National Treatment Program Research Articles

Designing an implementation science clinical trial to integrate hypertension and cardiovascular diseases care into existing HIV services package in Botswana (InterCARE)

BackgroundDespite success in HIV treatment, diagnosis and management of hypertension (HTN) and cardiovascular disease (CVD) remains suboptimal among people living with HIV (PLWH) in Botswana, with an overall HTN control of only 19% compared to 98% HIV viral suppressed. These gaps persist despite CVD primary care national guidelines and availability of free healthcare including antihypertensive medications. Our study aims to develop and test strategies to close the HTN care gap in PLWH, through integration into HIV care, leveraging the successful national HIV care and treatment program and strategies.MethodsThe InterCARE trial is a cluster randomized controlled hybrid type 2 effectiveness-implementation trial at 14 sites designed to enroll 4652 adults living with HIV and HTN plus up to 2326 treatment partners. Primary outcomes included effectiveness (HTN control) and implementation outcomes using the Reach Effectiveness Adoption Implementation and Maintenance framework, with explanatory mixed methods used to understand variability in outcomes.InterCARE trial’s main strategies include healthcare worker HTN and CVD care training plus long-term practice facilitation, electronic health record (EHR) documentation of key indicators and use of reminders, and use of treatment partners to provide social support to people living with HIV and HTN. InterCARE started with formative research to identify contextual factors influencing care gaps using the Consolidated Framework for Implementation Research. Results were used to adapt initial and develop additional implementation strategies to address barriers and leverage facilitators. The package was pilot tested in two clinics, with findings used to further adapt or add strategies for the clinical trial.DiscussionIf successful, the InterCARE model can be scaled up to HIV clinics nationwide to improve diagnosis, management, and support in Botswana. The trial will provide insights for scale-up of HTN integration into HIV care in the region.Trial registrationClinicalTrials.gov reference NCT05414526. Registered 18 May 2022, https://clinicaltrials.gov/study/NCT05414526?term=NCT05414526.&rank=1.

The potential impact of the Comprehensive and Progressive Agreement for Trans-Pacific Partnership on Thailand’s hepatitis C treatment program

BackgroundThailand has expressed interest in joining the Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP), a twelve-country plurilateral trade agreement whose original incarnation included the United States of America (USA). When the USA withdrew from this agreement, key intellectual property clauses relevant to pharmaceuticals were suspended. These could be reinstated should the CPTPP Parties decide to do so. MethodsThis study uses two scenarios to cost the impact the CPTPP would have had on Thailand’s 2020 hepatitis C treatment regime if Thailand joined the CPTPP and suspended clauses were reinstated.ResultsJoining the CPTPP could have increased the cost more than tenfold if suspended CPTPP clauses were reinstated and Thailand was not willing or able to issue compulsory licenses. Based on the 2020 budget, the price for this possible scenario could have reduced hepatitis C treatment coverage by 90%.ConclusionsAcceding to trade agreements such as the CPTPP that require increasing intellectual property protection, could compromise Thailand’s hepatitis C program and other national treatment programs reliant on affordable generic medicines. The CPTPP could also prevent Thailand from relying on its own pharmaceutical capabilities to manufacture medicines needed to sustain its treatment programs.

Evaluating a multifaceted implementation strategy and package of evidence-based interventions based on WHO PEN for people living with HIV and cardiometabolic conditions in Lusaka, Zambia: protocol for the TASKPEN hybrid effectiveness-implementation stepped wedge cluster randomized trial

