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The COVID-19 pandemic interrupted routine healthcare services. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are often asymptomatic, and therefore, screening and on/post-treatment monitoring are required. Our aim was to determine the effect of the first, second and third waves of the pandemic on HBV and HCV testing in Ontario, Canada. We extracted data from Public Health Ontario for HBV and HCV specimens from 1 January 2019 to 31 May 2021. Testing volumes were evaluated and stratified by age, sex and region. Changes in testing volumes were analysed by per cent and absolute change. Testing volumes decreased in April 2020 with the first wave of the pandemic and recovered to 72%-75% of prepandemic volumes by the end of the first wave. HBsAg testing decreased by 33%, 18% and 15%, and HBV DNA testing decreased by 37%, 27% and 20%, in each consecutive wave. Anti-HCV testing decreased by 35%, 21% and 19%, and HCV RNA testing decreased by 44%, 30% and 36% in each consecutive wave. These trends were consistent by age, region and sex. Prenatal HBV testing volumes were stable. In conclusion, significant decreases in HBV and HCV testing occurred during the first three waves of the pandemic and have not recovered. In addition to direct consequences on viral hepatitis elimination efforts, these data provide insight into the impacts of the pandemic on chronic disease screening and management. Strategies to make up for missed testing will be critical to avoid additional consequences of COVID-19 long after the pandemic has resolved.

Background Antivirals for the treatment of hepatitis C virus (HCV) infection are effective, but many patients remain untreated and treatment is not yet routine in primary care. We evaluated the characteristics of patients who engaged in HCV treatment, and clinician perspectives on the barriers and facilitators to treatment. Methods Our mixed-method, parallel-design study was conducted at a multisite primary care centre in downtown Toronto. In a retrospective chart review, we searched records from 2011 to 2017 to collect quantitative data, including HCV infection status and HCV treatment status. To contextualize the data, we conducted in-depth interviews with select physicians between Aug. 1 and Nov. 1, 2017, and analyzed the transcripts using content analysis. Results Of the 40 381 charts reviewed, 727 patients (1.8%, 95% confidence interval [CI] 1.7%-1.9%) were infected with HCV, and 542 (74.6%) had HCV infection requiring treatment. Of those, 255 patients (47.0%) had engaged in treatment. Patients who had engaged in treatment were more likely to be male (odds ratio [OR] 1.63, 95% CI 1.10-2.42), older (OR 1.04 per year increase in age, 95% CI 1.02-1.05) and housed (OR 2.2, 95% CI 1.36-3.75), and they were more likely not to have engaged in injection drug use (OR 1.87, 95% CI 1.33-2.63). Based on interviews with 8 physicians, treatment barriers included a lack of knowledge about HCV treatment, concerns that patients would not adhere to medications and challenges related to medication access. Facilitators of treatment included access to specialist consultation, pharmacist support and primary care treatment guidelines. Common themes that emerged in both quantitative and qualitative components were the roles of unstable housing and intravenous drug use as barriers to engaging in and completing treatment. Interpretation Our study captured provider-identified barriers to HCV care and the key factors related to retention in HCV care, including gender, age, housing status and experience with drug use. Successful primary-care-led HCV treatment programs may incorporate specialist and pharmacy support and focus on younger, female, underhoused populations and people who use drugs.

BACKGROUND: Ontario is 1 of 5 provinces that immunize adolescents for hepatitis B virus (HBV), despite the World Health Organization recommendation for universal birth dose vaccination. One rationale for not vaccinating at birth is that universal prenatal screening and related interventions prevent vertical transmission. The aims of our study were to evaluate the uptake and epidemiology of prenatal HBV screening, and to determine the number of children in Ontario with a diagnosis of HBV before adolescent vaccination. METHODS: We extracted data from ICES, Public Health Ontario and Better Outcomes & Registry Network (BORN) Ontario databases. We assessed prenatal screening uptake and prevalence of prenatal hepatitis B surface antigen (HBsAg) from 2012 to 2016, as well as subsequent hepatitis B e-antigen (HBeAg) and HBV DNA testing and percent positivity. We used age and region to subcategorize the results. In a separate unlinked analysis, we evaluated the number of children positive for HBV aged 0–11 years who were born in Ontario from 2003 to 2013. RESULTS: From 2012 to 2016, 93% of pregnant women were screened for HBV, with an HBsAg prevalence of 0.6%. Prevalence of HBsAg increased with age, peaking at older than 45 years at 3%. North Toronto had the highest overall prevalence of 1.5%, whereas northern Ontario had the lowest. Of women who were HBsAg positive, HBeAg and HBV DNA tests were subsequently ordered in 13% and 38%, respectively. Of children born in Ontario between 2003 and 2013, 139 of 23 759 tested positive for HBV. INTERPRETATION: Prenatal HBV screening is not universal and subsequent evaluation is poor, limiting optimal intervention and possibly contributing to some Ontario-born children being given a diagnosis of HBV before age 12 years. These findings underscore the limitations of the province’s adolescent vaccination strategy.

Case A 37-year-old farmer presented with previously operated open type 2 infected nonunion of distal radius. A wrist-spanning external fixator was applied after implant removal, debridement, and postoperative antibiotics for 6 weeks. At 6 weeks' follow-up, a volar locking plate and bone grafting for the gap nonunion over distal radius and the modified Sauve-Kapandji procedure for distal radioulnar joint (DRUJ) were performed. The patient had excellent results at 3 years' follow-up. Conclusion Distal radius nonunion with disrupted DRUJ can be treated with internal fixation, and the modified Sauve-Kapandji technique provided thorough debridement is performed.

Introduction: Individuals with severe sleep related breathing disorders (SRBD) tend to experience intermittent hypoxia, sleep fragmentation and highly fluctuating intrathoracic pressures. Chronic exposure to these stressors sensitizes the parasympathetic system while suppressing the sympathetic system. Parasympathetic over-reactivity among patients with severe sleep related breathing disorders has been proposed as a predisposing factor for neurally mediated syncope. Goal: We sought to determine the relative risk for neurally mediated syncope in patients with severe SRBD compared to the general population. Methods: This is a retrospective cohort study of 228 cases selected from 2,598 patients who were referred for polysomnography on discharge from hospitalization. Incidence of neurally mediated syncope (NMS) was compared between patients with apnea-hypopnea-index (AHI) scores of 30 or greater and those with an AHI score below 5. Results: Approximately 32% of patients with severe SRBD had a history of neurally mediated syncope compared to only 14% in patients with normal sleep breathing patterns (OR = 3.09, 95% CI: 1.25 - 7.62, p = 0.015). Conclusion: Our multi-center retrospective study supports an association between SRBD and NMS.

markdownabstractBackground & Aims The use of complementary and alternative medicine (CAM) in patients with chronic hepatitis B (CHB) can interact with antiviral treatment or influence health‐seeking behaviour. We aimed to study the use of individual CAM modalities in CHB and explore determinants of use, particularly migration‐related, socio‐economic and clinical factors. Methods A total of 436 CHB outpatients who attended the Toronto Centre for Liver Disease in 2015‐2016 were included in this cross‐sectional study. Using the comprehensive I‐CAM questionnaire and health records, data were collected on socio‐demographic and clinical variables and on usage of 16 CAM modalities in the last year. Results Sixty percent of patients were male, 74% were Asian and 46% were using antiviral treatment. Three‐hundred and nine (71%) patients used CAM. Vitamin/mineral preparations (45% of patients) were most commonly used. Overall CAM use and the specific use of potentially injurious CAM, such as green tea extract (9.2%) and St. John's wort (0.2%), were not associated with liver disease severity. Female sex, family history of CHB, lower serum HBV DNA, and higher socio‐economic status were independently associated with bio‐holistic CAM use, the clinically most‐relevant CAM group (P < 0.05); ethnicity, antiviral therapy use and liver disease severity were not. Conclusions CAM use among CHB patients was extensive, especially use of vitamin and mineral preparations, but without direct influence on liver disease severity. Bio‐holistic CAM use appeared to be associated with socio‐economic status rather than with ethnicity or liver disease severity. Despite the rare use of hepatotoxins, physicians should actively inquire about it.

