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1.
BMC Geriatr ; 22(1): 680, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978306

RESUMO

BACKGROUND: Older people receive care from multiple providers which often results in a lack of coordination. The Information and Communication Technology (ICT) enabled value-based methodology for integrated care (ValueCare) project aims to develop and implement efficient outcome-based, integrated health and social care for older people with multimorbidity, and/or frailty, and/or mild to moderate cognitive impairment in seven sites (Athens, Greece; Coimbra, Portugal; Cork/Kerry, Ireland; Rijeka, Croatia; Rotterdam, the Netherlands; Treviso, Italy; and Valencia, Spain). We will evaluate the implementation and the outcomes of the ValueCare approach. This paper presents the study protocol of the ValueCare project; a protocol for a pre-post controlled study in seven large-scale sites in Europe over the period between 2021 and 2023. METHODS: A pre-post controlled study design including three time points (baseline, post-intervention after 12 months, and follow-up after 18 months) and two groups (intervention and control group) will be utilised. In each site, (net) 240 older people (120 in the intervention group and 120 in the control group), 50-70 informal caregivers (e.g. relatives, friends), and 30-40 health and social care practitioners will be invited to participate and provide informed consent. Self-reported outcomes will be measured in multiple domains; for older people: health, wellbeing, quality of life, lifestyle behaviour, and health and social care use; for informal caregivers and health and social care practitioners: wellbeing, perceived burden and (job) satisfaction. In addition, implementation outcomes will be measured in terms of acceptability, appropriateness, feasibility, fidelity, and costs. To evaluate differences in outcomes between the intervention and control group (multilevel) logistic and linear regression analyses will be used. Qualitative analysis will be performed on the focus group data. DISCUSSION: This study will provide new insights into the feasibility and effectiveness of a value-based methodology for integrated care supported by ICT for older people, their informal caregivers, and health and social care practitioners in seven different European settings. TRIAL REGISTRATION: ISRCTN registry number is 25089186 . Date of trial registration is 16/11/2021.


Assuntos
Prestação Integrada de Cuidados de Saúde , Qualidade de Vida , Idoso , Cuidadores/psicologia , Comunicação , Ensaios Clínicos Controlados como Assunto , Europa (Continente)/epidemiologia , Humanos , Qualidade de Vida/psicologia
2.
Breast Cancer ; 27(3): 426-434, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31832891

RESUMO

PURPOSE: The aim of this study was to compare patient-reported outcomes (PROs) of BRCA1/2 mutation carriers, either after bilateral prophylactic mastectomy (BPM) or during breast surveillance, to improve shared decision-making in their cancer risk management. METHODS: Unaffected BRCA1/2 mutation carriers at least one year after BPM followed by immediate breast reconstruction (BPM-IBR) or one year under surveillance were eligible. After informed consent, the Hospital Anxiety and Depression Scale (HADS) and BREAST-Q were administered and compared between the different strategies. PROs were also compared to available normative data. RESULTS: Ninety-six participants were analyzed in this study and showed significant differences between strategies in age, age at genetic testing, and time since BPM or starting breast surveillance. All HADS scores were below 8 suggesting no signs of anxiety or depression in both groups. Higher mean 'Q-physical well-being' scores were reported by the surveillance group (81.78 [CI 76.99-86.57]) than the BPM group (76.96 [CI 73.16 - 80.75]; p = 0.011). Overall, for both questionnaires better scores were seen when compared to age-matched normative data. CONCLUSIONS: No signs of anxiety or depression were seen in the surveillance or BPM-IBR group. Slightly better mean BREAST-Q scores were seen for the surveillance group in comparison to BPM-IBR, except for 'Q-psychological well-being'. The difference in 'Q-physical well-being' was significantly worse for BPM-IBR. Approaches to obtain longitudinal PROs and reference values should be explored in the future, which could add value to shared decision-making in regards to breast cancer risk management in this specific patient population.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/cirurgia , Tomada de Decisão Compartilhada , Mastectomia/métodos , Medidas de Resultados Relatados pelo Paciente , Gestão de Riscos/normas , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos
4.
Eur J Surg Oncol ; 45(7): 1163-1170, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30638807

