SQ HDM sublingual immunotherapy tablet for the treatment of HDM allergic rhinitis and asthma improves subjective sleepiness and insomnia: an exploratory analysis of the real-life CARIOCA study.

BACKGROUND AND OBJECTIVE: There are still gaps in the knowledge regarding the effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) on allergic rhinitis (AR) and asthma (AA)-associated sleep disorders. A non-interventional study was conducted to assess the effect of the Standardized quality (SQ) HDM SLIT-tablet on safety and symptoms in adults with HDM respiratory allergies. The aim was to describe the status of insomnia and daytime sleepiness in AR and/or AA patients treated with the SQ HDM SLIT-tablet. METHODS: This was a 12-month multicenter, longitudinal and prospective study. Participants started the SQ HDM SLIT-tablet for moderate-to-severe HDM AR, persistent despite the use of symptom-relieving medication; or HDM AA not well controlled by inhaled corticosteroids and associated with mild-to-severe HDM AR. Sleep symptoms were measured using the Insomnia Severity Index (ISI) questionnaire and the Epworth Sleepiness Scale (ESS). RESULTS: A total of 1,526 adult patients were enrolled and 1,483 were included in the analysis. At baseline, 41.5% of patients reported sleep disorders: 77.0% of them had insomnia and 28.9% suffered from excessive daytime sleepiness. Insomnia was significantly more frequent among patients with uncontrolled AR (83.1%) than those with controlled AR (52.6%) (p<0.0001). Over time, 48.3% and 59.7% of patients reported an improvement greater than the minimal clinically important difference on the ISI and ESS scales respectively. CONCLUSION: In patients with HDM AR and/or asthma associated sleep disorders, an improvement in subjective insomnia and sleepiness was observed after one year of treatment with the SQ HDM SLIT-tablet in a real-life setting.

Antibiotics associated with acquisition of carbapenem-resistant Pseudomonas aeruginosa in ICUs: a multicentre nested case-case-control study.

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains are involved in severe infections, mostly in ICUs. Exposure to antibiotics other than carbapenems may be associated with isolation of CRPA; therefore, we aimed to identify those antibiotics using the case-case-control study design. Methods: A case-case-control study was conducted in 2015 in a prospective multicentre cohort that included 1808 adults hospitalized in 2009 in 10 French ICUs. Patients were screened for P. aeruginosa at admission to the ICU and then weekly. Cases were patients with CRPA and patients with carbapenem-susceptible P. aeruginosa (CSPA) isolation. Controls were patients without P. aeruginosa isolation, matched with each case according to centre, length of stay and hospitalization period. Effects of antibiotic exposure were explored, after adjusting for prior treatment with carbapenems and confounding factors comprising colonization pressure with two logistic regression models. The two models were compared to identify specific risk factors for CRPA isolation. Results: Fifty-nine CRPA, 83 CSPA and 142 controls were compared. In adjusted multivariable analyses, exposure to carbapenems and to antibiotics belonging to the group of ß-lactams inactive against P. aeruginosa were independent risk factors for CRPA isolation (OR, 1.205; 95% CI, 1.079-1.346 and OR, 1.101; 95% CI, 1.010-1.201, respectively). Conversely, exposure to ß-lactams active against P. aeruginosa was an independent protective factor for CSPA isolation (OR, 0.868; 95% CI, 0.772-0.976). Conclusions: Besides carbapenem exposure, exposure to ß-lactams inactive against P. aeruginosa was a specific risk factor for CRPA isolation. Clinicians should counterweigh the potential benefits of administering these antibiotics against the increased risk of CRPA infection.

Pollen-based quantitative reconstructions of Holocene regional vegetation cover (plant-functional types and land-cover types) in Europe suitable for climate modelling.

