Contribution of Potentially Inappropriate Medications to Polypharmacy-Associated Risk of Mortality in Middle-Aged Patients: A National Cohort Study.

BACKGROUND: The role of potentially inappropriate medications (PIMs) in mortality has been studied among those 65 years or older. While middle-aged individuals are believed to be less susceptible to the harms of polypharmacy, PIMs have not been as carefully studied in this group. OBJECTIVE: To estimate PIM-associated risk of mortality and evaluate the extent PIMs explain associations between polypharmacy and mortality in middle-aged patients, overall and by sex and race/ethnicity. DESIGN: Observational cohort study. SETTING: Department of Veterans Affairs (VA), the largest integrated healthcare system in the US. PARTICIPANTS: Patients aged 41 to 64 who received a chronic medication (continuous use of ≥ 90 days) between October 1, 2008, and September 30, 2017. MEASUREMENT: Patients were followed for 5 years until death or end of study period (September 30, 2019). Time-updated polypharmacy and hyperpolypharmacy were defined as 5-9 and ≥ 10 chronic medications, respectively. PIMs were identified using the Beers criteria (2015) and were time-updated. Cox models were adjusted for demographic, behavioral, and clinical characteristics. RESULTS: Of 733,728 patients, 676,935 (92.3%) were men, 479,377 (65.3%) were White, and 156,092 (21.3%) were Black. By the end of follow-up, 104,361 (14.2%) patients had polypharmacy, 15,485 (2.1%) had hyperpolypharmacy, and 129,992 (17.7%) were dispensed ≥ 1 PIM. PIMs were independently associated with mortality (HR 1.11, 95% CI 1.04-1.18). PIMs also modestly attenuated risk of mortality associated with polypharmacy (HR 1.07, 95% CI 1.03-1.11 before versus HR 1.05, 95% CI 1.01-1.09 after) and hyperpolypharmacy (HR 1.18, 95% CI 1.09-1.28 before versus HR 1.12, 95% CI 1.03-1.22 after). Patterns varied when stratified by sex and race/ethnicity. LIMITATIONS: The predominantly male VA patient population may not represent the general population. CONCLUSION: PIMs were independently associated with increased mortality, and partially explained polypharmacy-associated mortality in middle-aged people. Other mechanisms of injury from polypharmacy should also be studied.

Use of sodium-glucose cotransporter-2 inhibitors in France: Analysis of French nationwide health insurance database.

AIM: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have been commercialized in France for type 2 diabetes since April 2020 and later for heart and renal diseases. Given the recent developments in treating diabetes and the widening of SGLT-2i indications, we aimed to study changes in the use of glucose-lowering drugs in France and to characterize SGLT-2i new users. METHODS: We performed a nationwide utilization study using the French health insurance database. Trends in incidence and prevalence of glucose-lowering drug use were assessed by a repeated cross-sectional study in 2019 and 2021. A cohort study of incident SGLT-2i users was then conducted to describe patient characteristics and the strategy for treating diabetes. RESULTS: The prevalence of SGLT-2i use gradually reached 0.1% in the third quarter of 2021 and increased more significantly to 0.2% thereafter. SGLT-2i became the second most prescribed glucose-lowering drug class after metformin at the end of 2021 (0.1%). Among the cohort of 125 387 SGLT-2i new users (mean age 65.0 years; 60.1% of men), 87.6% presented a diabetic comorbidity. The patient profile changed over the study period with an increasing proportion of patients with cardiovascular (28.7% in 2020 vs. 40.2% in 2021) or renal (7.7% in 2020 vs. 11.8% in 2021) comorbidities at initiation. The main combinations used at SGLT-2i initiation were metformin (12.5%) and metformin plus dipeptidyl peptidase-4 inhibitors (8.1%). One-year probability of SGLT-2i persistence was estimated to be 55%. CONCLUSION: The expansion of indications for SGLT-2i and the broadening of the target population make it essential to assess the reasons for discontinuation and review their safety profile.

Invasive fungal infection incidence and risk factors in patients receiving ibrutinib in real-life settings: A nationwide population-based cohort study.

