Monkeypox: a review of epidemiological modelling studies and how modelling has led to mechanistic insight.

Human monkeypox (mpox) virus is a viral zoonosis that belongs to the Orthopoxvirus genus of the Poxviridae family, which presents with similar symptoms as those seen in human smallpox patients. Mpox is an increasing concern globally, with over 80,000 cases in non-endemic countries as of December 2022. In this review, we provide a brief history and ecology of mpox, its basic virology, and the key differences in mpox viral fitness traits before and after 2022. We summarize and critique current knowledge from epidemiological mathematical models, within-host models, and between-host transmission models using the One Health approach, where we distinguish between models that focus on immunity from vaccination, geography, climatic variables, as well as animal models. We report various epidemiological parameters, such as the reproduction number, R0, in a condensed format to facilitate comparison between studies. We focus on how mathematical modelling studies have led to novel mechanistic insight into mpox transmission and pathogenesis. As mpox is predicted to lead to further infection peaks in many historically non-endemic countries, mathematical modelling studies of mpox can provide rapid actionable insights into viral dynamics to guide public health measures and mitigation strategies.

Tweeting for Health Using Real-time Mining and Artificial Intelligence-Based Analytics: Design and Development of a Big Data Ecosystem for Detecting and Analyzing Misinformation on Twitter.

BACKGROUND: Digital misinformation, primarily on social media, has led to harmful and costly beliefs in the general population. Notably, these beliefs have resulted in public health crises to the detriment of governments worldwide and their citizens. However, public health officials need access to a comprehensive system capable of mining and analyzing large volumes of social media data in real time. OBJECTIVE: This study aimed to design and develop a big data pipeline and ecosystem (UbiLab Misinformation Analysis System [U-MAS]) to identify and analyze false or misleading information disseminated via social media on a certain topic or set of related topics. METHODS: U-MAS is a platform-independent ecosystem developed in Python that leverages the Twitter V2 application programming interface and the Elastic Stack. The U-MAS expert system has 5 major components: data extraction framework, latent Dirichlet allocation (LDA) topic model, sentiment analyzer, misinformation classification model, and Elastic Cloud deployment (indexing of data and visualizations). The data extraction framework queries the data through the Twitter V2 application programming interface, with queries identified by public health experts. The LDA topic model, sentiment analyzer, and misinformation classification model are independently trained using a small, expert-validated subset of the extracted data. These models are then incorporated into U-MAS to analyze and classify the remaining data. Finally, the analyzed data are loaded into an index in the Elastic Cloud deployment and can then be presented on dashboards with advanced visualizations and analytics pertinent to infodemiology and infoveillance analysis. RESULTS: U-MAS performed efficiently and accurately. Independent investigators have successfully used the system to extract significant insights into a fluoride-related health misinformation use case (2016 to 2021). The system is currently used for a vaccine hesitancy use case (2007 to 2022) and a heat wave-related illnesses use case (2011 to 2022). Each component in the system for the fluoride misinformation use case performed as expected. The data extraction framework handles large amounts of data within short periods. The LDA topic models achieved relatively high coherence values (0.54), and the predicted topics were accurate and befitting to the data. The sentiment analyzer performed at a correlation coefficient of 0.72 but could be improved in further iterations. The misinformation classifier attained a satisfactory correlation coefficient of 0.82 against expert-validated data. Moreover, the output dashboard and analytics hosted on the Elastic Cloud deployment are intuitive for researchers without a technical background and comprehensive in their visualization and analytics capabilities. In fact, the investigators of the fluoride misinformation use case have successfully used the system to extract interesting and important insights into public health, which have been published separately. CONCLUSIONS: The novel U-MAS pipeline has the potential to detect and analyze misleading information related to a particular topic or set of related topics.

Analysis of Fluoride-Free Content on Twitter: Topic Modeling Study.

