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Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

Background In intensive care units, patients are frequently unable to take oral drugs because of orotracheal intubation or sedation. Local Problem Adverse events occurred during the administration of drugs by feeding tube. This study assessed the impact of implementing good practice guidelines by a clinical pharmacist on the prescription and administration of drugs through feeding tubes. Methods Nonconformity of drug prescription and administration in patients with feeding tubes was assessed before and after implementation of good practice guidelines in the intensive care unit of a large teaching hospital. Data were collected from medical records and interviews with physicians and nurses using a standardized form. Assessment of prescription nonconformity included compatibility of a drug’s absorption site with the administration route. Assessment of administration nonconformity included the preparation method. Results The analysis included 288 prescriptions and 80 administrations before implementation and 385 prescriptions and 211 administrations after implementation. Prescriptions in which the drug’s absorption site was not compatible with the administration route decreased significantly after implementation (19.8% vs 7.5%, P < .01). Administration nonconformity decreased significantly in regard to crushing tablets and opening capsules (51.2% vs 4.3%, P < .01) and the solvent used (67.1% vs 3.5%, P < .01). Simultaneous mixing of drugs in the same syringe did not decrease significantly (71.2% vs 62.9%, P = .17). Conclusion Implementation of good practice guidelines by a multidisciplinary team in the intensive care unit significantly improved practices for administering crushed, opened, and dissolved oral forms of drugs by feeding tube.

BACKGROUND Mobile health applications (apps) are increasing in interest for enhancing patient self-management in rheumatology. Inflammatory arthritis (IA) represents painful chronic conditions impairing quality of life, for which disease-modifying anti-rheumatic drugs (DMARDs) are used to control disease activity and reduce functional disability. DMARDs are increasing in availability (>15 DMARDs in France) and have a wide variety of targets and modes of administration, but their use is associated with risk of adverse effects such as infections. Few apps in rheumatology have been developed with the involvement of patients and health professionals (HPs) and are actually used by patients. Patient education, including e-education, is advocated to improve patients’ autonomy over their own health. Apps may be appropriate tools for self-managing medications, problem-solving or care coordination. OBJECTIVE To develop a self-management mobile app for patients with IA by using a user-centred step-by-step approach and assess its real-life use. METHODS The development was promoted by the French Society of Rheumatology. A mixed-method qualitative–quantitative study including 42 and 344 patients, respectively, identified the impact of IA on daily life, patients’ treatments practices, social relationships, use of health apps and potential use needs. A multidisciplinary team including 7 rheumatologists, 3 patient association representatives and 5 members of a digital company developed the first version of the app via face-to-face meetings and patient feedback during the process. After launch, 2 in-depth users’ tests including 13 patients and 3 rheumatologists led to the app’s current version. The number of app installations, current users, and user requests were collected, as were scores and comments at stores. RESULTS The qualitative study revealed needs for information and counselling, development of a HP–patient partnership, development of skills to cope with daily life and risk situations with treatment aids; 86.8% participants in the quantitative study would be ready to use an app primarily on their rheumatologist’s recommendation. Six functionalities were implemented: a safety checklist before treatment administration, aids in daily life situations, treatment reminders, global well-being self-assessment, periodic counselling messages, and a diary. Aids for risk situations were based on the French academic recommendations for DMARD management, drug leaflets and websites of national health authorities. The app is free, with no personal data collection. The presentation is a “companion” called Hiboot (“owl” in English). Hiboot was installed 20,500 times from 2017 to 2020, with 4300 regular current users and still-increasing usage curves. Overall, 18,000 requests on treatment self-management were identified over an 8-month period in 2020. Scores were 4.4/5 stars at Android and iOS stores. CONCLUSIONS Hiboot is a free self-management app for patients with inflammatory arthritis developed by a step-by-step process including patients and HPs. The number of current users is substantial. Further evaluation of the Hiboot benefit is needed.

A chronic disease management model of care (Empower Health) was launched in rural and urban areas of Ghana and Kenya in 2018. The goal was to improve disease awareness, reduce the burden of disease, and improve the clinical effectiveness and efficiency of managing hypertension. Leveraging the model, clinicians provide patients with tailored management plans. Patients accessed regular blood pressure checks at home, at the clinic, or at community-partner locations where they received real-time feedback. On the mobile application, clinicians viewed patient data, provided direct patient feedback, and wrote electronic prescriptions accessible through participating pharmacies. To date, 1266 patients had been enrolled in the "real-world" implementation cohort and followed for an average of 351 ± 133 days across 5 facilities. Average baseline systolic blood pressure (SBP) was 145 ± 21 mmHg in the overall cohort and 159 ± 16 mmHg in the subgroup with uncontrolled hypertension (n = 743) as defined by baseline SBP ≥ 140 mmHg. SBP decreased significantly through 12 months in both the overall cohort (-9.4 mmHg, p .001) and in the uncontrolled subgroup (-17.6 mmHg, p .001). The proportion patients with controlled pressure increased from 46% at baseline to 77% at 12 months (p .001). In summary, a new chronic disease management model of care improved and sustained blood pressure control to 12 months, especially in those with elevated blood pressure at enrollment.

