[Prerequisites for the implementation of Ultra® packaging to replace containers for three surgical departments: Budget impact analysis]. / Pré-requis à la mise en place de l'emballage Ultra® en remplacement des conteneurs au sein de trois blocs opératoires : analyse d'impact budgétaire.

OBJECTIVES: Budgetary impact analysis of the replacement of three surgical departments containers with a new perforation-resistant packaging: Ultra® pouches and reels. METHODS: Comparison of projections of containers costs of use to those of Ultra® packaging over six years. For containers, the costs include washing, packaging, curative maintenance (annual costs), and preventive maintenance (every five years). For Ultra® packaging, the costs include the first year, the purchase of a suitable storage arsenal and a pulse welder, and the transformation of the transport system. Annual costs for Ultra® include packaging and welders maintenance and qualification. RESULTS: In the first year, the costs with Ultra® packaging are higher than the cost related to the container model because the initial investment for the installation is not completely offset by the cost of preventive maintenance of the containers. However, from the second year of use of the Ultra®, an annual saving of €19,356 is expected and up to €49,849 in the sixth year (new preventive maintenance of containers needed). In six years, a saving of €116,186 is expected, which represents 40.4% savings compared to the container model. CONCLUSIONS: The budget impact analysis is in favor of the implementation of Ultra® packaging. The expenses related to the purchase of the arsenal, a pulse welder and the adaptation of the transport system should be amortized from the second year. Significant savings are even expected.

Liquid chromatography with tandem mass spectrometry for the simultaneous identification and quantification of cardiovascular drugs applied to the detection of substandard and falsified drugs.

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.

Opportunity to monitor immunosuppressive drugs in peripheral blood mononuclear cells: where are we and where are we going?

Immunosuppressive (IS) drugs are now widely used as preventive treatments of allograft rejection in transplantation. Therapeutic drug monitoring (TDM) using trough whole blood concentrations is usually warranted and therapeutic range is recommended to ensure efficacy and prevent toxicity from these drugs. This intensive TDM reduces acute graft rejection but despite this management, the acute rejection rate still remains high in the first two years post-transplantation and few improvements have been made recently to reduce this rate. Moreover, in some patients, acute rejections occur despite adequate trough whole blood IS concentrations. Thus, other ways to monitor immunosuppressive drug effects have to be investigated. As lymphocyte cells are the site of action of IS drugs and so the effect compartment of the drug, monitoring IS drugs in lymphocytes, or for practical reasons in peripheral blood mononuclear cells (PBMC), could be more relevant than standard TDM. The aim of this paper is to review the recent work conducted on the advantages of monitoring IS drugs in PBMC, particularly for calcineurin inhibitors and mammalian target of rapamycin (m-TOR) inhibitors, from an analytical point of view as well as a clinical point of view.

Real-life temocillin use in Greater Paris area, effectiveness and risk factors for failure in infections caused by ESBL-producing Enterobacterales: a multicentre retrospective study.

Background: Temocillin is a ß-lactam that is not hydrolysed by ESBLs. Objectives: To describe the real-life use of temocillin, to assess its effectiveness in infections caused by ESBL-producing Enterobacterales, and to identify risk factors for treatment failure. Methods: Retrospective multicentric study in eight tertiary care hospitals in the Greater Paris area, including patients who received at least one dose of temocillin for ESBL infections from 1 January to 31 December 2018. Failure was a composite criterion defined within 28 day follow-up by persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment and/or death from infection. A logistic regression with univariable and multivariable analysis was performed to identify risks associated with failure. Results: Data on 130 infection episodes were collected; 113 were due to ESBL-producing Enterobacterales. Mean age was 65.2 ±â€Š15.7 years and 68.1% patients were male. Indications were mostly urinary tract infections (UTIs) (85.8%), bloodstream infections (11.5%), respiratory tract infections (RTIs) (3.5%) and intra-abdominal infections (3.5%). Bacteria involved were Escherichia coli (49.6%), Klebsiella pneumoniae (44.2%) and Enterobacter cloacae (8.8%). Polymicrobial infections occurred in 23.0% of cases. Temocillin was mostly used in monotherapy (102/113, 90.3%). Failure was found in 13.3% of cases. Risk factors for failure in multivariable analysis were: RTI (aOR 23.3, 95% CI 1.5-358.2) and neurological disease (aOR 5.3, 95% CI 1.5-18.6). Conclusions: The main use of temocillin was UTI due to ESBL-producing E. coli and K. pneumoniae, with a favourable clinical outcome. The main risk factor for failure was neurological disease.

