Evaluation of an e-Learning Program for Community Pharmacists for Dispensing Emicizumab (Hemlibra) in France: Nationwide Cross-Sectional Study.

BACKGROUND: Since June 2021, patients with hemophilia A with antifactor VIII inhibitors and those with severe hemophilia A without antifactor VIII inhibitors treated with Hemlibra have had to choose between a community or hospital pharmacy. The French reference center for hemophilia developed the HEMOPHAR e-learning program for community pharmacists for dispensing emicizumab. OBJECTIVE: This study aims to evaluate the efficiency and safety of this new care pathway by assessing the HEMOPHAR e-learning program. METHODS: The methodology is based on Kirkpatrick's model for evaluating the immediate reaction of trained community pharmacists (level 1), their level of acquired knowledge (level 2), and their professional practice after 3 months of dispensation (level 3). RESULTS: The HEMOPHAR e-learning program reached a large audience, with 67% (337/502) of the eligible community pharmacists following it. The immediate reaction was overall satisfying. High rates of engagement were reported with 63.5% (214/337) to 73.3% (247/337) of completed training modules, along with high rates of success with quizzes of 61.5% (174/337) to 95.7% (244/337). We observed that 83.9% (193/230) of the community pharmacists needed less than 2 attempts to pass the quiz of the module related to professional practice, while the other quizzes required more attempts. Advice on compliance and drug interactions were most frequently provided to patients by the community pharmacists. CONCLUSIONS: This study suggests ways to improve the training of community pharmacists and to optimize coordination with treatment centers. This study also reports on the feasibility of switching to a community pharmacy in a secure pharmaceutical circuit, including in the context of a rare bleeding disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT05449197; https://clinicaltrials.gov/study/NCT05449197. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/43091.

Improving EMS response times for out-of-hospital cardiac arrest in urban areas using drone-like vertical take-off and landing air ambulances: An international, simulation-based cohort study.

BACKGROUND: Advances in vertical take-off and landing (VTOL) technologies may enable drone-like crewed air ambulances to rapidly respond to out-of-hospital cardiac arrest (OHCA) in urban areas. We estimated the impact of incorporating VTOL air ambulances on OHCA response intervals in two large urban centres in France and Canada. METHODS: We included adult OHCAs occurring between Jan. 2017-Dec. 2018 within Greater Paris in France and Metro Vancouver in Canada. Both regions utilize tiered OHCA response with basic (BLS)- and advanced life support (ALS)-capable units. We simulated incorporating 1-2 ALS-capable VTOL air ambulances dedicated to OHCA response in each study region, and computed time intervals from call reception by emergency medical services (EMS) to arrival of the: (1) first ALS unit ("call-to-ALS arrival interval"); and (2) first EMS unit ("call-to-first EMS arrival interval"). RESULTS: There were 6,217 OHCAs included during the study period (3,760 in Greater Paris and 2,457 in Metro Vancouver). Historical median call-to-ALS arrival intervals were 21 min [IQR 16-29] in Greater Paris and 12 min [IQR 9-17] in Metro Vancouver, while median call-to-first EMS arrival intervals were 11 min [IQR 8-14] and 7 min [IQR 5-8] respectively. Incorporating 1-2 VTOL air ambulances improved median call-to-ALS arrival intervals to 7-9 min and call-to-first EMS arrival intervals to 6-8 min in both study regions (all P < 0.001). CONCLUSION: VTOL air ambulances dedicated to OHCA response may improve EMS response intervals, with substantial improvements in ALS response metrics.

Evaluation of the care pathway in the context of the dispensing of emicizumab (Hemlibra) in community and hospital pharmacies in France: A patient satisfaction survey.

