ABSTRACT
Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for patients with high-risk relapsed/refractory Hodgkin lymphoma (R/R HL). The AETHERA study showed survival gain with Brentuximab Vedotin (BV) maintenance after ASCT in BV-naive patients, which was recently confirmed in the retrospective AMAHRELIS cohort, including a majority of BV-exposed patients. However, this approach has not been compared to intensive tandem auto/auto or auto/allo transplant strategies, which were used before BV approval. Here, we matched BV maintenance (AMAHRELIS) and tandem SCT (HR2009) cohorts, and observed that BV maintenance was associated with better survival outcome in patients with HR R/R HL.
Subject(s)
Hematopoietic Stem Cell Transplantation , Hodgkin Disease , Immunoconjugates , Humans , Brentuximab Vedotin , Hodgkin Disease/drug therapy , Retrospective Studies , Immunoconjugates/therapeutic use , Stem Cell Transplantation , Cohort StudiesABSTRACT
Hyperventilation syndrome (HVS) is a common source of dyspnea and disability. While pulmonary rehabilitation (PR) including breathing exercises is indicated, randomized controlled trial are warranted to recommend one type of breathing exercise than another. We aimed to compare during PR, the effect of 5 sessions of nasal ventilation exercise (NV+PR) versus voluntary hypoventilation (vHV+PR) on exercise dyspnea (primary outcome) and capacity and health-related quality of life in patients. In this open label randomized controlled trial, 19 HVS patients (age=48.3 ± 15.2 y.o, female/male=18/1, Nijmegen score=33 ± 7.7) were randomized in a NV+PR (n = 9) or vHV+PR (n = 10) group. Modified Medical Research Council (mMRC) dyspnea, 6-minute walking distance (6MWD) with nasal/oral ventilation were assessed before and after 3 months of PR, and questionnaires (Nijmegen, VQ-11). There was a significant effect of PR of but no significant difference between groups in the improvements of dyspnea@max exercise (time effect (T): p < 0.01; group (G): p = 0.63; group*time interaction (G*T): p = 0.49), mMRC dyspnea (T: p < 0.01; G: p = 0.45; G*T: p = 0.62), 6MWD (T: p < 0.05; G: p = 0.36; G*T: p = 0.31), VQ-11 (T: p < 0.001; G: p = 0.16; G*T: p = 0.09) and plasma HCO3- (T: p < 0.05; G: p = 0.93; G*T; p = 0.36), Yet, Nijmegen score (T: p < 0.01; G: p = 0.32; G*T: p < 0.05) improvement was larger in NV+PR group. The exercise oronasal breathing shift during the 6MWT was significantly delayed in all patients (T: p < 0.05; G: p = 0.30; G*T: p = 0.32) and positively correlated with plasma HCO3-(r = 0.42; p < 0.05). Nasal exercise was not superior versus voluntary hypoventilation during PR in HVS patients. Yet, nasal exercise appeared feasible, leading to acquisition of a nasal breathing pattern during walking, improvement of PR outcomes and ventilatory alkalosis. The link between nasal breathing and hyperventilation is discussed in the light of the nasal ventilation rhythm in the limbic system and its role on the limbic emotional and ventilatory functions.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Male , Female , Adult , Middle Aged , Pulmonary Disease, Chronic Obstructive/rehabilitation , Quality of Life , Hyperventilation , Hypoventilation , Feasibility Studies , Pilot Projects , Dyspnea/rehabilitation , Respiration , Exercise ToleranceABSTRACT
