Severe asthma: One disease and multiple definitions

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods: Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results: 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions: The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Kinetic-based indexes for the functional evaluation of gait in diplegic children: a preliminary report

We evaluated the feasibility of a set of indexes based on ground reaction forces to discriminate between the degree of severity of spastic diplegia, identified via Gross Motor Function Classification System (GMFCS). A stepwise discriminant ordinal regression analysis performed on a sample of 58 children returned a subset of variables related to the ratio between braking and propulsive vertical forces and anteroposterior timings. Rather, parameters concerning bilateral symmetry were poorly discriminating. The relative simplicity of the selected indexes allows for their easy implementation on existing gait analysis applications for screening purposes

Anticipatory postural adjustments and kinematic analysis of step ascent and descent in adults with Down syndrome

BackgroundStep ascent and descent is one of the most common daily tasks. Although it is generally considered a rather simple movement, it may not be so easy for participants with Down syndrome. MethodsA kinematic analysis of step ascent and descent was conducted, and a comparison between 11 adult participants with Down syndrome and 23 healthy participants was carried out. This analysis was accompanied by a posturographic analysis with the aim of evaluating aspects relating to balance. The principal aim of postural control was to investigate the trajectory of the centre of pressure, while the kinematic analysis of movement included the following: (1) the analysis of anticipatory postural adjustments, (2) the calculation of spatiotemporal parameters and (3) the evaluation of articular range of motion. ResultsA general instability for participants with Down syndrome, highlighted in the postural control by an increased anteroposterior and mediolateral excursion, when the test was conducted with both open and closed eyes, was found out. Regarding anticipatory postural adjustments, this deficit in balance control was revealed by the execution of small steps before completing the movement and by a much longer preparation time anticipating the movement. In addition, the kinematic analysis reported a longer ascent and descent time and a lower velocity, accompanied by a greater rising of both limbs in ascent, which indicates an increased perception of the obstacle. Finally, a wider trunk range of motion in both the sagittal and frontal planes was revealed. ConclusionsAll the data confirm a compromised balance control that could be associated with damage to the sensorimotor centre

Men and women with Down syndrome exhibit different kinematic (but not spatio-temporal) gait patterns

Background: Gait phenotypes are well documented in people with Down syndrome (pwDS), but sex-related differences are still unexplored. This study investigated the existence of possible differences in spatio-temporal and kinematic parameters of gait between men and women with DS using quantitative three-dimensional gait analysis. Methods: Gait patterns of 117 pwDS (53 F, 64 M) who underwent a computerised gait analysis from 2002 to 2017 were retrospectively analysed to obtain spatio-temporal gait parameters and kinematics in the sagittal plane at hip, knee and ankle joints, as well as foot progression. Results: Overall, when considered as a single group, the gait patterns found for pwDS confirmed the findings of previous studies. However, when analysed by sex, our data revealed that women with DS exhibit a larger hip flexion at late stance (42% to 54% of the gait cycle) and reduced knee flexion at the beginning of the swing phase (61% to 69% of the gait cycle). In contrast, men are characterised by larger foot extra-rotation angles through most of the stance phase (from 0% to 55% of the gait cycle) and at the end of the swing phase (92% to 99% of the gait cycle). No differences between men and women with DS were found concerning ankle dorsi- plantar-flexion or in all spatio-temporal parameters normalised by individuals' anthropometry, excluding cadence (higher in women). Conclusions: The findings of the present study highlight the need to investigate gait dysfunctions in pwDS by taking their sex into consideration. Such an approach may be useful not only in gaining a better understanding of the pathophysiology of gait disturbances associated with DS but also in supporting a better orientation of rehabilitative treatments

A Study on the Intersection of Ground Reaction Forces during Overground Walking in Down Syndrome: Effects of the Pathology and Left-Right Asymmetry

Motor dysfunctions in patients with Down Syndrome (DS) result in poor locomotion and an altered gait phenotype, characterized by compromised stability management and frequent bilateral asymmetries. Directing ground reaction forces to a point above the center of mass, referred to as the virtual pivot point (VPP), is one means of maintaining stability during walking. This cross-sectional observational study compared the dynamic gait function of 33 individuals with DS (mean age: 17.7 +/- 6.4 years, 13 females) to a group of 36 healthy controls (mean age: 15.5 +/- 6.1 years, 15 females), using the concept of the VPP. Results showed that the VPP was located more anteriorly in individuals with DS compared to healthy controls, with no differences in the variability (R-2) or symmetry of VPP coordinates. This anterior VPP position is likely due to the larger hip moments observed in patients with DS during the propulsive phase of stance. High R-2 values in DS suggest that the VPP is strongly related to dynamic stability during walking