BACKGROUND: Although social media has the potential to spread misinformation, it can also be a valuable tool for elucidating the social factors that contribute to the onset of negative beliefs. As a result, data mining has become a widely used technique in infodemiology and infoveillance research to combat misinformation effects. On the other hand, there is a lack of studies that specifically aim to investigate misinformation about fluoride on Twitter. Web-based individual concerns on the side effects of fluoridated oral care products and tap water stimulate the emergence and propagation of convictions that boost antifluoridation activism. In this sense, a previous content analysis-driven study demonstrated that the term fluoride-free was frequently associated with antifluoridation interests. OBJECTIVE: This study aimed to analyze "fluoride-free" tweets regarding their topics and frequency of publication over time. METHODS: A total of 21,169 tweets published in English between May 2016 and May 2022 that included the keyword "fluoride-free" were retrieved by the Twitter application programming interface. Latent Dirichlet allocation (LDA) topic modeling was applied to identify the salient terms and topics. The similarity between topics was calculated through an intertopic distance map. Moreover, an investigator manually assessed a sample of tweets depicting each of the most representative word groups that determined specific issues. Lastly, additional data visualization was performed regarding the total count of each topic of fluoride-free record and its relevance over time, using Elastic Stack software. RESULTS: We identified 3 issues by applying the LDA topic modeling: "healthy lifestyle" (topic 1), "consumption of natural/organic oral care products" (topic 2), and "recommendations for using fluoride-free products/measures" (topic 3). Topic 1 was related to users' concerns about leading a healthier lifestyle and the potential impacts of fluoride consumption, including its hypothetical toxicity. Complementarily, topic 2 was associated with users' personal interests and perceptions of consuming natural and organic fluoride-free oral care products, whereas topic 3 was linked to users' recommendations for using fluoride-free products (eg, switching from fluoridated toothpaste to fluoride-free alternatives) and measures (eg, consuming unfluoridated bottled water instead of fluoridated tap water), comprising the propaganda of dental products. Additionally, the count of tweets on fluoride-free content decreased between 2016 and 2019 but increased again from 2020 onward. CONCLUSIONS: Public concerns toward a healthy lifestyle, including the adoption of natural and organic cosmetics, seem to be the main motivation of the recent increase of "fluoride-free" tweets, which can be boosted by the propagation of fluoride falsehoods on the web. Therefore, public health authorities, health professionals, and legislators should be aware of the spread of fluoride-free content on social media to create and implement strategies against their potential health damage for the population.

Characterization of False or Misleading Fluoride Content on Instagram: Infodemiology Study.

BACKGROUND: Online false or misleading oral health-related content has been propagated on social media to deceive people against fluoride's economic and health benefits to prevent dental caries. OBJECTIVE: The aim of this study was to characterize the false or misleading fluoride-related content on Instagram. METHODS: A total of 3863 posts ranked by users' total interaction and published between August 2016 and August 2021 were retrieved by CrowdTangle, of which 641 were screened to obtain 500 final posts. Subsequently, two independent investigators analyzed posts qualitatively to define their authors' interests, profile characteristics, content type, and sentiment. Latent Dirichlet allocation analysis topic modeling was then applied to find salient terms and topics related to false or misleading content, and their similarity was calculated through an intertopic distance map. Data were evaluated by descriptive analysis, the Mann-Whitney U test, the Cramer V test, and multiple logistic regression models. RESULTS: Most of the posts were categorized as misinformation and political misinformation. The overperforming score was positively associated with older messages (odds ratio [OR]=3.293, P<.001) and professional/political misinformation (OR=1.944, P=.05). In this context, time from publication, negative/neutral sentiment, author's profile linked to business/dental office/news agency, and social and political interests were related to the increment of performance of messages. Although political misinformation with negative/neutral sentiments was typically published by regular users, misinformation was linked to positive commercial posts. Overall messages focused on improving oral health habits, side effects, dentifrice containing natural ingredients, and fluoride-free products propaganda. CONCLUSIONS: False or misleading fluoride-related content found on Instagram was predominantly produced by regular users motivated by social, psychological, and/or financial interests. However, higher engagement and spreading metrics were associated with political misinformation. Most of the posts were related to the toxicity of fluoridated water and products frequently motivated by financial interests.

