Blockchain Papers

Phunchai Charatcharoenwitthaya, Tawesak Tanwandee, Pisit Tangkijvanich, Teerha Piratvisuth · 7 authors

No abstract is available for this record.

Mateusz Mach

Chapter 4 takes you on a journey from Bitcoin’s origins in the Cypherpunk movement to its evolution into a million-dollar business. You’ll learn how Bitcoin merged ideals with finance, transforming from a tech novelty to a wealth-generating force. The chapter explores the security measures that make Bitcoin and other cryptocurrencies generally safe, as well as the concept of a limited supply of 21 million Bitcoins. It also delves into the economics of mining, emphasizing the importance of commitment, industry knowledge, and economic understanding. The chapter also touches on environmental considerations and emphasizes adaptability and innovation in cryptocurrency mining.

Huma Qureshi, Hassan Mahmood, Ahmed Sabry, Joumana Hermez

BACKGROUND: Pakistan has a high hepatitis burden for both hepatitis C virus (HCV) and hepatitis B virus (HBV). To achieve World Health Organization (WHO) 2030 targets for hepatitis elimination, there is a need to constitute progress in the country, find the barriers and strategies for HCV elimination, and take actions to address the gaps. METHODS: We collected data from (1) WHO estimates in 2020, (2) midterm review questionnaire of the WHO regional action plan, and (3) WHO estimates on immunization. We analyzed these data to inform (1) the burden defined as prevalence and mortality and (2) response in 3 thematic areas: governance, policy, and finance; strategic information; and service delivery. RESULTS: The prevalence of hepatitis B in the general population is 1.6% with 12 000 deaths/year. The prevalence of hepatitis C in the general population is 7.5% with 19 000 deaths and 545 000 new cases (incidence)/year. The selected indicators to monitor progress on viral hepatitis in Pakistan were governance and financing, policies and guidelines, and strategic information. The overall governance indicators are good with a focal point, a national hepatitis strategy, an operational plan, strategy for price reduction, and involvement of civil society but the costed action plan and the advocacy strategy are missing. The indicators on policies and guidelines are also adequately addressed. The hepatitis B and C testing and treatment guidelines are available, there is a policy to screen all blood donations, and there is an injection safety policy, but the policy for timely hepatitis B vaccine birth dose and hepatitis B vaccination for the vulnerable is missing. Both indicators regarding strategic information, that is measures of key hepatitis indicators and regular data review, are missing. The status of 5 key interventions in Pakistan show that the hepatitis B vaccination coverage is 74% and only 3% of newborn children are given the hepatitis B vaccine birth dose. Only 22% of HCV cases have been diagnosed and 2% have received treatment. Treatment response is 96%. Same-day testing and treatment of hepatitis C reduced the overall dropout rate and improved the cascade of care. Decentralization and task shifting are important tools to improve service delivery and reach communities. Finances to implement hepatitis elimination is a major barrier. CONCLUSIONS: Pakistan has the highest hepatitis disease burden. With the current pace, hepatitis elimination appears impossible. Introduction of the birth dose of hepatitis B vaccine and improving access and affordability of testing can improve the testing and treatment numbers. Finances need to be mobilized from within the country and outside to support disease elimination.

