Correction: Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1003818.].

Changes in the prevalence of hepatitis B and C viral infections in Sindh province, Pakistan: Findings from two sero-surveys in 2007 and 2019.

Pakistan harbours a large burden of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. We utilised repeat sero-surveys to assess progress achieved towards hepatitis elimination in Pakistan. Multilevel logistic regression evaluated the change in HBV infection (HBV surface antigen (HBsAg)-positive) prevalence and HCV exposure (HCV antibody (HCV-Ab)-positive) prevalence between two sero-surveys from 2007 and 2019 for Sindh province and associated risk factors. Adjusted odds ratios (aORs) were estimated and population-attributable fractions (PAF) for modifiable risk factors for HCV exposure. The 2007 and 2019 surveys included 8855 and 6672 individuals. HBsAg prevalence decreased from 2.6% (95% confidence intervals (95% CI): 2.2-2.9) in 2007 to 1.1% (95% CI: 0.8-1.3) in 2019, while HCV-Ab prevalence increased from 5.1% (95% CI: 4.6%-5.5%) to 6.2% (95% CI: 5.6%-6.8%). The age and gender-adjusted HBsAg prevalence decreased by 80% (aOR = 0.2, 95% CI: 0.1-0.4) among children and 60% (aOR = 0.4, 95% CI: 0.3-0.6) among adults over 2007-2019, while HCV-Ab prevalence decreased by 60% (aOR = 0.4, 95%CI:0.2-0.7) in children and increased by 40% (aOR = 1.4, 95% CI: 1.2-1.7) in adults. HCV-Ab prevalence was lower in adults with secondary (aOR = 0.6, 95% CI: 0.5-0.8) and higher (aOR = 0.5, 95%CI:0.3-0.8) education compared to illiterates and higher among adults reporting blood transfusion (aOR = 1.7, 95% CI: 1.2-2.4), family history of hepatitis (aOR = 2.5, 95% CI: 1.9-3.3), past year medical injection (aOR = 2.1, 95% CI: 1.6-2.7), being tattooed (aOR = 1.4, 95% CI: 1.0-1.9) and shaved by traditional barber (aOR = 1.2, 95% CI: 1.0-1.5). Modifiable risk factors accounted for 45% of HCV exposure, with medical injection(s) accounting for 38% (95%CI,25.7-48.4%). Overall HCV has increased over 2007-2019 in Sindh province, while HBV prevalence has decreased. Medical injections should be an important focus of prevention activities.

Cost-effectiveness of testing for Mycoplasma genitalium among men who have sex with men in Australia.

OBJECTIVES: Mycoplasma genitalium (MG) disproportionately affects men who have sex with men (MSM). We determined the cost-effectiveness of different testing strategies for MG in MSM, taking a healthcare provider perspective. METHODS: We used inputs from a dynamic transmission model of MG among MSM living in Australia in a decision tree model to evaluate the impact of four testing scenarios on MG incidence: (1) no one tested; (2) symptomatic MSM; (3) symptomatic and high-risk asymptomatic MSM; (4) all MSM. We calculated the incremental cost-effectiveness ratios (ICERs) using a willingness-to-pay threshold of $A30 000 per quality-adjusted life year (QALY) gained. We explored the impact of adding an antimicrobial resistance (AMR) tax (ie, additional cost per antibiotic consumed) to identify the threshold, whereby any testing for MG is no longer cost-effective. RESULTS: Testing only symptomatic MSM is the most cost-effective (ICER $3677 per QALY gained) approach. Offering testing to all MSM is dominated (ie, higher costs and lower QALYs gained compared with other strategies). When the AMR tax per antibiotic given was above $150, any testing for MG was no longer cost-effective. CONCLUSION: Testing only symptomatic MSM is the most cost-effective option, even when the potential costs associated with AMR are accounted for (up to $150 additional cost per antibiotic given). For pathogens like MG, where there are anticipated future costs related to AMR, we recommend models that test the impact of incorporating an AMR tax as they can change the results and conclusions of cost-effectiveness studies.

Prison-based interventions are key to achieving HCV elimination among people who inject drugs in New South Wales, Australia: A modelling study.