Impact of direct-acting antivirals for HCV on mortality in a large population-based cohort study.

BACKGROUND & AIMS: We evaluated the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia, Canada. METHODS: We used data from the British Columbia Hepatitis Testers Cohort, which includes people tested for HCV since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modelling to assess the effect of DAAs on mortality. RESULTS: Our cohort comprised 10,851 people treated with DAAs (SVR 10,426 [96%], no-SVR: 425) and 10,851 matched untreated individuals. Median follow-up time was 2.2 years (IQR 1.3-3.6; maximum 6.2). The all-cause mortality rate was 19.5/1,000 person-years (PY) among the SVR group (deaths = 552), 86.5/1,000 PY among the no-SVR group (deaths = 96), and 99.2/1,000 PY among the untreated group (deaths = 2,133). In the multivariable model, SVR was associated with significant reduction in all-cause (adjusted hazard ratio [aHR] 0.19; 95% CI 0.17-0.21), liver- (adjusted subdistribution HR [asHR] 0.22, 95% CI 0.18-0.27) and drug-related mortality (asHR 0.26, 95% CI 0.21-0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use (IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality. CONCLUSIONS: DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people who inject drugs. LAY SUMMARY: We assessed the effect of treatment of hepatitis C virus infection with direct-acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct-acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.

Biobehavioral Aspects of the COVID-19 Pandemic: A Review.

OBJECTIVE: This review highlights the scope and significance of the coronavirus disease 2019 (COVID-19) pandemic with a focus on biobehavioral aspects and critical avenues for research. METHODS: A narrative review of the published research literature was undertaken, highlighting major empirical findings emerging during the first and second waves of the COVID-19 pandemic. RESULTS: Interactions among biological, behavioral, and societal processes were prominent across all regions of the globe during the first year of the COVID-19 emergency. Affective, cognitive, behavioral, socioeconomic, and technological factors all played a significant role in the spread of infection, response precautions, and outcomes of mitigation efforts. Affective symptoms, suicidality, and cognitive dysfunction have been widely described consequences of the infection, the economic fallout, and the necessary public health mitigation measures themselves. The impact of COVID-19 may be especially serious for those living with severe mental illness and/or chronic medical diseases, given the confluence of several adverse factors in a manner that appears to have syndemic potential. CONCLUSIONS: The COVID-19 pandemic has made clear that biological and behavioral factors interact with societal processes in the infectious disease context. Empirical research examining mechanistic pathways from infection and recovery to immunological, behavioral, and emotional outcomes is critical. Examination of how emotional and behavioral factors relate to the pandemic-both as causes and as effects-can provide valuable insights that can improve management of the current pandemic and future pandemics to come.

HCV reinfection rates after cure or spontaneous clearance among HIV-infected and uninfected men who have sex with men.