BACKGROUND AND PURPOSE: Carotid webs (CaW) may be an under-recognized cause of anterior circulation cryptogenic ischemic stroke (ACIS). Prevalence is still unknown in European patients with ACIS. OBJECTIVE: To evaluate the prevalence of CaW in ACIS and describe patients with CaW phenotype in a cohort of patients from a French stroke center. METHODS: We conducted a retrospective monocentric cohort study from 01/01/2015 to 31/12/2019 (Montpellier University Hospital, France), in consecutive anterior ischemic stroke (AIS) patients ≤65 years old from a prospective stroke database. Using ASCOD phenotyping, ACIS patients were selected and cervical CTA were reviewed to find CaW. RESULTS: Among 1053 consecutive AIS patients, 266 ACIS patients with CTA were included. Among patients included (mean age 50, women 58%), CaW was in the ipsilateral carotid (iCaW) in 21 patients: 7.9% (95%CI [4.6-11.1]), (mean age 51, 11 women, 16 Caucasian). iCaW were uncovered during study review of CTA in 6/21 (29%) patients. Comparison between patients with iCaW and those without iCaW showed no differences except that of a higher rate of intracranial large vessel occlusion (LVO) (62.4 vs 37.6%; p = 0.03). Patients with iCaW under conservative medical therapy had an annualized stroke recurrence rate (SRR) of 11.4% (95%CI [8.4-15.1]. CONCLUSIONS: iCaW was identified as a source of stroke in about 8% of a French population ≤65 years with ACIS. iCaW was associated with a higher rate of LVO and a high SRR under conservative medical therapy.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Aged , Cohort Studies , Female , Humans , Middle Aged , Prevalence , Prospective Studies , Retrospective Studies , Stroke/epidemiologyABSTRACT
OBJECTIVES: To assess CT signs to discriminate an appendiceal tumor versus a non-tumoral appendix in an acute appendicitis context. METHODS: A 10-year bicentric retrospective case-control study was performed in adults. Patients with a histopathological appendiceal tumor and appendicitis were paired for age and sex with patients with non-tumorous appendicitis (1/3 ratio, respectively). Two senior radiologists blindly analyzed numerous CT findings with final consensus to perform univariate and multivariate statistical analyses. A diagnostic CT scan score was calculated with a bootstrap internal validation. Reproducibility was assessed based on the kappa statistic. RESULTS: A total of 208 patients (51 +/- 21 years; 114 males) were included (52 patients in the tumor group and 156 in the non-tumor group). In the multivariate analysis, an appendicolith and fat stranding were protective factors with OR = 0.2 (p = 0.01) and OR = 0.3 (p = 0.02), respectively, while mural calcifications (OR = 47, p = 0.0001), an appendix mass (OR = 7.1, p = 0.008), a focal asymmetric wall abnormality (OR = 4.9, p = 0, 001), or a ≥ 15 mm diameter (OR = 3.5, p = 0.009) were positive predictive factors of an underlying tumor. Using a ≥1 cut-off, our diagnostic score had an AUC = 0.87 (95 % CI, 0.82-0.93) and a positive likelihood ratio = 13.5 (95 % CI, 6.7-27.1). CONCLUSION: We developed a reliable scoring system based on CT findings, which is highly predictive of an underlying appendiceal neoplasm in an appendicitis context using a ≥1 cut-off.
Subject(s)
Appendiceal Neoplasms , Appendicitis , Acute Disease , Adult , Appendiceal Neoplasms/diagnostic imaging , Appendicitis/diagnostic imaging , Appendicitis/surgery , Case-Control Studies , Humans , Male , Reproducibility of Results , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
Agreement between observers (i.e., inter-rater agreement) can be quantified with various criteria but their appropriate selections are critical. When the measure is qualitative (nominal or ordinal), the proportion of agreement or the kappa coefficient should be used to evaluate inter-rater consistency (i.e., inter-rater reliability). The kappa coefficient is more meaningful that the raw percentage of agreement, because the latter does not account for agreements due to chance alone. When the measures are quantitative, the intraclass correlation coefficient (ICC) should be used to assess agreement but this should be done with care because there are different ICCs so that it is important to describe the model and type of ICC being used. The Bland-Altman method can be used to assess consistency and conformity but its use should be restricted to comparison of two raters.
