French Drug Research Articles

Clinical and radiological pattern of olaparib-induced interstitial lung disease

BackgroundPARP inhibitors (PARPi) are used in the treatment of ovarian, breast, pancreatic, and prostate cancers. Pneumonitis has been identified as a potential side effect, with a higher meta-analysis-assessed risk for olaparib versus other PARPi. Olaparib-induced interstitial lung disease (O-ILD) was first described within the Japanese population, with few information available for Caucasian patients.MethodsWe performed a retrospective study by pooling data from the French and Belgian pharmacovigilance databases from 2018 to 2022. Patients with O-ILD were included following a central review by: 1) pharmacologists using the French drug causality assessment method; 2) senior pneumologists or radiologists, using the Fleischner Society’s recommendations.ResultsFive patients were identified and analysed. All were females, with ovarian or breast cancer. Median age at O-ILD diagnosis was 71 (38–72) years old, with no smoking history. Median delay between treatment initiation and symptom occurrence was 12 (6–33) weeks. Pneumonitis severity assessed using the Common Terminology Criteria for Adverse Events V5 was Grade 3 (n = 4) or 2 (n = 1). CT-scan review (n = 3) described hypersensitivity pneumonitis reaction as a common pattern. Bronchioalveolar lavage (n = 4) revealed lymphocytic alveolitis. Treatments relied on olaparib discontinuation (n = 5) and glucocorticoid intake (n = 4), with no fatal issue. Safe re-challenge with PARPi occurred in two patients. Forty additional O-ILD cases were identified in the WHO VigiBase database, including one fatal case.ConclusionsPARPi-ILD is a rare but potentially life-threatening disease, presenting as a hypersensitivity pneumonitis pattern within 3 months of PARPi initiation. Treatment primarily relies on medication discontinuation. Re-challenging with another PARPi could be considered.Clinical trial numberCEPRO #2023–010.

Phase IB Study of Oral Selinexor in Combination with Rituximab and Platinum Chemotherapy in Patients with Relapsed/Refractory B-Cell Lymphoma-Final Analysis.

Selinexor is an oral selective inhibitor of exportine-1 (XPO1) with efficacy as a single agent in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We conducted a study investigating the combination of selinexor with rituximab and platinum-based chemotherapy in B-cell lymphoma. We conducted a phase 1b, dose-escalation, and expansion trial, which enrolled patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Patients received oral selinexor according to a 3 + 3 design in combination with rituximab and dexamethasone, high-dose cytarabine, oxaliplatine (DHAOX) or gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy. A total of 39 patients were enrolled, 27 during the escalation phase and 12 during the expansion phase. Most patients had diffuse large B-cell lymphoma (DLBCL; 77%). Group R-DHAOX was prematurely closed to inclusion due to a recommendation from the French drug agency, independent of this trial. A recommended phase 2 dose (RP2D) of selinexor in association with R-GPD was established at 40 mg on days 1, 8, and 15 of each 21-day cycle. In a population of 18 patients treated at this dose of selinexor, the most frequent grade 3-4 adverse events were hematological. With this regimen, seven obtained a complete metabolic response and five a partial response. The median PFS was 5.8 months. Among the patients with R/R B-cell lymphoma, selinexor at a weekly dose of 40 mg with R-GDP is feasible for outpatients, with a generally acceptable safety profile.

Canadian status of "not acceptable" drugs as evaluated by Prescrire: A cohort study.

The independent French drug bulletin Prescrire International rates the therapeutic innovation of new drug-indications approved for marketing in France using an ordinal scale with the lowest rating being "not acceptable". This study investigates whether these drugs were approved by Health Canada. A list of "not acceptable" drug-indications was generated by handsearching all issues of Prescrire International between January 2013 and December 2022. The generic names, indications and reasons why Prescrire labeled them not acceptable were recorded. The approval date was determined by consulting the website of the European Medicines Agency (EMA). The status of these drug-indications in Canada was determined by searching multiple Health Canada websites. Therapeutic Evaluations for new drug-indications done by the Patented Medicine Prices Review Board (PMPRB) were recorded. Prescrire rated 57 new drug-indications and 42 new indications for existing drugs as not acceptable. Seventy of these drug-indications were available in Canada- 42 new drug-indications and 28 new indications for existing drugs. Twenty (90.9%) of the 22 new drugs evaluated by the PMPRB were rated as slight/no therapeutic improvement and 2 as moderate therapeutic improvement. The median difference, in days, between approval times by the EMA/ANSM and Health Canada was 129 (interquartile range -102, 341) in favour of the former. The majority of the not acceptable drug-indications were approved by Health Canada. The difference between when Prescrire and Health Canada examined the evidence for these drug-indications is unlikely to explain the difference in their evaluations. A change in regulatory standards at Health Canada may be one factor behind the presence of these drugs. To what degree those drugs led to more harms than benefits for patients who are taking them needs to be urgently investigated. Finally, the reasoning behind Health Canada's approval of these drugs should be interrogated.

