Major postpartum haemorrhage after frozen embryo transfer: A population-based study.

OBJECTIVE: To investigate the effect on major postpartum haemorrhage (PPH) of mode of conception, differentiating between naturally conceived pregnancies, fresh embryo in vitro fertilisation (fresh-IVF) and frozen embryo transfer (frozen-IVF). DESIGN: Retrospective cohort study. SETTING: The French Burgundy Perinatal Network database, including all deliveries from 2006 to 2020, was linked to the regional blood centre database. POPULATION OR SAMPLE: In all, 244 336 women were included, of whom 240 259 (98.3%) were singleton pregnancies. METHODS: The main analyses were conducted in singleton pregnancies, including 237 608 naturally conceived, 1773 fresh-IVF and 878 frozen-IVF pregnancies. Multivariate logistic regression models adjusted on maternal age, body mass index, smoking, parity, induction of labour, hypertensive disorders, diabetes, placenta praevia and/or accreta, history of caesarean section, mode of delivery, birthweight, birth place and year of delivery, were used. MAIN OUTCOME MEASURES: Major PPH was defined as PPH requiring blood transfusion and/or emergency surgery and/or interventional radiology. RESULTS: The prevalence of major PPH was 0.74% (n = 1749) in naturally conceived pregnancies, 1.92% (n = 34) in fresh-IVF pregnancies, and 3.30% (n = 29) in frozen-IVF pregnancies. The risk of major PPH was higher in frozen-IVF pregnancies than in both naturally conceived pregnancies (adjusted odds ratio [aOR] 2.63, 95% CI 1.68-4.10) and fresh-IVF pregnancies (aOR 2.78, 95% CI 1.44-5.35). CONCLUSIONS: We found that frozen-IVF pregnancies have a higher risk of major PPH and they should be subject to increased vigilance in the delivery room.

Impact of hospital volume in liver surgery on postoperative mortality and morbidity: nationwide study.

BACKGROUND: This nationwide retrospective study was undertaken to evaluate impact of hospital volume and influence of liver transplantation activity on postoperative mortality and failure to rescue after liver surgery. METHODS: This was a retrospective study of patients who underwent liver resection between 2011 and 2019 using a nationwide database. A threshold of surgical activities from which in-hospital mortality declines was calculated. Hospitals were divided into high- and low-volume centres. Main outcomes were in-hospital mortality and failure to rescue. RESULTS: Among 39 286 patients included, the in-hospital mortality rate was 2.8 per cent. The activity volume threshold from which in-hospital mortality declined was 25 hepatectomies. High-volume centres (more than 25 resections per year) had more postoperative complications but a lower rate of in-hospital mortality (2.6 versus 3 per cent; P < 0.001) and failure to rescue (5 versus 6.3 per cent; P < 0.001), in particular related to specific complications (liver failure, biliary complications, vascular complications) (5.5 versus 7.6 per cent; P < 0.001). Liver transplantation activity did not have an impact on these outcomes. CONCLUSION: From more than 25 liver resections per year, rates of in-hospital mortality and failure to rescue declined. Management of specific postoperative complications appeared to be better in high-volume centres.

Time to onset of cardiovascular and cerebrovascular outcomes after hypertensive disorders of pregnancy: a nationwide, population-based retrospective cohort study.

