Background and purpose
The objective of this study was to analyze the relationship between motor complications and non‐motor symptom (NMS) burden in a population of patients with Parkinson’s disease ...(PD) and also in a subgroup of patients with early PD.
Methods
Patients with PD from the COPPADIS cohort were included in this cross‐sectional study. NMS burden was defined according to the Non‐Motor Symptoms Scale (NMSS) total score. Unified Parkinson’s Disease Rating Scale (UPDRS) part IV was used to establish motor complication types and their severity. Patients with ≤5 years of symptoms from onset were included as patients with early PD.
Results
Of 690 patients with PD (62.6 ± 8.9 years old, 60.1% males), 33.9% and 18.1% presented motor fluctuations and dyskinesia, respectively. The NMS total score was higher in patients with motor fluctuations (59.2 ± 43.1 vs. 38.3 ± 33.1; P < 0.0001) and dyskinesia (63.5 ± 40.7 vs. 41.4 ± 36.3; P < 0.0001). In a multiple linear regression model and after adjustment for age, sex, disease duration, Hoehn & Yahr stage, UPDRS‐III score and levodopa equivalent daily dose, UPDRS‐IV score was significantly related to a higher NMSS total score (β = 0.27; 95% confidence intervals, 2.81–5.61; P < 0.0001), as it was in a logistic regression model on dichotomous NMSS total score (≤40, mild or moderate vs. >40, severe or very severe) (odds ratio, 1.31; 95% confidence intervals, 1.17–1.47; P < 0.0001). In the subgroup of patients with early PD (n = 396; mean disease duration 2.7 ± 1.5 years), motor fluctuations were frequent (18.1%) and similar results were obtained.
Conclusions
Motor complications were frequent and were associated with a greater NMS burden in patients with PD even during the first 5 years of disease duration.
Allogeneic hematopoietic stem cell transplantation (HSCT) represents the best therapeutic option for many patients with acute myeloid leukemia (AML). However, relapse remains the main cause of ...mortality after transplantation. The detection of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in AML, before and after HSCT, has been described as a powerful predictor of outcome. Nevertheless, multicenter and standardized studies are lacking. A retrospective analysis was performed, including 295 AML patients undergoing HSCT in 4 centers that worked according to recommendations from the Euroflow consortium. Among patients in complete remission (CR), MRD levels prior to transplantation significantly influenced outcomes, with overall (OS) and leukemia free survival (LFS) at 2 years of 76.7% and 67.6% for MRD-negative patients, 68.5% and 49.7% for MRD-low patients (MRD < 0.1), and 50.5% and 36.6% for MRD-high patients (MRD ≥ 0.1) (
< 0.001), respectively. MRD level did influence the outcome, irrespective of the conditioning regimen. In our patient cohort, positive MRD on day +100 after transplantation was associated with an extremely poor prognosis, with a cumulative incidence of relapse of 93.3%. In conclusion, our multicenter study confirms the prognostic value of MRD performed in accordance with standardized recommendations.
(1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by β-III spectrin (
) mutations has emerged, mimicking spinocerebellar ataxia, autosomal recessive type 14 (SCAR14). The ...pattern of inheritance, however, resembles that of autosomal dominant classical spinocerebellar ataxia type 5 (SCA5). (2) Methods: In-depth phenotyping of two boys studied by a customized gene panel. Candidate variants were sought by structural modeling and protein expression. An extensive review of the literature was conducted in order to better characterize the
-associated NPCA. (3) Results: Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits. Both probands presented with progressive global cerebellar volume loss in consecutive cerebral magnetic resonance imaging studies, characterized by decreasing midsagittal vermis relative diameter measurements. Cortical hyperintensities were observed on fluid-attenuated inversion recovery (FLAIR) images, suggesting a neurodegenerative process. Each patient carried a novel de novo
substitution: c.193A > G (p.K65E) or c.764A > G (p.D255G). Modeling and protein expression revealed that both mutations might be deleterious. (4) Conclusions: The reported findings contribute to a better understanding of the
-associated phenotype. The mutations may preclude proper structural organization of the actin spectrin-based membrane skeleton, which, in turn, is responsible for the underlying disease mechanism.
Objectives
We investigated the natural history of patients after a first episode of acute heart failure (FEAHF) requiring emergency department (ED) consultation, focusing on: the frequency of ED ...visits and hospitalisations, departments admitting patients during the first and subsequent hospitalisations, and factors associated with difficult disease control.