Study of physicians' preferences for optimizing the pharmacy assortment of glocose-lowering drugs

For the stable operation of the pharmacy and the proper support of patients with diabetes, it is necessary to optimize the assortment of glucose-lowering drugs (GLD), taking into account the significant prevalence of this disease. The demand for prescription drugs is formed by doctors who choose therapy and prescribe drugs.
 The purpose of this study was to determine the factors that influence of choosing GLD for the treatment of type 2 diabetes and the preferences of doctors when choosing GLD for therapy.
 They used a remote questionnaire form using Google forms. 732 doctor questionnaires were processed. Statistical processing was carried out using structural, comparative and graphic analysis.
 A survey of doctors established the factors that influence the prescription of drugs for the treatment of type 2 diabetes: high effectiveness and inclusion of drugs in treatment standards, their safety, and their own positive experience in prescribing drugs. It was also found that when choosing a GLD type, almost half of doctors take into account the patient's purchasing power and the presence of a GLD in the reimbursement program. The survey showed that a third of doctors prefer domestic GLD, and half of the respondents do so sometimes. When choosing foreign medical medications, doctors prefer German, French, and Swiss-made medical drugs. A significant part of doctors do not have preferences when choosing trade name (TN), but the majority of doctors who have preferences prefer TN mainly of foreign production and prolonged forms. It was found that about 10% of the responding doctors do not prescribe combined GLD. The majority of respondent doctors have preferences for combinations: metformin/glimepiride, dapagliflozin propanediol/metformin and sitagliptin/metformin. Problems have been identified at the stage of pharmacological supervision of GLD. Despite the fact that doctors noted in their practice the side effects of drugs in patients, only a fourth (22.7%) of respondents recorded these effects in accordance with the current legislation and made reports.
 It is advisable to use the results of the questionnaire to improve the care of patients with diabetes and to meet their needs by optimizing the pharmacy assortment.
 It is advisable to increase the list of International Nonproprietary Name of GLDs for reimbursement, which will contribute to the availability of modern treatment regimens, because the price of medicines limits the quality of modern treatment regimens for type 2 diabetes.

Psychotropic drugs consumption during 2020 COVID-19 pandemic and lockdowns: Evidence of a surprising resilience of the drugs delivery system in France

