portent sur 3 volets : les voies d'administration de la naloxone, le contenu des trousses de NàE et les interventions en cas de situations de surdose. Les trousses distribuées par les programmes de naloxone à emporter doivent offrir le choix entre les préparations intramusculaire et intranasale. Le contenu recommandé de la trousse comprend la naloxone, un dispositif d'administration de la naloxone, un équipement de protection individuelle, des instructions et un étui de transport. Les intervenants et intervenantes communautaires formés à la réponse aux surdoses doivent prioriser la respiration artificielle en cas de dépression respiratoire, et la réanimation cardiorespiratoire (RCR) conventionnelle en cas d'arrêt cardiaque, entre autres interventions. INTERPRÉTATION : Ce projet d'élaboration d'un document d'orientation vise à guider les programmes de NàE au Canada dans un contexte où les données probantes publiées sont rares; les recommandations ont été élaborées en collaboration avec diverses parties prenantes.

A frailty index predicts post-liver transplant morbidity and mortality in HIV-positive patients.

BACKGROUND: We hypothesized that frailty acts as a measure of health outcomes in the context of LT. The aim of this study was to explore frailty index across LT, as a measure of morbidity and mortality. This was a retrospective observational study including all consecutive 47 HIV+patients who received LT in Modena, Italy from 2003 to June 2015. METHODS: frailty index (FI) was constructed from 30 health variables. It was used both as a continuous score and as a categorical variable, defining 'most frail' a FI > 0.45. FI change across transplant (deltaFI, ΔFI) was calculated as the difference between year 1 FI (FI-Y1) and pre-transplant FI (FI-t0). The outcomes measures were mortality and "otpimal LT" (defined as being alive without multi-morbidity). RESULTS: Median value of FI-t0 was 0.48 (IQR 0.42-0.52), FI-Y1 was 0.31 (IQR 0.26-0.41). At year five mortality rate was 45%, "optimal transplant" rate at year 1 was 38%. All the patients who died in the post-LT were most frail in the pre-LT. ΔFI was a predictor of mortality after correction for age and MELD (HR = 1.10, p = 0.006) and was inversely associated with optimal transplant after correction for age (HR = 1.04, p = 0.01). CONCLUSIONS: We validated FI as a valuable health measure in HIV transplant. In particular, we found a relevant correlation between FI strata at baseline and mortality and a statistically significant correlation between, ΔFI and survival rate.

Late presentation increases risk and costs of non-infectious comorbidities in people with HIV: an Italian cost impact study.

BACKGROUND: Late presentation (LP) at the time of HIV diagnosis is defined as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells/mm. The objective of our study was to assess the prevalence of non-infectious comorbidities (NICM) and multimorbidity among HIV-positive individuals with and without a history of LP (HIV + LP and HIV + EP, respectively), and compare them to matched HIV-negative control participants from a community-based cohort. The secondary objective was to provide estimates and determinants of direct cost of medical care in HIV patients. METHODS: We performed a matched cohort study including HIV + LP and HIV + EP among people attending the Modena HIV Metabolic Clinic (MHMC) in 2014. HIV-positive participants were matched in a 1:3 ratio with HIV-negative participants from the CINECA ARNO database. Multimorbidity was defined as the concurrent presence of ≥2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and multimorbidity. RESULTS: We analyzed 452 HIV + LP and 73 HIV + EP participants in comparison to 1575 HIV-negative controls. The mean age was 46 ± 9 years, 27.5% were women. Prevalence of NICM and multimorbidity were fourfold higher in the HIV + LP compared to the general population (p < 0.001), while HIV + EP present an intermediate risk. LP was associated with increased total costs in all age strata, but appear particularly relevant in patients above 50 years of age, after adjusting for age, multimorbidity, and antiretroviral costs. CONCLUSIONS: LP with HIV infection is still very frequent in Italy, is associated with higher prevalence of NICM and multimorbidity, and contributes to higher total care costs. Encouraging early testing and access to care is still urgently needed.

Frailty in people aging with human immunodeficiency virus (HIV) infection.

