Antibiotic prescription in ambulatory care for COVID-19 patients: a cohort analysis in four European countries.

OBJECTIVE: To analyse antibiotic prescription rates in ambulatory care for COVID-19 patients by general practitioners (GPs) in four European countries. METHODS: A total of 4,513,955 anonymised electronic prescribing records of 3656 GPs in four European countries were analysed. Diagnosis and prescriptions were retrieved. Antibiotic prescription rates during COVID-19 consultations were analysed and compared between France, the UK, Belgium and Romania. RESULTS: Overall prescription rate was in France and Belgium (6.66 and 7.46%). However, analysing median GP prescribing rates, we found that 33.9% of the GPs in Belgium prescribed antibiotics with a median of 16 prescriptions per 100 COVID-19 consultations, while 55.21% of the GPs in France prescribed a median of 8 antibiotic prescriptions per 100 COVID-19 consultations. Overall antibiotic prescription rates were less in Romania than in the UK (22% vs 32%); however, 73% of the Romanian GPs vs 57% of the British GPs prescribed antibiotics. Depending on the country, the proportion of each type of antibiotic was statistically different, with the proportion of azithromycin being more than 50% of all antibiotics in each country except for the UK where it was less than 1%. CONCLUSION: Both individual GPs prescribing patterns in addition to overall consumption patterns should be analysed in order to implement a tailored antimicrobial stewardship programme. Furthermore, antibiotic prescribing rates in COVID-19 are lower than other respiratory tract infections.

Treatment patterns in essential tremor: Real-world evidence from a United Kingdom and France primary care database.

BACKGROUND AND PURPOSE: Essential tremor (ET) is one of the most common neurological disorders, but information on treatment pattern is still scant. The aim of this study was to describe the demographic and clinical characteristics, treatment patterns, and determinants of drug use in patients with newly diagnosed ET in France and the United Kingdom. METHODS: Incident cases of ET diagnosed between January 1, 2015 and December 31, 2018 with 2 years of follow-up were identified by using The Health Improvement Network (THIN®) general practice database. During the follow-up, we assessed the daily prevalence of use and potential switches from first-line to second-line treatment or other lines of treatment. Logistic regression models were conducted to assess the effect of demographic and clinical characteristics on the likelihood of receiving ET treatment. RESULTS: A total of 2957 and 3249 patients were selected in the United Kingdom and France, respectively. Among ET patients, drug use increased from 12 months to 1 month prior the date of index diagnosis (ID). After ID, nearly 40% of patients received at least one ET treatment, but during follow-up drug use decreased and at the end of the follow-up approximately 20% of patients were still on treatment. Among treated patients, ≤10% maintained the same treatment throughout the entire follow-up, nearly 20% switched, and 40%-75% interrupted any treatment. Results from the multivariate analysis revealed that, both in France and the United Kingdom, patients receiving multiple concomitant therapies and affected by psychiatric conditions were more likely to receive an ET medication. CONCLUSION: This study shows that ET is an undertreated disease with a lower-than-expected number of patients receiving and maintaining pharmacological treatment. Misclassification of ET diagnosis should be acknowledged; thus, results require cautious interpretation.

Association Between Diseases and Symptoms Diagnosed in Primary Care and the Subsequent Specific Risk of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Previous studies have reported a possible prodrome in multiple sclerosis (MS) defined by nonspecific symptoms including mood disorder or genitourinary symptoms and increased health care use detected several years before diagnosis. This study aimed to evaluate agnostically the associations between diseases and symptoms diagnosed in primary care and the risk of MS relative to controls and 2 other autoimmune inflammatory diseases with similar population characteristics, namely lupus and Crohn disease (CD). METHODS: A case-control study was conducted using electronic health records from the Health Improvement Network database in the United Kingdom and France. We agnostically assessed the associations between 113 diseases and symptoms in the 5 years before and after diagnosis in patients with subsequent diagnosis of MS. Individuals with a diagnosis of MS were compared with individuals without MS and individuals with 2 other autoimmune diseases, CD and lupus. RESULTS: The study population consisted of patients with MS (n = 20,174), patients without MS (n = 54,790), patients with CD (n = 30,477), and patients with lupus (n = 7,337). Twelve ICD-10 codes were significantly positively associated with the risk of MS compared with controls without MS. After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, 5 ICD-10 codes remained significantly associated with MS: depression (UK: odds ratio 1.22, 95% CI 1.11-1.34), sexual dysfunction (1.47, 1.11-1.95), constipation (1.5, 1.27-1.78), cystitis (1.21, 1.05-1.39), and urinary tract infections of unspecified site (1.38, 1.18-1.61). However, none of these conditions was selectively associated with MS in comparisons with both lupus and CD. All 5 ICD-10 codes identified were still associated with MS during the 5 years after diagnosis. DISCUSSION: We identified 5 health conditions associated with subsequent MS diagnosis, which may be considered not only prodromal but also early-stage symptoms. However, these health conditions overlap with prodrome of 2 other autoimmune diseases; hence, they lack specificity to MS.

