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The authors conducted a population-based case-control study to investigate whether clinically observed chickenpox, linked with a level of intensity for clinical expression, increases the risk of multiple sclerosis (MS) in childhood. The cases were MS patients whose disease onset occurred between 1994 and 2003, before age 16 years, in France. Each case was matched for age, sex, and geographic origin with as many as 12 controls randomly selected from the general population. Information about clinically observed chickenpox in cases and controls before the index date regarding onset of MS was collected with a standardized questionnaire and was checked against health certificates. Conditional logistic regression was used to estimate the odds ratio for an association between MS and chickenpox. The 137 MS cases were matched with 1,061 controls. Clinically observed chickenpox had occurred in 76.6% of the cases and 84.9% of their matched controls. The adjusted odds ratio of MS onset associated with chickenpox occurrence was 0.58 (95% confidence interval: 0.36, 0.92). The authors concluded that clinically observed chickenpox was associated with a lower risk of childhood-onset MS in a French population. [ABSTRACT FROM AUTHOR]

Abstract Background Little is known concerning risk factors for herpes zoster in the general population. We hypothesised that inhaled corticosteroids (ICS) are a risk factor for herpes zoster especially among users of inhibitors of cytochrome P450 enzymes involved in their metabolism. Methods We identified a cohort of adult users of respiratory medications in the General Practice Research Database and carried out a nested case control analysis of inhaled corticosteroid use among 8900 new cases of herpes zoster and 88032 controls matching on age and calendar time. Results The adjusted odds ratio for the relationship between current use of ICS and the occurrence of herpes zoster was 1.00 (95% confidence interval (CI), 0.94-1.07). There was no increase in risk of herpes zoster even at higher ICS doses; odds ratio 1.05 (95% CI, 0.96-1.14). Among subjects with concomitant prescriptions for an ICS and an inhibitor of cytochrome P450 3A4, the point estimate for the association between herpes zoster and the use of higher doses of inhaled corticosteroids was 1.23 (95% CI, 0.81-1.88). Conclusions The use of inhaled corticosteroids, even at high doses and in conjunction with inhibitors of their metabolism, was not a significant risk factor for the occurrence of herpes zoster in adults.

The fight against the SARS-CoV-2 pandemic was carried out through strong restrictive measures, including general population lockdown, which allowed the convergence of risk factors for child abuse. During this period, the French national hotline for children in danger recorded a 56% increase in calls. Calls followed by an alert to departmental child protection services increased by 30%. Through an algorithm created by our team, we showed a 50% increase in the relative frequency of hospitalizations for physical abuse in children aged 0-5 years during the lockdown. This has fueled thinking about subsequent health measures to protect the youngest children. Our goal is now to use this algorithm for epidemiological purposes as a barometer of abuse or in daily practice to help the diagnosis of physical abuse in young children., (© 2023 médecine/sciences – Inserm.)

Background: Little is known to date about the impact of COVID-19 pandemic on self-harm., Methods: The number of hospitalizations for self-harm (ICD-10 codes X60-X84) in France from 1st January to 31st August 2020 (including a two-month confinement) was compared to the same periods in 2017-2019. Statistical methods comprised Poisson regression, Cox regression and Student's t -test, plus Spearman's correlation test relating to spatial analysis of hospitalizations., Outcomes: There were 53,583 self-harm hospitalizations in France during January to August 2020. Compared to the same period in 2019, this represents an overall 8·5% decrease (Relative Risk [95% Confidence Interval] = 0·91 [0·90-0·93]).This decrease started in the first week of confinement and persisted until the end of August. Similarly, decrease was found in both women (RR=0·90 [0·88-0·92]) and men (RR=0·94 [0·91-0·95]), and in all age groups, except 65 years and older. Regarding self-harm hospitalizations by means category, increases were found for firearm (RR=1·20 [1·03-1·40]) and for jumping from heights (RR=1·10 [1·01-1·21]). There was a trend for more hospitalizations in intensive care (RR=1·03 [0·99-1·07]). The number of deaths at discharge from hospital also increased (Hazard Ratio = 1·19 [1·09-1·31]). Self-harm hospitalizations were weakly correlated with the rates of hospitalization for COVID-19 across administrative departments (Spearman's rho =-0·21; p  = 0·03), but not with overall hospitalizations., Interpretation: The COVID-19 pandemic had varied effects on self-harm hospitalizations during the early months in France. Active suicide prevention strategies should be maintained., Funding: French National Research Agency., Competing Interests: All authors have nothing to declare., (© 2021 The Authors.)

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess whether the risk of incident systemic lupus erythematosus (SLE) is associated with the use of combined oral contraceptives (COCs), because studies of the link between exogenous hormonal exposure and the risk of SLE have produced conflicting results., Methods: We conducted a population-based nested case-control study among women ages 18-45 years, using the UK's General Practice Research Database. All incident cases of SLE from 1994-2004 (n = 786) were identified in the database and matched with up to 10 controls (n = 7,817) among women without SLE at the time of the case's diagnosis., Results: The adjusted rate ratio (RR) of incident SLE associated with any use of COC was 1.19 (95% confidence interval [95% CI] 0.98-1.45), whereas with current use it was 1.54 (95% CI 1.15-2.07). The rate was particularly increased in current users who had only recently started COC use (RR 2.52, 95% CI 1.14-5.57) compared with longer-term current users (RR 1.45, 95% CI 1.06-1.99). The risk appeared to be particularly elevated with current exposure to first- or second-generation contraceptives (RR 1.65, 95% CI 1.20-2.26), and increasing with the dose of ethinyl estradiol (RR 1.42, 1.63, and 2.92 for < or =30 microg, 31-49 microg, and 50 microg, respectively)., Conclusion: The use of COCs is associated with an increased risk of SLE. This risk is particularly elevated in women who recently started contraceptive use, suggesting an acute effect in a small subgroup of susceptible women.

