Virus-triggered exacerbation in allergic asthmatic children: neutrophilic airway inflammation and alteration of virus sensors characterize a subgroup of patients.

BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function. METHODS: Virus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells. RESULTS: Viruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-ß, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state. CONCLUSION: Our results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation. TRIAL REGISTRATION: This multicenter prospective study was approved by the regional investigational review board (ref: 08/07).

Prenatal factors related to face presentation: a case-control study.

PURPOSE: Face presentation is rare. Its risk factors are debated and its mechanism is practically unknown. The objectives of the study were to determine the prenatal factors associated with face presentation at delivery and discuss the mechanism by which it occurs. METHODS: Retrospective case-control study including all cases of face presentation of infants born at a gestational age between 22 and 42 weeks of gestation over a 16 year period. For each case, we selected three control women who gave birth the same day. RESULTS: During the study period, there were 64 cases of face presentation (incidence: 0.8 per 1000 births), which we compared with 191 controls. After logistic regression, the four factors most closely associated with delivery in face presentation were twin pregnancy [OR 25.8 (4.7-141.8)], birth weight <2500 g [OR 8.9 (2.1-38.0)], polyhydramnios [OR 7.1 (2.0-25.2)], and multiparity [OR 3.6 (1.5-8.6)]. CONCLUSION: These factors are all associated with a reduction in the uterine constraints on fetal attitude. This may play a role in the mechanism resulting in face presentation.

Does prenatal diagnosis modify neonatal treatment and early outcome of children with esophageal atresia?

OBJECTIVE: Our study aimed at (1) evaluating neonatal treatment and outcome of neonates with either a prenatal or a postnatal diagnosis of esophageal atresia (EA) and (2) analyzing the impact of prenatal diagnosis on outcome based on the type of EA. STUDY DESIGN: We conducted a population-based study using data from the French National Register for infants with EA born from 2008-2010. We compared prenatal, maternal, and neonatal characteristics among children with prenatal vs postnatal diagnosis and EA types I and III. We defined a composite variable of morbidity (anastomotic esophageal leaks, recurrent fistula, stenosis) and death at 1 year. RESULTS: Four hundred sixty-nine live births with EA were recorded with a prenatal diagnosis rate of 24.3%; 82.2% of EA type I were diagnosed prenatally compared with 17.9% of EA type III (P < .001). Transfer after birth was lower in case of prenatal diagnosis (25.6% vs 82.5%; P < .001). The delay between birth and first intervention did not differ significantly among groups. The defect size was longer among the prenatal diagnosis group (2.61 vs 1.48 cm; P < .001). The composite variables were higher in prenatal diagnosis subset (44% vs 27.6%; P = .003) and in EA type I than in type III (58.1% vs 28.3%; P < .001). CONCLUSION: Despite the excellent survival rate of EA, cases with antenatal detection have a higher morbidity rate related to the EA type (type I and/or long gap). Even though it does not modify neonatal treatment and the 1-year outcome, prenatal diagnosis allows antenatal parental counselling and avoids postnatal transfers.

Renal involvement in children with HNF1ß mutation: early sonographic appearances and long-term follow-up.

OBJECTIVES: The aim was to report ultrasound (US) patterns of hepatocyte nuclear factor (HNF1ß) mutation throughout childhood and determine whether ultrasound could be predictive of renal failure. METHODS: The sonographic examinations in 34 children with HNF1ß mutation were reviewed. Their sonographic characteristics were compared with renal function. RESULTS: At first postnatal examination renal length was normal in 44 % of the patients, decreased in 24 %, increased in 12 % and asymmetrical in 20 %. Renal cortex was hyperechoic in 97 %. Corticomedullary differentiation was abnormal in 59 %. Cysts were present in 77 % of patients. Cysts were mostly subcapsular (64 %). Twenty-eight patients had follow-up examinations. A modification of the sonographic appearance was observed in 91 % of patients. Eight patients (23 %) had renal failure; no specific US pattern could be demonstrated. CONCLUSIONS: At birth, HNF1ß mutation was typically associated on US with the combination of hyperechoic, normal-sized kidneys with abnormal corticomedullary differentiation (CMD) and multiple cortical cysts. In older children, the appearances can be variable: kidneys may have decreased (32 %) or normal size (33 %); they are usually hyperechoic (50 %) with abnormal CMD (78 %) and (sub)cortical cysts (71 %). No pattern appears to be associated with renal failure. KEY POINTS: • HNF1ß mutations determine significant anomalies of sonographic appearances of kidneys in children. • Kidneys appear mainly hyperechoic, with or without CMD and with subcapsular cysts. • The US pattern may evolve throughout childhood in the same patient. • No correlation was found between any sonographic pattern and renal failure.

