RESUMO
The aim of the present study was to examine parental experiences of homeschooling during the COVID-19 pandemic in families with or without a child with a mental health condition across Europe. The study included 6720 parents recruited through schools, patient organizations and social media platforms (2002 parents with a child with a mental health condition and 4718 without) from seven European countries: the UK (n = 508), Sweden (n = 1436), Spain (n = 1491), Belgium (n = 508), the Netherlands (n = 324), Germany (n = 1662) and Italy (n = 794). Many parents reported negative effects of homeschooling for themselves and their child, and many found homeschooling to be of poor quality, with insufficient support from schools. In most countries, contact with teachers was limited, leaving parents with primary responsibility for managing homeschooling. Parents also reported increased levels of stress, worry, social isolation, and domestic conflict. A small number of parents reported increased parental alcohol/drug use. Some differences were found between countries and some negative experiences were more common in families with a child with a mental health condition. However, differences between countries and between families with and without a mental health condition were generally small, indicating that many parents across countries reported negative experiences. Some parents also reported positive experiences of homeschooling. The adverse effects of homeschooling will likely have a long-term impact and contribute to increased inequalities. Given that school closures may be less effective than other interventions, policymakers need to carefully consider the negative consequences of homeschooling during additional waves of the COVID-19 pandemic and future pandemics.
Assuntos
COVID-19 , Transtornos Mentais , Criança , Humanos , Transtornos Mentais/epidemiologia , Saúde Mental , Pandemias , Pais/psicologiaRESUMO
We aimed to analyze whether the lack of inclusion of specific recommendations for the management of candidemia is an independent risk factor for early and overall mortality. Multicenter study of adult patients with candidemia in 13 hospitals. We assessed the proportion of patients on whom nine specific ESCMID and IDSA guidelines recommendations had been applied, and analyzed its impact on mortality. 455 episodes of candidemia were documented. Patients who died within the first 48 hours were excluded. Sixty-two percent of patients received an appropriate antifungal treatment. Either echinocandin or amphotericin B therapy were administered in 43% of patients presenting septic shock and in 71% of those with neutropenia. Sixty-one percent of patients with breakthrough candidemia underwent a change in antifungal drug class. Venous catheters were removed in 79% of cases. Follow-up blood cultures were performed in 72% of cases. Ophthalmoscopy and echocardiogram were performed in 48% and 50% of patients, respectively. Length of treatment was appropriate in 78% of cases. Early (2-7 days) and overall (2-30 days) mortality were 8% and 27.7%, respectively. Inclusion of less than 50% of the specific recommendations was independently associated with a higher early (HR = 7.02, 95% CI: 2.97-16.57; P < .001) and overall mortality (HR = 3.55, 95% CI: 2.24-5.64; P < .001). In conclusion, ESCMID and IDSA guideline recommendations were not performed on a significant number of patients. Lack of inclusion of these recommendations proved to be an independent risk factor for early and overall mortality.
Assuntos
Antifúngicos/uso terapêutico , Candidemia/tratamento farmacológico , Candidemia/mortalidade , Gerenciamento Clínico , Fidelidade a Diretrizes/estatística & dados numéricos , Idoso , Candida/efeitos dos fármacos , Candidemia/complicações , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/microbiologia , Guias de Prática Clínica como Assunto , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/microbiologia , Choque Séptico/mortalidade , Espanha , Resultado do TratamentoRESUMO
The outcome of invasive aspergillosis (IA) continues to be associated with significant attributable mortality, especially in patients with hematological malignancies and in hematopoietic stem cell transplant recipients. In this context, antifungal combined therapy (ACT) has become an emerging strategy against IA. In an attempt to evaluate the benefits of ACT, a large number of experimental studies, clinical series, and randomized trials have been performed, with varying results. In addition, several controlled trials have been registered; however, in most cases, their final results have not been made available. In summary, there is an imbalance between the lack of published evidence regarding the benefits of ACT and its extensive and increasing use in current clinical practice, despite its associated cost. Here, we present a critical analysis of the available information regarding ACT for the treatment of IA as well as the authors' opinion with respect to its use.
Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Animais , Antifúngicos/efeitos adversos , Ensaios Clínicos como Assunto , Análise Custo-Benefício , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Humanos , Resultado do TratamentoRESUMO
OBJECTIVES: Escherichia coli belonging to clonal group ST131 has emerged as a significant contributor to infection caused by antibiotic-resistant E. coli worldwide. We investigated the risk factors for infections caused by ST131 E. coli and their clinical implications. METHODS: One thousand and seventy-seven E. coli isolates were screened for ST131 by molecular methods. Risk factors for ST131 were investigated separately for patients with E. coli producing and not producing extended-spectrum ß-lactamases (ESBLs) in the Seville area, Spain. Multivariate analysis using logistic regression was performed. Patients with infections caused by ST131 and non-ST131 isolates were prospectively followed. RESULTS: Independent risk factors for non-ESBL-producing ST131 were female gender (OR: 1.94; 95% CI: 1.07-3.51), diabetes mellitus (OR: 2.17; 95% CI: 1.29-3.67), bedridden status (OR: 7.75; 95% CI: 0.70-85.07) and exposure to amoxicillin/clavulanate (OR: 2.07; 95% CI: 1.08-3.96) or fluoroquinolones (OR: 2.48; 95% CI: 1.41-4.34). For ESBL-producing ST131, male gender was an independent risk factor (OR: 2.20; 95% CI: 0.94-5.11), while healthcare-related acquisition and exposure to any previous antibiotic were protective (OR: 0.30; 95% CI: 0.13-0.71; and OR: 0.43; 95% CI: 0.19-1.00, respectively). Overall, the severity of sepsis, bacteraemia and mortality were similar among ST131 and non-ST131 groups. The presence of typical factors predisposing to E. coli infection was more frequent in non-ESBL-producing ST131 than in controls (76% versus 57.2%, Pâ=â0.005). CONCLUSIONS: Previous use of antibiotics selecting for ST131 isolates was the main modifiable risk factor for infections caused by these isolates. Our results also suggest that the clinical virulence of ST131 is not higher than that of other common E. coli causing infections.
Assuntos
Epidemias , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Escherichia coli/classificação , Escherichia coli/enzimologia , Tipagem Molecular , beta-Lactamases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sepse/epidemiologia , Sepse/microbiologia , Sepse/patologia , Espanha/epidemiologia , Análise de Sobrevida , Adulto JovemRESUMO
Invasive fungal infections (IFIs) are becoming more frequent due to the increasing number of patients at risk. Over the last decade, their prognosis has improved with the diagnostic and therapeutic advances, including new antifungals. In the two years, from 2007 to 2009, antifungal consumption increased by 27%, 67 times more than antibacterial consumption, albeit with great differences between hospitals. The scientific evidence of the indications for antifungal prophylaxis and targeted antifungal therapy is strong; however, it is weak for empirical antifungal therapy, which is the most common indication. Antifungals are not harmless, since they are associated with a wide range of adverse effects and drug interactions, favor the development of resistance, contribute to other fungal superinfections and cause significant healthcare spending. Therefore, the question arises whether this extraordinary increase in consumption is justified, whether the use of antifungals is optimal, or whether it is necessary to reconsider the current treatment of IFIs instead.
Assuntos
Antifúngicos/uso terapêutico , Micoses/tratamento farmacológico , Antifúngicos/efeitos adversos , Candidíase Invasiva/tratamento farmacológico , Ensaios Clínicos como Assunto , Estado Terminal , Gerenciamento Clínico , Farmacorresistência Fúngica , Uso de Medicamentos/tendências , Doenças Hematológicas/complicações , Transplante de Células-Tronco Hematopoéticas , Humanos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Micoses/epidemiologia , Micoses/etiologia , Neoplasias/complicações , Neutropenia/complicações , Fatores de RiscoRESUMO
New approaches of empirical antifungal therapy (EAT) in selected hematological patients with persistent febrile neutropenia (PFN) have been proposed in recent years, but their cost-effectiveness has not been studied. The aim of this study was to compare the cost-effectiveness of two different approaches of EAT in hematological patients with PFN: the diagnosis-driven antifungal therapy (DDAT) approach versus the standard approach of EAT. A decision tree to assess the cost-effectiveness of both approaches was developed. Outcome probabilities and treatment pathways were extrapolated from two studies: a prospective cohort study following the DDAT approach and a randomized clinical trial following the standard approach. Uncertainty was undertaken through sensitivity analyses and Monte Carlo simulation. The average effectiveness and economic advantages in the DDAT approach compared to the standard approach were 2.6% and 5,879 (33%) per PFN episode, respectively. The DDAT was the dominant approach in the 99.5% of the simulations performed with average cost-effectiveness per PFN episode of 32,671 versus 52,479 in the EAT approach. The results were robust over a wide range of variables. The DDAT approach is more cost-effective than the EAT approach in the management of PFN in hematological patients.
