Spousal bereavement and four-year trajectories of medication use: A nationwide register-based study in Swedish older adults.

BACKGROUND: Medication use around widowhood has been poorly described for most medication classes. Medication use patterns can reflect health consequences of spousal loss, as previously shown for psychotropic drugs. METHODS: We used data from nationwide health registers (2008-2020) to describe the patterns of use of dispensed medications in all widowed Swedes aged ≥65 years followed between 2 years before and 2 years after spousal death. All prescription drugs used by at least 5% of the cohort were considered according to their therapeutic subgroups (Anatomical Therapeutic Chemical [ATC] classification system 2nd level). We used group-based trajectory models to cluster widowed individuals into up to 4 distinct longitudinal patterns of monthly medication use. We ranked the therapeutic subgroups with similar patterns according to their plausibility to reflect potential health effects of spousal loss, compared to those of psycholeptics (mainly anxiolytics, hypnotics) and psychoanaleptics (mainly antidepressants) as the references. RESULTS: From 212,111 widowed adults included (68% female and 70% aged ≥75 years), we observed a significant increasing trend in medication use, especially after spousal death, for 21 out of the 39 different therapeutic subgroups that were used by at least 5% (most represented pharmacological groups: cardiovascular system, nervous system, and alimentary tract and metabolism). This increasing trend often concerned only a small proportion of individuals, with varying magnitude and speed of change in medication use across therapeutic subgroups. The patterns of use of antiepileptics, laxatives, skin emollients/protectives, analgesics, and drugs for anemia, constipation, or peptic ulcers, were the closest to those of references, displaying the largest changes in use, and were therefore ranked as the most likely to reflect health effects of spousal loss. CONCLUSION: Our results confirmed the increase in psychotropic medications' use in widowed older adults and identified several potential physical health effects of spousal loss that warrant further research.

Long-term care use, hospitalizations and mortality during COVID-19 in Finland and Sweden: A nationwide register-based study in 2020.

AIM: To describe long-term care (LTC) use in Finland and Sweden in 2020, by reporting residential entry and exit patterns including hospital admissions and mortality, compared with the 2018-2019 period and community-living individuals. METHODS: From national registers in Finland and Sweden, all individuals 70+ were included. Using the Finnish and Swedish study populations in January 2018 as the standard population, we reported changes in sex- and age-standardized monthly rates of entry into and exit from LTC facilities, mortality and hospital admission among LTC residents and community-living individuals in 2020. RESULTS: Around 850,000 Finns and 1.4 million Swedes 70+ were included. LTC use decreased in both countries from 2018 to 2020. In the first wave (March/April 2020), Finland experienced a decrease in LTC entry rates and an increase in LTC exit rates, both more marked than Sweden. This was largely due to short-term movements. Mortality rates peaked in April and December 2020 for LTC residents in Finland, while mortality peaked for both community-living individuals and LTC residents in Sweden. A decrease in hospital admissions from LTC facilities occurred in April 2020 and was less marked in Finland versus Sweden. CONCLUSIONS: During the first wave of the pandemic mortality was consistently higher in Sweden. We also found a larger decrease in LTC use and, among LTC residents, a smaller decrease in hospital admissions in Finland than in Sweden. This study calls for assessing the health consequences of the differences observed between these two Scandinavian countries as part of the lessons from the COVID-19 pandemic.

Cholinesterase inhibitors and non-steroidal anti-inflammatory drugs and the risk of peptic ulcers: A self-controlled study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution in adults aged 65 years and older. Their gastrointestinal adverse event risk might be further reinforced when using concomitant cholinesterase inhibitors (ChEIs). We aimed to investigate the association between NSAIDs and ChEI use and the risk of peptic ulcers in adults aged 65 years and older. METHODS: Register-based self-controlled case series study including adults ≥65 years with a new prescription of ChEIs and NSAIDs, diagnosed with incident peptic ulcer in Sweden, 2007-2020. We identified persons from the Total Population Register individually linked to several nationwide registers. We estimated the incidence rate ratio (IRR) of peptic ulcer with a conditional Poisson regression model for four mutually exclusive risk periods: use of ChEIs, NSAIDs, and the combination of ChEIs and NSAIDs, compared with the non-treatment in the same individual. Risk periods were identified based on the prescribed daily dose, extracted via a text-parsing algorithm, and a 30-day grace period. RESULTS: Of 70,060 individuals initiating both ChEIs and NSAIDs, we identified 1500 persons with peptic ulcer (median age at peptic ulcer 80 years), of whom 58% were females. Compared with the non-treatment periods, the risk of peptic ulcer substantially increased for the combination of ChEIs and NSAIDs (IRR: 9.0, [6.8-11.8]), more than for NSAIDs alone (5.2, [4.4-6.0]). No increased risks were found for the use of ChEIs alone (1.0, [0.9-1.2]). DISCUSSION: We found that the risk of peptic ulcer associated with the concomitant use of NSAIDs and ChEIs was over and beyond the risk associated with NSAIDs alone. Our results underscore the importance of carefully considering the risk of peptic ulcers when co-prescribing NSAIDs and ChEIs to adults aged 65 years and older.

