Impact of the COVID-19 health crisis on psychotropic drug use in children and adolescents in France.

BACKGROUND: In 2019, the world faced a pandemic brought about by a severe acute respiratory infection caused by SARS-CoV-2 virus. The spread of this virus has profoundly affected societies, particularly in terms of their economic, human and social dimensions, as well as their healthcare systems. Several restrictive measures (reduced social interaction, periodic school closures,…) had to be taken to contain the spread of the virus. These measures have had an impact on the psychological well-being of both adults and children. The aim of this study was to assess the changes in psychotropic drugs prescriptions for children and adolescents living in Limousin, a French region, over the period 2018 to 2021. METHODS: The consumption of psychotropic drugs was studied using a national database of drug reimbursement. These data were extracted and supplied from the nationwide French reimbursement healthcare system database (SNDS). The following therapeutic classes were studied: N05A (antipsychotics), N05B (anxiolytics), N05C (hypnotics and sedatives), N06A (antidepressants) and N06B (psychostimulants). Data were collected for insured persons under the age of 18 who received at least one reimbursement for a psychotropic drug between 2018 and 2021. RESULTS: Over a 4-year period, 7949 patients under the age of 18 were included with an average age of 12.1 years and a sex ratio of 0.97 M/F. The number of patients increased from 2018 to 2021, as did the number of reimbursements. We observed a statistically significant difference of means of patients reimbursed per week for on five therapeutic classes, with the greatest difference in 2021 (p < 0.0001). An increase in the number of patients of between + 20.7% and + 689% was observed, depending on the drug classes studied. Comparisons between the COVID-19 and pre-COVID-19 periods showed a significantly higher COVID average for psychotropic drugs reimbursements in general and individually for all classes except psychostimulants. CONCLUSION: The results show a significant increase in the consumption of psychotropic drugs among youth. The increase in psychotropic drug use was continuous and progressive throughout the pandemic. All five classes were increased, but particularly anxiolytics and antidepressants. The COVID-19 context may have been at the origin of a deterioration in the mental health of children and adolescents, or of a heightened awareness of psychiatric care among young people.

Predictors of drug-resistant epilepsy in childhood epilepsy syndromes: A subgroup analysis from a prospective cohort study.

OBJECTIVE: Previous studies assessing factors associated with drug-resistant epilepsy (DRE) were constrained by their amalgamation of all epilepsy syndromes in their analyses and the absence of uniform criteria for defining DRE. Our objective was to identify predictors of DRE among the four primary childhood epilepsy syndrome groups within a cohort of children with new onset seizures, using the International League Against Epilepsy (ILAE) definition of DRE and the recent classification of epilepsies. METHODS: This is a prospective study of 676 children with new onset seizures initiated on antiseizure medication. Patients were monitored for the occurrence of DRE according to the ILAE criteria and were categorized into one of four epilepsy groups: self-limited focal epilepsies (SeLFEs), genetic generalized epilepsies (GGEs), developmental epileptic encephalopathies (DEEs), and focal epilepsies. Cox regression analysis was performed to identify predictors of DRE within each epilepsy group. RESULTS: Overall, 29.3% of children were classified as having DRE, with the highest incidence observed among children diagnosed with DEEs (77.7%), followed by focal epilepsies (31.5%). Across the entire cohort, predictors of DRE included the presence of an epileptogenic lesion, a higher pretreatment number of seizures, experiencing multiple seizure types, presence and severity of intellectual and developmental delay, myoclonus, and younger age at epilepsy onset. Within the GGEs, only a younger age at seizure onset and experiencing multiple seizure types predicted DRE. Among focal epilepsies, predictors of DRE included the presence of an epileptogenic lesion, experiencing multiple seizure types, and having a greater number of pretreatment seizures. Within the DEEs, predictors of DRE were the occurrence of tonic seizures. Predictors of DRE within SeLFEs could not be identified. SIGNIFICANCE: This study indicates that different epilepsy syndromes are associated with distinct predictors of drug resistance. Anticipation of drug resistance within various groups is feasible using accessible clinical variables throughout the disease course.

Effects of antidepressant and antipsychotic medication on peripheral brain-derived neurotrophic factor concentration: Systematic review and meta-analysis.

