To assess the association between long term prescription opioid treatment medically dispensed for non-cancer pain and the initiation of injection drug use (IDU) among individuals without a history of ...substance use.
Retrospective cohort study.
Large administrative data source (containing information for about 1.7 million individuals tested for hepatitis C virus or HIV in British Columbia, Canada) with linkage to administrative health databases, including dispensations from community pharmacies.
Individuals age 11-65 years and without a history of substance use (except alcohol) at baseline.
Episodes of prescription opioid use for non-cancer pain were identified based on drugs dispensed between 2000 and 2015. Episodes were classified by the increasing length and intensity of opioid use (acute (lasting <90 episode days), episodic (lasting ≥90 episode days; with <90 days' drug supply and/or <50% episode intensity), and chronic (lasting ≥90 episode days; with ≥90 days' drug supply and ≥50% episode intensity)). People with a chronic episode were matched 1:1:1:1 on socioeconomic variables to those with episodic or acute episodes and to those who were opioid naive. IDU initiation was identified by a validated administrative algorithm with high specificity. Cox models weighted by inverse probability of treatment weights assessed the association between opioid use category (chronic, episodic, acute, opioid naive) and IDU initiation.
59 804 participants (14 951 people from each opioid use category) were included in the matched cohort, and followed for a median of 5.8 years. 1149 participants initiated IDU. Cumulative probability of IDU initiation at five years was highest for participants with chronic opioid use (4.0%), followed by those with episodic use (1.3%) and acute use (0.7%), and those who were opioid naive (0.4%). In the inverse probability of treatment weighted Cox model, risk of IDU initiation was 8.4 times higher for those with chronic opioid use versus those who were opioid naive (95% confidence interval 6.4 to 10.9). In a sensitivity analysis limited to individuals with a history of chronic pain, cumulative risk for those with chronic use (3.4% within five years) was lower than the primary results, but the relative risk was not (hazard ratio 9.7 (95% confidence interval 6.5 to 14.5)). IDU initiation was more frequent at higher opioid doses and younger ages.
The rate of IDU initiation among individuals who received chronic prescription opioid treatment for non-cancer pain was infrequent overall (3-4% within five years) but about eight times higher than among opioid naive individuals. These findings could have implications for strategies to prevent IDU initiation, but should not be used as a reason to support involuntary tapering or discontinuation of long term prescription opioid treatment.
The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study ...aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries.
Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5.
Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5.
This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.
Prescription opioid use (POU) is often a precursor to opioid use disorder (OUD) and subsequent consequences. Persons with chronic hepatitis C virus infection (CHC) may be at a higher risk of POU due ...to a higher comorbidity burden and social vulnerability factors. We sought to determine the burden of POU and associated risk factors among persons with CHC in the context of social vulnerability. We identified CHC persons and propensity-score matched HCV- controls in the electronically retrieved Cohort of HCV-Infected Veterans and determined the frequency of acute, episodic long-term and chronic long-term POU and the prevalence of social vulnerability factors among persons with POU. We used logistic regression analysis to determine factors associated with POU. Among 160,856 CHC and 160,856 propensity-score matched HCV-controls, acute POU was recorded in 38.4% and 38.0% (P = 0.01) respectively. Episodic long-term POU was recorded in 3.9% in each group (P = 0.5), while chronic long-term POU was recorded in 28.4% and 19.2% (P < 0.0001). CHC was associated with a higher risk of chronic long-term POU (OR 1.66, 95%CI 1.63, 1.69), but not with acute or episodic long-term POU. Black race, female sex and homelessness were associated with a higher risk of chronic long-term POU. Presence of ≥ 1 factor was associated with a higher risk of all POU patterns. Persons with CHC have more social vulnerability factors and a higher risk of chronic long-term POU. Presence of ≥ 1 social vulnerability factor is associated with a higher risk of POU. Downstream consequences of POU need further study.
Co-occurrence of social conditions and infections may affect HIV/HCV disease risk and progression. We examined the changes in relationship of these social conditions and infections on HIV and ...hepatitis C virus (HCV) infections over time in British Columbia during 1990-2013.