BACKGROUND & AIMS: People who inject drugs (PWID) experience high incarceration rates which are associated with increased hepatitis C virus (HCV) transmission risk. We assess the importance of prison-based interventions for achieving HCV elimination among PWID in New South Wales (NSW), Australia. METHODS: A model of incarceration and HCV transmission among PWID was calibrated in a Bayesian framework to epidemiological and incarceration data from NSW, incorporating elevated HCV acquisition risk among recently released PWID. We projected the contribution of differences in transmission risk during/following incarceration to HCV transmission over 2020-2029. We estimated the past and potential future impact of prison-based opioid agonist therapy (OAT; ~33% coverage) and HCV treatment (1500 treatments in 2019 with 32.9%-83.3% among PWID) on HCV transmission. We estimated the time until HCV incidence reduces by 80% (WHO elimination target) compared to 2016 levels with or without prison-based interventions. RESULTS: Over 2020-2029, incarceration will contribute 23.0% (17.9-30.5) of new HCV infections. If prison-based interventions had not been implemented since 2010, HCV incidence in 2020 would have been 29.7% (95% credibility interval: 22.4-36.1) higher. If current prison and community HCV treatment rates continue, there is an 98.8% probability that elimination targets will be achieved by 2030, with this decreasing to 10.1% without current prison-based interventions. CONCLUSIONS: Existing prison-based interventions in NSW are critical components of strategies to reduce HCV incidence among PWID. Prison-based interventions are likely to be pivotal for achieving HCV elimination targets among PWID by 2030.

Interpersonal dysfunction predicts subsequent financial exploitation vulnerability in a sample of adults over 50: a prospective observational study.

OBJECTIVES: The goal of this study was to test whether interpersonal dysfunction, characterized by loneliness and/or dissatisfaction with relationships, is an imminent predictor of financial exploitation vulnerability (FEV) among adults age 50+ within a 6-month observation period. This study also tests whether FEV prospectively predicts interpersonal dysfunction. METHODS: Twenty-six adults aged 50 or older completed a study involving baseline data collection and 13 follow-ups over 6 months. Linear mixed models were used for primary analyses. RESULTS: After adjustment for demographic, psychological and cognitive covariates, there were between-person effects of FEV and interpersonal dysfunction across follow-ups, suggesting that those with generally higher interpersonal dysfunction compared to other participants also reported greater FEV (B(SE) = 1.09(.33), p = .003). There was a within-person effect (B(SE) = .08(.03), p = .007) of elevated interpersonal dysfunction predicting greater FEV two weeks later across all follow-ups. Within-person effect of FEV was not predictive of interpersonal dysfunction (B(SE) = .25(.15), p = .10). There was also a significant effect of age (B(SE) = -.06(.02), p = .007), such that older individuals had lower FEV throughout follow-ups. CONCLUSION: Among adults age 50+, individuals with higher interpersonal dysfunction relative to others in the study reported greater FEV throughout the 6-month observation period. Increased loneliness and social dissatisfaction, relative to one's average level, predicts subsequent increases in FEV, and may be an imminent risk factor for exploitation.

Estimates of hepatitis B virus prevalence among general population and key risk groups in EU/EEA/UK countries: a systematic review.

BackgroundThe burden of chronic hepatitis B virus (HBV) varies across the European Union (EU) and European Economic Area (EEA).AimWe aimed to update the 2017 HBV prevalence estimates in EU/EEA countries and the United Kingdom for 2018 to 2021.MethodsWe undertook a systematic review, adding to HBV prevalence estimates from an existing (2005-2017) database. Databases were searched for original English-language research articles including HBV surface antigen prevalence estimates among the general population, pregnant women, first-time blood donors (FTB), men who have sex with men (MSM), migrants and people in prison. Country experts contributed grey literature data. Risk of bias was assessed using a quality assessment framework.FindingsThe update provided 147 new prevalence estimates across the region (updated total n = 579). Median HBV prevalence in the general population was 0.5% and the highest was 3.8% (Greece). Among FTB, the highest prevalence was 0.8% (Lithuania). Estimates among pregnant women were highest in Romania and Italy (5.1%). Among migrants, the highest estimate was 31.7% (Spain). Relative to 2017 estimates, median prevalence among pregnant women decreased by 0.5% (to 0.3%) and increased by 0.9% (to 5.8%) among migrants. Among MSM, the highest estimate was 3.4% (Croatia). Prevalence among people in prison was highest in Greece (8.3%) and the median prevalence increased by 0.6% (to 2.1%).ConclusionsThe HBV prevalence is low in the general population and confined to risk populations in most European countries with some exceptions. Screening and treatment should be targeted to people in prison and migrants.