Subject(s)
Radiology , Humans , Observer Variation , Radiography , Reproducibility of ResultsABSTRACT
OBJECTIVE: The medical world is continuously evolving, with techniques being created or improved almost daily. Immersive virtual reality (VR) is a technology that could be harnessed to develop tools that meet the educational challenges of this changing environment. We previously described the immersive tutorial, a 3D video (filmed from the first-person point of view), displayed on a VR application. This tool offers access to supplementary educational data in addition to the video. Here we attempt to assess improvement in learning a technique using this new educational format. MATERIAL AND METHODS: We selected a single neurosurgical technique for the study: external ventricular drainage. We wrote a technical note describing this procedure and produced the corresponding immersive tutorial. We conducted a prospective randomized comparative study with students. All participants read the technical note, and one group used the immersive tutorial as a teaching supplement. The students completed a multiple-choice questionnaire immediately after the training and again at six months. RESULTS: One hundred seventy-six fourth-year medical students participated in the study; 173 were included in assessing the immediate learning outcomes and 72 were included at the six-month follow-up. The VR group demonstrated significantly better short-term results than the control group (P=0.01). The same trend was seen at six months. CONCLUSION: To our knowledge, this study presents one of the largest cohorts for VR. The use of the immersive tutorial could enable a large number of healthcare professionals to be trained without the need for expensive equipment.
Subject(s)
Neurosurgery/education , Virtual Reality , Adult , Cerebral Ventricles , Clinical Competence , Drainage/methods , Educational Measurement , Female , Humans , Male , Problem-Based Learning , Prospective Studies , Simulation Training , Students, Medical , Surveys and Questionnaires , Video RecordingABSTRACT
BACKGROUND: Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. OBJECTIVES: To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. METHODS: We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. CONCLUSIONS: A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.
Subject(s)
Ectodermal Dysplasia/diagnosis , Failure to Thrive/diagnosis , Heart Defects, Congenital/diagnosis , Acitretin/administration & dosage , Administration, Cutaneous , Administration, Oral , Adolescent , Child , Child, Preschool , Costello Syndrome/diagnosis , Diagnosis, Differential , Ectodermal Dysplasia/drug therapy , Ectodermal Dysplasia/genetics , Facies , Failure to Thrive/drug therapy , Failure to Thrive/genetics , Female , France , Genetic Association Studies , Heart Defects, Congenital/drug therapy , Heart Defects, Congenital/genetics , Humans , MAP Kinase Kinase 1/genetics , MAP Kinase Kinase 2/genetics , Male , Mutation , Noonan Syndrome/diagnosis , Prospective Studies , Proto-Oncogene Proteins B-raf/genetics , Sirolimus/administration & dosage , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise. OBJECTIVES: To describe the dermatological manifestations of NS, compare them with the literature findings, and test for dermatological phenotype-genotype correlations with or without the presence of PTPN11 mutations. METHODS: We performed a large 4-year, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and café-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations. CONCLUSIONS: The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.
Subject(s)
Genetic Association Studies , Noonan Syndrome/complications , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Skin Diseases/genetics , Adolescent , Adult , Aged , Child , Child, Preschool , DNA Mutational Analysis , Female , Humans , Infant , Male , Middle Aged , Mutation , Noonan Syndrome/genetics , Phenotype , Prospective Studies , Young AdultABSTRACT
Coarse-grained molecular dynamics simulations are used to elucidate molecular mechanisms responsible for different mechanical behaviours of elastomers containing spherical particles with different volume fractions. We observe that different filler volume fractions result in qualitatively different responses of the polymer nanocomposite to tensile strain. At relatively low filler volume fraction a yield drop appears in the stress-strain curve. As the filler volume fraction increases there is a reduction in the rate of plastic hardening, becoming plastic softening at sufficiently high filler volume fraction. We demonstrate that these behaviours are a result of the network formed by the polymer chains and filler particles. We identify three distinct molecular structural motifs between polymer and filler particles whose relative prevalence varies with the filler volume fraction and as the system is dynamically strained. We show how this evolution in molecular structure is directly linked to the observed mechanical response.