BACKGROUND: The increased maternal cardiocerebrovascular risk after a pregnancy complicated by hypertensive disorders of pregnancy, is well documented in the literature. Recent evidence has suggested a shorter timeframe for the development of these postnatal outcomes, which could have major clinical implications. OBJECTIVE: This study aimed to determine the risk of and time to onset of maternal cardiovascular and cerebrovascular outcomes after a pregnancy complicated by hypertensive disorders of pregnancy. STUDY DESIGN: This study included 2,227,711 women, without preexisting chronic hypertension, who delivered during the period 2008 to 2010: 37,043 (1.66%) were diagnosed with preeclampsia, 34,220 (1.54%) were diagnosed with gestational hypertension, and 2,156,448 had normotensive pregnancies. Hospitalizations for chronic hypertension, heart failure, coronary heart disease, cerebrovascular disease, and peripheral arterial disease were studied. A classical Cox regression was performed to estimate the average effect of hypertensive disorders of pregnancy over 10 years compared with normotensive pregnancy; moreover, an extended Cox regression was performed with a step function model to estimate the effect of the exposure variable in different time intervals: <1, 1 to 3, 3 to 5, and 5 to 10 years of follow-up. RESULTS: The risk of chronic hypertension after a pregnancy complicated by preeclampsia was 18 times higher in the first year (adjusted hazard ratio, 18.531; 95% confidence interval, 16.520-20.787) to only 5 times higher at 5 to 10 years after birth (adjusted hazard ratio, 4.921; 95% confidence interval, 4.640-5.218). The corresponding risks of women with gestational hypertension were 12 times higher (adjusted hazard ratio, 11.727; 95% confidence interval, 10.257-13.409]) and 6 times higher (adjusted hazard ratio, 5.854; 95% confidence interval, 5.550-6.176), respectively. For other cardiovascular and cerebrovascular outcomes, there was also a significant effect with preeclampsia (heart failure: adjusted hazard ratio, 6.662 [95% confidence interval, 4.547-9.762]; coronary heart disease: adjusted hazard ratio, 3.083 [95% confidence interval, 1.626-5.844]; cerebrovascular disease: adjusted hazard ratio, 3.567 [95% confidence interval, 2.600-4.893]; peripheral arterial disease: adjusted hazard ratio, 4.802 [95% confidence interval, 2.072-11.132]) compared with gestational hypertension in the first year of follow-up. A dose-response effect was evident for the severity of preeclampsia with the averaged 10-year adjusted hazard ratios for developing chronic hypertension after early, preterm, and late preeclampsia being 10, 7, and 6 times higher, respectively. CONCLUSION: The risks of cardiovascular and cerebrovascular outcomes were the highest in the first year after a birth complicated by hypertensive disorders of pregnancy. We found a significant relationship with both the severity of hypertensive disorders of pregnancy and the gestational age of onset suggesting a possible dose-response relationship for the development of cardiovascular and cerebrovascular outcomes. These findings call for an urgent focus on research into effective postnatal screening and cardiocerebrovascular risk prevention for women with hypertensive disorders of pregnancy.

Hospitalisation for non-lethal self-harm and premature mortality in the 3 years following adolescent pregnancy: Population-based nationwide cohort study.

OBJECTIVE: To evaluate the risk of non-lethal self-harm and mortality related to adolescent pregnancy. DESIGN: Nationwide population-based retrospective cohort. SETTING: Data were extracted from the French national health data system. POPULATION: We included all adolescents aged 12-18 years with an International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) code for pregnancy in 2013-2014. METHODS: Pregnant adolescents were compared with age-matched non-pregnant adolescents and with first-time pregnant women aged 19-25 years. MAIN OUTCOME MEASURES: Any hospitalisation for non-lethal self-harm and mortality during a 3-year follow-up period. Adjustment variables were age, a history of hospitalisation for physical diseases, psychiatric disorders, self-harm and reimbursed psychotropic drugs. Cox proportional hazards regression models were used. RESULTS: In 2013-2014, 35 449 adolescent pregnancies were recorded in France. After adjustment, pregnant adolescents had an increased risk of subsequent hospitalisation for non-lethal self-harm in comparison with both non-pregnant adolescents (n = 70 898) (1.3% vs 0.2%, HR 3.06, 95% CI 2.57-3.66) and pregnant young women (n = 233 406) (0.5%, HR 2.41, 95% CI 2.14-2.71). Rates of hospitalisation for non-lethal self-harm were lower during pregnancy and higher between 12 and 8 months pre-delivery, 3-7 months postpartum and in the month following abortion. Mortality was significantly higher in pregnant adolescents (0.7‰) versus pregnant young women (0.4‰, HR 1.74, 95% CI 1.12-2.72), but not versus non-pregnant adolescents (0.4‰, HR 1.61, 95% CI 0.92-2.83). CONCLUSIONS: Adolescent pregnancy is associated with an increased risk of hospitalisation for non-lethal self-harm and premature death. Careful psychological evaluation and support should be systematically implemented for adolescents who are pregnant.

Risk of non-fatal self-harm and premature mortality in the three years following hospitalization in adolescents and young adults with an eating disorder: A nationwide population-based study.