The COVID-19 pandemic imposed two lockdowns of eight and six weeks in France. While access to care was reduced during lockdown periods, these stressful situations with the pandemic and lockdown periods may have a negative impact on mental health, especially in vulnerable subgroups. Monitoring of psychotropic drugs consumption in France is a comprehensive and reliable tool for indirectly analyzing the mental health of French people. This historical cohort study (n = 767 147) investigated the short-term and long-term evolution of the weekly trend of psychotropic drugs users in 2020 by performing a Seasonal Trend decomposition time series analysis. Rate of progression of consumers per week increased from 186 in the last week of 2019 to 261 per week in the last week of 2020 (+40.3%). Our results did not show a significant break in psychotropic drugs consumption trends during the year 2020 and its two lockdowns. The increase in trend regarding psychotropic drugs consumptions was greatest in young people (<15 years) and patients not being socially deprived. Despite the increase in consumers with restrictive health measures, the French drugs delivery system has been able to adapt with the support of government and pharmacy network. This point should be kept in mind as the necessary reforms to the health care system are undertaken.The COVID-19 pandemic has a negative impact on mental health and two lockdowns occurred in France with reduced access to care. In this context, monitoring of psychotropic drugs consumption is a comprehensive and reliable tool for analyzing the mental health of French people. We hypothesized that the psychotropic drugs consumption has increased during the 2020 COVID-19 pandemic, testifying to French people mental health deterioration, with psychotropic drugs consumption breaks during lockdowns, especially during the first “grand national lockdown”, due to the closure or difficulties for accessing to health care structures. By carrying out a historical cohort study among Pays de la Loire residents (n = 767 147), we investigated evolution of the weekly trend of psychotropic drugs users in 2020 compared to 2019 by performing a Seasonal Trend decomposition time series analysis. Between 2019 to 2020, we found a + 40.3% rate of progression of consumers per week. During the year 2020, changes in trend regarding psychotropic drugs consumptions was observed in various sub-groups, e.g. greater in the youngest (< 15 years), which may indicate a vulnerable group strongly impacted by COVID-19 negative consequences, and patients not being socially deprived, which may indicate a group with probably an easier access to care. Lockdown periods were not associated with a significant change in psychotropic drug use, suggesting a form of resilience in the French health care system to maintain its capacity to deliver psychotropic treatments. We mainly discussed that despite the increase in consumers and the policies of restricting access to care during lockdown periods, the French drugs delivery system has been able to adapt thanks to supportive policy actions (extension of the prescriptions validity without the need for a renewal by a physician during periods of lockdowns), an efficient pharmacy network with a collaborative practice of health actors that need to be developed and/or conserved to face potential future health crises.

On the use of logistics data to anticipate drugs shortages through data mining

Drugs shortages have become a major issue affecting healthcare systems worldwide. With the growing use of electronic records, data analytics techniques have been identified as a major asset to provide support in managing pharmaceutical supply chains. However, applications addressing drugs shortages, which arise from various complex factors, are still expected. Therefore, this paper investigates whether the use of logistics data at the national level can provide insights into drugs supply disruptions issues. Basic features were defined from a dataset of 1.281.545 electronic data interchange records between French hospitals and drugs distributors in 2021. Additionally, anomaly detection and correlation analysis were performed to (i) detect supply disruptions of four products in 2021; and (ii) assess whether the features defined can be used in future time series predictive models. Findings highlight a promising opportunity to harness these data through more advanced analytics techniques to anticipate and manage drugs shortages at local, national, and European levels.

Using Crack or Smoking Cocaine, That Is the Question: The Association of Sociodemographic Factors with Self-Labeling Choices in France

ABSTRACT The label “crack user” is profoundly stigmatizing. Such labels are foundational to an individual’s identity, affecting how others view them, their self-perceptions, and subsequent behavior. Individuals can also resist labels such as “crack user,” creating distinctions for the same behavior. To elucidate characteristics associated with self-application of stigmatizing labels, we use data from individuals (N = 50,721) serviced for smoking cocaine in French drug treatment centers (N = 263) from 2010–2020 to assess who self-labels their behavior “crack use” or does not in favor of “smoked cocaine,” which are identical behaviors. Multilevel models reveal higher odds of using the less stigmatizing “smoked cocaine” in earlier years, among those with less risky cocaine use profiles, and among those not using other stimulants. Importantly, this less stigmatizing label is more common among those of high SES and outside the Paris region. An interaction demonstrates that even within Paris, those of high SES have higher odds of using this label than their lower SES Parisian counterparts. Those in privileged positions may use this alternative label to avoid stigmatization of the “crack user” label. Such distinctions potentially perpetuate inequalities associated with the more stigmatized label. We suggest that treatment centers can act as sites to combat these differences.

Did the New French Regulation of Zolpidem Decrease the Problematic Consumption of Zolpidem? A Field Study among Users.

Background: The French national drug regulatory authority stated, in 2017, that a secured prescription pad must be used for zolpidem prescriptions. This study aimed to evaluate the evolution of the problematic consumption of zolpidem at the individual level since the new regulation. Methods: Two nationwide populations of at-risk users of zolpidem were recruited: one in general practitioner (GP) offices and one in specialized care centers dedicated to drug dependence (SCDDs). Participants were asked about their zolpidem consumption before and after the regulation change. The primary outcome was the evolution of problematic zolpidem consumption, as defined by at least one of the following criteria: overconsumption, fraudulent ways of obtaining, effects sought other than hypnotic, and modes of administration other than oral. Results: A total of 243 participants were included: 125 from GP offices and 118 from SCDDs. In the GP population, the prevalence of patients who were identified as problematic consumers decreased from 24.8% to 20.8% (p = 0.593), whereas the prevalence decreased from 73.7% to 51.7% in the SCDD population (p < 0.001). The most prevalent criteria for problematic status were overconsumption and fraudulent ways. Conclusions: The new French regulation of zolpidem had different impacts among two different populations of at-risk zolpidem consumers.