A Comparison Between Early Presentation of Dementia with Lewy Bodies, Alzheimer's Disease, and Parkinson's Disease: Evidence from Routine Primary Care and UK Biobank Data.

OBJECTIVE: The purpose of this study was to simultaneously contrast prediagnostic clinical characteristics of individuals with a final diagnosis of dementia with Lewy Bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD) compared with controls without neurodegenerative disorders. METHODS: Using the longitudinal THIN database in the United Kingdom, we tested the association of each neurodegenerative disorder with a selected list of symptoms and broad families of treatments, and compared the associations between disorders to detect disease-specific effects. We replicated the main findings in the UK Biobank. RESULTS: We used data of 28,222 patients with PD, 20,214 with AD, 4,682 with DLB, and 20,214 healthy controls. All neurodegenerative disorders were significantly associated with the presence of multiple clinical characteristics before their diagnosis, including sleep disorders, falls, psychiatric symptoms, and autonomic dysfunctions. When comparing patients with DLB with patients with PD and patients with AD patients, falls, psychiatric symptoms, and autonomic dysfunction were all more strongly associated with DLB in the 5 years preceding the first neurodegenerative diagnosis. The use of statins was lower in patients who developed PD and higher in patients who developed DLB compared to patients with AD. In patients with PD, the use of statins was associated with the development of dementia in the 5 years following PD diagnosis. INTERPRETATION: Prediagnostic presentations of falls, psychiatric symptoms, and autonomic dysfunctions were more strongly associated with DLB than PD and AD. This study also suggests that although several associations with medications are similar in neurodegenerative disorders, statin usage is negatively associated with PD but positively with DLB and AD as well as development of dementia in PD. ANN NEUROL 2023;94:259-270.

Prescription of antibiotics by general practitioners for patients with a diagnosis of SARS- CoV-2 infection: Analysis of an electronic French health record.

OBJECTIVE: To define the factors associated with overprescription of antibiotics by general practitioners (GPs) for patients diagnosed with COVID-19 during the first wave of the pandemic. METHODS: Anonymised electronic prescribing records of 1370 GPs were analysed. Diagnosis and prescriptions were retrieved. The initiation rate by GP for 2020 was compared with 2017-2019. Prescribing habits of GPs who initiated antibiotics for > 10% of COVID-19 patients were compared with those who did not. Regional differences in prescribing habits of GPs who had consulted at least one COVID-19 patient were also analysed. RESULTS: For the March-April 2020 period, GPs who initiated antibiotics for > 10% of COVID-19 patients had more consultations than those who did not. They also more frequently prescribed antibiotics for non-COVID-19 patients consulting with rhinitis and broad-spectrum antibiotics for treating cystitis. Finally, GPs in the Île-de-France region saw more COVID-19 patients and more frequently initiated antibiotics. General practitioners in southern France had a higher but non-significant ratio of azithromycin initiation rate over total antibiotic initiation rate. CONCLUSION: This study identified a subset of GPs with overprescribing profiles for COVID-19 and other viral infections; they also tended to prescribe broad-spectrum antibiotics for a long duration. There were also regional differences concerning antibiotic initiation rates and the ratio of azithromycin prescribed. It will be necessary to evaluate the evolution of prescribing practices during subsequent waves.

Association of Adherence to Endocrine Therapy Among Patients With Breast Cancer and Potential Drug-Drug Interactions.