RESUMO

PURPOSE: Adding value of care to patients is crucial for all stakeholders. The use of both provider and patient reported outcome data was implemented in a single academic breast cancer center. We describe the development of the outcomes set, data integration within electronical health records (EHR) and clinical use. METHODS: An Integrated Practice Unit (IPU) was constructed providing the full care cycle for breast cancer patients. Provider reported outcomes and patient reported outcomes (PROs) were defined, reflecting the entire cycle of care and long-term sustainability of quality of life. Multidisciplinary provider and patient perspectives were obtained via focus groups and surveys. Patient pathways were redesigned in order to identify suitable opportunities for data collection during the entire care cycle. RESULTS: A Standard Set for Breast Cancer Outcomes together with case-mix variables and timelines was agreed upon within the IPU. A secure electronic platform, directly linked to the EHR, was designed to measure PROs during the outpatient phase. First year evaluation showed a decrease of response rates over time, from 83.3% at baseline to 45.2% at 12 months after surgery. Patients reacted positively to the use of PROMs in daily clinical cancer care. CONCLUSION: Assessment of patient reported as well as provider reported outcomes was implemented within our standard of breast cancer care. For this, dedicated resources, change of culture and practice, and improved knowledge and awareness about Value-based healthcare (VBHC) were essential. Our proposed framework aims to serve as a blueprint for implementation of VBHC in daily care.


Assuntos
Neoplasias da Mama/terapia , Análise Custo-Benefício , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Centros Médicos Acadêmicos , Institutos de Câncer , Registros Eletrônicos de Saúde , Feminino , Grupos Focais , Hospitalização/estatística & dados numéricos , Humanos , Ciência da Implementação , Países Baixos , Equipe de Assistência ao Paciente , Qualidade da Assistência à Saúde , Inquéritos e Questionários , Taxa de Sobrevida , Resultado do Tratamento
5.
Ann Surg Oncol ; 25(12): 3563-3571, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30178391

RESUMO

PURPOSE: Considering the comparable prognosis in early-stage breast cancer after breast-conserving therapy (BCT) and mastectomy, quality of life should be a focus in treatment decision(s). We retrospectively collected PROs and analyzed differences per type of surgery delivered. We aimed to obtain reference values helpful in shared decision-making. PATIENTS AND METHODS: pTis-T3N0-3M0 patients operated between January 2005 and September 2016 were eligible if: (1) no chemotherapy was administered < 6 months prior to enrolment, and (2) identical surgeries were performed in case of bilateral surgery. After consent, EQ-5D-5L, EORTC-QLQ-C30/BR23, and BREAST-Q were administered. PROs were evaluated per baseline characteristics using multivariable linear regression models. Outcomes were compared for different surgeries as well as for primary (PBC) and second primary or recurrent (SBC) breast cancer patients using analyses of variance (ANOVAs). RESULTS: The response rate was 68%. PROs in 612 PBC patients were comparable to those in 152 SBC patients. Multivariable analyses showed increasing age to be associated with lower "physical functioning" [ß - 0.259, p < 0.001] and "sexual functioning" [ß - 0.427, p < 0.001], and increasing time since surgery with less "fatigue" [ß - 1.083, p < 0.001]. Mastectomy [ß - 13.596, p = 0.003] and implant reconstruction [ß - 13.040, p = 0.007] were associated with lower "satisfaction with breast" scores than BCT. Radiation therapy was associated with lower satisfaction scores than absence of radiotherapy. DISCUSSION: PRO scores were associated with age, time since surgery, type of surgery, and radiation therapy in breast cancer patients. The scores serve as a reference value for different types of surgery in the study population and enable prospective use of PROs in shared decision-making.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Mastectomia , Satisfação do Paciente , Qualidade de Vida , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/patologia , Carcinoma Lobular/radioterapia , Estudos Transversais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Radioterapia , Estudos Retrospectivos
7.
Ned Tijdschr Tandheelkd ; 125(2): 70-75, 2018 Feb.
Artigo em Holandês | MEDLINE | ID: mdl-29461539