INTRODUCTION: Since June 2021 in France, patients with haemophilia A with anti-factor VIII inhibitors and patients with severe haemophilia A without anti-factor VIII inhibitors, and treated with emicizumab (Hemlibra), have to choose the dispensing circuit community or hospital pharmacy. AIM: To evaluate satisfaction of patients whether they choose dispensation from a community pharmacy or retained dispensation from the hospital pharmacy, to understand the main motivation for choosing the community or the hospital pharmacy. METHODS: All patients living in France, regardless of age, were eligible to participate. Between September 13, 2022, and January 9, 2023, 175 respondents answered the satisfaction survey, including 123 in community pharmacy and 52 in hospital pharmacy. RESULTS: Eighteen months after availability in community pharmacies, treatment accessibility is improved for the benefit of the patient. The door-to-door travel times are significantly reduced to the community pharmacy with an average gain of 16.5 min saved from the place of residence. Patients are mostly satisfied with the new dispensing circuit especially concerning the overall satisfaction (p < .0001), the travel time (p < .0001) and the strong relationship with the pharmacist (p = .0022) compared to hospital pharmacy. CONCLUSION: Innovation in care pathways is showing its full potential in improving access to medication, made possible by the implementation of a rigorous organization accompanied by training to enable healthcare professionals involved in primary care to provide appropriate management.

Evaluation of the Care Pathway in the Context of the Dispensing of Emicizumab (Hemlibra) in Community Pharmacies in France: Protocol for a Cross-sectional Study Based on the Kirkpatrick Model.

BACKGROUND: Commercialized since 2019, emicizumab (Hemlibra) was available only in French hospital pharmacies for prophylaxis of hemophilia A with or without inhibitors. Since June 15, 2021, patients can choose between a hospital and community pharmacy. These changes in the care pathway have important organizational consequences for patients, their relatives, and health professionals. Two training programs are available for community pharmacists: the "HEMOPHAR" training program proposed by the national reference center for hemophilia and the Roche training program proposed by the laboratory that markets the product. OBJECTIVE: The PASODOBLEDEMI study aims to evaluate the direct impact of the training programs provided to community pharmacists in the context of the dispensing of emicizumab, and to evaluate patients' satisfaction with their treatment whether they choose dispensation from a community pharmacy or retained dispensation from the hospital pharmacy. METHODS: We designed a cross-sectional study based on the 4-level Kirkpatrick evaluation model: the immediate reaction of community pharmacists following training (Reaction), the knowledge acquired during the training (Learning), the professional practice of community pharmacists during dispensing of the product (Behavior), and patients' satisfaction related to the treatment whether it is dispensed from a hospital or from a community pharmacy (Results). RESULTS: Considering that single outcome measures cannot adequately reflect the complexity of this new organization, the Kirkpatrick evaluation model provides 4 distinct outcomes: the immediate reaction after the HEMOPHAR training program, the level of knowledge acquired after the HEMOPHAR training program, the impact of training on professional practice, and patient satisfaction with access to emicizumab. We developed specialized questionnaires for each of the 4 levels of the Kirkpatrick evaluation model. All community pharmacists involved in dispensing emicizumab, whether they have followed the HEMOPHAR or the Roche training program or neither, were eligible for inclusion. All patients with severe hemophilia A were eligible, irrespective of inhibitor use, age, treatment with emicizumab, and whether they chose dispensation from a community pharmacy or retained dispensation from a hospital pharmacy. CONCLUSIONS: The new organization for dispensing emicizumab to patients with hemophilia A in French community pharmacies must be accompanied by optimal safety and quality conditions due to the risk of serious and urgent bleeding situations in the management of rare bleeding diseases. The elaboration of the PASODOBLEDEMI protocol has already a positive impact with the commitment of all health professionals, physicians, hospital and community pharmacists, and the patient community. The results will be disseminated among the French authorities and will enable, if necessary, proposing this access model to other rare diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT05449197, https://clinicaltrials.gov/ct2/show/NCT05449197?term=NCT05449197; ClinicalTrials.gov NCT05450640, https://clinicaltrials.gov/ct2/show/NCT05450640?term=NCT05450640. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43091.

Impact of the 2015 European guidelines for resuscitation on traumatic cardiac arrest outcomes and prehospital management: A French nationwide interrupted time-series analysis.