Is venoarterial extracorporeal membrane oxygenation an option for managing septic shock.

PURPOSE OF REVIEW: To describe sepsis-induced cardiomyopathy. Discuss indications and current evidence of using venoarterial extracorporeal membrane oxygenation (VA-ECMO) in setting of sepsis-induced cardiomyopathy. RECENT FINDINGS: Recent data suggests a survival benefit with the use of VA-ECMO in patients with septic shock complicated by septic-induced cardiomyopathy with severe left ventricular systolic dysfunction. VA-ECMO was associated with poor outcomes in adults with septic shock without severe systolic dysfunction. The evidence is generated from retrospective and meta-analysis of observational studies. SUMMARY: Sepsis-induced cardiomyopathy is an increasingly recognized entity characterized by reversible ventricular dysfunction in the setting of sepsis. When hypotension persists despite standard management of septic shock (e.g. adequate fluid resuscitation, vasopressors, inotropes) and there is evidence of severe cardiac systolic dysfunction and end-organ hypoperfusion, VA-ECMO should be considered as a bridge therapy to recovery. VA-ECMO should not be used for isolated vasodilatory septic shock without significant myocardial dysfunction.

The Cognitive Correlates of Financial Literacy in Older Adults.

OBJECTIVES: This study examined the cognitive correlates of financial literacy using a comprehensive neuropsychological battery, and whether education modifies the relationship between cognition and financial literacy. METHODS: Sixty-six participants completed sociodemographic questionnaires, an assessment of financial literacy, and a neuropsychological assessment. Multiple linear regression models that controlled for age, sex, and education examined the main effects of cognitive measures that showed a significant bivariate association with financial literacy. RESULTS: After correcting for multiple comparisons, the Crystallized Composite score (p = .002) and the Picture Vocabulary test (p = .002) from the NIH Toolbox, and the Multilingual Naming Test (p > .001) from the Uniform Data Set 3 were associated with financial literacy. Contrary to our hypothesis, education did not interact with cognitive measures when considering financial literacy scores. CONCLUSIONS: Findings suggest that vocabulary knowledge and semantic memory may play an important role in financial literacy in older age. CLINICAL IMPLICATIONS: Assessing vocabulary knowledge and semantic processes may help to identify older adults with lower financial literacy skills. Additionally, financial literacy interventions may consider targeting individuals with lower vocabulary knowledge and semantic processing skills.

Evaluating the Prevention Benefit of HCV Treatment: Modeling the SToP-C Treatment as Prevention Study in Prisons.

BACKGROUND AND AIMS: Between 2014 and 2019, the SToP-C trial observed a halving in HCV incidence in four Australian prisons following scale-up of direct-acting antiviral (DAA) therapy. However, the contribution of HCV treatment to this decline is unclear because the study did not have a control group. We used modeling to consider this question. APPROACH AND RESULTS: We parameterized and calibrated a dynamic model of HCV transmission in prisons to data from each SToP-C prison on incarceration dynamics, injecting drug use, HCV prevalence trends among prison entrants, baseline HCV incidence before treatment scale-up, and subsequent HCV treatment scale-up. The model projected the decrease in HCV incidence resulting from increases in HCV treatment and other effects. We assessed whether the model agreed better with observed reductions in HCV incidence overall and by prison if we included HCV treatment scale-up, and its prevention benefits, or did not. The model estimated how much of the observed decrease in HCV incidence was attributable to HCV treatment in prison. The model projected a decrease in HCV incidence of 48.5% (95% uncertainty interval [UI], 41.9-54.1) following treatment scale-up across the four prisons, agreeing with the observed HCV incidence decrease (47.6%; 95% CI, 23.4-64.2) from the SToP-C trial. Without any in-prison HCV treatment, the model indicated that incidence would have decreased by 7.2% (95% UI, -0.3 to 13.6). This suggests that 85.1% (95% UI, 72.6-100.6) of the observed halving in incidence was from HCV treatment scale-up, with the remainder from observed decreases in HCV prevalence among prison entrants (14.9%; 95% UI, -0.6 to 27.4). CONCLUSIONS: Our results demonstrate the prevention benefits of scaling up HCV treatment in prison settings. Prison-based DAA scale-up should be an important component of HCV elimination strategies.