RESUMO

The quality of care for patients with cleft lip and palate is extremely variable across the world. Treatment protocols differ and methods of data registration are not uniform. Improving this care by means of comparative research is challenging. The best treatment programmes can be identified by uniformly registering patient-orientated outcomes and comparing the outcomes with those of other treatment centres. That knowledge can be used to improve one's own care. An international team consisting of specialists and cleft lip and palate patients has developed a set of outcome measures that are considered by patients to be most important. This team is coordinated by the International Consortium of Health Outcomes Measurement (ICHOM). The cleft lip and palate outcome set can be used by all centres worldwide in following up on cleft lip and palate patients. In the Erasmus Medical Centre in Rotterdam, the 'Zorgmonitor Schisis' (Care Monitor Cleft Lip and Palate) has been built, an application in which these outcome measures are collected at fixed times. Implementing this set of outcome measures in other cleft lip and palate treatment centres and using the outcomes as (inter)national benchmarks will result in transparency and the improvement of the treatment of cleft lip and palate worldwide.


Assuntos
Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Odontologia/normas , Qualidade da Assistência à Saúde , Odontologia/métodos , Humanos , Resultado do Tratamento
8.
Intensive Crit Care Nurs ; 26(3): 128-37, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20171889

RESUMO

OBJECTIVES: To assess psychological distress, styles of coping and disease-related psychosocial limitations in parents of children and adolescents who survived meningococcal septic shock (MSS) 4-16 years ago. RESEARCH METHODOLOGY: An exploratory design using standardised questionnaires and interviews. SETTING: The psychological investigation took place in the department of Child and Adolescent Psychiatry of the ErasmusMC-Sophia Children's Hospital. MAIN OUTCOME MEASURES: 87 mothers and 77 fathers participated in this study. The General Health Questionnaire was used to assess parents' psychological distress; the Utrecht Coping List to assess styles of coping. A semi-structured disease-specific interview served to explore long-term disease-related psychosocial limitations for parents. RESULTS: MSS parents reported similar psychiatric symptoms and styles of coping in comparison to reference groups. Severity of illness and the child's age at time of illness were not significant predictors of parental psychological distress and styles of coping. The presence of somatic sequelae, cognitive or behavioural and emotional problems was not associated with the levels of parental psychiatric symptoms or styles of coping. The vast majority of parents reported no current disease-related psychosocial limitations due to the MSS. CONCLUSION: Parents of children who survived MSS show recovery. Nevertheless a minority still experiences emotional burden and disease-related limitations.


Assuntos
Pais/psicologia , Choque Séptico/microbiologia , Estresse Psicológico , Adaptação Psicológica , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Lactente , Infecções Meningocócicas , Estresse Psicológico/epidemiologia , Sobreviventes
9.
Arch Dis Child ; 94(5): 381-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19147623