Hypertension treatment in sub-Saharan Africa: a systematic review.

Sub-Saharan Africa (SSA) faces the highest rate of hypertension worldwide. Blood pressure (BP) control rests on the association of lifestyle modification and antihypertensive medicines. We aimed to systematically review antihypertensive strategies implemented in SSA to achieve BP control. A systematic search beginning in 2003 was performed in MEDLINE, COCHRANE and EMBASE. We included only original and observational studies in SSA countries. Thirty studies were included from 11 countries. No study was multinational. The number of patients varied from 111 to 897 (median: 294; IQR: 192-478). Overall, 21% of patients received monotherapy, 42.6% two-drug and 26.6% three-drug combinations. Out of all the strategies, renin-angiotensin system (RAS) blockers were mostly prescribed, followed by diuretics and calcium channel blockers. In monotherapy, RAS blockers were the first to be prescribed. Only 10 articles described antihypertensive strategies beyond triple combinations. BP control was highly variable (range: 16.4 to 61.2%). Multicentre studies performed in several SSA countries are needed to ensure international guidelines actually do improve outcomes in SSA.

Determination of plasma concentration of Belimumab by LC-MS/MS: Method development, validation, and clinical application.

INTRODUCTION: Belimumab is a monoclonal antibody against B cell activating factor (BLyS). This monoclonal antibody (mAb) has been shown to be effective in reducing disease activity in patients with systemic lupus erythematosus (SLE). Belimumab is available in two forms as a lyophilized powder for intravenous (IV) use, or single-dose syringe for subcutaneous (SC) use. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitation of belimumab in human serum. MATERIAL AND METHODS: All analyses relied on nano-surface and molecular-orientation limited (nSMOL) proteolysis coupled with LC-MS/MS. Quantifications was performed in multiple reactions monitoring (MRM) mode, and electrospray ionization was conducted in positive mode. RESULTS: Belimumab was quantified with signature peptide QAPGQGLEWMGGIPFGTAK and normalized using P14R. The total run time per assay was 10 min. Linearity was measured from 5 to 800 µg/mL (r² > 0.995). Accuracy and precision based on three quality control levels range from 11.2 - 9.51 % and 1.24 - 13.12 % respectively. The carryover was less than 7 %. In all, 87 patient samples were processed (65, IV; 22, SC). Mean concentration of belimumab was significantly higher for SC (93.0 ± 74.0 µg/mL) than for IV (67.4 ± 38.9 µg/mL) administration. CONCLUSION: We have developed the first method of belimumab quantification combining LC-MS/MS and nSMOL proteolysis. It can be used for future clinical pharmacokinetic studies of belimumab and for investigating the relationship between belimumab concentration, efficacy, and toxicity in SLE patients.

Population pharmacokinetics of everolimus in cardiac recipients: comedications, ABCB1, and CYP3A5 polymorphisms.