The BC Hepatitis Testers Cohort (BC-HTC) includes ~1.5 million individuals tested for HIV or HCV, or reported as a case of HCV, HIV, HBV, or tuberculosis linked to administrative healthcare databases. We classified HCV and HIV infection status into five combinations: HIV-/HCV-, HIV+monoinfected, HIV-/HCV+seroconverters, HIV-/HCV+prevalent, and HIV+/HCV+.
Of 1.37 million eligible individuals, 4.1% were HIV-/HCV+prevalent, 0.5% HIV+monoinfected, 0.3% HIV+/HCV+ co-infected and 0.5% HIV-/HCV+seroconverters. Overall, HIV+monoinfected individuals lived in urban areas (92%), had low injection drug use (IDU) (4%), problematic alcohol use (4%) and were materially more privileged than other groups. HIV+/HCV+ co-infected and HIV-/HCV+seroconverters were materially most deprived (37%, 32%), had higher IDU (28%, 49%), problematic alcohol use (14%, 17%) and major mental illnesses (12%, 21%). IDU, opioid substitution therapy, and material deprivation increased in HIV-/HCV+seroconverters over time. In multivariable multinomial regression models, over time, the odds of IDU declined among HIV-/HCV+prevalent and HIV+monoinfected individuals but not in HIV-/HCV+seroconverters. Declines in odds of problematic alcohol use were observed in HIV-/HCV+seroconverters and coinfected individuals over time.
These results highlight need for designing prevention, care and support services for HIV and HCV infected populations based on the evolving syndemics of infections and social conditions which vary across groups.
Background & Aims
Public health measures introduced to limit transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (COVID‐19), also ...disrupted various healthcare services in many regions worldwide, including British Columbia (BC), Canada. We assessed the impact of these measures, first introduced in BC in March 2020, on hepatitis C (HCV) testing and first‐time HCV‐positive diagnoses within the province.
Methods
De‐identified HCV testing data for BC residents were obtained from the provincial Public Health Laboratory. Weekly changes in anti‐HCV, HCV RNA and genotype testing episodes and first‐time HCV‐positive (anti‐HCV/RNA/genotype) diagnoses from January 2018 to December 2020 were assessed and associations were determined using segmented regression models examining rates before vs after calendar week 12 of 2020, when measures were introduced.
Results
Average weekly HCV testing and first‐time HCV‐positive diagnosis rates fell immediately following the imposition of public health measures by 62.3 per 100 000 population and 2.9 episodes per 1 000 000 population, respectively (P < .0001 for both), and recovered in subsequent weeks to near pre‐March 2020 levels. Average weekly anti‐HCV positivity rates decreased steadily pre‐restrictions and this trend remained unchanged afterwards.
Conclusions
Reductions in HCV testing and first‐time HCV‐positive diagnosis rates, key drivers of progression along the HCV care cascade, occurred following the introduction of COVID‐19‐related public health measures. Further assessment will be required to better understand the full impact of these service disruptions on the HCV care cascade and to inform strategies for the re‐engagement of people who may have been lost to care because of these measures.
Display omitted
•Alcohol use disorder is a major contributor to HCV-related liver disease burden.•Alcohol use could reduce individual and population level benefits of HCV treatment.•Impact of alcohol ...use on liver disease should be monitored in the DAA era.•World Health Organization has set a 65% HCV mortality reduction target by 2030.•To achieve this target, strategies are needed to manage the use and impact of alcohol.
The advent of direct-acting antivirals (DAAs) has led to ambitious targets for hepatitis C virus (HCV) elimination. However, in the context of alcohol use disorder the ability of DAAs to achieve these targets may be compromised. The aim of this study was to evaluate the contribution of alcohol use disorder to HCV-related decompensated cirrhosis in three settings.
HCV notifications from British Columbia, Canada; New South Wales, Australia, and Scotland (1995–2011/2012/2013, respectively) were linked to hospital admissions (2001–2012/2013/2014, respectively). Alcohol use disorder was defined as non-liver-related hospitalisation due to alcohol use. Age-standardised decompensated cirrhosis incidence rates were plotted, associated factors were assessed using Cox regression, and alcohol use disorder-associated population attributable fractions (PAFs) were computed.