ABSTRACT
BACKGROUND: Identification of myositis-specific autoantibodies (MSAs) for dermatomyositis (DM) could allow the characterization of an antibody-associated clinical phenotype. OBJECTIVE: We sought to define the clinical phenotype of DM and the risk of cancer, interstitial lung disease (ILD) and calcinosis based on MSA. METHODS: A 3.5-year multicentre prospective study of adult DM patients was conducted to determine the clinical phenotype associated with MSAs and the presence of cancer, ILD and calcinosis. RESULTS: MSAs were detected in 47.1% of 117 included patients. Patients with antimelanoma differentiation-associated protein-5 antibodies (13.7%) had significantly more palmar violaceous macules/papules [odds ratio (OR) 9.9], mechanic's hands (OR 8), cutaneous necrosis (OR 3.2), articular involvement (OR 15.2) and a higher risk of ILD (OR 25.3). Patients with antitranscriptional intermediary factor-1 antibodies (11.1%), antinuclear matrix protein-2 antibodies (6.8%) and antiaminoacyl-transfer RNA synthetase (5.1%) had, respectively, significantly more poikiloderma (OR 5.9), calcinosis (OR 9.8) and articular involvement (OR 15.2). Cutaneous necrosis was the only clinical manifestation significantly associated with cancer (OR 3.1). CONCLUSION: Recognition of the adult DM phenotype associated with MSAs would allow more accurate appraisal of the risk of cancer, ILD and calcinosis.
Subject(s)
Antibodies/blood , Dermatomyositis/blood , Dermatomyositis/complications , Interferon-Induced Helicase, IFIH1/immunology , Neoplasms/complications , Skin/pathology , Adenosine Triphosphatases/immunology , Adult , Aged , Aged, 80 and over , Amino Acyl-tRNA Synthetases/immunology , Calcinosis/blood , Calcinosis/complications , DNA-Binding Proteins/immunology , Female , Hand Dermatoses/blood , Hand Dermatoses/complications , Humans , Joint Diseases/blood , Joint Diseases/complications , Lung Diseases, Interstitial/blood , Lung Diseases, Interstitial/complications , Male , Middle Aged , Necrosis , Phenotype , Prospective Studies , Transcription Factors/immunology , Young AdultABSTRACT
BACKGROUND: Behavioural pain tools are used in Intensive Care Unit (ICU) patients unable to self-report their pain-intensity but need sustained efforts to educate and train the ICU team because of the subjective nature of these clinical tools. This study measured the validity and performance of an electrophysiological monitoring tool based on the spectral analysis of heart rate variability, the Analgesia Nociception Index (ANI) which varies from 0 (minimal parasympathetic tone, maximal stress-response and pain) to 100 (maximal parasympathetic tone, minimal stress-response and pain). METHODS: Mean-ANI (ANIm) and Instant-ANI (ANIi) were continuously recorded then compared with the Behavioral Pain Scale (BPS) before, during and after routine care procedures in critically-ill non-comatose patients. RESULTS: 969 assessments were performed in 110 patients. ANIi was the most discriminative pain tool. It was significantly correlated with BPS (r=-0.30; 95%CI -0.37 to -0.25; P<0.001). For an ANIi threshold of 42.5, the sensitivity, specificity, positive and negative predictive values were respectively 61.4%, 77.4%, 37.0%, and 90.4%. Compared with the BPS, ANIi had no significantly different ability to change during turning and tracheal-suctioning but changed significantly more during dressing change. ANIi increased independently with age, obesity and severity of illness, and controlled mechanical-ventilation, vasopressors use and analgesia. ANIi decreased independently when vigilance status and respiratory rate increased. ANIm demonstrated poor psychometric properties to detect pain. CONCLUSIONS: Despite low sensitivity/specificity, ANIi≥43 had a Negative-Predictive-Value of 90%. Hence ANIi may be of highest benefit for excluding significant pain. A randomized controlled trial should compare sedation-analgesia protocols based on ANIi to presently recommended behavioural-pain-tools.