BackgroundDespite increasing morbidity and mortality from non-communicable diseases (NCD) globally, health systems in low- and middle-income countries (LMICs) have limited capacity to address these chronic conditions, particularly in sub-Saharan Africa (SSA). There is an urgent need, therefore, to respond to NCDs in SSA, beginning by applying lessons learned from the first global response to any chronic disease—HIV—to tackle the leading cardiometabolic killers of people living with HIV (PLHIV). We have developed a feasible and acceptable package of evidence-based interventions and a multi-faceted implementation strategy, known as “TASKPEN,” that has been adapted to the Zambian setting to address hypertension, diabetes, and dyslipidemia. The TASKPEN multifaceted implementation strategy focuses on reorganizing service delivery for integrated HIV-NCD care and features task-shifting, practice facilitation, and leveraging HIV platforms for NCD care. We propose a hybrid type II effectiveness-implementation stepped-wedge cluster randomized trial to evaluate the effects of TASKPEN on clinical and implementation outcomes, including dual control of HIV and cardiometabolic NCDs, as well as quality of life, intervention reach, and cost-effectiveness.MethodsThe trial will be conducted in 12 urban health facilities in Lusaka, Zambia over a 30-month period. Clinical outcomes will be assessed via surveys with PLHIV accessing routine HIV services, and a prospective cohort of PLHIV with cardiometabolic comorbidities nested within the larger trial. We will also collect data using mixed methods, including in-depth interviews, questionnaires, focus group discussions, and structured observations, and estimate cost-effectiveness through time-and-motion studies and other costing methods, to understand implementation outcomes according to Proctor’s Outcomes for Implementation Research, the Consolidated Framework for Implementation Research, and selected dimensions of RE-AIM.DiscussionFindings from this study will be used to make discrete, actionable, and context-specific recommendations in Zambia and the region for integrating cardiometabolic NCD care into national HIV treatment programs. While the TASKPEN study focuses on cardiometabolic NCDs in PLHIV, the multifaceted implementation strategy studied will be relevant to other NCDs and to people without HIV. It is expected that the trial will generate new insights that enable delivery of high-quality integrated HIV-NCD care, which may improve cardiovascular morbidity and viral suppression for PLHIV in SSA. This study was registered at ClinicalTrials.gov (NCT05950919).

Population impacts of conditional financial incentives and a male-targeted digital decision support application on the HIV treatment cascade in rural KwaZulu Natal: findings from the HITS cluster randomized clinical trial.

In South Africa, the HIV care cascade remains suboptimal. We investigated the impact of small conditional financial incentives (CFIs) and male-targeted HIV-specific decision-support application (EPIC-HIV) on the HIV care cascade. In 2018, in uMkhanyakude district, 45 communities were randomly assigned to one of four arms: (i) CFI for home-based HIV testing and linkage to care within 6 weeks (R50 [US$3] food voucher each); (ii) EPIC-HIV which are based on self-determination theory; (iii) both CFI and EPIC-HIV; and (iv) standard of care. EPIC-HIV consisted of two components: EPIC-HIV 1, provided to men through a tablet before home-based HIV testing, and EPIC-HIV 2, offered 1 month later to men who tested positive but had not yet linked to care. Linking HITS trial data to national antiretroviral treatment (ART) programme data and HIV surveillance programme data, we estimated HIV status awareness after the HITS trial implementation, ART status 3 month after the trial and viral load suppression 1 year later. Analysis included all known individuals living with HIV in the study area including those who did not participated in the HITS trial. Among the 33,778 residents in the study area, 2763 men and 7266 women were identified as living with HIV by the end of the intervention period and included in the analysis. After the intervention, awareness of HIV-positive status was higher in the CFI arms compared to non-CFI arms (men: 793/908 [87.3%] vs. 1574/1855 [84.9%], RR=1.03 [95% CI: 0.99-1.07]; women: 2259/2421 [93.3%] vs. 4439/4845 [91.6%], RR=1.02 [95% CI: 1.00-1.04]). Three months after the intervention, no differences were found for linkage to ART between arms. One year after the intervention, only 1829 viral test results were retrieved. Viral suppression was higher but not significant in the EPIC-HIV intervention arms among men (65/99 [65.7%] vs. 182/308 [59.1%], RR=1.11 [95% CI: 0.88-1.40]). Small CFIs can contribute to achieve the first step of the HIV care cascade. However, neither CFIs nor EPIC-HIV was sufficient to increase the number of people on ART. Additional evidence is needed to confirm the impact of EPIC-HIV on viral suppression.

Position statement for improvement in reperfusion of ST-elevation myocardial infarction in Latin America

The treatment of ST-segment elevation myocardial infarction has barriers depending on the geographic region. Primary coronary angioplasty is the treatment of choice, if it is performed on time and by experienced operators. However, when it is not available, the administration of fibrinolysis and referral for rescue angioplasty, in case of negative reperfusion, is the best strategy. In the same way, coronary angioplasty, as part of a pharmacoinvasive strategy, is the best alternative when there is positive reperfusion. The development of infarct treatment networks increases the number of patients reperfused within the recommended times and improves outcomes. In Latin America, national myocardial infarction treatment programs should focus on improving outcomes, and long-term success depends on working toward defined goals and enhancing functionality, therefore programs should develop capacity to measure their performance. The following document discusses all of these alternatives and suggests opportunities for improvement.