Karan Singla, Caroline E. Boeke, Roli Tandon, Umesh Chawla · 8 authors

INTRODUCTION: ESTABLISHMENT OF A PUBLIC SECTOR HEPATITIS C VIRUS CONTROL PROGRAM IN PUNJAB The state of Punjab in India has a higher hepatitis C virus (HCV) prevalence compared to other states in the country; estimates range from 0.56% to 3.6%1,2 compared to 0.32% nationally.2 With a population of 28 million state-wide,3 this translates to 150,000 to 1 million anti-HCV positive people, many of whom have progressive chronic liver disease due to the virus. Infections are thought to be primarily fuelled by injecting drug use and unsafe medical injections, compounded by a low level of awareness among the general population about the disease and modes of transmission. However, limited information is available on the specific factors driving transmission locally.1 In 2016, due to the higher HCV prevalence and availability of direct acting antivirals, the Government of Punjab launched the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF),4 becoming one of the first states in India to provide free antiviral treatment and subsidized diagnostic services for HCV at public sector facilities. Government buy-in and leadership were crucial factors in program success. Punjab entered a public private partnership with an empaneled lab to ensure availability of diagnostic and confirmatory viral load tests to patients at an affordable rate at their treating facility. Other initial areas of focus included developing HCV testing and treatment guidelines and referral mechanisms, streamlining commodity procurement, ensuring consistent availability of diagnostics and treatment through supply chain management, building staff capacity through trainings at a large number of health facilities, and implementing an electronic monitoring and evaluation system to assess program progress and gaps. NATIONAL VIRAL HEPATITIS CONTROL PROGRAM In 2018, the National Viral Hepatitis Control Program (NVHCP) was launched to achieve elimination of HCV in India by 2030.5 With the launch of the national program along with HCV treatment, diagnostic services were made available free of cost to patients.6 The national program released treatment7 and diagnostic guidelines8 standardizing hepatitis management across the country. The guidelines were designed to be simple, evidence-based, and minimize visits to the health facility. Individuals presenting to a clinician with clinical symptoms of and/or risk factors for HCV undergo a rapid diagnostic test for anti-HCV antibodies. If confirmed anti-HCV antibody positive, individuals are tested for current HCV viremia (HCV RNA viral load). Viremic patients undergo baseline investigations to detect presence of liver cirrhosis, if any. Twelve weeks after completing the treatment, patients are required to come back for a sustained virological response test (SVR12) to confirm whether the patient was cured. Diagnostic services including HCV antibody and RNA are available at all treatment centers. HCV RNA tests are processed under a public private partnership model; samples are collected at each facility and transported to a private facility in the state for testing on centralized equipment. Figure 1 shows the algorithm for cost-effective management of hepatitis C in Punjab.FIGURE 1: Algorithm by National Viral Hepatitis Control Program (NVHCP) for cost-effective management of hepatitis C, as presented in National Operational Guidelines.6 Abbreviations: APRI, AST to platelet ratio index; DCV, daclatasvir; SOF, sofosbuvir; VEL, velpatasvir.The increased focus and dedicated resources from the national program aided expansion in states including Punjab, while robust program monitoring and evaluation and research have helped identify new and strategic interventions. This manuscript describes strategies and approaches utilized in Punjab, India’s HCV program, with the ultimate goal of achieving HCV elimination in the state. METHODS This manuscript presents some aggregate-level program data in addition to describing strategies and approaches utilized by the program. Data were downloaded from Punjab’s HCV Management Information System (MIS) and include information from program initiation in 2016 through December 31, 2021. Data on number of treatment sites and number of patients screened were disaggregated by year and site type, and the total number of HCV services accessed across the cascade of care were included. MOVING TOWARD ELIMINATION: STRATEGIES FOR SUCCESS Rapid scale-up of screening and treatment sites One key strategy for success in this state-wide program has been the rapid scale-up and decentralization of sites offering HCV services over time (Fig. 2). Initially, the program offered diagnostic and treatment services at all 22 district hospitals and 3 government medical colleges. Once the program was successfully established, the state envisaged pursuing a more active screening strategy to identify and treat people living with HCV. Hence, in October 2018, the state launched the strategy focused on high-risk populations by offering HCV screening to people living with HIV at 13 antiretroviral treatment centers and persons who inject drugs at 11 oral substitution therapy sites across the state. During the COVID-19 pandemic, to mitigate reduced mobility and increase treatment accessibility, these 24 antiretroviral treatment and