Introduction and aim. The prevalence and incidence of chronic liver disease is increasing resulting, in substantial direct and indirect medical costs. Overuse of investigations, treatments and procedures contribute to rising health care costs and can expose patients to unnecessary harm and delay in receiving care. The Choosing Wisely Canada (CWC) campaign has encouraged professional societies to develop statements that are directly actionable by their members in an effort to promote higher-value health care that will lead to downstream effect on how other practitioners make decisions. Material and methods. The Canadian Association for the Study of the Liver (CASL) established its Choosing Wisely top five list of recommendations using the framework put forward by CWC. CASL convened a task force that developed a list of draft recommendations and shared this with CASL membership electronically with eventual ranking of the top five recommendations by consensus at Canadian Digestives Disease Week (CDDW) 2017. Following revisions, the CASL Executive Committee endorsed the final list, which was disseminated online by CWC (July 2017). Results. The top five recommendations physicians and patients should question include: 1) Don’t order serum ammonia to diagnose or manage hepatic encephalopathy (HE). 2) Don’t routinely transfuse fresh frozen plasma, vitamin K, or platelets to reverse abnormal tests of coagulation in patients with cirrhosis prior to abdominal paracentesis, endoscopic variceal band ligation, or any other minor invasive procedures. 3) Don’t order HFE genotyping based on serum ferritin values alone to diagnose hereditary hemochromatosis. 4) Don’t perform computed tomography (CT) or magnetic resonance imaging (MRI) routinely to monitor benign focal liver lesions. 5) Don’t repeat hepatitis C viral load testing in an individual who has established chronic infection, outside of anti-viral treatment. Conclusion. The Choosing Wisely recommendations will foster patient-physician discussions, reduce unnecessary treatment and testing, avert adverse effects from testing and treatment along with reducing medical expenditure in hepatology.

IntroductionIn 2011, through a multipartner Integrated Family Health Initiative (IFHI), CARE started supporting maternal and neonatal health (MNH) improvement goals in 8 of 38 districts in Bihar, India. The programme included a frontline health worker (FHW) component offering health advice through household visits and benefited from CARE’s direct engagement during IFHI, which then evolved into statewide Technical Support Unit (TSU) to the Government of Bihar in 2014.MethodsUsing eight rounds of state-representative household surveys with mothers of infants aged 0–2 months (N=73 093) linked with two facility assessments conducted during 2012–2017, we assessed changes in FHW visit coverage, intensity and quality between IFHI and TSU phases. Using logistic regression models, we ascertained associations between FHW outputs and three MNH core practices: ≥3 antenatal care check-ups (ANC3+), institutional delivery and early breastfeeding initiation.ResultsWomen’s receipt of 1+ FHW visits declined from 60.2% (IFHI phase) to 46.3% (TSU phase) in the eight IFHI districts, being below 40% statewide during the TSU phase. Despite a parallel decline in FHW visit quality measured as the number of health advice received, all three outcomes improved during the TSU versus IFHI phase in IFHI districts. We found significant positive associations between all three outcomes and receipt of 1+ FHW visits and programme phase (TSU vs IFHI) in the eight IFHI districts. During the TSU phase, receipt of 2+ FHW visits in the third trimester increased the odds of women receiving ANC3+ (adjusted OR (aOR)=1.21; 95% CI: 1.13 to 1.31), delivering in a facility (aOR=1.64; 95% CI: 1.51 to 1.77) and initiating breast feeding early (aOR=1.18; 95% CI: 1.05 to 1.18). Independent of the number and timing of FHW visits, we also found positive associations between women reporting higher than lower quality of FHW interactions and receiving outcome-specific advice and all three MNH outcomes.ConclusionImplementation of large community-based interventions under the technical support model should be continuously and strategically evaluated and adapted.

BACKGROUND: Development of robust treatment programs among core transmitters (CT) of hepatitis C virus (HCV) are needed, including strategies to address reinfection risk. The aim of this study was to describe the effectiveness of direct-acting antiviral (DAA) treatment in CT versus non-CT populations and assess reinfection rates after successful treatment. METHODS: Characterizing Risk Behaviour and Reinfection Rates for Successful Programs to Engage Core Transmitters in HCV Elimination (C-RESPECT) was a prospective, observational study of HCV-infected Canadian adult patients (genotypes 1, 3, and 4) treated with DAAs between 2017 and 2020. RESULTS: The full analysis set included 429 participants (259 CT, 170 non-CT). Key differences were observed in baseline profiles: CT participants were younger (mean 42.3 [SD 11.2] y versus 55.0 [SD 11.1] y, respectively) and reported higher rates of social assistance (35.7% versus 14.8%), smoking (83.7% versus 52.4%), low socioeconomic status (yearly income

As India moves toward the elimination of visceral leishmaniasis (VL) as a public health problem, comprehensive timely case detection has become increasingly important, in order to reduce the period of infectivity and control outbreaks. During the 2000s, localized research studies suggested that a large percentage of VL cases were never reported in government data. However, assessments conducted from 2013 to 2015 indicated that 85% or more of confirmed cases were eventually captured and reported in surveillance data, albeit with significant delays before diagnosis. Based on methods developed during these assessments, the CARE India team evolved new strategies for active case detection (ACD), applicable at large scale while being sufficiently effective in reducing time to diagnosis. Active case searches are triggered by the report of a confirmed VL case, and comprise two major search mechanisms: 1) case identification based on the index case’s knowledge of other known VL cases and searches in nearby houses (snowballing); and 2) sustained contact over time with a range of private providers, both formal and informal. Simultaneously, house-to-house searches were conducted in 142 villages of 47 blocks during this period. We analyzed data from 5030 VL patients reported in Bihar from January 2018 through July 2019. Of these 3033 were detected passively and 1997 via ACD (15 (0.8%) via house-to-house and 1982 (99.2%) by light touch ACD methods). We constructed multinomial logistic regression models comparing time intervals to diagnosis (30-59, 60-89 and ≥90 days with =90 days compared to the referent of