The Evolution of Anorexia Nervosa in Singapore: A 30-year Demographic Analysis

IntroductionNew prevalence and time trend data from various Asian countries show that Eating Disorders (ED) are increasingly common in Asia. (Youl-Ri Kim. Int J Eat Disord. Dec 2020). A recent study estimating the prevalence of ED in Singapore found an alarming 6.2% screened positive for a clinical ED diagnosis, 19.5% were screened to be at high risk, and estimated the point prevalence of Anorexia Nervosa (AN) to be 0.9%. (Chua SN et al. Int J Eat Disord. Jan 2021). The ED unit in Singapore General Hospital (SGH) was set up in 2003 as a National Treatment Programme for patients with ED. Two local studies have been published to date on the demographics and clinical profile of patients with AN. The first study examined 126 patients from 1994 – 2002 (HY Lee et al. Singapore Med J 2005; 46(6): 275-281). The second study reported on 271 cases from our SGH ED unit from 2003-2010 (Kuek et al. SIngapore Med J 2015; 56(6): 324-328). There have been no further studies in the last decade.Objectives1.Study the demographics and clinical profile of patients who presented with AN to our ED unit from 2011-20222.Compare our data with the 2 previous studies and examine for any changes and trends in the past 30 years.MethodsWe conducted a review of the ED unit new case registry at SGH from 2011-2022. A total of 910 patients were diagnosed with AN at presentation. The data was analysed with approval from the hospital instituitional review board.ResultsA total of 910 cases presented with AN over 12 years. Comparing with the 2 previous studies, the number of new cases each year has continued to increase from <15 in the 1990s to hit a peak of 109 per year in 2022. 94% were females, with a mean presenting age of 19. 79.2% were Chinese, 5.2% were Indians and 2.9% were of Malay ethnicity. The Malay population continue to be under-represented whereas other ethnic groups continue to be over-represented, increasing from 3.2% to 7% in the previous studies to 11.1%. Referrals were mainly from tertiary healthcare intuitions accounting for 41.4% of cases. Self-referrals have decreased over the last decade whereas referrals from primary care has increased. The mean presenting body mass index (BMI) was 15.9. Compared to a previous study, there was a significant increase in presenting BMI (15.9+/- 0.78 vs 14.4 +/- 1.77, p value 0.0074).ConclusionsThe number of new cases of AN has seen an almost 10-fold increase in the last 30years. The Malay ethnicity continues to be under-represented – more research is needed if they are somehow culturally protected or if they are not coming forth for treatment. Majority of referrals are from tertiary healthcare institutions but referrals from primary care have increased, reflecting a possible increase in awareness amongst primary care doctors. The mean presenting BMI has increased – hopefully reflecting an increase in ED awareness such that patients are coming forward earlier for treatment.Disclosure of InterestNone Declared

Impacts of the Egyptian national screening and treatment programme for viral hepatitis C: A cost-effectiveness model.

Egypt used to have one of the highest prevalences of HCV infection worldwide. The Egyptian Ministry of Health launched a national campaign for the detection and management of HCV to reduce its burden. This study aims to carry out a cost-effectiveness analysis to evaluate the costs and benefits of the Egyptian national screening and treatment programme. A disease burden and economic impact model was populated with the Egyptian national screening and treatment programme data to assess direct medical costs, health effects measured in disability-adjusted life years and the incremental cost-effectiveness ratio. The scenario was compared to a historical base case, which assumed that no programme had been conducted. Total number of viremic cases is expected to decrease in 2030 by 86% under the national screening and treatment programme, versus by 41% under the historical base case. Annual discounted direct medical costs are expected to decrease from $178 million in 2018 to $81 million by 2030 under the historical base case, while annual direct medical costs are estimated to have peaked in 2019 at $312 million before declining to $55 million by 2030 under the national screening and treatment programme. Under the programme, annual disability-adjusted life years are expected to decline to 127 647 by 2030, leading to 883 333 cumulative disability-adjusted life years averted over 2018-2030. The national screening and treatment programme is highly cost-effective by the year 2021, cost-saving by 2029 and expected to save about $35 million in direct costs and $4705 million in indirect costs by 2030.

