Impact of Hospitalization in an Endocrinology Department on Vaccination Coverage in People Living with Diabetes: A Real-Life Study.

Background and Objectives: Vaccination coverage is suboptimal in people living with diabetes. The objectives of this study were to determine the impact of hospitalization on vaccination coverage and the variables associated with vaccination during hospital stay. Materials and Methods: This observational study was conducted from May 2019 to December 2019 in the Endocrinology-Nutrition-Diabetes Department of the University Hospital of Montpellier, France. This department encompasses three medical units, two of which have a full-time clinical pharmacist involved in the multidisciplinary management of patients. All adult diabetic patients who completed a questionnaire about vaccines were prospectively included by a clinical pharmacist and followed until department discharge. Coverage at the time of admission for the tetanus, diphtheria, pertussis (Tdap), pneumococcal, influenza, and herpes zoster vaccines was assessed from patient interviews and/or contact with the general practitioner and/or with the community pharmacist. Multivariable logistic regression analysis was performed to identify the factors associated with a vaccination update during the hospital stay. Results: A total of 222 patients were included (mean age: 59.4 years, 68.5% type 2 diabetes). Vaccination coverage increased by 26.7% (47.3% to 59.9%), 188.0% (10.8% to 31.1%) and 8.9% (45.9% to 50.0%), respectively, for the Tdap, pneumococcal and influenza vaccines during hospital stay. Female sex, admission to a diabetes care unit with a full-time pharmacist, favorable feelings about vaccination, unknown immunization coverage for pneumococcal vaccines, and evaluation and recording of vaccine coverage at admission in the patient medical records were associated with at least one vaccination during hospital stay. Conclusions: Our real-life study highlights that hospitalization and multidisciplinary management (i.e., physician-pharmacist) may be key points in the diabetes care pathway to improve vaccination coverage, especially for patients with advanced diabetes and comorbidities.

Impact of medication characteristics and adverse drug events on hospital admission after an emergency department visit: Prospective cohort study.

OBJECTIVES: Emergency department (ED) overcrowding is a problem for the delivery of adequate and timely emergency care. To improve patient flow and the admission process, the quick prediction of a patient's need for admission is crucial. We aimed to investigate the variables associated with hospitalisation after an ED visit, with a particular focus on the variables related to medication. METHODS: This prospective study was conducted from 2011 to 2018 in subacute medical ED of a French University Hospital. Specialised EDs (paediatric, gynaecologic, head and neck and psychiatric) and the outpatient unit of the ED were not included. Participation in this study was proposed to all adult patients who underwent a medication history interview with a pharmacist. Pharmacists conducted structured interviews for the completion of the medication history and the detection of adverse drug events (ADE). Relations between patient characteristics and hospitalisation were analysed using logistic regression. RESULTS: Among the 14 511 included patients, 5972 (41.2%) were hospitalised including 69 deaths. In total, 7458 patients (51.4%) took more than 5 medications and 2846 patients (19.6%) had an ADE detected during the ED visit. In hospitalised patients, bleeding (32.2%) and metabolic disorders (16.8%) were the most observed ADE symptoms. Variables associated with increased hospital admission included 2 demographic variables (age, male gender), 4 clinical variables (renal and hepatic failures, alcohol addiction, ED visit for respiratory reason) and 6 medication-related variables (medications >5, use of blood, systemic anti-infective, metabolism and antineoplastic/immunomodulating medications and ADE). CONCLUSION: We identified variables associated with hospitalisation including drug-related variables. These results point out the importance and the relevance of collecting medication data in a subacute medical ED (study registered on ClinicalTrials.gov, NCT03442010).

Compliance with Prescription Guidelines for Glucose-Lowering Therapies According to Renal Function: Real-Life Study in Inpatients of Internal Medicine, Endocrinology and Cardiology Units.

Background and objectives: Renal failure is a contraindication for some glucose-lowering drugs and requires dosage adjustment for others, particularly biguanides, sulfonylureas, and inhibitors of dipeptidyl peptidase 4. In this study, we assessed adherence to prescription recommendations for glucose-lowering drugs according to renal function in hospitalized diabetic subjects. Materials and Methods: This prospective cohort study was carried out over a 2-year period in a university hospital. Glomerular filtration rate (GFR) was determined by averaging all measurements performed during hospitalization. Glucose-lowering drug dosages were analyzed according to the recommendations of the relevant medical societies. Results: In total, 2071 diabetic patients (53% hospitalized in cardiology units) were examined. GFR was <30 mL/min/1.73 m2 in 13.4% of these patients, 30-44 in 15.1%, 45-60 in 18.3%, and >60 in 53.3%. Inappropriate oral glucose-lowering treatments were administered to 273 (13.2%) patients, including 53 (2.6%) with a contraindication. In cardiology units, 53.1% and 14.3% of patients had GFRs of <60 and <30 mL/min/1.73 m2, respectively, and 179 (15.4%) patients had a contraindication or were prescribed an excessive dose of glucose-lowering drugs. Conclusions: We showed that the burden of inappropriate prescriptions is high in diabetic patients. Given the high number of patients receiving these medications, particularly in cardiology units, a search for potential adverse effects related to these drugs should be performed.