AIM: To evaluate the impact of the 2015 European Resuscitation Council (ERC) guidelines on patient outcomes following traumatic cardiac arrest (TCA) and on advanced life support interventions carried out by physician-staffed ambulances. METHODS: Data of TCA patients aged ≥18 years were extracted from the French nationwide cardiac arrest registry. A pre- (2011-2015) and a post-publication period (2016-2020) were defined. In the guidelines, a specific TCA management algorithm was introduced to prioritise the treatment of reversible causes. Its impact was evaluated using adjusted interrupted time series analysis. RESULTS: 4,980 patients were treated (2,145 during the pre-publication period and 2,739 during the post-publication period). There was no significant change in the rates of prehospital ROSC (22.4% vs. 20.2%, p = 0.07 in the pre- and post- intervention respectively), survival (1.4% vs. 1.4%, p = 0.87) or good neurological outcome (71.4% vs. 66.7%, p = 0.93) or in the incidence of organ donation (1.6% vs. 1.3%, p = 0.50). There were nonsignificant changes in the adjusted temporal trend for ROSC (aOR 0.88; 95% CI [0.77; 1.00]), survival (aOR 1.34; 95% CI [0.83;2.17]), good neurological outcome (aOR 1.57; 95% CI [0.82;3.05]), and organ donation (aOR 1.06; 95% CI [0.71;1.60]). The use of intraosseous catheters (13.0% vs. 19.2%, p < 0.001), external haemorrhage control measures (23.9% vs. 64.8%, p < 0.001), bilateral chest decompression (13.7% vs. 16.5%, p = 0.009), and packed red cell transfusion (2.7% vs. 6.5%, p < 0.001) increased in the post-publication period. CONCLUSIONS: Despite the increased frequency of trauma rescue interventions performed by on-scene physicians, no change in patient-centred outcomes was associated with the publication of the 2015 ERC guidelines in France.

Association between location of out-of-hospital cardiac arrest, on-scene socioeconomic status, and accessibility to public automated defibrillators in two large metropolitan areas in Canada and France.

AIM: To compare walking access times to automated external defibrillators (AEDs) between area-level quintiles of socioeconomic status (SES) in out-of-hospital cardiac arrest (OHCA) cases occurring in 2 major urban regions of Canada and France. METHODS: This was an international, multicenter, retrospective cohort study of adult, non-traumatic OHCA cases in the metropolitan Vancouver (Canada) and Rhône County (France) regions that occurred between 2014 and 2018. We calculated area-level SES for each case, using quintiles of country-specific scores (Q5 = most deprived). We identified AED locations from local registries. The primary outcome was the simulated walking time from the OHCA location to the closest AED (continuous and dichotomized by a 3-minute 1-way threshold). We fit multivariate models to analyze the association between OHCA-to-AED walking time and outcomes (Q5 vs others). RESULTS: A total of 6,187 and 3,239 cases were included from the Metro Vancouver and Rhône County areas, respectively. In Metro Vancouver Q5 areas (vs Q1-Q4), areas, AEDs were farther from (79 % over 400 m from case vs 67 %, p < 0.001) and required longer walking times to (97 % above 3 min vs 91 %, p < 0.001) cases. In Rhône Q5 areas, AEDs were closer than in other areas (43 % over 400 m from case vs 50 %, p = 0.01), yet similarly poorly accessible (85 % above 3 min vs 86 %, p = 0.79). In multivariate models, AED access time ≥ 3 min was associated with decreased odds of survival at hospital discharge in Metro Vancouver (odds ratio 0.41, 95 % CI [0.23-0.74], p = 0.003). CONCLUSIONS: Accessibility of public AEDs was globally poor in Metro Vancouver and Rhône, and even poorer in Metro Vancouver's socioeconomically deprived areas.

PHAREO study: Perceived and observed accessibility to therapeutic drugs used for treating patients with inherited bleeding disorders.