BACKGROUND & AIMS Global elimination of hepatitis C virus (HCV) will require increases in diagnosis. Point of care (POC) tests that detect antibodies against HCV can be useful for testing large and difficult to reach populations. The most accurate POC test requires a 20 min read time to identify antibody-positive samples. We investigated whether viremic patients could be identified using a shorter read time, to increase efficiency and reduce the need for reflex tests (a follow-up test for HCV RNA on the same specimen to confirm viremia). METHODS Patients with past or current HCV infections provided samples at 2 clinics in Canada for evaluation by the OraQuick HCV Rapid antibody POC test. A community HCV-screening program in Madrid, Spain (real-world cohort) invited people to be tested for HCV with the same OraQuick test. Patients provided samples of whole blood, via finger prick. Fingerprick samples were tested immediately after collection. In the clinic cohort, photographs of the developing test were taken at 15 second intervals, and blinded readers recorded the time to positivity. In the real-world cohort, readers recorded the OraQuick result at 5 minutes, and each minute after, up to 10 minutes, and then again at 20 minutes; viremia was then evaluated using a POC HCV RNA test (GeneXpert HCV Viral Load Assay). Sera from viremic and non-viremic clinic patients were used to quantify antibody titers to investigate the relationship between the time of band appearance and antibody concentration. Fisher's exact test and exact logistic regression were used to determine factors associated with a positive result at 5 minutes. RESULTS Blood from all viremic patients produced a positive result in the antibody POC test by 5 min. Median time to a positive result for 171 viremic patients was 2.6 min (range, 1.8-4.6 min), vs 4.1 min (range, 2.3-14.4 min) for 108 patients with resolved infection (P < .001). The 5-min threshold identified all viremic cases among 176 HCV antibody-positive patients in the real-world cohort, confirmed by testing for HCV RNA. In the pooled cohorts, antibody positivity at 5 min identified viremic patients with 100% sensitivity (95% CI, 98.4%-100%); the negative predictive value was 100% (95% CI, 94.9%-100%). The positive predictive value at 5 min was 62.0% (95% CI, 56.7%-67.0%) and therefore insufficient alone to detect viremia; an HCV RNA test would still be necessary to confirm active infection. CONCLUSIONS The wait time for the OraQuick HCV Rapid antibody POC blood test can be reduced from 20 min to 5 min and continue to reliably identify patients with HCV infection. Shortening the test time could increase high-throughput screening, reduce loss to follow up, and reduce the need for reflex HCV RNA testing.

SummaryWe used social network analysis (SNA) to study the novel coronavirus (COVID-19) outbreak in Karnataka, India, and assess the potential of SNA as a tool for outbreak monitoring and control. We analyzed contact tracing data of 1147 Covid-19 positive cases (mean age 34.91 years, 61.99% aged 11–40, 742 males), anonymized and made public by the government. We used software tools Cytoscape and Gephi to create SNA graphics and determine network attributes of nodes (cases) and edges (directed links, determined by contact tracing, from source to target patients). Outdegree was 1–47 for 199 (17.35%) nodes, and betweenness 0.5–87 for 89 (7.76%) nodes. Men had higher mean outdegree and women, higher betweenness. Delhi was the exogenous source of 17.44% cases. Bangalore city had the highest caseload in the state (229, 20%), but comparatively low cluster formation. Thirty-four (2.96%) “super-spreaders” (outdegree≥5) caused 60% of the transmissions. Real-time social network visualization can allow healthcare administrators to flag evolving hotspots and pinpoint key actors in transmission. Prioritizing these areas and individuals for rigorous containment could help minimize resource outlay and potentially achieve a significant reduction in COVID-19 transmission.

Background: To achieve global hepatitis C virus (HCV) elimination, scale-up of testing is required as diagnosis rates remain low. Point-of-care (POC) antibody testing increases access for difficult-to-reach populations, however the current 20-40 minute read time limits utility. We sought to determine whether there was a relationship between time to antibody positivity and presence of viremia. Methods: HCV viremic and non-viremic antibody-positive patients were tested with the OraQuick POC HCV antibody test using whole blood or oral fluid. Results were recorded at 15 second intervals to determine time to positivity. Results were validated in an independent screening cohort of high-risk individuals. Findings: All viremic patients had a positive blood result by 5 minutes. Median time to positivity for 171 viremic patients was 2.6 (1.8-4.6) versus 4.1 minutes (2.3-14.4) for 108 with resolved infection (p

The purpose of this study was to demonstrate the reduced chances of iatrogenic femoral neck fracture while removing the Richard's screw using the dynamic hip screw-femur head conjoint removal technique. This retrospective cohort study analyzed 16 hips operated on with total hip arthroplasty from March 2010 to February 2015. All cases were previously treated with dynamic hip screws (DHS) for proximal femur fractures. The age of the patients ranged from 20 to 75 years. We used uncemented sockets in 15 patients and cemented sockets in 1 patient. We used conical fluted straight stems in 9 cases, ML (Mediolateral) tapered stems in 5 patients and CLS (Cementless Spotorno) stems in 2 patients. The head of the femur was removed together with the attached Richard's screw after taking a neck cut during hip replacement after previous dynamic hip screw fixation. At 2-year follow-up, there was a statistically significant improvement in the Harris hip score: from a mean preoperative score of 35 ± 7.975 to a mean postoperative score of 89.38 ± 4.870 (P < 0.001). Stem sinking and Type AL (Vancouver classification for periprosthetic fracture) periprosthetic fracture in 1 patient with a tapered stem was noted. Good acetabular inclination was achieved in all cases. At 2-year follow-up, all patients were able to carry out their daily activities. This is a novel technique with the advantage of avoiding iatrogenic femoral neck fracture in an osteoporotic bone.

Background Screening for hepatitis C virus (HCV) followed by direct-acting antiviral (DAA) treatment in individuals born between 1945 and 1964 has been shown to be both effective and cost-effective, but the question of affordability remains unresolved. We looked at long-term cost and health outcomes of HCV screening for Ontario up to 2030. Methods We used a validated state-transition model to analyze the budget and health impact of HCV screening followed by DAA treatment in individuals born between 1945 and 1964 versus current practice. We used a payer’s perspective, discounting costs at an annual rate of 1.5%. Costs, liver-related deaths, and hepatocellular carcinoma (HCC) and decompensated cirrhosis (DC) cases detected were measured over a 14-year period. Results By 2030, the cost of implementing a HCV screening program for individuals born between 1945 and 1964 will add an additional $845 million to the Ontario health care budget. Sensitivity analyses showed that DAA costs had the largest effect on the budget, and decreasing DAA costs to $16,000 will lead to a significantly lower budget impact of $331 million. Regarding population health, a screen-and-treat strategy will prevent 1,199 cases of HCC, 1,565 cases of DC, and 1,665 liver-related deaths by 2030. Conclusions Contrasting the budget impact of this HCV screening strategy with other recommended health services and technologies, we conclude that HCV screening should be considered affordable. If Canada is committed to meeting the targets set out by the World Health Organization, then provinces cannot afford to not expand current screening programs.

Introduction Liver disease forms a global health burden and is a cause of significant morbidity and mortality. Good patient education has proven to be a key tool in disease management, providing significant benefit in knowledge and behavioral modifications. To develop effective educational tools, a good understanding of patient educational needs and preferred learning methods is necessary. Few studies have evaluated the educational needs of patients with liver disease. This study aims to assess the educational needs of patients at a large tertiary liver center. Method This study was a questionnaire-based cross-sectional study evaluating patient demographics,perceived and unperceived educational needs (hepatitis B and hepatitis Cknowledge) at a tertiary liver centre Results A total of 300 patients completed the questionnaire. Most patients stated they were “extremely” or “quite” interested in learning more about their liver condition (84.9%, n=242), in either “moderate” or “a lot of” detail (94.6%, n=202). There was no association between gender, age, level of education, annual income and interest of patients in learning more about their liver condition. There was a significant association between number of clinic visits and interest to learn more (p=0.022), but there was no association between the duration of their follow-up at the clinic and their interest to learn more (p=0.243). Conclusions Overall, patients showed great interest in learning more about their liver condition, potentially indicating a need for more educational programs. Most patients prefer reading (via internet or pamphlets/brochures) or one-to-one discussions, giving us a good sense of potentially successful educational strategies that will fit the needs of most patients.

Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. We aimed to assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk.A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system was evaluated in an external cohort for validation.Of 2,079 patients with cirrhosis and ≥6months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease (p0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low-risk (120points), medium-risk (120-240) and high-risk (240) groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with primary biliary cirrhosis, hepatitis B viral and hepatitis C viral cirrhosis (n=1,144), with similar predictive ability (Harrell's c statistic 0.77) in the validation and derivation cohorts.HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.HCC incidence varies markedly depending on the underlying cause of cirrhosis. Herein, using readily available clinical and laboratory parameters we describe a risk score, THRI, which has a good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.