Skin Testing and Drug Provocation Tests in Epidermal Necrolysis: A French Experience

There are limited data on the use of skin testing, other than patch testing, and challenges in the evaluation of epidermal necrolysis (EN), including Stevens-Johnson syndrome and toxic epidermal necrolysis. To report a French multicenter experience in skin testing and challenges in EN, and investigate the factors associated with tests' positivity. All patients who were evaluated by patch tests (PTs), skin prick tests, intradermal tests (IDTs), or drug provocation tests (DPTs) for EN between 2010 and 2020 were retrospectively included through 2 French drug reaction networks. In total, 113 patients were included from 8 centers. Median (interquartile range) time from EN to hypersensitivity workup was 7.9 months (5.1-15 months). All patients had PTs, 17 (15%) had skin prick tests or IDTs with delayed readings and 32 (28.3%) had DPTs. One mild reaction occurred after a DPT. Overall, 22 patients (19.5%) had positive PTs, and the only factors associated with positivity were Algorithm of Drug Causality for Epidermal Necrolysis (ALDEN) score and drug class. Only 1 IDT was positive but considered irrelevant. The DPTs were never performed to prove responsibility of a highly suspected drug but were used to confirm current tolerance of needed medications. Allergological workup in EN, performed by specialists involved in EN, seems safe. Skin tests, although of limited sensitivity, can be helpful for considering the reintroduction of essential drugs according to a benefit-to-risk decision. We propose an algorithm for approaching hypersensitivity testing in patients with EN, to be adapted to each patient.

Perception of the Regulatory Change for Zolpidem Prescription by French General Practitioners and Its Relation to Prescription Behavior.

Background: To “limit the risk of abuse and misuse” and “encourage correct usage”, the French drug regulatory authority stated that—from April 2017—zolpidem prescription must be performed on a secured prescription pad. This national study aims to evaluate the perception of general practitioners (GPs) towards this new regulation and its link with prescription strategies. Methods: We conducted structured interviews of GPs. Data were collected about GPs’ perception of the measure and therapeutic strategies towards zolpidem. The primary outcome was the description of the GPs’ strategy of prescription, based on the perception towards the new regulation for zolpidem. Results: For 206 GPs, the new regulation was mainly perceived as helpful (61%) and as a difficulty (55%). Other perceptions were the awareness of the risks of zolpidem (18%), awareness of the risks of hypnotics (13%), and nothing changed (5%). Four clusters of GPs were identified. In the clusters with the perception as a difficulty (only or associated with helpful), the GPs who applied the strategy “no modification” for >50% of their patients were more frequently compared to awareness and helpful only clusters (60.8%; 42.9%; 20.4%; 26.7%) (p < 0.001). Conclusions: We highlighted an association between the perception of the new regulation of zolpidem prescription by GPs and a strategy of prescription.

Did the pattern of use of zolpidem change since the enforcement of a new prescription rule? A latent class analysis using the French health insurance database

ABSTRACT Background In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency decreed the implementation of secure prescription pads in April, 2017. The objective of this study was to characterize the impact of this regulatory change on the patterns of zolpidem use. Research design and methods We included patients with at least one reimbursement for zolpidem before and/or after the regulatory change using a sample of the French health insurance database. For each period, we identified profiles of users using a latent class analysis (LCA). Results In total, 15,550 zolpidem users were identified before the measure and 8,301 after the measure. We identified the same three profiles of zolpidem users before and after the measure: non-problematic users (the most prevalent), users whose drug prescriptions suggest psychiatric disorder and potential problematic users. The profile of potential problematic users was similar after the regulatory change but represented a lower absolute number of patients. Conclusion In conclusion, the regulatory change had a positive impact on the patterns of zolpidem use, but the impact should be reevaluated, because withdrawal can take a long time, especially in long-term users. Trial registration The study was registered at www.clinicaltrials.gov under the reference number NCT03584542.