Dispensing of Potentially Harmful Prescription Drugs in 1.8 Million Pregnant Women in France: A Nationwide Study Based on Two Risk Classification Systems.

INTRODUCTION: Nationwide prevalence of potentially harmful drug prescribing during pregnancy is unknown in France, and several risk classification systems (RCS) exist to guide prescribers. OBJECTIVE: The aim of this study was to estimate the nationwide prevalence of potentially harmful drug prescribing during pregnancy in France and to describe maternal characteristics associated with this prescription. METHODS: This drug utilisation study, conducted on the French health databases (67 million beneficiaries), included all pregnancies beginning in 2016-2017, regardless of pregnancy outcome. Potentially harmful drug prescribing was defined as at least one reimbursement during pregnancy of Swedish RCS category D drugs, Australian RCS category D/X drugs, or contraindicated drugs in France for drugs not listed in these two RCSs. Maternal characteristics associated with potentially harmful drug prescribing were described using a univariate logistic regression analysis. RESULTS: Among the 1,844,447 pregnant women identified, the prevalence of potentially harmful drug prescribing was higher according to the Australian RCS (3.9%) than according to the Swedish RCS (2.2%), with good agreement between the two RCSs (Kappa = 0.81 [0.74-0.87]). This prevalence increased to 9.2% and 6.9%, respectively, when considering contraindications in France. Prescribing of teratogenic drugs, including retinoids and valproate, was highest during the first trimester, whereas prescribing of foetotoxic drugs decreased after the first trimester but remained high for nonsteroidal anti-inflammatory drugs (N = 10,021). In women with no chronic diseases, polymedication (five or more drugs) was the strongest maternal characteristic associated with potentially harmful drug prescribing in both RCSs. CONCLUSIONS: Potentially harmful drug prescribing during pregnancy is not uncommon in France. This study supports the comparative analysis of RCS to assess potentially harmful drug prescribing in claims databases.

Risk of early neurodevelopmental disorders associated with in utero exposure to valproate and other antiepileptic drugs: a nationwide cohort study in France.

Information available on the risks of neurodevelopmental disorders (NDs) associated with in utero exposure to valproate (VPA) and to other antiepileptic drugs (AEDs) is limited. A nationwide population-based cohort study was conducted based on comprehensive data of the French National Health Data System (SNDS). Liveborn infants without brain malformation, born between January 2011 and December 2014, were followed from birth up to December 2016. NDs were identified based on diagnoses of mental or behavioural disorders and utilization of speech therapy, orthoptic or psychiatric services. The risk of NDs was compared between children exposed in utero to AED monotherapy and unexposed children, using Cox proportional hazard models adjusted for maternal and neonatal characteristics. The cohort included 1,721,990 children, 8848 of whom were exposed in utero to AED monotherapy. During a mean follow-up of 3.6 years, 15,458 children had a diagnosis of mental or behavioural disorder. In utero exposure to VPA was associated with an increased risk of NDs overall (aHR: 3.7; 95% CI 2.8-4.9) and among children born to a mother without mental illness (aHR 5.1; 95% CI 3.6-7.3). A dose-response relationship was demonstrated and the risk of NDs was more particularly increased for an exposure to VPA during the second or third trimesters of pregnancy. Among the other AEDs, only pregabalin was consistently associated with an increased risk of NDs (aHR: 1.5; 95% CI 1.0-2.1). This study confirms a four to fivefold increased risk of early NDs associated with exposure to VPA during pregnancy. The risk associated with other AEDs appears much lower.