Economic, social, and clinic influences on opioid treatment program retention in Dar es Salaam, Tanzania: a qualitative study

BackgroundMedications for opioid use disorder (MOUD) are associated with positive health outcomes. People remaining on MOUD have a reduced likelihood of drug overdose and mortality. Tanzania supports a national opioid treatment program (OTP) offering MOUD, but retention is a continual challenge. To date, most research on MOUD retention in Tanzania and other Sub-Saharan Africa settings has been focused on the individual-level, with little attention to economic, social, and clinic-level factors.MethodsWe qualitatively examined economic, social, and clinic factors that affect retention on MOUD, specifically methadone maintenance therapy, among former and current clients attending an OTP clinic Dar es Salaam, Tanzania. We conducted in-depth interviews with a total of 40 current and former clients receiving MOUD and four focus groups with an additional 35 current clients on MOUD between January and April 2020. We utilized a thematic analysis approach.ResultsDaily OTP clinic attendance posed a financial burden to current and former clients and was a barrier to remaining on MOUD. Though treatment is free, clients described struggles to attend clinic, including being able to afford transportation. Female clients were differentially impacted, as sex work was the most common income-generating activity that they participated in, which presented its own set of unique challenges, including barriers to attending during set clinic hours. Drug use stigma acted as a barrier to MOUD and prevented clients from securing a job, rebuilding trust within the community, and accessing transportation to attend the clinic. Being able to rebuild trust with family facilitated remaining on MOUD, as family provided social and financial support. Caretaking responsibilities and familial expectations among female clients conflicted with MOUD adherence. Finally, clinic level factors, such as clinic dispensing hours and punitive consequences for breaking rules, posed barriers to clients on MOUD.ConclusionSocial and structural factors, both within (e.g., clinic policies) and outside of (e.g., transportation) the clinic impact MOUD retention. Our findings can inform interventions and policies to address economic and social barriers to MOUD, that can contribute to sustained recovery.

Circulation of Human Immunodeficiency Virus 1 A6 Variant in the Eastern Border of the European Union-Dynamics of the Virus Transmissions Between Poland and Ukraine.

The human immunodeficiency virus (HIV) type 1 A6 variant is dominating in high-prevalence Eastern European countries, with increasing prevalence over the remaining regions of Europe. The recent war in Ukraine may contribute to further introductions of this A6 lineage. Our aim was to model the transmission dynamics of the HIV-1 A6 variant between Poland and Ukraine. HIV-1 A6 partial pol sequences originating from Poland (n = 1185) and Ukraine (n = 653) were combined with publicly available sequences (n = 7675) from 37 other countries. We used maximum likelihood-based tree estimation followed by a bayesian inference strategy to characterize the putative transmission clades. Asymmetric discrete phylogeographic analysis was used to identify the best-supported virus migration events across administrative regions of Poland and Ukraine. We identified 206 clades (n = 1362 sequences) circulating in Poland or Ukraine (63 binational clades, 79 exclusively Polish, and 64 exclusively Ukrainian). Cross-border migrations were almost exclusively unidirectional (from Ukraine to Poland, 99.4%), mainly from Eastern and Southern Ukraine (Donetsk, 49.7%; Odesa, 17.6% regions) to the Central (Masovian, 67.3%; Lodz, 18.2%) and West Pomeranian (10.1%) districts of Poland. The primary sources of viral dispersal were the Eastern regions of Ukraine, long affected by armed conflict, and large population centers in Poland. The Polish outbreak of the A6 epidemic was fueled by complex viral migration patterns across the country, together with cross-border transmissions from Ukraine. There is an urgent need to include war-displaced people in the national HIV prevention and treatment programs to reduce the further spread of transmission networks.

Ophthalmological results in the Hungarian comprehensive health care screening program, 2011-2022

The World Health Organisation's VISION 2020 and World report on vision programs prioritize blindness prevention and vision rehabilitation development. The ophthalmology program, which is part of Hungary's comprehensive health care screening program, plays an important role in the national implementation of these. Summary of the results of Hungary's comprehensive health care screening program's ophthalmology program, which has been going on for 12 years. The ophthalmological data of 168522 people aged between 12 and 99 years who participated in the national screening program were analyzed in nine categories: the presence of eye disease, the use of glasses, the refractive power of the glasses, refractive errors (myopia, anisometropia), the functional vision questionnaire, dry eye, colour vision, educational and communication activities. 18.1% of the participants reported having an eye disease, which was much more common in women and the elderly. The proportion of people who wore glasses reached 66%, with roughly one-third of them lacking appropriate glass strength. Myopia was the most common (58.7%) in people aged 18 to 35. Anisometropia was found in 6.5% of people. Women were more likely than men to have dry eyes (26.1%). Men had a higher rate of colour vision deficiency (5.7%) than women (0.7%). As blindness is 80% preventable, national screening tests and comprehensive educational activities that contribute to the early detection and treatment of eye diseases are important. It is critical to call attention to the significant growth in the prevalence of myopia in young people as well as the urgent need for the effective implementation of preventive measures. The importance of proper glasses must also be brought to the attention of the general population because incorrect glasses cause visual problems. The national ophthalmology screening and educational activity should be continued in the future, with the goal of reducing the incidence of eye diseases associated with visual impairment and increasing the proportion of people who wear appropriate glasses. To stop the spread of myopia, a national preventive and treatment program should be launched. Orv Hetil. 2023; 164(7): 253-259.