Assuntos
Antifúngicos/uso terapêutico , Neutropenia Febril/tratamento farmacológico , Adolescente , Adulto , Idoso , Algoritmos , Antifúngicos/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
Background: Limited information is available on the active process of seeking medical help in patients with Alzheimer's disease (AD) at early stages. The aim of this study was to assess the phenomenon of medical help-seeking in early AD and to identify associated factors. Methods: A multicenter, non-interventional study was conducted including patients of 50-90 years of age with prodromal or mild AD (National Institute on Aging/Alzheimer's Association criteria), a Mini-Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5-1.0. A multivariate logistic regression analysis was conducted. Results: A total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years, 50.3% were female, and 87.2% had a CDR-GS score of 0.5. Mean disease duration was 1.4 (1.8) years. Ninety-four (63.1%) patients sought medical help, mostly from neurologists. Patients with help-seeking intentions were mostly female (60.6%) with a CDR-GS score of 0.5 (91.5%) and had a greater awareness of diagnosis, poorer quality of life, more depressive symptoms, and a more severe perception of their condition than their counterparts. Lack of help-seeking intentions was associated with male sex (p = 0.003), fewer years of education (p = 0.005), a low awareness of diagnosis (p = 0.005), and a low emotional consequence of the condition (p = 0.016). Conclusion: Understanding the phenomenon of active medical help-seeking may facilitate the design of specific strategies to improve the detection of cognitive impairment, especially in patients with a lower level of educational attainment and poor awareness of their condition.
RESUMO
BACKGROUND: Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients' risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. DESIGN AND METHODS: This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. RESULTS: Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. CONCLUSIONS: Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients who have received a hematopoietic stem cell transplant, the approach is useful for identifying patients who are not likely to develop invasive fungal infection and do not, therefore, require antifungal therapy. The effectiveness of the strategy is similar to that of universal empirical antifungal therapy reported in controlled trials.
Assuntos
Antifúngicos/uso terapêutico , Micoses/diagnóstico , Micoses/tratamento farmacológico , Neutropenia/diagnóstico , Neutropenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Febre/diagnóstico , Febre/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/mortalidade , Neutropenia/etiologia , Neutropenia/mortalidade , Estudos Prospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: One of the COVID-19 pandemic consequences that has affected families the most is school lockdowns. Some studies have shown that distance learning has been especially challenging for families with a child with neurodevelopmental disorders such as ADHD or ASD. However, previous studies have not taken the heterogeneity of these disorders into account. The aim of the present study was therefore to investigate differences between families with a child with ADHD, ASD, or both conditions, and to examine the role of underlying deficits in executive functioning (EF) in both children and parents in relation to negative and positive effects of distance learning. METHODS: Survey data assessing both negative and positive experiences of distance learning were collected from parents with a child aged 5-19 years in seven Western European countries: the UK, Germany, Spain, Sweden, the Netherlands, Italy, and Belgium. Altogether, the study included 1010 families with a child with ADHD and/or ASD and an equally large comparison group of families with a child without mental health problems. We included measures of three different types of negative effects (i.e., effects on the child, effects on the parent, and lack of support from school) and positive effects on the family. RESULTS: Results confirmed that families with a child with ADHD, ASD or a combination of ADHD and ASD showed higher levels of both negative and positive effects of distance learning than the comparison group. However, few differences were found between the clinical groups. Group differences were more pronounced for older compared to younger children. Regarding the role of both ADHD/ASD diagnosis and EF deficits, primarily children's EF deficits contributed to high levels of negative effects. Parent EF deficits did not contribute significantly beyond the influence of child EF deficits. Families of children with ADHD/ASD without EF deficits experienced the highest levels of positive effects. CONCLUSIONS: School closings during COVID-19 have a major impact on children with EF problems, including children with neurodevelopmental disorders. The present study emphasizes that schools should not focus primarily on whether a student has a neurodevelopmental disorder, but rather provide support based on the student's individual profile of underlying neuropsychological deficits.