Methods and results
We included consecutive patients diagnosed with FEAHF (either with or without previous heart failure diagnosis) in four EDs during 5 months in three different time periods (2009, 2011, 2014). Diagnosis was adjudicated by local principal investigators. The clinical characteristics of the index event were prospectively recorded, and all post‐discharge ED visits and hospitalisations related/unrelated to acute heart failure (AHF), as well as departments involved in subsequent hospitalisations were retrospectively ascertained. ‘Uncontrolled disease’ during the first year after FEAHF was considered if patients were attended at ED (≥ 3 times) or hospitalised (≥ 2 times) for AHF or died. Overall, 505 patients with FEAHF were included and followed for a mean of 2.4 years. In‐hospital mortality was 7.5%. Among 467 patients discharged alive, 288 died median survival 3.9 years, 95% confidence interval (CI) 3.5–4.4, 421 (90%) revisited the ED (2342 ED visits; 42.4% requiring hospitalisation, 34.0% AHF‐related) and 357
(77%) were hospitalised (1054 hospitalisations; 94.1% through ED, 51.4% AHF‐related). AHF‐related hospitalisations were mainly in internal medicine (28.0%), short‐stay unit (26.3%), cardiology (20.8%), and geriatrics (14.1%). Only 47.4% of AHF‐related hospitalisations were in the same department as the FEAHF, and internal medicine involvement significantly increased with subsequent hospitalisations (P = 0.01). Uncontrolled disease was observed in 31% of patients, which was independently related to age > 80 years odds ratio (OR) 1.80, 95% CI 1.17–2.77, systolic blood pressure < 110 mmHg at ED arrival (OR 2.61, 95% CI 1.26–5.38) and anaemia (OR 2.39, 95% CI 1.51–3.78).
Conclusion
In the present aged cohort of AHF patients from Barcelona, Spain, the natural history after FEAHF showed different patterns of hospital department involvement. Advanced age, low systolic blood pressure and anaemia were factors related to uncontrolled disease during the year after debut.
Background
Azole resistance screening in Aspergillus fumigatus isolates can be routinely carried out by using azole‐containing plates (E.Def 10.2 method), that requires filtering conidial suspensions ...prior inoculum adjustment.
Objectives
We evaluated whether skipping the filtration step of conidial suspensions negatively influences the performance of the E.Def 10.2.
Patients/Methods
A. fumigatus sensu stricto isolates (n = 92), classified as azole‐susceptible or azole‐resistant according to the EUCAST microdilution E.Def 9.4 method, were studied. Azole‐resistant isolates had either wild type cyp51A gene sequence (n = 3) or the TR34‐L98H (n = 26), G54R (n = 5), TR46‐Y121F‐T289A (n = 1), F46Y‐M172V‐N248T‐D255E‐E427K (n = 1), F165L (n = 1) or G448S (n = 1) cyp51A gene substitutions. In‐house azole‐containing agar plates were prepared according to the EUCAST E.Def 10.2 procedure. Conidial suspensions were obtained by adding distilled water (Tween 20 0.1%). Subsequently, the suspensions were either filtered or left unfiltered prior to inoculum adjustment to 0.5 McFarland. Using microdilution as the gold standard, agreement, sensitivity and specificity of the agar plates inoculated with two inoculums were assessed.
Results
Agreements for the agar screening method with either unfiltered or filtered conidial suspensions were high for itraconazole (100%), voriconazole (100%) and posaconazole (97.8%). Sensitivity (100%) and specificity (98.2%) of the procedure to rule in or out resistance when unfiltered suspensions were used were also high. Isolates harbouring the TR34‐L98H, G54R and TR46‐Y121F‐T289A substitutions were detected with the modified method.
Conclusions
Unfiltered conidial suspensions does not negatively influence the performance of the E.Def 10.2 method when screening for A. fumigatus sensu stricto.
Objective
To investigate the association of corrected QT (QTc) interval duration and short-term outcomes in patients with acute heart failure (AHF).
Methods
We analyzed AHF patients enrolled in 11 ...Spanish emergency departments (ED) for whom an ECG with QTc measurement was available. Patients with pace-maker rhythm were excluded. Primary outcome was 30-day all-cause mortality and secondary outcomes were need of hospitalization, in-hospital mortality and prolonged hospitalization (> 7 days). Association between QTc and outcomes was explored by restricted cubic spline (RCS) curves. Results were expressed as odds ratios (OR) and 95%CI adjusted by patients baseline and decompensation characteristics, using a QTc = 450 ms as reference.