RESUMO

OBJECTIVE: To assess the incidence of skin scarring and orthopaedic sequelae (amputation, limb-length discrepancy) in patients who survived meningococcal septic shock (MSS) in childhood and to determine the severity and predictors of these sequelae. METHODS: 179 consecutive patients (170 of whom were eligible) with septic shock and purpura requiring intensive care between 1988 and 2001 in Rotterdam, the Netherlands were invited to visit a follow-up clinic 4-16 years after paediatric intensive care unit (PICU) discharge. RESULTS: 58 (48%) of 120 follow-up patients (median follow-up interval 10 years; median age at follow-up 14.5 years) had skin scarring due to purpura. This varied from barely visible to extremely disfiguring scars. Ten patients (8%) had undergone amputation(s) of extremities, ranging from one toe to both legs and one arm. Seven patients (6%) had lower limb-length discrepancy, in most cases together with angular deformity, requiring one or more late surgical intervention(s). Patients with scars or orthopaedic sequelae had significantly higher severity of illness scores, determined by the Pediatric Risk of Mortality score, Vasopressor score and Disseminated Intravascular Coagulation score. Gender or Neisseria meningitidis serogroup had no significant influence on the presence of scars or orthopaedic sequelae. Patients with lower limb-length discrepancy were significantly younger at the time of PICU admission. CONCLUSIONS: The incidence of long-term skin scarring and orthopaedic sequelae was high (48% and 14%, respectively) in patients who survived MSS in childhood. The severity of these sequelae varied from mild to severe. Patients with scars or orthopaedic sequelae had significantly higher severity of illness scores.


Assuntos
Amputação Cirúrgica/estatística & dados numéricos , Cicatriz/etiologia , Infecções Meningocócicas/complicações , Púrpura/complicações , Choque Séptico/complicações , Adolescente , Criança , Pré-Escolar , Cicatriz/epidemiologia , Cicatriz/patologia , Estudos Transversais , Feminino , Humanos , Incidência , Lactente , Desigualdade de Membros Inferiores/epidemiologia , Desigualdade de Membros Inferiores/etiologia , Masculino , Países Baixos , Qualidade de Vida , Autoimagem , Índice de Gravidade de Doença , Sobreviventes , Fatores de Tempo , Resultado do Tratamento
10.
Br J Clin Psychol ; 48(Pt 2): 195-208, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19091165

RESUMO

AIMS: To assess long-term cognitive functioning and its predictors, in children and adolescents who survived meningococcal septic shock (MSS) 4 to 16 years ago. METHODS: The Wechsler Intelligence Scale for Children-third edition was used to measure intellectual functioning and neuropsychological tests were used to measure attention, verbal memory, visual-motor integration, and executive skills. RESULTS: Overall, results of the total MSS sample (N=77) as to neuropsychological functioning were similar to those of normative reference groups. On social and practical reasoning and visual-motor integration, however, MSS children obtained poorer outcomes compared to normative data. Two children had mental retardation (estimated IQ<70) due to the MSS. The percentage of children with mental retardation or borderline intellectual functioning (15%) was similar to that in the general population (16%). Eighteen children (23%) had a z score<-2, indicating unusual poor functioning, on one or more domains of neuropsychological functioning (selective attention, sustained attention, and executive functioning). Compared to normative data, significantly more children had received special education services in the past. Older age at time of follow-up was the most important significant predictor of poorer long-term cognitive functioning. CONCLUSION: Overall, long-term outcomes as to cognitive functioning of the total MSS sample were similar to those of normative reference groups, but MSS children showed long-term impairments on social and practical reasoning, visual-motor integration, attention, and executive functioning. Older age at time of follow-up was a significant predictor.


Assuntos
Transtornos Cognitivos/diagnóstico , Neisseria meningitidis , Testes Neuropsicológicos , Choque Séptico/psicologia , Sobreviventes/psicologia , Adolescente , Fatores Etários , Criança , Transtornos Cognitivos/psicologia , Educação Inclusiva , Feminino , Seguimentos , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/psicologia , Deficiência Intelectual/reabilitação , Estudos Longitudinais , Masculino , Neisseria meningitidis/isolamento & purificação , Choque Séptico/microbiologia , Escalas de Wechsler
11.
Br J Clin Psychol ; 47(Pt 3): 251-63, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18039432

