This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in ...children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days,
< 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (
< 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 10
/L) and neutrophil (>10 × 10
/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74-0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.
The aim of this study was to identify factors predictive of nursing home admission (NHA) over a period of 1 year among elderly subjects with dementia.
The study population was drawn from the SAFES ...cohort that was formed within a national research program into the recruitment of emergency departments in 9 teaching hospitals. Subjects were to have been hospitalized in a medical ward in the same hospital as the emergency department to which they were initially admitted. Subjects who experienced NHA before emergency department admission were excluded. Those with a confirmed diagnosis of dementia were considered in the present analysis. NHA has been defined as the incident admission into either a nursing home or other long term care facility within the follow-up period. Data obtained from a Comprehensive Geriatric Assessment were used in a Cox model to predict 1-year NHA.
The 425 subjects of the study were 86 ± 6 years old, and were mainly women (63%). NHA rate was 40% (n = 172). Four factors were identified to increase NHA risk: age 85 or older (hazard ratio HR = 1.5; 95% confidence interval CI = 1.1-2.1), inability to use the toilet (HR = 2.5; 95% CI = 1.5-4.2), balance disorders (HR = 1.5; 95% CI = 1.1-2.1), and living alone (HR = 1.5; 95% CI = 1.1-2.1). Three factors decreased this risk significantly: inability to transfer (HR = 0.5; 95% CI = 0.3-0.8), increased number of children (HR = 0.88; 95% CI = 0.96-0.99), and increased initial Mini-Mental State Examination score (HR = 0.97; 95% CI = 0.8-0.9).
NHA determinants in dementia are strongly linked to the patient's own characteristics but also to his or her physical or social environment. Interventions should target both members of the dyad "patient-caregiver" because both are affected by the disease.
Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease resulting from the consumption of meat products contaminated by the agent causing bovine spongiform encephalopathy. Evidence ...supporting the presence of a population of silent carriers that can potentially transmit the disease through blood transfusion is increasing. The development of a blood-screening assay for both symptomatic vCJD patients and asymptomatic carriers is urgently required. We show that a diagnostic assay combining plasminogen-bead capture and protein misfolding cyclic amplification (PMCA) technologies consistently detected minute amounts of abnormal prion protein from French and British vCJD cases in the required femtomolar range. This assay allowed the blinded identification of 18 patients with clinical vCJD among 256 plasma samples from the two most affected countries, with 100% sensitivity 95% confidence interval (CI), 81.5 to 100%, 99.2% analytical specificity (95% CI, 95.9 to 100%), and 100% diagnostic specificity (95% CI, 96.5 to 100%). This assay also allowed the detection of silent carriage of prions 1.3 and 2.6 years before the clinical onset in two blood donors who later developed vCJD. These data provide a key step toward the validation of this PMCA technology as a blood-based diagnostic test for vCJD and support its potential for detecting presymptomatic patients, a prerequisite for limiting the risk of vCJD transmission through blood transfusion.
Delayed hemolytic transfusion reaction (DHTR) is a life‐threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated because its symptoms mimic those ...of vaso‐occlusive crisis and antibodies (Abs) are often not detectable. No predictive factors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single‐center observational study over 30 months in adult sickle cell patients. We included 694 transfusion episodes (TEs) in 311 patients, divided into occasional TEs (OTEs: 360) and chronic transfusion program (CTEs: 334). During follow‐up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR incidence was 4.2% per OTE (95% CI 2.6; 6.9) and 6.8% per patient during the 30 months of the study (95% CI 4.2; 11.3). We studied 11 additional DHTR cases, to construct a predictive score for DHTR. The DHTR mortality is high, 3 (11.5%) of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The resulting DHTR‐predictive score had an area under the ROC curve of 0.850 95% CI: 0.780‐0.930, a negative‐predictive value of 98.4% and a positive‐predictive value of 50%. We report in our study population, for the first time, the incidence of DHTR, and, its occurrence exclusively in occasionally transfused patients. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients.