Trends in the delivery of reimbursed nicotine replacement therapies between 2016 and 2019 in France

Describe the evolution of the expenses and the number of boxes of nicotine replacement therapy reimbursed by the French health insurance between 2016 (flat rate of €.150/year with advance payment) and 2019 (65% reimbursement without in advance payment and without a spending limit). Descriptive and analytical epidemiological study between January 1, 2016 and December 31, 2019 based on a retrospective collection of data from OpenMEDIC (the merged French health insurances drug claim database) on the number of reimbursed NRT boxes dispensed by community pharmacies and their annual cost. During 4 years, 7.4 million boxes of NRT were reimbursed (total cost of 148.4 million euros): approximately 300,000 in 2016, 650,000 in 2017, 1.9 million in 2018 and 4.6 million in 2019, namely a fifteen-fold increase between 2016 and 2019 (a geometric growth ratio of 2.5 each year). This increase was slightly more pronounced among men than among women, and concerned more NRT delivered from time to time (gums, tablets): transdermal devices proportion decreased from 79.7% of reimbursed NRT in 2016 to 52.9% in 2019, with an increase in gums (8% to 13.3%) and sublingual tablets (8.4% to 15.8%) over the same period. The evolution of NRT reimbursement comes with an increase in NRT deliveries. This suggests a real medical need rather than a short trend: therefore, this suggests a catch-up in the access to care.

HoSAGE: sarcopenia in older patient with intermediate / high-risk prostate cancer, prevalence and incidence after androgen deprivation therapy: study protocol for a cohort trial

BackgroundSarcopenia is defined by a loss of muscle strength associated to a decrease in skeletal muscle mass. Ageing greatly contributes to sarcopenia as may many other factors such as cancer or androgen deprivation therapies (ADT). This cohort study aims to evaluate (1) the prevalence of muscle disorders and sarcopenia in older patients before initiation of intermediate to high risk prostate cancer treatment with ADT and radiotherapy, and (2) the occurrence and/or aggravation of muscle disorders and sarcopenia at the end of cancer treatment.MethodsThis cohort study is monocentric and prospective. The primary objectives are to determine the risk factor of sarcopenia prevalence and to study the relationship between ADT and sarcopenia incidence, in patients 70 years and older with histologically proven localized or locally advanced prostate cancer, addressed to a geriatrician (G8 score ≤14) for comprehensive geriatric assessment (CGA) in Marseille University Hospital. Secondary objectives encompass, measurement of sarcopenia clinical criteria along prostate oncological treatment; evaluation of the quality of life of patients with sarcopenia; evaluation of the impact of socio-behavioral and anthropological factors on sarcopenia evolution and incidence; finally the evaluation of the impact of ADT exposure on sarcopenia. Sarcopenia prevalence was estimated to be between 20 and 30%, therefore the study will enroll 200 patients.DiscussionThe current guidelines for older patients with prostate cancer recommend a pelvic radiotherapy treatment associated to variable duration (6 to 36 months) of ADT. However ADT impacts muscle mass and could exacerbate the risks of sarcopenia. Our study intends to assess the specific effect of ADT on sarcopenia incidence and/or worsening as well as to estimate sarcopenia prevalence in this population. The results of this cohort trial will lead to a better understanding of sarcopenia prevalence and incidence necessary to further elaborate a prevention plan.Trial registrationThe protocol was registered to the French drug and device regulation agency under the number 2019-A02319-48, before beginning the study (11/12/2019). The ClinicalTrials.gov identifier is NCT04484246, registration on the ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT04484246).

Эффективность и безопасность применения гомеопатических лекарственных препаратов при острых респираторных вирусных инфекциях с позиции доказательной медицины (международный опыт)