We present quantitative reconstructions of regional vegetation cover in north-western Europe, western Europe north of the Alps, and eastern Europe for five time windows in the Holocene [around 6k, 3k, 0.5k, 0.2k, and 0.05k calendar years before present (bp)] at a 1° × 1° spatial scale with the objective of producing vegetation descriptions suitable for climate modelling. The REVEALS model was applied on 636 pollen records from lakes and bogs to reconstruct the past cover of 25 plant taxa grouped into 10 plant-functional types and three land-cover types [evergreen trees, summer-green (deciduous) trees, and open land]. The model corrects for some of the biases in pollen percentages by using pollen productivity estimates and fall speeds of pollen, and by applying simple but robust models of pollen dispersal and deposition. The emerging patterns of tree migration and deforestation between 6k bp and modern time in the REVEALS estimates agree with our general understanding of the vegetation history of Europe based on pollen percentages. However, the degree of anthropogenic deforestation (i.e. cover of cultivated and grazing land) at 3k, 0.5k, and 0.2k bp is significantly higher than deduced from pollen percentages. This is also the case at 6k in some parts of Europe, in particular Britain and Ireland. Furthermore, the relationship between summer-green and evergreen trees, and between individual tree taxa, differs significantly when expressed as pollen percentages or as REVEALS estimates of tree cover. For instance, when Pinus is dominant over Picea as pollen percentages, Picea is dominant over Pinus as REVEALS estimates. These differences play a major role in the reconstruction of European landscapes and for the study of land cover-climate interactions, biodiversity and human resources.

Inspiratory muscle training during pulmonary rehabilitation in chronic obstructive pulmonary disease: A randomized trial.

Although recommended by international guidelines, the benefit of inspiratory muscle training (IMT) in addition to rehabilitation remains uncertain. The objective was to demonstrate the effectiveness of IMT on dyspnea using Borg scale and multidimensional dyspnea profile questionnaire at the end of a 6-minute walk test (6MWT) in patients with chronic obstructive pulmonary disease (COPD) with preserved average maximum inspiratory pressure (PImax) of 85 cm H2O (95% of predicted (pred.) value) and admitted for a rehabilitation program in a dedicated center. In a randomized trial, comparing IMT versus no IMT in 32 COPD patients without inspiratory muscle weakness (PImax >60 cm H2O) who were admitted for pulmonary rehabilitation (PR) for 3 weeks, we evaluated the effect of IMT on dyspnea, using both Borg scale and multidimensional dyspnea profile (MDP) at the end of the 6MWT, and on functional parameters included inspiratory muscle function (PImax) and 6MWT. All testings were performed at the start and the end of PR. In unadjusted analysis, IMT was not found to be associated with an improvement of either dyspnea or PImax. After adjustment on confounders (initial Borg score) and variables of interaction (forced expiratory volume in 1 second (FEV1)), we found a trend toward an improvement of "dyspnea sensory intensity", items from MDP and a significant improvement on the variation in the 2 items of MDP ("tight or constricted" and "breathing a lot"). In the subgroup of patients with FEV1 < 50% pred., 5 items of MDP were significantly improved, whereas no benefit was observed in patients with FEV1 > 50% pred. IMT did not significantly improve dyspnea or functional parameter in COPD patients with PImax > 60 cm H2O. However, in the subgroup of patients with FEV1 < 50% pred., MDP was significantly improved.

Usefulness of omalizumab in ten patients with severe occupational asthma.

BACKGROUND: The management of severe occupational asthma (OA) remains problematic and new alternative treatments providing better disease control are required, ideally enabling affected individuals to remain in their job. METHODS: Ten patients with severe uncontrolled OA were treated with the monoclonal anti-IgE antibody omalizumab. In six cases the causative agent was a high molecular weight (HMW) compound and in four cases it was a low molecular weight (LMW) chemical. All of the patients had well documented OA despite workplace adjustments. RESULTS: During treatment, nine patients exhibited a lower rate of asthma exacerbations and used less oral or inhaled corticosteroids. Seven patients were able to continue working at the same workplace as before treatment. CONCLUSION: We have demonstrated that omalizumab is a potential treatment for severe uncontrolled OA and enabled seven of the ten patients in the study to remain in their job.

[Approaching patient experience following pulmonary embolism: A systematic review]. / Approche de l'expérience du patient suite à une embolie pulmonaire : une revue systématique de la littérature.