BACKGROUND & AIMS: Hepatitis C virus (HCV) reinfection among high-risk groups threatens HCV elimination goals. We assessed HCV reinfection rates among men who have sex with men (MSM) in British Columbia (BC), Canada. METHODS: We used data from the BC Hepatitis Testers Cohort, which includes nearly 1.7 million individuals tested for HCV or HIV in BC. MSM who had either achieved sustained virologic response (SVR) after successful HCV treatment, or spontaneous clearance (SC) and had ≥1 subsequent HCV RNA measurement, were followed from the date of SVR or SC until the earliest of reinfection, death, or last HCV RNA measurement. Predictors of reinfection were identified by Cox proportional modelling. The earliest study start date was 6 November 1997 and latest end date was 13 April 2018. RESULTS: Of 1349 HCV-positive MSM who met the inclusion criteria, 493 had SC while 856 achieved SVR. 349 (25.65%) had HIV coinfection. We identified 98 reinfections during 5203 person-years (PYs) yielding a reinfection rate of 1.88/100PYs. The reinfection rate among SC (2.74/100PYs) was more than twice that of those with SVR (1.03/100 PYs). Problematic alcohol use (aHR 1.73, 95% CI 1.003-2.92), injection drug use (aHR 2.60, 95% CI 1.57-4.29) and HIV coinfection (aHR 2.04, 95% CI 1.29-3.23) were associated with increased risk of HCV reinfection. Mental health counselling history (aHR 0.24, 95% CI 0.13-0.46) was associated with reduced HCV reinfection risk. CONCLUSIONS: There is the need to engage MSM in harm reduction and prevention services following treatment to reduce reinfection risk.

The impact of SVR from direct-acting antiviral- and interferon-based treatments for HCV on hepatocellular carcinoma risk.

We evaluated the effect of sustained virologic response (SVR) from direct-acting antiviral (DAA)- and interferon-based treatments on hepatocellular carcinoma (HCC) risk in a large population-based cohort in Canada. We used data from the BC Hepatitis Testers Cohort, which includes ~1.3 million individuals tested for HCV since 1990, linked with healthcare administrative and registry datasets. Patients were followed from the end of HCV treatment to HCC, death or 31 December 2016. We assessed HCC risk among those who did and did not achieve SVR by treatment type using proportional hazard models. Of 12 776 eligible individuals, 3905 received DAAs while 8871 received interferon-based treatments, followed for a median of 1.0 [range: 0.6-2.7] and 7.9 [range: 4.4-17.1] years, respectively. A total of 3613 and 6575 achieved SVR with DAAs- and interferon-based treatments, respectively. Among DAAs-treated patients, HCC incidence rate was 6.9 (95%CI: 4.7-10.1)/1000 person yr (PY) in SVR group (HCC cases: 26) and 38.2 (95%CI: 20.6-71.0) in the no-SVR group (HCC cases: 10, P < .001). Among interferon-treated individuals, HCC incidence rate was 1.8 (95%CI: 1.5-2.2) in the SVR (HCC cases: 99) and 13.9 (95%CI: 12.3-15.8) in the no-SVR group (HCC cases: 239, P < .001). Compared with no-SVR from interferon, SVR from DAA- and interferon-based treatments resulted in significant reduction in HCC risk (adjusted subdistribution hazard ratio (adjSHR) DAA = 0.30, 95%CI: 0.19-0.48 and adjSHR interferon = 0.2, 95%CI: 0.16-0.26). Among those with SVR, treatment with DAAs compared to interferon was not associated with HCC risk (adjSHR = 0.93, 95%CI: 0.51-1.71). In conclusion, similar to interferon era, DAA-related SVR is associated with 70% reduction in HCC risk.

Loss to follow-up: A significant barrier in the treatment cascade with direct-acting therapies.

Effectiveness of direct-acting antiviral (DAA) therapies could be influenced by patient characteristics such as comorbid conditions, which could lead to premature treatment discontinuation and/or irregular medical follow-ups. Here, we evaluate loss to follow-up and treatment effectiveness of sofosbuvir/ledipasvir ± ribavirin (SOF/LDV ± RBV), ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) for hepatitis C virus (HCV) genotype 1 (GT1) and sofosbuvir + ribavirin (SOF + RBV) for genotype 3 (GT3) in British Columbia Canada: The British Columbia Hepatitis Testers Cohort includes data on individuals tested for HCV since 1992, integrated with medical visit, hospitalization and prescription drug data. HCV-positive individuals who initiated DAA regimens, irrespective of treatment completion, for GT1 and GT3 until 31 December, 2017 were included. Factors associated with sustained virological response (SVR) and loss to follow-up were assessed by using multivariable logistic regression models. In total 4477 individuals initiated DAAs. The most common prescribed DAA was SOF/LDV ± RBV with SVR of 95%. The highest SVR of 99.5% was observed among OBV/PTV/r + DSV-treated patients. Overall, 453 (10.1%) individuals were lost to follow-up. Higher loss to follow-up was observed among GT1 patients treated with OBV (17.8%) and GT3 patients (15.7%). The loss to follow-up rate was significantly higher among individuals aged <60 years, those with a history of injection drug use (IDU), on opioid substitution therapy and with cirrhosis. Our findings indicate that loss to follow-up exceeds viral failure in HCV DAA therapy and its rate varies significantly by genotype and treatment regimen. Depending on the aetiology of lost to follow-up, personalized case management for those with medical complications and supporting services among IDU are needed to achieve the full benefits of effective treatments.