Elder abuse in the COVID-19 era based on calls to the National Center on Elder Abuse resource line.

BACKGROUND: The COVID-19 pandemic has exacerbated circumstances that place older adults at higher risk for abuse, neglect, and exploitation. Identifying characteristics of elder abuse during COVID-19 is critically important. This study characterized and compared elder abuse patterns across two time periods, a one-year period during the pandemic, and a corresponding one-year period prior to the start of the pandemic. METHODS: Contacts (including social media contacts, and email; all referred to as "calls" for expediency) made to the National Center on Elder Abuse (NCEA) resource line were examined for differences in types of reported elder abuse and characteristics of alleged perpetrators prior to the pandemic (Time 1; March 16, 2018 to March 15, 2019) and during the pandemic (Time 2; March 16, 2020 to March 15, 2021). Calls were examined for whether or not abuse was reported, the types of reported elder abuse, including financial, physical, sexual, emotional, and neglect, and characteristics of callers, victims, and alleged perpetrators. Chi-square tests of independence compared frequencies of elder abuse characteristics between time periods. RESULTS: In Time 1, 1401 calls were received, of which 795 calls (56.7%) described abuse. In Time 2, 1009 calls were received, of which 550 calls (54.5%) described abuse. The difference between time periods in frequency of abuse to non-abuse calls was not significant ([Formula: see text]). Time periods also did not significantly differ with regard to caller, victim, and perpetrator characteristics. Greater rates of physical abuse ([Formula: see text] and emotional abuse ([Formula: see text] were reported during Time 2 after adjustment for multiple comparisons. An increased frequency of multiple forms of abuse was also found in Time 2 compared to Time 1 ([Formula: see text]. CONCLUSIONS: Findings suggest differences in specific elder abuse subtypes and frequency of co-occurrence between subtypes between time periods, pointing to a potential increase in the severity of elder abuse during COVID-19.

Evaluating FIML and multiple imputation in joint ordinal-continuous measurements models with missing data.

Missing data is a common occurrence in confirmatory factor analysis (CFA). Much work had evaluated the performance of different techniques when all observed variables were either continuous or ordinal. However, few have investigated these techniques when observed variables are a mix of continuous and ordinal variables. This study investigated the performance of four approaches to handling missing data in these models: a joint ordinal-continuous full information maximum likelihood (FIML) approach and three multiple imputation approaches (fully conditional specification, fully conditional specification with latent variable formulation, and expectation-maximization with bootstrapping) combined with the weighted least squares with mean and variance adjustment (WLSMV) estimator. In a Monte-Carlo simulation, the FIML approach produced unbiased estimations of factor loadings and standard errors in almost all conditions. Fully conditional specification combined with WLSMV was second best, producing accurate estimates when the sample size was large. However, FIML encountered slight non-convergence issues when certain ordinal categories have extremely low frequencies, which is typical of skewed data. If the sample is large, fully conditional specification combined with weighted least squares is recommended when the FIML approach is not feasible (e.g., non-convergence, impractical computation durations, and variables that predict missingness are not of interest to the analysis).

MAP 65-is it enough?

PURPOSE OF REVIEW: The purpose of this review is to look at the current evidence on the consequences of intraoperative hypotension and discuss improvements that can be implemented for its prevention. RECENT FINDINGS: Literature continues to supply convincing evidence that even brief periods of intraoperative hypotension are associated with increased perioperative morbidity and mortality. Recent randomized controlled trial showed intraoperative early use of vasopressor and maintaining blood pressure within tight ranges improves outcomes. SUMMARY: There should be a shift in paradigm in focusing on the prevention of intraoperative hypotension instead treatment. The suggested goals to help maintaining hemodynamic stability during anesthesia include ensure adequate blood pressure and flow; hypotension prevention; and ensure adequate anesthetic depth without overdose.

Health and economic benefits of achieving hepatitis C virus elimination in Pakistan: A modelling study and economic analysis.