RESUMO
INTRODUCTION: Limited information is available on people's experiences of living with Alzheimer's disease (AD) at earlier stages. This study assessed awareness of diagnosis among people with early-stage AD and its impact on different person-centered outcome measures. METHODS: We conducted an observational, cross-sectional study in 21 memory clinics in Spain. Persons aged 50-90 years, diagnosed with prodromal or mild AD (NIA/AA criteria), a Mini Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5 or 1.0 were recruited. The Representations and Adjustment to Dementia Index (RADIX) was used to assess participants' beliefs about their condition and its consequences. RESULTS: A total of 149 persons with early-stage AD were studied. Mean (SD) age was 72.3 (7.0) years and 50.3% were female. Mean duration of AD was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1) and 87.2% had a CDR-GS score of 0.5. Most participants (n = 84, 57.5%) used a descriptive term related to specific AD symptoms (e.g., memory difficulties) when asked what they called their condition. Participants aware of their diagnosis using the term AD (n = 66, 45.2%) were younger, had more depressive symptoms, and poorer life satisfaction and quality of life compared to those without awareness of their specific diagnosis. Practical and emotional consequences RADIX scores showed a significant negative correlation with Quality of Life in Alzheimer's Disease score (rho = - 0.389 and - 0.413, respectively; p < 0.0001). Years of education was the only predictor of awareness of AD diagnosis [OR = 1.04 (95% CI 1.00-1.08); p = 0.029]. CONCLUSIONS: Awareness of diagnosis was a common phenomenon in persons with early-stage AD negatively impacting their quality of life. Understanding illness representations in earlier stages may facilitate implementing optimized care that supports improved quality of life and well-being.
RESUMO
BACKGROUND: There is a need to better understand the experience of patients living with Alzheimer's disease (AD) in the early stages. OBJECTIVE: The aim of the study was to evaluate the perception of quality of life in patients with early-stage AD. METHODS: A multicenter, non-interventional study was conducted including patients of 50-90 years of age with prodromal or mild AD, a Mini-Mental State Examination (MMSE) score ≥22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5.-1.0. The Quality of Life in Alzheimer 's Disease (QoL-AD) questionnaire was used to assess health-related quality of life. A battery of self-report instruments was used to evaluate different psychological and behavioral domains. Associations between the QoL-AD and other outcome measures were analyzed using Spearman's rank correlations. RESULTS: A total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years and mean disease duration was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1). The mean QoL-AD score was 37.9 (4.5). Eighty-three percent (n = 124) of patients had moderate-to-severe hopelessness, 22.1% (n = 33) had depressive symptoms, and 36.9% (n = 55) felt stigmatized. The quality of life showed a significant positive correlation with self-efficacy and negative correlations with depression, emotional and practical consequences, stigma, and hopelessness. CONCLUSION: Stigma, depressive symptoms, and hopelessness are frequent scenarios in AD negatively impacting quality of life, even in a population with short disease duration and minimal cognitive impairment.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , AutorrelatoRESUMO
This is a prospective, observational study of a consecutive cohort of allogeneic hematopoietic stem cell transplantation (allo-HSCT) adult recipients conducted between July 2003 and May 2006, with the aim of identifying the current incidence, etiology, risk factors for infections and associated mortality up to two yr after allo-HSCT. Seventy-four episodes of infection were recorded in 38 patients, 50 consecutive adult patients underwent 54 allo-HSCT. The incidence of infection was 1.36 (68/50) episodes/patient after the first year of transplantation and 1.48 (74/50) episodes/patient after first two yr of transplantation. The most common syndrome was cytomegalovirus (CMV) infection, followed by catheter-related bloodstream infection and pneumonia. An etiological diagnosis was established in 85.1% of the episodes. Bacteria were the most common etiology (55.5%), followed by viruses (41.3%) and fungi (4.8%). CMV was the most common viral agent (73%), and all fungal infections were caused by molds. Myeloablative conditioning regimen, chronic graft-versus-host disease, and medical complications post-transplant were independent risk factors for infection. The global mortality two yr after transplantation was 32%, and death was infection related in 12%. In spite of advances, infections continue to be a common cause of morbidity and mortality following allo-HSCT.