BACKGROUND: The aim of this study was, using routine drug monitoring data, to identify patient characteristics that may influence everolimus (EVE) pharmacokinetic parameters and to develop a population pharmacokinetic model to predict EVE whole blood concentrations in cardiac recipients. METHODS: Fifty-nine patients were enrolled in the prospective study. Patient's characteristics were recorded including biological covariates and treatments. CYP3A5 and ABCB1 polymorphisms were determined. Seven hundred seventy-five EVE blood samples were collected for routine drug monitoring. Population pharmacokinetic modeling was carried out using the nonlinear mixed-effects modeling program. Results were analyzed according to a 1-compartment pharmacokinetic model with linear absorption and elimination. The model was evaluated using a bootstrap method and a visual predictive check procedure. RESULTS: The pharmacokinetic of EVE in cardiac recipients was best described by a 1-compartment model. Interindividual variability was best described by an exponential error model and residual error by a proportional plus additive error model. Estimation of EVE apparent clearance (3.33 ± 0.20 L/h) and apparent volume of distribution (146 ± 33 L) were in accordance with previously published data. Bilirubinemia and cyclosporine significantly influenced EVE clearance. Some covariates that were expected to influence EVE clearance, for example, ABCB1 and CYP3A5 polymorphisms, were not evidenced. No covariates influenced the volume of distribution of EVE. CONCLUSIONS: This study is the first population pharmacokinetic model of EVE in heart transplantation patients. It allows a better description of the pharmacokinetics of EVE. The present population pharmacokinetic model allows estimating a priori and a posteriori EVE concentrations in cardiac recipients and could limit the over and under drug exposure in this population.

Impact of extracorporeal membrane oxygenation and continuous venovenous hemodiafiltration on the pharmacokinetics of oseltamivir carboxylate in critically ill patients with pandemic (H1N1) influenza.

PURPOSE: The neuraminidase inhibitor oseltamivir is a recommended treatment for influenza A (H1N1) infection. In rare cases, some patients develop influenza-associated multiple organ failures, requiring rescue therapies such as extracorporeal membrane oxygenation (ECMO) or continuous venovenous hemodiafiltration (CVVHDF). This study was designed to evaluate the impact of ECMO and CVVHDF on the pharmacokinetics of oseltamivir carboxylate (OC) in critically ill patients with pandemic (H1N1) influenza treated with oseltamivir. PATIENTS AND METHODS: Seven critically ill patients on venovenous ECMO for severe pandemic (H1N1) influenza associated with acute respiratory distress syndrome were treated with various doses of oseltamivir (75 or 150 mg twice daily). Because of acute kidney injury, 3 of them also received CVVHDF. OC, the active form of oseltamivir, was quantified in plasma, and main pharmacokinetic parameters were determined. RESULTS: OC Cmax (1029 ± 478 ng/mL) and area under the curve (9.00 ± 4.52 mcg·h/mL) for patients on ECMO with preserved renal function were comparable with those of healthy volunteers or noncritically ill patients. Patients both on ECMO and CVVHDF had 4-to 5-fold higher OC Cmax and area under the curve. CONCLUSIONS: ECMO by itself did not impact on the pharmacokinetics of OC. However, the drug accumulated in the plasma of patients on ECMO who also received CVVHDF for renal failure. Based on these results, we recommend that oseltamivir dosage should be decreased and plasma levels of OC be monitored in patients receiving CVVHDF because of acute kidney injury.

Assessment of Good Practice Guidelines for Administration of Drugs via Feeding Tubes by a Clinical Pharmacist in the Intensive Care Unit.

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.

Development and real-life use assessment of a self-management smartphone application for patients with inflammatory arthritis. A user-centred step-by-step approach.

BACKGROUND: Mobile health applications (apps) are increasing in interest to enhance patient self-management. Few apps are actually used by patients and have been developed for patients with inflammatory arthritis (IA) treated with disease-modifying anti-rheumatic drugs which use entails risk of adverse effects such as infections. OBJECTIVE: To develop Hiboot, 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 app development included first a qualitative study with semi-guided audiotaped interviews of 21 patients to identify the impact of IA on daily life and patient treatments practices and an online cross-sectional survey of 344 patients to assess their health apps use in general and potential user needs. A multidisciplinary team developed the first version of the app via five face-to-face meetings. After app launch, a second qualitative study of 21 patients and a users' test of 13 patients and 3 rheumatologists led to the app's current version. The number of app installations, current users and comments were collected from the Google Play store and the Apple store. RESULTS: The qualitative study revealed needs for counselling, patient-health professional partnership, and skills to cope with risk situations; 86.8% participants 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 based on the French academic recommendations, treatment reminders, global well-being self-assessment, periodic counselling messages, and a diary. The Hiboot app was installed 20,500 times from September 2017 to October 2020, with 4300 regular current users. Scores were 4.4/5 stars at Android and iOS stores. CONCLUSION: Hiboot is a free self-management app for patients with IA developed by a step-by-step process including patients and health professionals. Further evaluation of the Hiboot benefit is needed.