Brain-derived neurotrophic factor (BDNF) is an important regulatory protein in the pathophysiology of psychiatric disorders. Several studies have reported the relationship between peripheral BDNF concentrations and the use of psychoactive drugs. However, the results remain controversial. This study aimed to evaluate the effects of psychoactive drugs on BDNF concentrations and to explore the association between changes in BDNF concentrations and improvements in clinical scores. A systematic review and meta-analysis were conducted. Six electronic databases, including PubMed, Scopus, Medline, Web of Science, Google Scholar and Science Direct, were searched. Changes in BDNF concentrations were compared before and after psychoactive treatment, using the standardized mean difference (SMD) and 95 % confidence interval (95 % CI). Twenty-three studies were included. A significant increase in serum BDNF concentrations was observed after treatment with antipsychotics (SMD=0.43; 95 %CI: 0.26, 0.60) and antidepressants (SMD=0.49; 95 %CI: 0.23, 0.74). However, the plasma BDNF concentration was not affected by antidepressant and antipsychotic medication. Although an improvement in clinical scores was observed after treatment, no significant association was observed between changes in BDNF concentrations and the changes in the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAM-D) scores. In conclusion, antidepressants and antipsychotics increase serum BDNF concentrations.

[Interest of a short educational intervention coordinated by community pharmacists for elderly type 2 diabetes patients in a rural area]. / Intérêt d'une séance éducative « flash ¼ coordonnée par des pharmaciens d'officine pour des patients âgés diabétiques de type 2 en milieu rural.

The number of elderly people with type 2 diabetes (T2D) is increasing worldwide. Community pharmacies, thanks to their proximity, provide more easy access to therapeutic education for rural patients. Populations living in isolated areas require specific educational resources related to their condition. The aim of this project was to perform a short (FLASH) educational intervention, coordinated by community pharmacists, and then evaluate the impact of this intervention on patient knowledge of their disease. The study was performed in Issoudun, a rural French town of approximately 10,000 inhabitants. Educational priorities were defined and the project was presented to health authorities and local health professionals. Pharmacies in Issoudun recruited patients, either alone or accompanied by their caregivers. The educational intervention lasted 2h and focused on 4 teaching objectives: knowledge concerning diabetes, diabetic complications and how to monitor them; how to react to hypoglycemia; understanding treatments; and understanding glycated hemoglobin. The impact of this educational intervention was assessed using a questionnaire delivered before the intervention, immediately after, and after 6months. Forty-five patients aged 71±6years with T2D duration of 14±6years were recruited over 6months. Some false beliefs were identified before the intervention. The educational session led to a significant improvement in the percentage of correct answers (before: 60.3%±7.5, after: 99%±0.4, P=0.0002) and at 6months (99.5%±0.3, P=0.0002) compared with the patients' initial knowledge. Almost all false beliefs were corrected by the intervention and patients were able to recall the mechanism of action of their drugs, with the help of a "key and lock" schematic. This short FLASH educational intervention, coordinated by community pharmacists, showed that the model was both interesting to patients and effective. This method could be expanded to other rural communities and medical deserts.

The association of benzodiazepine and benzodiazepine-related drugs with outcomes after surgery for colorectal cancer.

Benzodiazepines increase plasma brain-derived neurotrophic factor (BDNF) level which, in turn, may improve survival in colorectal cancer (CRC) patients. This study aimed to evaluate the associations between benzodiazepine and benzodiazepine-related drugs (BZRD) use and outcomes of patients operated for CRC. This is a retrospective cohort study including patients operated for CRC at Limoges' University Hospital between 2010 and 2019. Data were collected from two sources: medical records of patients in the digestive, general and endocrine surgery department at Limoges University Hospital and from the Haute-Vienne general cancer registry. Patients were divided into benzodiazepine users and non-users. Outcomes were overall survival (OS) and recurrence-free survival (RFS). Among 504 patients who underwent surgery for CRC, 125 (24.8%) patients were treated with benzodiazepine/BZRD drugs. Users and non-users of benzodiazepine/BZRD showed no statistically significant differences in 5-year OS (45.5 ± 1.9% vs. 46.5 ± 1.1% p = 0.25) and 5-year RFS (41.0 ± 2.1% vs. 39.6 ± 1.3%, p = 0.94), even after adjustment for confounders and propensity score (OS: aHR=1.02, 95%CI: 0.71-1.48; RFS: aHR=1.00, 95%CI: 0.72-1.40). Subgroup analysis on CRC patients with psychiatric disorders revealed that benzodiazepine users had better RFS (aHR=0.58, 95%CI: 0.35-0.96) compared with non-users, particularly, patients with stages III or IV of CRC had better OS (aHR=0.27; 95%CI: 0.12-0.59) and RFS (aHR=0.30, 95%CI: 0.15-0.62). OS and RFS was significantly better in patients taking benzodiazepines classified as anxiolytics, having longer half-life, and producing active metabolites. In conclusion, benzodiazepine use was not associated with outcomes in CRC patients. Nevertheless, in subgroup of patients with psychiatric disorders and advanced CRC stage, benzodiazepine could improve survival.