Ruxolitinib is a Janus Kinase inhibitor currently approved for the treatment of myelofibrosis. It is also a promising drug for the treatment of skin and infectious diseases. In terms of pharmaceutical stability, although ruxolitinib has been established as being sensitive to light, no data on photodegradation processes are available to date, while these may be useful for quality risk management and any potential development of other pharmaceutical forms for other routes of administration. One way to partially fill this gap was to carry out a study that combines a consistent determination of the most sensitive sites of the molecule to photolysis through theoretical calculations based on functional density, with the identification of the main photodegradation products obtained after forced degradation. This integrated approach has shown converging results describing the mechanisms based on photo-oxidation that can lead to the opening of the pyrrole ring. Having access to the structure of the degradation products and intermediates then made it possible to carry out an in silico evaluation of their potential mutagenicity and it appears that some of them feature alert structures.

Background Mobile health applications (apps) are increasing in interest for enhancing patient self-management in rheumatology. However, few have been developed with the involvement of patients and health professionals and actually used by patients. Objective To develop and implement a mobile app for safety, self-assessment and medication adherence for patients with inflammatory arthritis treated with disease modifying anti-rheumatic drugs (DMARDs) and assess its real-life use. Methods A mixed qualitative-quantitative study including 42 and 344 patients, respectively, identified patients’ treatment practices and their use of health apps in general and their needs in terms of content and potential use. A multidisciplinary team including 7 rheumatologists, 3 patient association representatives and 4 members of a digital company developed the first version of the app with face-to-face meetings and patient feedback during the process. After the launch of the app, users’ feedback assessment included 7 patients and 3 rheumatologists. The number of app installations, current users, users’ requests and functionalities used were collected. Results Preliminary studies indicated numerous safety issues and needs for counselling, leading to the 6 functionalities of the app HIBOOT (OWL in English): a safety checklist before treatment administration, aid in daily life situations related to self-management and safety, treatment reminders, global well-being self-assessment, periodic counselling messages, and a diary to note comments and appointments. The app is free, with no personal data collection. The presentation is a friendly companion that interacts with the user. The content was based on the French recommendations for DMARD management, drug leaflets and public national health websites. HIBOOT was installed 20,500 times from 2017 to 2020, with 4300 regular current users and still increasing usage curves. The checklist, diary and queries on daily life situations were the most used functionalities. Overall, 18,000 requests were identified for information on safety or other patient matters over a 8-month period in 2020. Scores were 4.4/5 stars at Android and iOS stores. Conclusion HIBOOT is a free app for patients with inflammatory arthritis that was developed with a preliminary qualitative–quantitative study including patients during the process and has scientifically validated content. The number of current users is substantial. Future evaluation of the HIBOOT benefit is needed.

International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.

ObjectivesThe incidence of cardiovascular diseases is increasing and there is a growing need to provide access to quality cardio drugs in Africa. In the SEVEN study, we analysed 1530 cardiovascular drug samples randomly collected from 10 African countries. By that time, of the seven drugs products analysed, only those containing amlodipine and captopril had very low assay values with active substance contents that could be less than 75% of those expected. In this article we investigate complementary aspects of the amlodipine and captopril samples so to explain the previously observed low assays for these two drugs.DesignPost hoc analysis of the captopril and amlodipine drugs samples and their packages collected in the context of the SEVEN study.Setting10 countries were concerned: Benin, Burkina Faso, Congo, Democratic Republic of the Congo, Guinea, Côte d’Ivoire, Mauritania, Niger, Senegal and Togo.ParticipantsLocal scientists and hospital practitioners collected the drug samples in the 10 African countries.Outcome measuresThe drug amount and the relative amounts of drug impurities, as well as the main compounds of the drugs packaging, were analysed.ResultsIdentification of the blister packaging of the samples led to separate both amlodipine and captopril drug samples in two groups. Mann Whitney’s bilateral test showed a significant difference (pConclusionBased on these results, particular attention should be paid to the materials and types of packaging used in order to minimise the lack of control over the exposures and drug circuits present in these different countries.

Summary Background Sub-Saharan Africa is experiencing a rising burden of hypertension. Antihypertensive medications and diet are the cornerstone of effective hypertension control. Aims To assess adherence to medication and salt restriction in 12 sub-Saharan countries, and to study the relationship between adherence and blood pressure control in patients with hypertension. Methods We conducted a cross-sectional survey in urban clinics in twelve sub-Saharan countries. Data were collected on demographics, treatment and adequacy of blood pressure control in patients with hypertension attending the clinics. Adherence was assessed by questionnaires completed by the patients. Hypertension grades were defined according to European Society of Cardiology guidelines. Association between adherence and blood pressure control was investigated using multilevel logistic regression analysis, adjusting for age, sex and country. Results Among the 2198 patients, 77.4% had uncontrolled blood pressure, 34.0% were poorly adherent to salt restriction, 64.4% were poorly adherent to medication and 24.6% were poorly adherent to both. Poor adherence to salt restriction (odds ratio [OR] 1.33, 95% confidence interval [CI] 1.03–1.72), medication (OR 1.56, 95% CI 1.25–1.93) or both (OR 1.91 1.39–2.66) was related to uncontrolled blood pressure. Moreover, poor adherence to both medication and salt restriction was related to a 1.52-fold (95% CI 1.04–2.22), 1.8-fold (95% CI 1.22–2.65) and 3.08-fold (95% CI 2.02–4.69) increased likelihood of hypertension grade 1, 2 and 3, respectively. Conclusions High levels of poor adherence to salt restriction and medication were noted in this urban sub-Saharan study; both were significantly associated with uncontrolled blood pressure, representing major opportunities for intervention to improve hypertension control in sub-Saharan Africa.