Subject(s)
Analgesia/methods , Critical Care/methods , Heart Rate/physiology , Monitoring, Physiologic/methods , Nociception/physiology , Pain Measurement/methods , Aged , Critical Illness , Electrophysiological Phenomena , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and SpecificitySubject(s)
Health Care Costs , Pulmonary Disease, Chronic Obstructive/economics , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/therapy , Acute Disease , Disease Progression , France/epidemiology , Health Care Costs/statistics & numerical data , Hospitalization/economics , Hospitalization/statistics & numerical data , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , Socioeconomic FactorsABSTRACT
Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.
Subject(s)
Pulmonary Disease, Chronic Obstructive/therapy , Acute-Phase Reaction , Disease Progression , France , Humans , Language , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/pathology , Quality of Life , Severity of Illness Index , Societies, Medical/standards , Survival AnalysisABSTRACT
Chronic obstructive pulmonary disease (COPD) is the chronic respiratory disease with the most important burden on public health in terms of morbidity, mortality and health costs. For patients, COPD is a major source of disability because of dyspnea, restriction in daily activities, exacerbation, risk of chronic respiratory failure and extra-respiratory systemic organ disorders. The previous French Language Respiratory Society (SPLF) guidelines on COPD exacerbations were published in 2003. Using the GRADE methodology, the present document reviews the current knowledge on COPD exacerbation through 4 specific outlines: (1) epidemiology, (2) clinical evaluation, (3) therapeutic management and (4) prevention. Specific aspects of outpatients and inpatients care are discussed, especially regarding assessment of exacerbation severity and pharmacological approach.(AU)
La bronchopneumopathie chronique obstructive (BPCO) est la maladie respiratoire chronique dont le poids sur la santé publique est le plus grand par sa morbidité, sa mortalité et les dépenses de santé qu'elle induit. Pour les individus atteints, la BPCO est une source majeure de handicap du fait de la dyspnée, de la limitation d'activité, des exacerbations, du risque d'insuffisance respiratoire chronique et des manifestations extra-respiratoires qu'elle entraîne. Les précédentes recommandations de la Société de pneumologie de langue française (SPLF) sur la prise en charge des exacerbations BPCO date de 2003. Se fondant sur une méthodologie adaptée de GRADE, le présent document propose une actualisation de la question des exacerbations de BPCO en développant un argumentaire couvrant quatre champs d'investigation : (1) épidémiologie, (2) évaluation clinique, (3) prise en charge thérapeutique et (4) prévention. Les modalités spécifiques de la prise en charge hospitalière et ambulatoire y sont discutées, particulièrement les aspects relevant de l'évaluation de la sévérité de l'exacerbation et de la prise en charge pharmacologique.(AU)
Subject(s)
Humans , Bronchodilator Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Severity of Illness Index , Acute-Phase Reaction , Pulmonary Disease, Chronic Obstructive/prevention & controlABSTRACT
BACKGROUND: Several techniques exist for measuring central venous pressure (CVP) but little information is available about the accuracy of each method. The aim of this study was to compare different methods of CVP measurements in mechanically ventilated patients. METHODS: CVP was measured in mechanically ventilated patients without spontaneous breathing using four different techniques: 1) end expiratory CVP measurement at the base of the" c" wave (CVPMEASURED), chosen as the reference method; 2) CVP measurement from the monitor averaging CVP over the cardiac and respiratory cycles (CVPMONITOR); 3) CVP measurement after a transient withdrawing of mechanical ventilation (CVPNADIR); 4) CVP measurement corrected for the transmitted respiratory pressure induced by intrinsic PEEP (calculated CVP: CVPCALCULATED). Bias, precision, limits of agreement, and proportions of outliers (difference > 2 mm Hg) were determined. RESULTS: Among 61 included patients, 103 CVP assessments were performed. CVPMONITOR bias [-0.87 (1.06) mm Hg] was significantly different from those of CVPCALCULATED [1.42 (1.07), P < 0.001 and CVPNADIR (1.04 (1.29), P < 0.001]. The limits of agreement of CVPMONITOR [-2.96 to 1.21 mm Hg] were not significantly different to those of CVPNADIR (-1.49 to 3.57 mm Hg, P = 0.39) and CVPCALCULATED (-0.68 to 3.53 mm Hg, P = 0.31). The proportion of outliers was not significantly different between CVPMONITOR (n = 5, 5%) and CVPNADIR (n = 9, 9%, P = 0.27) but was greater with CVPCALCULATED (n = 16, 15%, P = 0.01). CONCLUSIONS: In mechanically ventilated patients, CVPMONITOR is a reliable method for assessing CVPMEASURED Taking into account transmitted respiratory pressures, CVPCALCULATED had a higher proportion of outliers and precision than CVPNADIR.