Use of traditional medicine and control of hypertension in 12 African countries.

BACKGROUND: Use of traditional medicine (TM) is widespread in sub-Saharan Africa as a treatment option for a wide range of disease. We aimed to describe main characteristics of TM users and estimate the association of TM use with control of hypertension. METHODS: We used data on 2128 hypertensive patients of a cross-sectional study (convenience sampling), who attended cardiology departments of 12 sub-Saharan African countries (Benin, Cameroon, Congo, Democratic Republic of the Congo, Gabon, Guinea, Côte d'Ivoire, Mauritania, Mozambique, Niger, Senegal, Togo). To model association of TM use with odds of uncontrolled, severe and complicated hypertension, we used multivariable mixed logistic regressions, and to model the association with blood pressure (systolic (SBP) and diastolic (DBP)) we used mixed linear models. All models were adjusted for age, sex, wealth, adherence to hypertension conventional treatment and country (random effect). RESULTS: A total of 512 (24%) participants reported using TM, varying across countries from 10% in the Congo to 48% in Guinea. TM users were more likely to be men, living in rural area, poorly adhere to prescribed medication (frequently due to its cost). Use of TM was associated with a 3.87 (95% CI 1.52 to 6.22)/1.75 (0.34 to 3.16) mm Hg higher SBP/DBP compared with no use; and with greater odds of severe hypertension (OR=1.34; 95% CI 1.04 to 1.74) and of any hypertension complication (OR=1.27; 95% CI 1.01 to 1.60), mainly driven by renal complication (OR=1.57; 95% CI 1.07 to 2.29) after adjustment for measured confounders. CONCLUSIONS: The use of TM was associated with higher blood pressure, more severe hypertension and more complications in Sub-Saharan African countries. The widespread use of TM needs to be acknowledged and worked out to integrate TM safely within the conventional healthcare.

Barriers to up-titrated antihypertensive strategies in 12 sub-Saharan African countries: the Multination Evaluation of hypertension in Sub-Saharan Africa Study.

BACKGROUND: Sub-Saharan Africa (SSA) faces the highest rate of hypertension worldwide. The high burden of elevated blood pressure (BP) in black people has been emphasized. Guidelines recommend two or more antihypertensive medications to achieve a BP control. We aimed to identify factors associated with prescription of up-titrated antihypertensive strategies in Africa. METHODS: We conducted a cross-sectional study on outpatient consultations for hypertension across 12 SSA countries. Collected data included socioeconomic status, antihypertensive drugs classes, BP measures, cardiovascular risk factors and complication of hypertension. We used ordinal logistic regression to assess factors associated with prescription of up-titrated strategies. RESULTS: The study involved 2123 treated patients with hypertension. Patients received monotherapy in 36.3 vs. 25.9%, two-drug in 42.2 vs. 45% and three and more drugs strategies in 21.5 vs. 29.1% in low (LIC) and middle (MIC) income countries, respectively. Patients with sedentary lifestyle [OR 1.4 (1.11-1.77)], complication of hypertension [OR 2.4 (1.89-3.03)], former hypertension [OR 3.12 (2.3-4.26)], good adherence [OR 1.98 (1.47-2.66)], from MIC [OR 1.38 (1.10-1.74)] and living in urban areas [OR 1.52 (1.16-1.99)] were more likely to be treated with up-titrated strategies. Stratified analysis shows that in LIC, up-titrated strategies were less frequent in rural than in urban patients (P for trend <0.01) whereas such difference was not observed in MIC. CONCLUSION: In this African setting, in addition to expected factors, up-titrated drug strategies were associated with country-level income, patient location and finally, the interplay between both in LIC. These results highlight the importance of developing policies that seek to make multiple drug classes accessible particularly in rural and LIC.