Risk of early neurodevelopmental outcomes associated with prenatal exposure to the antiepileptic drugs most commonly used during pregnancy: a French nationwide population-based cohort study.

OBJECTIVES: To assess the association between prenatal exposure to monotherapy with the antiepileptic drugs (AEDs) most commonly used during pregnancy and the risk of various neurodevelopmental outcomes compared with lamotrigine. DESIGN: Nationwide population-based cohort study. SETTING: French national healthcare databases. PARTICIPANTS: Children born alive between 2011 and 2014 and prenatally exposed to AED monotherapy. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes included neurodevelopmental disorders (NDD), defined by International Classification of Diseases, 10th Revision codes F70-F98-pervasive developmental disorders (PDD, F84) and mental retardation (MR, F70-F79) were studied separately-and visits to speech therapists. The reference group comprised children prenatally exposed to lamotrigine. Children were followed until outcome, loss to follow-up, death or 31 December 2016. We performed inverse probability of treatment weighting analyses using the propensity score, which included maternal and infant characteristics. Hazard ratios (HRs) were calculated using Cox models. RESULTS: The cohort comprised 9034 children, 2916 of which were exposed to lamotrigine, 1627 to pregabalin, 1246 to clonazepam, 991 to valproic acid (VPA), 621 to levetiracetam, 502 to carbamazepine, 477 to topiramate, 378 to gabapentin and 143 to oxcarbazepine. None of these AEDs, except VPA, was associated with an increased risk of any of the four neurodevelopmental outcomes investigated. Exposure to VPA was associated with increased risks of NDDs (HR=2.7, 95% CI (1.8 to 4.0)), PDD (HR=4.4 (2.1 to 9.3)), MR (HR=3.1 (1.5 to 6.2)) and visits to speech therapists (HR=1.5 (1.1 to 1.9)), with a dose-response relationship. CONCLUSIONS: No increased risk of any of the neurodevelopmental outcomes investigated in this study was observed with prenatal exposure to levetiracetam, pregabalin, oxcarbazepine, topiramate, gabapentin, clonazepam or carbamazepine, compared with lamotrigine. However, this study corroborates the well-known association between maternal use of VPA during pregnancy and the risk of neurodevelopmental disorders in the offspring. Longer follow-up is necessary to confirm these findings.

Risks of 23 specific malformations associated with prenatal exposure to 10 antiepileptic drugs.

OBJECTIVE: To assess the association between exposure to monotherapy with 10 different antiepileptic drugs (AEDs) during the first 2 months of pregnancy and the risk of 23 major congenital malformations (MCMs). METHODS: This nationwide cohort study, based on the French health care databases, included all pregnancies ≥20 weeks and ending between January 2011 and March 2015. Women were considered to be exposed when an AED had been dispensed between 1 month before and 2 months after the beginning of pregnancy. The reference group included pregnant women with no reimbursement for AEDs. MCMs were detected up to 12 months after birth (24 months for microcephaly, hypospadias, and epispadias). Odds ratios (ORs) were adjusted for potential confounders for MCMs with at least 5 cases. Otherwise, we calculated crude ORs with exact confidence intervals (CIs). RESULTS: The cohort included 1,886,825 pregnancies, 2,997 of which were exposed to lamotrigine, 1,671 to pregabalin, 980 to clonazepam, 913 to valproic acid, 579 to levetiracetam, 517 to topiramate, 512 to carbamazepine, 365 to gabapentin, 139 to oxcarbazepine, and 80 to phenobarbital. Exposure to valproic acid was associated with 8 specific types of MCMs (e.g., spina bifida, OR 19.4, 95% CI 8.6-43.5), and exposure to topiramate was associated with an increased risk of cleft lip (6.8, 95% CI 1.4-20.0). We identified 3 other signals. We found no significant association for lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, and gabapentin. CONCLUSIONS: These results confirm the teratogenicity of valproic acid and topiramate. Because of the small numbers of cases and possible confounding, the other 3 signals should be interpreted with appropriate caution.

Patient, Procedure, and Endoscopist Risk Factors for Perforation, Bleeding, and Splenic Injury After Colonoscopies.