Subject(s)
Central Venous Pressure , Critical Illness , Respiration, Artificial , Adult , Aged , Blood Pressure Determination , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
Inconsistent results have been reported regarding IL-5 blockade treatment in asthma. There were no direct between-treatment comparisons. Only differences between each drug and placebo were studied. We identified all RCTs with anti-IL5 treatments for patients with asthma over the 1990-September 2015 period. RCTs were searched on Medline, Cochrane and Embase. At least 50 patients were enrolled in each study. Outcomes considered were exacerbation rate reduction, FEV1 changes, ACQ-5 improvement, adverse events and serious adverse events. A global meta-analysis was first conducted followed by an indirect comparison of each IL-5-targeting drug: benralizumab, reslizumab and mepolizumab. Further eosinophilic subgroup analysis and sensitivity analysis were also conducted in case of heterogeneity. Ten trials involving 3421 patients were eligible for meta-analysis. IL-5 blockade significantly reduced annual exacerbation rates vs. placebo by 40% [29-50] (P < 0.01, I2 = 0.61). ACQ-5 was significantly improved vs. placebo but below the recognized MCID level (-0.31 [-0.41, -0.21], P < 0.01, I2 = 0.11). FEV1 changes from baseline were improved vs. placebo by 0.09 L [0.05-0.12] (P < 0.01, I2 = 0.28). The subgroup analysis identified a slight additional improvement in mean treatment effects in eosinophilic (> 300 mm3 /L) patients with severe asthma. Similar patterns and rates of adverse events and severe adverse events were reported with the three drugs. The data interpretations were not affected by the sensitivity analysis. IL-5 blockade appears to be a relevant treatment strategy to improve severe asthma management, particularly for eosinophilic patients. No clear superiority appeared between the drugs when appropriate doses were compared.
Subject(s)
Anti-Asthmatic Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Asthma/drug therapy , Interleukin-5/antagonists & inhibitors , Anti-Asthmatic Agents/administration & dosage , Anti-Asthmatic Agents/adverse effects , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Asthma/diagnosis , Asthma/immunology , Asthma/metabolism , Biomarkers , Disease Progression , Humans , Randomized Controlled Trials as Topic , Respiratory Function Tests , Severity of Illness Index , Treatment OutcomeABSTRACT
BACKGROUND: To consolidate the new classification model addressed to the allergic and hypersensitivity conditions according to the International Classification of Diseases (ICD)-11 revision timeline, we here propose real-life application of quality assurance methodology to evaluate sensitivity and accuracy of the 'Anaphylaxis' subsection. METHODS: We applied field-testing methodology by analysing all the consecutive inpatients' files documented as allergies from the University Hospital of Montpellier electronic database for the period of 1 year. The files clinically validated as being anaphylaxis were manually blind-coded under ICD-10 and current ICD-11 beta draft. The correspondence of coding and the impressions regarding sensibility were evaluated. RESULTS: From all 2318 files related to allergic or hypersensitivity conditions, 673 had some of the anaphylaxis ICD-10 codes; 309 files (46%) from 209 patients had anaphylaxis and allergic or hypersensitivity comorbidities description. The correspondence between the two coders was perfect for 162 codes from all 309 entities (52.4%) (Cohen-kappa value 0.63) with the ICD-10 and for 221 codes (71.5%) (Cohen-kappa value 0.77) with the ICD-11. There was a high agreement regarding sensibility of the ICD-11 usability (Cohen-kappa value 0.75). CONCLUSION: We here propose the first attempt of real-life application to validate the new ICD-11 'Anaphylaxis' subsection. Clearer was the improvement in accuracy reaching 71.5% of agreement when ICD-11 was used. By allowing all the relevant diagnostic terms for anaphylaxis to be included into the ICD-11 framework, WHO has recognized their importance not only to clinicians but also to epidemiologists, statisticians, healthcare planners and other stakeholders.