Background: Hypothyroidism is the most common pathological hormone deficiency. To study various cardiac manifestations in overt and subclinical hypothyroidism.Methods: The cross-sectional analytic study is carried out on 60 patients of hypothyroid subjects in indoor facility of general medicine department in SMIMER hospital.Results: This study shows positive correlation between thyroid stimulating hormone (TSH) level, electrocardiogram (ECG) and echocardiographic findings. In this study, there is female predominance, ECG findings most commonly suggestive of sinus bradycardia and ECHO findings are most commonly suggestive of diastolic dysfunction with pericardial effusion.Conclusions: The early recognition and early initiation of treatment of hypothyroidism may helpful to lowering heart changes as hypothyroidism is reversible cause for cardiac manifestation.

Background & Aims: Direct-acting antivirals (DAAs) cure most cases of chronic hepatitis C virus (HCV) infection. However, a small percentage of patients relapse with reappearance of viremia after a full course of therapy. Although most who relapse require retreatment, some patients spontaneously clear HCV without additional therapy. We studied patients who relapsed with detectable HCV RNA after a full course of DAA therapy and then spontaneously cleared the HCV infection without retreatment. Methods: We performed a case–control study of patients who spontaneously cleared chronic HCV infection following a documented relapse after DAA therapy at the Toronto Centre for Liver Disease, from January 2014 through December 2017. We collected clinical information at baseline, 12 weeks after treatment, and 6 months after relapse and compared data among spontaneous clearers, patients with persistent relapse, and patients who achieved a sustained virologic response to therapy 12 weeks after treatment (SVR12). The strength and breadth of interferon gamma cytokine secretion by HCV-specific T cells from peripheral blood were quantified using the ELISPOT assay. Results: Of the 1032 individuals with chronic HCV infection who were treated with DAAs, 93 patients had a documented relapse. Of these patients, 12 patients (13%) spontaneously cleared HCV within 6 months after the documented relapse without additional therapy. The spontaneous clearers had low levels of HCV RNA (

Background: the aim of the study was to find and understand the relation between electrolytes and viral hepatitis E. To study electrolyte abnormality in patients with hepatitis E virus (HEV).Methods: This study is a single centre cross sectional study on the patients with HEV infection. Consecutive cases affected with HEV-at department of medicine, SMIMER (Surat Municipal institute of medical education and research) hospital, Surat during the period of 1 year (July-2019 to June-2020) are taken up for the study.Results: Abnormal electrolytes are associated with higher mortality in patients infected with HEV.Conclusions: A higher mean serum creatinine, total bilirubin, SGOT, SGPT; lower total protein, albumin, and abnormal electrolytes in body fluid (Na+, K+, Cl-, Ca++) values are associated with higher mortality in patients infected with HEV.

Summary Background Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. Methods The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid. Patients, recruited at 29 sites in North America and Europe, were randomly assigned to placebo, seladelpar 50 mg/day, or seladelpar 200 mg/day while ursodeoxycholic acid was continued. Randomisation was done centrally (1:1:1) by a computerised system using an interactive voice–web response system with a block size of three. Randomisation was stratified by region (North America and Europe). The primary outcome was the percentage change from baseline in alkaline phosphatase over 12 weeks, analysed in the modified intention-to-treat (ITT) population (any randomised patient who received at least one dose of medication and had at least one post-baseline alkaline phosphatase evaluation). This study is registered with ClinicalTrials.gov (NCT02609048) and the EU Clinical Trials Registry (EudraCT2015-002698-39). Findings Between Nov 4, 2015, and May 26, 2016, 70 patients were screened at 29 sites in North America and Europe. During recruitment, three patients treated with seladelpar developed fully reversible, asymptomatic grade 3 alanine aminotransferase increases (one on 50 mg, two on 200 mg), ranging from just over five to 20 times the ULN; as a result, the study was terminated after 41 patients were randomly assigned. The modified ITT population consisted of 12 patients in the placebo group, 13 in the seladelpar 50 mg group, and 10 in the seladelpar 200 mg group. Mean changes from baseline in alkaline phosphatase were −2% (SD 16) in the placebo group, −53% (14) in the seladelpar 50 mg group, and −63% (8) in the seladelpar 200 mg group. Changes in both seladelpar groups versus placebo were significant (p vs placebo), with no significant difference between the two seladelpar groups (p=0·1729). All five patients who received seladelpar for 12 weeks had normal alkaline phosphatase values at the end of treatment, based on a central laboratory ULN for alkaline phosphatase of 116 U/L. The most frequently reported adverse events were pruritus (16%; one patient on placebo, four on seladelpar 50 mg, and one on seladelpar 200 mg), nausea (13%; one patient on placebo, three on seladelpar 50 mg, and one on seladelpar 200 mg), diarrhoea (10%; two patients on placebo, one on seladelpar 50 mg, and one on seladelpar 200 mg), dyspepsia (8%; two patients on seladelpar 50 mg and one on seladelpar 200 mg), muscle spasms (8%; three patients on seladelpar 200 mg), myalgia (8%; one patient on placebo and two on seladelpar 200 mg), and dizziness (8%; one patient on placebo and two on seladelpar 50 mg). Interpretation Seladelpar normalised alkaline phosphatase levels in patients who completed 12 weeks of treatment. However, treatment was associated with grade 3 increases in aminotransferases and the study was stopped early. The effects of seladelpar should be explored at lower doses. Funding CymaBay Therapeutics.

Introduction Radiofrequency ablation (RFA) is a recommended curative intent treatment option for patients with early stage hepa-tocellular carcinoma (HCC). We investigated if wait times for RFA were associated with residual tumor, tumor recurrence, need for liver transplantation, or death. Material and methods We conducted a retrospective study of patients diagnosed with HCC between January 2010 and December 2013 presenting to University Health Network (UHN) in Toronto, Canada. All patients receiving curative intent RFA for HCC were included. Multivariable Cox regression was used to determine if wait times were associated with clinical outcomes. Results 219 patients were included in the study. 72.6% were male and the median age was 62.7 years (IQR 55.6-71). Median tumor size at diagnosis was 21.5 mm (IQR 17-26); median MELD was 8.7 (IQR 7.2-11.4) and 57.1% were Barcelona stage 0. The cause of liver disease was viral hepatitis in 73.5% (Hepatitis B and C). The median time from HCC diagnosis to RFA treatment was 96 days (IQR 75-139). In multivariate analysis, wait time was not associated with requiring liver transplant or tumor recurrence, however, each incremental 30-day wait time was associated with an increased risk of residual tumor (HR = 1.09; 95% CI 1.01-1.19; p = 0.033) as well as death (HR = 1.23; 95% CI 1.11-1.36; p ≤ 0.001). Conclusion Incremental 30-day wait times are associated with a 9% increased risk of residual tumor and a 23% increased risk of death. We have identified system gaps where quality improvement measures can be implemented to reduce wait times and allocate resources for future RFA treatment, which may improve both quality and efficiency of HCC care.