BACKGROUND & AIMS: We investigated perforations, bleeding, and splenic injuries after screening or diagnostic colonoscopies to identify patient-, procedure-, endoscopist-, and facility-associated risk factors. METHODS: We analyzed data from the SNIIRAM-PMSI national claims databases in France. A total of 4,088,799 patients, 30 years or older, undergoing a first screening or diagnostic colonoscopy from 2010 through 2015 were identified. Rates of severe adverse events (SAEs) were estimated using stringent and broad definitions. Risk factors associated with perforations and major bleeding were estimated using multilevel logistic regression models, adjusted for patient, colonoscopy, and endoscopist characteristics. RESULTS: Perforation rates ranged from 3.5 (stringent definition) to 7.3 (broad definition) per 10,000 procedures, bleeding rates ranged from 6.5 to 23.1 per 10,000 procedures, and splenic injury rates ranged from 0.20 to 0.34 per 10,000 procedures. Rates of 30-day mortality were 13.2 per 1000 bleeds, 29.2 per 1000 perforations, and 36.1 per 1000 splenic injuries (stringent definitions). Patient characteristics associated with SAEs were increasing age (especially for perforation), cancer, and cardiovascular comorbidities. Procedure characteristics associated with SAEs included polypectomy-especially of polyps larger than 1 cm with an increased risk of perforation (odds ratio, 4.1; 95% CI, 3.4-5.0) and bleeding (odds ratio, 13.3; 95% CI, 11.7-15.1). Less-experienced endoscopists and endoscopists who performed a smaller number of colonoscopies were independently associated with a risk of SAEs. CONCLUSION: In an analysis of national claims databases in France, we found SAEs related to screening and diagnostic colonoscopies to be more frequent in older patients, in patients with comorbidities, and with less-experienced endoscopists. Patients at risk of SAE should be identified and colonoscopies should be performed or supervised by experienced endoscopists.

Development of an algorithm to identify pregnancy episodes and related outcomes in health care claims databases: An application to antiepileptic drug use in 4.9 million pregnant women in France.

PURPOSE: Access to claims databases provides an opportunity to study medication use and safety during pregnancy. We developed an algorithm to identify pregnancy episodes in the French health care databases and applied it to study antiepileptic drug (AED) use during pregnancy between 2007 and 2014. METHODS: The algorithm searched the French health care databases for discharge diagnoses and medical procedures indicative of completion of a pregnancy. To differentiate claims associated with separate pregnancies, an interval of at least 28 weeks was required between 2 consecutive pregnancies resulting in a birth and 6 weeks for terminations of pregnancy. Pregnancy outcomes were categorized into live births, stillbirths, elective abortions, therapeutic abortions, spontaneous abortions, and ectopic pregnancies. Outcome dates and gestational ages were used to calculate pregnancy start dates. RESULTS: According to our algorithm, live birth was the most common pregnancy outcome (73.9%), followed by elective abortion (17.2%), spontaneous abortion (4.2%), ectopic pregnancy (1.1%), therapeutic abortion (1.0%), and stillbirth (0.4%). These results were globally consistent with French official data. Among 7 559 701 pregnancies starting between 2007 and 2014, corresponding to 4 900 139 women, 6.7 per 1000 pregnancies were exposed to an AED. The number of pregnancies exposed to older AEDs, comprising the most teratogenic AEDs, decreased throughout the study period (-69.4%), while the use of newer AEDs increased (+73.4%). CONCLUSIONS: We have developed an algorithm that allows identification of a large number of pregnancies and all types of pregnancy outcomes. Pregnancy outcome and start dates were accurately identified, and maternal data could be linked to neonatal data.

Dental procedures, antibiotic prophylaxis, and endocarditis among people with prosthetic heart valves: nationwide population based cohort and a case crossover study.