INTRODUCTION: Pulmonary embolism (PE) is the major complication of thromboembolic disease. While a few qualitative studies have explored patient experience after PE, to our knowledge no literature review is available to date. The aim of this work was to explore patient experience after a PE episode through a systematic review of the literature comprising: patient experience, clinicians' perception of the patients' attitude and knowledge, and the patients' perception of VTE prevention strategies. METHODS: A search of PubMed, Web of science, Cochrane and EMBASE databases. The search was conducted without filters. Search results were combined and duplicates were removed. The selection was blinded by two independent researchers using the Rayyan application. RESULTS: Fifty studies were assessed for quality and 23 were included. Individual semi-structured interviews and focus groups were widely used to explore patient experience after a PE episode. Patients described deterioration in their quality of life, their psychological state and an initial feeling of carer abandonment. The trends observed appear to be more pronounced in patients with an episode characterized as unprovoked. CONCLUSION: These preliminary results call for further longitudinal studies, the objective being to better understand the evolution of these factors in the short and long terms.

Highlighting extended-spectrum beta-lactamase-producing Klebsiella pneumoniae outbreak by routine genomic typing.

Whole genome sequencing has become the gold standard for any microbiological investigations. Taking the opportunity to doing it prospectively and routinely allowed to detect undeclared outbreaks. Thanks to that, we investigated and ended a rare epidemic extended-spectrum beta-lactamase-producing Klebsiella pneumoniae ST584 strain on two intensive care units over a 4-month period.

[Patient expectations in asthma care]. / Attentes des patients asthmatiques vis-à-vis de leur prise en charge.

Asthma, a common chronic disease characterized by variable levels of severity, requires patient-centered management to achieve the best health outcomes. Studies have highlighted the gap between consensus management recommendations and patient goals, which represent a potential source of therapeutic wandering and of poor compliance. Patient expectations are continually evolving and are dependent on knowledge, feelings and individual experience. From this perspective, listening carefully to patients and caregivers makes it easier to exchange views and define common goals. The active participation of patients at all levels of decision-making and transmission of information may improve asthma control and other quality of life parameters.

[Pneumo-Quest: A standardised self-questionnaire to be completed at home before a first appointment at a respiratory clinic]. / Pneumo-Quest, auto-questionnaire standardisé à compléter au domicile avant une première consultation en pneumologie : étude de validation.

The Pneumo-Quest self-questionnaire was developed to standardize the practice of recollection when welcoming a new patient. It consists of 82 main questions and 34 subsidiary questions to be completed at home by the patients before their first visit to a pulmonologist. This evaluation was carried out on the basis of 137 returned questionnaires. The feasibility (main criterion) was good with 93±5% of the questions answered and an average completion time of 15.1±9.8minutes (mean±SD). The reliability of the responses (secondary criterion) was good with the agreement between the patient's response and the doctor's opinion being excellent or good for the majority of medical histories and treatments, as evidenced by the high values of the kappa coefficient (>0.90; <0.90; <0.75). Patient and physician perception of the questionnaire was good with 99% and 90% positive ratings, respectively. The use of the questionnaire was unhelpful in the course of the consultation in only 2% of cases. Doctors found the tool useful for obtaining a comprehensive history in 87% of cases and patients declared that it helped them "forgot nothing" in 93% of the cases. The questionnaire helped the doctor to identify the patient's problems rapidly in 71% of cases and saved time in 64%. These positive results encourage a wide dissemination of the questionnaire (www.pneumo-quest.com).

Exogenous acquisition of Pseudomonas aeruginosa in intensive care units: a prospective multi-centre study (DYNAPYO study).

BACKGROUND: Pseudomonas aeruginosa remains one of the most common nosocomial pathogens in intensive care units (ICUs). Although exogenous acquisition has been widely documented in outbreaks, its importance is unclear in non-epidemic situations. AIM: To elucidate the role of exogenous origin of P. aeruginosa in ICU patients. METHODS: A chronological analysis of the acquisition of P. aeruginosa was performed using samples collected in 2009 in the DYNAPYO cohort study, during which patients and tap water were screened weekly. Molecular relatedness of P. aeruginosa isolates was investigated by pulsed-field gel electrophoresis. Exogenous acquisition was defined as identification of a P. aeruginosa pulsotype previously isolated from another patient or tap water in the ICU. FINDINGS: The DYNAPYO cohort included 1808 patients (10,402 samples) and 233 water taps (4946 samples). Typing of 1515 isolates from 373 patients and 375 isolates from 81 tap water samples identified 296 pulsotypes. Analysis showed exogenous acquisition in 170 (45.6%) of 373 patients. The pulsotype identified had previously been isolated from another patient and from a tap water sample for 86 and 29 patients, respectively. The results differed according to the ICU. CONCLUSION: Exogenous acquisition of P. aeruginosa could be prevented in half of patients. The overall findings of this survey support the need for studies on routes of transmission and risk assessment approach to better define how to control exogenous acquisition in ICUs.

