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2.
Pediatr Pulmonol ; 55(12): 3358-3363, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32877001

RESUMO

OBJECTIVE: The prevalence of sleep disorders in patients with cystic fibrosis (CF) is unknown, and no standardized screening or treatment guidelines exist to address sleep disorders in CF. The objective of this study is to characterize current sleep screening practices in adult, pediatric, combined, and affiliate CF programs. METHODS: A survey was developed in Research Electronic Data Capture and distributed to program directors of accredited CF programs in the United States. RESULTS: Eighty-eight program directors responded (36% adult, 43% pediatric, 16% combined, 3% affiliate, and 1% unidentified). Of the respondents, 68% were part of an academic institution, 24% were associated with an academic institution, and 8% were part of a community or private program. Program sizes ranged from less than 50 to more than 500 patients. Routine or informal sleep screening was not performed in 44% of adults, 29% of pediatricians, and 35% of combined and affiliate programs. Most programs (>80%) have access to otolaryngology and sleep medicine although not all of these programs refer patients for evaluation of sleep disorders. Most program directors (77%) perceive sleep disorders as a problem in CF and would recommend routine sleep screening. Possible barriers to sleep screening included clinic flow, screening fatigue, and lack of recommendations for sleep screening. CONCLUSIONS: Formal sleep screening is inconsistent among CF care centers although most survey respondents would recommend the inclusion of screening in routine CF care. Future work is needed to further evaluate the impact of sleep disorders in CF and determine best practices for standardization of sleep screening and treatment.

4.
Free Radic Res ; 54(7): 517-524, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32781874

RESUMO

The present study reports radiation-chemical yields of 2.5-diaminoimidazolone (Iz) derivatives in X-irradiated phosphate-buffered solutions of guanosine and double-stranded DNA. Various gassing conditions (air, N20/O2 (4:1), N2O, vacuum) were employed to elucidate the contribution of several alternative pathways leading to Iz in reactions initiated by hydroxyl radical attack on guanine. In all systems, Iz was identified as the second by abundance guanine degradation product after 8-oxoguanine, formed in 1:5 (guanosine) and 1:3.3 (DNA) ratio to the latter in air-saturated solutions. Experimental data strongly suggest that the addition of molecular oxygen to the neutral guanine radical G(-H)• plays a major in Iz production in oxygenated solutions of double-stranded DNA while in other systems it may compete with recombination of G(-H)• with superoxide and/or alkyl peroxyl radicals. The production of Iz through hydroxyl radical attack on 8-oxoguanine was also shown to take place although the chemical yield of Iz (ca 6%) in this process is too low to compete with the other pathways. The linearity of Iz accumulation with dose also indicates a negligible contribution of this channel to its yield in all systems.


Assuntos
Dano ao DNA , DNA/química , Radicais Livres/química , Radical Hidroxila/química , Imidazóis/química , 8-Hidroxi-2'-Desoxiguanosina/química , Animais , DNA/efeitos da radiação , Diaminas/química , Guanosina/química , Masculino , Salmão
5.
Br J Anaesth ; 125(6): 962-969, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32859363

RESUMO

BACKGROUND: Penicillin allergy is associated with a range of poor health outcomes. Allergy testing can be made simpler by using a direct drug provocation test in patients at low risk of genuine allergy. This approach could allow population-level 'de-labelling'. We sought to determine the incidence and nature of penicillin allergy labels in UK surgical patients and define patient and anaesthetist attitudes towards penicillin allergy testing. METHODS: A prospective cross-sectional questionnaire study was performed in 213 UK hospitals. 'Penicillin allergic' patients were interviewed and risk-stratified. Knowledge and attitudes around penicillin allergy were defined in patients and anaesthetists. RESULTS: Of 21 219 patients, 12% (n=2626) self-reported penicillin allergy; 27% reported low-risk histories potentially suitable for a direct drug provocation test; an additional 40% reported symptoms potentially suitable for a direct drug provocation test after more detailed assessment. Of 4798 anaesthetists, 40% claimed to administer penicillin routinely when they judged the label low risk. Only 47% of anaesthetists would be happy to administer penicillin to a patient previously de-labelled by an allergy specialist using a direct drug provocation test; perceived lack of support was the most common reason for not doing so. CONCLUSIONS: At least 27% of patients with a penicillin allergy label may be suitable for a direct drug provocation test. Anaesthetists demonstrated potentially unsafe prescribing in patients with penicillin allergy labels. More than half of anaesthetists lack confidence in the results of a direct drug provocation tests undertaken by a specialist. Our findings highlight significant barriers to the effective implementation of widespread de-labelling in surgical patients.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32845301