WHAT IS KNOWN AND OBJECTIVE: The dispensing of clotting factor concentrates in hospital pharmacies imposes accessibility constraints on patients and their caregivers, thereby increasing the disease burden. Very few studies have addressed these issues so far in terms of individual perceptions and actual difficulties. The PHAREO study aims to report patient's perception of treatment accessibility and evaluate spatial accessibility. METHODS: The PHAREO study is an observational survey based on a questionnaire specifically designed for the study purpose in collaboration with patients' representatives in the second demographic and economic French region. RESULTS AND DISCUSSION: We collected 293 responses (participation rate of 64.1%) which show that 89.8% of respondents were either very or rather satisfied with regard to access to treatment. However, respondents reported difficulties in accessing the hospital pharmacy. The data also showed that 79.2% of respondents tended to over-estimate travel time which was reported above their acceptable threshold for 39.2% of them. The main determinants of dissatisfaction were parental burden (OR 2.5 [1.3; 4.8], p = 0.008) and waiting time at the hospital pharmacy (OR 1.5 [1.1;2.0], p = 0.016, per 10 min increase). WHAT IS NEW AND CONCLUSION: The PHAREO study provides subjective and objective data regarding satisfaction levels of persons with haemophilia and other coagulation deficiencies, with a high representativeness rate for patients on prophylaxis (87.5%). Both respondents and hospital pharmacists pled for an evolution of the current dispensing circuit to improve access to treatment and reduce the burden for patients. Currently, the community pharmacists are apart from the dispensing circuit. The authors propose improvements in the pathway of care for patients and their caregivers by including the community pharmacists alongside the hospital pharmacists in a centralized coordination scheme.

Rationale, development and implementation of the ReACanROC registry for out-of-hospital cardiac arrests in France and Canada.

France and Canada prehospital systems and care delivery in out-of-hospital cardiac arrests (OHCAs) show substantial differences. This article aims to describe the rationale, design, implementation and expected research implications of the international, population-based, France-Canada registry for OHCAs, namely ReACanROC, which is built from the merging of two nation-wide, population-based, Utstein-style prospectively implemented registries for OHCAs attended to by emergency medical services. Under the supervision of an international steering committee and research network, the ReACanROC dataset will be used to run in-depth analyses on the differences in organisational, practical and geographic predictors of survival after OHCA between France and Canada. ReACanROC is the first Europe-North America registry ever created to meet this goal. To date, it covers close to 80 million people over the two countries, and includes approximately 200 000 cases over a 10-year period.

Development and Validation of a Predictive Model of Hypovitaminosis D in General Adult Population: SCOPYD Study.

The worldwide global increase in serum 25-hydroxyvitamin D (25(OH)D) measurements has led some countries to restrict reimbursement for certain clinical situations only. Another approach could consist in providing physicians with screening tools in order to better target blood test prescription. The objective of the SCOPYD study was to identify the best combination of predictors of serum VitD concentration among adults aged 18-70 years. Potential risk factors for VitD deficiency were collected using a comprehensive self-administered questionnaire. A multivariable linear regression was used to build a predictive model of serum 25(OH)D concentration. Among 2488 participants, 1080 (43.4%) had VitD deficiency (<50 nmol/L) and 195 (7.8%) had severe deficiency (<25 nmol/L). The final model included sunlight exposure in the preceding week and during the last holidays, month of blood sampling, age, sex, body mass index, skin phototype, employment, smoking, sport practice, latitude, and VitD supplementation in preceding year. The area under the curve was 0.82 (95% CI (0.78; 0.85)) for severe deficiency. The model predicted severe deficiency with a sensitivity of 77.9% (95% CI (69.1; 85.7)) and a specificity of 68.3% (95% CI (64.8; 71.9)). We identified a set of predictors of severe VitD deficiency that are easy to collect in routine that may help to better target patients for serum 25(OH)D concentration determination.

Discovering the underlying typology of emergency departments.

BACKGROUND: We hypothesized that monitoring the volume of activity and overall performance indicators is not sufficient to understand the underlying differences between emergency departments. We aimed to understand the underlying common characteristics of emergency departments and map their typology in order to propose adaptive solutions, that would take into account territorial specificities and manage existing resources. METHODS: We applied a multifactorial analysis based on input data at three levels; 1) the health care available in the area surrounding the emergency departments, 2) the level of medical technicality of the hospitals and 3) the profile of emergency department visits. RESULTS: We included 73 emergency departments in this study, representing 93.6% of the emergency departments in our region and seven groups were retained. The smallest group (n = 5) included both public and private structures with low volumes of activity. These medical structures were associated with the shortest length of stay and one of the lowest hospitalisation rates. The largest group (n = 21) included only public structures in peri-urban areas, which were associated with the highest rate of hospitalization in the region. The surrounding population was representative of the regional population, but the patients were older. CONCLUSIONS: This approach represents a systemic response to target the organisational needs and constraints, propose appropriate solutions and adjust the financial resources allocated to hospitals. Future policies to improve care delivery may benefit from stratifying solutions and performance objectives depending on these groups.