Assuntos
Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções/etiologia , Infecções/mortalidade , Adolescente , Adulto , Estudos de Coortes , Feminino , Seguimentos , Neoplasias Hematológicas/cirurgia , Humanos , Incidência , Infecções/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Autólogo , Adulto JovemRESUMO
BACKGROUND: The use of pre-emptive or prophylactic treatment to control cytomegalovirus (CMV) replication after solid organ transplant (SOT) remains controversial. The aim of this study was to evaluate whether administration of pre-emptive treatment to control viral replication guided by a highly sensitive diagnostic tool is an effective approach for preventing CMV disease, even in high-risk transplant recipients. METHODS: Plasma samples from eight SOT patients were tested using antigenaemia and real-time PCR (RT-PCR) assays. Pre-emptive treatment was administered guided by RT-PCR when viral load values were >1,000 copies/ml. RESULTS: All patients developed episodes of CMV infection, but none of them developed CMV disease or indirect effects. No patient in this study died or experienced graft rejection. Treatment was needed in 10 replication episodes. At the end of treatment, four had undetectable levels and the other six were cleared 3 weeks later. In 42.6% of tested samples RT-PCR was more sensitive for detecting viral infection. CONCLUSIONS: Pre-emptive monitoring of SOT patients at high risk for CMV infection protected patients from developing CMV disease during the first 6 months after transplant. The use of this sensitive method for guiding pre-emptive treatment diminished viral load early enough that it did not have consequences for patient health.
Assuntos
Antivirais , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/efeitos dos fármacos , Ganciclovir/análogos & derivados , Transplante de Órgãos/efeitos adversos , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Citomegalovirus/genética , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Feminino , Ganciclovir/administração & dosagem , Ganciclovir/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Risco , Sensibilidade e Especificidade , Resultado do Tratamento , Valganciclovir , Carga Viral , Proteínas da Matriz Viral/sangueRESUMO
UNLABELLED: Infections are frequent and serious in pediatric RT recipients; however, the information available is scarce. The aim of this study was to determine the incidence, etiology, and risk factors for infection in these patients. This was a prospective, observational study of a consecutive pediatric RT recipient cohort. Risk factors for infection and descriptive analyses during the first two post-transplantation years were performed. Twenty-one patients (58.3%) had at least one infection (incidence 1.5 episodes/patient/first year of transplantation). There were 33 bacterial infections (73.3%), 11 viral infections (24.4%), and one protozoal infection. UTI was the most common syndrome (48.3%), followed by CMV infection (15.5%). The main microorganisms isolated were Escherichia coli (28.9%), 46.1% of which were ESBL producers, and CMV (20%). Patient and graft survival at the end of follow-up were 97.2% and 83.3%, respectively. The only risk factor for infection was cold ischemia time >800 min (OR 5.7, CI 95% 1.7-19.3). CONCLUSIONS: In pediatric RT recipients, UTI is the most frequent syndrome. Bacterial infections are the most common, with a high rate of ESBL producer strains. Despite their good prognosis, infections are a cause of morbidity that could potentially be reduced by decreasing cold ischemia times.
Assuntos
Infecções/epidemiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imunossupressores/uso terapêutico , Incidência , Infecções/complicações , Infecções/diagnóstico , Infecções/etiologia , Falência Renal Crônica/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , EspanhaRESUMO
BACKGROUND: Continuation of empirical antimicrobial therapy (EAT) for febrile neutropenia in patients with haematological malignancies until neutrophil recovery could prolong the therapy unnecessarily. We aimed to establish whether EAT discontinuation driven by a clinical approach regardless of neutrophil recovery would optimise the duration of therapy. METHODS: We did an investigator-driven, superiority, open-label, randomised, controlled phase 4 clinical trial in six academic hospitals in Spain. Eligible patients were adults with haematological malignancies or haemopoietic stem-cell transplantation recipients, with high-risk febrile neutropenia without aetiological diagnosis. An independent, computer-generated randomisation sequence was used to randomly enrol patients (1:1) to the experimental or control group. Investigators were masked to assignment only before randomisation. EAT based on an antipseudomonal ß-lactam drug as monotherapy (ceftazidime or cefepime, meropenem or imipenem, or piperacillin-tazobactam) or as combination therapy (with an aminoglycoside, fluoroquinolone, or glycopeptide) was started according to local protocols and following international guidelines and recommendations. For the experimental group, EAT was withdrawn after 72 h or more of apyrexia plus clinical recovery; for the control group, treatment was withdrawn when the neutrophil count was also 0·5â×â109 cells per L or higher. The primary efficacy endpoint was the number of EAT-free days. Primary analyses were done in the intention-to-treat population. Efficacy and safety analyses were done in the intention-to-treat population and the per-protocol population. This trial is registered with ClinicalTrials.gov, number NCT01581333. FINDINGS: Between April 10, 2012, and May 31, 2016, 157 episodes among 709 patients assessed for eligibility were included in analyses. 