Psychosocial factors associated with overdose subsequent to Illicit Drug use: a systematic review and narrative synthesis.

BACKGROUND AND AIMS: Psychological and social status, and environmental context, may mediate the likelihood of experiencing overdose subsequent to illicit drug use. The aim of this systematic review was to identify and synthesise psychosocial factors associated with overdose among people who use drugs. METHODS: This review was registered on Prospero (CRD42021242495). Systematic record searches were undertaken in databases of peer-reviewed literature (Medline, Embase, PsycINFO, and Cinahl) and grey literature sources (Google Scholar) for work published up to and including 14 February 2023. Reference lists of selected full-text papers were searched for additional records. Studies were eligible if they included people who use drugs with a focus on relationships between psychosocial factors and overdose subsequent to illicit drug use. Results were tabulated and narratively synthesised. RESULTS: Twenty-six studies were included in the review, with 150,625 participants: of those 3,383-4072 (3%) experienced overdose. Twenty-one (81%) studies were conducted in North America and 23 (89%) reported polydrug use. Psychosocial factors associated with risk of overdose (n = 103) were identified and thematically organised into ten groups. These were: income; housing instability; incarceration; traumatic experiences; overdose risk perception and past experience; healthcare experiences; perception of own drug use and injecting skills; injecting setting; conditions with physical environment; and social network traits. CONCLUSIONS: Global rates of overdose continue to increase, and many guidelines recommend psychosocial interventions for dependent drug use. The factors identified here provide useful targets for practitioners to focus on at the individual level, but many identified will require wider policy changes to affect positive change. Future research should seek to develop and trial interventions targeting factors identified, whilst advocacy for key policy reforms to reduce harm must continue.

Increased risk of chronic kidney disease and mortality in a cohort of people diagnosed with metabolic dysfunction associated steatotic liver disease with hepatic fibrosis.

BACKGROUND AND AIMS: Metabolic dysfunction associated steatotic liver disease (MASLD) increases the risk of incident chronic kidney disease (CKD). However, the relative risk of CKD associated with increasing hepatic fibrosis, and consequent mortality risk, remains underexplored in real-world cohorts. In this study, we sought to establish whether hepatic fibrosis is associated with increased CKD risk and explore differences in mortality risk in a cohort of people living with MASLD, contingent on liver fibrosis and CKD status. METHODS: This was an observational study of people who underwent routine liver function testing in Tayside, Scotland. MASLD was defined as: elevated ALT (>30 U/L) or GGT (>73 U/L); presence of diabetes, and/or hypertension, and/or obesity; weekly alcohol consumption <14 units (112g (+/-8g) alcohol); and negative screen for other aetiologies. Data was collected from digital health records. We used log-binomial models to quantify the risk of CKD among those with and without fibrosis, and Cox regression models to estimate differences in mortality risk dependent on fibrosis and CKD. RESULTS: In our cohort (n = 2,046), 1,448 (70.8%) people had MASLD without fibrosis and 598 (29.2%) with fibrosis; 161 (11.1%) and 117 (19.6%) respectively also had CKD. After excluding individuals with structural, autoimmune, or malignant CKD (n = 22), liver fibrosis (n = 593; 18.9% with CKD) was associated with increased CKD risk (aRR = 1.31, 1.04-1.64, p = 0.021). Increased mortality risk was observed for those with liver fibrosis (aHR = 2.30, 1.49-3.56, p = <0.001) and was higher again among people with both fibrosis and CKD (aHR = 5.07, 3.07-8.39, p = <0.014). CONCLUSIONS: Liver fibrosis was an independent risk factor for CKD in this cohort of people living with MASLD. Furthermore, those with MASLD with liver fibrosis had higher risk for mortality and this risk was further elevated among those with co-morbid CKD. Given the increased risk of CKD, and consequent mortality risk, among people living with MASLD fibrosis, renal function screening should be considered within liver health surveillance programmes and guidelines.