Objective To assess the relation between invasive dental procedures and infective endocarditis associated with oral streptococci among people with prosthetic heart valves.Design Nationwide population based cohort and a case crossover study.Setting French national health insurance administrative data linked with the national hospital discharge database.Participants All adults aged more than 18 years, living in France, with medical procedure codes for positioning or replacement of prosthetic heart valves between July 2008 and July 2014.Main outcome measures Oral streptococcal infective endocarditis was identified using primary discharge diagnosis codes. In the cohort study, Poisson regression models were performed to estimate the rate of oral streptococcal infective endocarditis during the three month period after invasive dental procedures compared with non-exposure periods. In the case crossover study, conditional logistic regression models calculated the odds ratio and 95% confidence intervals comparing exposure to invasive dental procedures during the three month period preceding oral streptococcal infective endocarditis (case period) with three earlier control periods.Results The cohort included 138 876 adults with prosthetic heart valves (285 034 person years); 69 303 (49.9%) underwent at least one dental procedure. Among the 396 615 dental procedures performed, 103 463 (26.0%) were invasive and therefore presented an indication for antibiotic prophylaxis, which was performed in 52 280 (50.1%). With a median follow-up of 1.7 years, 267 people developed infective endocarditis associated with oral streptococci (incidence rate 93.7 per 100 000 person years, 95% confidence interval 82.4 to 104.9). Compared with non-exposure periods, no statistically significant increased rate of oral streptococcal infective endocarditis was observed during the three months after an invasive dental procedure (relative rate 1.25, 95% confidence interval 0.82 to 1.82; P=0.26) and after an invasive dental procedure without antibiotic prophylaxis (1.57, 0.90 to 2.53; P=0.08). In the case crossover analysis, exposure to invasive dental procedures was more frequent during case periods than during matched control periods (5.1% v 3.2%; odds ratio 1.66, 95% confidence interval 1.05 to 2.63; P=0.03).Conclusion Invasive dental procedures may contribute to the development of infective endocarditis in adults with prosthetic heart valves.

Low dose oestrogen combined oral contraception and risk of pulmonary embolism, stroke, and myocardial infarction in five million French women: cohort study.

OBJECTIVE: To assess the risk of pulmonary embolism, ischaemic stroke, and myocardial infarction associated with combined oral contraceptives according to dose of oestrogen (ethinylestradiol) and progestogen. DESIGN: Observational cohort study. SETTING: Data from the French national health insurance database linked with data from the French national hospital discharge database. PARTICIPANTS: 4 945 088 women aged 15-49 years, living in France, with at least one reimbursement for oral contraceptives and no previous hospital admission for cancer, pulmonary embolism, ischaemic stroke, or myocardial infarction, between July 2010 and September 2012. MAIN OUTCOME MEASURES: Relative and absolute risks of first pulmonary embolism, ischaemic stroke, and myocardial infarction. RESULTS: The cohort generated 5 443 916 women years of oral contraceptive use, and 3253 events were observed: 1800 pulmonary embolisms (33 per 100 000 women years), 1046 ischaemic strokes (19 per 100 000 women years), and 407 myocardial infarctions (7 per 100 000 women years). After adjustment for progestogen and risk factors, the relative risks for women using low dose oestrogen (20 µg v 30-40 µg) were 0.75 (95% confidence interval 0.67 to 0.85) for pulmonary embolism, 0.82 (0.70 to 0.96) for ischaemic stroke, and 0.56 (0.39 to 0.79) for myocardial infarction. After adjustment for oestrogen dose and risk factors, desogestrel and gestodene were associated with statistically significantly higher relative risks for pulmonary embolism (2.16, 1.93 to 2.41 and 1.63, 1.34 to 1.97, respectively) compared with levonorgestrel. Levonorgestrel combined with 20 µg oestrogen was associated with a statistically significantly lower risk than levonorgestrel with 30-40 µg oestrogen for each of the three serious adverse events. CONCLUSIONS: For the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial thromboembolism compared with levonorgestrel. For the same type of progestogen, an oestrogen dose of 20 µg versus 30-40 µg was associated with lower risks of pulmonary embolism, ischaemic stroke, and myocardial infarction.

Conditions of prescription of anti-TNF agents in newly treated patients with inflammatory bowel disease in France (2011-2013).

BACKGROUND: Tumour necrosis factor inhibitors (anti-TNFs) are active but expensive drugs that induce and maintain remission in patients with Crohn's disease (CD) and ulcerative colitis (UC). AIMS: To assess the trends in anti-TNF prescription and the conditions of prescription of these drugs in patients with inflammatory bowel disease (IBD) in France. METHODS: Incidence study of anti-TNF use was performed based on French medico-administrative databases (SNIIRAM/PMSI). IBD patients who initiated adalimumab or infliximab between 2011 and 2013 were selected. RESULTS: The number of new anti-TNF users increased from 4571 to 5875 between 2011 and 2013 (+29%). More specifically, the number of patients not treated with immunosuppressants (IS) during the previous 12 months increased from 2100 to 3007 (+43%), among whom 379 patients in 2011 and 570 patients in 2013 started combination therapy (+50%). These trends were observed for both CD and UC. Patients who were naïve of IS were hospitalised more frequently than those treated with IS prior to anti-TNF therapy. CONCLUSION: This study shows a rapid increase in new prescriptions of anti-TNF for both CD and UC in France between 2011 and 2013. These results suggest a change in medical practices, with anti-TNF agents prescribed more often as first-line maintenance treatment.