BACKGROUND: Modelling suggests that achieving the WHO incidence target for hepatitis C virus (HCV) elimination in Pakistan could cost US$3.87 billion over 2018 to 2030. However, the economic benefits from integrating services or improving productivity were not included. METHODS AND FINDINGS: We adapt a HCV transmission model for Pakistan to estimate the impact, costs, and cost-effectiveness of achieving HCV elimination (reducing annual HCV incidence by 80% by 2030) with stand-alone service delivery, or partially integrating one-third of initial HCV testing into existing healthcare services. We estimate the net economic benefits by comparing the required investment in screening, treatment, and healthcare management to the economic productivity gains from reduced HCV-attributable absenteeism, presenteeism, and premature deaths. We also calculate the incremental cost-effectiveness ratio (ICER) per disability-adjusted life year (DALY) averted for HCV elimination versus maintaining current levels of HCV treatment. This is compared to an opportunity cost-based willingness-to-pay threshold for Pakistan (US$148 to US$198/DALY). Compared to existing levels of treatment, scaling up screening and treatment to achieve HCV elimination in Pakistan averts 5.57 (95% uncertainty interval (UI) 3.80 to 8.22) million DALYs and 333,000 (219,000 to 509,000) HCV-related deaths over 2018 to 2030. If HCV testing is partially integrated, this scale-up requires an investment of US$1.45 (1.32 to 1.60) billion but will result in US$1.30 (0.94 to 1.72) billion in improved economic productivity over 2018 to 2030. This elimination strategy is highly cost-effective (ICER = US$29 per DALY averted) by 2030, with it becoming cost-saving by 2031 and having a net economic benefit of US$9.10 (95% UI 6.54 to 11.99) billion by 2050. Limitations include uncertainty around what level of integration is possible within existing primary healthcare services as well as a lack of Pakistan-specific data on disease-related healthcare management costs or productivity losses due to HCV. CONCLUSIONS: Investment in HCV elimination can bring about substantial societal health and economic benefits for Pakistan.

Cost-effectiveness of screening and treatment using direct-acting antivirals for chronic Hepatitis C virus in a primary care setting in Karachi, Pakistan.

Despite the availability of effective direct-acting antiviral (DAA) treatments for Hepatitis C virus (HCV) infection, many people remain undiagnosed and untreated. We assessed the cost-effectiveness of a Médecins Sans Frontières (MSF) HCV screening and treatment programme within a primary health clinic in Karachi, Pakistan. A health state transition Markov model was developed to estimate the cost-effectiveness of the MSF programme. Programme cost and outcome data were analysed retrospectively. The incremental cost-effectiveness ratio (ICER) was calculated in terms of incremental cost (2016 US$) per disability-adjusted life year (DALY) averted from the provider's perspective over a lifetime horizon. The robustness of the model was evaluated using deterministic and probabilistic sensitivity analyses (PSA). The ICER for implementing testing and treatment compared to no programme was US$450/DALY averted, with 100% of PSA runs falling below the per capita Gross Domestic Product threshold for cost-effective interventions for Pakistan (US$1,422). The ICER increased to US$532/DALY averted assuming national HCV seroprevalence (5.5% versus 33% observed in the intervention). If the cost of liver disease care was included (adapted from resource use data from Cambodia which has similar GDP to Pakistan), the ICER dropped to US$148/DALY, while it became cost-saving if a recently negotiated reduced drug cost of $75/treatment course was assumed (versus $282 in base-case) in addition to cost of liver disease care. In conclusion, screening and DAA treatment for HCV infection are expected to be highly cost-effective in Pakistan, supporting the expansion of similar screening and treatment programmes across Pakistan.

Behavioral Economic Demand for Alcohol and Cigarettes in Heavy Drinking Smokers: Evidence of Asymmetric Cross-commodity Reinforcing Value.