[Factors associated with drug prescription in general practice: a multicenter cross-sectional study]. / Facteurs associés à la prescription médicamenteuse en médecine générale : une étude transversale multicentrique.

OBJECTIVE: Iatrogenic, environmental and economic consequences of drug prescription are public health issues. This study was designed to identify physician, patient and consultation characteristics that influence drug prescription in general practice. METHODS: A national multicentre cross-sectional study was conducted in general practice from December 2011 to Apri/2012. Bivariate analyses were performed, followed by multivariate analyses based on a mixed model. RESULTS: At least one drug was prescribed in 16,626 (80.7%) of 20,600 consultations conducted by 128 practitioner. Apart from the number of health problems managed (OR= 10.6 [8.8; 13.0] if :2 4), independent patient-related factors were female gender (OR= 1.1 [1.0; 1.2]), extreme ages (OR= 1.3 [1.1; 1.5]younger than 4 years, OR= 1.5 [1.3; 1.8] from 5 to 14 years, and OR= 1.3 {1.2; 1.5] older than 60 years vs. between 15 to 29 years), new patients (OR= 0.8 {0. 7; 0.9]), work accident or occupational disease (OR= 0.3 {0.3; 0.4]). For the physician, drug prescription was linked to visits by pharmaceutical representatives (OR = 1.6 [1.2; 2.0] if :2 5 times a week) but not to visits by Public Health Insurance delegates or signature of the contract designed to improve individual practices (CAP/). CONCLUSIONS: Independently of health problems, patient and physician characteristics, including visits by pharmaceutical representatives, influence drug prescription.

Relevance of the ISGLS definition of posthepatectomy liver failure in early prediction of poor outcome after liver resection: study on 680 hepatectomies.

OBJECTIVE: To assess the relevance of the International Study Group of Liver Surgery (ISGLS) definition of posthepatectomy liver failure compared with 2 well-established criteria, 50-50 and PeakBili>7, as early predictors of posthepatectomy outcome. BACKGROUND: There is limited data on the postoperative use of ISGLS definition of posthepatectomy liver failure as early predictor of outcome. METHODS: Between 2007 and 2012, a total of 680 hepatectomies were analyzed from a prospective database. The value of each definition for prediction of 3-month major complications (Clavien III-V) and mortality was assessed either within 10 days of surgery or on postoperative day 5. RESULTS: Three-month major morbidity and mortality rates were 16.5% and 4.4%, respectively. Within 10 days, 79 patients fulfilled ISGLS definition compared with 24 for 50-50 and 44 for PeakBili>7 criteria. Sensitivities of ISGLS definition and 50-50 and PeakBili>7 criteria for prediction of major morbidity and mortality were 35.8, 17.4, 24.8% and 56.7, 36.7, 56.7%, respectively. Patients with no positive score had a risk of death or major complication below 5% and 15%, respectively. In patients with a positive score, the ISGLS definition was the least relevant to predict major complications and mortality (positive predictive values of 49.4% and 21.8% vs 79.2% and 47.8% for 50-50 and 61.4% and 40.5% for PeakBili>7 criteria). The relative risk of death was 6.9 (95% confidence interval, 3.1-15.4) if the ISGLS definition was evaluated on postoperative day 5 versus 21.1 (95% confidence interval, 7.7-57.7) for 50-50 and 21.7 (95% confidence interval, 7.4-63.3) for PeakBili>7 criteria. CONCLUSIONS: ISGLS definition was less discriminatory than 50-50 and PeakBili>7 criteria in identifying patients at risk of posthepatectomy major complications or death.

Apathy in untreated early-stage Parkinson disease: relationship with other non-motor symptoms.