Treatment Outcomes After Switching to Second-Line Anti-Retroviral Therapy: Results From the Thai National Treatment Program.

This study aimed to assess second-line antiretroviral therapy (ART) outcomes in a National HIV Treatment program. People living with HIV aged ≥18 years initiating first-line ART who switched to second-line protease inhibitor-based regimens from January 2008 to May 2019, with a minimum of 1-year follow-up were studied. The primary outcome was second-line treatment failure (two consecutive virological failure episodes (viral load ≥1000 copies/mL)). Of 318,506 PLH initiating ART, 29,015 (9.1%) switched to second-line regimens after a median (IQR) ART duration of 1.63 (0.60-3.59) years. Lost to follow-up (LTFU) occurred in 5316 (18.3%) of whom 1376 (5%) remained LTFU and alive; 4606 (15.9%) died. Cumulative second-line failure incidence was 9.8% at 6 years, more common in females, younger PLH those with lower switch CD4 cell counts. Multidisciplinary, innovative support systems are needed to improve second-line treatment outcomes, particularly those relating to modifiable risk factors.

Temporal changes in paediatric and adolescent HIV outcomes across the care continuum in Zambia: an interrupted time-series analysis

Paediatric and adolescent HIV treatment programmes in sub-Saharan Africa have rapidly expanded and evolved over the past decade. Real-world evidence of how the implementation of new policies over time has affected treatment outcomes is inadequate, but is crucial for guiding the implementation of the next phases of the HIV treatment response for children. We examined how treatment outcomes in Zambia's national paediatric and adolescent HIV treatment programmes have changed over time as new policies were implemented. We used data from Zambia's routine electronic health record to analyse children and adolescents living with HIV who were antiretroviral therapy (ART) naive between the ages of 0 and 19 years who were newly enrolled in care between Jan 1, 2011, and March 31, 2019, at 102 health facilities in Lusaka and Western provinces supported by the Centre for Infectious Disease Research in Zambia. Sociodemographic factors, clinical data, facility-level data, and visit history were obtained from the national electronic health record and laboratory systems used in routine HIV care in Zambia. We aimed to characterise the changes in the distribution of the age and sex of new enrolees over time. We used an interrupted time-series design to examine the rates of ART initiation, retention in care, time to ART initiation, and first-line ART regimens among new enrolees across different age strata as they changed over time with the adoption of new ART guidelines in 2014 and 2017. Between Jan 1, 2011, and March 31, 2019, 26 214 children and adolescents living with HIV who were ART naïve were newly enrolled at one of 102 ART facilities in two provinces in Zambia. Rates of new enrolees increased by 25-35% among children younger than 15 years over time, but by 92·3% between 2011 and 2017 among adolescents, with the largest absolute increase among adolescent girls. Rates of ART initiation increased steadily and in parallel across all age groups from before the implementation of the 2014 guidelines to after the implementation of the 2017 guidelines (<2 years, 42·4% for 2014 and 81·6% for 2017; 2 to <5 years, 39·3% for 2014 and 82·8% for 2017; 5 to <15 years, 49·2% for 2014 and 86·6% for 2017; 15 to 19 years, 52·4% for 2014 and 86·2% for 2017); median time to ART initiation went from 2-3 months to same-day initiation during this same time period. Rates of retention on ART 6 months after linkage saw much smaller improvements over time (<2 years, 35·4% for 2014 and 52·0% for 2017; 2 to <5 years, 40·2% for 2014 and 54·4% for 2017; 5 to <15 years, 46·7% for 2014 and 63·4% for 2017; 15 to 19 years, 40·1% for 2014 and 52·7% for 2017). Improvements in ART initiation occurred largely in parallel across age groups over time, despite universal treatment being implemented at different timepoints for different ages. Although the rates of ART initiation reach high levels, retention on ART was low. This analysis provides a comprehensive examination of how paediatric and adolescent outcomes have evolved over the past decade in Zambia and identifies where more targeted efforts will be needed over the next decade. National Institutes of Health.