Considerations for an Individual-Level Population Notification System for Pandemic Response: A Review and Prototype.

The outbreak of the coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, spread worldwide after its emergence in China. Whether rich or poor, all nations are struggling to cope with this new global health crisis. The speed of the threat's emergence and the quick response required from public health authorities and the public itself makes evident the need for a major reform in pandemic surveillance and notification systems. The development and implementation of a graded, individual-level pandemic notification system could be an effective tool to combat future threats of epidemics. This paper describes a prototype model of such a notification system and its potential advantages and challenges for implementation. Similar to other emergency alerts, this system would include a number of threat levels (level 1-5) with a higher level indicating increasing severity and intensity of safety measures (eg, level 1: general hygiene, level 2: enhanced hygiene, level 3: physical distancing, level 4: shelter in place, and level 5: lockdown). The notifications would be transmitted to cellular devices via text message (for lower threat levels) or push notification (for higher threat levels). The notification system would allow the public to be informed about the threat level in real time and act accordingly in an organized manner. New Zealand and the United Kingdom have recently launched similar alert systems designed to coordinate the ongoing COVID-19 pandemic response more efficiently. Implementing such a system, however, faces multiple challenges. Extensive preparation and coordination among all levels of government and relevant sectors are required. Additionally, such systems may be effective primarily in countries where there exists at least moderate trust in government. Advance and ongoing public education about the nature of the system and its steps would be an essential part of the system, such that all members of the public understand the meaning of each step in advance, similar to what has been established in systems for other emergency responses. This educational component is of utmost importance to minimize adverse public reaction and unintended consequences. The use of mass media and local communities could be considered where mobile phone penetration is low. The implementation of such a notification system would be more challenging in developing countries for several reasons, including inadequate technology, limited use of data plans, high population density, poverty, mistrust in government, and tendency to ignore or failure to understand the warning messages. Despite the challenges, an individual-level pandemic notification system could provide added benefits by giving an additional route for notification that would be complementary to existing platforms.

Correction: Considerations for an Individual-Level Population Notification System for Pandemic Response: A Review and Prototype.

[This corrects the article DOI: 10.2196/19930.].

Sustained virological response from interferon-based hepatitis C regimens is associated with reduced risk of extrahepatic manifestations.