Apathy is a frequent and disabling behavioral disorder in patients with Parkinson's disease (PD). Its prevalence in treatment-naive patients with early-stage PD has not been extensively investigated. Moreover, whether apathy is related to other non-motor symptoms in early-stage PD is unknown. Our objective was to determine the prevalence and features of apathy and associated factors in a group of treatment-naive patients with early-stage PD. Ninety-five treatment-naive patients with early-stage PD participated in the study. Apathy, depression, motor symptoms, and overall cognitive efficiency were assessed. The presence of the main non-motor symptoms was checked during a detailed clinical interview. Group comparisons were carried out to investigate the association with apathy. Eighteen patients (18.95%) were diagnosed as apathetic, and five of the latter had concomitant depression. Apathetic patients had significantly more severe motor symptoms (P < 0.001) and a lower cognitive status (P = 0.032) than non-apathetic patients. When considering non-motor symptoms, apathy was significantly associated only with fatigue (P = 0.007) and anhedonia (P = 0.010), both of which were more prevalent in apathetic patients than in non-apathetic patients. In treatment-naive patients with early-stage PD, apathy was significantly associated with more severe motor symptoms and a lower cognitive status. After adjustment for these factors, apathy appeared to be a relatively isolated, independent symptom because the only other associated non-motor symptoms were fatigue and anhedonia.

Determinants of exercise capacity in cystic fibrosis patients with mild-to-moderate lung disease.

BACKGROUND: Adult patients with cystic fibrosis (CF) frequently have reduced exercise tolerance, which is multifactorial but mainly due to bronchial obstruction. The aim of this retrospective analysis was to determine the mechanisms responsible for exercise intolerance in patients with mild-to-moderate or severe disease. METHODS: Cardiopulmonary exercise testing with blood gas analysis at peak exercise was performed in 102 patients aged 28 ± 11 years: 48 patients had severe lung disease (FEV1 < 50%, group 1) and 54 had mild-to-moderate lung disease (FEV1 ≥ 50%, group 2). VO2 peak was measured and correlated with clinical, biological, and functional parameters. RESULTS: VO2 peak for all patients was 25 ± 9 mL/kg/min (65 ± 21% of the predicted value) and was < 84% of predicted in 82% of patients (100% of group 1, 65% of group 2). VO2 peak was correlated with body mass index, C-reactive protein, FEV1, FVC, RV, DLCO, VE/VCO2 peak, VD/VT, PaO2, PaCO2, P(A-a)O2, and breathing reserve. In multivariate analysis, FEV1 and overall hyperventilation during exercise were independent determinants of exercise capacity (R(2) = 0.67). FEV1 was the major significant predictor of VO2 peak impairment in group 1, accounting for 31% of VO2 peak alteration, whereas excessive overall hyperventilation (reduced or absent breathing reserve and VE/VCO2) accounted for 41% of VO2 alteration in group 2. CONCLUSION: Exercise limitation in adult patients with CF is largely dependent on FEV1 in patients with severe lung disease and on the magnitude of the ventilatory response to exercise in patients with mild-to-moderate lung disease.

The spectrum of cognitive disorders in Parkinson's disease: a data-driven approach.

The objective of this study was to identify different cognitive phenotypes in Parkinson's disease (PD) using a data-driven approach. A model-based cluster analysis was conducted on the neuropsychological test results of 558 PD patients from 2 European movement disorder centers (Lille, n = 403; Maastricht, n = 155). The number of clusters was determined according to their clinical relevance as well as on the basis of 3 statistical criteria: the cubic cluster criterion, the pseudo F statistic, and the total squared correlation ratio (R(2)). A factorial discriminant analysis was performed to assess the quality of the cluster's separation. Descriptive variables were used to further characterize the clusters. A 5-cluster model was considered the clinically most relevant. The 5 clusters comprised: (1) cognitively intact patients (19.39%); (2) patients without cognitive deficits but with slight mental slowing (41.29%); (3) patients with slightly impaired overall cognitive efficiency and deficits in all cognitive domains except recognition memory (12.93%); (4) patients with severe mental slowing, impaired overall cognitive efficiency, and severe cognitive impairment in all domains, including memory (23.88%); and (5) patients with very severe impairment in all cognitive domains (2.51%). Cognitively intact patients were significantly younger and had received more years of formal education. Patients in the last 3 clusters had more severe motor symptoms, longer disease duration, and more axial signs. In the last cluster, most patients were demented. Our results confirm the heterogeneity of cognitive presentations in PD, ranging from cognitively intact patients with rather high levels of performance in each cognitive domain to very severely impaired patients.