Early predictors of remission in children and adolescents with new-onset epilepsy: A prospective study.

PURPOSE: This study aims to identify predictive factors of a two-year remission (2YR) in a cohort of children and adolescents with new-onset seizures based on baseline clinical characteristics, initial EEG and brain MRI findings. METHODS: A prospective cohort of 688 patients with new onset seizures, initiated on treatment with antiseizure medication was evaluated. 2YR was defined as achieving at least two years of seizure freedom during the follow-up period. Multivariable analysis was performed and recursive partition analysis was utilized to develop a decision tree. RESULTS: The median age at seizure onset was 6.7 years, and the median follow-up was 7.4 years. 548 (79.7%) patients achieved a 2YR during the follow up period. Multivariable analysis found that presence and degree of intellectual and developmental delay (IDD), epileptogenic lesion on brain MRI and a higher number of pretreatment seizures were significantly associated with a lower probability of achieving a 2YR. Recursive partition analysis showed that the absence of IDD was the most important predictor of remission. An epileptogenic lesion was a significant predictor of non-remission only in patients without evidence of IDD, and a high number of pretreatment seizures was a predictive factor in children without IDD and in the absence of an epileptogenic lesion. CONCLUSION: Our results indicate that it is possible to identify patients at risk of not achieving a 2YR based on variables obtained at the initial evaluation. This could allow for a timely selection of patients who require close follow-up, consideration for neurosurgical intervention, or investigational treatments trials.

Development of a decision tree for the pharmacy-led consultation of elderly patients with haematological malignancies.

INTRODUCTION: Elderly patients with haematological malignancies are a population at risk of iatrogenic for whom these activities could optimize therapeutic management. However, the limitation of human resources requires optimization of the process in order to improve the efficiency of pharmaceutical activities. The objective was to build a decision tree to optimize the pharmaceutical consultation in these population within a multidisciplinary team in haematology. METHOD: Pharmaceutical consultations were proposed to elderly subjects with haematological malignancies followed up in a haematology day hospitalization at the University Hospital of Limoges. Risk factors for prescribing risky drugs in this population were determined by logistic regression models. A decision tree was constructed based on these results and by agreement between pharmacist, geriatrician and hematologist. RESULTS: Female gender (aOR[CI95%] = 1.71 [1.14-2.57]), polypharmacy (aOR[CI95%] = 1.89 [1.14-3.13]), hyper-polypharmacy (aOR[CI95%] = 5.73 [3.03-10.84]) and moderate cholinergic load (aOR[CI95%] = 2.15 [1.04-4.45]) were risk factors for the prescription of inappropriate medicine. Female gender (aOR[CI95%] = 1.55 [1.02-2.35]) and hyper-polypharmacy (aOR[CI95%] = 6.19 [1-1.28]) were risk factors for prescribing anticholinergic drugs or anticoagulants; in contrast, frailty status was a protective factor for prescribing anticholinergics (aOR[CI95%] = 0.51 [0.33-0.81]). Prioritization of pharmaceutical consultations is based on frailty status, prescription of a target drug and polypharmacy. DISCUSSION: Pharmaceutical consultations during the day hospitalization of elderly subjects with hematological diseases allow to propose therapeutic optimizations. The prioritization proposed in our study would increase the efficiency of pharmaceutical activities in order to improve quality and safety throughout the care pathway of these patients.

Statins in Primary Prevention in People Over 80 Years.