BACKGROUND & AIMS: HCV infection is associated with several extrahepatic manifestations (EHMs). We evaluated the impact of sustained virological response (SVR) on the risk of 7 EHMs that contribute to the burden of extrahepatic disease: type 2 diabetes mellitus, chronic kidney disease or end-stage renal disease, stroke, ischemic heart disease, major adverse cardiac events, mood and anxiety disorders, and rheumatoid arthritis. METHODS: A longitudinal cohort study was conducted using data from the British Columbia Hepatitis Testers Cohort, which included ~1.3 million individuals screened for HCV. We identified all HCV-infected individuals who were treated with interferon-based therapies between 1999 and 2014. SVR was defined as a negative HCV RNA test ≥24 weeks post-treatment or after end-of-treatment, if unavailable. We computed adjusted subdistribution hazard ratios (asHR) for the effect of SVR on each EHM using competing risk proportional hazard models. Subgroup analyses by birth cohort, sex, injection drug exposure and genotype were also performed. RESULTS: Overall, 10,264 HCV-infected individuals were treated with interferon, of whom 6,023 (59%) achieved SVR. Compared to those that failed treatment, EHM risk was significantly reduced among patients with SVR for type 2 diabetes mellitus (asHR 0.65; 95%CI 0.55-0.77), chronic kidney disease or end-stage renal disease (asHR 0.53; 95% CI 0.43-0.65), ischemic or hemorrhagic stroke (asHR 0.73; 95%CI 0.49-1.09), and mood and anxiety disorders (asHR 0.82; 95%CI 0.71-0.95), but not for ischemic heart disease (asHR 1.23; 95%CI 1.03-1.47), major adverse cardiac events (asHR 0.93; 95%CI 0.79-1.11) or rheumatoid arthritis (asHR 1.09; 95% CI 0.73-1.64). CONCLUSIONS: SVR was associated with a reduction in the risk of several EHMs. Increased uptake of antiviral therapy may reduce the growing burden of EHMs in this population. LAY SUMMARY: We estimated the rates of chronic comorbidities other than liver disease between those who were cured and those who failed treatment for hepatitis C virus (HCV) infection. Our findings showed that the rates of these non-liver diseases were largely reduced for those who were cured with interferon-based treatments. Early HCV treatments could provide many benefits in the prevention of various HCV complications beyond liver disease.

Applying core theory and spatial analysis to identify hepatitis C virus infection "core areas" in British Columbia, Canada.

"Core areas" of transmission for bacterial sexually transmitted infections have been identified. However, it is unclear whether core areas apply to viral infections, such as hepatitis C virus (HCV). We used geographic mapping and spatial analysis to identify distinct core areas of HCV infection in British Columbia (BC) using the BC Hepatitis Testers Cohort (BC-HTC), 1990-2013. The BC-HTC includes all BC residents tested for HCV (~1.5 million; 1990-2013). Core HCV infection areas were identified spatially and temporally for five time periods (1990-1993, 1994-1998, 1999-2003, 2004-2008 and 2009-2013) through thematic mapping, Kernel Density Estimation, Hotspot analysis and cluster analysis at the Census dissemination area level in ArcGIS and SatScan. HCV infection core areas were consistently identified. HCV core areas expanded from the downtown of major cities in different regions of BC (Metro Vancouver, Vancouver Island, and Northern BC; 1990-1998), to smaller cities in Metro Vancouver and Interior BC (2000 onwards). Statistically significant clusters, or hotspots, were also observed for downtown Vancouver, Northern BC (Prince George) and Vancouver Island from 1990 to 2008 with expansion to other urban areas in Metro Vancouver from 1990-2013. Statistically significant clusters persisted after adjustment for injection drug use, number of HCV tests, age, sex, material and social deprivation. Persistence of areas with high HCV diagnoses rates in Vancouver and Prince George supports the theory of core areas of HCV transmission. Identification of core areas can inform prevention, care and treatment programme interventions and evaluate their impact over time.

The population level care cascade for hepatitis C in British Columbia, Canada as of 2018: Impact of direct acting antivirals.