Background and Aim. Despite advances in the treatment of chronic hepatitis C infection (CHC), it remains a major public health problem in Canada and globally. The knowledge of healthcare providers (HCPs) is critical to improve the care of CHC in Canada. To assess the current knowledge and educational needs of healthcare providers (HCPs) in the area of CHC management a national online survey was conducted. Method. An interprofessional steering committee designed a 29-question survey distributed through various direct and electronic routes. The survey assessed several domains (e.g., participant and practice demographics, access to resources, knowledge of new treatments, and educational preferences). Results. A total of 163 HCPs responded to the survey. All hepatologists and 8% of primary care providers (PCPs) reported involvement in treatment of CHC. Physicians most frequently screened patients who had abnormal liver enzymes, while nurses tended to screen based on lifestyle factors. More than 70% of PCPs were not aware of new medications and their mechanisms. Conclusion. Overall, the needs assessment demonstrated that there was a need for further education, particularly for primary care physicians, to maximize the role that they can play in screening, testing, and treatment of hepatitis C in Canada.

Background Bihar, India has higher maternal mortality rates than the country on average. A Collaborative Quality Improvement (CQI) program was created to improve data transparency and accuracy, with the aim of increasing maternal complication identification and improving key life-saving processes for cesarean section and blood transfusion. Objectives To estimate the impact of the CQI program on identification of maternal complications and use of C-section and blood transfusion for maternal complications in participating hospitals relative to non-participating facilities in Bihar. Methods Ten district hospitals participated in the collaborative from February 2018 to September 2019. Activities included leadership and improvement workshops; learning sessions; and monthly onsite support provided by IHI and CARE India. Data from HMIS was used to assess change from baseline to after the start of the collaborative in CQI district hospitals, compared to non-participating district hospitals for: maternal complication identification, C-sections, and blood transfusions. Results Figures 1–3 illustrate improvement over time for all measures. For example, across all CQI hospitals, control chart methodology suggested C-sections (percent all births) increased from a rate of 6.2% (95% CI 5.9%, 6.7%) at baseline to 8.3% (95% CI 7.8%, 9.0%) after the start of the collaborative. Comparative analysis found C -sections increased by 2.2% (95% CI 1.8%, 2.64%) per month in CQI facilities during the collaborative period, relative to non-CQI facilities. Conclusions Application of this QI collaborative led to improvement in identification of maternal complications and use of C-section and blood transfusion.

Background: Limited access to safe, timely banked blood is a critical barrier to providing basic surgical care in resource-limited settings globally. Contextual, locally driven data are required to elucidate country needs, develop effective interventions, and guide policy decisions. Objective: We employ qualitative methodology to describe barriers faced and solutions proposed by front-line obstetric providers in Bihar – a poor, populous Indian state where maternal mortality exceeds the national average. We aim to make locally driven recommendations for ongoing policy work in India to strengthen the country’s blood transfusion system. Methods: From February to May 2016, two researchers conducted semi-structured interviews with 19 obstetric providers across Bihar. Snowball sampling was employed until thematic saturation was reached. Following immersion into de-identified texts and dual codebook development, a primary analyst completed topical coding, and a secondary analyst confirmed reproducibility. Results: Providers report that pervasive banked blood shortages force hospitals to require replacement donation, but patients’ families often cannot or will not donate. Providers wait one to six hours for blood, depending on availability of staff and supplies, blood bank proximity, and the ability of the patient being treated to navigate the system. Providers feel forced to refer their patients, often to distant, poorly equipped centers. Providers identify donor education, improved infrastructure, and improved local coordination as focus areas for intervention. Conclusions: A multi-stakeholder approach that aims to increase blood donation through community education, mitigate limited infrastructure through short-term workarounds, and improve local-level coordination through state support and policy change is required in Bihar. This study generates data to guide policy and future research aimed at generating affordable, contextually appropriate interventions to the blood drought.

Introduction: Epidemiologic and modeling studies suggest that between 45 and 70% of individuals with chronic hepatitis C virus (HCV) infection in Canada remain undiagnosed. The Canadian Association for the Study of the Liver (CASL) recommends one-time screening of baby boomers (1945-1975). Screening programs in the US have shown a very high prevalence of previously undiagnosed HCV among patients seen in the emergency department (ED). We sought to assess the feasibility of implementing a targeted birth-cohort HCV screening program in a Canadian ED setting. Methods: Patients born from 1945 to 1975 presenting to the ED of a downtown Toronto hospital were offered HCV testing. Patients with life-threatening conditions, unable to provide verbal consent in English or intoxication were excluded. Blood samples were collected by finger prick on Dried Blood Spot (DBS) collection cards and tested for anti-HCV antibody with reflex to HCV RNA. Patients with positive HCV RNA were referred to a liver specialist. Results: During a 27-month period (July 2017 - Sept 2019), 8363 patients in the birth cohort presented to the ED during daytime hours. 80% (6714) met eligibility criteria, and 48.4% (3247) were offered testing. Screening was performed by non-medical staff (mean 8/day, median spots on DBS 4). 345 (10.6%) had been previously tested, and 639 (19.7%) declined. 2136 (65.8%) patients underwent testing: median age 58.4 years (40-82), 1117 male (52.3%). Of these, 45 patients (2.1%; 95% CI 1.5%-2.7%) were anti-HCV positive: 32 (76.2%) were HCV RNA positive, 10 (23.8%) negative and 3 not done due to inadequate DBS sample. 26 patients (81.3%) were linked to care and 3 (9.4%) lost to follow-up. HCV prevalence in the ED was significantly higher than the general Canadian population (2.1% vs 0.7%; p Conclusion: Acceptance of HCV screening in the ED birth cohort was high and easily performed using DBS to ensure the majority of positive samples were tested for HCV RNA. Challenges included implementation that limited number of people tested, and linkage to care for HCV positive patients. HCV prevalence among this ED birth cohort was higher than the general population but lower than seen in the ED in the US. This may in part be due to exclusion of individuals with more severe medical issues, refusal by higher risk subgroups, or population and healthcare system differences between countries.

BACKGROUND There is a wealth of data documenting the epidemiology of primary biliary cholangitis (PBC) globally; however, the epidemiology of PBC has not been as well studied in Canada. Our study characterized the Canadian prevalence of PBC and the number of liver transplantations because of PBC. METHODS For this retrospective cohort study we used national hospital administrative records from the Canadian Institute for Health Information, with the exception of Quebec for the prevalence estimate and Quebec and British Columbia for the transplant analysis. Prevalent patients were identified through a diagnostic code for PBC of the Canadian version of the 10th revision of the International Classification of Diseases. PBC transplant patients were identified from their transplant record. Descriptive statistics were used to summarize the characteristics of the study cohorts. RESULTS In 2015, 8680 patients with PBC were identified in Canada, translating to a prevalence of 318 cases per million. Annual prevalence by province varied, ranging from 283 (95% confidence interval [CI] 269-297) cases per million to 465 (95% CI 426-504) cases per million, and the 6-year PBC liver transplantation rate ranged from 3.17 (95% CI 1.27-6.54) to 5.92 (95% CI 3.71-9.08) per million. The Atlantic provinces exhibited the highest PBC prevalence and close to the highest 6-year liver transplantation rate (465 [95% CI 426-504] cases per million and 5.70 [95% CI 426-504, 3.19-9.56] cases per million, respectively). We observed the lowest PBC prevalence (283 [95% CI 269-297] cases per million) and the second lowest 6-year liver transplantation rate in Ontario (3.37 [95% CI 2.47-4.50] cases per million). INTERPRETATION The prevalence of PBC that we found in Canada is similar to the prevalence reported in other studies, but our work also indicates geographic variation within this country. Given our finding of geographic clustering of PBC across Canada, we hypothesize that environmental and genetic factors contribute to the pathogenesis of this condition.