Involvement of Pharmacists in the Emergency Department to Correct Errors in the Medication History and the Impact on Adverse Drug Event Detection.

(1) Incomplete or wrong medication histories can lead to missed diagnoses of Adverse Drug Effects (ADEs). We aimed to evaluate pharmacist-identified ED errors in the medication histories obtained by physicians, and their consequences for ADE detection. (2) This prospective monocentric study was carried out in an ED of a university hospital. We included adult patients presenting with an ADE detected in the ED. The best possible medication histories collected by pharmacists were used to identify errors in the medication histories obtained by physicians. We described these errors, and identified those related to medications involved in ADEs. We also identified the ADEs that could not have been detected without the pharmacists' interventions. (3) Of 735 patients presenting with an ADE, 93.1% had at least one error on the medication list obtained by physicians. Of the 1047 medications involved in ADEs, 51.3% were associated with an error in the medication history. In total, 23.1% of the medications involved in ADEs were missing in the physicians' medication histories and were corrected by the pharmacists. (4) Medication histories obtained by ED physicians were often incomplete, and half the medications involved in ADEs were not identified, or were incorrectly characterized in the physicians' medication histories.

Frequency, Characteristics, and Predictive Factors of Adverse Drug Events in an Adult Emergency Department according to Age: A Cross-Sectional Study.

Adverse drug events (ADEs) are a major public health concern, given their consequences in terms of morbi-mortality and associated healthcare costs. Many studies have focused on the elderly, who are considered particularly vulnerable in this respect. We aimed to determine and compare the frequency, characteristics, and predictive factors of ADEs according to age in an adult population. A prospective seven-year cross-sectional study was conducted in a university hospital emergency department. Structured medication reviews and ADE detection were performed. Patient data and ADE characteristics were collected. Descriptive statistics and logistic regression were performed in two age groups: Group 1 (age < 65 years) and 2 (age ≥ 65 years). Among the 13,653 patients included, 18.4% in Group 1 and 22.6% in Group 2 experienced an ADE. Differences were identified in terms of the ADE type (more ADEs due to noncompliance in Group 1) and ADE symptoms (greater bleeding in Group 2). In the multivariable analysis, several specific predictive factors were identified, including kidney failure and antidiabetic drug use in Group 1 and inappropriate prescription and antithrombotic treatment in Group 2. Analysis by age provided a more refined vision of ADEs as we identified distinct profiles of iatrogenesis. These results will lead to a better detection of ADEs.

Hypoglycemia While Driving in Insulin-Treated Patients: Incidence and Risk Factors.

OBJECTIVES: This study aimed to investigate a potential daily-life concern for patients with diabetes hypoglycemia while driving by (1) estimating their incidence in insulin-treated drivers, (2) determining factors associated with their occurrence, and (3) analyzing patients' behavior regarding prevention of hypoglycemia. METHODS: We conducted an observational study from November 2013 to May 2018 in the endocrinology-diabetology-nutrition department of our university hospital. All patients treated for diabetes older than 18 years admitted in the department were eligible. A specific questionnaire assessing attitudes, knowledge, and consequences of hypoglycemia was provided. In this study, only insulin-treated patients who regularly drive were analyzed. RESULTS: On the 233 insulin-treated drivers included, 45 (19%) self-reported at least 1 hypoglycemia while driving in the preceding year. Two factors were significantly associated with their occurrence: type 1 diabetes (odds ratio [OR] = 3.19; 95% confidence interval [CI] = 1.55-6.57) and experiences of asymptomatic hypoglycemia (OR = 2.20; 95% CI = 1.05-4.63). Awareness of the treatment hypoglycemia risk because of information provided by a medical specialist was also but nonsignificantly associated with hypoglycemia while driving (OR = 2.61; 95% CI = 0.86-7.92). Forty-one patients (18%) combined those 3 variables, 20 (49%) of them self-reported hypoglycemia while driving. Thirty-four percent of the patients never carried carbohydrates for hypoglycemia correction. Seventy-six percent do not monitor blood glucose level before driving. CONCLUSIONS: Our questionnaire allowed us to highlight that 19% our cohort of insulin-treated drivers declared experiencing hypoglycemia while driving. Risk factors identified and prevention data collected should help us better target patient education.

Adverse Drug Events Detected by Clinical Pharmacists in an Emergency Department: A Prospective Monocentric Observational Study.