International audience

Resume Introduction La securisation du circuit du medicament represente aujourd’hui une preoccupation majeure pour les etablissements de sante. L’objectif de ce travail est de realiser un etat des lieux a l’hopital de la detention des medicaments hors dotations dument autorisees, dans les postes de soins et les chariots de distribution de medicaments et d’evaluer la qualite de ce stockage. Materiels et methodes Un audit a ete realise du 25 mars au 10 juin 2015, au sein des hopitaux universitaires de l’Est parisien (1949 lits). Un unique auditeur a controle les postes de soins et les chariots de distribution de medicaments selon une methode standardisee a l’aide de grilles de recueil. Resultats Cent sept postes de soins et 55 chariots ont ete audites sur la periode de recueil. Des medicaments etaient stockes dans 100 % (107/107) des postes de soins audites. Le pourcentage global de non-conformite dans les postes de soins s’elevait a 36 % [0–67 %] et 20 % [5–36 %] de non-conformites ont ete retrouvees dans les chariots audites. Discussion-conclusion Dans les services de soins, le stockage des medicaments en dehors de leur reserve principale et au plus proche de l’administration au patient est une pratique courante mais ne respecte pas les regles de conformite etablies par les etablissements de sante.

Objective Hypertension results in more deaths than any other risk factor and has been on the rise in sub-Saharan Africa over the past few decades. Generic drugs have helped improve accessibility and affordability of antihypertensive therapy in developing countries. However, assessment of quality standards of these products is important. We performed a quality assessment of five commonly used antihypertensive generic drugs in 10 sub-Saharan African countries and studied the impact of price on quality. Methods Drug samples were prospectively collected using standardized methods between 2012 and 2014. We developed a validated reversed-phase liquid chromatography with tandem mass spectrometry method to accurately quantify the active ingredient in a certified public laboratory. Quality was defined based on the percentage ratio of measured to expected dosage of active ingredient. Results A total of 1185 samples were assessed, of which 70.0% were generic (n = 830). Among the generic drugs, the percentage of poor-quality drugs was 24.3% (n = 202/830). The percentage ratio of measured to expected dosage of active ingredient ranged from 49.2 to 111.3%; the majority (81.7%) of the poor-quality samples had insufficient quantity of the active ingredient. Moreover, poor quality was not associated with purchase price of the drug. Conclusion In this study from 10 sub-Saharan African countries, nearly one-quarter of the available generic antihypertensive drugs were found to be of poor quality. Concerted measures to improve the quality of antihypertensive drugs could lead to major improvements in hypertension control with attendant reduction of its deleterious consequences in low-income and middle-income countries.

Resume Introduction L’aerosoltherapie par nebulisation est un mode d’administration des medicaments particulierement efficace mais dont la mise en œuvre est complexe. Des recommandations de bonnes pratiques existent mais peu de donnees sont disponibles quant a leur reelle application. L’objectif de l’enquete est de faire un etat des lieux des connaissances et des pratiques des soignants en termes de nebulisation. Methodes Deux auto-questionnaires destines aux infirmiers ou aux medecins ont ete elabores par un groupe de travail et presentes aux soignants des hopitaux universitaires de l’Est Parisien. Un interne en pharmacie a analyse les resultats a l’aide d’un outil de sondage en ligne. Resultats Au total, 481 auto-questionnaires ont ete completes (67 % d’infirmiers et 33 % de medecins). Seulement 241/480 soignants (50 %) savent que les medicaments injectables ne sont pas tous nebulisables, 94/422 soignants (22 %) utilisent systematiquement l’oxygene comme fluide medical et 239/311 infirmiers (77 %) pensent qu’ils peuvent re-utiliser un nebuliseur a usage unique. Conclusions Cette enquete a mis en evidence un manque de connaissances et des mesusages de la part de nombreux soignants. Un guide pratique de la nebulisation a ete elabore pour harmoniser les pratiques dans le groupe hospitalier et aider les soignants a suivre les recommandations.

International audience

Background High Blood Pressure is the worldwide leading global burden of disease risk factor. In Sub-Saharan Africa, the number of adults with raised blood pressure has alarmingly increased from 0.59 to 1.13 billion between 1975 and 2015. Blood pressure-lowering medicines are cornerstone of cardiovascular risk reduction. Data on management of anti-hypertensive drugs in sub-Saharan Africa are squarce. Purpose Our study aims to describe antihypertensive drugs strategies in Africa. Methods We conducted a cross-sectional survey in urban clinics during outpatient consultation specialized in hypertension cardiology departments of 29 medical centers from 17 cities across 12 African countries (Benin, Cameroon, Congo, Democratic Republic of Congo, Gabon, Guinea, Ivory Coast, Mauritania, Mozambic, Niger, Senegal, Togo). Data were collected on demographics, treatment and standardized BP measures were made among the hypertensive patients attending the clinics. Country income was retrieved from the World Bank database. All analyses were performed through scripts developed in the R software (3.4.1 (2017–06–30)). Results A total of 2198 hypertensive patients (58.4±11.8 years; 39.9% male) were included. Among whom 2123 (96.6%) had at least one antihypertensive drug. Overall, 30.8% (n=653) received monotherapy and calcium-channel blockers (49.6%) were the most common monotherapy prescribed follow by diuretics (18.7%). Two-drug strategies were prescribed for 927 patients (43.6%). Diuretics and Angiotensin-converting enzyme inhibitors was the combination most frequently prescribed (33.7%). Combination of three drugs or more was used in 25.6% (n=543) of patients. The proportion of drugs strategies differed significantly according to countries (p Antihypertensive strategies by country Conclusion Our study described antihypertensive drugs use across 12 sub-Saharan countries, and identified disparities specific to the income context. Inequity in access to drugs combination is a serious barrier to tackle the burden of hypertension in Africa.