The Best Use of the Charlson Comorbidity Index With Electronic Health Care Database to Predict Mortality.

BACKGROUND: The most used score to measure comorbidity is the Charlson index. Its application to a health care administrative database including International Classification of Diseases, 10th edition (ICD-10) codes, medical procedures, and medication required studying its properties on survival. Our objectives were to adapt the Charlson comorbidity index to the French National Health Insurance database to predict 1-year mortality of discharged patients and to compare discrimination and calibration of different versions of the Charlson index. METHODS: Our cohort included all adults discharged from a hospital stay in France in 2010 registered in the French National Health Insurance general scheme. The pathologies of the Charlson index were identified through ICD-10 codes of discharge diagnoses and long-term disease, specific medical procedures, and reimbursement of specific medications in the past 12 months before inclusion. RESULTS: We included 6,602,641 subjects at the date of their first discharge from medical, surgical, or obstetrical department in 2010. One-year survival was 94.88%, decreasing from 98.41% for Charlson index of 0-71.64% for Charlson index of ≥5. With a discrimination of 0.91 and an appropriate calibration curve, we retained the crude Cox model including the age-adjusted Charlson index as a 4-level score. CONCLUSIONS: Our study is the first to adapt the Charlson index to a large health care database including >6 million of inpatients. When mortality is the outcome, we recommended using the age-adjusted Charlson index as 4-level score to take into account comorbidities.

Risk of bleeding and arterial thromboembolism in patients with non-valvular atrial fibrillation either maintained on a vitamin K antagonist or switched to a non-vitamin K-antagonist oral anticoagulant: a retrospective, matched-cohort study.

BACKGROUND: Patients with non-valvular atrial fibrillation who are receiving or have been previously exposed to a vitamin K antagonist could be switched to a non-vitamin K-antagonist oral anticoagulant (NOAC) but little information is available about the risk of bleeding and arterial thromboembolism after such a switch. We aimed to compare the risk of bleeding between individuals who switched and those who remained on a vitamin K antagonist (non-switchers) in real-world conditions. METHODS: We did a matched-cohort study with information from French health-care databases. We extracted data for adults (aged ≥18 years) with non-valvular atrial fibrillation who received their first prescription for a vitamin K antagonist (fluindione, warfarin, or acenocoumarol) between Jan 1, 2011, and Nov 30, 2012, and who were either switched to a NOAC (dabigatran or rivaroxaban) or maintained on the vitamin K antagonist. Each switcher was matched with up to two non-switchers on the basis of eight variables, including sex, age, and international normalised ratio number. The primary endpoint was incidence of bleeding (intracranial haemorrhage, gastrointestinal haemorrhage, or other) in switchers versus non-switchers, and switchers stratified by type of NOAC versus non-switchers, noted from databases of hospital admissions. Each patient was followed up to 1 year; the study closed on Oct 1, 2013. FINDINGS: Of 17,410 participants, 6705 switched to a NOAC (switchers) and 10,705 remained on vitamin K-antagonist therapy (non-switchers). Median age of participants was 75 years (IQR 67-82), 8339 (48%) were women, and the median duration of vitamin K-antagonist exposure before a switch was 8.1 months (IQR 3.9-14.0). After a median follow-up of 10.0 months (IQR 9.8-10.0), we noted no difference between groups for bleeding events (99 [1%] in switchers vs 193 [2%] in non-switchers, p=0.54). In adjusted multivariate analyses, the risk of bleeding in switchers was not different from that in non-switchers (hazard ratio [HR] 0.87; 95% CI 0.67-1.13, p=0.30). Additionally, no differences were noted when the risk of bleeding was compared between switchers from a vitamin K antagonist to dabigatran (HR 0.78, 95% CI 0.54-1.09, p=0.15), switchers from a vitamin K antagonist to rivaroxaban (HR 1.04, 95% CI 0.68-1.58, p=0.86), and non-switchers. INTERPRETATION: In this matched-cohort study, our findings suggest that patients with non-valvular atrial fibrillation who switch their oral anticoagulant treatment from a vitamin K antagonist to a non-vitamin K antagonist are not at increased risk of bleeding. Future studies with longer follow-up might be needed. FUNDING: None.

