Impact of the COVID-19 pandemic and its control measures on cardiovascular and antidiabetic drugs use in France in 2020: a nationwide repeated cohort study.

Since pandemic start, patients may have faced difficulties in accessing to care and treatment. This study aimed at assessing the impact of COVID-19 pandemic and its control measures on the use of drugs indicated in cardiovascular prevention and diabetes mellitus in France. From 09/17/2018 to 09/20/2020, a repeated cohort analysis was performed using the French nationwide health insurance databases. The pandemic impact was assessed using time-series analyses and unobserved components model for the weekly number of patients with (i) drug dispensing, (ii) ongoing treatment, (iii) treatment initiation, (iv) treatment disruption. Overall, 14,822,132 patients with cardiovascular drug dispensings and 3,231,618 with antidiabetic ones were identified. After a sharp spike in the amount of dispensings in the week the first national lockdown was announced, the period was marked by decreased levels and trends. Altogether, the estimated impact of the pandemic on dispensings appeared limited over the lockdown period (1-3% lack in dispensings). During lockdown, the weekly numbers of treatment disruptions remained stable whereas a significant decrease in treatment initiations was observed for almost all drug classes (e.g. ß-blockers initiations: - 8.9%). Conversely, the post-lockdown period showed increases in treatment disruptions especially for antihypertensive and lipid lowering drugs (e.g. statins disruptions: + 4.9%). The pandemic and associated measures had a significant impact on cardiovascular and antidiabetic drugs use in France, mostly consisting in decreases of treatment initiations over lockdown and increases in treatment disruptions afterwards. Both could result in increased morbimortality that remains to be assessed.

Risk of bradyarrhythmia related to ticagrelor: A systematic review and meta-analysis.

CONTEXT: Ticagrelor was related to bradycardia in DISPERSE-II trial. This risk has been integrated into the European risk-management plan, and its use is warned in at-risk patients. Nevertheless, this risk was not systematically assessed nor measured. OBJECTIVES: To estimate the risk of bradyarrhythmia associated with ticagrelor. STUDY DESIGN: Systematic review and meta-analysis. DATA-SOURCE: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, ISI web of Science, clinicaltrial.gov, clinicaltrialsregister.eu. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies in patients treated with ticagrelor or comparator(s). META-ANALYSIS: Risk of bias in each RCT was assessed using Cochrane tool. Relative Risks (RR) with 95 % confidence intervals (95 %CI) were calculated for each RCT, and pooled using fixed-effect or random-effects models, when appropriate. Subgroup and sensitivity analyses were performed. A potential publication bias was searched. RESULTS: Among 82 eligible studies, event data were missing for 56 studies, due to detected reporting bias (i.e. inability to confirm zero events). Fifteen RCTs were selected and the combined RR of bradyarrhythmia was 1.15 (95 %CI 1.05-1.26), and 1.29 (1.02-1.65) for severe bradyarrhythmia. The risk appeared to be dose dependent. Restricting the analysis only to RCTs performed in patients without previous bradyarrhythmia resulted in a non-increased risk. CONCLUSION: This meta-analysis confirmed the risk of bradyarrhythmia or severe bradyarrhythmia related to ticagrelor, and its use in patients without previous bradycardia was effective in preventing it. The evidence coming from this meta-analysis was low to moderate due to missing outcome in 2/3 of eligible studies. Waiting for access to these data, the use of ticagrelor in patients with risk factors of bradycardias should be avoided.

Impact of COVID-19 epidemic on antihypertensive drug treatment disruptions: results from a nationwide interrupted time-series analysis.

Background: The COVID-19 epidemic has disrupted care and access to care in many ways. It was accompanied by an excess of cardiovascular drug treatment discontinuations. We sought to investigate a deeper potential impact of the COVID-19 epidemic on antihypertensive drug treatment disruptions by assessing whether the epidemic induced some changes in the characteristics of disruptions in terms of duration, treatment outcome, and patient characteristics. Methods: From March 2018 to February 2021, a repeated cohort analysis was performed using French national health insurance databases. The impact of the epidemic on treatment discontinuations and resumption of antihypertensive medications was assessed using preformed interrupted time series analyses either on a quarterly basis. Results: Among all adult patients on antihypertensive medication, we identified 2,318,844 (18.7%) who discontinued their antihypertensive treatment during the first blocking period in France. No differences were observed between periods in the characteristics of patients who interrupted their treatment or in the duration of treatment disruptions. The COVID-19 epidemic was not accompanied by a change in the proportion of patients who fully resumed treatment after a disruption, neither in level nor in trend/slope [change in level: 2.66 (-0.11; 5.42); change in slope: -0.67 (-1.54; 0.20)]. Results were similar for the proportion of patients who permanently discontinued treatment within 1 year of disruption [level change: -0.21 (-2.08; 1.65); slope change: 0.24 (-0.40; 0.87)]. Conclusion: This study showed that, although it led to an increase in cardiovascular drug disruptions, the COVID-19 epidemic did not change the characteristics of these. First, disruptions were not prolonged, and post-disruption treatment outcomes remained unchanged. Second, patients who experienced antihypertensive drug disruptions during the COVID-19 outbreak were essentially similar to those who experienced disruptions before it.

