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•A mathematical model was used to investigate HCV elimination in Iceland.•HCV elimination in Iceland is achievable by 2020 with additional screening of PWID.•This would make Iceland ...one of the first countries to achieve HCV elimination.•If current harm reduction were maintained, future outbreaks would be unlikely.•Large cities could feasibly reach and sustain HCV elimination using similar methods.
In Iceland a nationwide program has been launched offering direct-acting antiviral (DAA) treatment for everyone living with hepatitis C virus (HCV). We estimate (i) the time and treatment scale-up required to achieve the World Health Organization’s HCV elimination target of an 80% reduction in incidence; and (ii) the ongoing frequency of HCV testing and harm reduction coverage among people who inject drugs (PWID) required to minimize the likelihood of future HCV outbreaks occurring.
We used a dynamic compartmental model of HCV transmission, liver disease progression and the HCV cascade of care, calibrated to reproduce the epidemic of HCV in Iceland. The model was stratified according to injecting drug use status, age and stage of engagement. Four scenarios were considered for the projections.
The model estimated that an 80% reduction in domestic HCV incidence was achievable by 2030, 2025 or 2020 if a minimum of 55/1,000, 75/1,000 and 188/1,000 PWID were treated per year, respectively (a total of 22, 30 and 75 of the estimated 400 PWID in Iceland per year, respectively). Regardless of time frame, this required an increased number of PWID to be diagnosed to generate enough treatment demand, or a 20% scale-up of harm reduction services to complement treatment-as-prevention incidence reductions. When DAA scale-up was combined with annual antibody testing of PWID, the incidence reduction target was reached by 2024. Treatment scale-up with no other changes to current testing and harm reduction services reduced the basic reproduction number of HCV from 1.08 to 0.59, indicating that future outbreaks would be unlikely.
HCV elimination in Iceland is achievable by 2020 with some additional screening of PWID. Maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that outbreaks are unlikely to occur once elimination targets have been reached.
In Iceland, a nationwide program has been launched offering treatment for the entire population living with hepatitis C virus (HCV). A mathematical model was used to estimate the additional health system requirements to achieve the HCV elimination targets of the World Health Organization (WHO), as well as the year that this could occur. With some additional screening of people who inject drugs, Iceland could reach the WHO targets by 2020, becoming one of the first countries to achieve HCV elimination. The model estimated that once elimination targets were reached, maintaining current monitoring and harm reduction services while providing ongoing access to DAA therapy for people diagnosed with HCV would ensure that future HCV outbreaks are unlikely to occur.
Cannabis is the most frequently used illicit psychoactive substance worldwide; around one in ten users become dependent. The risk for cannabis use disorder (CUD) has a strong genetic component, with ...twin heritability estimates ranging from 51 to 70%. Here we performed a genome-wide association study of CUD in 2,387 cases and 48,985 controls, followed by replication in 5,501 cases and 301,041 controls. We report a genome-wide significant risk locus for CUD (P = 9.31 × 10
) that replicates in an independent population (P
= 3.27 × 10
, P
= 9.09 × 10
). The index variant (rs56372821) is a strong expression quantitative trait locus for cholinergic receptor nicotinic α2 subunit (CHRNA2); analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with CUD in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance. The results provide biological insights and inform on the genetic architecture of CUD.
Thus far, a handful of highly penetrant mutations conferring risk of psychosis have been discovered. Here we used whole-genome sequencing and long-range phasing to investigate an Icelandic kindred ...containing ten individuals with psychosis (schizophrenia, schizoaffective disorder or psychotic bipolar disorder). We found that all affected individuals carry RBM12 (RNA-binding-motif protein 12) c.2377G>T (P = 2.2 × 10
), a nonsense mutation that results in the production of a truncated protein lacking a predicted RNA-recognition motif. We replicated the association in a Finnish family in which a second RBM12 truncating mutation (c.2532delT) segregates with psychosis (P = 0.020). c.2377G>T is not fully penetrant for psychosis; however, we found that carriers unaffected by psychosis resemble patients with schizophrenia in their non-psychotic psychiatric disorder and neuropsychological test profile (P = 0.0043) as well as in their life outcomes (including an increased chance of receiving disability benefits, P = 0.011). As RBM12 has not previously been linked to psychosis, this work provides new insight into psychiatric disease.