INTRODUCTION: Previous studies have highlighted a strong bidirectional relationship between cigarette and alcohol consumption. To advance our understanding of this relationship the present study uses a behavioral economic approach in a community sample (N = 383) of nontreatment seeking heavy drinking smokers. AIMS AND METHODS: The aims were to examine same-substance and cross-substance relationships between alcohol and cigarette use, and latent factors of demand. A community sample of nontreatment seeking heavy drinking smokers completed an in-person assessment battery including measures of alcohol and tobacco use as well as the Cigarette Purchase Task and the Alcohol Purchase Task. Latent factors of demand were derived from these hypothetical purchase tasks. RESULTS: Results revealed a positive correlation between paired alcohol and cigarette demand indices (eg, correlation between alcohol intensity and cigarette intensity) (rs = 0.18-0.46, p ≤ .003). Over and above alcohol factors, cigarette use variables (eg, Fagerström Test for Nicotine Dependence and cigarettes per smoking day) significantly predicted an additional 4.5% (p < .01) of the variance in Persistence values but not Amplitude values for alcohol. Over and above cigarette factors, alcohol use variables predicted cigarette Persistence values (ΔR2 = .013, p = .05), however, did not predict Amplitude values. CONCLUSIONS: These results advance our understanding of the overlap between cigarette and alcohol by demonstrating that involvement with one substance was associated with demand for the other substance. This asymmetric profile-from smoking to alcohol demand, but not vice versa-suggests that it is not simply tapping into a generally higher reward sensitivity and warrants further investigation. IMPLICATIONS: To our knowledge, no study to date has examined alcohol and cigarette demand, via hypothetical purchase tasks, in a clinical sample of heavy drinking smokers. This study demonstrates that behavioral economic indices may be sensitive to cross-substance relationships and specifically that such relationships are asymmetrically stronger for smoking variables affecting alcohol demand, not the other way around.

The "Little MonSta" Deep-Sea Benthic, Precision Deployable, Multi-Sensor and Sampling Lander Array.

The "Little MonSta" benthic lander array consists of 8 ROV-deployable (remotely operated vehicle) instrumented lander platforms for monitoring physical and chemical oceanographic properties and particle sampling developed as part of the MMMonKey_Pro program (mapping, modeling, and monitoring key processes and controls in cold-water coral habitats in submarine canyons). The Little MonStas offer flexible solutions to meet the need to monitor marine benthic environments during a historically unprecedented time of climate-driven oceanic change, develop an understanding of meso-scale benthic processes (natural and man-made), and to calibrate geological environmental archives. Equipped with acoustic Doppler current profilers (ADCPs), sediment traps, nylon settlement plates and homing beacons, the compact and upgradable lander platforms can be deployed by ROVs to precise locations in extreme terrains to a water depth of 3000 m. The array allows cluster-monitoring in heterogeneous environments or simultaneous monitoring over wider areas. A proof-of-concept case study was presented from the cold-water coral habitable zone in the upper Porcupine Bank Canyon, where the Little MonStas collected 868.8 h of current speed, direction, temperature, and benthic particulate flux records, as well as 192 particle samples subsequently analyzed for particular organic carbon (POC), lithic sediment, live foraminifera, and microplastics. The potential to upgrade the Little MonStas with additional sensors and acoustic releases offers greater and more flexible operational capabilities.

Alcohol Cue-Induced Ventral Striatum Activity Predicts Subsequent Alcohol Self-Administration.

BACKGROUND: Human laboratory paradigms are a pillar in medication development for alcohol use disorders (AUD). Neuroimaging paradigms, in which individuals are exposed to cues that elicit neural correlates of alcohol craving (e.g., mesocorticolimbic activation), are increasingly utilized to test the effects of AUD medications. Elucidation of the translational effects of these neuroimaging paradigms on human laboratory paradigms, such as self-administration, is warranted. The current study is a secondary analysis examining whether alcohol cue-induced activation in the ventral striatum is predictive of subsequent alcohol self-administration in the laboratory. METHODS: Non-treatment-seeking heavy drinkers of East Asian descent (n = 41) completed a randomized, placebo-controlled, double-blind, crossover experiment on the effects of naltrexone on neuroimaging and human laboratory paradigms. Participants completed 5 days of study medication (or placebo); on day 4, they completed a neuroimaging alcohol taste cue-reactivity task. On the following day (day 5), participants completed a 60-minute alcohol self-administration paradigm. RESULTS: Multilevel Cox regressions indicated a significant effect of taste cue-elicited ventral striatum activation on latency to first drink, Wald χ2  = 2.88, p = 0.05, such that those with higher ventral striatum activation exhibited shorter latencies to consume their first drink. Similarly, ventral striatum activation was positively associated with total number of drinks consumed, F(1, 38) = 5.90, p = 0.02. These effects were significant after controlling for alcohol use severity, OPRM1 genotype, and medication. Other potential regions of interest (anterior cingulate, thalamus) were not predictive of self-administration outcomes. CONCLUSIONS: Neuroimaging alcohol taste cue paradigms may be predictive of laboratory paradigms such as self-administration. Elucidation of the relationships among different paradigms will inform how these paradigms may be used synergistically in experimental medicine and medication development.

Executive function moderates naltrexone effects on methamphetamine-induced craving and subjective responses.