[See related article at [www.cmaj.ca/lookup/doi/10.1503/cmaj.170931][2]][2] KEY POINTS Chronic hepatitis C virus (HCV) is a highly burdensome public health problem in Canada, causing more years of life lost than any other infectious disease in the country. [1][2]–[3][3] A recent modelling study

BACKGROUND: Obeticholic acid (OCA) is a potent FXR agonist investigated for the treatment of primary biliary cholangitis (PBC) in 3 randomized, double-blind (DB), placebo (PBO)-controlled trials ± UDCA. AIMS: This analysis pools data from all 3 trials to investigate the efficacy and safety of OCA in patients treated in Canada. METHODS: Key Entry Criteria: ALP 1.5 to 10x ULN and conjugated bilirubin ≤2x ULN (Phase 2 trials, DB phase=3 months); ALP ≥1.67x ULN or total bilirubin >ULN but

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide.(1) Radiofrequency ablation (RFA) is the current recommended curative treatment option for non-surgical patients with early stage disease.(2) A recent report by Cancer Care Ontario shows the expected number of HCC cases requiring RFA will grow at a greater rate than RFA capacity estimates.(3) Currently, no recommended wait times exist for HCC. AIMS: In this study, we look at wait times for patients with HCC undergoing RFA and the development of adverse events. We also aimed to identify system gaps where quality improvement measures can be implemented. METHODS: This was a retrospective study conducted at the University Health Network looking at all patients diagnosed with HCC and referred for RFA between January 2010 until December 2013. Data on demographics and co-morbidities were obtained along with biochemistry, hematology and virology values. The time from diagnosis of HCC to presentation at Tumor Board rounds and the time from Tumor Board rounds to treatment were documented. Outcomes defined a priori were all-cause death and all-cause liver transplantation. Statistical analysis was performed with a help of a statistician. The study was approved by the UHN Research Ethics Board. RESULTS: 225 patients were included in the study. 72.4% percent were male and the median age was 63 years (SD+/-10.4). Median tumor size at diagnosis was 22 mm (SD +/-8.3), mean MELD was 8.7 (Range=7.2–11.3) and 55.6% had Barcelona stage 0. The cause of liver disease was viral hepatitis in 73% (Hepatitis B and C). The median time from HCC diagnosis to RFA treatment was 97 days (IQR 75–139). In multivariable analysis wait times per 30 days was associated with an increased risk of death (HR=1.16; 95% CI 1.08–1.25; p=

Background Patients with chronic hepatitis B (CHB) infection are at an increased risk of developing hepatocellular carcinoma (HCC). Risk scores have been developed in Asian populations to predict HCC risk over time. Aim To assess the performance of HCC risk prediction models in a heterogeneous population of patients with CHB. Methods Scores were calculated at baseline using CU-HCC, REACH-B, NGM1-HCC, NGM2-HCC and GAG-HCC models and the incidence of HCC was determined. The predictive ability of each score was evaluated using the area under the receiver operating characteristic curve (AUROC), Cox regression and plots of observed versus predicted HCC. The predictive value of the scores was compared between Asian and non-Asian patients and between cirrhotic versus non-cirrhotic with and without treatment. Results Of 2105 patients, 70 developed HCC. Increasing risk score was associated with HCC in all models. The CU-HCC model had the highest AUROC in Asian (0.85) and non-Asian (0.91) patients. Patients identified as low risk by any model had a very low incidence of HCC (0–0.15 per year), with the highest proportion of patients identified as low risk using CU-HCC (67%) or GAG-HCC (78%). The risk of HCC was similar to predicted for low-risk and medium-risk patients but was lower than predicted for high-risk patients. Treated patients had a lower than predicted risk of HCC, particularly in non-cirrhotic high-risk patients with longer follow-up. Conclusions Although all models predicted the risk of HCC, models that incorporated parameters of liver function or cirrhosis (CU-HCC/GAG-HCC) were most accurate. Low-risk patients likely require reduced HCC surveillance.

The current system of blood banks in India is such that rural patients are deprived of timely access to an adequate volume of life-saving blood, adding to preventable mortality. On the basis of an academic framework for a blood transfusion system, we describe an alternative approach in which rural practitioners utilise unbanked blood transfusions from a voluntary pool of pre-screened donors. This system would provide safe blood - as evidenced by international experience and limited projected increase in transfusion-transmissible infection in India - at a fraction of the financial cost imposed by the current system. Given the failing status quo and the undue burden placed on rural clinicians and patients to procure blood, it is imperative that policy-makers further explore the use of unbanked, direct blood transfusion for patients facing emergent, life-threatening haemorrhage.

Mixed cryoglobulinemia is strongly associated with hepatitis C virus (HCV) infection and ranges from being asymptomatic to causing life-threatening vasculitis. In those with symptoms, treatment with pegylated interferon (pegIFN) and ribavirin (RBV) reduces mortality. However, few data are available on the safety and efficacy of antiviral therapy with direct acting antivirals (DAAs) in the treatment of HCV-related cryoglobulinemia.Patients treated for HCV-related cryoglobulinemia with DAA±pegIFN were retrospectively evaluated at a tertiary care center. Primary outcomes were virological, immunological, and clinical response. Complete (normalization), partial (50% reduction), or non-response (50% reduction) were used to describe change in cryocrit or vasculitic manifestations at week 12 post treatment. Side effects, hospitalizations, and decompensating events were recorded.Eighteen symptomatic and 65 asymptomatic patients were reviewed (61% male, median age 58 years) including 10 with severe/life-threatening vasculitis. Sixty-six (79.5%) patients received pegIFN-free therapy. Sustained virological response (SVR) was attained in 16 (88.9%) symptomatic and 59 (90.8%) asymptomatic patients. Cryoglobulins disappeared in 5 (29.4%) symptomatic and 27 (52.9%) asymptomatic patients. Of symptomatic patients with SVR, clinical response was complete in 7 (38.8%) and partial response in 4 (22.2%). Of the 5 viral relapsers, 1 had a complete response during therapy with no symptomatic recurrence, while the other patients had no clinical response. Among 7 with severe vasculitis, 6 achieved SVR but only 1 had a complete clinical response, with 3 showing a partial response and 2 showing no improvement. All four with life-threatening vasculitis required plasmapheresis and three received rituximab. All achieved SVR leading to partial clinical response in two, but no response in two. Skin manifestations (39% reduction) were most likely to completely resolve with lower responses seen in renal (11.2% reduction) and neurological symptoms (11.1%). Eighty-two (98.8%) patients completed therapy, with 19 (22.8%) reporting adverse events. Hospitalization for decompensation or worsening vasculitis occurred in five (6.0%) and four (22.2) patients respectively.DAAs resulted in high rates of SVR in patients with cryoglobulinemia. Safety and tolerability were excellent; however, most patients did not have a complete clinical or immunological response, suggesting a delay to clinical response particularly in those with severe/life-threatening vasculitis. Further follow-up will be required to determine if clinical improvement continues after viral clearance.

BACKGROUND: An estimated 350 million people worldwide have chronic hepatitis B (CHB), which is a major cause of cirrhosis and hepatocellular carcinoma.OBJECTIVE: To assess the level of knowledge among family medicine trainees regarding the identification and management of CHB.METHODS: A questionnaire to assess knowledge regarding screening and management of patients with CHB and cirrhosis was developed. The questionnaire was pilot tested among primary care physicians, subsequently revised and distributed to family medicine trainees across Canada through an online survey program (QuestionPro).RESULTS: A total of 158 trainees completed the questionnaire. Of these, 54% to 56% routinely offered vaccination against hepatitis A or hepatitis B virus (HBV), and 42% regularly screened patients for HBV risk factors. The percentage who recognized the need to screen high-risk populations for CHB, ie, individuals from an HBV-endemic country, men who have sex with men, or intravenous drug users was 73%, 66% and 74%, respectively. While less than 50% of respondents used the appropriate HBV screening tests, 86% to 91% correctly interpreted various HBV serological patterns. Only 3% recognized cirrhosis in our case scenario. Almost 80% of respondents inappropriately preferred prescribing a narcotic or nonsteroidal anti-inflammatory drug over acetaminophen (4%) for pain control in a patient with cirrhosis. While less than 60% recognized HBeAg negative CHB as an indication for referral and treatment, 90% would have referred a patient in the immune-tolerant phase, even though treatment is not indicated.CONCLUSIONS: Knowledge gaps regarding CHB among family medicine trainees in the areas of primary prevention, disease recognition and management of cirrhosis were identified. Results suggest that opportunities to prevent potentially life-threatening complications are being missed.

