Cost-utility analysis of four WHO-recommended sofosbuvir-based regimens for the treatment of chronic hepatitis C in sub-Saharan Africa

Background Although direct-acting antivirals (DAA) have become standard care for patients with chronic hepatitis C worldwide, there is no evidence for their value for money in sub-Saharan Africa. We assessed the cost-effectiveness of four sofosbuvir-based regimens recommended by the World Health Organization (WHO) in Cameroon, Côte d’Ivoire and Senegal. Methods Using modelling, we simulated chronic hepatitis C progression with and without treatment in hypothetical cohorts of patients infected with the country’s predominant genotypes (1, 2 and 4) and without other viral coinfections, history of liver complication or hepatocellular carcinoma. Using the status-quo ‘no DAA treatment’ as a comparator, we assessed four regimens: sofosbuvir-ribavirin, sofosbuvir-ledipasvir (both recommended in WHO 2016 guidelines and assessed in the TAC pilot trial conducted in Cameroon, Côte d’Ivoire and Senegal), sofosbuvir-daclatasvir and sofosbuvir-ledipasvir (two pangenotypic regimens recommended in WHO 2018 guidelines). DAA effectiveness, costs and utilities were mainly estimated using data from the TAC pilot trial. Secondary data from the literature was used to estimate disease progression probabilities with and without treatment. We considered two DAA pricing scenarios: S1) originator prices; S2) generic prices. Uncertainty was addressed using probabilistic and deterministic sensitivity analyses and cost-effectiveness acceptability curves. Results With slightly higher effectiveness and significantly lower costs, sofosbuvir/velpatasvir was the preferred DAA regimen in S1 with incremental cost-effectiveness ratios (ICERs) ranging from US$526 to US$632/QALY. At the cost-effectiveness threshold (CET) of 0.5 times the 2017 country’s per-capita gross domestic product (GDP), sofosbuvir/velpatasvir was only cost-effective in Senegal (probability > 95%). In S2 at generic prices, sofosbuvir/daclatasvir was the preferred regimen due to significantly lower costs. ICERs ranged from US$139 to US$216/QALY according to country i.e. a 95% probability of being cost-effective. Furthermore, this regimen was cost-effective (probability> 95%) for all CET higher than US$281/QALY, US$223/QALY and US$195/QALY in Cameroon, Côte d’Ivoire and Senegal, respectively, corresponding to 0.14 (Côte d’Ivoire and Senegal) and 0.2 (Cameroon) times the country’s per-capita GDP. Conclusions Generic sofosbuvir/daclatasvir is very cost-effective for treating chronic hepatitis C in sub-Saharan Africa. Large-scale use of generics and an increase in national and international funding for hepatitis C treatment must be priorities for the HCV elimination agenda

COVID-19-related attitudes, risk perceptions, preventive behaviours and economic impact in sub-Saharan African countries: Implementing a longitudinal phone-based survey protocol in rural Senegalese households

International audienceIntroduction Rural areas are considered safe havens against the increased spread of COVID-19 and associated restrictive measures, especially in contexts where public authorities are not in a position to systematically and substantially ease COVID-19-induced economic shocks. In the current sub-Saharan Africa context, still marked by uncertainty surrounding the spread of COVID-19, we present the protocol of an ongoing longitudinal study aimed at investigating COVID-19-related attitudes, risks perceptions, preventive behaviours and economic impact in rural areas in Senegal.Methods and analysis A prospective randomised longitudinal study of 600 households located in three semiurban villages and nine randomly selected rural villages in the Niakhar area (located 135 km East of Dakar). Three ad hoc phone surveys are administered to 600 heads of households, their housewives in charge of managing the household and a relative living temporarily in the household, respectively. In addition to sharing identical sets of questions on several topics (risks perceptions, attitudes to curfew, attitudes to vaccines, beliefs about COVID-19 infection), the three separate survey questionnaires also include other topics (economic impact, local preventive strategies) whose related questions differ between questionnaires. As analysing evolutions is the study's primary focus, data on all the topics covered will be collected in three waves unless the spread of COVID-19 by mid-2021 justifies extending data collection. The present article presents the study protocol and details about the implementation of the first wave of data collection which started in July 2020. The decision to wait before presenting the protocol was based on the unprecedented context the COVID-19 pandemic.Ethics and dissemination The survey's protocol was approved by the Senegalese National Ethical Committee for Research in Health (131/MSAS/CNERS/Sec) and received authorisation from both the Senegalese Ministry of Health (619/MSAS/DPRS/DR) and the French Commission on Information Technology and Liberties (CNIL 2220771). © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