INTRODUCTION: Eating disorders (ED) are associated with high rates of suicide attempts and premature mortality. However, data in large samples of adolescents and young adults are limited. This study aims to assess the risk of self-harm and premature mortality in young people hospitalized with an ED. METHODS: Individuals aged 12 to 25 years old hospitalized in 2013-2014 in France with anorexia nervosa and/or bulimia nervosa as a primary or associated diagnosis were identified from French national health records. They were compared to two control groups with no mental disorders, and with any other mental disorder than ED. The main outcomes were any hospitalization for deliberate self-harm and mortality in the 3 years following hospitalization. Logistic regression models were used. RESULTS: This study included 5, 452 patients hospitalized with an ED, 14,967 controls with no mental disorder, and 14,242 controls with a mental disorder other than an ED. During the three-year follow-up, 13.0% were hospitalized for deliberate self-harm (vs. 0.2 and 22.0%, respectively) and 0.8% died (vs. 0.03 and 0.4%). After adjustment, hospitalization with an ED was associated with more self-harm hospitalizations (hazard ratio [HR] = 46.0, 95% confidence interval [32.3-65.3]) and higher all-cause mortality (HR = 12.6 [4.3-37.3]) relative to youths without any mental disorder; less self-harm hospitalizations (HR = 0.5 [0.5-0.6]) but higher mortality (HR = 1.6 [1.0-2.4]) when compared to youths with any other mental disorder. CONCLUSION: Young patients hospitalized with an ED are at high risk of self-harm and premature mortality. It is urgent to evaluate and implement the best strategies for post-discharge care and follow-up. PUBLIC SIGNIFICANCE: We found that the risk of being hospitalized for a suicide attempt is 46 times higher and mortality 13 times higher than the general population in adolescents and young adults during the 3 years following hospitalization with an eating disorder. Eating disorders are also associated with a 1.5 higher risk of premature mortality relative to other mental disorders. This risk is particularly high in the 6 months following hospitalization. It is therefore crucial to implement careful post-discharge follow-up in patients hospitalized for eating disorders.

Trends in psychotropic drug consumption among French military personnel during the COVID-19 epidemic.

BACKGROUND: The coronavirus disease (COVID-19) pandemic may have had significant mental health consequences for military personnel, which is a population already exposed to psychological stress. To assess the potential impact of the COVID-19 pandemic, we analyzed the dispensing of three classes of psychotropic drugs (anxiolytics, hypnotics, and antidepressants) among French military personnel. METHODS: A retrospective analysis was conducted using the individualized medico-administrative data of persons insured by the National Military Social Security Fund from the National Health Data System. All active French military personnel aged 18-64 who received outpatient care and to whom drugs were dispensed between January 1, 2019, and April 30, 2021, were included from the French national health database. Rate ratios of dispensed anxiolytics, hypnotics and antidepressants (based on drug reimbursement) were estimated from negative binomial regressions before and after the start of the COVID-19 pandemic. RESULTS: Three hundred eighty-one thousand seven hundred eleven individuals were included. Overall, 45,148 military personnel were reimbursed for anxiolytics, 10,637 for hypnotics, and 4328 for antidepressants. Drugs were dispensed at a higher rate in 2020 and 2021 than in 2019. There was a notable peak at the beginning of the first lockdown followed by a decrease limited to the duration of the first lockdown. During the first lockdown only, there were temporary phenomena including a brief increase in drug dispensing during the first week followed by a decrease during the rest of lockdown, possibly corresponding to a stocking-up effect. For the study period overall, while there was a significant downward trend in psychotropic drug dispensing before the occurrence of COVID-19 (p < 0.001), the pandemic period was associated with an increase in dispensed anxiolytics (rate ratio, 1.03; 95% CI, 1.02-1.04, p < 0.05), hypnotics (rate ratio, 1.13; 95% CI, 1.11-1.16, p < 0.001) and antidepressants (rate ratio, 1.12; 95% CI, 1.10-1.13, p < 0.001) in the military population. CONCLUSIONS: The COVID-19 pandemic has probably had a significant impact on the mental health of French military personnel, as suggested by the trends in dispensed psychotropic drugs. The implementation of mental health prevention measures should be investigated for this population.

Impact of the first COVID-19 pandemic peak and lockdown on the interventional management of carotid artery stenosis in France.