Background Cardiovascular diseases are rapidly growing epidemic in Sub-Saharan Africa. Unlike other regions of the world, death rates due to hypertension are greater for women than men in Africa. Scarce data were available on factors associated with gender in cardiovascular risk factors and complications in Sub-Saharan Africa. Purpose To assess gender differences in cardiovascular risk factors pattern in patients with hypertension in 12 Sub-Saharan countries. Methods We conducted a cross-sectional survey in urban clinics of twelve countries in Africa. Data were collected on demographics, treatment and standardized BP measures were made among the hypertensive patients attending the clinics. BP control was defined as BP Results The EIGHT study enrolled 2198 patients with hypertension in 12 sub-Saharan countries between January 2014 and November 2015. The proportion of women (60,2%) was higher than men and varied significantly according to countries (p Compared to men, women had a higher rate of family cardiovascular background (79% vs 70%, for women and men respectively) (p However, African women had less cardiovascular complications than men (39% vs 52.4%) (p Conclusions Our study highlighted gender differences in cardiovascular risk factors pattern in Sub-Saharan hypertensive patients. Tailoring medical (public health) programs to improve cardiovascular disease prevention that take into women characteristics may enhance their effectiveness.

Background Epidemiological transition in the developing world has resulted in a shift from infectious to non-communicable diseases as leading causes of morbidity and mortality, cardiovascular (CV) disease (CVD) is the first cause of death in Africa. However, data regarding the characteristic of patients with CVD are scarce, especially in Sub-Saharan Africa. Purpose We built an observatory recording the characteristics of all patients admitted to hospital in CV departments and hospital care components in Sub-Saharan Africa (FEBRUARY Study). Methods We conducted a transversal and longitudinal study in CV departments of 29 hospitals from 14 African countries. FEBRUARY study was designed by a multidisciplinary collaborative team of epidemiologists, pharmacists and cardiologists from Africa and France. This ongoing observatory included all patients admitted in hospitalization during the month of February every year since 2016 and will continue every year. Data including socio-demographic and clinical characteristics, causes of admission, clinical, biological, complementary examinations, treatments, length of stay and discharge diagnosis were collected by the investigating physicians. Results Overall 2680 patients were admitted to hospital in February 2016 (n=736), 2017 (n=967), and 2018 (n=987) in CV departments from 14 countries: Benin, Burkina Faso, Burundi, Cameroon, Congo, Côte d'Ivoire, Gabon, Guinea, Mali, Niger, Dem. Rep of The Congo, Senegal, Togo and Sudan (figure). Men represented 58,8%. Mean age of age was 54 years and Women 52 years. The mean length of stay was 9 days, and death rate 10,1%. The main cause of admission was cardiac failure (40,3%) followed by acute coronary syndrome (10.1%) and stroke (9,3%). Among CV risk factors, high blood pressure, sedentary behavior, diabetes, active tobacco consumption and dyslipidemia were present in 46%, 19%, 13%, 11% and 6% of patients, respectively. In a longitudinal analysis, hospital admission due coronary syndrome increased from 7% in 2016 to 10.5% in 2018 (p for trend = 0.03). Length of hospital stay and rate of hospital death remain stable. Hospitalizations by country (FEBRUARY) Conclusion The FEBRUARY observatory is an important tool to describe cardiovascular characteristics of patients in transversal analysis, but also the longitudinal evolution over the coming years in Sub-Saharan Africa.

Background Over the past few decades, the prevalence of hypertension has dramatically increased in Sub-Saharan Africa. Poor adherence has been identified as a major cause of failure to control hypertension. Scarce data are available in Africa. Purpose We assessed adherence to medication and identified socioeconomics, clinical and treatment factors associated with low adherence among hypertensive patients in 12 sub-Saharan African countries. Methods We conducted a cross-sectional survey in urban clinics of both low and middle income countries. Data were collected by physicians on demographics, treatment and clinical data among hypertensive patients attending the clinics. Adherence was assessed by questionnaires completed by the patients. Factors associated with low adherence were investigated using logistic regression with a random effect on countries. Results There were 2198 individuals from 12 countries enrolled in the study. Overall, 678 (30.8%), 738 (33.6%), 782 (35.6%) participants had respectively low, medium and high adherence to antihypertensive medication. Multivariate analysis showed that the use of traditional medicine (OR: 2.28, 95% CI [1.79–2.90]) and individual wealth index (low vs. high wealth: OR: 1.86, 95% CI [1.35–2.56] and middle vs. high wealth: OR: 1.42, 95% CI [1.11–1.81]) were significantly and independently associated with poor adherence to medication. In stratified analysis, these differences in adherence to medication according to individual wealth index were observed in low-income countries (p Conclusion This study revealed the high frequency of poor adherence in African patients and the associated factors. These findings should be useful for tailoring future programs to tackle hypertension in low income countries that are better adapted to patients, with a potential associated enhancement of their effectiveness. Figure 1. Percentage of patients according to their adherence level by patient wealth index stratified by country-level income.