This article uses the Chipko movement in northeastern India to propose an additional way to think alternatively about communication and development. The Chipko movement took place in the 1970s. Movement members demanded better local resource management by the state and for a greater voice in the determining the use of the local forests. Acknowledging that alternatives to the dominant paradigm of communication and development already exist (the participatory communication models and the participatory action research models), this essay shows even these alternatives did not address certain problems associated with the dominant paradigm. After a brief review of the dominant paradigm and the alternatives this article examines certain dimensions of the Chipko movement, such as the role of movement leaders, resource management, and strategies of communication, and argues that a Chipko-based ‘regions in protest’ model should take a place among the various models posed as alternatives to the dominant paradigm.

Background & Aims: The U.S. Multi-Society Task Force on Colorectal Cancer sets a target of cecal intubation in at least 90% of colonoscopies. We conducted a population-based study to determine the colonoscopy completion rate and to identify factors associated with incomplete procedures. Methods: Men and women 50 to 74 years of age who underwent a colonoscopy in Ontario between January 1, 1999, and December 31, 2003, were identified. The first (index) colonoscopy was classified as complete or incomplete. A generalized estimating equations model was used to evaluate the association between patient, endoscopist (specialty, colonoscopy volume), and setting (academic hospital, community hospital, private office) factors and incomplete colonoscopy. Results: A total of 331,608 individuals had an index colonoscopy, of which 43,483 (13.1%) were incomplete. Patients with an incomplete colonoscopy were older (odds ratio [OR] 1.20 per 10-year increment; 95% confidence interval [CI] = 1.18–1.22), more likely to be female (OR 1.35; 95% CI: 1.30–1.39), have a history of prior abdominal surgery (OR 1.07; 95% CI: 1.05–1.09) or prior pelvic surgery (OR 1.04; 95% CI: 1.01–1.06). For colonoscopies done in a private office, the odds of an incomplete procedure were more than 3-fold greater than for procedures done in an academic hospital (OR 3.57; 95% CI: 2.55–4.98). Conclusions: In usual clinical practice in Ontario, 13.1% of colonoscopies are incomplete. The factors most strongly associated with incomplete colonoscopy were increased patient age, female sex, and having the procedure in a private office. Quality improvement programs are needed to improve colonoscopy completion rates.

Characterization of the optical and electrical properties of organic solar cell materials is of prime importance to organic solar cell design. This thesis describes the use of capacitive photocurrent measurements to study the exciton generation and dissociation mechanisms of organic solar cell materials. The emphasis is on the study of the methanofullerene derivatives (e.g., PCBM) which act as the electron acceptor material. This is because much work has already been done studying electron donating polymers used in organic solar cells (in an effort to enhance their absorbance coefficient), but less information is available on the acceptor material. In the blend films of MDMO-PPV: PCBM, the charge generation rate in PCBM was discovered to be much higher than would be expected from the absorbance cross-section. This observation led to design of a photovoltage bleaching experiment to examine the charge generation mechanism. Here the effect of illumination by a tunable light source on the open circuit photovoltage of a MDMO-PPV: PCBM bulk heterojunction solar cell was measured. Illumination of light at the PCBM ground state singlet exciton causes a sharp decrease in the photovoltage, while illumination at the ground state MDMO-PPV exciton shows no change. A direct pathway of recombination of above gap generated charge carriers was identified. Photovoltage bleaching results suggests that excitation at the PCBM ground singlet state exciton increases the recombination rate of higher energy excitations, either by acting as a recombination center or by forcing higher energy carriers into short lived states that recombine before reaching the contacts. The fact that the photovoltage bleaching correlates with the ground state PCBM singlet exciton suggests that charge dissociation from PCBM preferentially generates long-lived localized states. Capacitive photocurrent measurements were then performed on isolated methanofullerene derivatives, with the polymer donor material absent. Several low energy transitions were resolved in the optical spectroscopy of methanofullerene derivatives. These low energy states lay below the optical energy band-gap of these materials, so that their presence was unexpected. It was determined that the low energy states overlapped with the plasmon state of the highly conducting substrates (Indium Tin Oxide) which were in close proximity with the PCBM. Plasmon states in ITO have been observed previously, but the results presented in this thesis are unique in that this is the first evidence of charge transfer from the plasmon state of ITO to a high electron affinity fullerene derivative. The results show the evidence of charge transfer from PCBM to ITO over a broad wavelength range of 400 - 2400 nm (3 eV - 0.5 eV). Few materials have been observed to have absorbance and charge transfer over such a large range of energies in the infra-red regime. These results open a new direction for development of organic solar cell design with higher power conversion efficiencies.

CASE PRESENTATION “Mr. K,” a 52-year-old single Caucasian man, was diagnosedwith hepatitis C virus (HCV) infection nearly two decades ago after routine testing revealed an elevated alanine transaminase (ALT) level. Additional blood work identified an HCV genotype 1 infection with a viral load of 5.2310 IU/mL. While liver biopsy demonstrated cirrhosis, esophagogastroduodenoscopy showed no varices, and ultrasonography of the liver showed nodularity but no hepatocellular carcinoma. The patient’s only risk factor for HCV infection was a 1-month period of injection drug use (cocaine) 15 years earlier. Mr. K’s psychiatric history was significant for a major depressive episode with psychotic features requiring hospitalization, 6 years before the HCV diagnosis. He had a history of alcohol dependence, consuming up to 75 drinks/week episodically over the 20 years preceding the HCV diagnosis. At the time of his admission fordepression,hehadnotusedalcohol for3months.For the next 6 years, hewas treatedwith an antidepressant, at times in combinationwith an antipsychotic. After his diagnosis of HCV infection, he achieved abstinence from alcohol and was treated with citalopram (30 mg/day). Three years after theHCV diagnosis,Mr. K started weekly pegylatedinterferonalfa-2B(IFN-a2B)injectionsanddailyoral ribavirin forHCVinfection.After the initial IFN-a injection,he experienced significant sideeffects, includingexcessive fatigue, nausea, fevers, and worsening mood symptoms. He decided to take his ribavirin every other day without notifying his care team. At week 6, his HCV therapy was stopped because of delirium caused by the interferon. After a brief hospital admission, his mental status returned to baseline and he was discharged,withoutmodificationofhispsychiatricmedication. For the next 10 years, Mr. K was followed regularly for HCV infection by a hepatologist. Treatment was deferred because of the hepatologist’s concerns about psychiatric side effects. After 10 years, Mr. K developed mild ascites, which was controlledwithdiuretics. At that time, his liver enzymes remained elevated and his liver function had declined. After attending a collaborative-care hepatology and psychiatry clinic,hewasreassessed for interferon-basedtherapy.The clinic psychiatrist monitored Mr. K closely as IFN-a was initiated. Mr. K was started on boceprevir, pegylated IFNa2A, and ribavirin, with the aim of completing 48 weeks of treatment. At week 2, he complained of fatigue and poor sleep, and mirtazapine (15 mg/day) was used to augment the citalopram. Despite attempts to further optimize the citalopram and mirtazapine dosages, Mr. K’s fatigue worsened.Atweek22,hedeveloped liver failure andpresented to the emergency department with hepatic encephalopathy. HCV therapy was stopped and the patient’s mental status soon returned to baseline and his liver function improved. For the next 3 years, Mr. K remained stable with early liver failure. Then, on the eveningnews, heheard about new treatments forHCVinfection thatdonot require IFN-a, and he asked his psychiatrist and hepatologist about them. Simeprevir/sofosbuvir therapy was started, with a planned treatment duration of 12 weeks. Mr. K experienced mild nausea but no other side effects. Hewas followedweekly to monitorandencourageadherence to thisonce-daily two-pill regimen.Hecompleted the full course andwasconfirmed to have sustained virological response. No adjustments to his psychiatric medications were needed, and his depressive symptoms remained stable throughout his treatment.