Long-term risk factors for developing Barrett's oesophagus in patients with gastro-oesophageal reflux disease: a longitudinal cohort study.

BACKGROUND AND AIMS: Several characteristics are known to affect the risk of Barrett's oesophagus (BO) in the general population, with symptomatic gastro-oesophageal reflux disease (GORD) being a critical risk factor. In this study, we examined factors that influence BO development in people living with GORD. DESIGN: People living with GORD were recruited from an endoscopy unit with lifestyle, medical and prescribing history collected. Logistic regression analysis was undertaken to assess the effects of multiple parameters on the likelihood of developing BO. RESULTS: 1197 participants were recruited. Most were Caucasian (n=1188, 99%), had no formal educational qualifications (n=714; 59.6%) and lived with overweight (mean body mass index >25 kg/m2). Many lived in areas of least socioeconomic resource (n=568; 47.4%). 139 (11.6%) had BO at baseline. In adjusted baseline analysis (n=1197), male sex (adjusted OR, aOR 2.04 (95% CI 1.92 to 4.12), p≤0.001), increasing age (aOR 1.03 (95% CI 1.01 to 1.04), p≤0.0001) and proton pump inhibitor use (aOR 3.03 (95% CI 1.80 to 5.13), p≤0.0001) were associated with higher odds of BO. At follow-up (n=363), 22 (6.1%) participants developed BO; male sex (aOR 3.18 (95% CI 1.28 to 7.86), p=0.012), pack-years cigarettes smoked (aOR 1.04 (95% CI 1.00 to 1.08), p=0.046) and increased alcohol intake (aOR 1.02 (95% CI 1.00 to 1.04), p=0.013), were associated with increased odds of BO. CONCLUSION: Male sex, pack-years cigarettes smoked, and increasing alcohol intake, were independently associated with increased odds of developing BO over 20-year follow-up. These results align with research linking male sex and smoking with BO and extend this by implicating the potential role of alcohol in developing BO, which may require communication through public health messaging.

Viral hepatitis testing and treatment in community pharmacies: a systematic review and meta-analysis.

Background: The World Health Organization seeks to eliminate viral hepatitis as a public health threat by 2030. This review and meta-analysis aims to evaluate the effectiveness of programs for hepatitis B and C testing and treatment in community pharmacies. Methods: Medline, Embase, Cochrane CENTRAL, and Global Health were searched from database inception until 12 November 2023. Comparative and single arm intervention studies were eligible for inclusion if they assessed delivery of any of the following interventions for hepatitis B or C in pharmacies: (1) pre-testing risk assessment, (2) testing, (3) pre-treatment assessment or (4) treatment. Primary outcomes were proportions testing positive and reaching each stage in the cascade. Random effects meta-analysis was used to estimate pooled proportions stratified by recruitment strategy and setting where possible; other results were synthesised narratively. This study was pre-registered (PROSPERO: CRD42022324218). Findings: Twenty-seven studies (4 comparative, 23 single arm) were included, of which 26 reported hepatitis C outcomes and four reported hepatitis B outcomes. History of injecting drug use was the most identified risk factor from pre-testing risk assessments. The pooled proportion hepatitis C antibody positive from of 19 studies testing 5096 participants was 16.6% (95% CI 11.0%-23.0%; heterogeneity I2 = 96.6%). The pooled proportion antibody positive was significantly higher when testing targeted people with specified risk factors (32.5%, 95% CI 24.8%-40.6%; heterogeneity I2 = 82.4%) compared with non-targeted or other recruitment methods 4.0% (95% CI 2.1%-6.5%; heterogeneity I2 = 83.5%). Meta-analysis of 14 studies with 813 participants eligible for pre-treatment assessment showed pooled attendance rates were significantly higher in pharmacies (92.7%, 95% CI 79.1%-99.9%; heterogeneity I2 = 72.4%) compared with referral to non-pharmacy settings (53.5%, 95% CI 36.5%-70.1%; heterogeneity I2 = 92.3%). The pooled proportion initiating treatment was 85.6% (95% CI 74.8%-94.3%; heterogeneity I2 = 75.1%). This did not differ significantly between pharmacy and non-pharmacy settings. Interpretation: These findings add pharmacies to the growing evidence supporting community-based testing and treatment for hepatitis C. Few comparative studies and high degrees of statistical heterogeneity were important limitations. Hepatitis B care in pharmacies presents an opportunity for future research. Funding: None.