BACKGROUND: Data on the risk of invasive fungal infections (IFI) with ibrutinib treatment are scarce. OBJECTIVES: This study aimed to determine IFI incidence and risk factors in ibrutinib-treated patients in real-life settings. METHODS: We constituted a cohort of ibrutinib incident users in the French National Healthcare Database. All patients ≥18 years with a first dispensing of ibrutinib between 21 November 2014 and 31 December 2019 were included. Patients were followed from the cohort entry date until IFI, ibrutinib discontinuation, death, or 31 December 2020, whichever came first. The cumulative incidence function method was used to estimate the probability of IFI accounting for competing risk of death. A multivariate cause-specific Cox proportional hazards model was used to assess independent IFI risk factors. RESULTS: Among 6937 ibrutinib-treated patients, 1-year IFI cumulative incidence was 1.3%, with invasive aspergillosis being the most frequent. Allogenic or autologous stem cell transplantation (ASCT) (hazard ratio [HR] 3.59, 95% confidence interval [1.74; 7.41]), previous anticancer treatment (HR 2.12, CI 95% [1.34; 3.35]) and chronic respiratory disease (HR 1.66, [1.03; 2.67]) were associated with higher risk of IFI. Besides neutropenia and corticosteroids, use of anti-CD20 agents was significantly more frequent in patients having experienced IFI (HR 3.68, [1.82; 7.45]). CONCLUSIONS: In addition to patients with ASCT history, severe neutropenia or treated with corticosteroids, our findings support active surveillance of IFIs in those with chronic respiratory disease, previously treated, or treated with anti-CD20 agents in combination with ibrutinib. Further studies are needed to optimise IFI prophylaxis in these patient subgroups.

Psychoactive substance intoxication leading to general hospital admission in young and middle-aged people during and after the first lockdown.

INTRODUCTION: Incidence of hospitalisations related to psychoactive substance (H-PS) intoxication has been strongly decreased during the coronavirus disease 2019 (COVID-19) pandemic especially in young adult and French region of Nouvelle-Aquitaine was mostly concerned. This study aimed to describe (i) the incidence of H-PS in Bordeaux teaching hospital during and after the first 2020 lockdown in adults aged 18-29 years or 30+ then (ii) their characteristics specifically associated with the pandemic period by comparing 2020 with 2017-2019 baseline period. MATERIAL AND METHODS: This historical cohort study was conducted in adults admitted to the Bordeaux teaching hospital with main or associated diagnosis codes of intoxication with benzodiazepine, methadone, buprenorphine, codeine, morphine, heroin, cocaine, ecstasy and alcohol. Data were collected locally through the discharge database. Incidence and characteristics of H-PS were described according to patients' age, in 2020 before (01/01-16/03), during (17/03-10/05), and after the first lockdown (11/05-31/07). RESULTS: Among the 5,824 stays included over the study period, PS most involved were alcohol and benzodiazepines. Compared to baseline, the decrease in H-PS's incidence was more important in young adults (-40%; nbaseline=450) in comparison to those aged 30+ (-18%; nbaseline=1,101) during the pandemic period, especially during the lockdown compared to 2017 (-59%; n2017=145 vs. -35%; n2017=166) with far decrease in alcohol and ecstasy intoxications. Seriousness of hospitalisation indications was increased regardless of age during the pandemic. Particularly in young adults, the proportion of suicides attempts increased during lockdown compared to the baseline period (almost 50% vs. 29%) and the period after lockdown was associated with 1.7 more-time road accident increased and 3 more-time fights compared with pre-lockdown period. DISCUSSION/CONCLUSION: The period following lockdown should be considered at risk H-PS due to accident. Recreational use of alcohol and ecstasy could be a target for minimize serious consequences associated to PS use in young adult.

Statin treatment is not associated with an increased risk of adrenal insufficiency in real-world setting.