Virological Characterization of Hepatitis B Virus Infection at a Major Gastrointestinal Clinic in Accra, Ghana

Introduction : Hepatitis B is prevalent in sub-Saharan Africa. Adverse outcomes of infection include cirrhosis and hepatocellular carcinoma with prognosis worse in endemic areas. Hepatitis B treatment guidelines recommend treatment in patientswith active chronic inflammation or liver cirrhosis to reduce risk of disease progression. However, there is as yet no national hepatitis B treatment program in Ghana. This study risk-stratifies new patients by serology and viremia at the tertiary centre in Accra.Methods : Retrospective study of new patients referred with chronic hepatitis B at the Korle-Bu Teaching Hospital, Accra. Serologic data were obtained from medical records using standard data collection form. Means, medians, linear range (±SD) were presented for continuous variables and frequencies for categorical variables.Results : Overall, 387 patients with hepatitis B were reviewed. Of the 255 patients with serology, 209 (82.0%) were HBeAg-negative. Serum ALT was elevated, &gt; 40 IU/mL, in 38.5%. HBV DNA &gt; 2,000 IU/mL in 52.7% (n = 167). ALT &gt; 40 IU/mL and HBV DNA &gt; 2,000 IU/mL in 23.3% (n = 150). Patients with ALT &gt; 40 IU/mL were more likely to have HBV DNA &gt; 2,000 IU/ml, P=0.001. In patients with liver ultrasound (n=51), liver cirrhosis and hepatocellular carcinoma were diagnosed in 8 and 9 patients respectively.Conclusions : Liver cirrhosis and hepatocellular carcinoma were evident at presentation in some patients. Furthermore, 23.3% had ALT &gt; 40 IU/mL and HBV DNA &gt; 2,000 IU/mL, associated with increased risk of liver-related complications. In achieving current hepatitis B guidelines, there is the need for a sustainable national treatment program for eligible patients in Ghana.

Costs and health impact of delayed implementation of a national hepatitis B treatment program in China.

BackgroundHepatitis B virus (HBV) infection is a leading public health problem in China. COVID-19 pandemic has interrupted the delivery of health care interventions worldwide, including HBV infection control.MethodsIn this study, we used a Markov model to quantify the costs and population health impact of HBV treatment in China for the following scenarios: 1) current practice with only 17% of treatment eligible HBV infected adults receiving antiviral treatment; 2) reaching the World Health Organization (WHO) treatment target of 80% by 2030 with a steady increase in treatment rate beginning in 2022; and 3) the effect of a 1-5-year delay in meeting the 2030 WHO treatment target. A one-way as well as a probabilistic sensitivity analysis were conducted.ResultsWithout increasing antiviral treatment for treatment eligible HBV infected adults, the life-time health care costs for the estimated 89.2 million adults living with HBV in China is US$1305 billion and 10.8 million (12%) will die from HBV-related liver disease. Increasing treatment to achieve the WHO 80% target by 2030 would save US$472 billion and prevent 3.3 million HBV-related deaths. We estimated that a 1-year delay beyond 2030 in reaching the WHO 80% treatment target would likely lead to US$55 billion increase in future health care costs, and an additional 334 000 future deaths from HBV-related liver disease or cancer.ConclusionsReaching the WHO 2030 with minimal delays would have an immense health and economic benefit. Implementing a national treatment program for HBV in China should be a key priority for policymakers.

Opioid overdose deaths and the expansion of opioid agonist treatment: a population-based prospective cohort study.