Fenfluramine-like cardiovascular side-effects of benfluorex.

Since 1976, benfluorex has been approved in Europe as a hypolipidemic and hypoglycemic drug, and is commonly used in the treatment of the metabolic syndrome. As a derivative of fenfluramine with an appetite suppressant action, benfluorex is preferentially used in overweight patients. In contrast to fenfluramine and dexfenfluramine, to date, benfluorex has not been reported to be associated with frequent cardiovascular side-effects. The present study reports five cases of severe pulmonary arterial hypertension and one case of valvular heart disease occurring in patients exposed to benfluorex. These individuals were middle age, diabetic females with a body mass index ranging 24.2-49 kg x m(-2). No definite causal effect for cardiovascular disease with benfluorex can be drawn from such case reports. However, as benfluorex, like dexfenfluramine and fenfluramine, is metabolised into active metabolite norfenfluramine, further extensive assessment of drug exposure in newly diagnosed pulmonary arterial hypertension or valvular heart disease patients is warranted.

Masitinib, a c-kit/PDGF receptor tyrosine kinase inhibitor, improves disease control in severe corticosteroid-dependent asthmatics.

BACKGROUND: Masitinib is a tyrosine kinase inhibitor targeting stem cell factor receptor (c-kit) and platelet-derived growth factor (PDGF) receptor, which are expressed on several cell types including mast cells and bronchial structural cells, respectively. We hypothesized that c-kit and PDGF receptor inhibition may decrease bronchial inflammation and interfere with airway remodeling, which are crucial features of severe asthma. OBJECTIVES: The primary endpoint was the percent change from baseline in oral corticosteroids after 16 weeks of treatment. Change in asthma control (asthma control questionnaire), exacerbation rate, pulmonary function tests, rescue medication requirement and safety were secondary endpoints. METHODS: A 16-week randomized, dose-ranging (3, 4.5, and 6 mg/kg/day), placebo-controlled study was undertaken in 44 patients with severe corticosteroid-dependent asthma who remained poorly controlled despite optimal asthma management. RESULTS: At 16 weeks of treatment, a comparable reduction in oral corticosteroids was achieved with masitinib and placebo (median reduction of -78% and -57% in the masitinib and placebo arms, respectively). Despite this similar reduction, the Asthma Control Questionnaire score was significantly better in the masitinib arm as compared to placebo with a reduction by 0.99 unit at week 16 (P < 0.001) vs 0.43 unit in the placebo arm. Masitinib therapy was associated with more transient skin rash and edema. CONCLUSIONS: Masitinib, a c-kit and PDGF-receptor tyrosine kinase inhibitor, may represent an innovative avenue of treatment in corticosteroid-dependent asthma. These preliminary results warrant further long-term clinical studies in severe asthma

[Risk factors for thromboembolic disease in young women-the role of hormones]. / Facteurs de risque de maladie veineuse thromboembolique chez les jeunes femmes en contexte hormonal: Risque de survenue d'une maladie thromboembolique veineuse chez les membres de la famille au 1er degré de femmes ayant une maladie veineuse thromboembolique en contexte hormonal : étude « FIT ­ H ¼.

Hormonal exposure in young women increases the risk of venous thromboembolic disease (VTE). Thrombophilia testing is often proposed in women of childbearing age before the initiation of contraception. However, the presence of a familial history of VTE has the potential to be more accurate than the presence of inherited thrombophilia. OBJECTIVE: To demonstrate an association between the risk of VTE in young women with hormonal exposure (pregnancy or oral contraceptive use) and the presence of a previous episode of VTE in their first-degree relatives, according to whether or not a detectable inherited thrombophilia was present. METHODS: We will perform a multicenter case-control cross-sectional study. The main risk factor is defined by the presence of a symptomatic VTE in young women with hormonal exposure. The principle variable is the presence of an objectively diagnosed episode of VTE in first-degree relatives. We will need to include 2,200 family members in 440 cases. EXPECTED RESULTS: We expect to improve understanding of the thrombotic risk in first-degree relatives of patients in hormonal context with or without a past history of VTE.