OBJECTIVES: Adverse drug events (ADEs) are a major public health issue in hospitals. They are difficult to detect because of incomplete or unavailable medication history. In this study, we aimed to assess the rate and characteristics of ADEs identified by pharmacists in an emergency department (ED) to identify factors associated with ADEs. METHODS: In this prospective observational study, we included consecutive adult patients presenting to the ED of a French 2600-bed tertiary care university hospital from November 2011 to April 2015. Clinical pharmacists conducted structured interviews and collected the medication history to detect ADEs (i.e., injuries resulting directly or indirectly from adverse drug reactions and noncompliance to medication prescriptions). Unsure ADE cases were reviewed by an expert committee. Relations between patient characteristics, type of ED visit, and ADE risk were analyzed using logistic regression. RESULTS: Among the 8275 included patients, 1299 (15.7%) presented to the ED with an ADE. The major ADE symptoms were bleeding, endocrine problems, and neurologic disorders. Moreover, ADEs led to the ED visit, hospitalization, and death in 87%, 49.3%, and 2.2% of cases, respectively. Adverse drug event risk was independently associated with male sex, ED visit for neurological symptoms, visit to the ED critical care unit, or ED short stay hospitalization unit, use of blood, anti-infective, antineoplastic, and immunomodulating drugs. CONCLUSIONS: This study improves the knowledge about ADE characteristics and on the patients at risk of ADE. This could help ED teams to better identify and manage ADEs and to improve treatment quality and safety.

The COVID-19 Pandemic Led to a Small Increase in Changed Mentality Regarding Infection Risk without Any Change in Willingness to Be Vaccinated in Chronic Diseases Patients.

The objective of this study was to assess the impact of the COVID-19 pandemic on patients' perceptions regarding infection risk and vaccination in subjects suffering from chronic diseases. A prospective observational multicentric study conducted from December 2020 to April 2021 in three French University Hospitals. Patients with chronic diseases were proposed to complete a questionnaire regarding the impact of the COVID-19 pandemic on infectious risk knowledge and vaccination. A total of 1151 patients were included and analyzed (62% of which were people with diabetes). The COVID-19 pandemic increased awareness of infectious risks by 19.3%, significantly more in people with diabetes (23.2%, from 54.4% to 67.0%, p < 0.01) when compared to the other high-risk patients (12.5%, from 50.5% to 56.8%, p = 0.06). Respectively, 30.6% and 16.5% of patients not up-to-date for pneumococcal and flu vaccines reported wanting to update their vaccination due to the COVID-19 pandemic. By contrast, the proportion of patients against vaccines increased during the COVID-19 pandemic (6.0% vs. 9.5%, p < 0.01). The COVID-19 pandemic has led to a small increase in awareness regarding the risks of infection in patients with chronic diseases, including people with diabetes, but without any change in willingness to be vaccinated. This underlines the urgent need to sensibilize people with diabetes to infection risk and the importance of vaccination.

Kinetics of circulating cell-free DNA for biomedical applications: critical appraisal of the literature.

Circulating cell-free DNA is considered as one of the major breakthroughs in the field of innovative diagnosis, used as a liquid biopsy. The kinetic parameters of a biomarker are mandatory to assess its usefulness as a diagnostic tool. Obtaining precise mathematical values for the kinetic parameters (e.g., half-life) is then crucial because it could be used for therapeutic monitoring as a prognostic factor. However, little is known about the intrinsic properties of circulating cell-free DNA, more especially, its kinetic properties within the organism. We summarized the basic principles that may affect the kinetics of circulating cell-free DNA within the organism in the light of biological and clinical evidence. We also meta-analyzed the reported data in the literature and the methodologies that have been used to study the kinetic parameters of human circulating cell-free DNA in vivo.

Target-Mediated Drug Disposition Population Pharmacokinetics Model of Alirocumab in Healthy Volunteers and Patients: Pooled Analysis of Randomized Phase I/II/III Studies.

BACKGROUND AND OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 inhibition with monoclonal antibodies such as alirocumab significantly reduces low-density lipoprotein-cholesterol levels ± other lipid-lowering therapies. We aimed to develop and qualify a population pharmacokinetics (PopPK) model for alirocumab in healthy subjects and patients, taking into account the mechanistic target-mediated drug disposition (TMDD) process. METHODS: This TMDD model was developed using a subset of the alirocumab clinical trial database, including nine phase I/II/III studies (n = 527); the model was subsequently expanded to a larger data set of 13 studies (n = 2870). Potential model parameters and covariate relationships were explored, and predictive ability was qualified using a visual predictive check. RESULTS: The TMDD model was built using the quasi-steady-state approximation. The final TMDD-quasi-steady-state model included a significant relationship between distribution volume of the central compartment and disease state: distribution volume of the central compartment was 1.56-fold higher in patients vs. healthy subjects. Separately, application of the model to the expanded data set revealed a significant relationship between linear clearance and statin co-administration: linear clearance was 1.27-fold higher with statins. The good predictive performance of the TMDD model was assessed based on graphical and numerical quality criteria, together with the visual predictive check and comparison of the predictions to those from a PopPK model with parallel linear and Michaelis-Menten clearances (i.e., simplification of the TMDD PopPK model). CONCLUSIONS: This mechanistic TMDD PopPK model integrates the interaction of alirocumab with its target and accurately predicts both alirocumab and total proprotein convertase subtilisin/kexin type 9 concentrations in healthy subjects and patients.