Importance: Suboptimal adherence to endocrine therapy (ET) among patients with hormone-receptor-positive breast cancer significantly affects survival outcomes and is associated with higher hospitalization rates and health care costs. Weak adherence to long-term treatments has multiple determinants, including disease characteristics, treatment adverse effects, and patients' attributes, such as age and comorbidities. Objective: To examine whether potential drug-drug interactions (PDDI) with tamoxifen or aromatase inhibitor were associated with adherence to ET in patients with early and advanced breast cancer. Design, Setting, and Participants: This cohort study used anonymized health record data of women with breast cancer who received ET in a private observational primary care database. Patients eligible for analysis included women aged 18 years or older who had a reported diagnosis of breast cancer and received ET with tamoxifen or aromatase inhibitor between 1994 and 2021. Data were analyzed 2021. Exposures: Adherence to ET during a given year was defined by a medication possession ratio of 80% or greater over 1-year prescription periods. PDDI were categorized into absent, minor (a combination to take into account), moderate (combination requiring precautions for use), major (combination not recommended), and contraindicated according to guidelines in the Claude Bernard Drug Database. Main Outcomes and Measures: We used regression models to estimate odds ratios (ORs) and 95% CIs for the associations between adherence and age, baseline comorbidities, PDDI, and adherence to ET during the previous year. Results: A total of 10 863 patients who were prescribed ET for breast cancer were eligible for the analysis (age 70 years or older, 3509 patients [32.3%]). In the tamoxifen cohort (3564 patients), PDDI were reported in 497 of 3670 patients (13.5%) at baseline (moderate, 254 patients [51.1%]; major, 227 patients [45.7%]), 2047 of 4831 patients (42.4%) at year 1, 1127 of 2751 patients (41.0%) at year 2, 761 of 1861 patients (40.9%) at year 3, 376 of 1058 patients (35.5%) at year 4, and 201 of 593 patients (33.9%) at year 5. In the aromatase inhibitor cohort (7299 patients), PDDI were reported in 592 of 7437 patients (8.0%) at baseline (moderate in 588 of 592 patients [99.3%]), which reached 2875 of 9031 patients (31.8%) at year 1 and ranged between 31.4% (1802 of 5730 patients in year 2) and 32.8% (791 of 2411 in year 4) throughout the study period. No association between adherence and PDDI was found in the tamoxifen (OR, 0.99; 95% CI, 0.91-1.08) or aromatase inhibitor (OR, 1.05; 95% CI, 0.95-1.15) cohort. Conclusions and Relevance: In this cohort of patients with hormone-receptor-positive breast cancer, PDDI with tamoxifen and aromatase inhibitors were not associated with adherence to ET.

Time trends in the incidence of essential tremor: Evidences from UK and France primary care data.

Introduction: Although essential tremor (ET) is considered a common adult movement disorder, evidence on its incidence is still scant. This study aims at estimating ET incidence in two European countries, namely, the UK and France. Methods: Incident cases of ET were identified within the Health Improvement Network (THIN®) database between 1st January 2014 and 31 December 2019. Yearly crude and standardized incidence rates (IR) were estimated across the study period for both countries. Poisson regression models were built to assess temporal trends in IRs and differences between sexes and age classes. Results: In total, 4,970 and 4,905 incident cases of ET were identified in the UK and France, respectively. The yearly average crude IR (per 100,000 person-years) was 18.20 (95%CI: 15.09-21.32) in UK and 21.42 (17.83-25.00) in France, whereas standardized ones were 19.51 (18.97-20.01) and 19.50 (18.97-20.05). Regression analyses showed slightly increasing trends in both countries, higher incidence among males, and a significant increase with age. Yearly average IR increased from 3.96 (0.95-6.97) and 5.28 (1.12-9.44) in subjects aged <20 years to 49.27 (26.29-72.24) and 51.52 (30.19-72.86) in those aged >80 year in UK and France. Conclusions: Standardized ET incidence was comparable in the UK and France, showing a slight increase in both countries, reporting a higher value among people aged 60 years and older. This study outlines the need to conduct future studies to estimate the burden of ET in terms of disease control and healthcare resource utilization.

Identifying health conditions associated with Alzheimer's disease up to 15 years before diagnosis: an agnostic study of French and British health records.