oral substitution therapy sites additionally began to offer HCV treatment. Antiretroviral treatment and oral substitution therapy sites have contributed to ~10% of the total positive cases identified in the state (Fig. 3). Most recently, the program was decentralized to subdistrict hospitals. As of December 2021, there are a total of 68 sites successfully screening and treating people living with HCV, allowing for a large number of patients to access services.FIGURE 2: Treatment site expansion in Punjab.FIGURE 3: Number of anti-HCV positive tests from June 2016 to December 2021 at various service delivery sites in Punjab.Building strong monitoring and evaluation systems To monitor the program effectively, the Government of Punjab developed the MIS. Initially, the MIS was a comprehensive paper-based tool to capture patient-level data, which presented the challenge of large-scale data management and analysis. To overcome this, a mobile-based application was created along with tools in Microsoft Excel. The existing health care workers were trained on these tools to increase their uptake and usage. A web-based reporting dashboard was also developed for easy access to patient information at the individual as well at the aggregate level across the state program. The online reporting dashboard enabled real-time monitoring of program progress across the state and at substate levels. This enabled program managers to recommend corrective action as needed. Figure 4 depicts examples of the monitoring and evaluation tools developed.FIGURE 4: Examples of monitoring and evaluation tools developed.The learnings from Punjab’s MIS system were instrumental in development of the National Viral Hepatitis Control Program Management Information System (NVHCP-MIS), developed and rolled out in the other states of the country. Conducting rigorous research studies to guide program improvement Analysis of the data collected in the MIS system identified program gaps requiring intervention and emphasized a need for additional evidence to support program improvement. Recent studies undertaken by states include an investigation of the primary local risk factors for HCV transmission, which will be used to develop prevention and screening strategies; a study to understand the primary reasons for early treatment cessation, to develop strategies to avert this loss to follow-up which occurs in nearly 15% of patients; and an analysis of HCV elimination costs and cost-savings,9 to understand resource requirements. The results from these studies will be used to guide program financing and strengthen the success of the program. PROGRAM ACHIEVEMENTS TO DATE Under the Punjab model of HCV management, 104,817 people living with HCV have been initiated on treatment in 5 years (Fig. 5). Out of these, 85,135 people living with HCV have completed treatment and 65,078 have had a SVR12 test; a total of 60,213 persons have a documented cure of their HCV infection. A high percentage of treatment initiations and a cure rate of ~93% are a testament to the programmatic and clinical success of the interventions introduced in the state. In addition, in 2017, Punjab launched the “injection safety implementation project”10 across all public health facilities to work toward reducing transmission with measures such as increasing availability of harm reduction services, disposal of contaminated needles and syringes, and promotion of disposable medical equipment and safe medical practices.FIGURE 5: Number of patients accessing HCV services in Punjab from June 2016 to December 2021. *Additionally, a total of 419 deaths has been recorded.During COVID-19, in addition to antiretroviral treatment and oral substitution therapy sites beginning to offer HCV services to increase accessibility, multimonth dispensation and doorstep delivery of medicine were adopted during lockdown periods. Multimonth dispensation has now been adopted as a program strategy and is provided to patients at their request and at the clinician’s discretion. THE WAY FORWARD While many factors have contributed to the success of Punjab’s HCV program to date, a strong commitment and willingness from the government has been essential to program progress. Even with a well-established and mature program, more effort will be required to ensure universal access to screening, diagnosis, and treatment and achieve HCV elimination goals by 2030. Some clear focus areas have been identified to accelerate progress toward elimination, such as improving accessibility by decentralizing services to the lowest levels of care (Community Health Centres and Primary Health Centres) and piloting telemedicine as a service delivery model. Whole blood diagnostic kits will be procured to facilitate screening and diagnostic tests during the same visit, thereby reducing the number of patient visits required for care. Active screening of high-risk groups and mass screening camps in vulnerable areas will be instrumental to improving case discovery and getting care to infected people. Evidence-driven program planning and increasing awareness among the general population and health care providers continue to be pivotal to ensuring program success. With additional focus on increased investment from the government and continuously evolving program strategies, Punjab is committed to achieving hepatitis elimination by 2030.