Mechanisms of splenic hypertrophy following hepatic resection.

BACKGROUND: Following hepatic resection, liver regeneration has been associated with concurrent splenic hypertrophy. The mechanisms of this phenomenon are unknown, may be multiple and include: splanchnic sequestration caused by a reduction in the hepatic mass; hepatic growth factors that may indirectly act on the spleen, and the redistribution of the total reticuloendothelial system. METHODS: Seventy-five patients (40 males; median age: 60 years) who underwent minor (16%) or major (84%) hepatectomy between September 2004 and October 2009 were included. Prospective measurements of liver and spleen volumes were obtained preoperatively and postoperatively 1 month after hepatectomy using computed tomography (CT). The future remnant liver volume (RLV) was calculated on preoperative CT and the extent of resection was expressed as the RLV divided by total liver volume (TLV). Liver and spleen hypertrophy were expressed according to the absolute gain or relative increase in the initial volumes (%).The presence of fibrosis >F1, associated extrahepatic resection (except minor resections), and previous hepatectomy (major or minor) within 3 months represented exclusion criteria. RESULTS: Mean ± standard deviation (SD) liver volume at 1 month was higher than RLV (1187 ± 286 cm(3) versus 764 ± 421 cm(3) ; P < 0.001). Mean ± SD splenic volume increased from 252 ± 100 cm(3) preoperatively to 300 ± 111 cm(3) at 1 month (P < 0.001). Liver and splenic hypertrophy were significant after major hepatectomies (+100% and +26%, respectively; P < 0.001), but not after minor hepatectomies. Liver hypertrophy was inversely correlated to RLV/TLV (r = -0.687, P < 0.001). Splenic hypertrophy was not correlated to RLV/TLV. Liver and splenic hypertrophy were linearly correlated (r = 0.495, P < 0.001). Neoadjuvant chemotherapy (n = 37), preoperative portal vein embolization (n = 10) and postoperative complications (overall: n = 25; major: n = 10; infectious: n = 6) had no impact on hepatic or splenic hypertrophy. CONCLUSIONS: Splenic hypertrophy occurred after major hepatectomy, but was not correlated to the extent of resection, by contrast with liver hypertrophy. Nevertheless, there was a linear correlation between splenic and liver hypertrophy. This correlation suggests the hypothesis of a splenic action of hepatic growth factors or a redistribution of the total reticuloendothelial system rather than an effect of reduction of the portal bed or hepatic outflow.

Single-Use System Integrity I: Using a Microbial Ingress Test Method to Determine the Maximum Allowable Leakage Limit (MALL).

