Evaluation of risk management in a natalizumab home infusion procedure.

Natalizumab is a well-established disease-modifying therapy used in active multiple sclerosis (MS). The most serious adverse event is progressive multifocal leukoencephalopathy. For safety reasons, hospital implementation is mandatory. The SARS-CoV-2 pandemic has deeply affected hospital practices leading French authorities to temporarily authorize to administer the treatment at home. The safety of natalizumab home administration should be assessed to allow ongoing home infusion. The aim of the study is to describe the procedure and assess the safety in a home infusion natalizumab model. Patients presenting relapsing-remitting MS treated by natalizumab for over two years, non-exposed to John Cunningham Virus (JCV) and living in the Lille area (France) were included from July 2020 to February 2021 to receive natalizumab infusion at home every four weeks for 12 months. Teleconsultation occurrence, infusion occurrence, infusion cancelling, JCV risk management, annual MRI completion were analyzed. The number of teleconsultations allowing infusion was 365 (37 patients included in the analysis), all home infusions were preceded by a teleconsultation. Nine patients did not complete the one-year home infusion follow-up. Two teleconsultations canceled infusions. Two teleconsultations led to a hospital visit to assess a potential relapse. No severe adverse event was reported. All 28 patients who have completed the follow-up benefited from biannual hospital examination and JCV serologies and annual MRI. Our results suggested that the established home natalizumab procedure was safe using the university hospital home-care department. However, the procedure should be evaluated using home-based services outside the university hospital.

Survival and prognosis factors in systemic sclerosis: data of a French multicenter cohort, systematic review, and meta-analysis of the literature.

BACKGROUND: Data on survival and prognosis factors in incident cohorts are scarce in systemic sclerosis (SStc). To describe survival, standardized mortality ratio (SMR), and prognosis factors in systemic sclerosis (SSc), we analyzed a multicenter French cohort of incident patients and performed a systematic review of the literature and meta-analysis. METHODS: A multicenter, French cohort study was conducted between January 1, 2000, and December 31, 2013. Patients were followed-up until July 1, 2016. A systematic review of the literature was carried out in MEDLINE and EMBASE up to July 2017. Meta-analysis was performed using all available data on SMR and hazard ratios of prognosis factors. RESULTS: A total of 625 patients (493 females, 446 lcSSc) were included. During the study period, 104 deaths (16.6%) were recorded and 133 patients were lost to follow-up. Overall survival rates at 1, 3, 5, and 10 years from diagnosis were 98.0%, 92.5%, 85.9%, and 71.7% respectively in the French cohort. Overall SMR was 5.73 (95% CI 4.68-6.94). Age at diagnosis > 60 years, diffuse cutaneous SSc, scleroderma renal crisis, dyspnea, 6-min walking distance (6MWD), forced vital capacity < 70%, diffusing capacity of the lungs for carbon monoxide < 70%, pulmonary hypertension (PH), telangiectasia, valvular disease, malignancy, anemia, and CRP > 8 mg/l were associated with a poorer survival after adjustment. Eighteen studies (11,719 patients) were included in the SMR meta-analysis and 36 studies (26,187 patients) in the prognosis factor analysis. Pooled SMR was 3.45 (95%CI 3.03-3.94). Age at disease onset, male sex, African origin, diffuse cutaneous SSc, anti-Scl70 antibodies, cardiac and renal involvement, interstitial lung disease, PH, and malignancy were significantly associated with a worse prognosis. Anti-centromere antibodies were associated with a better survival. CONCLUSIONS: Overall, our study highlights a high mortality rate in SSc patients and confirms previously described prognosis factors related to skin extension and organ involvement while identifying additional prognosis factors such as autoantibody status, telangiectasia, 6MWD, and valvular disease.

Both exhaled nitric oxide and blood eosinophil count were associated with mild allergic asthma only in non-smokers.