GLP-1 Receptor Agonists and the Risk of Thyroid Cancer.

OBJECTIVE: To determine whether use of glucagon-like peptide 1 (GLP-1) receptor agonists (RA) is associated with increased risk of thyroid cancer. RESEARCH DESIGN AND METHODS: A nested case-control analysis was performed with use of the French national health care insurance system (SNDS) database. Individuals with type 2 diabetes treated with second-line antidiabetes drugs between 2006 and 2018 were included in the cohort. All thyroid cancers were identified through hospital discharge diagnoses and medical procedures between 2014 and 2018. Exposure to GLP-1 RA was measured within the 6 years preceding a 6-month lag-time period and considered as current use and cumulative duration of use based on defined daily dose (≤1, 1 to 3, >3 years). Case subjects were matched with up to 20 control subjects on age, sex, and length of diabetes with the risk-set sampling procedure. Risk of thyroid cancer related to use of GLP-1 RA was estimated with a conditional logistic regression with adjustment for goiter, hypothyroidism, hyperthyroidism, other antidiabetes drugs, and social deprivation index. RESULTS: A total of 2,562 case subjects with thyroid cancers were included in the study and matched with 45,184 control subjects. Use of GLP-1 RA for 1-3 years was associated with increased risk of all thyroid cancer (adjusted hazard ratio [HR] 1.58, 95% CI 1.27-1.95) and medullary thyroid cancer (adjusted HR 1.78, 95% CI 1.04-3.05). CONCLUSIONS: In the current study we found increased risk of all thyroid cancer and medullary thyroid cancer with use of GLP-1 RA, in particular after 1-3 years of treatment.

Role of spontaneous reporting in investigating the relationship between mRNA COVID-19 vaccines and myocarditis: The French perspective.

AIM OF THE STUDY: Post-mRNA coronavirus diseases 2019 (COVID-19) vaccines myocarditis emerged as a rare adverse effect, particularly in adolescents and young adults, and was labeled as such for both vaccines in the summer of 2021. This study aims to summarize the timeline and process of signal detection, substantiation, and quantification of myocarditis cases related to mRNA vaccines in France. METHODS: The intensive monitoring plan for COVID-19 vaccine safety was based on case-by-case analysis of all cases collected in the French spontaneous reporting database (Base nationale de pharmacovigilance, BNPV). Cases were evaluated by drug safety medical professionals and discussed at a national level for signal detection purposes. Reported cases were compared to the number of vaccine-exposed persons up to September 30th, 2021. Reporting rates (Rr) of myocarditis per 100,000 injections were calculated and stratified according to age, gender, and injection rank of BNT162b2 and mRNA-1273 vaccines. Poisson distribution was used to compute Rrs 95% Confidence Interval (95% CI). RESULTS: The case-by-case analysis detected a possible cluster of myocarditis in April 2021 (5 cases, 4 after the 2nd injection). In June 2021, the signal was substantiated with 12 cases (9 related to BNT162b2, and 3 to mRNA-1273). As of September 2021, almost 73 million BNT162b2 and 10 million mRNA-1273 doses had been injected. The Rr per 100,000 injections was 0.5 (0.5-0.6) for BNT162b2 and 1.1 (95% CI 0.9-1.3) for mRNA-1273. The difference among vaccines was more pronounced after the second injection, particularly in men aged 18-24 years (4.3 [3.4-5.5] for BNT162b2 vs. 13.9 [9.2-20.1] for mRNA-1273) and aged 25-29 years (1.9 [1.2-2.9] vs. 7.0 [3.4-12.9]). CONCLUSION: The study highlighted the role of the spontaneous reporting system in the detection, assessment, and quantification of myocarditis related to m-RNA vaccines. It suggested from September 2021 that mRNA-1273 was reasonably related to a higher risk of myocarditis than BNT162b2 in people under 30, particularly after the second injection.

Psychoactive substance use among students: A cross-sectional analysis.

Little is known about psychoactive substance use in students, apart from tobacco, alcohol, and cannabis. This study investigated the prevalence of substance use and overlap between various psychoactive substances in students. This cross-sectional study was conducted in 10 066 students included in the i-Share cohort between January 1, 2015, and December 31, 2017. The baseline questionnaire was the key source of information. Psychoactive substances of interest (PSI) were cannabis, cocaine, amphetamines, nitrous oxide, poppers, and MDMA. Their patterns of use were categorized as lifetime, past year, and current use. The use of other psychoactive substances including alcohol and tobacco was described in PSI users and non-users. Most participants were female (75%), and their average age was 21 years. Lifetime use of at least one PSI was reported by 65.5% of participants. Cannabis was the most frequently used substance both over lifetime (57% of students) and past year (35%), followed by poppers and nitrous oxide (28% and 26% of students over lifetime, respectively). Among polydrug users (n = 1242), 65% used only nitrous oxide and poppers, showing a strong link between these two substances. Regular alcohol use, binge drinking, and current tobacco use were higher in PSI users than in non-users. Substance use was higher than previously found in both French and European studies in young people. Nitrous oxide use was particularly high. Regular alcohol use, binge drinking, and tobacco use could be used as markers to identify students at risk of PSI use to be targeted by prevention programs.