An aerosol microbial ingress test was specifically designed and used to create a predictive model in order to determine the maximum allowable leakage limit (MALL) of single-use systems (SUSs). The MALL is defined as the greatest leak size that does not pose any risk to the product. The procedure involved taking test samples of film material from single-use bags. As test samples, an ethylene vinyl acetate multilayer film (300 µm thick) and a polyethylene multilayer film (400 µm thick) were cut into 50 mm patches. Artificial defects of 1-100 µm were laser-drilled in the middle of each film patch. The patch was assembled on a holder and properly sealed. The test units were filled aseptically with culture media and placed inside an aerosol chamber. Various pressures were applied to the test unit to simulate the constraints that single-use systems may be subject to under real-world conditions. After an aerosolization cycle with spores of Bacillus atrophaeus, a minimum concentration of 106 CFU/cm2 was reached on the film surface. The test units were incubated for 14 days at 30°C-35°C and visually inspected for bacterial ingress. Thirty samples per defect size were tested. Logistic regression was used to indicate the MALL for a single-use system according to the required risk level. With this method, the probability of the occurrence or absence of ingress for a specific defect size was reported according to the experimental data. In addition to physical parameters, such as the pressure applied and the film material, the effect of the probabilistic nature of the microorganisms in determining the MALL is considered. Although finding an experimental model to predict the MALL for real-life process conditions was the ultimate objective, this paper also presents the microbial ingress test data obtained so far for two extreme conditions. Potential constraints, such as vibration, shock, acceleration, liquid movement, and pressure differentials, observed during normal usage were simulated using two extreme differential pressures, 0 mbar and 300 mbar. The estimated MALL for typical use-case conditions are 10-20 µm for storage applications and 2-10 µm for shipping conditions. The microbial integrity test method used in this article was able to detect bacterial ingress down to 3 µm defect size.LAY ABSTRACT: As use of single-use systems (SUSs) is increasingly expanding into all process steps of commercial manufacturing, integrity failure can significantly impact drug safety, availability, and costs. Consequently, growing industry scrutiny on single-use system integrity (SUSI) is raising the need to develop good science behind reliable determinations of liquid leakage and microbial ingress as well as the appropriate physical integrity testing technologies. In the current study, microbial ingress testing by the aerosol method is used to determine the maximum allowable leakage limit (MALL) for SUSs. To define the MALL, it is generally assumed that a system or product will not show any microbial ingress or leakage at a certain defect size. Statistical analysis of the experimental data in this study indicated the MALL with probability at a certain defect size for each system. As a result, the method studied provides a more accurate way of predicting ingress and increasing safety down the line for drug manufacturers and patients alike.

Effects of hypoxia and hypercapnia on nonnutritive swallowing in newborn lambs.

The aim of the present study was to investigate the effect of hypercapnia and hypoxia on apnea and nonnutritive swallowing (NNS) frequency, as well as on the coordination between NNS and phases of the respiratory cycle in newborn lambs, while taking into account the potential effects of states of alertness. Six lambs were chronically instrumented for recording electroencephalogram, eye movements, diaphragm and thyroarytenoid muscle (a glottal adductor) activity, nasal airflow, and electrocardiogram. Polysomnographic recordings were performed in nonsedated lambs exposed to air (control), 10% O(2), and 5% CO(2) in a random order at 3, 4, and 5 days of age. Although hypercapnia decreased apnea frequency in wakefulness and active sleep (P = 0.002 vs. air and hypoxia), hypoxia had no significant effect on apnea. In addition, although hypercapnia increased NNS frequency during wakefulness and quiet sleep (P < 0.005 vs. air and hypoxia), hypoxia tended to decrease NNS frequency. Finally, only hypercapnia altered NNS-breathing coordination by increasing NNS at the transition from inspiration to expiration (ie-type NNS; P < 0.001 vs. air and hypoxia). In conclusion, whereas hypercapnia increases overall NNS frequency by specifically increasing ie-type NNS, hypoxia has the inverse tendency. Results were identical in all three states of alertness.

Physiologic Determinants of Exercise Capacity in Pulmonary Langerhans Cell Histiocytosis: A Multidimensional Analysis.

BACKGROUND: Reduced exercise capacity severely impacts quality of life in pulmonary Langerhans cell histiocytosis. Ascertaining mechanisms that impair exercise capacity is necessary to identify targets for symptomatic treatments. METHODS: Dyspnea, pulmonary function tests and cardiopulmonary exercise test were analysed in 62 study participants. Data were compared between subjects with impaired and normal aerobic capacity (V'O2 peak less than 84% versus 84% predicted or more). Data were reduced using a principal component analysis. Multivariate analysis included V'O2 peak as the dependent variable and principal components as covariates. RESULTS: V'O2 peak was reduced in 44 subjects (71%). Subjects with impaired aerobic capacity presented: (i) decreased FEV1, FVC, FEV1/FVC, DLCO and DLCO/VA and increased AaDO2, (ii) increased ventilatory equivalents at ventilatory threshold, VD/VT peak, AaDO2 peak and PaCO2 peak and decreased ventilatory reserve and PaO2 peak. There was no difference between groups in dyspnea scores. Principal component analysis extracted 4 principal components interpreted as follows: PC1: gas exchange; PC2: "pseudorestriction"; PC3: exercise-induced hyperpnea; PC4: air trapping. Multivariate analysis explained 65% of V'O2 peak. The 4 principal components were independently associated with V'O2 peak (ßcoefficients: PC1: 9.3 [4.6; 14], PC2: 7.5 [3; 11.9], PC3: -5.3 [-9.6;-1.], PC4: -9.8 [-14,9;-4.7]). CONCLUSION: Impaired exercise capacity is frequent in pulmonary Langerhans cell histiocytosis. It is mainly caused by pulmonary changes but is not associated with increased dyspnea intensity. Therefore, treating the lung represents a relevant approach for improving exercise capacity, even in patients experiencing mild dyspnea.