[Prolongation of anti vitamin K treatment for 18 months versus placebo after 6 months treatment of a first episode of ideopathic pulmonary embolism: a mutlicentre, randomised double blind trail. The PADIS-EP Trial]. / Prolongation d'un traitement par antivitamine K pendant dix-huit mois versus placebo au décours d'un premier épisode d'embolie pulmonaire idiopathique traité six mois: un essai randomisé multicentrique en double aveugle. Essai "PADIS-EP".

BACKGROUND: After stopping a 3 to 6 months course of oral anticoagulation for a first episode of idiopathic venous thromboembolism (VTE), the risk of recurrent VTE is high (10% per year). In this setting, international guidelines recommend at least 6 months treatment. However, this recommendation is not satisfactory for the following reasons: (1) no randomized trial has compared 6 months to extended duration (2 years) anticoagulation; and (2), even though the frequency of recurrent VTE is similar after pulmonary embolism (PE) and deep vein thrombosis (DVT), the fatality rate of recurrent VTE after PE is higher than that after DVT. METHODS: A French multicentre double blind randomized trial. The main objective is to demonstrate, after a first episode of symptomatic idiopathic PE treated for 6 months using a vitamin K antagonist, that extended anticoagulation for 18 months (INR between 2 and 3) is associated with an increased benefit / risk ratio (recurrent VTE and severe anticoagulant-related bleeding) compared to placebo. The double blind evaluation is ensured using by active warfarin and placebo, and blinded INR. The protocol was approved by the ethics board of the Brest Hospital on the 7th of March 2006. For an alpha risk of 5% and a beta risk of 20%, the estimated sample size is 374 patients. EXPECTED RESULTS: This study has the potential to: (1) demonstrate that the benefit / risk ratio of extended anticoagulation for 18 months is higher than that observed with placebo in patients with a first episode of idiopathic PE initially treated for 6 months, during and after the treatment period; and (2) to validate or invalidate the contribution of isotope lung scans, lower limb Doppler ultrasound and D-Dimer at 6 months of treatment as predictors of recurrent VTE (medico-economic analysis included).

[Care of acute pulmonary embolism]. / Prise en charge de l'embolie pulmonaire à la phase aiguë

Pulmonary embolism (PE) is common and potentially serious. Three stages are described: mild PE, moderate PE (associated with an ultrasound right ventricular dysfunction) and severe PE (associated with a shock). In the first category, the prognosis is highly favourable (mortality under 5%) and the initial phase of anticoagulant treatment is well documented and codified: the treatment is based on heparin therapy (non fractionated or derivatives) and oral anticoagulants. In the severe forms, fibrinolysis is indicated in addition to the heparin therapy, given the very high mortality (up to 50%). However, the optimum care of moderate PE (intermediate mortality between 10 and 15%) remains uncertain, due to the inability to demonstrate a benefits-risk ratio in favour of fibrinolysis. In addition, this entity is still poorly defined. Although cardiac ultrasound data is useful, other parameters, such as pro-BNP, provide a better identification of these forms of intermediate prognosis. Although the evaluation of the new oral and injectable anticoagulants is promising, it mainly concerns mild PE. In addition, trials are currently under way in patients with a gloomier prognosis. The purpose is to validate or invalidate the indication of classic treatments (fibrinolysis) or new treatments (optional caval filters).

[Pulmonary embolism: the extent of computerized tomography]. / Embolie pulmonaire : faut-il tendre vers le << tout angioscanner >> ?