Prediction tacrolimus blood levels based on the Bayesian method in adult kidney transplant patients.

The use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. We have previously described a tacrolimus population pharmacokinetics model obtained in an adult kidney transplant cohort. The aims of the present study were (1) to validate that model using an external dataset and (2) to evaluate the prediction using a Bayesian method. Data were retrospectively collected from 34 adult patients receiving kidney transplantation. Trough blood concentrations of tacrolimus were predicted using the empirical Bayesian method with sparse samples obtained during the previous week. The system performance was evaluated by the mean prediction error (ME), mean absolute prediction error (MAE). and root mean square error (RMSE). Patients were administrated oral or intravenous tacrolimus as part of a triple immunosuppressive regimen with mycophenolate mofetil and corticosteroids. Subsequent doses were adjusted on the basis of clinical evidence of efficacy and toxicity and by routine therapeutic drug monitoring. In our previous model, clearance increased with post transplantation days and with prednisone dosage. Concentrations predicted by the population mean pharmacokinetic parameter values match well with observed concentrations during oral therapy. Bayesian prediction using trough concentrations obtained after 21 days of treatment significantly decreased ME, MAE, and RMSE compared with predictions from data including this period. After 21 days of treatment, there was an insignificant bias ME (0.22 ± 2.59 ng/ml), a reasonable precision MAE (1.97 ± 1.69 ng/ml) and RMSE (1.28 ± 0.58 ng/ml). The present study demonstrates the suitability of the Bayesian method for the prediction of trough blood concentrations of tacrolimus using only few samples in adult kidney transplantation recipients.

Multidisciplinary team intervention to reduce the nocebo effect when switching from the originator infliximab to a biosimilar.

OBJECTIVES: To evaluate an intervention to reduce the nocebo effect (NE) when switching from the originator infliximab (OI) to the infliximab biosimilar SB2 in chronic inflammatory rheumatic disease (CIRD). METHODS: An intervention was built with healthcare professionals (HPs) and a patient representative, based on a systematic review of interventions reducing the NE in musculoskeletal diseases and semi-directed questioning of five patients. Our strategy consisted of training HPs, switch information given by the nurses, a consistent vocabulary. All CIRD patients switched from OI to SB2 were included for the intervention. The primary outcome was the SB2 retention rate (RR) at 34 weeks. Secondary outcomes were the SB2 RR at 12 months, discontinuation rates due to a possible NE and comparison with a historical cohort of CIRD patients receiving the OI and 6 published European cohorts. RESULTS: 45 patients were included from March 2018 (rheumatoid arthritis, n=17, spondylarthritis, n=28). After 34 weeks, the SB2 RR was 91.2%, similar to the historical cohort RR (p=0.41) but higher than the 3 European cohort RRs (p<0.05). At 12 months, the SB2 RR was 84.5% vs 88.4% for the historical cohort (p=0.52). SB2 discontinuation due to a possible NE was 6.6% after 12 months. CONCLUSIONS: A tailored communication with a prominent role of nurses reduced the NE in non-medical switches from the OI to SB2 as compared to published results. The RR was similar to the historical cohort RR. The methodology used to construct this intervention may help improve the outcomes of switches with upcoming biosimilars.

Ruxolitinib photodegradation mechanisms by theoretical and experimental chemistry.

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.

Intrinsic stability of the antiviral drug umifenovir by stress testing and DFT studies.

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.

Blood pressure-lowering medicines implemented in 12 African countries: the cross-sectional multination EIGHT study.

