Uptake of hepatitis C specialist services and treatment following diagnosis by dried blood spot in Scotland

Background: Dried blood spot (DBS) testing for hepatitis C (HCV) was introduced to Scotland in 2009. This minimally invasive specimen provides an alternative to venipuncture and can overcome barriers to testing in people who inject drugs (PWID). Objectives: The objective of this study was to determine rates and predictors of: exposure to HCV, attendance at specialist clinics and anti-viral treatment initiation among the DBS tested population in Scotland. Study design: DBS testing records were deterministically linked to the Scottish HCV Clinical database prior to logistic regression analysis. Results: In the first two years of usage in Scotland, 1322 individuals were tested by DBS of which 476 were found to have an active HCV infection. Linkage analysis showed that 32% had attended a specialist clinic within 12 months of their specimen collection date and 18% had begun anti-viral therapy within 18 months of their specimen collection date. A significantly reduced likelihood of attendance at a specialist clinic was evident amongst younger individuals (<35 years), those of unknown ethnic origin and those not reporting injecting drug use as a risk factor. Conclusion: We conclude that DBS testing in non-clinical settings has the potential to increase diagnosis and, with sufficient support, treatment of HCV infection among PWID

Expansions for the Bollobas-Riordan polynomial of separable ribbon graphs

We define 2-decompositions of ribbon graphs, which generalise 2-sums and tensor products of graphs. We give formulae for the Bollobas-Riordan polynomial of such a 2-decomposition, and derive the classical Brylawski formula for the Tutte polynomial of a tensor product as a (very) special case. This study was initially motivated from knot theory, and we include an application of our formulae to mutation in knot diagrams.Comment: Version 2 has minor changes. To appear in Annals of Combinatoric

Patient Perceptions and Expectations About Postoperative Analgesia

Introduction Opioid overdose deaths have nearly quadrupled since 1999. Nearly 2 out of 3 persons being prescribed medications are prescribed an opioid. Physicians may be prescribing opioids for more than what is required for postoperative pain control, leading to increased risk for opioid abuse and addiction. Patient perceptions of perioperative pain medications are poorly understood. Objective This survey aims to understand patient expectations of perioperative analgesics. Methods Following IRB approval, patients 18 years of age or older, were given a 13-question survey prior to their surgery at Thomas Jefferson University Hospital, to evaluate the perception of pain medications, medication efficacy, and risk profile. For this analysis, 503 patients were surveyed and only 5 questions were used. Results Overall, 100% of patients believed they would receive analgesics after surgery, with 76% of patients expecting opioids. Additionally, 94% of patients expecting to receive postoperative opioid prescriptions believed opioids would be effective in controlling their pain. Furthermore, 67.5% of patients not expecting to receive opioids postoperatively still believed opioids would be superior to non-opioid medications. Conclusion Patients expected to experience pain after surgery and be prescribed analgesics. Patients anticipated receiving analgesics they perceived most effective, which was most often an opioid. The perception of superior efficacy of opioids is worthy of further study as this is inconsistent with the literature, and education may be needed to bridge this gap. As the opioid crisis continues, cultural attitudes toward pain and medications will play a central role in reducing the prevalence of opioids in healthcare and society

The Mysterious Ultrahigh Energy Cosmic Ray Clustering

We examine the correlation between compact radio quasars (redshifts in the range $z = 0.3 - 2.2$) and the arrival direction of ultrahigh energy cosmic rays forming clusters. Our Monte Carlo simulation reveals a statistically significant correlation on the AGASA sample: the chance probability of this effect being less than 1%. The implications of this result on the origin of ultrahigh energy cosmic rays are discussed.Comment: Updates to match journal versio

Energy of Isolated Systems at Retarded Times as the Null Limit of Quasilocal Energy

We define the energy of a perfectly isolated system at a given retarded time as the suitable null limit of the quasilocal energy $E$. The result coincides with the Bondi-Sachs mass. Our $E$ is the lapse-unity shift-zero boundary value of the gravitational Hamiltonian appropriate for the partial system $\Sigma$ contained within a finite topologically spherical boundary $B = \partial \Sigma$. Moreover, we show that with an arbitrary lapse and zero shift the same null limit of the Hamiltonian defines a physically meaningful element in the space dual to supertranslations. This result is specialized to yield an expression for the full Bondi-Sachs four-momentum in terms of Hamiltonian values.Comment: REVTEX, 16 pages, 1 figur

Reduction in the population prevalence of hepatitis C virus viraemia among people who inject drugs associated with scale-up of direct-acting anti-viral therapy in community drug services:REAL WORLD DATA