BACKGROUND: The fractional exhaled nitric oxide (FENO) and the blood eosinophil count (B-eos) are markers of eosinophilic inflammation used in the diagnosis and management of asthma. The relationships between smoking cigarette and both FENO and B-eos are complex and raise questions about the association between these markers and asthma in smokers. OBJECTIVE: To determine the relationships between both FENO and B-eos on one hand and asthma and atopy on the other, according to smoking status. METHODS: FENO and B-eos were measured in, respectively, 1579 and 1496 of the 1607 middle-aged adults randomly selected from the general population in the cross-sectional ELISABET survey. Allergic asthma was defined as asthma (a self-report of physician-diagnosed asthma, and wheezing in the previous 12 months or the use of asthma medications) with atopy (allergic rhinitis or hayfever in the previous 12 months, or a previous positive prick test or allergen desensitization therapy). Non-allergic asthma was defined as asthma without atopy. RESULTS: The analysis included 812 (51.4%) never, 473 (30%) former and 294 (18.6%) current smokers. A total of 490 (32%) participants were atopic, 80 (5.1%) had allergic asthma, and 31 (2%) had non-allergic asthma. Only 16.2% (18/111) of asthmatics were treated with glucocorticoid inhalants, suggesting that among them a majority of participants had mild asthma. A positive interaction between smoking status and allergic asthma was observed in multivariate models explaining FENO (P = 0.003) and B-eos (P = 0.001). Thus, compared to those without allergic asthma, participants with allergic asthma had higher FENO values (+ 63.4%, 95% CI = [39; 92]) and higher B-eos (+ 63.2% [38.2; 92.7]) in never and former smokers, but not in current smokers. Lastly, an analysis of receiver-operating characteristic curves showed that each of the two markers was able to discriminate moderately allergic asthma but only in non-smokers. CONCLUSIONS & CLINICAL RELEVANCE: FENO and B-eos were associated with the presence of mild allergic asthma only in non-smokers, not in current smokers. These findings raise questions about the clinical value of FENO and B-eos in smokers.

Forecasts of health care utilization related to pandemic A(H1N1)2009 influenza in the Nord-Pas-de-Calais region, France.

OBJECTIVES: To describe and evaluate the forecasts of the load that pandemic A(H1N1)2009 influenza would have on the general practitioners (GP) and hospital care systems, especially during its peak, in the Nord-Pas-de-Calais (NPDC) region, France. STUDY DESIGN: Modelling study. METHODS: The epidemic curve was modelled using an assumption of normal distribution of cases. The values for the forecast parameters were estimated from a literature review of observed data from the Southern hemisphere and French Overseas Territories, where the pandemic had already occurred. Two scenarios were considered, one realistic, the other pessimistic, enabling the authors to evaluate the 'reasonable worst case'. Forecasts were then assessed by comparing them with observed data in the NPDC region--of 4 million people. RESULTS: The realistic scenarios forecasts estimated 300,000 cases, 1500 hospitalizations, 225 intensive care units (ICU) admissions for the pandemic wave; 115 hospital beds and 45 ICU beds would be required per day during the peak. The pessimistic scenario's forecasts were 2-3 times higher than the realistic scenario's forecasts. Observed data were: 235,000 cases, 1585 hospitalizations, 58 ICU admissions; and a maximum of 11.6 ICU beds per day. CONCLUSIONS: The realistic scenario correctly estimated the temporal distribution of GP and hospitalized cases but overestimated the number of cases admitted to ICU. Obtaining more robust data for parameters estimation--particularly the rate of ICU admission among the population that the authors recommend to use--may provide better forecasts.

Bayesian estimation for molecular profile reconstruction in proteomics based on liquid chromatography and mass spectrometry.

There is a need to precisely measure concentration of proteins in biological substance for early diagnosis of disease or knowledge of fundamental biological processes. Many apparatus have been proposed, and now data processing methods have to be investigated. This paper focuses on data processing of proteomic experiments combining nano liquid chromatography and mass spectrometry. Experimental fluctuations of this process raise an interest for robust methods. Consequently, we propose a model of this acquisition system and a probabilistic Bayesian method to estimate the proteins' concentrations and system parameters.

Multigate doppler signal analysis using 3-D regularized long AR modelling.

Autoregressive (AR) modelling has already been proposed as an alternative to fast Fourier transform to process ultrasound (US) Doppler signals. Previous works introduced long AR models, set up under a regularization framework. The latter may be in 1-D (frequency) or 2-D (frequency and space or time). This study generalizes the spectrum regularization in the three dimensions frequency, space and time. The problem of the penalization function is addressed, and a new convex solution is proposed, taking into account possible nonstationarity of the Doppler signal. The parameter tuning is based on simulations using a standard Doppler signal model. The first results show that this processing improves the spectral estimation, and is well suited to flow interpretation.

Infant and toddler pathways leading to early externalizing disorders.

OBJECTIVE: To examine pathways leading to specific types of early externalizing disorders. METHOD: Longitudinal data were collected on 310 low-income, male subjects followed from infancy until age 6 years. RESULTS: Support across informants was found for the importance of the caregiving environment during infancy in relation to the development of externalizing disorders at school entry. Support was also found for the significance of early child factors, but this was limited to child behavior at home. CONCLUSIONS: The results are consistent with social learning and attachment models, which suggest that severe conduct problems in early childhood are the result of deficits in the caregiving environment. Support was also found for Moffitt's hypothesis that children with the comorbid attention-deficit/hyperactivity disorder-oppositional defiant disorder/conduct disorder pattern experience multiple child and psychosocial risk factors that begin during infancy.

Evidence for the continuity of early problem behaviors: application of a developmental model.

Evidence of the continuity of early problem behaviors in young girls and boys was examined developmentally. Data were gathered on 104 mother-child dyads from low-income families when children were between 1 and 5 years of age. Difficult temperament, aggression, and noncompliance from 12 to 24 months, and externalizing and internalizing problems at 36 and 60 months, were assessed. The results provide evidence for the continuity of early behavioral and emotional problems and support for the early differentiation between internalizing and externalizing problems. Implications of the current findings for prevention efforts are presented.

Antecedents of preschool children's internalizing problems: a longitudinal study of low-income families.

OBJECTIVE: To examine antecedents of young children's internalizing problems using research related to emotion regulation to guide prediction. METHOD: Longitudinal data were collected on 86 low-income mother-child dyads to examine risk factors related to early internalizing problems as measured by the Child Behavior Checklist (CBCL). RESULTS: The following risk factors, assessed during infancy, were related to the development of preschool-age internalizing problems: negative emotionality, disorganized attachment classification, negative life events, exposure to child-rearing disagreements, and parenting hassles. In addition, the interaction of high negative emotionality and exposure to parental conflict added unique variance to the prediction of scores on the CBCL Withdrawal and Depression/Anxiety subscales. CONCLUSIONS: Children's preschool-age internalizing problems can be identified during infancy from multiple domains related to the development of emotion regulation. Further longitudinal work is encouraged that incorporates direct measurement of children's negative emotionality, parenting, and family factors that influence both parenting and children's emotion regulation.

DSM-III-R disorders in preschool children from low-income families.

OBJECTIVE: To generate rates of DSM-III-R disorders in a sample of preschool children from low-income families, examine impairment ratings for preschool children meeting criteria for DSM-III-R disorders, and compare rates of psychopathology using DSM-III-R criteria with rates generated by the Child Behavior Checklist (CBCL). METHOD: As part of an ongoing longitudinal study of 104 mother-child dyads from low-income families, data were gathered when children were 5 years of age. DSM-III-R disorders were diagnosed through the administration of the Schedule for Affective Disorders and Schizophrenia for School-Age Children to the mothers, and mothers competed the CBCL. RESULTS: Rates of DSM-III-R disorders among preschool children from low-income families were higher than those reported in community samples, but comparable with rates for low-income school-age children and adolescents. Children meeting criteria for DSM-III-R disorders were rated as significantly impaired. The prevalence of behavioral and emotional problems was similar by both DSM-III-R criteria and the CBCL. There was some evidence, however, that the two systems identified different children. CONCLUSIONS: DSM-III-R criteria appear to adequately identify preschool children with serious behavioral and emotional problems. Longitudinal studies are needed to explore further the relative utility of the DSM and CBCL in the identification of psychopathology in preschool children.

An adaptive approach to computing the spectrum and mean frequency of Doppler signals.

Modern ultrasound Doppler systems are facing the problem of processing increasingly shorter data sets. Spectral analysis of the strongly nonstationary Doppler signal needs to shorten the analysis window while maintaining a low variance and high resolution spectrum. Color flow imaging requires estimation of the Doppler mean frequency from even shorter Doppler data sets to obtain both a high frame rate and high spatial resolution. We reconsider these two estimation problems in light of adaptive methods. A regularized parametric method for spectral analysis as well as an adapted mean frequency estimator are developed. The choice of the adaptive criterion is then addressed and adaptive spectral and mean frequency estimators are developed to minimize the mean square error on estimation in the presence of noise. Two suboptimal spectral and mean-frequency estimators are then derived for real-time applications. Finally, their performance is compared to that of both the FFT based periodogram and the AR parametric spectral analysis for the spectral estimator, and, to both the correlation angle and the Kristoffersen's [8] estimators for the mean frequency estimator using Doppler data recorded in vitro.