OBJECTIVE: The aim of this study was to evaluate the impact of the COVID-19 pandemic on the trends of carotid revascularization (endarterectomy [CEA], transfemoral carotid artery stenting [TFCAS]) for symptomatic and asymptomatic carotid stenosis before, during, and after the end of the first lockdown in 2020 in France. METHODS: Nationwide data were provided by the French National Hospital Discharge database (Programme de Médicalisation des Systèmes d'Information). We retrospectively analyzed patients admitted for CEA or TFCAS in all French public and private hospitals during a 9-month period (January-September) in 2017, 2018, 2019, and 2020. Procedures were identified using the French Common Classification of Medical Procedures. Stenoses were considered symptomatic in the presence of stroke and/or transient ischemic attack codes (according to the International Classification of Diseases-Tenth Revision) during the stay, and asymptomatic in the absence of these codes. Hospitalization rates in 2020 were compared with the rates in the same period in the 3 previous years. RESULTS: Between January and September 2020, 12,546 patients were hospitalized for carotid artery surgery (CEA and TFCAS) in France. Compared with the 3 previous years, there was a decrease in hospitalization rates for asymptomatic (-68.9%) and symptomatic (-12.6%) CEA procedures in April, starting at the pandemic peak concomitant with the first national lockdown. This decrease was significant for asymptomatic CEA (P < .001). After the lockdown, while CEA for asymptomatic stenosis returned to usual activity, CEA for symptomatic stenosis presented a significant rebound, up 18.52% in August compared with previous years. Lockdown also had consequences on TFCAS procedures, with fewer interventions for both asymptomatic (-60.53%) and symptomatic stenosis (-16.67%) in April. CONCLUSIONS: This study demonstrates a severe decrease for all interventions during the first peak of the COVID-19 pandemic in France. However, the trends in the postlockdown period were different for the various procedures. These data can be used to anticipate future decisions and organization for cardiovascular care.

Impact of SARS-CoV-2 infection on risk of prematurity, birthweight and obstetric complications: A multivariate analysis from a nationwide, population-based retrospective cohort study.

OBJECTIVE: To determine the impact of maternal coronavirus disease 2019 (COVID-19) on prematurity, birthweight and obstetric complications. DESIGN: Nationwide, population-based retrospective cohort study. SETTING: National Programme de Médicalisation des Systèmes d'Information database in France. POPULATION: All single births from March to December 2020: 510 387 deliveries, including 2927 (0.6%) with confirmed COVID-19 in the mother and/or the newborn. METHODS: The group with COVID-19 was compared with the group without COVID-19 using the chi-square test or Fisher's exact test, and the Student's t test or Mann-Whitney U test. Logistic regressions were used to study the effect of COVID-19 on the risk of prematurity or macrosomia (birthweight ≥4500 g). MAIN OUTCOME MEASURES: Prematurity less than 37, less than 28, 28-31, or 32-36 weeks of gestation; birthweight; obstetric complications. RESULTS: In singleton pregnancies, COVID-19 was associated with obstetric complications such as hypertension (2.8% versus 2.0%, p < 0.01), pre-eclampsia (3.6% versus 2.0%, p < 0.01), diabetes (18.8% versus 14.4%, p < 0.01) and caesarean delivery (26.8% versus 19.7%, p < 0.01). Among pregnant women with COVID-19, there was more prematurity between 28 and 31 weeks of gestation (1.3% versus 0.6%, p < 0.01) and between 32 and 36 weeks of gestation (7.7% versus 4.3%, p < 0.01), and more macrosomia (1.0% versus 0.7%, p = 0.04), but there was no difference in small-for-gestational-age newborns (6.3% versus 8.7%, p = 0.15). Logistic regression analysis for prematurity showed an adjusted odds ratio (aOR) of 1.77 (95% CI 1.55-2.01) for COVID-19. For macrosomia, COVID-19 resulted in non-significant aOR of 1.38 (95% CI 0.95-2.00). CONCLUSIONS: COVID-19 is a risk factor for prematurity, even after adjustment for other risk factors. TWEETABLE ABSTRACT: The risk of prematurity is twice as high in women with COVID-19 after adjustment for factors usually associated with prematurity.

Impact of nutritional status on heart failure mortality: a retrospective cohort study.

BACKGROUND: Chronic heart failure (CHF) is one of the most common causes of mortality in industrialized countries despite regular therapeutic advances. Numerous factors influence mortality in CHF patients, including nutritional status. It is known that malnutrition is a risk factor for mortality, whereas obesity may play a protective role, a phenomenon dubbed the "obesity paradox". However, the effect of the obesity-malnutrition association on mortality has not been previously studied for CHF. Our aim was to study the effect of nutritional status on overall mortality in CHF patients. METHODS: This retrospective, multicenter study was based on a French nationwide database (PMSI). We included all CHF patients aged ≥18 years admitted to all public and private hospitals between 2012 and 2016 and performed a survival analysis over 1 to 4 years of follow-up. RESULTS: Malnutrition led to a significant decrease in life expectancy in CHF patients when compared with normal nutritional status (aHR=1.16 [1.14-1.18] at one year and aHR=1.04 [1.004-1.08] at four years), obese, and obese-malnutrition groups. In contrast, obesity led to a significant increase in life expectancy compared with normal nutritional status (aHR=0.75 [0.73-0.78] at one year and aHR=0.85 [0.81-0.90] at four years), malnutrition, and obese-malnutrition groups. The mortality rate was similar in patients presenting both malnutrition and obesity and patients with normal nutritional status. CONCLUSIONS: Our results indicate that the protective effect on mortality observed in obese CHF patients seems to be linked to fat massincrease. Furthermore, malnourished obese and normal nutritional status patients had similar mortality rates. Further studies should be conducted to confirm our results and to explore the physiopathological mechanisms behind these effects.