Subject(s)
Anaphylaxis/diagnosis , International Classification of Diseases , Databases, Factual , Female , Humans , Male , Quality Assurance, Health Care , Reproducibility of Results , Sensitivity and Specificity , World Health OrganizationABSTRACT
BACKGROUND: Drug provocation tests (DPT) are commonly performed as part of ß-lactam (BL) allergy workup, in case of negative skin tests (ST) and in the absence of contraindications. The recommendations of learned societies have created a frame for DPT performance, but protocols vary widely between centres, generating various hypothesis-driven protocols (i.e. empirical dosing, driven by both safety concerns and practical aspects). METHODS: The primary objective of this retrospective analysis was to detect eliciting dose thresholds (reactive doses) during BL DPT, using the survival analysis method, in order to suggest optimal step doses. Our secondary objective was to evaluate the safety of our 30-min incremental 1-day protocol. The study included all the patients explored in the Allergy Unit of the University Hospital of Montpellier (France), between September 1996 and July 2015 for a suspicion of drug hypersensitivity reaction to BLs, with negative ST and positive DPT. RESULTS: During the study period, 182 positive DPT (accounting for 171 hypersensitive patients) were analysed. We identified eliciting thresholds, and we suggest the following steps for DPT to BLs: 5-15-30-50% of daily therapeutic dose (with additional lower steps for index reactions of anaphylaxis). We confirm the safety of 1-day protocol for immediate and mild nonimmediate reactors, for both children and adults, with a surveillance period of 2 h after the last administered dose, and a prolonged surveillance after discharge of 48 h. CONCLUSION: This data-driven approach in designing DPT protocols is a step forward in improving DPT standardization, starting with the most frequently tested drugs, BL antibiotics.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Drug Hypersensitivity/diagnosis , Skin Tests , beta-Lactams/administration & dosage , beta-Lactams/adverse effects , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Retrospective Studies , Skin Tests/methods , Symptom Assessment , Time Factors , Young AdultABSTRACT
OBJECTIVE: The primary goal of this study was to determine the prevalence and topographic distribution of spinal lesions in lower thoracic and lumbar spine on magnetic resonance imaging (MRI) in patients with recently diagnosed with spondyloarthritis. The secondary goal was to identify variables associated with vertebral patterns consistent with spondyloarthritis on MRI. PATIENTS AND METHODS: A total of 112 HLA-B27 positive patients with recently diagnosed spondyloarthritis were retrospectively included. There were 70 women and 42 men, with a mean age of 41 years±12 (SD) (range: 17-70years). Mean symptom duration was 1year (range: 0-7years). MRI examinations of sacroiliac joints and thoracolumbar spine were reviewed for the presence of bone marrow edema, chronic structural abnormalities, and vertebral patterns consistent with spondyloarthritis. Age, gender and disease duration of patients with vertebral patterns on MRI consistent with spondyloarthritis were compared with those without MRI signs of spondyloarthritis. RESULTS: Thirty-six patients (32.1%) showed spinal patterns of spondyloarthritis, including 16 patients (14.3%) with no associated inflammatory sacroiliitis. Posterior inflammatory lesions were present in 20.5% of patients. Posterior spinal inflammatory lesions were significantly associated with vertebral corner inflammatory lesions (P=0.03). There were no differences in age, sex or mean duration of symptoms between the two groups of patients. CONCLUSION: Spinal involvement is observed in 32.1% of HLA-B27 positive patients with recently diagnosed spondyloarthritis and is not associated with sacroiliitis in 14.3%. Age, gender or symptom duration are not associated with spinal involvement on MRI.