Pregnancy, delivery and neonatal complications in women with schizophrenia: a national population-based cohort study.

BACKGROUND: Existing studies evaluating the association between schizophrenia and complications associated with pregnancy, delivery and neonatal outcomes are based on data prior to 2014 and have reported heterogeneous results. The objective of our study was to determine whether pregnant women with schizophrenia were at increased risk of pregnancy, delivery and neonatal complications compared with women without severe mental disorders. METHODS: We performed a population-based cohort study of all singleton deliveries in France between Jan. 1, 2015, and Dec. 31, 2019. We divided this population into cases (i.e., women with schizophrenia) and controls (i.e., women without a diagnosis of severe mental disorder). Cases and controls were matched (1:4) inside the same hospital and the same year by age, social deprivation, parity, smoking, alcohol and substance addictions, malnutrition, obesity, and comorbidities. Univariate and multivariate models with odds ratios and 95% confidence intervals (ORs [95% CIs]) were used to estimate the association between schizophrenia and 24 pregnancy, delivery and neonatal outcomes. FINDINGS: Over 5 years, 3,667,461 singleton deliveries were identified, of which 3,108 occurred in women with schizophrenia. Compared to controls, women with schizophrenia were found to be older; have more frequent smoking, alcohol and substance addictions; suffer from obesity, diabetes and chronic obstructive pulmonary disease; and often be hospitalized in tertiary maternity hospitals. Compared to matched controls, women with schizophrenia had more pregnancy complications (adjusted OR=1.41[95%CI 1.31-1.51]) (i.e., gestational diabetes, gestational hypertension, genito-urinary infection, intrauterine growth retardation and threatened preterm labour). They had more delivery complications (aOR=1.18[95%CI 1.09 1.29]) with more still births/medical abortions (aOR=2.17[95%CI 1.62-2.90]) and caesarean sections (aOR=1.15[95%CI 1.05-1.25]). Newborns of women with schizophrenia had more neonatal complications (aOR=1.38[95%CI 1.27-1.50]) with more born preterm (aOR=1.64[95%CI1.42 -1.90]), small for gestational age (aOR=1.34[95%CI 1.19-1.50]) and low birth weight (aOR=1.75[95%CI 1.53-2.00]). INTERPRETATION: Our results highlight the importance of health disparities between pregnant women with and without schizophrenia, as well as in their newborns. Our study calls for health policy interventions during and before pregnancy, including proportionate intensified care to the level of needs, effective case management and preventive and social determinant approaches. FUNDING: No funding.

Machine-learning prediction of unplanned 30-day rehospitalization using the French hospital medico-administrative database.

Predicting unplanned rehospitalizations has traditionally employed logistic regression models. Machine learning (ML) methods have been introduced in health service research and may improve the prediction of health outcomes. The objective of this work was to develop a ML model to predict 30-day all-cause rehospitalizations based on the French hospital medico-administrative database.This was a retrospective cohort study of all discharges in the year 2015 from acute-care inpatient hospitalizations in a tertiary-care university center comprising 4 French hospitals. The study endpoint was unplanned 30-day all-cause rehospitalization. Logistic regression (LR), classification and regression trees (CART), random forest (RF), gradient boosting (GB), and neural networks (NN) were applied to the collected data. The predictive performance of the models was evaluated using the H-measure and the area under the ROC curve (AUC).Our analysis included 118,650 hospitalizations, of which 4127 (3.5%) led to rehospitalizations via emergency departments. The RF model was the most performant model according to the H-measure (0.29) and the AUC (0.79). The performances of the RF, GB and NN models (H-measures ranged from 0.18 to 0. 29, AUC ranged from 0.74 to 0.79) were better than those of the LR model (H-measure = 0.18, AUC = 0.74); all P values <.001. In contrast, LR was superior to CART (H-measure = 0.16, AUC = 0.70), P < .0001.The use of ML may be an alternative to regression models to predict health outcomes. The integration of ML, particularly the RF algorithm, in the prediction of unplanned rehospitalization may help health service providers target patients at high risk of rehospitalizations and propose effective interventions at the hospital level.

The role of neighbourhood socioeconomic status in large for gestational age.