BACKGROUND AND AIMS: There has been little empirical evidence to show the 'real-world' impact of scaling-up direct-acting anti-viral (DAA) treatment among people who inject drugs (PWID) on hepatitis C virus (HCV) viraemia at a population level. We aimed to assess the population impact of rapid DAA scale-up to PWID delivered through community services-including drug treatment, pharmacies, needle exchanges and prisons-in the Tayside region of Scotland, compared with Greater Glasgow and Clyde (GGC) and the Rest of Scotland (RoS). FINDINGS: Uptake of HCV therapy (last year) among PWID between 2013-14 and 2017-18 increased from 15 to 43% in Tayside, 6 to 16% in GGC and 11 to 23% in RoS. Between 2010 and 2017-18, the prevalence of HCV viraemia (among antibody-positives) declined from 73 to 44% in Tayside, 67 to 58% in GGC and 64 to 55% in RoS. The decline in viraemia was greater in Tayside [2017-18 adjusted odds ratio (aOR) = 0.47, 95% confidence interval (CI) = 0.30-0.75, P = 0.001] than elsewhere in Scotland (2017-18 aOR = 0.89, 95% CI = 0.74-1.07, P = 0.220) relative to the baseline of 2013-14 in RoS (including GGC). Per-protocol SVR rates among PWID treated in community sites did not differ from those treated in hospital sites in Tayside (97.4 versus 100.0%, P = 0.099). CONCLUSIONS: Scale-up of direct-acting anti-viral treatment among people who inject drugs can be achieved through hepatitis C virus (HCV) testing and treatment in community drug services while maintaining high sustained viral response rates and, in the Tayside region of Scotland, has led to a substantial reduction in chronic HCV in the population

Competing risk bias in prognostic models predicting hepatocellular carcinoma occurrence: impact on clinical decision making

Existing models predicting hepatocellular carcinoma (HCC) occurrence do not account for competing risk events and, thus, may overestimate the probability of HCC. Our goal was to quantify this bias for patients with cirrhosis and cured hepatitis C. We analyzed a nationwide cohort of patients with cirrhosis and cured hepatitis C infection from Scotland. Two HCC prognostic models were developed: (1) a Cox regression model ignoring competing risk events and (2) a Fine-Gray regression model accounting for non-HCC mortality as a competing risk. Both models included the same set of prognostic factors used by previously developed HCC prognostic models. Two predictions were calculated for each patient: first, the 3-year probability of HCC predicted by model 1 and second, the 3-year probability of HCC predicted by model 2. The study population comprised 1629 patients with cirrhosis and cured HCV, followed for 3.8 years on average. A total of 82 incident HCC events and 159 competing risk events (ie, non-HCC deaths) were observed. The mean predicted 3-year probability of HCC was 3.37% for model 1 (Cox) and 3.24% for model 2 (Fine-Gray). For most patients (76%), the difference in the 3-year probability of HCC predicted by model 1 and model 2 was minimal (ie, within 0 to ±0.3%). A total of 2.6% of patients had a large discrepancy exceeding 2%; however, these were all patients with a 3-year probability exceeding >5% in both models. Prognostic models that ignore competing risks do overestimate the future probability of developing HCC. However, the degree of overestimation—and the way it is patterned—means that the impact on HCC screening decisions is likely to be modest

Evidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: implications for reinfection

Background: People who inject drugs (PWID) are at the greatest risk of hepatitis C virus (HCV) infection, yet are often denied immediate treatment due to fears of on-going risk behaviour. Our principal objective was to examine evidence of continued injecting drug use among PWID following successful treatment for HCV and attainment of a sustained viral response (SVR). Methods: PWID who attained SVR between 1992 and June 2012 were selected from the National Scottish Hepatitis C Clinical Database. Hospitalisation and mortality records were sourced for these patients using record linkage techniques. Our primary outcome variable was any hospitalisation or death, which was indicative of injecting drugs post-SVR. Results: The cohort comprised 1170 PWID (mean age at SVR 39.6y; 76% male). The Kaplan Meier estimate of incurring the primary outcome after three years of SVR was 10.59% (95% CI, 8.75–12.79) After adjusting for confounding, the risk of an injection related hospital episode or death post-SVR was significantly increased with advancing year of SVR: AHR:1.07 per year (95% CI, 1.01–1.14), having a pre-SVR acute alcohol intoxication-related hospital episode: AHR:1.83 (95% CI, 1.29–2.60), and having a pre-SVR opiate or injection-related hospital episode: AHR:2.59 (95% CI, 1.84–3.64). Conclusion: Despite attaining the optimal treatment outcome, these data indicate that an increasing significant minority of PWID continue to inject post-SVR at an intensity which leads to either hospitalisation or death and increased risk of reinfection

The risk of hepatocellular carcinoma in cirrhotic patients with hepatitis C and sustained viral response:role of the treatment regimen

Background & Aims: Previous studies have reported a high frequency of hepatocellular carcinoma (HCC) occurrence in patients with advanced liver disease, after receipt of interferon (IFN)-free therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account for this phenomenon using data from the Scottish HCV clinical database. Methods: We identified HCC-naïve individuals with liver cirrhosis receiving a course of antiviral therapy in Scotland from 1997–2016 resulting in a sustained virologic response. Patients were followed-up from their treatment start date to the earliest of: date of death, date of HCC occurrence, or 31 January 2017. We used Cox regression to compare the risk of HCC occurrence according to treatment regimen after adjusting for relevant co-factors (including: demographic factors; baseline liver disease stage; comorbidities/health behaviours, virology, and previous treatment experience). HCC occurrence was ascertained through both the HCV clinical database and medical chart review. For our main analysis, treatment regimen was defined as IFN-free vs. IFN-containing. Results: A total of 857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free therapy was associated with a significantly increased risk of HCC (HR: 2.48; p = 0.021). However, after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, p = 0.744). Conclusion: These findings suggest that the higher incidence of HCC following sustained virologic response with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se. Lay summary: We examined the risk of liver cancer in 857 patients with cirrhosis in Scotland who received hepatitis C antiviral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer