Prevention of Flares in Children with Atopic Dermatitis with Regular Use of an Emollient Containing Glycerol and Paraffin: A Randomized Controlled Study.

BACKGROUND/OBJECTIVES: Emollients are part of the standard treatment for atopic dermatitis (AD), although there is limited evidence that regular use of emollients as management therapy reduces the frequency of flares and corticosteroid consumption. The objective of this study was to evaluate the benefit of emollient use in the management of mild to moderate AD in children by assessing the ability of two different emollients (particularly V0034CR) to prevent flares and to reduce the use of corticosteroids. METHODS: In this randomized, open-label study, patients with a current flare were treated with a potent topical corticosteroid. After flare resolution, patients were centrally randomized to V0034CR emollient, reference emollient, or no emollient (1:1:1 ratio) for 12 weeks. New flares were medically assessed before being treated with a moderately potent corticosteroid. RESULTS: A total of 335 children 2 to 6 years of age were randomized. At 12 weeks, the percentage of patients with one or more flares was statistically significantly lower with V0034CR (35.1%) than without emollient (67.6%; p < 0.001). Fewer patients treated with V0034CR required any corticosteroids or immunosuppressants (23.6%) than patients with no emollient (43.3%) at 12 weeks. The difference was significant at all time points (p = 0.002). Patients treated with emollients had a longer time to first flare, fewer flares, higher complete remission rates, less corticosteroid consumption, lower Investigator Global Assessment scores, and lower Scoring Atopic Dermatitis scores than those who were not. V0034CR was well tolerated, with no specific safety concerns. CONCLUSION: Regular emollient use in children with mild to moderate AD reduces flares and corticosteroid consumption.

V0162 a new long-acting bronchodilator for treatment of chronic obstructive lung diseases: preclinical and clinical results.

BACKGROUND: Long acting bronchodilators are the standard of care in the management of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the efficacy and safety of V0162, a novel anticholinergic agent with bronchodilator properties, in preclinical models and in patients with COPD. METHODS: Guinea pigs were used to evaluate the impact of V0162 on the acetylcholine or histamine-induced bronchoconstriction. V0162 was also investigated in an allergic asthma model on ovalbumin-sensitized guinea pig. For clinical investigations, healthy volunteers were included in a dose-escalation, randomized, placebo-controlled phase I study to determine the maximal tolerated dose, followed by a randomized, placebo-controlled, cross-over phase II study in patients with COPD. V0162 was given via inhalation route. The objectives of the phase I/II study were to assess the safety and efficacy of V0162, in terms of bronchodilation and reduction in hyperinflation. RESULTS: Preclinical results showed that V0162 was able to prevent bronchoconstriction induced either by acetylcholine or histamine. V0162 reversed the bronchoconstriction and airway inflammation caused by ovalbumin challenge in sensitized guinea pigs. In the healthy volunteers study, 88 subjects were enrolled: 66 received V0162 and 22 received placebo. No particular safety concerns were raised. The maximal tolerated dose was not reached and the dose escalation was stopped at 2400 µg. A total of 20 patients with COPD were then enrolled. All patients received a single-dose of V0162 1600 µg and of placebo in two alternating periods. In COPD patients, V0162 demonstrated a significant increase in FEV1 compared with placebo (148 ± 137 ml vs. 36 ± 151 ml, p = 0.003). This bronchodilatory effect was corroborated by a reduction in hyperinflation. There was a trend toward dyspnea relief (change in visual analog scale at 22 h, -15.1 ± 26.0 mm vs.- 5.3 ± 28.8 mm with placebo, p = 0.054). No serious adverse events (AEs) were reported. Most common AEs were productive and non-productive cough, dyspnea and pruritus. CONCLUSIONS: V0162 improved pulmonary function and tended to improve dyspnea in patients with COPD over more than 24 h. The slight plasmatic exposure observed might support the good safety profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01348555.

Health-related quality of life in children and adolescents with Marfan syndrome or related disorders: a controlled cross-sectional study.

BACKGROUND: This cross-sectional controlled study aims to assess health-related quality of life (HRQoL) of children and adolescents with a molecular diagnosis of Marfan syndrome (MFS) or related disorders and to evaluate the factors associated with HRQoL in this population. Sixty-three children with MFS and 124 age- and sex-matched healthy children were recruited. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™) generic questionnaire. The correlation between HRQoL scores and the different continuous parameters (age, body mass index, disease severity, systemic score, aortic sinus diameter, and aerobic physical capacity) was evaluated using Pearson's or Spearman's coefficient. A multiple linear regression analysis was performed on the two health summary self-reported PedsQL™ scores (physical and psychosocial) to identify the factors associated with HRQoL in the MFS group. RESULTS: Except for emotional functioning, all other domains of HRQoL (psychosocial and physical health, social and school functions) were significantly lower in children with MFS compared to matched healthy children. In the MFS group, the physical health summary score was significantly lower in female than in male patients (self-report: absolute difference [95%CI] = -8.7 [-17.0; -0.47], P = 0.04; proxy-report: absolute difference [95%CI] = -8.6 [-17.3; 0.02], P = 0.05) and also negatively correlated with the systemic score (self-report: R = -0.24, P = 0.06; proxy-report: R = -0.29, P = 0.03) and with the height Z-score (proxy-report: R = -0.29, P = 0.03). There was no significant difference in the physical health summary scores between the different genetic subgroups. In the subgroup of 27 patients who performed a cardiopulmonary exercise test, self- and proxy-reported physical health summary scores were highly correlated with their aerobic physical capacity assessed by peak oxygen consumption (VO2max) and ventilatory anaerobic threshold (VAT). In the multivariate analysis, the most important independent predictors of decreased physical health were increased height, decreased body mass index, decreased VAT and use of prophylactic therapy. CONCLUSIONS: This study reports an impaired HRQoL in children and adolescents with MFS or related conditions, in comparison with matched healthy children. Educational and rehabilitation programs must be developed and evaluated to improve exercise capacity and HRQoL in these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03236571 . Registered 28 July 2017.

Assessing post-disaster consequences for health at the population level: experience from the AZF factory explosion in Toulouse.

BACKGROUND: A major explosion occurred in the AZF chemical factory in Toulouse in September 2001. A comprehensive programme of epidemiological surveillance was set up. OBJECTIVES: To present an overview of the programme and discuss the methods and potential utility of post-disaster epidemiology. The programme had three objectives: (1) to analyse comprehensively the short-term and long-term effects of air, water and secondary soil pollution on health; (2) to identify health problems needing special attention; and (3) to investigate the long-term direct and indirect effects on the population's health. METHODS: The programme was organised through three committees: (1) a scientific committee, (2) an executive programme committee and (3) an institutional committee which aimed to facilitate exchanges between the epidemiologists, the regional authorities, the population and the media. As the catastrophe was an industrial disaster that had a major effect on workers and companies, and also caused severe damage to many schools and buildings all over the city, routine and ad hoc surveillance systems were used and three specific ad hoc questionnaire surveys in workers, schoolchildren and the general population were planned. RESULTS AND CONCLUSIONS: Although the routine surveillance systems had limitations, several sources provided useful information for public health decisions and were found to be concordant with ad hoc epidemiological studies. Defining a victim was central to the choice of a programme design based on an approach either to victims of the disaster or to the entire population in the surrounding region. Anticipation and preparation for such disasters are thus required.

Lipid oxidation in overweight men after exercise and food intake.

Fat oxidation (FO) is optimized during low- to moderate-intensity exercise in lean and obese subjects, whereas high-intensity exercise induces preferential FO during the recovery period. After food intake during the postexercise period, it is unknown if FO differs according to the intensity exercise in overweight subjects. Fat oxidation was thus evaluated in overweight men after low- and high-intensity exercise during the recovery period before and after food intake as well as during a control session. Ten healthy, sedentary, overweight men (age, 27.9 +/- 5.6 years; body mass index, 27.8 +/- 1.3 kg m(-2); maximal oxygen consumption, 37 +/- 3.9 mL min(-1) kg(-1)) exercised on a cycloergometer (energy expenditure = 300 kcal) at 35% (E35) or 70% (E70) maximal oxygen consumption or rested (Cont). The subjects were fed 30 minutes after the exercise with 300 kcal (1256 kJ) more energy in the exercise sessions than in the Cont session. Respiratory quotient and FO were calculated by indirect calorimetry. Blood samples were analyzed to measure plasma glycerol, nonesterified fatty acid, glucose, and insulin. During exercise, mean respiratory quotient was lower (P < .05) and FO was higher (P < .01) in the E35 than in the E70 session (FO [in mg min(-1)]: E35 = 290 +/- 12, E70 = 256 +/- 38, and Cont = 131 +/- 7). Conversely, FO was higher in the E70 than in both the E35 session and the Cont session during the immediate recovery as well as during the postprandial recovery period (P = .005 for all; FO from the end of the exercise to the end of the session [in grams]: E70 = 45.7 +/- 8.9, E35 = 38.2 +/- 6.8, and Cont = 36.0 +/- 4.3). Blood parameters did not differ between the 3 sessions but changed according to the absorption of the nutrients. In overweight subjects, high-intensity exercise increased FO during the postexercise period even after food intake compared with the low-intensity exercise and the control session.

Lipid oxidation according to intensity and exercise duration in overweight men and women.

OBJECTIVE: Our objective was to compare the effect of different exercise intensities on lipid oxidation in overweight men and women. RESEARCH METHODS AND PROCEDURES: Nine young, healthy, overweight men and women were studied (age, 31.4 +/- 2.3 and 26.7 +/- 2.1 years; BMI, 27.9 +/- 0.4 and 27.2 +/- 0.5; for men and women, respectively). On one study day, the subjects first performed 30 minutes of cycling exercise at 30% of their maximal oxygen uptake (Vo(2max); E1 session), followed by 30 minutes of exercise at 50% Vo(2max) (E2 session). On a second study day, a similar E1 session was followed by 30 minutes of exercise at 70% Vo(2max) (E3 session). From the gas exchange measurements, the respiratory exchange ratio (RER) and the fat oxidation rate (FOR) were calculated. Plasma concentrations of glycerol and non-esterified fatty acids (NEFAs) were assayed. RESULTS: RER was significantly lower for women during only the E1 session. For both sexes, RER decreased over time during the E2 and E3 sessions. During the E1 session, the FOR per kilogram of lean mass (LM) was higher among women, and it did not change over time despite an increase in plasma NEFAs. FOR per kilogram of LM was higher during the E2 exercise for both sexes. During E2 and E3 sessions, as the exercise time was prolonged, the FOR/kg LM increased simultaneously with the increase in the plasma glycerol. DISCUSSION: Lipid oxidation during exercise is optimized for moderate and lengthy exercise. The enhancement of lipid oxidation occurring over time during moderate- and high-intensity exercises could be, in part, linked to the improvement of lipid mobilization. This fact is discussed to shed light on exercise modalities as a tool for the management of overweight.