Polin Chan, Linh‐Vi Le, Naoko Ishikawa, Philippa Easterbrook

Chronic hepatitis C (HCV) infection is a major global public health threat and in 2019 there were an estimated 58 million infected globally and 290,000 deaths. Elimination of viral hepatitis B/C as a public health threat by 2030 is defined as a 90% incidence reduction and a 65% mortality reduction. The Western Pacific region is one of the most affected regions with 10 million people living with HCV, one-fifth of the global burden. We review progress towards HCV elimination in the Western Pacific region since 2015. Key developments in the region, which comprises of 37 high-and-middle-income countries, include the following: 20 countries have national hepatitis action plans, 19 have conducted recent disease burden and investment cases, 10 have scaled-up hepatitis services at primary health care level, and in 11 countries, domestic financing including social health insurance support DAA costs. We highlight six countries' experience in navigating the path towards HCV elimination: Cambodia, China, Malaysia, Mongolia, Philippines, and Viet Nam. Future initiatives to accelerate elimination are expanding access to community-based testing using HCV point-of-care tests among at-risk and general populations; adopting decentralized and integrated HCV one-stop services at harm reduction sites, detention settings and primary care; expanding treatment to include children and adolescents; address stigma and discrimination; and ensuring sustainable financing through domestic resources to scale-up testing, treatment and prevention. The COVID-19 pandemic has a significant impact on hepatitis response across the region on community and facility-based testing, treatment initiation, monitoring and cancer screening, which is projected to delay elimination goals.

Sabin Nsanzimana, Michael J. Penkunas, Carol Liu, Dieudonné Sebuhoro · 10 authors

BACKGROUND: Direct-acting antivirals (DAAs) are becoming accessible in sub-Saharan Africa. This study examined the effectiveness of DAAs in patients treated through the Rwandan national health system and identified factors associated with treatment outcomes. METHODS: This retrospective study used data from the national hepatitis C virus (HCV) program for patients who initiated DAAs between November 2015 and March 2017. Sustained virological response at 12 weeks after treatment (SVR12) was the primary outcome. Logistic regression models were fit to estimate the relationship between patients' clinical and demographic characteristics and treatment outcome. RESULTS: 894 patients started treatment during the study period; 590 completed treatment and had SVR12 results. Among the 304 patients without SVR12 results, 48 were lost to follow-up and 256 had no SVR12 results but clinical data indicated they likely completed treatment; these patients were classified as nonvirological failure because viral clearance could not be determined. In a per-protocol analysis of 590 patients with SVR12 results, SVR12 was achieved in 540 (92%), and virological failure occurred in 50 (8%). Pretreatment HCV RNA above the median split was associated with virological failure. Intention-to-treat analyses including all patients showed that SVR12 was achieved in 540 (60%), with nonvirological failure in 304 (34%) and virological failure in 50 (6%). Patients in Western Province were more likely to experience nonvirological failure than patients in Kigali, likely owing to the 5-7-hour travel required to access testing and treatment. CONCLUSIONS: DAAs were effective when implemented through the Rwandan national health system. Decentralization and enhanced financing are underway in Rwanda, which could improve access to treatment and follow-up as the country prepares for HCV elimination.

Léa Duchesne, Gilles Hejblum, Ndèye Coumba Touré Kâne, Richard Njouom · 10 authors

No abstract is available for this record.

Aimable Mbituyumuremyi, Jennifer Ilo Van Nuil, Jeanne Umuhire, Jules Mugabo · 9 authors

With the introduction of direct-acting antiviral drugs, treatment of hepatitis C is both highly effective and tolerable. Access to treatment for patients, however, remains limited in low- and middle-income countries due to the lack of supportive health infrastructure and the high cost of treatment. Poorer countries are being encouraged by international bodies to organize public health responses that would facilitate the roll-out of care and treatment on a national scale. Yet few countries have documented formal plans and policies. Here, we outline the approach taken in Rwanda to a public health framework for hepatitis C control and care within the World Health Organization hepatitis health sector strategy. This includes the development and implementation of policies and programmes, prevention efforts, screening capacity, treatment services and strategic information systems. We highlight key successes by the national programme for the control and management of hepatitis C: establishment of national governance and planning; development of diagnostic capacity; approval and introduction of direct-acting antiviral treatments; training of key personnel; generation of political will and leadership; and fostering of key strategic partnerships. Existing challenges and next steps for the programme include developing a detailed monitoring and evaluation framework and tools for monitoring of viral hepatitis. The government needs to further decentralize care and integrate hepatitis C management into routine clinical services to provide better access to diagnosis and treatment for patients. Introducing rapid diagnostic tests to public health-care facilities would help to increase case-finding. Increased public and private financing is essential to support care and treatment services.