RESUMO

BACKGROUND: There is limited information describing the characteristics and outcomes of hospitalized older patients with confirmed coronavirus disease 2019 (COVID-19). METHODS: We conducted a multicentric retrospective cohort study in 13 acute COVID-19 geriatric wards, from March 13 to April 15, 2020, in Paris area. All consecutive patients aged ≥ 70 years, with confirmed COVID-19, were enrolled. RESULTS: Of the 821 patients included in the study, the mean (SD) age was 86 (7) years; 58% were female; 85% had ≥ 2 comorbidities; 29% lived in an institution; and the median (interquartile range) Activities of Daily Living Scale (ADL) score was 4 [2-6]. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%) and delirium (25%). The in-hospital mortality was 31% (95% confidence interval [CI], 27 to 33). On multivariate analysis, at COVID-19 onset, the probability of in-hospital mortality was increased with male gender (odds ratio [OR], 1.85; 95% CI, 1.30 to 2.63), ADL score < 4 (OR, 1.84; 95% CI, 1.25 to 2.70), asthenia (OR, 1.59; 95% CI, 1.08 to 2.32), quick Sequential Organ Failure Assessment score ≥ 2 (OR, 2.63; 95% CI, 1.64 to 4.22) and specific COVID-19 anomalies on chest computerized tomography (OR, 2.60; 95% CI, 1.07 to 6.46). CONCLUSIONS: This study provides new information about older patients with COVID-19 who are hospitalized. A quick bedside evaluation at admission of sex, functional status, systolic arterial pressure, consciousness, respiratory rate and asthenia can identify older patients at risk of unfavorable outcomes.

7.
Br J Haematol ; 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32700439

RESUMO

The nucleoside analogue, 2-chlorodeoxyadenosine (2CDA), was reported to be an active treatment for childhood Langerhans cell histiocytosis (LCH) without risk organ (RO-) involvement. However, we lack data on long-term effects of 2CDA treatment, including the disease reactivation rate, permanent sequelae and long-term tolerance. This study included 44 children from the French LCH registry, treated for a RO- LCH with 2CDA monotherapy (median number of six courses). The median age at the beginning of 2CDA was 3·6 years (range, 0·3-19·7 years) and the median follow-up after was 5·4 years (range, 0·6-15·1 years). Objective response to 2CDA was observed in 25 patients (56·8%), while six patients (13·6%) had stable disease and 13 patients (29·5%) exhibited progressive disease. Among patients without progression, only two experienced disease reactivation after 2CDA discontinuation. The five-year cumulative incidence of disease progression or reactivation after 2CDA therapy initiation was 34·3%. The lymphopenia reported in all cases [72% below absolute lymphocyte count (ALC) of 0·5 G/l], was addressed with appropriate prophylactic measures. Other toxicities above grade 2 were uncommon, and no second malignant neoplasm or neuropathy was reported. The five-year overall survival was 97·7%. In conclusion, we could confirm that 2CDA monotherapy was a beneficial long-term therapy for treating patients with RO- LCH. Appropriate management of induced immune deficiency is mandatory.

8.
J Perioper Pract ; : 1750458920936933, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32638654

RESUMO

AIM: To investigate patient anxiety at anaesthetic induction and whether this is affected by anaesthetic room interventions. METHODS: A mixed methods study was carried out: pre-induction interventions were directly observed. Patient anxiety was assessed quantitatively with cardiovascular changes, the visual analogue scale and the state-trait anxiety inventory. Interviews allowed qualitative assessment. RESULTS: Patient-reported anxiety did not correlate with cardiovascular changes. Anaesthetic room interventions were not predictive of anxiety. Postoperative interviews identified five sources of anxiety, mostly related to preparation for surgery. Staff responses to anxiety were also highlighted. DISCUSSION: Patient-reported anxiety and its biological response are not correlated. Pre-induction interventions do not contribute to anxiety. Anxiety levels at induction are similar to or lower than earlier in the preoperative period. CONCLUSIONS: On induction of anaesthesia, patients have little control over their situation but are actively reassured and distracted by theatre staff. Our data suggest staff are good at this. More could still be done to reduce preoperative sources of anxiety.