L’hémolyse post transfusionnelle retardée (HPTR) est une complication potentiellement mortelle de la transfusion dans la drépanocytose. Sa fréquence est sous-estimée et aucun facteur prédictif de sa ...survenue n'a encore été identifié. Nous avons mené une étude observationnelle prospective monocentrique pendant 30 mois. Nous avons inclus 694 épisodes transfusionnels (ET) chez 311 patients adultes drépanocytaires, divisés en ET ponctuels (ETP = 360) et en ET chronique dans le cadre d’un programme (ETC = 334). Au cours de ce suivi, 15 HPTR ont été enregistrées, exclusivement après un ETP. L'incidence cumulative d’HPTR sur 30 mois était de 4,2 % par ETP (IC 95 % 2,6 ; 6,9) ou 6,8 % par drépanocytaires transfusés (IC 95 % 4,2 ; 11,3). Le taux d’incidence était de 16,4 HPTR pour 1000 ETP-Année (IC 95 % 10,1 ; 27,2) ou 27,1 HPTR pour 1000 Personne-Année (IC 95% 16,7 ; 45,0). Nous avons étudié 11 HPTR supplémentaires afin de construire un score prédictif. Les variables retenues étaient un antécédent d’HPTR, le nombre d’unités précédemment transfusées et l’état d’immunisation pré transfusionnelle. L’adéquation du score était excellente (Hosmer-Lemeshow = 1,40, p = 0,71), sa capacité discriminante très satisfaisante (aire sous la courbe ROC = 0,85 ; p < 0,0001), une valeur prédictive négative de 98,4 % et une valeur prédictive positive de 50,0 %. La validité interne du score, réalisée par Bootstrap, montre une très bonne performance. Nous rapportons, pour la première fois, l'incidence de l’HPTR et montrons qu’elle survient uniquement suite à un ETP. Nous décrivons également un score simple de prédiction d’une HPTR avant un ETP afin de mieux prendre en charge cette transfusion.
Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated and no predictive fac-tors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single-center observational study over 30 months. We included 694 transfusion epi-sodes (TE) in 311 adult patients, divided into occasional TE (OTE: 360) and TE during a chronic program (CTE: 334). During follow-up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR cumulative incidence durin the 30 months was 4.2% per OTE (95% CI 2.6, 6.9) or 66.8% per patient (95% CI 4.2, 11.3). The incidence rate was 16.4 DHTR per 1000 OTE-Year (95% CI 10.1, 27.2) or 27.1 DHTR per 1000 Person-Year (95% CI 16.7 ; 45.0). We studied 11 additional DHTR cases to construct a score for predicting DHTR after OTE. Fifteen % of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The score adequacy was excellent (Hosmer-Lemeshow = 1.40, p = 0.71), very satisfactory dis-criminant capacity (area under ROC curve = 0.85, p <0.0001), negative-predictive value of 98.4% and a positive-predictive value of 50%. The internal validity of the score, realized by Bootstrap, shows a very good performance.We report, for the first time, the incidence of DHTR and we show that DHTR developed only in OTE. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients.
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Background
Delayed hemolytic transfusion reaction (DHTR) is a life threatening complication of transfusion in sickle cell disease (SCD). This syndrome is underestimated because of a clinical ...picture that resembles a vaso-occlusive crisis (VOC) and the frequent absence of detectable antibodies. Several retrospective studies have evaluated the frequency of DHTR based on case reports. We conducted a prospective, longitudinal, single center study to determine the incidence of DHTR and the risk of developing DHTR depending on the transfusion regimen: chronic versus punctual.
Methods and patients
SCD patients aged over 18 years, undergoing a transfusion, were enrolled in this study. A total of 697 transfusion episodes (TE) in 312 patients were included during 30 months. Some patients had multiple TE during the period. The post transfusion outcome of the patients was assessed up to one month after the included TE. DHTR was confirmed based on the rapid disappearance of HbA (> 50% 15 days post-transfusion) associated with two of the following criteria up to three weeks after transfusion: VOC symptoms, dark urine, worsening anemia, increased LDH. Transfusion episodes were divided into chronic (336 TE in 111 patients) and punctual (361 TE in 201 patients). Chronic transfusions were defined as regular transfusions to treat chronic complications or for primary/secondary prevention of complications. Short transfusion program during pregnancy was considered as punctual transfusions if patients were not previously regularly transfused. The study obtained approval of the local Ethics Committee.