Mediolateral episiotomy and risk of obstetric anal sphincter injuries and adverse neonatal outcomes during operative vaginal delivery in nulliparous women: a propensity-score analysis.

BACKGROUND: The potential protective effect of mediolateral episiotomy for obstetrical anal sphincter injuries (OASIs) remains controversial during operative vaginal delivery because of the difficulties to take into account the risk factors and clinical conditions at delivery; in addition, little is known about the potential benefits of mediolateral episiotomy on neonatal outcomes. The objectives were to investigate the associations between mediolateral episiotomy and both OASIs and neonatal outcomes, using propensity scores. METHODS: We performed a retrospective population-based observational study from a perinatal registry that includes all births in a French region between 2010 and 2017. All nulliparous women with singleton pregnancy delivering by operative vaginal deliveries at 37 weeks gestational age or later were included. Inverse-probability-of-treatment weighting with propensity scores was used to minimize indication bias. OASIs was defined as third and fourth-degree tears according to Royal College of Obstetricians and Gynecologists. Two neonatal outcomes were studied: condition at birth (5-min Apgar score less than 7 and/or umbilical artery pH less than 7.10), and admission to neonatal intensive care unit. RESULTS: The study population consisted of 7589 women; 2880 (38.0%) received mediolateral episiotomy. After applying propensity scores, episiotomy was associated with a lower rate of OASIs in forceps/spatula delivery (2.3 vs 6.8%, Risk Ratio (RR) 0.38, 95% Confidence Interval (CI) 0.28-0.52) and in vacuum delivery (1.3 vs 3.4%, RR 0.27, 95% CI 0.20-0.38) as compared with no episiotomy. Mediolateral episiotomy was associated with better condition at birth in case of forceps/spatula delivery (4.5 vs 8.8%, RR 0.56, 95% CI 0.39-0.81). In cases of fetal distress (40.7%), mediolateral episiotomy was associated with better condition of infant at birth in women who delivered by forceps/spatula (4.2 vs 13.5%, RR 0.52, 95% CI 0.31-0.89). No association was found with neonatal unit admission (RR 0.93, 95% CI 0.50-1.74). CONCLUSIONS: Use of mediolateral episiotomy was associated with a lower rate of OASIs during operative vaginal delivery, and in infants it was associated with better condition at birth following forceps/spatula delivery.

Hospitalizations for Stroke in France During the COVID-19 Pandemic Before, During, and After the National Lockdown.

BACKGROUND AND PURPOSE: In France, the entire population was put under a total lockdown from March 17 to May 11, 2020 during the peak of the coronavirus disease 2019 (COVID-19) pandemic. Whether the lockdown had consequences on the management of medical emergencies such as stroke and transient ischemic attack (TIA) has yet to be fully evaluated. This article describes hospitalization rates for acute stroke in 2 French regions that experienced contrasting rates of COVID-19 infection, before, during, and after the nationwide lockdown (January to June 2020). METHODS: All patients admitted for acute stroke/TIA into all public and private hospitals of the 2 study regions were included. Data were retrieved from the National Hospitalization Database (PMSI). In the most affected region (Grand-Est), the hospitalization rates observed in April 2020 were compared with the rates in the same period in the least affected region (Occitanie) and in the 3 prior years (2017-2019). RESULTS: There was a significant decline in hospitalization rates for stroke/TIA within the region most affected by COVID-19 during the month of April 2020 compared with previous years, while no significant change was seen in the least affected region. After lockdown, we observed a fast rebound in the rate of hospitalization for stroke/TIA in the most affected region, contrasting with a slower rebound in the least affected region. In both regions, patients with COVID-19 stroke more frequently had ischemic stroke, a nonsignificant greater prevalence of diabetes, they were less frequently admitted to stroke units, and mortality was higher than in patients without COVID-19. CONCLUSIONS: Our results demonstrates a significant drop in stroke/TIA hospitalizations and a fast recovery after the end of the French lockdown in the most affected region, while the least affected region saw a nonsignificant drop in stroke/TIA hospitalizations and a slow recovery. These results and recommendations could be used by the health authorities to prepare for future challenges.

Chronic pulmonary aspergillosis: prevalence, favouring pulmonary diseases and prognosis.