10.
Br J Haematol ; 189(5): 931-942, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32130726

RESUMO

Childhood chronic immune thrombocytopenic purpura (cITP) is a rare disease. In severe cases, there is no evidence for the optimal therapeutic strategy. Our aim was to describe the real-life management of non-selected children with cITP at diagnosis. Since 2004, patients less than 18 years old with cITP have been enrolled in the national prospective cohort, OBS'CEREVANCE. From 1990 to 2014, in 29 centres, 392 children were diagnosed with cITP. With a median follow-up of six years (2·0-25), 45% did not need second-line therapy, and 55% (n = 217) received one or more second lines, mainly splenectomy (n = 108), hydroxychloroquine (n = 61), rituximab (n = 61) or azathioprine (n = 40). The overall five-year further second-line treatment-free survival was 56% [95% CI 49·5-64.1]. The use of splenectomy significantly decreased over time. Hydroxychloroquine was administered to children with positive antinuclear antibodies, more frequently older and girls, and reached 55% efficacy. None of the patients died. Ten years after the initial diagnosis, 55% of the 56 followed children had achieved complete remission. Children with cITP do not need second-line treatments in 45% of cases. Basing the treatment decision on the pathophysiological pathways is challenging, as illustrated by ITP patients with positive antinuclear antibodies treated with hydroxychloroquine.

11.
Br J Haematol ; 189(2): 351-362, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31837008

RESUMO

We investigated the long-term outcome, the incidence of second neoplasms (SN) and the rate of late adverse effects (LAE) in children with central nervous system (CNS) negative medium/high-risk de novo acute lymphoblastic leukaemia (ALL), in first complete remission (CR1) at end of late intensification, randomized to receive no cranial radiotherapy (No CRT, n = 92) versus CRT (standard arm, n = 84) in the non-inferiority EORTC 58832 study (1983-1989). Median follow-up was 20 years (range 4-32 years). The 25-year disease-free survival rate (±SE) was 67·4 ± 4·9% without CRT and 70·2 ± 5·0% with CRT. The 25-year incidence of isolated (6·5 ± 2·6% vs. 4·8 ± 2·3%) and any CNS relapse {8·7 ± 2·9% vs. 11·9 ± 3·5%; hazard ratio (HR) 0·71 [95% confidence interval (CI) 0·28-1·79]; test of non-inferiority: P = 0·01} was not increased without CRT. The 25-year SN incidence in CR1 was 7·9 ± 4·6% vs. 11·0 ± 4·2%. The 25-year event-free and overall survival rates were quite similar in both arms [59·5 ± 6·3% vs. 60·5 ± 5·9%, HR 0·94 (95% CI 0·57-1·52), and 78·1 ± 4·3% vs. 78·5 ± 4·5%, HR 1·00 (95% CI 0·53-1·88)]. Omission of CRT was associated with dramatic decrease in CNS and endocrine LAE rates. In conclusion, our data suggest that, with proper systemic and intrathecal CNS prophylaxis, CRT could totally be omitted in CR1 without jeopardizing survival, while decreasing LAE in childhood ALL.

12.
Liver Int ; 40(2): 286-297, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31454466

RESUMO

BACKGROUNDS & AIMS: In Indonesia 1.9 million people are chronically infected with hepatitis C virus (HCV), but a national strategic plan for elimination has not yet been developed, despite the availability of low-cost treatments which could save many lives. We used epidemiological and cost modelling to estimate targets and resource requirements of a national elimination program and explore the potential impact and cost-effectiveness. METHODS: To model the HCV epidemic, we used a dynamic model, parameterised with Indonesia-specific data, accounting for disease progression, injecting drug use and demographics. Future scale-up scenarios were designed for 2018-2050 to capture possible policy choices. Costs of an initial 5-year national strategy and of long-term elimination were estimated for the most feasible scenario, as agreed with government and local partners. Cost savings from reduced drug and diagnostics prices were also estimated. The cost-effectiveness of baseline predictions and those with drug price reductions were compared to the no treatment scenario. RESULTS: Elimination by 2045, considered the most feasible path to scale-up, would prevent 739 000 new infections and avert 158 000 HCV-related deaths. The costs would be $5.6 billion (USD) using baseline prices but could fall to $2.7 billion if price reductions for HCV drugs and diagnostics are secured. With these price reductions, the incremental cost-effectiveness ratio for a 2045 elimination program would be cost-effective at $300 (USD) per year of life saved vs the no treatment scenario. CONCLUSIONS: This study has underpinned advocacy efforts to secure Indonesian government commitment to HCV elimination, and provides further inputs for HCV strategic planning efforts.