Results
Of 1800 patients meeting entry criteria (median age 84 years (IQR = 77–89), 56% female), their median QTc was 453 ms (IQR = 422–483). The 30-day mortality was 9.7%, while need of hospitalization, in-hospital mortality and prolonged hospitalization were 77.8%, 9.0% and 50.0%, respectively. RCS curves found longer QTc was associated with 30-day mortality if > 561 ms, OR = 1.86 (1.00–3.45), and increased up to OR = 10.5 (2.25–49.1), for QTc = 674 ms. A similar pattern was observed for in-hospital mortality; OR = 2.64 (1.04–6.69), for QTc = 588 ms, and increasing up to OR = 8.02 (1.30–49.3), for QTc = 674 ms. Conversely, the need of hospitalization had a U-shaped relationship: being increased in patients with shorter QTc OR = 1.45 (1.00–2.09) for QTc = 381 ms, OR = 5.88 (1.25–27.6) for the shortest QTc of 200 ms, and also increasing for prolonged QTc OR = 1.06 (1.00–1.13), for QTc = 459 ms, and reaching OR = 2.15 (1.00–4.62) for QTc = 588 ms. QTc was not associated with prolonged hospitalization.
Conclusion
In ED AHF patients, initial QTc provides independent short-term prognostic information, with increasing QTc associated with increasing mortality, while both, shortened and prolonged QTc are associated with need of hospitalization.
Graphical abstract
Objectives
To analyse time trends in patient characteristics, clinical course, hospitalisation rate, and outcomes in acute heart failure along a 10-year period (2007–2016).
Methods
The EAHFE registry ...has prospectively collected 13,971 consecutive AHF patients diagnosed in 41 Spanish emergency departments (EDs) at five different time points (2007/2009/2011/2014/2016). Eighty patient-related variables and outcomes were described and statistically significant changes along time were evaluated. We also compared our data with large ED- and hospital-based registries.
Results
Compared to other large registries, our patients were older 80 (10) years, more frequently women (55.5%), and had a higher prevalence of hypertension (83.5%) and a lower prevalence of ischaemic cardiomyopathy (29.4%). De novo AHF was observed in 39.6%. 63.6% showed some degree of functional dependence and 56.1% had preserved left ventricular ejection fraction (LVEF). 56.8% of the patients arrived at the ED by ambulance, 4.5% arrived hypotensive, and 21.3% hypertensive. Direct discharge from the ED home was seen in 24.9%, and internal medicine (32.5%) and cardiology (15.8%) were the main hospital destinations. Triggers for decompensation were identified in 75.4%, the most being frequent infection (35.2%) and rapid atrial fibrillation (14.7%). The AHF phenotypes were: warm/wet 82.0%, warm/dry 6.2%, cold/wet 11.1%, and cold/dry 0.7%. The length of hospitalisation was 9.3 (8.6) days, and in-hospital, 30-day, and 1-year all-cause mortality were 7.8, 10.2 and 30.3%, respectively; and 30-day re-hospitalisation and ED revisit due to AHF were 16.9 and 24.8%, respectively. Thirty-nine of the eighty characteristics studied showed significant changes over time, while all outcomes remained unchanged along the 10-year period.
Conclusions
The EAHFE Registry is the first European ED-based registry describing the characteristics, clinical course, and outcomes of a cohort resembling the universe of patients with AHF. Significant changes were observed over time in some aspects of AHF characteristics and management, but not in outcomes.
Background
Studies comparing gradient diffusion strips (GDSs) and the EUCAST E.Def 9.4 microdilution method are scarce, thwarted by a low number of isolates, and restricted to selected antifungal ...agents.
Objectives
We evaluated the performance of GDSs to detect azole resistance in A. fumigatus, including cryptic species.
Patients/Methods
A. fumigatus sensu stricto (n = 89) and cryptic species (n = 52) were classified as susceptible or resistant to itraconazole, voriconazole, posaconazole and isavuconazole (EUCAST E.Def 9.4; clinical breakpoints v10). A. fumigatus sensu stricto azole‐resistant isolates had the following cyp51A gene mutations: TR34‐L98H (n = 24), G54R (n = 5), TR46‐Y121F‐T289A (n = 1), F46Y‐M172V‐N248T‐D255E‐E427K (n = 1), F165L (n = 1) and cyp51A gene wild type (n = 3). GDSs (ETEST®, bioMèrieux, Marcy‐l'Etoile, France and Liofilchem®, Roseto degli Abruzzi, Italy) MICs were obtained by following the manufacturer's guidelines.