OBJECTIVE: To determine whether neighbourhood socioeconomic status (SES) was associated with large for gestational age (LGA) while considering key sociodemographic and clinical confounding factors. SETTING AND PATIENT: All singleton infants whose parents were living in the city of Marseilles, France, between 2013 and 2016. METHOD: Population-based study based on new-born hospital birth admission charts from the French National Uniform Hospital Discharge Data Set Database. LGA infants were compared to appropriate-for-gestational-age (AGA) infants. Multiple generalized logistic model analysis was used to examine factors associated with LGA. RESULTS: A total of 43,309 singleton infants were included, and 4,747 (11%) were born LGA. LGA infants were more likely to have metabolic and respiratory diseases and to be admitted to the neonatal intensive care unit. Multiparity, advanced maternal age, obesity and diabetes were associated with an increased risk of LGA. Lower neighbourhood SES was associated with LGA (aOR = 1.24, 95% CI: 1.14; 1.36; p<0.0001) independent of age, diabetes, obesity, maternal smoking and multiparity. The strength of this association increased with maternal age, reaching an aOR of 1.50 (95% CI: 1.26; 1.78; p<0.0001) for women > 35 years old. CONCLUSION: Neighbourhood SES could be considered an important factor for clinicians to better identify mothers at risk of having LGA births in addition to well-known risk factors such as maternal diabetes, obesity and age. The intensification of the association between SES and LGA with increasing maternal age suggests that neighbourhood disadvantage may act on LGA cumulatively over time.

End-of-life care among patients with schizophrenia and cancer: a population-based cohort study from the French national hospital database.

BACKGROUND: Patients with schizophrenia represent a vulnerable, underserved, and undertreated population who have been neglected in health disparities work. Understanding of end-of-life care in patients with schizophrenia and cancer is poor. We aimed to establish whether end-of-life care delivered to patients with schizophrenia and cancer differed from that delivered to patients with cancer who do not have diagnosed mental illness. METHODS: We did a population-based cohort study of all patients older than 15 years who had a diagnosis of advanced cancer and who died in hospital in France between Jan 1, 2013, and Dec 31, 2016. We divided this population into cases (ie, patients with schizophrenia) and controls (ie, patients without a diagnosis of mental illness) and compared access to palliative care and indicators of high-intensity end-of-life care between groups. In addition to unmatched analyses, we also did matched analyses (matched in terms of age at death, sex, and site of primary cancer) between patients with schizophrenia and matched controls (1:4). Multivariable generalised linear models were done with adjustment for social deprivation, year of death, time from cancer diagnosis to death, metastases, comorbidity, and hospital type (ie, specialist cancer centre vs non-specialist centre). FINDINGS: The main analysis included 2481 patients with schizophrenia and 222 477 controls. The matched analyses included 2477 patients with schizophrenia and 9896 controls. Patients with schizophrenia were more likely to receive palliative care in the last 31 days of life (adjusted odds ratio 1·61 [95% CI 1·45-1·80]; p<0·0001) and less likely to receive high-intensity end-of-life care-such as chemotherapy and surgery-than were matched controls without a diagnosis of mental illness. Patients with schizophrenia were also more likely to die younger, had a shorter duration between cancer diagnosis and death, and were more likely to have thoracic cancers and comorbidities than were controls. INTERPRETATION: Our findings suggest the existence of disparities in health and health care between patients with schizophrenia and patients without a diagnosis of mental illness. These findings underscore the need for better understanding of health inequalities so that effective interventions can be developed for this vulnerable population. FUNDING: Assistance Publique des Hôpitaux de Marseille and Aix-Marseille University.

Predictive risk score for unplanned 30-day rehospitalizations in the French universal health care system based on a medico-administrative database.

BACKGROUND: Reducing unplanned rehospitalizations is one of the priorities of health care policies in France and other Western countries. An easy-to-use algorithm for identifying patients at higher risk of rehospitalizations would help clinicians prioritize actions and care concerning discharge transitions. Our objective was to develop a predictive unplanned 30-day all-cause rehospitalization risk score based on the French hospital medico-administrative database. METHODS: This was a retrospective cohort study of all 2015 discharges from acute-care inpatient hospitalizations in a tertiary-care university center comprising four hospitals. The study endpoint was unplanned 30-day all-cause rehospitalization via emergency departments, and we collected sociodemographic, clinical, and hospital characteristics based on hospitalization database computed for reimbursement of fees. We derived a predictive rehospitalization risk score using a split-sample design and multivariate logistic regression, and we compared the discriminative properties with the LACE index risk-score. RESULT: Our analysis included 118,650 hospitalizations, of which 4,127 (3.5%) led to rehospitalizations via emergency departments. Variables independently associated with rehospitalization were age, gender, state-funded medical assistance, as well as disease category and severity, Charlson comorbidity index, hospitalization via emergency departments, length of stay (LOS), and previous hospitalizations 6 months before. The predictive rehospitalization risk score yielded satisfactory discriminant properties (C statistic: 0.74) exceeding the LACE index (0.66). CONCLUSION: Our findings indicate that the possibility of unplanned rehospitalization remains high for some patient characteristics, indicating that targeted interventions could be beneficial for patients at the greatest risk. We developed an easy-to-use predictive rehospitalization risk-score of unplanned 30-day all-cause rehospitalizations with satisfactory discriminant properties. Future works should, however, explore if other data from electronic medical records and other databases could improve the accuracy of our predictive rehospitalization risk score based on medico-administrative data.