Comparison of the short-term risk of bleeding and arterial thromboembolic events in nonvalvular atrial fibrillation patients newly treated with dabigatran or rivaroxaban versus vitamin K antagonists: a French nationwide propensity-matched cohort study.

BACKGROUND: The safety and effectiveness of non-vitamin K antagonist (VKA) oral anticoagulants, dabigatran or rivaroxaban, were compared with VKA in anticoagulant-naive patients with nonvalvular atrial fibrillation during the early phase of anticoagulant therapy. METHODS AND RESULTS: With the use of the French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort study included patients with nonvalvular atrial fibrillation who initiated dabigatran or rivaroxaban between July and November 2012 or VKA between July and November 2011. Patients presenting a contraindication to oral anticoagulants were excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by the use of 1:2 matching on the propensity score. Patients were followed for up to 90 days until outcome, death, loss to follow-up, or December 31 of the inclusion year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic events were estimated in an intent-to-treat analysis using Cox regression models. The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban new users. All dabigatran- and rivaroxaban-treated patients were matched to 16 014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-, and their VKA-matched-treated patients, 55 and 122 and 31 and 68 bleeding events and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during follow-up, respectively. After matching, no statistically significant difference in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64-1.21) or thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72-1.69) risk was observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95% confidence interval, 0.64-1.51) and ischemic (hazard ratio, 0.93; 95% confidence interval, 0.47-1.85) risks were comparable between rivaroxaban and VKA new users. CONCLUSIONS: In this propensity-matched cohort study, our findings suggest that physicians should exercise caution when initiating either non-VKA oral anticoagulants or VKA in patients with nonvalvular atrial fibrillation.

Perforations and haemorrhages after colonoscopy in 2010: a study based on comprehensive French health insurance data (SNIIRAM).

BACKGROUND AND OBJECTIVE: To estimate the perforation and haemorrhage rate after colonoscopy in the French population in 2010 and to identify risk factors for these complications. METHOD: Study based on SNIIRAM and the PMSI databases. Patients treated for IBD or colorectal cancer were excluded. Two types of complications were investigated: perforation and haemorrhage. OR adjusted for patient (gender, age, chronic disease) and colonoscopy (polypectomy, emergency) characteristics were calculated by using a logistic regression model. RESULTS: The cohort was composed of 947,061 individuals. The estimated perforation rate was between 4.5 and 9.7 per 10,000 procedures and the estimated haemorrhage rate was between 9.9 and 11.0 per 10,000 procedures. The main risk factors associated with perforation and haemorrhage were the patient's age (over 80 years compared to under 40, OR=7.51 and 3.23), resection of polyps larger than 1 cm or more than 4 polyps (compared to no polypectomy, OR=2.72 and 5.12) and emergency colonoscopy (OR=4.63 and 5.99). Colonoscopy performed by a gastroenterologist performing less than 244 colonoscopies per year was associated with an increased risk of perforation (OR=2.29). Complication rates were higher in institutions performing less than 510 colonoscopies per year, but this was no longer the case after adjustment for emergency colonoscopies. CONCLUSIONS: This study, which includes nearly one million colonoscopies, suggests taking the gastroenterologist's number of colonoscopies into account to ensure optimal organization of the management of very elderly patients requiring colonoscopy.

Does insulin glargine increase the risk of cancer compared with other basal insulins?: A French nationwide cohort study based on national administrative databases.