14.
Front Immunol ; 10: 2007, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31507604

RESUMO

Properdin (FP) is a positive regulator of the immune system stimulating the activity of the proteolytically active C3 convertase C3bBb in the alternative pathway of the complement system. Here we present two crystal structures of FP and two structures of convertase bound FP. A structural core formed by three thrombospondin repeats (TSRs) and a TB domain harbors the convertase binding site in FP that mainly interacts with C3b. Stabilization of the interaction between the C3b C-terminus and the MIDAS bound Mg2+ in the Bb protease by FP TSR5 is proposed to underlie FP convertase stabilization. Intermolecular contacts between FP and the convertase subunits suggested by the structure were confirmed by binding experiments. FP is shown to inhibit C3b degradation by FI due to a direct competition for a common binding site on C3b. FP oligomers are held together by two sets of intermolecular contacts, where the first is formed by the TB domain from one FP molecule and TSR4 from another. The second and largest interface is formed by TSR1 and TSR6 from the same two FP molecules. Flexibility at four hinges between thrombospondin repeats is suggested to enable the oligomeric, polydisperse, and extended architecture of FP. Our structures rationalize the effects of mutations associated with FP deficiencies and provide a structural basis for the analysis of FP function in convertases and its possible role in pattern recognition.

15.
J Crit Care ; 54: 180-184, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31514115

RESUMO

PURPOSE: Acute critical illness induce a high caregivers burden in the young population, however data in the older population are lacking. The objectives of this study were to evaluate caregiver burden in a critically ill old population and to assess factors associated with mild to severe burden level. MATERIALS AND METHODS: All patients from two participating centers of the ICE-CUB 2 trial were included in the study. Inclusion criteria were an age ≥75, at least one critical condition and preserved functional status. The primary endpoint was a Zarit Burden Interview (ZBI) ≥ 21 at 6 months. RESULTS: One hundred ninety-one patients (median age 86 [81-89] years) were included. Median caregiver ZBI at 6 months was 13 [5-27]. In the multivariate analysis, factors significantly associated with moderate to severe burden were the 6-month ADL decrease (OR: 1.3, p = .049) and the 6-month mental component of the quality of life score (OR: 0.94, p = .0009). In contrast, age, ICU admission and length of hospital stay were not associated with moderate to severe load. CONCLUSION: In our study, functional status and mental health at 6 months were associated with mild to severe burden unlike age and admission in ICU.

16.
South Med J ; 112(6): 320-324, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31158886

RESUMO

OBJECTIVE: To determine whether physician spirituality, religion, and sense of calling toward medicine are predictors of self-reported empathic compassion. METHODS: We sampled 2000 practicing US physicians from all specialties and used self-reported measures of general and clinical empathic compassion taken from previous studies. Independent variables were single-item measures of calling, spirituality, and religiosity (importance of religion). RESULTS: The survey response rate was 64.5% (1289/2000). Physicians with a strong sense of calling were more likely to report higher general empathic compassion (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.26-3.15) and higher clinical empathic compassion (OR 3.33, 95% CI 2.07-5.36). Similarly, physicians who considered themselves spiritual were more likely to report higher general empathic compassion (OR 2.76, 95% CI 1.69-4.50) and higher clinical empathic compassion (OR 2.32, 95% CI 1.38-3.90). We did not find an association between religiosity and measures of physicians' empathic compassion. CONCLUSIONS: This national study of practicing US physicians from various specialties found that spirituality (not religiousness) and the identification of medicine as a calling are associated with physicians' empathic compassion. Further study is needed to understand how spirituality and calling are linked to prosocial behaviors among physicians that may be enhancing their clinical empathy and promoting compassionate patient care.


Assuntos
Atitude do Pessoal de Saúde , Escolha da Profissão , Empatia , Médicos/psicologia , Religião e Medicina , Espiritualidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Estados Unidos
17.
Blood ; 134(1): 9-21, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-30940614

RESUMO

Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M- group). The M+ group displayed more severe disease than the M- group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.