Level of Asthma Controller Therapy Before Admission to the Hospital.

BACKGROUND: In asthma, choice of controller therapy and adherence to treatment can affect the risk of future severe exacerbations leading to hospitalization. OBJECTIVE: Our objective was to characterize treatment dispensation profiles before hospital admission for asthma. METHODS: Using a 1/97th random sample of the national French claims data, patients with asthma aged 6 to 40 years were identified between 2006 and 2014. Patients with subsequent asthma-related hospitalization were selected. On the basis of controller therapy dispensed in the 12 months before admission, treatment profiles were categorized into clusters, using Ward's minimum-variance hierarchical clustering method. RESULTS: Of 17,846 patients with asthma, we identified 275 patients (1.5%) with an asthma-related hospitalization. Three distinct clusters were identified. The first cluster (63.6%) included patients with few dispensations of any controller medication (<1 unit). The second cluster (32.4%) consisted of patients with frequent dispensations of long-acting beta agonists (LABAs)/inhaled corticosteroids (ICS) in fixed-dose combinations. The third cluster (4%) comprised patients receiving free combinations of ICS and LABAs, with more dispensations of LABAs than of ICS. CONCLUSIONS: In France, before an asthma-related hospitalization, more than 60% of patients received little controller therapy and 4% were exposed to higher dispensation of LABAs than of ICS. These results indicate that a large fraction of asthma-related hospitalizations can potentially be prevented with better pharmacotherapy.

Oxygen desaturation during a 6-minute walk test as a predictor of maximal exercise-induced gas exchange abnormalities in sarcoidosis.

BACKGROUND: Common tests for evaluating gas exchange impairment have different strengths and weaknesses. Alveolar-to-arterial oxygen pressure difference (AaDO2) at peak exercise is a sensitive indicator but it cannot be measured repeatedly. Diffusing capacity of the lung for carbon monoxide (DLco) is measured at rest and may be too insensitive to predict the effects of exercise on gas exchange impairment. Oxygen desaturation during a 6-minute walk test (∆SpO2-6MWT) can be measured repeatedly, but its value in sarcoidosis is unknown. Here, we evaluated the ability of ∆SpO2-6MWT and DLco to predict gas exchange impairment during exercise in sarcoidosis. METHODS: This retrospective study of 130 subjects with sarcoidosis investigated the relationship between DLco, ∆SpO2-6MWT, and peak AaDO2 using correlation tests, inter-test reliability analyses, and predictive values. For the analyses of inter-test reliability and predictive values, DLco, peak AaDO2, and ∆SpO2-6MWT were considered as binary variables (normal/abnormal) according to previously defined thresholds. RESULTS: Correlation coefficients between DLco, ∆SpO2-6MWT, and peak AaDO2 were intermediate (0.53-0.67, P<0.0003) and Kappa coefficients were low (0.21-0.42, P=0.0003-0.02). DLco predicted (I) increased peak AaDO2 with a positive predictive value (PPV) of 66% and a negative predictive value (NPV) of 78% and (II) increased ∆SpO2-6MWT with a PPV at 36% and an NPV at 88%. Normal DLco was a good predictor of the absence of severe desaturation during the 6MWT (94% NPV) and at peak exercise during cardiopulmonary exercise test (CPET) (100% NPV). ∆SpO2-6MWT predicted peak AaDO2 increase with a PPV of 74% and an NPV of 60%. CONCLUSIONS: In a large population of sarcoidosis patients, neither ∆SpO2-6MWT nor DLco was a good predictor of increased peak AaDO2. In contrast, normal DLco was a good predictor of the absence of severe desaturation during the 6MWT and at peak exercise during CPET.

Inappropriate asthma therapy-a tale of two countries: a parallel population-based cohort study.