Use of a multi-state model in a claims database: illustration with methadone.

PURPOSE: In pharmacoepidemiology, one of the main concerns is analysis of drug exposure time. However, in real-life settings, patient's behavior is complex and characterized by drug exposure dynamics. Multi-state models allow assessing the probabilities of various patterns, instead of just continuous use and/or discontinuation. The aim of this study was to illustrate with methadone, the use of multi-state model (MSM) in a large claims database. METHODS: This study is based on the French health insurance reimbursement database. Methadone exposure is defined using four states for each period of follow-up: syrup only, capsule only, syrup-capsule and no dispensing. The model considered 12 possible transitions (including reverse transitions) from one state to another. To describe these transitions a time-homogeneous Markov model was used. RESULTS: A total of 1265 methadone users were included. When patients belonged to the syrup-capsule state, they had a 61.8% chance of moving to capsules the following month and 20.9% of moving to syrup. The probability of moving from the syrup to the non-user state was 13.6% (11.7% from capsule state to non-user state). The average length of stay was 5.9 months (CI95%: [5.5-6.4]) in capsule state, 4.9 (CI95%: [4.6-5.2]) in syrup state and 5.9 (CI95%: [5.5-6.3]) in non user state. CONCLUSION: MSM provided a good description of methadone patterns of use. It outlined behaviors which have led to a rapid spread of capsule formulation among methadone users. Therefore, it illustrates the utility of MSM for modeling multiple sequences of drug use in a large claims database.

Assessment of abuse of tianeptine from a reimbursement database using 'doctor-shopping' as an indicator.

Doctor-shopping is a patient behaviour characterized by simultaneous consultations of several physicians during the same period. Some case reports have described an abuse of tianeptine, an atypical antidepressant. Our objective was to assess the extent of abuse of this drug with a method quantifying doctor-shopping in comparison with other antidepressants and benzodiazepines (BZD). All dispensations of antidepressants and BZD during the year 2005 in a French area of 4.5 million inhabitants were extracted from a reimbursement database. For each patient, two quantities were computed: quantity dispensed and obtained by doctor-shopping. Tianeptine and other drugs were compared using their doctor-shopping indicator (DSI), defined as the percentage of drug obtained by doctor-shopping among dispensed quantity; 410 525 patients received at least one antidepressant dispensation during the year 2005. Tianeptine was the sixth most dispensed antidepressant. The DSI of tianeptine was 2.0%, ranking it first among antidepressant (the second being mianserine with a DSI of 1%). Flunitrazepam has the highest DSI (30.2%), the DSI of the five following BZD (clonazepam, zolpidem, oxazepam, diazepam, bromazepam) range from 3.0% to 2.0%. Tianeptine is associated with higher DSI, compared with other antidepressants, suggesting that it may be subject to abuse in the population. Moreover, its DSI as a measure of diversion is similar to the DSI of diazepam or bromazepam.

Misuse of buprenorphine maintenance treatment since introduction of its generic forms: OPPIDUM survey.

PURPOSE: The purpose of the study was to compare, using data from Observation of Illicit Psychotropic Substances or Non-medical Used Medications (OPPIDUM) surveys, first, the profile of buprenorphine users and their modalities of buprenorphine use from 2006 to 2008 and, second, two subgroups: brand-name and generic buprenorphine users in 2008. METHODS: OPPIDUM is an annual, nationwide, multicentric, cross-sectional survey, including buprenorphine users followed in specialised centres dedicated to drug dependence. The evolution of the profile during three consecutive years (2006, 2007 and 2008) was analysed using Cochran-Armitage test for trend. A multivariate regression analysis was used to identify the factors associated with the use of generic compared with brand-name buprenorphine in 2008. RESULTS: In OPPIDUM, 1311 individuals used buprenorphine in 2006, 1688 in 2007 and 1696 in 2008. The proportion of users of generic buprenorphine increased from 4.2% in 2006 to 31.7% in 2008. From 2006 to 2008, a decrease in intravenous use and higher than recommended dosage, with an increase in occupation, have been observed. According to the multivariate analysis, factors associated with being generic buprenorphine user compared with brand-name buprenorphine user in 2008 were younger age, more education, absence of use of alcohol with buprenorphine, absence of heroin and/or cocaine use and absence of nasal route for buprenorphine. CONCLUSION: Three years after the launch of the buprenorphine generic, the health professionals' and buprenorphine users' perception of generic can still change. Additionally, the long-term impact of generic medications with abuse potential has not yet been studied. Thus, continued monitoring of buprenorphine is needed.