Estimating the Proportion of COVID-19 Contacts Among Households Based on Individuals With Myocardial Infarction History: Cross-sectional Telephone Survey.

BACKGROUND: Adults with cardiovascular diseases were disproportionately associated with an increased risk of a severe form of COVID-19 and all-cause mortality. OBJECTIVE: The aims of this study are to report the associated symptoms for COVID-19 cases, to estimate the proportion of contacts, and to describe the clinical signs and behaviors among individuals with and without myocardial infarction history among cases and contacts. METHODS: A 2-week cross-sectional telephone survey was conducted during the first lockdown period in France, from May 4 to 15, 2020. A total of 668 households participated, representing 703 individuals with pre-existing cardiovascular disease in the past 2 years and 849 individuals without myocardial infarction history. RESULTS: High rates of compliance with health measures were self-reported, regardless of age or risk factors. There were 4 confirmed COVID-19 cases that were registered from 4 different households. Based on deductive assumptions of the 1552 individuals, 9.73% (n=151) were identified as contacts, of whom 71.52% (108/151) were asymptomatic. Among individuals with a myocardial infarction history, 2 were COVID-19 cases, and the estimated proportion of contacts was 8.68% (61/703), of whom 68.85% (42/61) were asymptomatic. The cases and contacts presented different symptoms, with more respiratory signs in those with a myocardial infarction history. CONCLUSIONS: The telephone survey could be a relevant tool for reporting the number of contacts during a limited period and in a limited territory based on the presence of associated symptoms and COVID-19 cases in the households. This study advanced our knowledge to better prepare for future crises.

Management of decision of withholding and withdrawing life-sustaining treatments in French EDs.

BACKGROUND: Decisions of withholding or withdrawing life sustaining-treatments in emergency department are part of current practice but the decision-making process remains poorly described in the literature. STUDY OBJECTIVE: We conducted a study in two phases, the first comprising a retrospective chart review study of patients dying in the ED and the second comprising survey study of health care workers at 10 urban emergency departments in France. METHOD: In a first step, we analyzed medical records based on fifteen criteria of the decision-making process grouped into four categories: the collegiality, the traceability, the management and the communication as recommended by the international guidelines. In a second step, we conducted an auto-administrated survey to assess how the staff members (medical, paramedical) feel with the decision-making process. RESULTS: There were 273 deaths which occurred in the ED over the study period and we included 145 (53.1%) patients. The first-step analysis revealed that the traceability of the decision and the information given to patient or the relatives were the most reported points according to the recommendations. Three of the ten emergency departments had developed a written procedure. The collegial discussion and the traceability of the prognosis assessment were significantly increased in emergency department with a written procedure as well as management of pain, comfort care, and the communication with the patient or the relatives. In the second-step analysis, among the 735 staff members asked to take part in the survey, 287 (39.0%) answered. The medical and paramedical staff expressed difficult experience regarding the announcement and the communication with the patient and the relatives. CONCLUSION: The management of the decision to withhold or withdraw life-sustaining treatments must be improved in emergency departments according to the guidelines. A standard written procedure could be useful in clinical practice despite the lack of experienced difference between centers with and without procedures.

Spatial distribution and differences of stroke occurrence in the Rhone department of France (STROKE 69 cohort).