В данной обзорной статье речь идет о необходимости понимания основы эффективности и безопасности применения гомеопатических лекарственных препаратов при острых респираторных вирусных инфекциях (ОРВИ) с позиции доказательной медицины. Гомеопатические лекарственные препараты рассмотрены с точки зрения составляющей наномедицины с учетом открытий, сделанных в течение последних десятилетий в этой области знаний, а также с учетом того, что течение ОРВИ в основном проявляется функциональными нарушениями. Отмечена целесообразность использования отдельных компонентов гомеопатических лекарственных средств именно в низких/гомеопатических/наноконцентрациях с учетом их дозозависимого профиля безопасности. В качестве примера проанализированы препараты французского происхождения — Оциллококцинум, Коризалия, Гомеовокс и Стодаль. За многие десятилетия практического использования указанных препаратов наработана достаточно весомая научная база, существует ряд статей, опубликованных в различных странах мира, подтверждающих их эффективность и безопасность. Рассмотрены не только клинические исследования относительно вышеупомянутых препаратов, но также ­освещены вопросы механизма их действия на основе фармакодинамических свойств отдельных компонентов. Указана необходимость рассматривать любой лекарственный препарат, в том числе гомеопатический, как с позиции доказательной медицины, так и в более широком смысле, с учетом современного подхода к здравоохранению на основе ценности. С учетом проанализированной информации сделан вывод, что вышеупомянутые препараты — Оциллококцинум, Коризалия, Гомеовокс, Стодаль — отвечают этим требованиям и должны быть более широко внедрены в клиническую практику.

Baclofen approval in france: A balance between two conceptions of medicine

In October 2018, France became the first country to officially approve baclofen for alcohol use disorder (AUD), even if the French Drug Agency (ANSM) officially stated that the efficacy of baclofen in AUD could be not established at this stage, in the light of the available evidence. The decision of the ANSM comprised obvious political aspects, as baclofen approval followed a decade-long practice of off-label prescription, where doses used could reach 300 mg per day or more. This situation led to a prolonged and ferocious debate between those who questioned such a widespread and unevidenced practice, and those who defended the place of an “common sense” empirical medicine. The French story of baclofen echoes other similar controversial off-label prescribing practices in the country, from the pioneer use buprenorphine for opioid use disorder in the 1990s, to the more recent off-label use of hydroxychloroquine during the COVID-19 outbreak. In each case, similar “pros” and “cons” arguments were opposed, highlighting the difficult interpenetration between evidence-based medicine on the one hand, and on-the-ground practice on the other hand.DisclosureBenjamin Rolland declare having received fees for lectures and expertise from Ethypharm. He was the principal investigator of a phase-1 study funded by Ethypharm

Bonumose to make rare sugars in US

The food ingredient start-up Bonumose has partnered with the French drug services firm Novasep to manufacture rare sugars, including tagatose and allulose. The low-calorie sugars are naturally pres...

Change in the regulatory framework for zolpidem: What is the impact on the landscape of the prescription of sedative medications? The French national ZORRO study

In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency (ANSM) decreed in April 2017 the implementation of secure prescription pads. The objective of this study was to evaluate the impact of this regulatory measure on the prescription of zolpidem and other sedative medications (zopiclone, benzodiazepines and antihistamines) in long-term users of zolpidem and associated factors. We performed a historical cohort study using data from the Generalist Sample of Beneficiaries (EGB). All patients aged over 18 years old who were long-term users (at least 3 months) before the measure were enacted. We analysed the reimbursement trajectories of zolpidem, zopiclone, benzodiazepines and antihistamines (hydroxyzine and alimemazine) up to 2 years after the measure using a state sequence analysis. Overall, 2502 patients were analysed. A four-cluster typology was identified: continuation of zolpidem (n = 1044, 42%), discontinuation of sedative medications (n = 766, 31%), change to zopiclone (n = 537, 21%) and change to hypnotic benzodiazepines (n = 155, 6%). The most frequently prescribed hypnotic benzodiazepine was lormetazepam. We identified age, sex, treatment for psychiatric or addictive disorder and volume of zolpidem use before the measure as factors associated with different reimbursement trajectories after the regulatory change. The regulatory change for zolpidem prescriptions reduced exposure to zolpidem among long-term users and also had a broad impact on prescriptions of other sedative medications. Switching to other medications that also present a potential risk of abuse or dependence should be carefully monitored.

Intravenous Artesunate for the Treatment of Severe Imported Malaria: Implementation, Efficacy, and Safety in 1391 Patients.