78 patients were randomly assigned to the experimental group and 79 to the control group. The mean number of EAT-free days was significantly higher in the experimental group than in the control group (16·1 [SD 6·3] vs 13·6 [7·2], absolute difference -2·4 [95% CI -4·6 to -0·3]; p=0·026). 636 adverse events were reported (341 in the experimental group vs 295 in the control group; p=0·057) and most (580 [91%]; 323 in the experimental group vs 257 in the control group) were considered mild or moderate (grade 1-2). The most common adverse events in the experimental versus the control group were mucositis (28 [36%] of 78 patients vs 20 [25%] of 79 patients), diarrhoea (23 [29%] of 78 vs 24 [30%] of 79), and nausea and vomiting (20 [26%] of 78 vs 22 [28%] of 79). 56 severe adverse events were reported, 18 in the experimental group and 38 in the control group. One patient died in the experimental group (from hepatic veno-occlusive disease after an allogeneic haemopoietic stem-cell transplantation) and three died in the control group (one from multiorgan failure, one from invasive pulmonary aspergillosis, and one from a post-chemotherapy intestinal perforation). INTERPRETATION: In high-risk patients with haematological malignancies and febrile neutropenia, EAT can be discontinued after 72 h of apyrexia and clinical recovery irrespective of their neutrophil count. This clinical approach reduces unnecessary exposure to antimicrobials and it is safe. FUNDING: Instituto de Salud Carlos III, Spanish Ministry of Economy (PI11/02674).
Assuntos
Anti-Infecciosos/uso terapêutico , Neutropenia Febril/tratamento farmacológico , Neoplasias Hematológicas/complicações , Adulto , Anti-Infecciosos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Diarreia/etiologia , Quimioterapia Combinada , Neutropenia Febril/complicações , Neutropenia Febril/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/epidemiologia , Náusea/etiologia , Risco , Resultado do TratamentoRESUMO
Social psychologists have shown a profound interest in intergroup relationships, but there are very few papers focusing on the developmental aspects that explain the psychological mechanisms involved in the construction of group and cultural identity. Our research aims to explore how the self-categorization of Andalusian children evolves. We tried to assess the degree to which they self-identify as Andalusian, Spanish, and European, and how this identification changes with age. We were also interested in the affective evaluation of different groups (French, Italian, English, German, Spanish, Catalonian, and Andalusian) made by Andalusian children. Furthermore, we analyzed the relationship between self-categorization and the evaluation of these groups. Results show that the development of national (autonomous community) identity in these children is influenced by their cognitive development, as well as by the relationships among the regional communities of Spain and the relationships between Spain and other countries. The peculiarity of Andalusians as a group is that they assume both identities: Spanish and Andalusian, from a very early age. In-group favoritism is an extended phenomenon at all ages, and Andalusian children have a negative stereotype of the other Spanish groups and other European communities.
Assuntos
Etnicidade/psicologia , Identificação Social , Estereotipagem , Adolescente , Criança , Pré-Escolar , Diversidade Cultural , Feminino , Humanos , Masculino , Preconceito , EspanhaRESUMO
Incidence, etiology, and outcome of infectious episodes in patients with myeloid neoplasms receiving azacitidine are uncertain, with no prospective data available in this group of patients. The aim of the current study was to analyze the incidence and factors related to the probability of infection in a cohort of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with azacitidine who did not receive any type of antimicrobial prophylaxis. Significantly, the group of patients who received prior intensive chemotherapy had more infectious episodes (P = 10(-4)), and particularly, invasive aspergillosis (P = .015), than patients who received frontline azacitidine. Primary antifungal prophylaxis might be recommended in MDS and AML patients receiving azacitidine as salvage therapy after intensive regimens.