OBJECTIVE: In Africa, the number of patients with hypertension is expected to reach 216.8 million by 2030. Large-scale data on antihypertensive medications used in Sub-Saharan Africa (SSA) are scarce.Here, we describe antihypertensive drug strategies and identify treatment factors associated with blood pressure (BP) control in 12 Sub-Saharan countries. SETTING: Outpatient consultations for hypertension in urban tertiary cardiology centres of 29 hospitals from 17 cities across 12 SSA countries between January 2014 and November 2015. PARTICIPANTS: Patients ≥18 years of age with hypertension were enrolled at any visit during outpatient consultations in the cardiology departments MAIN OUTCOME MEASURE: We collected BP levels, demographic characteristics and antihypertensive treatment use (including traditional medicine) of patients with hypertension attending outpatient visits. BP control was defined as seated office BP <140/90 mm Hg. We used logistic regression with a random effect on countries to assess factors of BP control. RESULTS: Overall, 2198 hypertensive patients were included and a total of 96.6% (n=2123) were on antihypertensive medications. Among treated patients, 653 (30.8%) patients received a monotherapy by calcium channel blocker (n=324, 49.6%), renin-angiotensin system blocker (RAS) (n=126, 19.3%) or diuretic (n=122, 18.7%). Two-drug strategies were prescribed in 927 (43.6%) patients including mainly diuretics and RAS (n=327, 42% of two-drug strategies). Prescriptions of three-drugs or more were used in 543 (25.6%) patients. Overall, among treated patients, 1630 (76.7%) had uncontrolled BP, of whom 462 (28.3%) had BP levels ≥180/110 mm Hg, mainly in those on monotherapy. After adjustment for sociodemographic factors, the use of traditional medicine was the only factor significantly associated with uncontrolled BP (OR 1.72 (1.19 to 2.49) p<0.01). CONCLUSION: Our study provided large-scale data on antihypertensive prescriptions in the African continent. Among patients declared adherent to drugs, poor BP control was significantly associated with the use of traditional medicine.

Pharmacists' role in antimicrobial stewardship and relationship with antibiotic consumption in hospitals: An observational multicentre study.

OBJECTIVES: Antimicrobial stewardship (AMS) teams around the world include pharmacists; however, their impact is relatively unknown. This study aimed to explore the relationship between pharmacists' actions and antibiotic consumption. METHODS: Hospital pharmacists involved in the French antibiotic consumption surveillance network (ATB-Raisin) were invited to participate in a retrospective observational multicentre study. Collected data were: the previous year's (2016) antibiotic consumption expressed in daily defined dose per 1000 patient-days; AMS measures, including pharmacist-specific actions; and use of a computerised prescription order entry (CPOE) system. Associations between antibiotic consumption and AMS measures were assessed by linear regression, after adjustment for hospital activities. RESULTS: Annual data for 2016 from 77 hospitals (7260000 bed-days in 24000 beds) were analysed. Pharmacists were involved in AMS programs in 73% of hospitals, and were the antibiotic advisor in 25%. Pharmaceutical review of prescriptions was organised in almost all hospitals (97%). The univariable analysis identified five measures associated with lower overall antibiotic consumption: CPOE use (if >80% of prescriptions or 100%), pharmaceutical review (if >80% of beds or 100%) and the antibiotic advisor being a pharmacist (P=0.04, P=0.004 and P=0.003, respectively). In the multivariable analysis, two explanatory variables were significantly and independently associated with a lower overall antibiotic consumption: the antibiotic advisor being a pharmacist and a pharmaceutical review covering all beds (-19.9% [-31.6%; -8.1%], P=0.002 and -18.3% [-34.0%; -2.6%], P=0.03, respectively). CONCLUSIONS: Antibiotic consumption was lower when the antibiotic advisor was a pharmacist and when the pharmaceutical team reviewed all prescriptions. These results highlight that actions initiated by pharmacists have a positive impact and should be supported.