Background: Emerging evidence suggests that opioid receptor antagonists, such as naltrexone, are effective pharmacotherapies for alcohol, opioid, and possibly stimulant use disorders. It is posited that naltrexone exerts its effects, in part, by increasing functional connectivity between neural reward circuitry and frontal systems implicated in executive function. Yet no studies had examined whether executive function moderates these effects. Objectives: This study examined whether a composite measure of executive function (EF) moderates the effect of naltrexone on craving for methamphetamine and subjective responses following infusion of the drug. Methods: Individuals with methamphetamine use disorder (N = 30; 27% female) completed baseline neurocognitive assessments of premorbid and executive function, and an executive function factor was computed. Participants then underwent a randomized, double-blind, cross-over study of titration with naltrexone and placebo. Participants then received a 30-mg intravenous methamphetamine infusion and completed subjective response questionnaires at 8 times in the 120 minutes post-infusion. Results: Multilevel mixed models indicated a significant EF × medication interaction, reflecting greater effects of naltrexone to decrease "desire to access the drug", "want more of the drug", "crave the drug", "feel drug effects" and "feel high" in participants with low EF compared to those with high EF (Bs = .36-1.29, SEs = .14-.17, ps<0.01). These effects remained significant after controlling for premorbid cognitive functioning, baseline responses to methamphetamine, severity of methamphetamine use, and methamphetamine-related functional problems. Conclusion: Naltrexone may be especially effective in methamphetamine-dependent individuals with low EF. Neuropsychological assessments may also provide predictive clinical utility not captured by traditional measures of substance use severity.

Modelling the potential prevention benefits of a treat-all hepatitis C treatment strategy at global, regional and country levels: A modelling study.

The World Health Organization (WHO) recently produced guidelines advising a treat-all policy for HCV to encourage widespread treatment scale-up for achieving HCV elimination. We modelled the prevention impact achieved (HCV infections averted [IA]) from initiating this policy compared with treating different subgroups at country, regional and global levels. We assessed what country-level factors affect impact. A dynamic, deterministic HCV transmission model was calibrated to data from global systematic reviews and UN data sets to simulate country-level HCV epidemics with ongoing levels of treatment. For each country, the model projected the prevention impact (in HCV IA per treatment undertaken) of initiating four treatment strategies; either selected randomly (treat-all) or targeted among people who inject drugs (PWID), people aged ≥35, or those with cirrhosis. The IA was assessed over 20 years. Linear regression was used to identify associations between IA per treatment and demographic factors. Eighty-eight countries (85% of the global population) were modelled. Globally, the model estimated 0.35 (95% credibility interval [95%CrI]: 0.16-0.61) IA over 20 years for every randomly allocated treatment, 0.30 (95%CrI: 0.12-0.53) from treating those aged ≥35 and 0.28 (95%CrI: 0.12-0.49) for those with cirrhosis. Globally, treating PWID achieved 1.27 (95%CrI: 0.68-2.04) IA per treatment. The IA per randomly allocated treatment was positively associated with a country's population growth rate and negatively associated with higher HCV prevalence among PWID. In conclusion, appreciable prevention benefits could be achieved from WHO's treat-all strategy, although greater benefits per treatment can be achieved through targeting PWID. Higher impact will be achieved in countries with high population growth.

An Octahedral Cobalt(III) Complex with Axial NH3 Ligands that Templates and Selectively Stabilises G-quadruplex DNA.

Guanine-rich sequences of DNA are known to readily fold into tetra-stranded helical structures known as G-quadruplexes (G4). Due to their biological relevance, G4s are potential anticancer drug targets and therefore there is significant interest in molecules with high affinity for these structures. Most G4 binders are polyaromatic planar compounds which π-π stack on the G4's guanine tetrad. However, many of these compounds are not very selective since they can also intercalate into duplex DNA. Herein we report a new class of binder based on an octahedral cobalt(III) complex that binds to G4 via a different mode involving hydrogen bonding, electrostatic interactions and π-π stacking. We show that this new compound binds selectivity to G4 over duplex DNA (particularly to the G-rich sequence of the c-myc promoter). This new octahedral complex also has the ability to template the formation of G4 DNA from the unfolded sequence. Finally, we show that upon binding to G4, the complex prevents helicase Pif1-p from unfolding the c-myc G4 structure.