Chronic pulmonary aspergillosis (CPA) is an emerging disease in patients with common chronic pulmonary diseases (CPDs). While its prevalence is linked to tuberculosis (TB) in endemic countries, epidemiological and prognostic data are lacking in low TB incidence countries. The aim of this study was to describe these features in CPA patients hospitalised in France between 2009 and 2018.We estimated the prevalence and mortality of hospitalised CPA patients using the French nationwide administrative hospital database. We also assessed the association with CPD, thoracic interventions and malnutrition.From 2009 to 2018, 17 290 patients were hospitalised in France for CPA, with an increasing prevalence during this period. Most patients were male (63.5%) with a median age of 65 years at CPA diagnosis, living in farming regions and large cities. The proportion of underlying chronic obstructive pulmonary disease (COPD) and emphysema during the previous 5 years was 44% and 22%, respectively, whereas it was only 3% for both TB and non-TB mycobacterial (NTM) infections. The mortality rates during the first hospitalisation, at 1 year and at 5 years were 17%, 32% and 45%, respectively. In multivariate analysis, mortality rates were increased in patients aged >65 years, male patients and patients with malnutrition, diabetes or lung cancer history. The risk of mortality in patients with COPD or emphysema was higher than in those with previous mycobacterial lung infection.In France, CPA is an emerging infection commonly associated with non-mycobacterial CPD. This shift in the distribution profile of underlying CPD will likely worsen CPA mortality.

Chronic respiratory diseases are predictors of severe outcome in COVID-19 hospitalised patients: a nationwide study.

BACKGROUND: Influenza epidemics were initially considered to be a suitable model for the COVID-19 epidemic, but there is a lack of data concerning patients with chronic respiratory diseases (CRDs), who were supposed to be at risk of severe forms of COVID-19. METHODS: This nationwide retrospective cohort study describes patients with prior lung disease hospitalised for COVID-19 (March-April 2020) or influenza (2018-2019 influenza outbreak). We compared the resulting pulmonary complications, need for intensive care and in-hospital mortality depending on respiratory history and virus. RESULTS: In the 89 530 COVID-19 cases, 16.03% had at least one CRD, which was significantly less frequently than in the 45 819 seasonal influenza patients. Patients suffering from chronic respiratory failure, chronic obstructive pulmonary disease, asthma, cystic fibrosis and pulmonary hypertension were under-represented, contrary to those with lung cancer, sleep apnoea, emphysema and interstitial lung diseases. COVID-19 patients with CRDs developed significantly more ventilator-associated pneumonia and pulmonary embolism than influenza patients. They needed intensive care significantly more often and had a higher mortality rate (except for asthma) when compared with patients with COVID-19 but without CRDs or patients with influenza. CONCLUSIONS: Patients with prior respiratory diseases were globally less likely to be hospitalised for COVID-19 than for influenza, but were at higher risk of developing severe COVID-19 and had a higher mortality rate compared with influenza patients and patients without a history of respiratory illness.

Impact of COVID-19 and lockdowns on pulmonary embolism in hospitalized patients in France: a nationwide study.

BACKGROUND: This study assessed the impact of the COVID-19 epidemic on overall hospitalizations for pulmonary embolism (PE) in France in comparison with previous years, and by COVID-19 and non-COVID-19 status. METHODS: Hospitalization data (2017-2020) were extracted from the French National Discharge database (all public and private hospitals). We included all patients older than 18 years hospitalized during the 3 years and extracted PE status and COVID-19 status (from March 2020). Age, sex and risk factors for PE (such as obesity, cancer) were identified. We also extracted transfer to an intensive care unit (ICU) and hospital death. The number of PE and the frequency of death in patients in 2019 and 2020 were described by month and by COVID-19 status. Logistic regressions were performed to identify the role of COVID-19 among other risk factors for PE in hospitalized patients. RESULTS: The overall number of patients hospitalized with PE increased by about 16% in 2020 compared with 2019, and mortality also increased to 10.3% (+ 1.2%). These increases were mostly linked to COVID-19 waves, which were associated with PE hospitalization in COVID-19 patients (PE frequency was 3.7%; 2.8% in non-ICU and 8.8% in ICU). The final PE odds ratio for COVID-19 hospitalized patients was 4 compared with other hospitalized patients in 2020. The analyses of PE in non-COVID-19 patients showed a 2.7% increase in 2020 compared with the previous three years. CONCLUSION: In 2020, the overall number of patients hospitalized with PE in France increased compared to the previous three years despite a considerable decrease in scheduled hospitalizations. Nevertheless, proactive public policy focused on the prevention of PE in all patients should be encouraged.