Optimal ALT threshold for the automated diagnosis of MASLD: A population-based study using iLFT.

INTRODUCTION AND OBJECTIVES: Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to the increased risk of complications and mortality. Serum alanine aminotransferase (ALT) is commonly used; however, many patients have normal ranges (<55 U/L) who may remain undetected. We investigated the clinical implications of a lower ALT cut-off (>30 U/L) using intelligent liver function testing (iLFT) to identify MASLD patients with and without advanced fibrosis in primary care. MATERIALS AND METHODS: All patients entering the iLFT diagnostic pathway had liver aetiological screening investigations if ALT >30 U/L. In those with MASLD the proportions with and without advanced fibrosis at different ALT thresholds: 31-41 U/L, 42-54 U/L and ≥55 U/L were compared. RESULTS: 16,373 patients underwent iLFT between March 2016 to April 2022. 762 (5 %) patients had MASLD with abnormal fibrosis scores, while 908 (6 %) had MASLD with normal fibrosis scores. 428 (56 %) patients were assessed in liver clinics, where 169 (39 %) had evidence of fibrosis. Of these, 22 (13 %) had ALT 31-41 U/L, 31 (18 %) had ALT 42-54 U/L and 116 (69 %) had ALT ≥55 U/L. 145 (86 %) patients had advanced fibrosis or cirrhosis, where 20 (14 %) had ALT 31-41 U/L, 28 (19 %) had ALT 42-54 U/L and 97 (67 %) had ALT ≥55 U/L. CONCLUSIONS: 33 % of MASLD patients with advanced fibrosis or cirrhosis had ALT 31-54 U/L, who would have been missed using the conventional ALT range. This suggests that lowering the ALT cut-off improves diagnosis of MASLD with advanced fibrosis in primary care.

A multicomponent holistic care pathway for people who use drugs in Tayside, Scotland.

BACKGROUND: People Who Use Drugs (PWUD) are at high risk of non-fatal overdose and other drug-related harms. The United Kingdom drugs policy landscape makes it challenging to support those at risk. Tayside, in East Scotland, has a sizeable population at risk of drug-related harms. In 2021, the National Health Service implemented a care pathway for PWUD to provide multidimensional healthcare interventions. We aimed to quantify drug-related harms; assess wider health and well-being; and understand substance use trends and behaviours, among those engaged in the pathway. METHODS: Existing community-embedded blood-borne virus pathways were adapted to provide multiple healthcare assessments over three visits. We undertook an observational cohort study to analyse uptake and outcomes for the initial cohort of PWUD engaged at appointment one. RESULTS: From August 2021-September 2022, 150 PWUD engaged with the pathway. Median age was 39 (34-42) years, 108 (72%) were male, and 124 (83%) lived in deprived areas. Seventy (47%) had been disengaged from healthcare for over a year. Polysubstance use was reported by 124 (83%), 42 (28%) disclosed injecting daily, and 54 (36%) shared equipment. Fifty-four (36%) experienced recent non-fatal overdose, and there were six overdose fatalities (4.1 [1.5-9.0] per 100PY). The offer of take-home naloxone was accepted by 108 (72%). Fourteen (9%) were diagnosed with Hepatitis C and two (1%) with HIV. Renal, hepatological, and endocrine impairment were observed among 30 (20%), 23 (15%), and 11 (7%), people respectively. Ninety-six (65%) had high risk of clinical depression. Forty-eight (32%) declined Covid-19 vaccination. CONCLUSION: The pathway engaged PWUD with high exposure to recent non-fatal overdose and other drug-related harms, alongside co-morbid health issues. Our results suggest multi-dimensional health assessments coupled with harm reduction in community settings, with appropriate linkage to care, are warranted for PWUD. Service commissioners should seek to integrate these assessments where possible.