Effective policies to reduce drug-related overdoses remain a public health priority. We aimed to estimate the causal effects of a national opioid agonist treatment (OAT) program on population level drug fatalities. Population-based prospective cohort study exploiting supply driven variation in treatment uptake across cohort-age groups generated by the introduction and scale-up of a national OAT program. A Poisson difference-in-differences model with an intention-to-treat design was used to assess how treatment uptake altered the age profile of risks and infer treatment effects on drug fatalities. Norway, from 1996 through 2016. The data include a total of 5634 drug-related overdose deaths and cover the introduction of the Norwegian OAT program in 1998 and its initial growth period, reaching 12 286 ever-treated recipients by 2016. Fatal opioid-related overdoses were defined as deaths with a primary cause assigned an International Classification of Diseases 10th Revision (ICD-10) code F11, or X42, X44, X62 or X64 in combination with T40.0-T40.4. Other non-opioid related fatal overdoses were defined by a primary cause registered as F12, F14, F15, F16 or F19, or X42, X44, X62 or 64 in combination with T40.5-T40.9. An additional 887 deaths (95% credibility interval [CI] = 265-1563) would have been expected in the absence of OAT, which implies one death avoided per 111 (95% CI = 61-342) treatment-exposed person-years. At scale, the program reduced annual overdose mortality by 27% in 2016 (95% CI = 10%-41%) relative to a no-OAT counterfactual, corresponding to 99 fewer expected fatal overdoses (95% CI = 28-180) in 2016. Analysing fatal opioid-related and other drug overdoses separately found similar numbers for avoided opioid-related fatalities (921, with 95% CI = 373-1526) and no treatment effects on non-opioid related fatalities (-38, with 95% CI = -193-154). The introduction and rapid scale-up of a national opioid agonist treatment program in Norway was associated with substantial and plausibly causal reductions in drug fatalities.

Spinal muscular atrophy: epidemiology and health burden in children - a Polish national healthcare database perspective before introduction of SMA-specific treatment.

Spinal muscular atrophy (SMA) is one of the most frequent autosomal recessive neuromuscular disorders. It leads to progressive muscle weakness, premature death or permanent ventilation. Significant disability, scoliosis, severe pulmonary infections and other problems require in- and outpatient medical care. Various approaches have been used to evaluate SMA epidemiology, healthcare burden and adherence to standard of care. The recent introduction of pharmacological treatment in a large SMA population will change the course of the disease and the healthcare requirements of patients. We have used the National Health Fund database to identify children with SMA and the healthcare service they received in the pre-pharmacological treatment era. Pivotal phase II and III medical trials for nusinersen were conducted between 2013 and 2015. The National Treatment Programme of SMA patients with nusinersen in our country was started in January 2019. The year 2014 was used to evaluate incident cases. 51 new SMA cases (incidence 1:7,356) and 518 SMA patients younger than 18 were identified in 2014. 32 (6.2%) deaths were recorded, half in the first two years of life. 35 (6.8%) patients received palliative and 115 (22.2%) long-term care (including assisted ventilation). A total number of 3,057 days of hospital stay were reported. Only 65/518 (12.6%) patients did not receive publicly-funded healthcare service other than specialist or general practitioner's consultation. SMA caused significant mortality and morbidity in children. The National Health Fund database can be used to reliably record incident cases and track the care provided to paediatric SMA patients.

Pharmacokinetics and placental transfer of dolutegravir in pregnancy.

Dolutegravir is currently recommended by the WHO as the preferred first-line treatment for all people with HIV, including pregnant women. Estimates indicate that, by 2024, nearly 22 million adults in low- and middle-income countries will have transitioned to dolutegravir-based ART. It is therefore critical that there is a clear appreciation and understanding of the risks that may be associated with in utero exposure to dolutegravir. In this review we consolidate data from studies on dolutegravir and the placenta. The studies have largely focused on the pharmacokinetics and placental transfer of dolutegravir in pregnancy. These include studies on transplacental transfer of dolutegravir, ex vivo placenta perfusion models, physiologically based pharmacokinetic (PBPK) models and animal studies. The data available clearly demonstrate that placental transfer of dolutegravir occurs in moderate to high concentrations. Intracellular placental dolutegravir has been demonstrated in the placental villous tissue. There are limited data suggesting that pregnancy is associated with decreased maternal dolutegravir levels. In addition, PBPK models have great potential in predicting the passage of drugs through the placenta and further contributing towards the elucidation of fetal exposure. The animal studies available demonstrate that in utero dolutegravir exposure can be associated with neural tube defects. Taking into consideration that antiretroviral exposure may be associated with poor placental development or function and increased risk of adverse effects to the fetus, it is crucially important that these risks are evaluated, especially with the rapid scale up of dolutegravir-based ART into national treatment programmes.

Retreatment of Chronic Hepatitis C Infection: Real-World Regimens and Outcomes From National Treatment Programs in Three Low- and Middle-Income Countries.