Introduction: Statins could reduce the synthesis of steroid hormones, thereby could cause adrenal insufficiency. We investigated this risk in a large nationwide database. Methods: We conducted a nested case-control study using a cohort of individuals affiliated to the French health insurance system in 2010, ≥18y and without adrenal insufficiency history. Each case had a first event of adrenal insufficiency between 2015 and 2017 and was matched to up to ten controls on age, sex, and prior treatment with corticosteroids. Statin exposure was measured over the five years preceding the index date, considering a six-month censoring lag-time. Association was estimated using a conditional logistic regression adjusted for confounders included in a disease risk score. Analyses were stratified on age, sex and corticosteroid history of use. Results: 4 492 cases of adrenal insufficiency were compared with 44 798 controls (median age 66y, 58% women), of which 39% vs. 33% were exposed to statins, respectively. No association between statin use and adrenal insufficiency was found when adjusting the model for confounders (adjusted odds ratio 0.98; 95% confidence interval 0.90-1.05). These results were consistent regardless of the exposure definition and stratifications considered. Conclusion: Statin-related adrenal insufficiency risk, if any, seems to be very limited and does not compromise the benefit of statin treatment.

Use of Bisphosphonates and the Risk of Skin Ulcer: A National Cohort Study Using Data from the French Health Care Claims Database.

INTRODUCTION: Previous pre-clinical and pharmacovigilance disproportionality analyses highlighted a safety signal of cutaneous ulcer with bisphosphonate use. Therefore, our objective is to evaluate this risk and assess whether unmeasured confounding factors could explain this association. METHODS: This study is a population-based cohort study from a representative sample (1/97th) of the French health insurance claims database: Echantillon Généraliste des Bénéficiaires (EGB) from 2006 to 2019. To limit the impact of our study design and methodological choices on any association between skin ulceration and exposure to bisphosphonates, we used several methods: a Cox proportional hazards analysis and a prior event rate ratio (PERR) analysis, using two propensity matched control groups, and either the first episode of incident ulceration or multiple event-time outcomes. RESULTS: There were 7402 individuals newly exposed to bisphosphonates matched to 29,605 unexposed individuals on propensity score. The primary outcome was skin ulcer occurrence assessed by at least 2 deliveries of wound dressing during the period of one month. Among 6911 individuals newly exposed to bisphosphonates and 28,072 unexposed individuals with no previous skin ulcer, the Cox regression yielded a hazard ratio (HR) of 1.40 (95% CI 1.26-1.56) for newly exposed individuals. Among 7402 exposed and 29,605 unexposed individuals, the PERR analysis found a non-significant HR of 1.03 (95% CI 0.87-1.24). Results were similar on the different sensitivity analyses. CONCLUSION: No association between bisphosphonate and skin ulcers was found in the French population. The association observed in previous pharmacovigilance studies and in the Cox regression analysis is likely due to unmeasured confounding factors.

Bleeding risk with concurrent use of anticoagulants and ibrutinib: A population-based nested case-control study.

Data regarding the safety of co-administration of ibrutinib with anticoagulants in real-life settings are scarce. Using a nationwide database, we conducted a nested case-control study in a cohort of new users of ibrutinib to assess the risk of clinically relevant bleeding (CRB) associated with anticoagulation. Cases were patients with a diagnosis of CRB, defined as hospitalization with a diagnosis of bleeding. The date of CRB constituted the index date. Up to four controls were matched on sex, age at index date and duration of follow-up. The risk of CRB associated with anticoagulation in patients receiving ibrutinib was estimated using conditional logistic regression models, providing odds ratios (OR) adjusted for risk factors of bleeding. Among 614 cases and 2407 matched controls, the risk of CRB was significantly higher in patients receiving both ibrutinib and anticoagulants (adjusted OR [aOR] 2.54, confidence interval [CI] 95% [1.94; 3.32]). When considering anticoagulant class, aOR was 1.99 (CI 95% [1.19; 3.33]) for VKA, 2.48 (CI 95% [1.76; 3.47]) for direct oral anticoagulants and 3.40 (CI 95% [2.01; 5.75]) for parenteral anticoagulants. In conclusion, this study found a 2.5-fold increased risk of CRB in patients receiving both ibrutinib and anticoagulants in real-life settings, and similar aOR among oral anticoagulants.

Risk of suicide attempt and suicide associated with benzodiazepine: A nationwide case crossover study.