Assuntos
Antifúngicos/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/microbiologia , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação/métodosRESUMO
PURPOSE: Catheter-related bloodstream infections (CRBSI) are common among patients undergoing long-term hemodialysis (HD) worldwide. The aim of this study was look into the incidence, epidemiology, and risk factors for CRBSI in four medical centers and Spanish dialysis facilities following a common protocol for insertion and management of tunneled hemodialysis catheters (THCs). METHODS: Prospective study including all THCs inserted from September-04 to October-05. Follow-up was from THC insertion to its withdrawal, onset of CRBSI or end of study. Data of all THCs, CRBSI episodes, and catheter complications were collected. A descriptive analysis of CRBSI incidence and etiology and multivariate Cox regression to identify risk factors for CRBSI was performed. RESULTS: A total of 130 THCs in 123 patients were inserted. There were 34 879 catheter-days. Twelve CRBSI in 11 patients with a CRBSI rate of 0.34/1000 catheter-days were recorded. CRBSI was caused by gram-positive coccus in 91.7% of the cases. Vascular cause of renal disease (HR 25.5 CI95% 5.5-117.2), and a previous THC (HR 5.1 CI95% 1.3-19.1) were identified as risk factors for CRBSI. CRBSI were satisfactorily resolved in 83.3% of the cases. Overall mortality was 14.6% (18/123), in two cases (2/11) death occurred within 30 days after CRBSI onset. CONCLUSIONS: Although some factors, such as vascular cause of renal disease and previous THC medical history, have been related to the onset of tunneled catheter-related bloodstream infections, the incidence of these bacteremia, mainly produced by gram-positive coccus, is low among hemodialysis patients and the mortality rate is not high.
Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Infecções por Bactérias Gram-Positivas/epidemiologia , Diálise Renal/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Relacionadas a Cateter/sangue , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/mortalidade , Cateterismo Venoso Central/instrumentação , Cateterismo Venoso Central/mortalidade , Feminino , Infecções por Bactérias Gram-Positivas/sangue , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/mortalidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Diálise Renal/instrumentação , Diálise Renal/mortalidade , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: It has been suggested that preemptive therapy against cytomegalovirus (CMV) infection after transplantation promotes a CMV-specific immune response. Our objective was to determine whether solid-organ transplant patients at high risk for CMV infection treated preemptively acquire a CMV-specific immune response and whether the acquired immune response confers immunity by controlling subsequent CMV replication episodes and by protecting from late-onset CMV disease. METHODS: Patients were followed up for 18 months after transplantation. CMV viral load was determined using real-time polymerase chain reaction assays, and the T-cell immune response was characterized by intracellular cytokine staining. RESULTS: The 21 patients studied developed CMV replication episodes at a median of 4 weeks (range 2-8 weeks) after transplantation and a CMV-specific T-cell response within a median of 12 weeks (range 10-20 weeks). The decline in the incidence of CMV replication episodes is inversely correlated with the acquisition of the CMV-specific T-cell response (linear regression r=0.781, Pearson correlation=-0.883; P=0.001). There were no CMV replication episodes after week 47 of transplantation. In addition, after acquisition of the immune response, 42 replication episodes were cleared without treatment. The time taken for immune clearance of replication correlated with the peak viral load (P=0.01). No incidence of CMV early or late-onset disease was detected. CONCLUSIONS: Our results demonstrate that preemptive therapy is a safe and an effective strategy for the control of CMV infection in solid-organ transplant recipients at high risk for CMV infection. This is the first study that reports a therapeutic effect of the acquisition of CMV-specific immune response during preemptive treatment.
Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/efeitos dos fármacos , Transplante de Órgãos/efeitos adversos , Adulto , Idoso , Citocinas/metabolismo , Citomegalovirus/genética , Citomegalovirus/crescimento & desenvolvimento , Citomegalovirus/imunologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Linfócitos T/imunologia , Linfócitos T/virologia , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Replicação ViralRESUMO
Walker-Warburg syndrome (WWS) is the most severe of a group of congenital disorders that have in common defects in the O-glycosylation of alpha-dystroglycan. WWS is characterized by congenital muscular dystrophy coupled with severe ocular and brain malformations. Moreover, in at least one-fifth of the reported cases, mutations in the POMT1 gene are responsible for this disease. During embryonic development (E8.5 to E11.5), the mouse Pomt1 gene is expressed in the tissues most severely affected in WWS, the muscle, eye, and brain. In this study, we show that mPomt1 expression is maintained in the muscle and eye in later developmental stages and, notably, that its expression is particularly strong in regions of brain and cerebellum that, when affected, could generate the defects observed in patients with WWS. We show that the Pomt1 protein is localized to the sarcoplasmic reticulum of muscle tissue cells in adult mice, where alpha-dystroglycan is O-glycosylated. Furthermore, the Pomt1 protein is localized to the acrosome of maturing spermatids, where alpha-dystroglycan is not glycosylated, so that Pomt1 might have a different target for O-mannosylation in the testes. This expression pattern in the testes could also be related to the gonadal anomalies observed in some patients with WWS.