In France, 110,000 patients are admitted to hospital per year for stroke. Even though the relationship between stroke and risk factors such as low socio-economic status is well known, research in the spatial distribution (SD) of stroke as a contributing risk factor is less documented. Understanding the geographic differences of the disease may improve stroke prevention. In this study, a statistical spatial analysis was performed using a French cohort (STROKE 69) to describe spatial inequalities in the occurrence of stroke. STROKE 69 was a cohort study of 3,442 patients, conducted in the Rhône department of France, from November 2015 to December 2016. The cohort included all consecutive patients aged 18 years or older, with a likelihood of acute stroke within 24 hours of symptoms onset. Patients were geolocated, and incidence standardized rates ratio were estimated. SD models were identified using global spatial autocorrelation analysis and cluster detection methods. 2,179 patients were selected for analysis with spatial autocorrelation methods, including 1,467 patients with stroke, and 712 with a transient ischemic attack (TIA). Within both cluster detection methods, spatial inequalities were clearly visible, particularly in the northern region of the department and western part of the metropolitan area where rates were higher. Geographic methods for SD analysis were suitable tools to explain the spatial occurrence of stroke and identified potential spatial inequalities. This study was a first step towards understanding SD of stroke. Further research to explain SD using socio-economic data, care provision, risk factors and climate data is needed in the future.

Access to treatment among persons with hemophilia: A spatial analysis assessment in the Rhone-Alpes region, France.

OBJECTIVES: In France, only hospital pharmacies can dispense clotting factor concentrates to persons with hemophilia, which limits the access to care for the treatment and the prevention of bleeding episodes. Moreover, the cost of clotting factor concentrates may restrain the maintenance of sufficient stocks in hospital pharmacies. The aim of this study was to investigate the accessibility of clotting factor concentrates to persons with hemophilia in the context of long-term prophylaxis and emergency treatment in the Rhone-Alpes region of France. METHODS: A geographic information system was used for evaluating accessibility of clotting factor concentrates. Persons with hemophilia and hospital pharmacies were geolocalized with the use of postal data, and the evaluation of accessibility was based on the road network. RESULTS: Approximately 72% of the study area was accessible in less than 30 minutes to a hospital pharmacy. Eighty-five percent of persons with hemophilia had access to clotting factor concentrates for prophylactic treatment in less than 20 minutes. Most of them were patients with severe or moderate hemophilia. Regarding emergency doses, factor VIII was accessible in less than 30 minutes in 45.6% of the study area, and factor IX in 30.5%. CONCLUSION: This study highlights that spatial access to clotting factor concentrates by persons with hemophilia in the Rhône-Alpes region is good for prophylactic treatment but is more uneven for emergency doses.

Sex-Related Differences in Management and Outcome of Acute Ischemic Stroke in Eligible Patients to Thrombolysis.

BACKGROUND: Literature has highlighted sex-based differences in the natural course of stroke and in response to treatment with intravenous tissue plasminogen activator (tPA). OBJECTIVES: We aimed to compare the management and outcome of acute ischemic stroke (AIS) among women and men on a French registry based on a federated network of emergency physicians and neurologists. METHOD: We included 2,790 patients received tPA between 2010 and 2016 from the stroke centers in the RESUVal area. We provided age-adjusted analysis and multivariate models for determining the role of sex in the outcome measures. RESULTS: After age-adjustment, women presented more moderate to severe stroke at admission with more proximal occlusions. Among tPA eligible patients, the therapeutic strategy and in-hospital hemorrhagic complications were proportionally identical whatever the sex. The total ischemic time from onset symptom to thrombolysis did not differ from women to men. Age-adjusted 3-month mortality did not differ between women and men, and the determinants of mortality were age (relative risk [RR] 1.56 [1.37-1.78], p < 0.0001), proximal occlusion (RR 2.5 [1.88-3.33], p < 0.0001), and at least one complication (RR 2.43 [1.89-3.13], p < 0.0001). The determinants of poor functional outcome at 3 months were the sex (RR 1.22 [1.01-1.48] for women, p = 0.0385) and the occurrence of onset symptom in rural landscape (RR 1.26 [1.03-1.55], p = 0.0219) compared to urban landscape. CONCLUSIONS: We provided an exhaustive overview and real-life professional practices conditions in thrombolyzed AIS. Despite a later prehospital management in neurovascular units and more severe strokes at admission, women and men had both similar outcomes at hospital discharge and in 3-month survival, but women were associated to worst functional outcome at 3 months.