The increasing life spans of people infected with human immunodeficiency virus (HIV) reflect enormous treatment successes and present new challenges related to aging. Even with suppression of viral loads and immune reconstitution, HIV-positive individuals exhibit excess vulnerability to multiple health problems that are not AIDS-defining. With the accumulation of multiple health problems, it is likely that many people aging with treated HIV infection may be identified as frail. Studies of frailty in people with HIV are currently limited but suggest that frailty might be feasible and useful as an integrative marker of multisystem vulnerability, for organizing care and for comprehensively measuring the impact of illness and treatment on overall health status. This review explains how frailty has been conceptualized and measured in the general population, critically reviews emerging data on frailty in people with HIV infection, and explores how the concept of frailty might inform HIV research and care.

Comparison of alternate scoring of variables on the performance of the frailty index.

BACKGROUND: The frailty index (FI) is used to measure the health status of ageing individuals. An FI is constructed as the proportion of deficits present in an individual out of the total number of age-related health variables considered. The purpose of this study was to systematically assess whether dichotomizing deficits included in an FI affects the information value of the whole index. METHODS: Secondary analysis of three population-based longitudinal studies of community dwelling individuals: Nova Scotia Health Survey (NSHS, n = 3227 aged 18+), Survey of Health, Ageing and Retirement in Europe (SHARE, n = 37546 aged 50+), and Yale Precipitating Events Project (Yale-PEP, n = 754 aged 70+). For each dataset, we constructed two FIs from baseline data using the deficit accumulation approach. In each dataset, both FIs included the same variables (23 in NSHS, 70 in SHARE, 33 in Yale-PEP). One FI was constructed with only dichotomous values (marking presence or absence of a deficit); in the other FI, as many variables as possible were coded as ordinal (graded severity of a deficit). Participants in each study were followed for different durations (NSHS: 10 years, SHARE: 5 years, Yale PEP: 12 years). RESULTS: Within each dataset, the difference in mean scores between the ordinal and dichotomous-only FIs ranged from 0 to 1.5 deficits. Their ability to predict mortality was identical; their absolute difference in area under the ROC curve ranged from 0.00 to 0.02, and their absolute difference between Cox Hazard Ratios ranged from 0.001 to 0.009. CONCLUSIONS: Analyses from three diverse datasets suggest that variables included in an FI can be coded either as dichotomous or ordinal, with negligible impact on the performance of the index in predicting mortality.

Health-care resource use among patients who use illicit opioids in England, 2010-20: A descriptive matched cohort study.

BACKGROUND AND AIMS: People who use illicit opioids have higher mortality and morbidity than the general population. Limited quantitative research has investigated how this population engages with health-care, particularly regarding planned and primary care. We aimed to measure health-care use among patients with a history of illicit opioid use in England across five settings: general practice (GP), hospital outpatient care, emergency departments, emergency hospital admissions and elective hospital admissions. DESIGN: This was a matched cohort study using Clinical Practice Research Datalink and Hospital Episode Statistics. SETTING: Primary and secondary care practices in England took part in the study. PARTICIPANTS: A total of 57 421 patients with a history of illicit opioid use were identified by GPs between 2010 and 2020, and 172 263 patients with no recorded history of illicit opioid use matched by age, sex and practice. MEASUREMENTS: We estimated the rate (events per unit of time) of attendance and used quasi-Poisson regression (unadjusted and adjusted) to estimate rate ratios between groups. We also compared rates of planned and unplanned hospital admissions for diagnoses and calculated excess admissions and rate ratios between groups. FINDINGS: A history of using illicit opioids was associated with higher rates of health-care use in all settings. Rate ratios for those with a history of using illicit opioids relative to those without were 2.38 [95% confidence interval (CI) = 2.36-2.41] for GP; 1.99 (95% CI = 1.94-2.03) for hospital outpatient visits; 2.80 (95% CI = 2.73-2.87) for emergency department visits; 4.98 (95% CI = 4.82-5.14) for emergency hospital admissions; and 1.76 (95% CI = 1.60-1.94) for elective hospital admissions. For emergency hospital admissions, diagnoses with the most excess admissions were drug-related and respiratory conditions, and those with the highest rate ratios were personality and behaviour (25.5, 95% CI = 23.5-27.6), drug-related (21.2, 95% CI = 20.1-21.6) and chronic obstructive pulmonary disease (19.4, 95% CI = 18.7-20.2). CONCLUSIONS: Patients who use illicit opioids in England appear to access health services more often than people of the same age and sex who do not use illicit opioids among a wide range of health-care settings. The difference is especially large for emergency care, which probably reflects both episodic illness and decompensation of long-term conditions.