Mixed-methods evaluation of point-of-care hepatitis C virus RNA testing in a Scottish prison.

OBJECTIVES: Hepatitis C virus (HCV) poses a global public health threat. Prisons are a focus of prevention efforts due to high infection burdens. Expedition of treatment for incarcerated people is critical, as many are short-term sentenced. We evaluated point-of-care (PoC) HCV RNA testing in a maximum-security Scottish prison and assessed its impact on transition to treatment. We also evaluated costs and determinants of implementation. DESIGN: Mixed-methods evaluation of a single-centre care pathway pilot using National Health Service (NHS) data from 2018 to 2021. Descriptive statistics and survival analysis were undertaken. Cost analysis was assessed from a provider perspective. Healthcare staff participated in semistructured interviews and thematic analysis with a deductive approach was undertaken to identify implementation determinants. SETTING: A large maximum-security Scottish prison health centre administered by the NHS. PARTICIPANTS: 296 incarcerated NHS patients (all men) and six NHS staff members (two men and four women). INTERVENTIONS: HCV testing using the Cepheid GeneXpert platform with Xpert HCV VL Fingerstick assay. OUTCOME MEASURES: The main outcome was survival (in days) from HCV test to treatment initiation. Secondary outcomes were cost-per-cure obtained and implementation determinants. RESULTS: During the pilot, 167 Xpert tests were administered, with an 84% completion rate, and treatment transition was superior for those who received it (p=0.014). Where PoC tests were administered, shorter survival to treatment was observed (19 vs 33 days: adjusted HR (aHR) 1.91 (1.03-3.55), p=0.040; 19 vs 50 days; aHR 3.76 (1.67-8.46), p=0.001). PoC was costlier than conventional testing. In qualitative analysis, most facilitators were observed among characteristics of individual domain while most barriers were noted in the inner setting. CONCLUSIONS: Integrating PoC HCV RNA diagnosis into nurse-led HCV care in a maximum-security prison health centre shortens survival to HCV treatment. However, there are cost implications to this approach and multiple determinants that impact on implementation should be addressed.

Laying the foundations for hepatitis C elimination: evaluating the development and contribution of community care pathways to diagnostic efforts.

BACKGROUND: Hepatitis C Virus (HCV) is a public health threat which contributes substantially to the global burden of liver disease. There is much debate about effective approaches to scaling up diagnosis of HCV among risk groups. Tayside, a region in the East of Scotland, developed low-threshold community pathways for HCV to lay the foundations of an elimination strategy. In this retrospective study, we sought to: quantify the contribution of community pathways to increasing HCV diagnosis; understand if shifting diagnosis to community settings led to a higher proportion of individuals tested for HCV being actively infected; and describe functional characteristics of the care pathways. METHODS: Descriptive statistics were used to for analysis of routinely-collected HCV testing data from 1999 to 2017, and a review of the development of the care pathways was undertaken. Community-based testing was offered through general practices (GP); nurse outreach clinics; prisons; drug treatment services; needle and syringe provision (NSP) sites; community pharmacies; and mosques. RESULTS: Anti-HCV screening was undertaken on 109,430 samples, of which 5176 (4.7%) were reactive. Of all samples, 77,885 (71.2%) were taken in secondary care; 25,044 (22.9%) in GPs; 2970 (2.7%) in prisons; 2415 (2.2%) in drug services; 753 (0.7%) in NSPs; 193 (0.2%) pharmacies; and 170 (0.1%) in mosques. The highest prevalence of HCV infection among those tested was in NSP sites (26%), prisons (14%), and drug treatment centres (12%). CONCLUSIONS: Decentralised care pathways, particularly in harm reduction and other drug service settings, were key to increasing diagnosis of HCV in the region, but primary and secondary care remain central to elimination efforts.