RESUMO

OBJECTIVES: To assess the occurrence of a wide range of behavioural, emotional, and post-traumatic stress problems in children and adolescents, long term after septic shock caused by Neisseria meningitidis (MSS). DESIGN: This study included 6- to 17-year-old patients who survived MSS and were admitted to the PICU of the Medical Centre between 1988 and 2001. To assess behavioural, emotional, and post-traumatic stress problems, the Child Behaviour Checklist (CBCL), the Teacher's Report Form (TRF), and the Youth Self-Report (YSR) were used. METHODS: Parents of 89 MSS children, aged 6-17 years, completed the CBCL. Teachers of 65 same-aged MSS children completed the TRF, and 45 11- to 17-year-old MSS children completed the YSR. These data were compared with those from the normative reference groups. RESULTS: Overall, the proportions of MSS children scoring in the deviant range for problem behaviour were comparable to the proportions in the reference groups, according to parents', teachers', and self-reports. As to the level of emotional and behavioural problems, mothers of the MSS children reported more somatic complaints regarding their children in comparison with the reference groups. Severity of illness was not a significant predictor of behavioural, emotional, and post-traumatic stress problems. Age at the time of illness was a significant predictor of behavioural, emotional, and post-traumatic stress problems in MSS children, indicating that the younger the child at the time of illness, the more problems were reported by parents at follow-up. CONCLUSION: Overall, the results showed long-term behavioural, emotional, and post-traumatic stress outcomes for MSS children, which were comparable to those in the general population.


Assuntos
Sintomas Afetivos/diagnóstico , Transtornos do Comportamento Infantil/diagnóstico , Infecções Meningocócicas/microbiologia , Transtornos Mentais/diagnóstico , Neisseria meningitidis/isolamento & purificação , Choque Séptico/microbiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Adolescente , Adulto , Sintomas Afetivos/etiologia , Sintomas Afetivos/psicologia , Criança , Transtornos do Comportamento Infantil/etiologia , Transtornos do Comportamento Infantil/psicologia , Filho de Pais com Deficiência/psicologia , Filho de Pais com Deficiência/estatística & dados numéricos , Grupos Controle , Feminino , Humanos , Estudos Longitudinais , Masculino , Infecções Meningocócicas/complicações , Infecções Meningocócicas/psicologia , Transtornos Mentais/etiologia , Transtornos Mentais/psicologia , Mães/psicologia , Mães/estatística & dados numéricos , Inventário de Personalidade/estatística & dados numéricos , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Índice de Gravidade de Doença , Choque Séptico/complicações , Choque Séptico/psicologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/diagnóstico , Estresse Psicológico/etiologia , Estresse Psicológico/psicologia , Inquéritos e Questionários , Sobreviventes/psicologia
12.
J Thromb Haemost ; 6(2): 268-76, 2008 02.
Artigo em Inglês | MEDLINE | ID: mdl-18021301

RESUMO

BACKGROUND AND OBJECTIVES: In pediatric meningococcal sepsis, an imbalance between coagulation and fibrinolysis and proinflammatory action play major roles. We hypothesized that thrombin activatable fibrinolysis inhibitor (TAFI) and/or TAFI activation markers are involved in the pathogenesis of meningococcal sepsis. PATIENTS AND METHODS: Children with severe meningococcal sepsis (n = 112) previously included in Rotterdam-based trials participated in this study. Clinical and laboratory parameters and severity scores were assessed. TAFI and TAFI activation markers were determined: TAFI activation peptide (TAFI-AP) and (in)activated TAFI [TAFIa(i)]. The -438G/A, Ala147Thr, and Thr325Ile polymorphisms were genotyped. RESULTS: TAFI levels were significantly decreased in patients with meningococcal disease at admission compared to the convalescence state. TAFI was decreased in patients with septic shock vs. those with no shock. TAFI-AP levels were increased in patients with disseminated intravascular coagulation (DIC) vs. patients without DIC. TAFI-AP and TAFIa(i) were significantly increased in non-survivors vs. survivors. TAFI-AP levels and the TAFI-AP/TAFI ratio were also strongly correlated to severity scores and laboratory parameters. The TAFI 325Ile/Ile genotype was overrepresented in patients with DIC. CONCLUSIONS: Activation markers of TAFI were associated with the occurrence of DIC and mortality in meningococcal sepsis patients. A determination of TAFI, TAFI-AP, and TAFIa(i) is required to enable coherent interpretation of the role of TAFI in disease.