Among 58,487, 84,529, and 31,924 people with HCV in British Columbia, New South Wales, and Scotland, 2,689 (4.6%), 3,169 (3.7%), and 1,375 (4.3%) had a decompensated cirrhosis diagnosis, and 28%, 32%, and 50% of those with decompensated cirrhosis had an alcohol use disorder, respectively. Age-standardised decompensated cirrhosis incidence rates were considerably higher in people with alcohol use disorder in New South Wales and Scotland. Decompensated cirrhosis was independently associated with alcohol use disorder in British Columbia (aHR 1.92; 95% CI 1.76–2.10), New South Wales (aHR 3.68; 95% CI 3.38–4.00) and Scotland (aHR 3.88; 95% CI 3.42–4.40). The PAFs of decompensated cirrhosis-related to alcohol use disorder were 13%, 25%, and 40% in British Columbia, New South Wales and Scotland, respectively.
Alcohol use disorder was a major contributor to HCV liver disease burden in all settings, more distinctly in Scotland. The extent to which alcohol use would compromise the individual and population-level benefits of DAA therapy needs to be closely monitored. Countries, where appropriate, must develop strategies combining promotion of DAA treatment uptake with management of alcohol use disorders, if World Health Organization 2030 HCV mortality reduction targets are going to be achieved.
The burden of liver disease has been rising among people with hepatitis C globally. The recent introduction of highly effective medicines against hepatitis C (called direct-acting antivirals or DAAs) has brought renewed optimism to the sector. DAA scale-up could eliminate hepatitis C as a public health threat in the coming decades. However, our findings show heavy alcohol use is a major risk factor for liver disease among people with hepatitis C. If continued, heavy alcohol use could compromise the benefits of new antiviral treatments at the individual- and population-level. To tackle hepatitis C as a public health threat, where needed, DAA therapy should be combined with management of heavy alcohol use.
Access to hepatitis C (HCV) testing and treatment is still limited globally. To address this, the Government of Rwanda launched a voluntary mass screening and treatment campaign in 2017. We studied ...the progression of patients through the cascade of HCV care during this campaign. We conducted a retrospective cohort study and included all patients screened at 46 hospitals between April 2017 and October 2019. We used hierarchical logistic regression to assess factors associated with HCV positivity, gaps in care, and treatment failure. A total of 860,801 people attended the mass screening during the study period. Some 5.7% tested positive for anti-HCV, and 2.9% were confirmed positive. Of those who were confirmed positive, 52% initiated treatment, and 72% of those initiated treatment, completed treatment and returned for assessment 12 weeks afterward. The cure rate was 88%. HCV positivity was associated with age, socio-economic status, sex, marital status, and HIV coinfection. Treatment failure was associated with cirrhosis, baseline viral load, and a family history of HCV. Our results suggest that future HCV screening and testing interventions in Rwanda and other similar settings should target high-risk groups. High dropout rates suggest that more effort should be put into patient follow-up to increase adherence to care.
Background. Cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States, primarily among children. We estimate ...levels of cross-reactive antibody to H3N2v by age and assess whether seasonal trivalent inactivated influenza vaccine (TIV), with or without adjuvant, may increase seroprotection. Methods. Antibody to H3N2v was assessed by hemagglutination inhibition (HI) assay and, for a subset, also by microneutralization assay. Seroprevalence and seroprotection were defined as an HI titer of ≥40, and levels were compared with those for ancestral and contemporary human strains. The analysis included 1116 sera collected during fall 2010, corresponding to approximately 100 sera per decade of life. Vaccine-induced antibody levels were also assessed in sera from 136 children aged <10 years and 65 adults aged 20-59 years before and after receipt of 2010-2011 split TIV and in sera from 182 elderly individuals aged > 65 years before and after receipt of 2011-2012 split TIV (for 31 individuals), MF59-adjuvanted TIV (for 72), or unadjuvanted subunit TIV (for 79). Results. The overall prevalence of HI titers of ≥40 against A(H3N2) v was 25%. No children aged <5 years and <20% of individuals aged ≤14 years or ≥40 years had an HI titer of ≥40. Conversely, among individuals aged 15-39 years, half of teens and adults showed H3N2v seroprotection. Following TIV receipt, <15% of individuals in any vaccine group developed a 4-fold increase in antibody level. Conclusions. A substantial proportion of adolescents and young adults have cross-reactive antibody against emerging H3N2v, whereas children and older adults show broad susceptibility. Recent formulations of TIV do not substantially increase seroprotection. A specific vaccine would be needed if H3N2v establishes epidemic spread.