BACKGROUND: Previous studies that found an association between benzodiazepines and suicidal behaviours were confounded by indication bias. AIMS: To limit this bias, a case crossover study (CCO) was conducted to estimate the risk of suicide attempt and suicide associated with benzodiazepines. METHOD: Patients ≥16 years, with hospitalised suicide attempt or suicide between 2013 and 2016, and at least one benzodiazepine dispensing within the 120 days before their act were selected in the nationwide French reimbursement healthcare system databases (SNDS). For each patient, frequency of benzodiazepine dispensing was compared between a risk period (days -30 to -1 before the event) and two matched reference periods (days -120 to -91, and -90 to -61). RESULTS: A total of 111,550 individuals who attempted suicide and 12,312 suicide victims were included, of who, respectively, 77,474 and 7958 had recent psychiatric history. Benzodiazepine dispensing appeared higher in the 30-day risk period than in reference ones. The comparison yielded adjusted odds ratios of 1.74 for hospitalised suicide attempt (95% confidence interval 1.69-1.78) and 1.45 for suicide (1.34-1.57) in individuals with recent psychiatric history, and of 2.77 (2.69-2.86) and 1.80 (1.65-1.97) for individuals without. CONCLUSION: This nationwide study supports an association between recent benzodiazepine use and both suicide attempt and suicide. These results strengthen the need for screening for suicidal risk carefully before initiation and during treatment when prescribing benzodiazepines. REGISTRATION NO: EUPAS48070 (http://www.ENCEPP.eu).

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.

Drug-Drug Interactions and the Risk of Emergency Hospitalizations: A Nationwide Population-Based Study.

BACKGROUND: Several studies suggest a significant risk of hospitalization because of drug-drug interactions in the general population. However, to our knowledge, this risk has never been measured precisely in a large population. OBJECTIVE: We aimed to estimate the risk of emergency hospitalization associated with exposure to the contraindicated concomitant use of interacting drugs in the general population. METHODS: A self-controlled case-series analysis was carried out on a cohort of 150,000 subjects randomly selected from the French national health insurance database, between 01/01/2016 and 31/12/2016. Exposure to the contraindicated concomitant use of interacting drugs was defined as the overlapping period of dispensings of drugs contraindicated because of clinically meaningful drug-drug interactions. The main outcome, incidence rate ratios, comparing the incidence rate of emergency hospitalizations during each category of exposure time periods with that during the reference period, was estimated using the conditional Poisson regression model. RESULTS: Over the study period, 967 subjects were exposed to at least one contraindicated concomitant use of interacting drug and 177 had been exposed and presented at least one emergency hospitalization. Compared to the unexposed follow-up time, the risk of emergency hospitalization increased during exposure to contraindicated concomitant use of interacting drug periods (incidence rate ratio: 2.41; 95% confidence interval 1.55-3.76). This could translate into 7200 (4500-8900) potentially preventable emergency hospitalizations yearly in France. CONCLUSIONS: We evidenced an almost 2.5-fold increase in the risk of emergency hospitalizations during periods of exposure to contraindicated concomitant use of interacting drugs, with a potential public health impact exceeding 7000 preventable hospitalizations yearly in France. These results confirm the need to reinforce training in prescription practices and tools for prevention concerning contraindicated concomitant use of interacting drugs. These would especially concern drugs involved in an increase in long QT syndrome when associated such as citalopram, and highly prescribed drugs with a risk of overdose if co-prescribed with cytochrome P450 inhibitors, such as antigout and lipid-lowering drugs.

Utilization patterns, cardiovascular risk, and concomitant serotoninergic medications among triptan users between 2008 and 2018: A gender analysis in one Italian region, Tuscany.