BACKGROUND: Population-level monitoring of hepatitis C virus (HCV) infected people across cascades of care identifies gaps in access and engagement in care and treatment. We characterized the population-level care cascade for HCV in British Columbia (BC), Canada before and after introduction of Direct Acting Antiviral (DAA) treatment. METHODS: BC Hepatitis Testers Cohort (BC-HTC) includes 1.7 million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2018 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV care cascade stages: (a) antibody diagnosed; (b) RNA tested; (c) RNA positive; (d) genotyped; (e) initiated treatment; and (f) achieved sustained virologic response (SVR). RESULTS: We estimated 61 127 people were HCV antibody positive in BC in 2018 (undiagnosed: 7686, 13%; diagnosed: 53 441, 87%). Of those diagnosed, 83% (44 507) had HCV RNA testing, and of those RNA positive, 90% (28 716) were genotyped. Of those genotyped, 61% (17 441) received therapy, with 90% (15 672) reaching SVR. Individuals from older birth cohorts had lower progression to HCV RNA testing. While people who currently inject drugs had the highest proportional progression to RNA testing, this group had the lowest proportional treatment uptake. CONCLUSIONS: Although gaps in HCV RNA and genotype testing after antibody diagnosis exist, the largest gap in the care cascade is treatment initiation, despite introduction of DAA treatment and removal of treatment eligibility restrictions. Further interventions are required to ensure testing and treatment is equitably accessible in BC.

Effectiveness of a School Based Smokeless Tobacco Intervention: A Cluster Randomized Trial.

To assess the effectiveness of intervention in improving knowledge, attitude and perception regarding smokeless tobacco (SLT) use and its harmful effects and intention to quit SLT among school going adolescents. A school-based cluster randomized control trial was carried out in 18 secondary schools targeting male and female students from grades 6 to 10 in Karachi. Primary outcome was knowledge about hazards of smokeless tobacco (SLT) and secondary outcomes were attitude and Perception about hazards of SLT, and intention to quit SLT. We enrolled 738 participants in intervention group and 589 in the control group. Mean score of knowledge significantly improved in intervention as compared to control group (P value < 0.01). Intention to quit was found to be proportionately higher (33%) in the intervention group as compared to control group. Generalized estimating equations were used to assess the association of factors with knowledge regarding harmful effects of SLT use. Significant predictors of increase in knowledge score were found in children: who had seen any anti SLT messages on social media in the past 30 days, who were getting information regarding harmful effects of SLT use in school or textbooks and who had friends using SLT. A school-based intervention was effective in increasing knowledge regarding the harmful effects of SLT use and intention to quit SLT use among school adolescents. Introduction of such educational programmes on a regular basis in schools or as part of school curriculum can have an impact on reducing prevalence of SLT use.Trial Registration NCT03418506. https://register.clinicaltrials.gov/NCT03418506 .

Hepatitis C virus reinfection after successful treatment with direct-acting antiviral therapy in a large population-based cohort.

BACKGROUND & AIMS: Direct-acting antiviral therapies (DAA) are an important tool for hepatitis C virus (HCV) elimination. However, reinfection among people who inject drugs (PWID) may hamper elimination targets. Therefore, we estimated HCV reinfection rates among DAA-treated individuals, including PWID. METHODS: We analyzed data from the British Columbia Hepatitis Testers Cohort which included ∼1.7 million individuals screened for HCV in British Columbia, Canada. We followed HCV-infected individuals treated with DAAs who achieved a sustained virologic response (SVR) and had ≥1 subsequent HCV RNA measurement to April 22nd, 2018. Reinfection was defined as a positive RNA measurement after SVR. PWID were identified using a validated algorithm and classified based on recent (<3 years) or former (≥3 years before SVR) use. Crude reinfection rates per 100 person-years (PYs) were calculated. Poisson regression was used to model adjusted incidence rate ratios (IRRs) and 95% CIs. RESULTS: Of 4,114 individuals who met the inclusion criteria, most were male (n = 2,692, 65%), born before 1965 (n = 3,411, 83%) and were either recent (n = 875, 21%) or former PWID (n = 1,793, 44%). Opioid-agonist therapy (OAT) was received by 19% of PWID. We identified 40 reinfections during 2,767 PYs. Reinfection rates were higher among recent (3.1/100 PYs; IRR 6.7; 95% CI 1.9-23.5) and former PWID (1.4/100 PYs; IRR 3.7; 95% CI 1.1-12.9) than non-PWID (0.3/100 PYs). Among recent PWID, reinfection rates were higher among individuals born after 1975 (10.2/100 PYs) and those co-infected with HIV (5.7/100 PYs). Only one PWID receiving daily OAT developed reinfection. CONCLUSIONS: Population-level reinfection rates remain elevated after DAA therapy among PWID because of ongoing exposure risk. Engagement of PWID in harm-reduction and support services is needed to prevent reinfections. LAY SUMMARY: Direct-acting antivirals are an effective tool for the treatment of hepatitis C virus, enabling the elimination of the virus. However, some patients who have been successfully treated with direct-acting antivirals are at risk of reinfection. Our findings showed that the risk of reinfection was highest among people with recent injection drug use. Among people who inject drugs, daily use of opioid-agonist therapy was associated with a lower risk of reinfection.