On-and-off chip cooling of a Coulomb blockade thermometer down to 2.8 mK

Cooling nanoelectronic devices below 10 mK is a great challenge since thermal conductivities become very small, thus creating a pronounced sensitivity to heat leaks. Here, we overcome these difficulties by using adiabatic demagnetization of both the electronic leads and the large metallic islands of a Coulomb blockade thermometer. This reduces the external heat leak through the leads and also provides on-chip refrigeration, together cooling the thermometer down to 2.8 ± 0.1 mK. We present a thermal model which gives a good qualitative account and suggests that the main limitation is heating due to pulse tube vibrations. With better decoupling, temperatures below 1 mK should be within reach, thus opening the door for μK nanoelectronics. Reaching ultralow temperatures in electronic transport experiments can be key to novel quantum states of matter such as helical nuclear spin phases,1–3 full nuclear spin polarization,4 quantum Hall ferromagnets,4 or fragile fractional quantum Hall states.5,6 In addition, the coherence of semiconductor and superconducting qubits7–9 as well as hybrid Majorana devices10–13 could benefit from lower temperatures. With this motivation in mind, we built a parallel network of nuclear refrigerators14 to adapt the very well established technique of Adiabatic Nuclear Demagnetization (AND)15–17 for electronic transport experiments. In this approach, the concept is to cool a nanoelectronic device directly through the electronic leads, which remain effective thermal conductors also below 1 mK. Each wire is cooled by its own, separate nuclear refrigerator in the form of a large Cu plate. However, despite recent progress,18–25 it remains very challenging to cool nanostructures even below 10 mK. Due to reduced thermal coupling, these samples are extremely susceptible to heat leaks such as vibrations,25 microwave radiation,26,27 heat release,17 and electronic noise.20 Metallic Coulomb blockade thermometers (CBTs) have been established as precise and reliable electronic thermometers,18,28,29 operating down to 10 mK and slightly below.21,22,24,30 These typically consist of linear arrays of Al/AlOx/Al tunnel junctions with metallic islands in-between, consisting mainly of copper, see Fig. 1. The array divides the electronic noise per island by the number of junctions in series. This makes them less susceptible to electronic noise, but thermal conduction via Wiedemann-Franz cooling is not very effective through a series of resistive tunnel junctions. For this reason, the islands were enlarged into giant cooling fins,29 providing a huge volume for effective electron-phonon coupling and cooling through the substrate. At low temperatures, however, this eventually fails due to the very strong T5 temperature dependence of the electron phonon coupling

Gender and Drug Use Discrimination Among People Who Inject Drugs: An Intersectional Approach Using the COSINUS Cohort

Ilhame Anwar,1 Aissatou Faye,1 Jessica Pereira Gonçalves,1 Laélia Briand Madrid,1 Gwenaëlle Maradan,2 Laurence Lalanne,3,4,* Marie Jauffret-Roustide,5– 7,* Marc Auriacombe,8– 10,* Perrine Roux1 1Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l’Information Médicale, ISSPAM, Marseille, France; 2ORS PACA, Observatoire régional de la santé Provence-Alpes-Côte d’Azur, Marseille, France; 3INSERM 1114, Department of Psychiatry and Addictology, University Hospital of Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France; 4Department of Psychiatry and Addictology, University Hospital of Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France; 5CERMES3 (Inserm U988/UMR CNRS 8211/EHESS/Paris Descartes University), Paris, France; 6British Columbia Center on Substance Use, Vancouver, Canada; 7Baldy Center on Law and Social Policy, Buffalo University, New York, NY, USA; 8Univ. Bordeaux, Bordeaux, France; 9Addiction Team (Laboratoire de psychiatrie)/SANPSY, CNRS USR 3413, Bordeaux, France; 10Pôle Addictologie, CH Charles Perrens and CHU de Bordeaux, Bordeaux, France*These authors contributed equally to this workCorrespondence: Ilhame Anwar, Sciences Economiques et Sociales de la Santé et Traitement de l’Information Médicale (SESSTIM), Faculté des sciences médicales et paramédicales, 27 Bd Jean Moulin 13385 Marseille Cedex 5, Marseille, France, Email [email protected]: Injection drug use is strongly associated with stigmatization by loved ones, healthcare providers, and society in general. This stigmatization can have negative consequences on the health of people who inject drugs (PWID) and limit their access to care. Women who inject drugs face greater stigma than men because of gendered social norms and the intersectional effect between gender and drug use identities. For this analysis, we aimed to study discrimination - which is closely linked to stigmatization - experienced by PWID, considering the intersectionality between drug use discrimination and gender discrimination in the French context.Methods: We used data from the COSINUS cohort study, conducted between June 2016 and May 2019 in four French cities. We selected 427 of the 665 PWID who regularly injected drugs enrolled in COSINUS, at three months of follow-up, and performed multivariable logistic regression to identify factors associated with self-reported drug use discrimination.Results: Women comprised 20.6% of the study sample. Sixty-nine percent of the participants declared drug use discrimination and 15% gender discrimination. In the multivariable regression analysis, PWID who had hurried injection out of fear of being seen were almost twice as likely to have experienced drug use discrimination (OR [95% CI]: 1.77 [1.15, 2.74], p = 0.010). Likewise, women experiencing gender discrimination were almost three times as likely to have experienced drug use discrimination (OR [95% CI]: 2.84 [1.07,7.56], p=0.037).Conclusion: Women who inject drugs experienced gender and drug use intersectional discrimination. This could be a reason for the low attendance rates of women in healthcare settings. In addition, discrimination negatively impacted injection drug use practices (eg, hurried injection), particularly for people with unstable housing who injected in public spaces. We recommend introducing adapted services in healthcare facilities for women who inject drugs, and creating a favorable social and physical environment for all PWID in order to improve their health and access to care.Keywords: gender, injection drug use, intersectionality, discriminatio