Background: Nonspecific subjective adverse effects (NSAE), usually considered as related to a nocebo effect (NE), have been identified as a barrier to the acceptability of switches from biologic originators (BO) to biosimilars (BS). Objectives: To assess the efficacy of a multidisciplinary team intervention to reduce the NE among inflammatory arthritis (IA) patients concerned by systematic switch from originator Infliximab (OI) to the biosimilar infliximab (BI) SB2. Methods: The intervention was part of a multidisciplinary patient education (PE) program. It was developed in 4 steps. Step 1: we conducted first semi-directive qualitative interviews with 5 patients treated by other intravenous (IV) biologics. Interviews showed: fears about efficacy and tolerability of BSs, need for information (particularly on the difference between BSs and generics), importance of sharing their experience of adverse effects (AE) with health practitioners (HP), and having the opportunity to switch back. The wish to discuss the nurses’ own experience of BSs was prominent. Step 2: a meeting with the multidisciplinary team (3 rheumatologists, 1 resident, 1 pharmacist, 3 nurses, 1 peer-patient from a patient’s association) was set up for designing the intervention based on the interviews, on non-systematic literature review about switches and on patients’ perspective regarding NE. Step 3: Consensual agreement on the intervention and the chosen pieces of language to be used by all HPs. The intervention included written and oral information by the nurses; nurse-led PE; if necessary, distribution of an informative leaflet made by the team. Step 4: Implementation of the intervention. The rheumatologist had the entire appreciation for discontinuing the BS or not. Inclusion criteria were all IA patients treated with OI. The primary outcome was SB2 retention rate (RT) at 34 weeks, secondary outcomes were the number of NSAEs leading to SB2 discontinuation; the comparison of the RT and NSAE rate of the cohort with 1) RT and NSAEs rate of a systematic switch from another Infliximab BS (CT-P13) to SB2 made at the same period in the same rheumatology department 2) RT and NSAEs rate of switches in other published European cohorts (1,2,3). Results: Fourty-five patients were included from March 12th, 2018 to May 25 th, 2018, median follow up was 34 weeks, 17 rheumatoid arthritis (RA), 23 spondyloarthritis (SpA) and 5 psoriatic arthritis (PSA) patients were included. Mean OI duration before switch was 9.4 years. The switch RT from OI to SB was 41/45 (91,2%) and NSAE (1/45). RT was significantly higher than in other European cohorts (p Conclusion: An intervention based on a multidisciplinary patient education team where nurses have a prominent role is effective in reducing the NE when switching from the originator infliximab to its biosimilar. Disclosure of Interests: None declared

Summary Background Medication reconciliation is a powerful formal process to decrease medication errors, but it has proved to be complex and time consuming. Aims To describe the frequency and types of medication discrepancies (between previous treatment and medication order at admission), and to identify predictors of unintentional medication discrepancies (UMDs). Methods This interventional study was carried out in the cardiology department of a French teaching hospital. Medication reconciliation was conducted at admission to the cardiology department over 1 month in 2016 by trained pharmacists for: (1) determination of best possible medication history using multiple sources; (2) comparison with the patient's admission medication order and identification of discrepancies; and (3) classification of discrepancies (intentional/unintentional) with the physician. Associations between UMDs and various factors were examined. Results Overall, 100 patients were included (mean age 67.6 ± 16.7 years; 56 men). The reconciliation process identified 544 drug discrepancies, 77 of which were UMDs; these occurred in 42 patients. The most common UMD type was omission (70.1%). Inability to speak French (P = 0.007), low educational level (P = 0.004), admission to a non-intensive care unit (P = 0.019), two or more co-morbidities (P = 0.001) and eight or more drugs on the admission order (P = 0.004) were significantly associated with UMDs. Educational level remained significantly and independently associated with UMDs in a multivariable analysis after adjustment for factors that were statistically significant in the univariate analysis. Conclusions This study highlights the high risk of medication discrepancies and the factors associated with UMDs. Our results allowed us to identify patients who should receive priority medication reconciliation in a cardiology department.

Background It is thought that low-income countries are undergoing an epidemiological transition from infectious to non-communicable diseases; however, this phenomenon is yet to be examined with long-term data on morbidity. Methods We performed a prospective evaluation of all emergency medical consultations at a major emergency service provider in Dakar, Senegal from 2005 to 2014. Using standardised definitions, the primary diagnosis for each consultation was classified using the International Classification of Diseases-10 and then broadly categorised as ‘infectious’, ‘non-communicable’ and ‘other’ diseases. Morbidity rates for each year in the 10-year observation period were plotted to depict the epidemiological transition over time. To quantify the yearly rate ratios of non-communicable over infectious diagnosis, we used a generalised Poisson mixed model. Results Complete data were obtained from 49 702 visits by African patients. The mean age was 36.5±23.2 and 34.8±24.3 years for women and men, respectively. Overall, infections accounted for 46.3% and 42.9% and non-communicable conditions 32.2% and 40.1% of consultations in women and men, respectively. Consultation for non-communicable compared with infectious conditions increased by 7% every year (95% CI: 5% to 9%; p