Summary Introduction: After a major disaster in a developing country, the graphic media coverage of the dead and injured invariably leads to an influx of volunteering healthcare personnel to the disaster zone. Very few studies document the outcomes of the treatment rendered in this field setting, under compromised conditions. We revisited the rural victims of the 2001 Gujarat earthquake in an attempt to analyse their surgical outcome and the status of their physical/psychosocial rehabilitation, 2 years after the disaster. Method: We traced displaced victims treated for earthquake-related injuries to their new homes. A community health worker interviewed patients with an oral questionnaire in the local language about injuries, the examining physician and first aid, orthopaedic implants, amputations, wounds, disability, deformity, residual pain, occupational and economic rehabilitation, post traumatic stress disorder (PTSD) and perceptions of healthcare rendered. Results: We located 133 of the 179 non-urban victims, from 11 villages. There were 10% missed injuries, 19% infection rate, restricted range of motion in 12%, non-union rate in 23% and reoperations in 30.5% patients. Fifty-one percent had resumed their previous occupation, but only 30% had recovered economically. Of 98% who had destroyed homes, 89% had their homes rebuilt. Residual sadness was the only significant PTSD symptom. Conclusion: This trauma outcome study highlights the shortcomings of surgeons for disaster-related work. One-tenth of the injuries were missed, suggesting that field examination at the site of disaster was more difficult than in the comfort of the hospital emergency room. Further there were inappropriately timed, aggressive implant operations, short time commitments, a lack of follow-up and a high rate of reoperations contributing to subsequent morbidity. These pointed to a need for training in disaster medicine within the curriculum of surgical residency. On the brighter side, despite poor sterility, prolonged transport times and no prehospital care, the postoperative infection rate was lower than expected. This perhaps was due to use of potent antibiotics in a previously unexposed rural population. Good physiotherapy given in the temporary shelters, by the informal carers within the family and by voluntary groups, kept up a good range of motion and reduced the final disability. PTSD was marked 3–6 months after the event, but was minimal 2 years postquake. Sadness about the event was the only residual PTSD symptom. While there were varying perceptions of satisfactory outcome, we found good coping mechanisms in place. The simple village folks were largely happy to be alive and accepted the residual deformities and cosmetic blemishes as a “small price to pay”.

A 49-year-old Brazilian male presented to the emergency department with a five-day history of abdominal pain, dark stools, and syncope. Physical examination did not reveal any melena on digital rectal examination and there were no stigmata of chronic liver disease. Laboratory results showed hemoglobin of 47 g/L, MCV of 80 fL, and ferritin of 6 ng/mL. Liver enzymes and liver function tests were normal. Abdominal ultrasound showed a cirrhotic liver with splenomegaly and varices suggestive of portal hypertension. His past history was significant for cirrhosis based on a previous variceal bleed but a workup for chronic liver disease was negative and a liver biopsy did not show steatosis, fibrosis, or cirrhosis. A gastroscopy in this admission showed large esophageal varices without high-risk stigmata and no overt bleeding was seen. A colonoscopy was subsequently completed to the terminal ileum and was normal aside from a 5 mm sessile polyp in the descending colon.

“Asian” culture has long been fodder for films and television shows produced in the United States. Four main stereotypes of Asians and Asian Americans emerged from the imagination of primarily white cultural producers in Hollywood: “Yellow Peril,” “Dragon Lady,” “Charlie Chan,” and “Lotus Blossom.” These images can be understood as “controlling images” in the sense that negative stereotypes provide justifications for social control and positive stereotypes provide normative models for Asian thought and behavior. Resistance to these images became substantial in the 1960s when Asian American filmmakers developed “triangular cinema,” a strategy for Asian American community building, political mobilization, and the creation of an Asian American film aesthetic. The films of triangular cinema are “liberating images” that stake out a position for independence and autonomy for Asian American communities.

Background: At 08:53 hours on 26 January 2001, an earthquake measuring 6.9 on the Richter scale devastated a large, drought-affected area of northwestern India, the state of Gujarat. The known number killed by the earthquake is 20,005, with 166,000 injured, of whom 20,717 were “seriously” injured. About 370,000 houses were destroyed, and another 922,000 were damaged. Methods: A community health worker using the local language interviewed all of the patients admitted to the Gandhi-Lincoln hospital with an on-site, oral, real-time, Victim Specific Questionnaire (VSQ). Results: The census showed a predominance of women, children, and young adults, with the average age being 28 years. The majority of the patients had other family members who were also injured (84%), but most had not experienced deaths among family members (86%). Most of the patients (91%) had traveled more than 200 kilometers using their family cars, pick-ups, trucks, or buses to reach the buffer zone hospitals. The daily hospital admission rate returned to pre-event levels five days after the event, and all of the hospital services were restored by nine days after the quake. Most of the patients (83%) received definitive treatment in the buffer zone hospitals; 7% were referred to tertiary-care centers; and 9% took discharge against medical advice. The entrapped village folk with their traditional architecture had lesser injuries and a higher rescue rate than did the semi-urban townspeople, who were trapped in collapsed concrete masonry buildings and narrow alleys. However, at the time of crisis, aware townspeople were able to tap the available health resources better than were the poor. There was a low incidence of crush injuries. Volunteer doctors from various backgrounds teamed up to meet the medical crisis. International relief agencies working through local groups were more effective. Local relief groups needed to coordinate better. Disaster tourism by various well-meaning agencies took a toll on the providers. Many surgeries may have contributed to subsequent morbidity. Conclusions: The injury profile was similar to that reported for most other daytime earthquakes. Buffer zone treatment outcomes were better than were the field and damaged hospital outcomes.

The burden of cleft lip and palate (CLP) in the developing world is being tackled by local hospitals and international surgical missions. However, the unmet surgical burden of these conditions is not known, because there are few population-based studies. We conducted this study to find the incidence and prevalence of cleft lip (CL), cleft palate (CP), and CLP and also estimate the unmet burden of these conditions. Four blocks comprising of half a million people in the Patan district of Gujarat were chosen as the study areas. This study was conducted over a period of 3 months in 2009. Patients with CL, CP, and CLP were identified by community health workers using snowball sampling method. Data collected included demographics, type of cleft, operated or not, and place of operation. Disability adjusted life years (DALY) was calculated to measure the unmet burden of this disease. The most common among the three conditions was CL (69.4 %). Overall, cleft abnormalities were more common in males (61 %). The overall incidence and prevalence of cleft deformity was 0.73 per 1,000 live births and 0.1 per 1,000 people respectively. The unmet burden of surgical disease of these four blocks was 230 to 494 DALYs. The incidence of CL with or without palate was found to be 0.7 per 1,000 live births. The large number of unoperated cases (backlog) of cleft deformities suggests a big burden of unmet need in rural India.