BACKGROUND: The identification of modifiable risk factors for Alzheimer's disease is paramount for early prevention and the targeting of new interventions. We aimed to assess the associations between health conditions diagnosed in primary care and the risk of incident Alzheimer's disease over time, up to 15 years before a first Alzheimer's disease diagnosis. METHODS: In this agnostic study of French and British health records, data from 20 214 patients with Alzheimer's disease in the UK and 19 458 patients with Alzheimer's disease in France were extracted from The Health Improvement Network database. We considered data recorded from Jan 1, 1996, to March 31, 2020 in the UK and from Jan 4, 1998, to Feb 20, 2019, in France. For each Alzheimer's disease case, a control was randomly assigned after matching for sex and age at last visit. We agnostically tested the associations between 123 different diagnoses of the International Classification of Diseases, 10th revision, extracted from health records, and Alzheimer's disease, by running a conditional logistic regression to account for matching of cases and controls. We focused on three time periods before diagnosis of Alzheimer's disease, to separate risk factors from early symptoms and comorbidities. FINDINGS: Unadjusted odds ratios (ORs) and 95% CIs for the association between Alzheimer's disease and various health conditions were estimated, and p values were corrected for multiple comparisons. In both the British and French studies, ten health conditions were significantly positively associated with increased Alzheimer's disease risk, in a window of exposure from 2-10 years before Alzheimer's disease diagnosis, comprising major depressive disorder (UK OR 1·34, 95% CI 1·23-1·46; France OR 1·73, 1·57-1·91), anxiety (UK OR 1·36, 1·25-1·47; France OR 1·50, 1·36-1·65), reaction to severe stress and adjustment disorders (UK OR 1·40, 1·24-1·59; France OR 1·83, 1·55-2·15), hearing loss (UK OR 1·19, 1·11-1·28; France OR 1·51, 1·21-1·89), constipation (UK OR 1·31, 1·22-1·41; France OR 1·59, 1·44-1·75), spondylosis (UK OR 1·26, 1·14-1·39; France OR 1·62, 1·44-1·81), abnormal weight loss (UK OR 1·47, 1·33-1·63; France OR 1·88, 1·56-2·26), malaise and fatigue (UK OR 1·23, 1·14-1·32; France OR 1·59, 1·46-1·73), memory loss (UK OR 7·63, 6·65-8·76; France OR 4·41, 3·07-6·34), and syncope and collapse (UK OR 1·23, 1·10-1·37; France OR 1·57, 1·26-1·96). Depression was the first comorbid condition associated with Alzheimer's disease, appearing at least 9 years before the first clinical diagnosis, followed by anxiety, constipation, and abnormal weight loss. INTERPRETATION: These results from two independent primary care databases provide new evidence on the temporality of risk factors and early signs of Alzheimer's disease that are observable at the general practitioner level. These results could guide the implementation of new primary and secondary prevention policies. FUNDING: Agence Nationale de la Recherche.

Changes in the use of psychotropic drugs during the course of Alzheimer's disease: A large-scale longitudinal study of French medical records.

INTRODUCTION: We aim to understand how patients with Alzheimer's disease (AD) are treated by identifying in a longitudinal fashion the late-life changes in patients' medical history that precede and follow AD diagnosis. METHODS: We use prescription history of 34,782 patients followed between 1996 and 2019 by French general practitioners. We compare patients with an AD diagnosis, patients with mild cognitive impairment (MCI), and patients free of mental disorders. We use a generalized mixed-effects model to study the longitudinal changes in the prescription of eight drug types for a period 15 years before diagnosis and 10 years after. RESULTS: In the decades preceding diagnosis, we find that future AD patients are treated significantly more than MCI patients with most psychotropic drugs and that most studied drugs are increasingly prescribed with age. At the time of diagnosis, all psychotropic drugs except benzodiazepines show a significant increase in prescription, while other drugs are significantly less prescribed. In the 10 years after diagnosis, nearly all categories of drugs are less and less prescribed including antidementia drugs. DISCUSSION: Pre-diagnosis differences between future AD patients and MCI patients may indicate that subtle cognitive changes are recognized and treated as psychiatric symptoms. The disclosure of AD diagnosis drastically changes patients' care, priority being given to the management of psychiatric symptoms. The decrease of all prescriptions in the late stages may reflect treatment discontinuation and simplification of therapeutic procedures. This study therefore provides new insights into the medical practices for management of AD.