Background. In April 2009, an elementary school outbreak of pandemic H1N1 (pH1N1) influenza was reported in a community in northern British Columbia, Canada-an area that includes both non-Aboriginal ...and Aboriginal residents living on or off a reserve. During the outbreak investigation, we explored the relationship between prior receipt of trivalent inactivated influenza vaccine (TIV) and pH1N1-related illness. Methods. A telephone survey was conducted from 15 May through 5 June 2009 among households of children attending any school in the affected community. Members of participating households where influenza-like illness (ILI) was described were then invited to submit blood samples for confirmation of pH1N1 infection by hemagglutination inhibition and microneutralization assays. Circulation of pH1N1 was concentrated among households of the elementary school and elsewhere on-reserve to which analyses of TIV effect were thus restricted. Odds ratios (ORs) for the TIV effect on ILI were computed through logistic regression, with adjustment for age, comorbidity, household density, and Aboriginal status. The influence of within-household clustering was assessed through generalized-linear-mixed models. Results. Of 408 participants, 92 (23%) met ILI criteria: 29 (32%) of 92 persons with ILI, compared with 61 (19%) 316 persons without ILI, had received the 2008–2009 formulation of TIV. Fully adjusted ORs for 2008- 2009 TIV effect on ILI were 2.45 (95% confidence interval, 1.34–4.48) by logistic regression and 2.68 95% confidence interval, 1.37–5.25) by generalized-linear-mixed model. Conclusions. An outbreak investigation in British Columbia during the late spring of 2009 provided the first indication of an unexpected association between receipt of TIV and pH1N1 illness. This led to 5 additional studies through the summer 2009 in Canada, each of which corroborated these initial findings.
•We compared the risk of COVID-19 hospitalization in people living with HIV (PLWH) and HIV-negative persons.•History of injecting drugs (42.9% vs 4.3%) was markedly higher in the PLWH cohort.•PLWH ...had two times the risk of hospitalization in crude models.•This increased risk was significantly attenuated in propensity score-weighted models.
To examine the risk of hospitalization within 14 days of COVID-19 diagnosis among people living with HIV (PLWH) and HIV-negative individuals who had laboratory-confirmed SARS-CoV-2 infection.
We used Cox proportional hazard models to compare the relative risk of hospitalization in PLWH and HIV-negative individuals. Then, we used propensity score weighting to examine the influence of sociodemographic factors and comorbid conditions on risk of hospitalization. These models were further stratified by vaccination status and pandemic period (pre-Omicron: December 15, 2020, to November 21, 2021; Omicron: November 22, 2021, to October 31, 2022).
The crude hazard ratio (HR) for risk of hospitalization in PLWH was 2.44 (95% confidence interval CI: 2.04-2.94). In propensity score-weighted models that included all covariates, the relative risk of hospitalization was substantially attenuated in the overall analyses (adjusted HR aHR: 1.03; 95% CI: 0.85-1.25), in vaccinated (aHR 1.00; 95% CI: 0.69-1.45), inadequately vaccinated (aHR: 1.04; 95% CI: 0.76-1.41) and unvaccinated individuals (aHR: 1.15; 95% CI: 0.84-1.56).
PLWH had about two times the risk of COVID-19 hospitalization than HIV-negative individuals in crude analyses which attenuated in propensity score-weighted models. This suggests that the risk differential can be explained by sociodemographic factors and history of comorbidity, underscoring the need to address social and comorbid vulnerabilities (e.g., injecting drugs) that were more prominent among PLWH.
PDF