Background:Biologic disease-modifying anti-rheumatic drug (bDMARDs) and JAK inhibitors (JAKi) may lead to an increased risk of infections, which could be prevented by enhancing patients’ safety skills (ref). We developed a self-administered questionnaire (BioSecure1, ref) in 2013 to assess the patients’ safety skills (Table 1). Following the appearance of new bDMARDs and JAKi and new information on safety, this questionnaire needed updating.Table 1.Nine domains of core safety skills and number of corresponding questions in BioSecure questionnaires.Domain of competenceBioSecure1BioSecure2General knowledge42Dealing with infectious symptoms and fever1011Dealing with other infectious symptoms44Dealing with injuries, preventing infectious complications, vaccinations88Dental hygiene, preventing infectious complications, information to share with the dentist22Planning surgery, information to share with the surgeon/anesthesiologist77Planning child conception21Communication: who to contact?22Subcutaneous treatments: cold chain/cold storage, subcutaneous injection techniques30Objectives:To update the BioSecure questionnaire assessing patients’ safety skillsMethods:Four steps by a 10 participants multidisciplinary steering committee. Step1: critical analysis of content and formulations of BioSecure1 on the basis of i) the participants’ own experience of the questionnaire use in current practice (5/10 participants) or research (6/10 participants) ii) assessment of BioSecure1 consistency with current guidelines for management of targeted drugs. Step2: development of a first updated version by a core group of 10 persons. Step3: comments by an extended panel of rheumatology teams interested in therapeutic patient education (TPE). Step4: testing of the final version (Biosecure2) by ten patients through cognitive debriefing.Results:In total, 10 rheumatologists, 6 rheumatology nurses, 1 pharmacist and 1 patient from a patient association participated. Inadequate formulations were reported regarding some situations for which recommendations had the most shifted since Biosecure1 development such as planning pregnancy, remission management and prevention measures before surgery. Features of some infectious conditions were clarified; barriers measures against infection and complications such as sigmoiditis and Herpes Zoster infection were added. BioSecure2 continues to assess the 9 domains of core safety skills (Table 1). The questionnaire was shortened to 50 items (mean filling in time is 10 minutes) with a good understanding and scoring was simplified (mean scoring time 3.5 minutes).Conclusion:BioSecure2 represents an updated outcome measure to evaluate the patient’s skills to prevent adverse events with targeted therapies. This questionnaire can be useful in the context of patient-health professional communication, and as a tool to measure TPE on safety issues.References:[1]Gossec et al, Joint Bone Spine. 2013;80:471–476Disclosure of Interests:None declared

Umifenovir is an antiviral drug approved in China and Russia for the treatment of influenza. The available dosage form consists of capsules marketed under the brand name Arbidol®. Due to its broad spectrum, umifenovir may also be used in other viral contexts, alone or combined with other antiviral drugs. Although knowledge of umifenovir intrinsic stability may be useful for any potential development of other pharmaceutical forms for other routes of administration and for quality risk management, no data regarding this matter is available to date. In this study, the exploration of the molecule's behaviour under hydrolytic, oxidative and photolytic conditions was carried out experimentally and supported by density functional theory (DFT) studies. It comes out that umifenovir is sensitive to these stress conditions giving rise to 6 structurally characterized degradation products. The one-electron oxidation process produced on the sulphur atom is probably the main cause of umifenovir degradation with reference to the structures of the degradation products formed and the DFT data.

Background:Nonspecific subjective adverse effects and symptoms (NSAE/NSS), usually considered as related to a nocebo effect (NE), have been identified as a barrier to the acceptability of switches from biologic originators (BO) to biosimilars (BS) in rheumatology. A multidisciplinary team intervention with a prominent role of nurses has provided a reduction of the NE assessed in the short-term during a systematic switch from originator Infliximab (OI) to the biosimilar infliximab SB2 (ref.1).Objectives:To assess the intervention outcomes after one-year follow up in comparison with a historical cohort.Methods:The intervention was developed after a literature search and semi-directive interviews of patients, and included consensual communication towards patients, with a prominent role of nurses (Ref.1). All patients with chronic inflammatory rheumatic diseases (CIRD) treated by OI were included and followed-up in routine care. The outcomes were I) SB2 retention rate (RR) II) SB2 discontinuation rate due to a presumed NE, defined as lack of efficacy with no objective criteria for increased inflammation or non-objective and non-specific adverse event, either occurring after the switch and disappearing after back-switch or change of biologic. Criteria for NSAE/NSS in the historical cohort were the same lack of efficacy or subjective adverse events and disappearance after change of biologic BD. Medium-term (12 months) SB2 outcomes were assessed and compared with I) the data obtained in the short-term (34 weeks) II) the data from an historical cohort of CIRD patients treated by OI in the same rheumatology department, using Kaplan-Meier survival curve.Results:Forty-five patients were prospectively included for the switch from March 2018 to August 2018: 17 with rheumatoid arthritis (RA), 28 with spondylarthritis (SpA); 55% were women, mean age was 53.2 (SD: 2,1), and mean time under OI was 113.5 (SD9.3). For the historical cohort, the 52 patients treated with OI between December 2016 and January 2017 were included and their data collected at baseline and one year. Fifty-nine percent were women, mean age at inclusion was 50.25 (1.2), and mean time under OI was 94.8 (9.4).SB2 RR did not differ from the OI RR in the historical cohort: 91.2% and 96.2% respectively at 34 weeks (p = 0.41); 84.4% and 88.5% respectively at 12 months (p = 0.52) (figure 1). The SB2 RR was significantly higher than in three other European cohorts at 34 weeks (mean RR 73.6%, pSB2 and OI discontinuations due to NSAE/NSS at 34 weeks were 2,2 % and 1.9% respectively; at 12 months 6,6% and 1.9% respectively (p= 0.6).Conclusion:An intervention based on a tailored communication with a prominent role of nurses was effective in reducing the NE when switching from OI to SB2 in the short term, compared with an historical cohort and other European cohorts. The one-year follow-up showed no statistical difference in RR or NE compared with our historical cohort. The present study shows that appropriate interventions may be developed to improve the outcome of switches to biosimilars.Figure 1:Treatment withdrawal free survival curves (SB2 in switched cohort and OI in historical cohort).Kaplan Meir survival curves. Comparison with Log-Rank test between OI to SB2 cohort and historical OI cohort, p = 0.520. OI : original infliximab.References:[1] Petit J. Ann Rheum Dis, volume 78, supplement 2, year 2019, page A1447[2] Glintborg B. et al. Ann Rheum Dis 2017;76:1426–31.[3] Nikiphorou E. et al. Expert Opin Biol Ther 2015;15:1677–83.[4] Boone NW. et al. Eur J Clin Pharmacol 2018;:1–7.Acknowledgments:Dr Margaux Boisson Service de rhumatologie du Professeur Kahan, Hôpital Cochin, APHP.Disclosure of Interests:Juliette Petit: None declared, Marie Antignac: None declared, Karine Louati: None declared, Sandra Desouches: None declared, Nathalie DEPARIS: None declared, Regine Baratto: None declared, Rosemarie POILVERD: None declared, Sylvie Dartout: None declared, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Catherine Beauvais Speakers bureau: Abbvie, MSD, Roche, UCB, Mylan, Sanofi