OBJECTIVE: To describe the pattern of triptan use by gender in Tuscany, Italy, focusing on special user populations in which evidence on triptan safety is still not conclusive. BACKGROUND: Growing evidence supports the role of gender differences in migraine pathophysiology and treatment. However, gender impact on triptan real-word utilization has been poorly investigated. METHODS: A retrospective, descriptive, cohort study was performed using the population-based Administrative Healthcare Database of Tuscany region (Italy). Subjects registered in the database on the January 1 of each year between 2008 and 2018 were identified. New users (NU) of triptans (ATC:N02CC*) were patients with one or more triptan dispensation during the year of interest and none in the past. Age, cardiovascular comorbidities representing an absolute or a possible contraindication to triptan utilization, concomitant serotonergic medications, and pattern of triptan use during 1-year follow-up were described by gender. RESULTS: A total of 86,109 patients who received one or more triptan dispensing were identified. Of 64,672 NU (men = 17,039; women = 47,633), 10.2% (6823/64,672) were aged >65 years, who were mostly women (n = 4613). Among NU, men and women with absolute cardiovascular contraindications were 4.3% (740/17,039) and 2.1% (1022/47,633), respectively, while those concomitantly taking serotonergic medications were 17.2% (267/1549) and 21.9% (949/4330), respectively (949/4330). Regular users (two or more dispensing with ≥3 months between first and last observed dispensing) accounted for 26.4% of women (12,597/47,633) and 19.11% of men (3250/17,039); frequent users (≥15 dosage units/month during ≥3 consecutive months) were overall 0.1% (94/64,672) and 62.0% (58/94) of them concomitantly received serotonergic medications. CONCLUSION: Considering gender differences in triptan use highlighted here, large scale observational studies are warranted to better define what populations are safe to use triptans and whether it is appropriate to tighten or relax certain recommendations on triptan use. In the meantime, any suspected adverse drug reaction observed in the special user populations highlighted in this study should be promptly reported.

Neurocognitive Disorders Associated with PCSK9 Inhibitors: a Pharmacovigilance Disproportionality Analysis.

PURPOSE: PCSK9 might affect central nervous system development, neuronal apoptosis, and differentiation. We investigate the neurocognitive adverse events associated with the use of PCSK9 inhibitors (alirocumab and evolocumab) using pharmacovigilance reports. METHODS: We used the World Health Organization pharmacovigilance database (VigiBase) to perform a disproportionality analysis comparing the proportion of neurocognitive adverse events reported with PCSK9 inhibitors versus the proportion of these effects reported since August 14, 2015 (date of first post-marketing report suspecting a PCSK9 inhibitor), for all drugs in the database. Associations between PCSK9 inhibitor use and neurocognitive adverse events were assessed using both proportional reporting ratio (PRR) and information component (IC). Complementary analyses were performed on other neurologic events, and different sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: Among the 81,108 reports involving at least one PCSK9 inhibitor, 1,941 concerned the occurrence of neurocognitive disorders. Most of patients (52.3%) were aged 45-74 years, and 58.0% were women. Signals of disproportionate reporting were found for PCSK9 inhibitors (PRR 1.22, 95% CI 1.17; 1.28; IC 0.28, IC025 0.21) and for each drug individually. No signal of disproportionality was found for any of the other neurologic events investigated. Signals of disproportionate reporting were found for the positive control (benzodiazepines), but not for the negative control (aspirin). The results of the main analysis were confirmed by sensitivity analyses. CONCLUSIONS: This study identified a signal of neurocognitive disorders associated with PCSK9 inhibitors and encourages paying attention to at-risk populations.

Systematic review on sex differences for drug use after stroke.

INTRODUCTION: Systematic reviews and meta-analyses have synthetized the existing knowledge on sex-differences for the risk of stroke, the most recent ones highlighting an increased risk of stroke for women. However, whether there are sex differences in post stroke treatment in real world setting is not known. We therefore conducted a systematic review on this subject. MATERIAL AND METHODS: All observational studies on sex-differences in poststroke drug use published until 20/04/2021 were identified from PubMed and Scopus. Articles were selected and assessed by two independent readers; a third resolved disagreements. Data extraction was performed using a standardized form; articles quality was assessed using the STROBE guidelines. The study is registered on PROSPERO: CRD42021250256. RESULTS: Of the 604 identified articles, 33 were included. Most were published before 2015 and presented methodological limitations. These limitations differentially affected studies with statistically significant and non-significant results, questioning the reliability of conflicting results. The exploration of sex-differences in drug use varied between therapeutic classes (articles focusing on thrombolytics: 25; antithrombotics: 23; on antihypertensive: 13; lipid-lowering drugs: 9). After stroke, women were found less likely to be prescribed antithrombotics in 48% of the articles investigating this class, and lipid-lowering drugs in 56%. Thirty-one percent of the studies concerning antihypertensive drugs reported the opposite. DISCUSSION/CONCLUSION: In women, a lack of use of antithrombotics and lipid-lowering drugs after stroke seem to emerge from this review. Conflicting results regarding sex-differences might relate to methodological limitations in studies with no statistical differences, and advocate for the conduct of newer and more comprehensive research.