In the much older population (≥80 years), the management of cardiovascular diseases requires specific research to avoid a plain transposition of medical practice from younger populations. Whether statins are useful in primary prevention in this population is not clear. The 3 intricate issues requiring attention are (1) the impact of hypercholesterolemia on mortality and major adverse cardiovascular events in subjects >80 years, (2) the efficacy of statins to prevent cardiovascular events at this age, and (3) the safety and tolerance of statins in this population. Three systematic reviews were performed using a search on EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science databases including publication until January 2021. Among the 7,617 references identified, 29 were finally retained. Regarding the first objective (16 studies, 121,250 participants), 7 studies (10,241 participants) did not find total cholesterol and low-density lipoprotein levels associated with an increased rate of major cardiovascular events in octogenarians. A total of 6 studies (14,493 participants) found increased levels associated with events, whereas 3 studies (96,516 participants) found the opposite, with increased risk of major adverse cardiovascular events with lower levels of cholesterol. In 8 studies (436,005 participants) addressing the efficacy of statins, most did not indicate a significant decrease in the rate of major cardiovascular events in these subjects. Finally, regarding tolerance (9 studies, 217,088 participants), the most important side effects in this population were muscular, hepatic, and gastrointestinal disorders. These events were more frequent than in the younger population. In conclusion, in the absence of convincing evidence, the benefit of statins in primary prevention for much older patients is not certain. Their prescription in this setting should only be considered case by case, taking into consideration physiological status, co-morbidities, level of risk, and expected life expectancy. Specific trials are mandatory.

Knowledge of epilepsy, quality of life, and psychiatric comorbidities in Lebanese adults with epilepsy.

INTRODUCTION: People with epilepsy (PWE) face a variety of psychosocial challenges. A lack of knowledge of epilepsy, a high level of depression and anxiety and a low quality of life (QoL) are among the major problems that affect most PWE. The objective of this study was to examine the association of sociodemographic characteristics, clinical factors and knowledge of epilepsy with the level of QoL, and the presence of psychiatric comorbidities. METHOD: A cross-sectional study was conducted in Lebanon. The PWE were recruited from neurologists' clinics in Beirut and its suburbs. A questionnaire translated into Arabic was used and composed of four parts: sociodemographic factors, clinical characteristics, psychosocial characteristics (QoL, psychiatric disorders), and knowledge epilepsy scale. Backward logistic regression models were developed, the associations were estimated by odds ratio (OR), and the level of significance was set at p ≤ 0.05. RESULTS: Four hundred and four PWE were recruited in this study. About a half of PWE had controlled epilepsy (46.3 %) and 40.3 % had epilepsy for less than 5 years. The QoL was low for 38.6 % of PWE and 30.2 % had psychiatric comorbidities. More than half of PWE had a good level of knowledge (71.5 %). Controlled epilepsy (OR = 1.8; 95 %CI: 1.2-2.9), and good knowledge about epilepsy (OR = 5.5; 95 %CI: 3.4-9.1) were associated with better QoL. Patients on polytherapy with anti-seizure drugs (OR = 0.6; 95 %CI: 0.4-0.9), experienced side effects of anti-seizure drugs (OR = 0.6; 95 %CI: 0.4-0.9) and with psychiatric comorbidities (OR = 0.6; 95 %CI: 0.3-0.9) had a lower QoL. A high number of nonpsychiatric comorbidities (OR = 2.5; 95 %CI: 2.0-3.1) and a polytherapy increased the risk of having psychiatric comorbidities (OR = 1.8; 95 %CI: 1.1-2.8). CONCLUSIONS: Good knowledge of epilepsy and the absence of psychiatric comorbidities are important predictors of good QoL in Lebanese PWE. Educational programs are needed to reduce misconceptions about epilepsy and improve mental health of PWE.

The effect of metformin on the survival of colorectal cancer patients with type 2 diabetes mellitus.

Evidence from previous studies suggests a protective effect of metformin in patients with colorectal cancer (CRC). The aim of this study was to examine the associations between metformin use and overall survival (OS) and disease-free survival (DFS) in CRC patients with type 2 diabetes mellitus (DM). We retrospectively included patients who underwent surgery for CRC at Limoges' University Hospital between 2005 and 2019 and diagnosed with type 2 DM. Data on the characteristics of patients, CRC, comorbidities and drug exposure were collected from the electronic medical records. The exposure was the use of metformin and the outcomes were OS and DFS. We identified 290 CRC patients with type 2 DM. A total of 144 (49.7%) of them were treated with metformin. Metformin users were significantly younger, with higher body mass index and less diabetes-related complications compared to non-users. The 2-year OS was significantly higher in metformin users than in non-users (86.9 ± 2.9% vs. 71.0 ± 4.0%, p = 0.001). In multivariate analysis, metformin use was associated with better OS (adjusted hazard ratios [aHR] = 0.45 95% confidence interval [95% CI]: 0.21-0.96) and better DFS (aHR = 0.31; 95% CI: 0.18-0.54). In conclusion, the use of metformin may improve OS and DFS in CRC patients with type 2 DM.