Assuntos
Anemia Hemolítica Autoimune/genética , Anemia Hemolítica Autoimune/imunologia , Trombocitopenia/genética , Trombocitopenia/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Mutação , Adulto Jovem
18.
Clin Immunol ; 202: 33-39, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30946917

RESUMO

PURPOSE: Severe combined immunodeficiency (SCID) refers to a group of genetic disorders characterized by greatly compromised cellular and humoral immunity. Children with SCID are asymptomatic at birth, but they die from infections within the first months of life if not treated. Quantification of T-cell receptor excision circles is an extremely sensitive screening method for detecting newborns who may have SCID.The goal of the DEPISTREC study was to evaluate the feasibility of nationwide newborn screening for severe T-cell lymphopenia in France as well as its economic and clinical utility. METHODS: The test universally used for neonatal screening for SCID was the quantification of TRECs on Guthrie cards. We compared a group of 190,517 babies from 48 maternities across the country who underwent newborn SCID screening with a control group of 1.4 million babies out of whom 28 were diagnosed with SCID without such screening during the course of the study. RESULTS: Within the screening group, 62 babies were found to be lymphopenic, including three with SCID. The cost of screening ranged from 4.7€ to €8.15 per newborn. The average 18-month cost was €257,574 vs €204,697 in the control group. CONCLUSIONS: In this large-scale study, we demonstrate that routine SCID screening is feasible and effective. This screening offers the additional benefit of aiding in the diagnosis of non-SCID lymphopenia. Economic evaluation allowed us to calculate the cost per test. Newborn screening may also prevent death by SCID before any curative treatment can be administered. The difference in cost between screened and control children could not be ascertained because of the very low numbers and death of one of the children tested.


Assuntos
Linfopenia/diagnóstico , Triagem Neonatal/economia , Imunodeficiência Combinada Severa/diagnóstico , Custos e Análise de Custo , Teste em Amostras de Sangue Seco/economia , Feminino , França , Humanos , Lactente , Recém-Nascido , Contagem de Linfócitos , Linfopenia/economia , Masculino , Receptores de Antígenos de Linfócitos T/imunologia , Imunodeficiência Combinada Severa/economia , Linfócitos T/imunologia
19.
Am J Med Genet A ; 179(6): 993-1000, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30888095

RESUMO

This report presents two families with interstitial 11q24.2q24.3 deletion, associated with malformations, hematologic features, and typical facial dysmorphism, observed in Jacobsen syndrome (JS), except for intellectual disability (ID). The smallest 700 Kb deletion contains only two genes: FLI1 and ETS1, and a long noncoding RNA, SENCR, narrowing the minimal critical region for some features of JS. Consistent with recent literature, it adds supplemental data to confirm the crucial role of FLI1 and ETS1 in JS, namely FLI1 in thrombocytopenia and ETS1 in cardiopathy and immune deficiency. It also supports that combined ETS1 and FLI1 haploinsufficiency explains dysmorphic features, notably ears, and nose anomalies. Moreover, it raises the possibility that SENCR, a long noncoding RNA, could be responsible for limb defects, because of its early role in endothelial cell commitment and function. Considering ID and autism spectrum disorder, which are some of the main features of JS, a participation of ETS1, FLI1, or SENCR cannot be excluded. But, considering the normal neurodevelopment of our patients, their role would be either minor or with an important variability in penetrance. Furthermore, according to literature, ARHGAP32 and KIRREL3 seem to be the strongest candidate genes in the 11q24 region for other Jacobsen patients.

20.
J Med Syst ; 42(12): 255, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30406430

RESUMO

Virtual rehabilitation yields outcomes that are at least as good as traditional care for improving upper limb function and the capacity to carry out activities of daily living. Due to the advent of low-cost gaming systems and patient preference for game-based therapies, video game technology will likely be increasingly utilized in physical therapy practice in the coming years. Gaming systems that incorporate low-cost motion capture technology often generate large datasets of therapeutic movements performed over the course of rehabilitation. An infrastructure has yet to be established, however, to enable efficient processing of large quantities of movement data that are collected outside of a controlled laboratory setting. In this paper, a methodology is presented for extracting and evaluating therapeutic movements from game-based rehabilitation that occurs in uncontrolled and unmonitored settings. By overcoming these challenges, meaningful kinematic analysis of rehabilitation trajectory within an individual becomes feasible. Moreover, this methodological approach provides a vehicle for analyzing large datasets generated in uncontrolled clinical settings to enable better predictions of rehabilitation potential and dose-response relationships for personalized medicine.


Assuntos
Movimento , Reabilitação do Acidente Vascular Cerebral/métodos , Jogos de Vídeo , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Fenômenos Biomecânicos , Feminino , Humanos , Articulações/fisiologia , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Processamento de Sinais Assistido por Computador
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