Evolution of opioids reimbursement since 2004 from the National Database of the General Health Insurance System.

OBJECTIVE: This study aims at evaluating trends in the consumption of opioids over the last years to assess the impact of public health measures on the management of pain and opiate addiction in France. METHODS: The evolution of opioids consumption was analysed by using the national database of the General Health Insurance System in France between 2004 and 2008. RESULTS: During the study period, the reimbursed quantities of opioids used for pain management have increased by 13%, except for dextropropoxyphene that has decreased by 9%. The reimbursed quantities of opioids used for substitution maintenance treatments for opioid dependence have increased by 34%, with a 116% increase for methadone. CONCLUSION: This study suggests that consumption of opioids is globally increasing in France and reveals discrepancies concerning the evolution of the different drugs. It allows to analyse switches of consumption between different opioids and constitutes the first step for further studies targetting signals of diversion and abuse.

Patterns of methylphenidate use and assessment of its abuse and diversion in two French administrative areas using a proxy of deviant behaviour determined from a reimbursement database: main trends from 2005 to 2008.

BACKGROUND: Methylphenidate is a psychostimulant drug indicated for the treatment of attention-deficit hyperactivity disorder (ADHD). Its abuse and diversion have been previously described in specific populations, such as students; however, few studies investigating abuse and diversion among the overall population are available. OBJECTIVES: The aim of this study was to describe patterns of methylphenidate use and to explore the magnitude of its abuse and diversion in two French administrative areas using data from a reimbursement database. A proxy of 'deviant behaviour' was used for the abuse and diversion of methylphenidate, defined using the following parameters: total number of defined daily doses (DDDs) of methylphenidate dispensed; number of different pharmacies seen for dispensing of methylphenidate; number of prescribers consulted for a prescription of methylphenidate; and number of dispensings of methylphenidate. Data from the reimbursement database were analysed by clustering methods. These data were assessed from 2005 to 2008. METHOD: The French General Health Insurance System (GHIS) database was used to obtain data on methylphenidate use in two French administrative areas. Individuals affiliated to the GHIS who had a prescription for methylphenidate reimbursed between 1 January and 31 March of 4 selected years (2005, 2006, 2007 and 2008) were included. After the first dispensing of methylphenidate for these individuals, all their dispensings (including methylphenidate and other psychoactive drugs) were monitored over a 9-month period. Following a descriptive analysis, a clustering method was used to identify different subgroups of subjects according to the methylphenidate consumer profile characteristics. RESULTS: With regard to the number of patients who had a dispensing for methylphenidate during the first quarter of the year, an 84% increase was observed between 2005 (n = 640) and 2008 (n = 1175). The clustering method identified two subgroups. One of them was characterized by a higher number of dispensings, different prescribers and pharmacies and a greater total dispensed quantity, suggesting a deviant behaviour and, thus, possible abuse and diversion of methylphenidate. These subjects were older (aged 35.4 ± 11.3 years) and were more frequently patients receiving benzodiazepines, antidepressants, antipsychotics and maintenance opioid treatment. The proportion of subjects with a deviant behaviour increased from 0.5% in 2005 to 2% in 2007 and then decreased to 1.2% in 2008. CONCLUSION: This method was able to assess the magnitude of methylphenidate abuse liability and to follow its evolution. The decrease in methylphenidate abuse and diversion seen between 2007 and 2008 can be explained by the enactment in April 2008 of specific regulations for prescription drugs (such as methylphenidate) that are deemed by the French government to have the potential for misuse; these regulations require the establishment of a 'contract of care' between the GHIS, prescriber and patient.

Which indicators can public health authorities use to monitor prescription drug abuse and evaluate the impact of regulatory measures? Controlling High Dosage Buprenorphine abuse.