OBJECTIVE: To explore in France the relationship between insulin glargine use and overall and specific cancer risks in type 2 diabetic patients compared with other basal insulins. RESEARCH DESIGN AND METHODS: Data were extracted from French health insurance information system (Système National d'Information Inter-Régimes de l'Assurance Maladie) linked with data from the French Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information). Included were 70,027 patients aged 40-79 years who started a basal insulin in 2007-2009. Cox proportional hazards models with age as time-scale were used to calculate multivariate-adjusted hazard ratios for associations between type of basal insulin and risk of overall cancer, breast cancer, and seven other cancer sites. RESULTS: The median follow-up was 2.67 years in patients exposed to insulin glargine. Absolute event rates for all cancer in patients exposed to glargine versus other basal insulin users were 1,622 and 1,643 per 100,000 person-years, respectively. No significant association was observed between glargine exposure and overall cancer incidence after adjustment for sex, with a hazard ratio of 0.97 (95% CI 0.87-1.07), or after additional adjustment for any other hypoglycemic agent use and duration of diabetes. No increased risk of breast cancer was observed for glargine users compared with other basal insulins users, with a fully adjusted hazard ratio of 1.08 (0.72-1.62). CONCLUSIONS: In a large cohort of patients newly treated by basal insulin, no increased risk of any cancer was observed in insulin glargine users compared with other basal insulin users. Because follow-up did not exceed 4 years, longer-term studies are needed.

[Mortality and hospital admissions rates and diagnosis among individuals with low income and full health insurance coverage in France, 2009]. / Surmortalité et hospitalisations plus fréquentes des bénéficiaires de la couverture médicale universelle complémentaire en 2009.

AIM: Complementary Universal Health insurance (CMUC) providing free access to health care has been available in France since 2000 for people with an annual income less than 60% of the poverty threshold. Hospital admission and mortality rates in 2009 were compared between beneficiaries of the general scheme under the age of 60 years with (4.5 millions) or without CMUC (34.1 millions) in 2008 and still alive at the end of the year. METHODS: Data were derived from the French national health insurance reimbursements and short-stay hospital admissions database for 2009 (80% of subjects under the age of 60 years in France). Rates and relative risks (RR) were standardised for the gender and age. RESULTS: CMUC beneficiaries had greater overall mortality rates (3.32/1000 vs. 1.36/1000, RR=2.4) for both gender (males RR=2.6, females RR=2.1) and each 10 years age class below 60 years. Standardised hospitalisation rate of CMUC beneficiaries was 17.5% and the rate for non-CMUC beneficiaries was 13.2%. Among CMUC beneficiaries, admissions were significantly more frequent for the following activity groups: toxicology, intoxication and alcohol (RR=3.5), psychiatry (RR=2.8), burns (2.7), respiratory medicine (RR=1.9), infectious disease (RR=2.1), endocrinology and cardiology (RR=1.7), obstetrics (RR=1.6). Their hospital mortality rate was also significantly higher (8.9/1000 vs. 5.1/1000, RR=1.73). CONCLUSION: In this low income population with free access to health care, hospitalisation and hospital mortality rates were higher for many diseases that are more or less known targets for prevention and screening actions.

[The cost of dialysis and kidney transplantation in France in 2007, impact of an increase of peritoneal dialysis and transplantation]. / Coût de la prise en charge de l'IRCT en France en 2007 et impact potentiel d'une augmentation du recours à la dialyse péritonéale et à la greffe.

INTRODUCTION: This study estimates the costs for the national health insurance in 2007 of the patients with end-stage renal disease (ESRD) according to therapies modalities. METHOD: Data for all patients covered by the general health insurance scheme (77% of the French population) from hospital discharge and outpatients reimbursement databases were linked. ESRD therapies were identified using an algorithm mainly based on discharge diagnosis and immunosuppressive drugs refunds. RESULTS: Extrapolated to all French population at the end of 2007, 60,900 patients had an ESRD therapy: 30,900 were treated on haemodialysis (HD) (51%), 2600 on peritonea dialysis (DP) (4%) and 27,300 had a kidney transplant (45%). Patients with dialysis therapies had more often complementary universal coverage for low earners. According to the French regions, patient treated with DP were between 0 to 26% and 19 to 57% for those with a transplant. The total refund cost for National Health Insurance was four billion euro of which 77% for HD. Annual mean costs per patient were 64 keuro for DP, 89 keuro for HD, 86 keuro for the year of transplantation and 20 keuro for the following years. A 25% increase of DP would allow a decrease of the annual cost of 155 millions euro and 900 transplantations more each year during 10 years a decrease of 2.5 billions euro. CONCLUSION: The increase of ESRD prevalence and its total cost require patients and professionals information and formation about the less expensive and more autonomous therapies and others alternatives facing the lack of kidney transplants from deceased donors.