Estimating the impact of early hepatitis C virus clearance on hepatocellular carcinoma risk.

Although achieving sustained virological response (SVR) through antiviral therapy could reduce the risk of hepatocellular carcinoma (HCC) attributable to hepatitis C virus (HCV) infection, the impact of early viral clearance on HCC is not well defined. In this study, we compared the risk of HCC among individuals who spontaneously cleared HCV (SC), the referent population, with the risk in untreated chronic HCV (UCHC), those achieved SVR, and those who failed interferon-based treatment (TF). The BC Hepatitis Testers Cohort (BC-HTC) includes individuals tested for HCV between 1990-2013, integrated with medical visits, hospitalizations, cancers, prescription drugs and mortality data. This analysis included all HCV-positive patients with at least one valid HCV RNA by PCR on or after HCV diagnosis. Of 46 666 HCV-infected individuals, there were 12 527 (26.8%) SC; 24 794 (53.1%) UCHC; 5355 (11.5%) SVR and 3990 (8.5%) TF. HCC incidence was lowest (0.3/1000 person-years (PY)) in the SC group and highest in the TF group (7.7/1000 PY). In a multivariable model, compared to SC, TF had the highest HCC risk (hazard ratio (HR):14.52, 95% confidence interval (CI): 9.83-21.47), followed by UCHC (HR: 5.85; 95% CI: 4.07-8.41). Earlier treatment-based viral clearance similar to SC could decrease HCC incidence by 69.4% (95% CI: 57.5-78.0), 30% (95% CI: 10.8-45.1) and 77.5% (95% CI: 69.4-83.5) among UCHC, SVR and TF patients, respectively. In conclusion, using SC as a real-world comparator group, it showed that substantial reduction in HCC risk could be achieved with earlier treatment initiation. These analyses should be replicated in patients who have been treated with direct acting antiviral therapies.

Are people getting quality thalassemia care in twin cities of Pakistan? A comparison with international standards.

OBJECTIVES: This study was conducted to determine if thalassemia patients were getting quality care in Rawalpindi and Islamabad, Pakistan, as per international standards and to identify determinants for better quality of thalassemia care. DESIGN: A cross sectional study was conducted using interview based structured questionnaire, which was developed using standards of thalassemia care used by International Thalassemia Foundation. SETTING: Five healthcare facilities catering to the needs of thalassemia patients in Rawalpindi and Islamabad, Pakistan. PARTICIPANTS: Data were collected from 315 thalassemia patients from May to August, 2016. MAIN OUTCOME MEASURE: Survey data on quality indicators. RESULTS: Results showed that almost half of thalassemia patients (48.5%) were getting poor quality of care. On average patients were getting only 63.93% of possible quality care for the disease. The most deficient quality area was management of complications where patients were getting only 49.1% of possible care. Better quality of care was likely to be received by those patients who were educated, patients with educated fathers, those visiting private facilities and those who were visiting facilities in Islamabad. Those with concomitant diseases were also likely to receive better care. CONCLUSION: Quality of care provided to thalassemia patients was well below the international standards for the care of thalassemia. There is a need to take urgent action to improve quality of care in the country.