Abstract
Background
The Treatment as Prevention for Hepatitis C program started in 2016 in Iceland, offering treatment with direct-acting antivirals to hepatitis C virus (HCV)-infected individuals. ...Reinfections through injection drug use (IDU) can hamper elimination efforts. We determined reinfection rates of HCV among patients in the program.
Methods
Clinical data were gathered prospectively. The study cohort consisted of HCV-cured patients with an estimated sustained virologic response between 1 February 2016 and 20 November 2018, with follow-up until 20 November 2019. The observation period and time until reinfection was estimated using a single random point imputation method coupled with Monte Carlo simulation. The reinfection rates were expressed as reinfections per 100 person-years (PY).
Results
In total, 640 treatments of 614 patients (417 male; mean age, 44.3 years) resulted in cure, with 52 reinfections subsequently confirmed in 50 patients (37 male). Follow-up was 672.1 PY, with a median time to reinfection of 232 days. History of IDU was reported by 523 patients (84.8%) and recent IDU with 220 treatments (34.4%). Stimulants were the preferred injected drug in 85.5% of patients with a history of IDU. The reinfection rate was 7.7/100 PY. Using multivariate Cox proportional hazards models for interval-censored data, age (hazard ratio, 0.96 95% confidence interval, .94–.99) and recent IDU (2.91 1.48–5.76) were significantly associated with reinfection risk.
Conclusions
The reinfection rate is high in a setting of widespread stimulant use, particularly in young people with recent IDU. Regular follow-up is important among high-risk populations to diagnose reinfections early and reduce transmission.
Clinical Trials Registration
NCT02647879.
Rates of reinfection with hepatitis C virus after successful treatment with direct-acting antivirals are high in Iceland, particularly among young individuals with recent injection drug use. Emphasis on further follow-up of high-risk groups is essential.
We use polygenic risk scores (PRSs) for schizophrenia (SCZ) and bipolar disorder (BPD) to predict smoking, and addiction to nicotine, alcohol or drugs in individuals not diagnosed with psychotic ...disorders. Using PRSs for 144 609 subjects, including 10 036 individuals admitted for in‐patient addiction treatment and 35 754 smokers, we find that diagnoses of various substance use disorders and smoking associate strongly with PRSs for SCZ (P = 5.3 × 10−50–1.4 × 10−6) and BPD (P = 1.7 × 10−9–1.9 × 10−3), showing shared genetic etiology between psychosis and addiction. Using standardized scores for SCZ and BPD scaled to a unit increase doubling the risk of the corresponding disorder, the odds ratios for alcohol and substance use disorders range from 1.19 to 1.31 for the SCZ‐PRS, and from 1.07 to 1.29 for the BPD‐PRS. Furthermore, we show that as regular smoking becomes more stigmatized and less prevalent, these biological risk factors gain importance as determinants of the behavior.
Using polygenic risk scores (PRSs) for schizophrenia (SCZ) and bipolar disorder (BPD) to predict smoking behavior and alcohol or drug addiction in 144,609 subjects, we find that smoking and diagnoses of various substance use disorders associate strongly with PRSs for SCZ (P = 5.3 × 10−50–1.4 × 10−6) and BPD (P = 1.7 × 10−9–1.9 × 10−3). Furthermore, we show that the impact of SCZ‐PRS on smoking is rising with time, increasingly casting regular smoking as a psychiatric condition sharing genetic risk with SCZ and BPD.
Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We ...applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry. Genetic correlations among the various OA phenotypes were uniformly high (r
> 0.9). We observed the strongest evidence to date for OPRM1: lead SNP rs9478500 (p = 2.56 × 10
). Gene-based analyses identified novel genome-wide significant associations with PPP6C and FURIN. Variants within these loci appear to be pleiotropic for addiction and related traits.
The objectives were to study alcohol consumption per capita and liver cirrhosis mortality in the population of Iceland.
The Statistic Iceland website supplied alcohol sales figures and death rates.
...The alcohol consumption increased 30% during the study period 1982-2009, because of increase in beer and wine, and decrease in spirits consumption. Chronic liver cirrhosis mortality increased significantly for men when comparing the 1982-88 rates (before beer ban was lifted) with the rates for 2003-09.
The findings do not support the suggestion that spirits consumption rather than the total alcohol consumption affect the cirrhosis mortality.
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