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.

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.

Potentially inappropriate medication use by level of polypharmacy among US Veterans 49-64 and 65-70 years old.

BACKGROUND: Potentially inappropriate medications (PIMs) are medications contra-indicated in particular circumstances. We sought to characterize PIMs by level of polypharmacy by age, sex, and race/ethnicity. METHODS: We performed a cross-sectional drug dispensing study using electronic health records available through the US Department of Veterans Affairs. We extracted pharmacy fill and refill records during fiscal year 2016 (i.e., October 1, 2015-September 30, 2016) for all patients aged 49-70 who accessed care in the preceding fiscal year. PIMs were defined by the combined Beers and Laroche (henceforth Beers Laroche) criteria used for older patients and the PROMPT criteria used for middle-aged. RESULTS: In the 1 499 586 patients aged 49-64, PIMs prevalence by PROMPT in patients with 0-4, 5-9, and ≥10 medications was 14.0%, 62.2%, and 86.1%, respectively, and by Beers Laroche was 14.3%, 63.4%, and 85.7%, respectively. In the 1 249 119 patients aged 65-70, PIMs prevalence by Beers Laroche was 14.8%, 59.9%, and 83.3%, and by PROMPT was 13.9%, 57.4%, and 82.0%, respectively. Meaningful differences in prevalence were shown by sex and race/ethnicity according to both set of criteria (e.g. PROMPT in patients with 5-9 medications: 66.1% women vs. 59.3% men; standardized-mean-differences [SMD] = 0.14; 61.7% of White vs. 54.5% of non-White; SMD = 0.15). The most common PIMs were digestive, analgesic, antidiabetic, and psychotropic medications. CONCLUSION: Prevalence of PIMs was high and increased with polypharmacy. Beers Laroche and PROMPT provided similar estimations inside and outside their target age, suggesting that PIMs are common among those with polypharmacy regardless of age.

Oral Morphine as an Alternative Substitution Treatment for Opioid Use Disorder, a Rare but Non-risk-free Use.

Background: National health monitoring agencies have reported the alternative use of morphine sulfate painkiller for maintenance treatment of opioid use disorder (OUD), associated with a potential increase in overdose risk. Objectives: This study sought to assess the prevalence of regular and occasional legally prescribed morphine use in patients treated for OUD and compare their characteristics to those of patients receiving conventional opioid maintenance treatment (OMT), buprenorphine or methadone. Then, we assessed the factors associated with opioid overdose risk. Methods: Data were extracted from the French national healthcare system database, covering the entire population in 2015. Diagnosis associated with hospital discharge and long-term disease codes were extracted to select the population and identify outcomes and covariates. OUD non-chronic pain patients were divided into regular (≤35 days between dispensing and ≥3 months of continuous treatment duration) morphine users, and occasional users. Their sociodemographic and health characteristics were compared to OMT controls. A multivariate logistic regression model was performed to determine factors associated with opioid overdose. Results: In patients treated for OUD, 2,237 (2.2%) morphine users (1,288 regular and 949 occasional), 64,578 (63.7%) buprenorphine and 34,638 (34.1%) methadone controls were included. The prevalence of regular morphine use among patients treated for OUD regularly receiving an opioid was 1.3%. Compared to users who receive morphine regularly, occasional users had an increased risk of overdose [OR = 2.2 (1.5-3.3)], while the risk was reduced in the buprenorphine group [OR = 0.5 (0.4-0.7)] and not significantly different for methadone [OR = 1.0 (0.7-1.4)]. Other overdose risk factors were low-income, comorbidity, i.e., psychiatric conditions, alcohol use disorder or complications related to intravenous drug use, and coprescription with benzodiazepines or pregabalin. These factors were more frequent in morphine groups. Conclusions: Patients that were prescribed oral morphine represented a small minority of the treated for OUD. The poorer health condition affected by numerous comorbidities and higher risk of opioid overdose in patients treated with oral morphine compared with OMT controls points toward the need to better supervise the practices of these patients, to strengthen multidisciplinary care and risk reduction measures.