Intravenous artesunate is the World Health Organization-recommended first-line treatment for severe malaria worldwide, but it is still not fully licensed in Europe. Observational studies documenting its safety and efficacy in imported malaria are thus essential. We prospectively collected clinical and epidemiological features of 1391 artesunate-treated patients among 110 participant centers during the first 7 years (2011-2017) of a national program implemented by the French Drug Agency. Artesunate became the most frequent treatment for severe malaria in France, rising from 9.9% in 2011 to 71.4% in 2017. Mortality was estimated at 4.1%. Treatment failure was recorded in 27 patients, but mutations in the Kelch-13 gene were not observed. Main reported adverse events (AEs) were anemia (136 cases), cardiac events (24, including 20 episodes of conduction disorders and/or arrhythmia), and liver enzyme elevation (23). Mortality and AEs were similar in the general population and in people with human immunodeficiency virus, who were overweight, or were pregnant, but the only pregnant woman treated in the first trimester experimented a hemorrhagic miscarriage. The incidence of post-artesunate-delayed hemolysis (PADH) was 42.8% when specifically assessed in a 98-patient subgroup, but was not associated with fatal outcomes or sequelae. PADH was twice as frequent in patients of European compared with African origin. Artesunate was rapidly deployed and displayed a robust clinical benefit in patients with severe imported malaria, despite a high frequency of mild to moderate PADH. Further explorations in the context of importation should assess outcomes during the first trimester of pregnancy and collect rare but potentially severe cardiac AEs.

Comparative analysis of medications for antibiotic therapy of chronic obstructive pulmonary disease in the pharmaceutical market of Ukraine and France

The aim of the work – comparative analysis of the assortment of registered medicines for antibiotic therapy of chronic obstructive pulmonary disease (COPD) in the domestic market and similar segment of the French market. Materials and methods. The study of drug assortment in Ukraine was carried out according to the State Register of Medicines of Ukraine , employing the directory of medicines Compendium online , Anatomical Therapeutic Chemical Classification , web-resource Tabletki.UA . Database Base de donnees publique des medicaments was consulted while studying the pharmaceutical market in France. The following methods were used: information search, marketing analysis, graphical, comparative and logical methods. Results . A comparative analysis of medicines employed in Ukraine and France for antibiotic therapy of chronic obstructive pulmonary disease (COPD) was performed. Conclusions . Pharmaceutical markets of drugs for antibiotic therapy of COPD in Ukraine and France are analyzed. As of January 2020, there are 43 brand names (BN) of medicines with 73 available range items registered in Ukraine, and 87 BN medicines with 150 available range items registered in France. The analysis of drugs assortment showed that foreign drugs predominate in Ukraine and France, their share is 84 % and 55 %, respectively. Among the drug-importing countries, the leaders in Ukraine are India and Germany, and in France they are Spain, England and Germany. The share of domestic drugs in Ukraine and France is lower – 16 % and 45 %, respectively. The leaders among domestic manufacturers in Ukraine are Yuria-Pharm LLC and Astrapharm LLC , in France they are Sanofi Winthrop Industrie , Mylan S.A.S. , Delpharm Tours , Delpharm Lille S.A.S. and Panpharma . In the two countries, the majority of drugs for COPD antibiotic therapy treatment is manufactured as powders for solutions and injections, and as tablets; their share in Ukraine is 41 % and 33 %, in France – 19 % and 59 %, respectively. Monocomponent drugs prevail in Ukraine and France. Since the Ukrainian pharmaceutical market, in comparison with the French drug market, is significantly dominated by foreign drugs, it is important to develop new domestic drugs that would be used in COPD treatment.

Mitsubishi names Jean-Marc Gilson its next CEO

Mitsubishi Chemical Holdings has named Jean-Marc Gilson, a Belgian-born chemical executive, its CEO effective April 1, 2021. He will succeed Hitoshi Ochi, who plans to retire. Currently the CEO of Roquette, a French food and drug ingredient company, Gilson has held executive positions at Dow Corning and Avantor Performance Materials. He worked for 5 years in Japan for Dow Corning. Gilson will be the first foreign CEO of Japan’s largest chemical company. His appointment comes as other Japanese chemical firms act to diversify their boards and management. JSR, for example, elevated the American executive Eric Johnson to CEO in 2018. In an Oct. 23 video press conference, Gilson declined to specify changes he would make to Mitsubishi’s diversified portfolio. But he cited DSM as a model for portfolio transformation, noting that the Dutch firm—a major competitor of Roquette’s—has shifted from chemicals to food, nutrition, and health products over the past