The use of computerised tomography in the diagnosis of pulmonary embolism has been the subject of clinical research while, at the same time, technical progress has provided the current multidetector-row spiral equipment. Computerised tomography has been assessed both with respect to reference strategies as well as in extensive pragmatic trials. The preliminary evaluation of the clinical probability and the assay of d-dimers has progressively become imperative. The value of the venous doppler ultrasound of the legs, in particular in the elderly, is limited by the variable accessibility according to the centre. In rare cases, uncertainty persists, for example with a good quality negative multidetector-row spiral computerised tomography associated with a high clinical probability, leaving room for complementary explorations. The confrontation between clinicians and radiologists is then all the more pertinent.

[Venous thromboembolism and cancer]. / Maladie veineuse thromboembolique et cancer.

Cancer and venous thromboembolism (VTE), VTE and cancer: there is a close bond between these two diseases. On the one hand, a cancer patient runs a high risk of developing VTE. Certain cancer-specific factors, such as its metastatic nature increase this risk. The means involved in the care of cancer (insertion of a venous catheter, chemotherapy, etc.) also increase the probability of a thromboembolism. On the other hand, VTE, especially if it is idiopathic, may be the harbinger of a neoplasm. The present paper involves the dual nature of this relationship, first dealing with several points specific to the occurrence of VTE in a cancer patient, before dealing with the specific care in a curative and prophylactic situation. VTE is then considered as a clinical manifestation prior to a cancer. Several characteristics evoking an underlying neoplasm are known. However, the benefits of the screening for cancer when confronted with an episode of VTE remains to be debated.

[Diagnosis and care of postembolic pulmonary hypertension: the role of the pneumologist]. / Diagnostic et prise en charge de l'hypertension pulmonaire postembolique : le rôle du pneumologue.

The prognosis of postembolic pulmonary hypertension, a rare and serious disease, has been transformed with the curative intervention of pulmonary endarteriectomy. The screening is based on two key non invasive examinations, the cardiac ultrasound and ventilation-perfusion scintigraphy. The confirmation of the diagnosis and the determination of the best therapeutic options then relies on the expertise of the national reference centre, based on the haemodynamics and the morphological data provided by pulmonary angiography and spiral computerised tomography. Although the technique of endarteriectomy is fully validated, a drug approach is in the assessment process, both in the inoperable forms or when confronted with persistent postsurgical pulmonary hypertension.

[A bilateral diaphragmatic paralysis due to Parsonage and Turner syndrome--its evolution over eight years]. / Paralysie diaphragmatique bilatérale imputable à un syndrome de Parsonage-Turner. Evolution à huit ans.

The diaphragmatic paralysis is a rare disease whose causes and evolving forms are numerous. We report the development to eight years of paralysis diaphragmatic bilateral attributed to a Parsonage-Turner syndrome: the lack of recovery is proved by respiratory functional follow-up. The therapeutic possibilities, limited, are discussed.

Risk factors for colonization and infection by Pseudomonas aeruginosa in patients hospitalized in intensive care units in France.

OBJECTIVE: To assess the role of environment, medical care and individual risks factors for P. aeruginosa colonization and infection. STUDY DESIGN AND SETTING: A French multicentric prospective study involved ten ICUs for a five months period. Every adult patient newly hospitalized in ICUs with no P. aeruginosa carriage up to 48 hours after admission was included and weekly screened before discharge or death. Screening swabs were either rectal, sputum or oropharyngeal samples. Hydric environment was also sampled each week. Data on patient clinical features, environmental and device exposures, and antibiotics supports were regularly collected. Multivariate analysis was performed with a multistate model. RESULTS: The overall prevalence of P. aeruginosa carriage was 15.3% (201/1314). Risk factors associated with patient colonization were: use of inactive antibiotics against P. aeruginosa (HR = 1.60 [1.15-2.21] p<0.01), tap water contamination at the entry in the room (HR = 1.66 [1.01-2.27] p<0.05) and mechanical invasive ventilation (HR = 4.70 [2.66-8.31] p<0.0001). Active antibiotics prevented from colonization (HR = 0.67 [0.48-0.93] p = 0.02) and from infection (HR = 0.64 [0.41-1.01] p = 0.05). Interaction between hydric environment antibiotics support was not statistically associated with patient colonization. CONCLUSION: Hydric contamination and antibiotics pressure seem to remain key independent risk factors in P. aeruginosa colonization. These results advocate the need to carry on preventive and targeted interventions toward healthcare associated infections.