Impact of the COVID-19 Epidemic on hospitalization for diabetic foot ulcers during lockdown: A French nationwide population-based study.

AIMS/HYPOTHESIS: The aim of this study was to examine the impact of the COVID-19 epidemic on the hospitalization rates for diabetic foot ulcer (DFU), osteomyelitis and lower limb revascularization procedure in people with DFU. METHODS: This nationwide retrospective cohort study included hospital data on all people hospitalized in France for diabetes in weeks 2-43 in 2020, including the COVID-19 lockdown period, compared to same period in 2019. RESULTS: The number of hospitalizations for DFU decreased significantly in weeks 12-19 (during the lockdown) (p < 10-4 ). Hospitalization for foot osteomyelitis also decreased significantly in weeks 12-19 (p < 10-4 ). The trend was the same for lower limb amputations and revascularizations associated with DFU or amputation. CONCLUSIONS/INTERPRETATION: The marked drop in hospitalization rates for DFU, osteomyelitis and lower limb revascularization procedures in people with DFU observed in France during the lockdown period suggests that COVID-19 was a barrier to DFU care, and may illustrate the combined deleterious effects of hospital overload and changes in health-related behaviour.

Impact of time-varying cumulative bevacizumab exposures on survival: re-analysis of data from randomized clinical trial in patients with metastatic colo-rectal cancer.

BACKGROUND: As cancer treatment, biotherapies can be as effective as chemotherapy while reducing the risk of secondary effects, so that they can be taken over longer periods than conventional chemotherapy. Thus, some trials aimed at assessing the benefit of maintaining biotherapies during chemotherapy-free intervals (CFI). For example, the recent PRODIGE9 trial assessed the effect of maintaining bevacizumab during CFI in metastatic colorectal cancer (mCRC) patients. However, its analysis was hindered by a small difference of exposure to the treatment between the randomized groups and by a large proportion of early drop outs, leading to a potentially unbalanced distribution of confounding factors among the trial completers. To address these limitations, we re-analyzed the PRODIGE9 data to assess the effects of different exposure metrics on all-cause mortality of patients with mCRC using methods originally developed for observational studies. METHODS: To account for the actual patterns of drug use by individual patients and for possible cumulative effects, we used five alternative time-varying exposure metrics: (i) cumulative dose, (ii) quantiles of the cumulative dose, (iii) standardized cumulative dose, (iv) Theoretical Blood Concentration (TBC), and (v) Weighted Cumulative Exposure (WCE). The last two metrics account for the timing of drug use. Treatment effects were estimated using adjusted Hazard Ratio from multivariable Cox proportional hazards models. RESULTS: After excluding 112 patients who died during the induction period, we analyzed data on 382 patients, among whom 320 (83.8%) died. All time-varying exposures improved substantially the model's fit to data, relative to using only the time-invariant randomization group. All exposures indicated a protective effect for higher cumulative bevacizumab doses. The best-fitting WCE and TBC models accounted for both the cumulative effects and the different impact of doses taken at different times. CONCLUSIONS: All time-varying analyses, regardless of the exposure metric used, consistently suggested protective effects of higher cumulative bevacizumab doses. However, the results may partly reflect the presence of a confusion bias. Complementing the main ITT analysis of maintenance trials with an analysis of potential cumulative effects of treatment actually taken can provide new insights, but the results must be interpreted with caution because they do not benefit from the randomization. TRIAL REGISTRATION: clinicaltrials.gov, NCT00952029 . Registered 8 August 2009.

Detecting Hospital Outliers in Post-Pancreatectomy Care Using Funnel Plots from 2009-2018 Based on Nationwide Medico-Administrative Data.

OBJECTIVES: Our objective was to identify hospitals with unusual mortality rates for major pancreatectomies over a period of ten years using 30-day mortality data from the French national database. METHODS: Data for all patients who underwent pancreatectomy were extracted from the national medico-economic database (Programme de Médicalisation des Systèmes d'Information). To identify quality outliers for each hospital, the observed-to-expected 30-day mortality rates were used as a quality indicator. RESULTS: A total of 19 494 patients underwent a major pancreatectomy in France between January 2009 and December 2018. The overall 30-day mortality rate was 4.8% (n = 944). For the 2009-2014 period, the funnel plot showed that 10 of the 176 hospitals lie outside the central 95% region and 7 lie outside the central 99.8% region. For the 2015-2018 period, out of 176 hospitals, 6 lie outside the central 95% region and 2 lie outside the central 99.8% region. The change in standardized mortality ratios between 2009-2014 and 2015-2018 testing for differences from the overall change, they were there 4 hospitals lie outside the central 95% region and 0 lie outside the central 99.8% region. CONCLUSION: Over time, the improvement in hospital quality was weak. This study suggests that there is a pressing need to reorganize the supply of care for pancreatic surgery in France.