Drug network identification predicts injecting risk behavior among people who inject drugs on hepatitis C virus treatment in Tayside, Scotland.

The risk of Hepatitis C Virus (HCV) acquisition among People Who Inject Drugs (PWID) remains high when injecting risk behavior within networks endures. Several psychosocial factors influence such behavior. Following a drive within Tayside, a geographic region in Scotland, to achieve World Health Organization HCV elimination targets, addressing HCV re-infection risk as a barrier to elimination is critically important. This cross-sectional study seeks to address this barrier to elimination by investigating associations between group identification (one's subjective sense of belonging and connectedness to a social group coupled with a sense of shared goals, beliefs and values with the other members of the group) and injecting risk behavior among PWID on HCV treatment at needle and syringe provision sites in Tayside. Participants completed psychosocial questionnaires between treatment weeks zero and three of treatment. Correlation analyses were undertaken, and significant factors included in multiple linear regression models for injecting risk behavior. Injecting frequency, drug network identification, and family identification, were correlated with injecting risk behavior, and drug network identification had a positive predictive on injecting risk behavior. Identification with a social group, conventionally associated with improved health, may pose health risks in specific contexts. Healthcare providers should consider stratifying individuals with higher group identification with PWID networks for enhanced harm reduction engagement to mitigate transmissible infection risk among PWID. Additionally, psychological interventions to strengthen group identification with networks which impact positively on health behavior should be explored.

Reaching people receiving opioid agonist therapy at community pharmacies with hepatitis C virus: an international randomised controlled trial.

BACKGROUND: Conventional healthcare models struggle to engage those at risk of hepatitis C virus (HCV) infection. This international study evaluated point-of-care (PoC) HCV RNA diagnostic outreach and direct-acting antiviral (DAA) treatment for individuals receiving opioid agonist therapy (OAT) in community pharmacies. AIMS: We assessed the effectiveness of a roving nurse-led pathway offering PoC HCV RNA testing to OAT clients in community pharmacies relative to conventional care. METHODS: Pharmacies in Scotland, Wales, and Australia were randomised to provide PoC HCV RNA testing or conventional referral. Pharmacists directed OAT clients to on-site nurses (intervention) or local clinics (control). Infected participants were treated with DAAs, alongside OAT. Primary outcome was the number of participants with sustained virologic response at 12 weeks (SVR) and analysed using mixed effects logistic regression in the intention-to-treat (ITT) population. RESULTS: Forty pharmacies were randomised. The ITT population contained 1410 OAT clients. In the conventional arm (n = 648), 62 (10%) agreed to testing, 17 (27%) were tested, 6 (35%) were positive and 5 (83%) initiated treatment. In the intervention arm (n = 762), 148 (19%) agreed to testing, 144 (97%) were tested, 23 (16%) were positive and 22 (96%) initiated treatment. SVR was obtained by 2 (40%; conventional) and 18 (82%; intervention). Intervention arm participants had higher odds of testing, OR 16.95 (7.07-40.64, p < 0.001); treatment, OR 4.29 (1.43-12.92, p = 0.010); and SVR, OR 8.64 (1.82-40.91, p = 0.007). CONCLUSIONS: Nurse-led PoC diagnosis in pharmacies made HCV care more accessible for OAT clients relative to conventional care. However, strategies to improve testing uptake are required. TRIAL REGISTRATION: NCT03935906.

A Global Systematic Review of Hepatitis C Elimination Efforts through Micro-Elimination.