A generalized additive model to disentangle age and diagnosis-specific cohort effects in psychological and behavioral outcomes in people living with HIV: the French cross-sectional ANRS-VESPA2 survey

International audienceBACKGROUND: Unlike their younger counterparts, some of today's older HIV patients were diagnosed before the advent of highly active antiretroviral therapy (HAART). The psychosocial and behavioral outcomes of people living with HIV (PLWH) have been widely studied, and associated factors are well known. However, their evolution both in terms of age and diagnosis-specific cohort effects is not well understood.METHODS: Data from the ANRS-VESPA2 cross-sectional survey, representative of French PLWH, were used to investigate whether psychosocial and behavioral outcomes such as quality of life, need for support and HIV status disclosure, evolve under both the influence of patients' age and diagnosis-specific cohort effects. A semi-parametric generalized additive model (GAM) was employed. The physical and mental components of health-related quality of life, the need for material and moral support, and HIV-status disclosure, constituted our outcomes.RESULTS: Non-linear diagnosis-specific cohort effects were found for physical and mental QoL and HIV-status disclosure. Overall, physical QoL was better in recently diagnosed patients than in those diagnosed in the early 1980s. An increasing influence of diagnosis-specific cohort effects between 1983 and 1995 was observed. No cohort effects were noticeable between 1996 and 2000, while an increasing influence was apparent for patients diagnosed with HIV from 2000 to 2011 (year of study). For mental QoL, the only increase was observed in participants diagnosed with HIV between 1983 and 2000. The relationship between diagnosis-specific cohort effects and HIV status disclosure was negative overall: participants diagnosed after 2000 were much less likely to disclose than those diagnosed before 1995. The effect of age was significantly associated with all outcomes, with a non-linear influence on mental QoL and with the need for material/moral support.CONCLUSIONS: Psychosocial and behavioral outcomes are complex processes which can be explained in different ways by a combination of the clinical and social contexts which PLWH are exposed to at the time of diagnosis, and by developmental characteristics. A greater understanding of these processes could inform healthcare policy-making for specific HIV generations and different HIV age groups

Impact of drug consumption rooms on non-fatal overdoses, abscesses and emergency department visits in people who inject drugs in France: results from the COSINUS cohort

International audienceBackground: The effectiveness of drug consumption rooms (DCRs) for people who inject drugs (PWID) has been demonstrated for HIV and hepatitis C virus risk practices, and access to care for substance use disorders. However, data on other health-related complications are scarce. Using data from the French COSINUS cohort, we investigated the impact of DCR exposure on non-fatal overdoses, abscesses and emergency department (ED) visits, all in the previous 6 months.Methods: COSINUS is a 12-month prospective cohort study of 665 PWID in France studying DCR effectiveness on health. We collected data from face-to-face interviews at enrolment, and at 6 and 12 months of follow-up. After adjusting for other correlates (P-value < 0.05), the impact of DCR exposure on each outcome was assessed using a two-step Heckman mixed-effects probit model, allowing us to adjust for potential non-randomization bias due to differences between DCR-exposed and DCR-unexposed participants, while taking into account the correlation between repeated measures.Results: At enrolment, 21%, 6% and 38% of the 665 participants reported overdoses, abscesses and ED visits, respectively. Multivariable models found that DCR-exposed participants were less likely to report overdoses [adjusted coefficient (95% CI): -0.47 (-0.88; -0.07), P = 0.023], abscesses [-0.74 (-1.11; -0.37), P < 0.001] and ED visits [-0.74 (-1.27; -0.20), P = 0.007].Conclusion: This is the first study to show the positive impact of DCR exposure on abscesses and ED visits, and confirms DCR effectiveness in reducing overdoses, when adjusting for potential non-randomization bias. Our findings strengthen the argument to expand DCR implementation to improve PWID injection environment and health