Access to recommended second-line treatments is limited for patients who fail initial hepatitis C virus (HCV) therapy in low- and middle-income countries. Alternative regimens and associated outcomes are not well understood. Through a pooled analysis of national program data in Egypt, Georgia, and Myanmar, we observed SVR rates >90% for alternative retreatment regimens.

Management of emotionally unstable personality disorder in an urban Irish setting

AimsTo determine the prevalence of emotionally unstable personality disorder (EUPD) attending a community mental health team (CMHT) in a major Irish cityTo describe the current psychiatric care afforded to this cohort of service userMethodClinical chart review of all 328 patients attending a CMHT outpatient in an urban setting was carried out. Patients diagnosed with EUPD or displayed features of EUPD were identified. Data on the various interventions offered to this cohort of service users were collected and compared against current guidelines.ResultOut of the 328 patients actively attending the service, almost 17% (n = 55) were diagnosed with EUPD and further 6% (n = 19) were found to display features of EUPD such as emotional dysregulation, self-harming behaviour and cognitive distortions. Comorbid psychiatric disorder such as mood or anxiety spectrum disorder was diagnosed in 23% (n = 17) of this cohort. Meanwhile, 8% (n = 6) was diagnosed with addiction disorders and 5% (n = 4) was diagnosed with a comorbid personality disorder. A significant proportion of 77% (n = 57) were prescribed psychotropic medication with 51% (n = 29) being on more than one psychotropic medication. Antidepressants, antipsychotics and hypnotics were the three most common medications prescribed at the rate of 89% (n = 51), 30% (n = 17) and 28% (n = 16) respectively. A majority of 66% (n = 49) were offered intervention from a multi-disciplinary team (MDT) member with 47% (n = 23) being offered more than one type of intervention. Referrals to community mental health nurses and psychology service were the two most common interventions offered with a referral rate of 59% (n = 29) and 55% (n = 27) respectively. 28% (n = 21) of service users with EUPD or EUPD traits has had at least one hospital admission while attending the CMHT and 46% (n = 34) have been admitted to the day hospital at least once.ConclusionThe prevalence of EUPD in our outpatient sample corresponds with findings in previous studies. Standard psychiatric care is the most common option available to the majority of general adult patients with EUPD in Ireland due to the lack of any national treatment programme and scarce availability of specialised therapeutic approaches such as dialectical behavioural therapy within community mental health teams. Our CMHT will attempt to integrate mentalization-based treatment into our outpatient management of EUPD patients taking into account current clinical guidelines for management of EUPD and resources needed for training and delivering the intervention.

Employment preferences of healthcare workers in South Africa: Findings from a discrete choice experiment.

There is a maldistribution of human resources for health globally, with many Lower- and Middle-Income Countries experiencing significant shortages. We examined healthcare workers’ job preferences in South Africa to identify factors which potentially influence employment decisions. A discrete choice experiment was conducted among 855 South African healthcare workers critical to its national HIV testing and treatment programs. Job characteristics included workload, workplace culture, availability of equipment, training opportunities, sector and facility type, location, salary and benefits. Main effects analysis was conducted using fixed effects logistic regression. Interaction effects identified divergence in preferences. Heavy workload (OR = 0.78; 95% C.I. 0.74–0.83), poor workplace culture (odds ratio 0.66; 95% C.I. 0.62–0.69), insufficient availability of equipment (OR = 0.67; 95% C.I. 0.63–0.70) and infrequent training opportunities (OR = 0.75; 95% C.I. 0.71–0.80) had large, significant effects on worker preferences. An increase in salary of 20% (OR = 1.29; 95% C.I. 1.16–1.44) had a positive effect on preferences, while a salary decrease of 20% (OR = 0.55; 95% C.I. 0.49–0.60) had a strong negative effect. Benefits packages had large positive effects on preferences: respondents were twice as likely to choose a job that included medical aid, pension and housing contributions worth 40% of salary (OR = 2.06; 95% C.I. 1.87–2.26), holding all else constant. Although salary was important across all cadres, benefits packages had larger effects on job preferences than equivalent salary increases. Improving working conditions is critical to attracting and retaining appropriate health cadres responsible for the country’s HIV services, especially in the public sector and underserved, often rural, communities. Crucially, our evidence suggests that factors amenable to improvement such as workplace conditions and remuneration packages have a greater influence on healthcare workers employment decisions than employment sector or location.