BACKGROUND: Two methods have been recently developed from a drug reimbursement database to provide useful indicators for public health authorities concerning the abuse potential of psychotropic drugs. The doctor-shopping indicator (DSI) measures the proportion of the drug obtained by doctor shopping among the overall quantity of the drug reimbursed and the clustering method reveals subgroups of deviant patients. OBJECTIVE: The objective of the study was to analyze and compare indicators resulting from these two methods, applied to High Dosage Buprenorphine (HDB) (a product well-known to be diverted in France), in order to determine which public health authorities needs they answer. DATA ANALYSIS: The patients with reimbursed HDB were grouped using the clustering method in terms of drug dispensations characteristics over a nine month period. The characteristics of the resulting subgroups, including their DSI, were then compared. RESULTS: 4787 Patients (73.4%) had no measurable doctor-shopping behaviour. But the comparison of the two methods demonstrated that the more a patient's profile was characterized by deviant behavior, the higher was the DSI: from 0.4% in a subgroup with a median profile to 72% in a subgroup with a deviant profile. CONCLUSION: These two methods are useful surveillance tools for public health authorities: the clustering method may help devise pertinent intervention strategies to reduce prescription drug abuse while the DSI method provides quantitative information demonstrating whether these strategies are useful. We discuss the advantages and disadvantages of using these two methods as useful indicators for public health authorities.

Evidence of clonazepam abuse liability: results of the tools developed by the French Centers for Evaluation and Information on Pharmacodependence (CEIP) network.

Recent observations suggest the existence of clonazepam abuse. To determine its importance in France, a quantitative and systematic synthesis of all clonazepam data of several epidemiological tools of the Centers for Evaluation and Information on Pharmacodependence (CEIP) network has been performed in comparison with data on others benzodiazepines (BZD). Data on clonazepam and other BZD have been analysed from different epidemiological tools: OSIAP survey that identifies drugs obtained by means of falsified prescriptions, Observation of Illegal Drugs and Misuse of Psychotropic Medications (OPPIDUM) survey that describes modalities of use and data from regional French health reimbursement system. In OSIAP survey, the proportion of clonazepam falsified prescriptions among all BZD falsified prescriptions increased. During the 2006 OPPIDUM survey, the analysis of the BZD modalities of use highlights clonazepam abuse liability (for example 23% of illegal acquisition), in second rank after flunitrazepam. Studies based on data from the French health reimbursed system show that 1.5% of subjects with clonazepam dispensing had a deviant behaviour. Among BZD, clonazepam has the second most important doctor-shopping indicator (3%) after flunitrazepam. All these data provide some arguments in favour of clonazepam abuse liability in real life and the necessity to reinforce its monitoring.

Estimation of clonazepam abuse liability: a new method using a reimbursed drug database.

Some observations suggest the existence of clonazepam abuse. The aim of this study was to assess its magnitude in real life by a new method, using a prescription database, and to assess its evolution between 2001 and 2006. Individuals from a region affiliated to the French health reimbursement system, who had a prescription of clonazepam reimbursed between 1 January and 15 February of two selected years were included. Their deliveries were monitored over a 9-month period. After a descriptive analysis, a clustering method illustrated by a factorial analysis was used to identify different subgroups of clonazepam consumers. An increase of 82% in participants who had a delivery of clonazepam between 2001 and 2006 was observed. Using the clustering method, this study identified some deviant participants. This group comprises a higher proportion of males, benzodiazepine users, and buprenorphine users. The number of deliveries by different prescribers and pharmacies are higher. The proportion of deviant participants increased between 2001 and 2006 (from 0.86 to 1.38%). Our method can be used to assess the magnitude of abuse liability of clonazepam and is also interesting for following its evolution, two important keys for assessing patterns of abuse.

Geriatric assessment and care for older cancer inpatients admitted in acute care for elders unit.

PURPOSE: The goal of this study was to characterize an elderly population admitted to an Acute Care for Elders Unit (ACE) and to determine their trajectory as well as the prevalence of functional dependencies. DESIGN AND METHODS: We conducted a retrospective chart review of 186 older cancer inpatients, admitted over a period of 30 months. Demographic and oncologic data, reasons for admission, and geriatric assessment (comorbidity, dependency, medication, nutritional status, neurosensory deficits, cognition, mood, and mobility) were recorded. RESULTS: Older cancer inpatients presented a high prevalence of disability, impaired mobility, malnutrition, and depression. Reasons for admission were mostly due to non-specific symptoms. For one-third of the patients, hospitalization led to the diagnosis of cancer. Patients already diagnosed with cancer presented advanced stage disease and progressive disease; only a few received specific care. CONCLUSION: Older cancer inpatients seen in ACE present numerous geriatric problems, non-specific symptoms, and advanced disease.