Against recurrent controversies around the safety of short- and long-acting ß2-agonists (SABA and LABA), and the National Review of Asthma Deaths inquiry in the United Kingdom, we investigated the prevalence of inappropriate therapy in asthma. Our study aimed to determine the prevalence of inappropriate use of asthma therapy in the United Kingdom and in France. Two interval, parallel, population-based cohorts (2007 and 2013) were developed in each country by using the UK OPCRD and the French EGB databases. Patients aged 6-40 years were studied over the 12-month period following inclusion, regarding overuse (⩾12 units) of SABA, use of LABA without inhaled corticosteroids (ICS) and ⩾2-fold higher use of LABA compared with that of ICS. Overall, 39,743 UK and 4,910 French patients were included in 2007, and 14,036 and 5,657 patients, respectively, were included in 2013. UK adults were more frequently exposed to SABA overuse compared with those in France in both periods, with an upward trend in the United Kingdom (P<0.05). In 2013, LABA use without ICS occurred in 0.1% and 1.5% of United Kingdom and French adults, respectively. Unbalanced use of LABA relative to ICS became marginal in both countries in 2013. Inappropriate use of therapy was less marked, but present, in children. Inappropriate therapy remains a common issue in asthma. Based on our figures, it may be estimated that >210,000 British and >190,000 French asthmatics aged 6-40 years were inappropriately treated in 2013.

Long-term evaluation of home-based pulmonary rehabilitation in patients with COPD.

INTRODUCTION: Personalized, global pulmonary rehabilitation (PR) management of patients with COPD is effective, regardless of the place in which this rehabilitation is provided. The objective of this retrospective observational study was to study the long-term outcome of exercise capacity and quality of life during management of patients with COPD treated by home-based PR. METHODS: Home-based PR was administered to 211 patients with COPD (mean age, 62.3±11.1 years; mean forced expiratory volume in 1 second, 41.5%±17.7%). Home-based PR was chosen because of the distance of the patient's home from the PR center and the patient's preference. Each patient was individually managed by a team member once a week for 8 weeks with unsupervised continuation of physical exercises on the other days of the week according to an individual action plan. Exercise conditioning, therapeutic patient education, and self-management were included in the PR program. The home assessment comprised evaluation of the patient's exercise capacity by a 6-minute stepper test, Timed Up and Go test, ten times sit-to-stand test, Hospital Anxiety and Depression score, and quality of life (Visual Simplified Respiratory Questionnaire, VQ11, Maugeri Respiratory Failure 28). RESULTS: No incidents or accidents were observed during the course of home-based PR. The 6-minute stepper test was significantly improved after completion of the program, at 6 months and 12 months, whereas the Timed Up and Go and ten times sit-to-stand test were improved after PR and at 6 months but not at 12 months. Hospital Anxiety and Depression and quality of life scores improved after PR, and this improvement persisted at 6 months and 12 months. CONCLUSION: Home-based PR for unselected patients with COPD is effective in the short term, and this effectiveness is maintained in the medium term (6 months) and long term (12 months). Home-based PR is an alternative to outpatient management provided all activities, such as exercise conditioning, therapeutic education, and self-management are performed.

Shear Wave Elastography (SWE): An Analysis of Breast Lesion Characterization in 83 Breast Lesions.

Qualitative and quantitative shear wave elastography (SWE) criteria were assessed to differentiate between malignant and benign breast lesions. This prospective study included 83 lesions. SWE features measured included maximal stiffness values inside the lesion (E(lesion)) and in the peri-lesion area (E(perilesion)) and ratio values (R(lesion) and R(perilesion)) according to the formula E(lesion) or E(perilesion)/E(fat), with E(fat) corresponding to normal fatty tissue. We compared ultrasonography (B-mode), SWE and histologic sizes. With qualitative and quantitative SWE analysis, sensitivity was 94% and specificity 73%. Malignant lesions appeared more heterogeneous, with higher stiffness and ratio values than benign lesions (p < 0.001). For malignant lesions, SWE size was better correlated to histologic size than B-mode size. Using benign SWE signs to selectively downgrade category 4a and 4b lesions, the specificity improved from 13% to 51% without loss in sensitivity (100%) compared to ultrasound.