Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis

Background The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. Methods We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018–30. We calibrated the model to country-level demographic data for 1960–2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007–08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. Findings One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4–14·1) individuals being screened and 350 000 (315 000–385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5–30·7) over 2018–30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1–55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to$3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. Interpretation Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. Funding UNITAID

A global research priority agenda to advance public health responses to fatty liver disease

Background & aims An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had 90% combined agreement. Conclusions Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat. Impact and implications An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat

Henrietta Bruce Green Personal Correspondence-Incoming (1879-10-09)

https://dspace.nku.edu/handle/11216/326

Henry Bruce, Jr. re Richard Lashbrook Green's Estate (1878-08-21)

https://dspace.nku.edu/handle/11216/326

Henry Bruce, Jr. re Richard Lashbrook Green's Estate (1878-09-28)

https://dspace.nku.edu/handle/11216/326

Henry Bruce, Jr. re Richard Lashbrook Green's Estate (1878-08-31)

https://dspace.nku.edu/handle/11216/326

Richard Lashbrook Green Business Records (1878-03-20)

https://dspace.nku.edu/handle/11216/326

Henrietta Bruce Green Personal Correspondence-Incoming (1879-02-06)

https://dspace.nku.edu/handle/11216/326

The 248 nm photodissociation of DOCl: laser excitation fluorescence spectra of OD

The dynamics of the 248 nm excimer-laser-induced photodissociation of DOCl has been investigated by the observation of the OD fragment by laser excitation fluorescence. The OD PI(A') lambda doublet state is strongly favoured in the dissociation and there is a small preference for the 2-PI-3/2 spin-orbit state. The observed OD rotational distribution differs for the two lambda doublets, and for the PI(A') component of the 2-PI-3/2 spin-orbit state the distribution is Gaussian. The results are interpreted in terms of a fast dissociation with most of the energy released into relative translational energy. The rotational distribution can be explained with a Franck-Condon type model

Surface second harmonic generation studies of the dodecane/water interface: the equilibrium and kinetic behaviour of p-nitrophenol and tri-n-butyl phosphate

The behaviour of p-nitrophenol (PNP) absorbed at the dodecane/water interface and the interaction with tri-n-butyl phosphate (TBP) were studied by surface second harmonic generation (SHG). The polarisation dependence of the PNP SHG signal, which is the same for all concentrations of PNP and TBP, is best described in terms of a limiting weak orientational order. In the presence of TBP, the SHG signal initially increases with PNP concentration, passes through a maximum and then it decreases. At low PNP concentrations, increasing the TBP concentration leads to an increase in the SHG intensity, but for higher PNP concentrations the intensity decreases. The free energies of adsorption for PNP and TBP to the dodecane/water interface were determined using Frumkin and Langmuir isotherms. The kinetics of the interaction between TBP and PNP was observed by monitoring the SHG signal along a liquid-liquid flow cell and found to be first-order at high interfacial coverage with rate constant, k, of 0.1 +/- 0.01 s(- 1)