Screening and treatment of familial hypercholesterolemia in a French sample of ambulatory care patients: A retrospective longitudinal cohort study.

BACKGROUND AND AIMS: Untreated Familial Hypercholesterolemia (FH) leads to premature morbidity and mortality. In France, its epidemiology and management are understudied in ambulatory care. We described the clinical profile, pharmacological management, and clinical outcomes in a French sample of FH patients. METHODS: This was a retrospective longitudinal study on patients from The Health Improvement Network (THIN®) database in France, between October 2016-June 2019. Patients ≥18 years, with probable/definite FH based on the Dutch Lipid Clinic Network (DLCN) criteria were included. Baseline characteristics, lipid profile, lipid-lowering therapy (LLT), low-density lipoprotein-cholesterol (LDL-C) goal achievement; and disease management at 6-month of follow-up were analyzed. RESULTS: 116 patients with probable (n = 70)/definite (n = 46) FH were included (mean age:57.8±14.0 years; 56.0% women; 9.5% with personal history of cardiovascular events); 90 patients had data available at follow-up. At baseline, 77.6% of patients had LDL-C>190 mg/dL, 27.6% were not receiving LLTs, 37.9% received statins alone, 20.7% statins with other LLTs, and 7.7% other LLTs. High-intensity statins were prescribed to 11.2% of patients, 30.2% received moderate-intensity statins, and 8.6% low-intensity statins. Only 6.0% of patients achieved LDL-C goal. At 6-month of follow-up, statins discontinuation and switching were 22.7% and 2.3%, respectively. None of the patients received proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors at baseline nor follow-up. CONCLUSIONS: Despite the existence of effective LLTs, FH patients are suboptimally-treated, do not achieve LDL-C goal, and exhibit worsened pharmacological management over time. Future studies with longer follow-up periods and assessment of factors affecting LDL-C management, including lifestyle and diet, are needed.

Pneumococcal vaccination coverage in France by general practitioners in adults with a high risk of pneumococcal disease.

Streptococcus pneumoniae, the main cause of community-acquired pneumonia (CAP), also leads to exacerbations, hospitalizations, and mortality in chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF). The risk of CAP is increased in patients with diabetes mellitus (DM), and the risk of invasive pneumococcal disease is increased in HIV-infected patients. Pneumococcal vaccination is recommended for these patients in France. The objective was a large survey of pneumococcal vaccination coverage (PVC) by general practitioners (GPs) in these patients in France. Diagnosis and treatment forms were extracted from the database of 2000 GPs. The GPs and population panels were representative of the metropolitan populations. The primary endpoint was the comparison of PVC in the adult patients diagnosed with COPD, CHF, DM, or HIV infection during the study (April 2013-April 2017) and the control (March 2012-March 2013) periods. Of the 17,865 and 4,690 patients identified, 756 (4%) and 267 (6%) were vaccinated, respectively. During the study period, the PVC was significantly higher (35/282, 12%) in HIV-infected patients and lower in patients with DM (95/5994, 2%) than in other patients. Even though French pneumococcal vaccine recommendations in adults were updated in 2013, the PVC did not increase according to the years of the study period and slightly increased according to time after diagnosis. S. pneumoniae is responsible only for some CAP and meningitis, and incomplete protection by vaccine, hesitancy from practitioners and patients, and the moving schedule of vaccination could explain the results. New tools and/or strategies must be implemented to increase PVC in France. Abbreviations: CAP: community-acquired pneumonia; COPD: chronic obstructive pulmonary diseases; CHF: congestive heart failure; DM: diabetes mellitus; IPD: invasive pneumococcal disease; HIV: human immunodeficiency virus; PVC: pneumococcal vaccination coverage; PCV7: 7-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; GPs: general practitioners; CLM: Cegedim Logiciels Médicaux; MLM: monLogicielMedical; ICD-10: International Classification of Diseases; CNIL: Commission nationale de l'informatique et des libertés; HPV: human papillomavirus; HBV: hepatitis B virus.