Patterns of Benzodiazepine Use and Excess Risk of All-Cause Mortality in the Elderly: A Nationwide Cohort Study.

INTRODUCTION: Despite the risks associated with their use, benzodiazepines remain used more widely than wisely. In this context, a better understanding of how their patterns of use can be associated with an increased risk of death appears essential. Indeed, the studies that investigated this association so far are inconsistent and question the influence of potential biases. OBJECTIVE: The objective of this study was to investigate the association of various patterns of benzodiazepine use with all-cause mortality. METHODS: A nationwide cohort of non-prevalent benzodiazepine users aged ≥ 65 years was identified using French healthcare insurance system claims databases. Exposure to benzodiazepines considered short-term, chronic (defined as a cumulated ≥ 6-month period over the previous 12 months), ongoing, and discontinued use. Using a Cox model, adjusted hazard ratios for all-cause mortality were estimated according to benzodiazepine patterns of use; exposure and confounders were treated as time-dependent variables. RESULTS: In the cohort of 54,958 individuals aged ≥ 65 years, adjusted hazard ratios for all-cause mortality and benzodiazepines were 2.26 (95% confidence interval 1.96-2.61) for short-term use, 3.86 (3.04-4.90) for chronic use-discontinued, and 3.05 (2.17-4.29) for chronic use-ongoing. At age 80 years, these were 1.62 (1.48-1.79), 2.00 (1.82-2.19) and 1.13 (1.02-1.26), respectively. Adjusted hazard ratios show similar decreases with age for all patterns of benzodiazepine use. CONCLUSIONS: These findings confirm the existence of an excess risk of mortality associated with benzodiazepine use and provide pattern- and age-specific estimates. Higher risks were observed for patients aged < 80 years, short-term use, or chronic use recently interrupted. If the two latter can relate to an indication bias, the associations found for ongoing chronic use and short-term use conversely support a potential causal hypothesis.

First-Line Pharmacotherapies and Survival among Patients Diagnosed with Non-Resectable NSCLC: A Real-Life Setting Study with Gender Prospective.

(1) Purpose: To describe first-line pharmacotherapy and overall survival in non-resectable non-small cell lung cancer (nrNSCLC) patients by gender. (2) Methods: Incident cases of nrNSCLC recorded between 2009 and 2019 (cohort entry) in the pathology registry of the regional administrative healthcare database of Tuscany were identified. Records of antineoplastic therapies delivered up to 4 months following cohort entry were classified as chemotherapy, target therapies, immunotherapies, and undefined monoclonal antibodies. First-line treatment and survival of patients receiving drug treatment was described. Analyses were stratified according to histology, gender, and cohort entry year. (3) Results: 4393 incident cases of nrNSCLC were included. Women with non-squamous-NSCLC received target-therapy more frequently than men (14.9% vs. 6.5%). Immunotherapy incidence of use varied between 3.8% (2017) and 9.1% (2019). The 2-year survival rate increased over time: for non-squamous-NSCLC, it was 22.3% (2009-2011) and 30.6% (2018-2019), while for squamous-NSCLC, it was 13.5% and 22.5%, respectively. After multivariate analysis, a low reduction in mortality risk in 2018-2019 vs. 2009-2011 was found (non-squamous: HR: 0.95 CI95%: 0.92-0.98; squamous: HR: 0.94 CI95%: 0.90-0.98). Among non-squamous NSCLC, median survival was longer in women than in men (389 vs. 276 days). (4) Conclusion: In light of sex-related biomolecular differences, among non-squamous NSCLC, women received target-therapy more frequently than men. Survival seemed to slightly improve over the study period for both histologies, despite a poor reduction in mortality risk was still observed.

Impact of benzodiazepine consumption reduction on future burden of dementia.

Dementia is a major public health issue worldwide and chronic use of benzodiazepine, which is very frequent in northern countries, was found to be a risk factor of dementia. This work aims at evaluating the impact of a reduction in chronic use of benzodiazepine on the future burden of dementia in France. Using estimations of dementia incidence and of benzodiazepine use and nation-wide projections of mortality and population sizes, a Monte Carlo approach based on an illness-death model provided projections of several indicators of dementia burden. With no change in benzodiazepine consumption, the prevalence of dementia between age 65 and 99 in France in 2040 was estimated at 2.16 millions (95% confidence interval (CI) 1.93-2.38), with a life expectancy without dementia at 65 years equal to 25.0 years (24.7-25.3) for women and 23.8 years (23.5-24.2) for men. Assuming a disappearance of chronic use of benzodiazepine in 2020, the prevalence would be reduced by about 6.6% in 2040 and the life expectancy without dementia would increase by 0.99 (0.93-1.06) year among women and 0.56 (0.50-0.62) among men. To conclude, a modest but significant reduction in future dementia burden could be obtained by applying current recommendation for duration of benzodiazepine use.