Microelimination targets specific subpopulations and/or geographic settings for hepatitis C virus (HCV) elimination. This review reports on global HCV microelimination literature published from 2013 to 2020. Data were extracted from publications to report a score based on the four key components defining microelimination. Sustained virologic response (SVR) and treatment initiation proportions were calculated for each manuscript and grouped means of these estimates were compared depending on microelimination score and care setting. A total of 83% of the studies were from high-income settings and mainly included people who use drugs or those incarcerated. Among manuscripts, 18 had "low" microelimination scores, 11 had "high" scores, and the differences in mean proportion who initiated treatment and achieved SVR between low and high score groups were statistically significant. Microelimination can be a useful complementary strategy for driving engagement in HCV treatment and cure. Our analysis suggests that adhering to more of the core microelimination components can improve outcomes. This study is registered with Prospero, registration identification: CRD42020175211.

Real-world outcomes of rapid regional hepatitis C virus treatment scale-up among people who inject drugs in Tayside, Scotland.

BACKGROUND: In 2017, Tayside, a region in the East of Scotland, rapidly scaled-up Hepatitis C Virus (HCV) outreach and treatment among People Who Inject Drugs (PWID) using novel community care pathways. AIMS: We aimed to determine treatment outcomes for PWID during the scale-up against pre-determined targets; and assess re-infection, mortality, and post-treatment follow up. METHODS: HCV treatment was delivered in community pharmacies, drug treatment centres, nurse-led outreach clinics, prisons, and needle exchanges, alongside conventional hospital care. We retrospectively analysed clinical outcomes and compared pathways using logistic regression models. RESULTS: Of 800 estimated HCV-infected PWID, 718 (90%) were diagnosed. 713 treatments commenced among 662 (92%) PWID, delivering 577 (81%) Sustained Virologic Responses (SVR). SVR was 91% among those who attended for testing. Forty-six individuals were treated more than once. Needle exchanges and community pharmacies initiated 49% of all treatments. Regression analyses implied pharmacies had superior follow-up, but there was no difference in likelihood of achieving SVR in community pathways relative to hospital care. Re-infection occurred 39 times over 256.57 person years (PY), yielding a rate of 15.20 per 100 PY (95% CI 10.81-20.78). 54 deaths occurred (29 drug related) over 1,553.04 PY, yielding a mortality rate of 3.48 per 100 PY (95% CI 2.61-4.54). Drug-related mortality was 1.87 per 100 PY (95% CI 1.25-2.68). CONCLUSIONS: Rapid HCV treatment scale-up to PWID in community settings, whilst maintaining high SVR, is achievable. However, other interventions are required to minimise re-infection; reduce drug-related deaths; and improve post-SVR follow-up testing regionally.

Meta-analysis of well-designed nonrandomized comparative studies of surgical procedures is as good as randomized controlled trials.

OBJECTIVE: To compare the results of meta-analysis of nonrandomized comparative studies (NRCSs) of a surgical procedure with that of randomized controlled trials (RCTs), and to assess the effect of design and conduct issues in NRCSs on measured outcomes. STUDY DESIGN AND SETTING: Two meta-analyses of RCTs and NRCSs (2,512 and 6,438 procedures, respectively) of laparoscopic resection for colorectal cancer were performed according to accepted protocols, and 13 outcomes common between them were compared. Odds ratios (ORs) and 95% confidence intervals (CI) for dichotomous outcomes were assessed for the degree of overlap. Continuous outcomes were compared using cumulative weighted ratios (CWRs) and percentages for which a mean and standard deviation (SD) were calculated. The effects of design and conduct issues in the meta-analysis of NRCSs on measured morbidity rates were assessed using subgroup analysis. RESULTS: The ORs of the three dichotomous outcomes overlapped widely. For the 10 continuous variables, the mean difference (SD) in the results of the two meta-analyses was only 5.6% (4.9%). Fulfillment of certain quality and conduct issues in the NRCSs determined the statistical homogeneity of the results of meta-analysis and their comparability with the "gold standard." CONCLUSION: Meta-analysis of well-designed NRCSs of surgical procedures is probably as accurate as that of RCTs.