An 8-year cohort study of nearly 500 children with a first demyelinating event, with only 8% of losses to follow-up, has changed our view of pediatric MS. The risk of MS was not increased by HBV vaccination, but was increased by passive smoking at home.

What Is Already Known About This Subject: Three previous epidemiological studies found an increased risk of severe skin and soft tissue infectious complications associated with exposure to NSAIDs in children with varicella. In vitro studies demonstrated that decreases in defences against infections induced by NSAIDs could be due to impairment of neutrophil blood cell function., What This Study Adds: The use of NSAIDs is associated with an increased risk of severe skin and soft tissue complication of varicella in children. The use of NSAIDs is also associated with a small increased risk of such complications in zoster disease in adults and the elderly. This study supports the limited prescription of NSAIDs in VZV infection., Aims: To assess the risk of severe skin and soft tissue complications associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in treating patients with varicella zoster virus infection., Methods: The design was a nested case-control study, with matching for age and practice. The setting was primary care in the United Kingdom (United Kingdom's General Practice Research Database). Two population-based cohorts of all patients with a primary varicella (n = 140,111) or zoster (n = 108,257) diagnosis during 1994-2005 were followed up for 2 months after diagnosis. Main outcome measures of severe skin or soft tissue complications (mostly cellulitis and abscess) associated with current NSAID or paracetamol use were estimated, and adjusted for potential confounding factors, including sex, drug use, and comorbidity., Results: In patients with varicella, there were 386 cases of severe skin or soft tissue complications (rate 2.8 per 1000) during the 2 month follow-up period (mean age 10.7 years). The rate of complications associated with exposure to NSAIDs was increased (rate ratio 4.9; 95% CI 2.1, 11.4). In patients with zoster disease, there were 681 cases of severe skin or soft tissue complications (rate 6.3 per 1000) during the 2 month follow-up (mean age 60.9 years). The rate ratio of complications associated with exposure to NSAIDs was 1.6 (95% CI 1.1, 2.4). In both conditions, there was no increased risk of complication associated with a current exposure to paracetamol., Conclusions: The use of NSAIDs is associated with an elevated risk of severe skin and soft tissue complications of varicella zoster virus infection, mostly in children with varicella.

The possibility of a link between active smoking and incident multiple sclerosis (MS) has been raised. However, possible links between incidence of MS and passive smoking, particularly in children, have not been analysed. We conducted a population-based, case-control study. The cases were patients with incident MS occurring between 1994 and 2003, before the age of 16 years, in France. Each case was matched for age, sex and geographic origin with 12 controls, randomly selected from the French general population. Information about the smoking history of the parents of the cases and controls was collected with a standardized questionnaire. Conditional logistic regression was used to estimate the rate ratio (RR) of MS associated with parental smoking at home. The 129 cases of MS were matched with 1038 controls. Information about parental smoking was obtained for all these cases and controls. Exposure to parental smoking was noted in 62.0% of cases and 45.1% of controls. The adjusted RR of a first episode of MS associated with exposure to parental smoking at home was 2.12 (95% confidence interval: 1.43-3.15). Stratification for age showed that this increase in risk was significantly associated with the longer duration of exposure in older cases (over 10 years of age at the time of the index episode)-RR 2.49 (1.53-4.08)-than in younger cases. Children exposed to parent smoking have a higher MS risk. The duration of exposure also affects the level of risk.

Purpose: To study the pharmacokinetics of topiramate (TPM) at steady state in children younger than 4 years comedicated with other antiepileptic drugs (AEDs)., Methods: Twenty-two children aged 6 months to 4 years with pharmacoresistant partial or generalized epilepsy were enrolled in an open-label prospective study. Children were assigned to different groups according to comedication with enzyme-inducing AEDs (n = 8), valproic acid (VPA) (n = 6), or other AEDs not known to affect drug metabolism (neutral AEDs, n = 7). One child was receiving treatment with both enzyme-inducing AEDs and VPA. After dose titration, blood samples were collected at steady state just before and 0.5, 1, 1.5, 2, 4, 6, 8, and 12 h after the morning dose of TPM. Pharmacokinetic parameters were determined by a noncompartmental method., Results: TPM apparent oral clearance (CL/F) was significantly higher in children taking enzyme-inducing AEDs (85.4 +/- 34.0 ml/h/kg) than in those receiving VPA (49.6 +/- 13.6 ml/h/kg) or neutral AEDs (46.5 +/- 12.8 ml/h/kg). Conversely, dose-normalized areas under the plasma TPM concentration curves (0-12 h) were significantly lower in enzyme-induced patients than in patients receiving VPA or other AEDs., Conclusions: Compared with children not receiving enzyme inducers, children younger than 4 years who receive concomitant enzyme-inducing AEDs need higher doses (milligrams per kilogram) to achieve comparable plasma TPM concentrations.