Introduction: Systemic hypertension is a rapidly growing epidemic in Sub-Saharan Africa. Adequacy of blood pressure(BP) control and the factors influencing it, especially the role of socio-economic status(SES) have not been well studied in this part of the world. Hypothesis: We therefore aimed to quantify the association of SES both at the individual and at the country level with BP control in Sub-Saharan Africa. Methods: We conducted a cross-sectional survey in urban clinics of twelve countries, both low-income and middle-income, in Sub-Saharan Africa. Data were collected on demographics, treatment and standardized BP measures were made among the hypertensive patients attending the clinics. BP control was defined as BP Results: A total of 2198 hypertensive patients (58.4±11.8years; 39.9% male) were included, of whom 1017(46.3%) were from low-income and 1181(53.7%) from middle-income countries. Individual wealth level was low, mid and high in 376(17.6%), 1053(49.2%) and 713(33.3%) patients respectively. Uncontrolled hypertension was present in 1692 patients(77.4%) including 1044(47.7%) with ≥grade 2 hypertension. The proportion of uncontrolled hypertension progressively increased with decreasing level of patient individual wealth, respectively 72.8%, 79.3% and 81.8%(p for trend Conclusions: Low individual wealth was significantly associated with poor hypertension control, especially in low-income countries. Strategies for hypertension control in Sub-Saharan Africa should especially focus on people in the lowest individual wealth groups who also reside in low-income countries.

Background In an intensive care unit (ICU), patients are frequently unable to take oral tablets and capsules due to invasive ventilation or sedation. Therefore medications are administered by nasogastric tube or jejunostomy. Moreover, it is to be expected that massive resection of the gastrointestinal tract will have consequences on the absorption of orally administered medication. Few data or guidelines are available to help physicians and nurses to prescribe and administer drugs to these patients. Purpose To assess prescriptions and administrations of oral medications through jejunostomy or the nasogastric tube in surgical ICU. Material and methods We conducted a prospective descriptive study between January and February 2017 among patients with stomy, or nasogastric tube and oral medications prescriptions. Medical data (type of surgical resection), prescription data (drugs) and administration data (modalities of preparation and administration) were collected in medical files and by nurses’ interviews by a clinical pharmacist student. Conformity of drugs administrations were assessed regarding preparation solvent, lack of simultaneous mix in the same syringe, administration by nasogastric tube or opening of capsules allowed. Results Overall, 283 medications were studied for patients presenting an enteral feeding tube or a jejunostomy. Finally, nurses were interrogated about their administration practices for 82 medications to describe the usual process. Concerning the prescription, 18.3% (52/283) of the oral medications were prescribed without indications about specific administration routes (stomy, nasogastric tube or other) when it was necessary and considerations for the digestive resection. Modalities of drugs preparation (solvent) were never prescribed. Regarding administration, habits are very different according to nurses, medications were mainly solved before administration (99%, n=82/83), into sodium bicarbonate (98%, n=81/82). Within those medications, 39% (32/82) were simultaneously administered in the same syringe that was exposed to potential physico-chemical interactions, and could induce reduced efficiency or toxic metabolites. After analysis, 69.5% (n=57/82) of drugs administrations were found to be improper. Conclusion This study highlights the importance of clear guidelines. After the survey, the pharmacists’ team propose administration guidelines. Hence, a pharmacist analyses orders, gives advice via a new individual summary sheet completed according to the patient’s gastrointestinal tract resection, examines the possibility of mashing the tablet or opening the capsules and available alternatives. No conflict of interest

BACKGROUND: Sub-Saharan Africa is experiencing a rising burden of hypertension. Antihypertensive medications and salt-restriction diet are the cornerstone of effective hypertension control. PURPOSE: We therefore, assessed adherence to medication and salt restriction in 12 sub-Saharan countries and studied their relationship with blood pressure (BP) control among hypertensive patients. MATERIAL AND METHODS: We conducted a cross-sectional survey in urban clinics of 12 sub-Saharan countries (Benin, Democratic Republic of Congo, Guinea, Mozambique, Niger, Togo, Cameroon, Congo (Brazzaville), Gabon, Côte d’Ivoire, Mauritania, Senegal). Data collected on demographics, treatment and standardised BP measures were made among the hypertensive patients attending the clinics. BP control was defined as BP