Results
Follow-up of the patients after transfusion showed 15 DHTR during the study. They all developed in punctually transfused patients. Thus, patients who are transfused punctually have a significantly higher risk of developing DHTR than those in a regular transfusion program (p < 0.001). When considering only punctual transfusions, the incidence of DHTR is 4.2% per transfusion episode (IC 95% 2.6; 6.9) and 7.5% per patient during the 30 months of the study (IC 95% 4.6; 12.4). In these DHTR cases, the transfusion indication was surgery (n = 6), pregnancy (n = 3), acute chest syndrome (n = 3), stroke (n = 1), profound anemia (n = 1), and VOC prevention before a school exam (n = 1 case). Two patients died of multi-organ failure following severe intravascular hemolysis. The median hemoglobin decrease for all DHTR cases after the triggering transfusion was 4.4 g/dl IQR 3.6-5.2; the highest LDH level was 879 IQR 680-1423. Ten patients developed newly formed antibodies, but only five among them displayed antibodies with significant serological features (anti-Fya, anti-S, anti-Jka, anti-HI). In the five other cases, the antibodies were of unspecified specificity or auto antibodies in the RH blood group (the genetic RH background was known). Finally, antibodies were undetectable for five cases, confirmed by long-term patient follow up.
Conclusion
This prospective study demonstrates, for the first time, that DHTR is a frequent reaction in adult SCD patients, developing only in occasionally transfused patients. This finding highlights that adult patients with regular transfusion who did not previously encountered DHTR are not susceptible to developing this severe reaction. A mechanism linked to acute situations can be suggested as already shown for the induction of allo-immunization. However, many cases developed without detectable antibodies, confirming the complex pathophysiology of this syndrome. A bio-clinical scoring system to predict DHTR, based on this study, is under development and will be presented.
Michel:Roche: Research Funding.
A comprehensive clinical and microbiological assessments of COVID-19 in front-line healthcare workers (HCWs) is needed. Between April 10th and May 28th, 2020, 319 HCWs with acute illness were ...reviewed. In addition to SARS-CoV-2 RT-PCR screening, a multiplex molecular panel was used for testing other respiratory pathogens. For SARS-CoV-2 positive HCWs, the normalized viral load, viral culture, and virus neutralization assays were performed weekly. For SARS-CoV-2 negative HCWs, SARS-CoV-2 serological testing was performed one month after inclusion. Among the 319 HCWs included, 67 (21.0%) were tested positive for SARS-CoV-2; 65/67 (97.0%) developed mild form of COVID-19. Other respiratory pathogens were found in 6/66 (9.1%) SARS-CoV-2 positive and 47/241 (19.5%) SARS-Cov-2 negative HCWs ( p = 0.07). The proportion of HCWs with a viral load > 5.0 log 10 cp/mL (Ct value < 25) was less than 15% at 8 days after symptom onset; 12% of HCWs were positive after 40 days (Ct > 37). More than 90% of cultivable virus had a viral load > 4.5 log 10 cp/mL (Ct < 26) and were collected within 10 days after symptom onset. Among negative HCWs, 6/190 (3.2%) seroconverted. Our data suggest that the determination of viral load can be used for appreciating the infectiousness of infected HCWs. These data could be helpful for facilitating their return to work.
Among alternative perovskite device architectures, mesoporous scaffolds based on metal oxide and carbon look highly promising due to their inherent high stability. In this study, the perovskite ...deposition has been realized on a 1.5 cm2 active surface area using inkjet infiltration through the mesoporous scaffold, affording a clean industrial process for large-scale and stable perovskite devices. A spectacular enhancement of photovoltaic performances from 10% to 14% was then obtained through the implementation of a maturation step. A study of the occurring mechanisms was conducted using a full set of characterization techniques including J-V measurements, UV–visible and PL spectroscopies, LBIC and PL imaging, XRD, and surface roughness measurements. In addition, the impact of this maturation step on the durability of the performances was investigated.
In this work we compare seven different types of natural and synthetic graphite particles and examine how their integration into the cathode of carbon-based perovskite solar cells (C–PSCs) is ...influencing their opto-electronic properties. By combining x-ray diffraction, Raman spectroscopy and 4-point probe measurements we show that the differences in graphite crystallinity significantly affect the sheet resistance of the carbon-based cathode. The most conductive carbon-based film with an exceptional sheet resistance of 4 Ω/sq. have been produced from scaly graphite with the crystallite dimensions of La = 60.6 nm and Lc = 28.6 nm. Electrochemical Impedance Spectroscopy further revealed that charge transfer resistance at the perovskite/carbon contact differ for each graphite type. Overall, the pyrolytic graphite was found to be the best compromise between high conductivity and low charge transfer resistance leading to least series resistance losses and a fill factor (FF) above 74% (in perovskite solar cells with area of 0.64 cm2). However, an overall efficient hole extraction and lower non-radiative charge recombination in C–PSCs with scaly graphite resulted in the highest average power conversion efficiency and a champion device reaching 14.63%. All the C–PSCs show exceptional moisture stability for 5,000 h under ambient condition, with a PCE decrease of less than 3%.
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