Variation in end-of-life care and hospital palliative care among hospitals and local authorities: A preliminary contribution of big data.

BACKGROUND: Many studies explore the clinical and ethical dimensions of care at the end-of-life, but fewer use administrative data to examine individual and geographic differences, including the use of palliative care. AIM: Provide a population-based perspective on end-of-life and hospital palliative care among local authorities and hospitals in France. DESIGN: Retrospective cohort study of care received by 17,928 decedents 65 and over (last 6 months of life), using the French national health insurance database. RESULTS: 55.7% of decedents died in acute-care hospitals; 79% were hospitalized in them at least once; 11.7% were admitted at least once for hospital palliative care. Among 31 academic medical centers, intensive care unit admissions ranged from 12% to 67.4%; hospital palliative care admissions, from 2% to 30.6%. Across local authorities, for intensive care unit days and hospital palliative care admissions, the ratios between the values at the third and the first quartile were 2.4 and 1.5. The odds of admission for hospital palliative care or to an intensive care unit for more than 7 days were more than twice as high among people ⩽85 years (aOR = 2.11 (1.84-2.43) and aOR = 2.59 (2.12-3.17), respectively). The odds of admission for hospital palliative care were about 25% lower (p = 0.04) among decedents living in local authorities with the lowest levels of education than those with the highest levels. CONCLUSION: The variation we document in end-of-life and hospital palliative care across different categories of hospitals and 95 local authorities raises important questions as to what constitutes appropriate hospital use and intensity at the end-of-life.

Failure to rescue in patients with distal pancreatectomy: a nationwide analysis of 10,632 patients.

BACKGROUND: FTR appears as a major cause of postoperative mortality (POM). Hospital volume has an impact on FTR in pancreatic surgery but no study has investigated this relationship more specifically in DP. METHODS: We analysed patients with DP between 2009 and 2018 through a nationwide database. FTR definition was mortality among patients who experiment major complications. The cutoff between high and low volume centers was 20 pancreatectomies per year. RESULTS: Some 10,632 patients underwent DP, 5048 (47.5%) were operated in 602 (95.4%) low volume centers and 5584 (52.5%) in 29 (4.6%) high volume centers. Overall FTR occurred in 11.2% of patients and was significantly reduced in high volume centers compared to low volume centers (10.2% vs 12.5%, p = 0.047). In multivariate analysis, surgery in a high volume center was a protective factor for POM (OR = 0.570, CI95% [0.505-0.643], p < 0.001) and also for FTR (OR = 0.550, CI95% [0.486-0.630], p < 0.001). CONCLUSION: Hospital volume has a positive impact on FTR in DP. Patients with higher risk of FTR are men, with high modified Charlson comorbidity index, malignant conditions and open procedures.

Association between hospital admission for ketoacidosis and subsequent suicide attempt in young adults with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the associations between hospitalisation for diabetic ketoacidosis and subsequent hospitalisation for suicide attempt in young adults with type 1 diabetes. METHODS: This nationwide historical cohort study included hospital data on all young people hospitalised in France for type 1 diabetes in 2008. Epidemiological follow-up focused on hospitalisations (medical and psychiatric hospital data) from the index hospitalisation to 2017. Survival analyses were done using a Cox proportional hazards regression model to explore the association between hospitalisation for ketoacidosis and subsequent hospitalisation for a suicide attempt. RESULTS: In 2008, 16,431 people aged 18-35 years had a hospitalisation mentioning type 1 diabetes. Among them, 1539 (9.4%) had at least one hospitalisation for ketoacidosis between 2008 and 2010. At 9 years, 7.2% of the group hospitalised for ketoacidosis had been hospitalised for a suicide attempt vs only 2.5% in the group not hospitalised for ketoacidosis. The association between hospitalisation for ketoacidosis and suicide attempt decreased over time and was no longer significant after 5 years. CONCLUSIONS/INTERPRETATION: We found that young adults admitted to hospital for diabetic ketoacidosis have an increased risk of being admitted to hospital for a subsequent suicide attempt. The risk of a suicide attempt was the highest in the 12 months following the ketoacidosis episode. Our findings support the recommendation that screening for depression and suicide risk should be part of the routine clinical assessment of individuals with type 1 diabetes and ketoacidosis.