Objectives Definitive diagnosis of invasive candidiasis (IC) may be difficult to achieve in patients with haematological malignancy (PHM). We aimed to evaluate the performance of BDG for the diagnosis and the follow-up of IC in PHM. Patients and methods We retrospectively reviewed the serological data of BDG assay in adult and paediatric PHM, who developed candidemia or chronic disseminated candidiasis (CDC) through a 4-year period. Sensitivity and kinetics of BDG were determined for both clinical forms. Results In a panel of 3027 PHM, incidence rates of candidemia and CDC ranged between 0.74 and 0.77 and 0.30 and 0.44 according to the group of patients. At the time of diagnosis, 43.5% and 73% of cases of candidemia and CDC had a positive BDG assay, respectively. We found a significant correlation between the level of BDG at diagnosis and the outcome of candidemia (p = 0.022). In all cases of CDC, BDG negative results were obtained 2 to 6 months before recovery of the CT-scan lesions. Conclusions BDG exhibits a low sensitivity to detect IC in PHM, but its kinetics correlates the clinical outcome. Additional studies are warranted in patients with CDC to evaluate the interest of monitoring BDG levels to anticipate the discontinuation of antifungal maintenance therapy.

The counterfeiting of pharmaceuticals has been detected since about 1990 and has alarmingly continued to pick up steam. We have been recently involved in an evaluation program of some of the most commonly prescribed cardiovascular drugs in Africa, for analysing an important number of tablets or capsules obtained from different places in seven African countries. A reversed-phase high-performance liquid chromatography with tandem mass spectrometry method was developed and validated to simultaneously control the identity and the quantity of acenocoumarol, amlodipine, atenolol, captopril, furosemide, hydrochlorothiazide and simvastatin in tablets. Their separation was performed on a Kinetex® C(18) (100 mm × 2.1 mm inside diameter, 2.6 μm) column using a gradient elution of 20 mM ammonium formate buffer and acetonitrile (90:10 10:90 v/v) at a flow rate of 0.5 mL/min. The analytes were detected using electrospray ionisation tandem mass spectrometry in both positive and negative modes with multiple reaction monitoring. Tandem mass spectrometry fragmentation patterns of captopril, furosemide and acenocoumarol, up to now not detailed in the literature, were also studied to assist in the selection of the most relevant transitions towards the objectives. The developed method was validated as per International Conference on Harmonisation guidelines with respect to specificity, linearity, trueness, precision, limits of detection and quantification. It has been successfully applied to the control of oral forms of seven cardiovascular drugs collected in African countries.

Systemic hypertension is a rapidly growing epidemic in Africa. The role of socioeconomic status on blood pressure control has not been well studied in this part of the world. We, therefore, aimed to quantify the association of socioeconomic status both at the individual and at the country level with blood pressure control in Sub-Saharan Africa. We conducted a cross-sectional survey in urban clinics of 12 countries, both low income and middle income, in Sub-Saharan Africa. Standardized blood pressure measures were made among the hypertensive patients attending the clinics. Blood pressure control was defined as blood pressure P for trend, P for trend, 0.03) and not in middle-income countries ( P for trend, 0.26). In low-income countries, the odds of uncontrolled hypertension increased 1.37-fold (odds ratio, 1.37 [0.99–1.90]) and 1.88-fold (odds ratio, 1.88 [1.10–3.21]) in patients with middle and low individual wealth as compared with high individual wealth. Similarly, the grade of hypertension increased progressively with decreasing level of individual patient wealth ( P for trend

Background The growing menace of poor quality and falsified drugs constitutes a major hazard, compromising healthcare and patient outcomes. Efforts to assess drug standards worldwide have almost exclusively focused on anti-microbial drugs; with no study to date on cardiovascular drugs. Our study aims to assess quality of seven routinely used cardiovascular medications (anticoagulants, antihypertensives and statins) in ten Sub-Saharan African countries. Methods Drugs were prospectively collected using standardized methods between 2012 and 2014 from licensed (random pharmacies) and unlicensed (street-markets) places of sale in Africa. We developed a validated reversed-phase liquid chromatography with tandem mass spectrometry method to accurately quantify the active ingredient in a certified public laboratory. Three quality categories were defined based on the ratio of the measured to the expected dosage of the active ingredient: A (good quality): 95% to 105%, B (low quality): 85 to 94.99% or 105.01 to 115%, C (very low quality): 115%. Results All expected medicines (n=3468 samples) were collected in Benin, Burkina-Faso, Congo-Brazzaville, the Democratic Republic of Congo, Guinea, Cote d'Ivoire, Mauritania, Niger, Togo and Senegal. Out of the 1530 samples randomly tested, poor quality (types B and C) was identified in 249 (16.3%) samples. The prevalence of poor quality was significantly increased in certain specific drugs (amlodipine 29% and captopril 26%), in generic versions (23%) and in drugs produced in Asia (35%). The proportion of poor quality reached 50% when drugs produced in Asia were sold in street-markets. Conclusion In this first study assessing the quality of cardiovascular drugs in Africa, we found a significant proportion of poor quality drugs. This requires continued monitoring strategies.