Results
For A. fumigatus sensu stricto, itraconazole MICs >1.5 mg/L, voriconazole >0.38 mg/L, posaconazole >0.75 mg/L, and isavuconazole >0.5 mg/L correctly separated resistant from susceptible isolates with two exceptions. Considering the aforementioned cut‐off MICs, sensitivity/specificity values of GDSs to detect azole resistance were: itraconazole (97%/100%), voriconazole (97%/100%), posaconazole (97%/100%) and isavuconazole (93.3%/100%). For cryptic species isolates, voriconazole MICs >1 mg/L and isavuconazole >0.75 mg/L separated resistant isolates from susceptible isolates with 15 and 27 exceptions, respectively. Considering the aforementioned cut‐off MICs, sensitivity/specificity values were as follows: voriconazole (68.1%/100%) and isavuconazole (25%/100%). For itraconazole and posaconazole, it was not possible to establish cut‐off values.
Conclusions
We set tentative cut‐off MIC values to correctly spot resistant Aspergillus fumigatus sensu stricto isolates using GDSs. The performance against cryptic species was poor.
Physical examination remains the cornerstone in the assessment of acute heart failure. There is a lack of adequately powered studies assessing the combined impact of both systolic blood pressure ...(SBP) and hypoperfusion on short-term mortality.
Patients with acute heart failure from 41 Spanish emergency departments were recruited consecutively in 3 time periods between 2011 and 2016. Logistic regression models were used to assess the association of 30-day mortality with SBP (<90, 90-109, 110-129, and ≥130 mm Hg) and with manifestations of hypoperfusion (cold skin, cutaneous pallor, delayed capillary refill, livedo reticularis, and mental confusion) at admission.
Among 10 979 patients, 1143 died within the first 30 days (10.2%). There was an inverse association between 30-day mortality and initial SBP (35.4%, 18.9%, 12.4%, and 7.5% for SBP<90, SBP 90-109, SBP 110-129, and SBP≥130 mm Hg, respectively;
<0.001) and a positive association with hypoperfusion (8.0%, 14.8%, and 27.6% for those with none, 1, ≥2 signs/symptoms of hypoperfusion, respectively;
<0.001). After adjustment for 11 risk factors, the prognostic impact of hypoperfusion on 30-day mortality varied across SBP categories: SBP≥130 mm Hg (odds ratio OR=1.03 95% CI, 0.77-1.36 and OR=1.18 95% CI, 0.86-1.62 for 1 and ≥2 compared with 0 manifestations of hypoperfusion), SBP 110 to 129 mm Hg (OR=1.23 95% CI, 0.86-1.77 and OR=2.18 95% CI, 1.44-3.31, respectively), SBP 90 to 109 mm Hg (OR=1.29 95% CI, 0.79-2.10 and OR=2.24 95% CI, 1.36-3.66, respectively), and SBP<90 mm Hg (OR=1.34 95% CI, 0.45-4.01 and OR=3.22 95% CI, 1.30-7.97, respectively);
-for-interaction =0.043.
Hypoperfusion confers an incremental risk of 30-day all-cause mortality not only in patients with low SBP but also in normotensive patients. On admission, physical examination plays a major role in determining prognosis in patients with acute heart failure.
To investigate the relationship of ambient temperature and atmospheric pressure (AP) at patient discharge after an episode of acute heart failure (AHF) with very early post-discharge adverse ...outcomes. We analyzed 14,656 patients discharged after an AHF episode from 26 hospitals in 16 Spanish cities. The primary outcome was the 7-day post-discharge combined adverse event (emergency department –ED- revisit or hospitalization due to AHF, or all-cause death), and secondary outcomes were these three adverse events considered individually. Associations (adjusted for patient and demographic conditions, and length of stay -LOS- during the AHF index episode) of temperature and AP with the primary and secondary outcomes were investigated. We used restricted cubic splines to model the continuous non-linear association of temperature and AP with each endpoint. Some sensitivity analyses were performed. Patients were discharged after a median LOS of 5 days (IQR = 1–10). The highest temperature at discharge ranged from − 2 to 41.6 °C, and AP was from 892 to 1037 hPa. The 7-day post-discharge combined event occurred in 1242 patients (8.4%), with percentages of 7-day ED-revisit, hospitalization and death of 7.8%, 5.1% and 0.9%, respectively. We found no association between the maximal temperature and AP on the day of discharge and the primary or secondary outcomes. Similarly, there were no significant associations when the analyses were restricted to hospitalized patients (median LOS = 7 days, IQR = 4–11) during the index event, or when lag-1, lag-2 or the mean of the 3 post-discharge days (instead of point estimation) of ambient temperature and AP were considered. Temperature and AP on the day of patient discharge are not independently associated with the risk of very early adverse events during the vulnerable post-discharge period in patients discharged after an AHF episode.
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