Assuntos
Carboxipeptidase B2/sangue , Infecções Meningocócicas/sangue , Adolescente , Carboxipeptidase B2/genética , Criança , Pré-Escolar , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/epidemiologia , Coagulação Intravascular Disseminada/etiologia , Ativação Enzimática , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Masculino , Infecções Meningocócicas/complicações , Infecções Meningocócicas/microbiologia , Infecções Meningocócicas/mortalidade , Mutação de Sentido Incorreto , Neisseria meningitidis/classificação , Neisseria meningitidis/isolamento & purificação , Mutação Puntual , Sorotipagem , Índice de Gravidade de Doença , Choque Séptico/sangue , Choque Séptico/epidemiologia , Choque Séptico/etiologia , Análise de Sobrevida , Resultado do Tratamento
13.
Emerg Med J ; 21(1): 61-4, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14734379

RESUMO

OBJECTIVE: To evaluate the inventory for initial treatment of critically ill children. DESIGN: Prospective study. SETTING: Paediatric emergency settings in 15 major district general hospitals. METHODS: Using an "expert opinion" created by paediatric intensivists, all hospitals were visited twice to check the inventory. Firstly, to examine the initial site of emergency care for children coming from outside the hospital. Secondly, to visit other emergency sites. A total score below 75% of the optimum was considered as not optimally equipped. MAIN RESULTS: Equipment to meet "respiratory problems" was considered by the experts as most essential. Seventy five per cent of all emergency sites scored below 75% (4 of 11 paediatric departments, 1 of 15 emergency rooms. The emergency room was in all aspects significantly better equipped than the paediatric department. Major differences and variations in the inventory were identified between all hospitals. CONCLUSIONS: Emergency rooms are better equipped to meet the needs of critically ill paediatric patients coming from outside the hospital than the paediatric departments. Paediatricians involved in the treatment of children who become critically ill during their stay in the hospital (the "indoor" patients), have less equipment and medication on the paediatric department at their disposal than on their emergency room. Obviously, emergency care on the paediatric wards should be equipped at the same level as in the emergency room because for both locations the "golden hour" is critically important in final outcome.


Assuntos
Serviços de Saúde da Criança , Serviço Hospitalar de Emergência , Criança , Serviços de Saúde da Criança/organização & administração , Emergências , Serviço Hospitalar de Emergência/organização & administração , Equipamentos e Provisões Hospitalares , Hospitais de Distrito , Hospitais Gerais , Humanos , Países Baixos , Estudos Prospectivos
14.
Lancet Infect Dis ; 3(9): 565-77, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12954563

RESUMO

The clinical presentation of infections caused by Neisseria meningitidis is highly diverse. Some patients develop meningitis, and others present with sepsis or even septic shock. After invasion of the bloodstream by the bacteria, three main cascade pathways are activated. These are the complement system, the inflammatory response, and the coagulation and fibrinolysis pathway. These pathways do not act independently but are able to interact with each other. Genetic polymorphisms among components of these pathways have been shown to be involved in the susceptibility, severity, and outcome of meningococcal disease. We review knowledge of genetic variations associated with susceptibility to and severity of meningococcal infection. Complement deficiencies and defects in sensing or opsonophagocytic pathways, such as the rare Toll-like receptor 4 single nucleotide polymorphisms (SNPs) and combinations of inefficient variants of Fcgamma-receptors, seem to have the most important role in genetically established susceptibility. Effect on severity has repeatedly been reported for FcgammaRIIa and plasminogen activator inhibitor type 1 (PAI1) polymorphisms. Outcome effects have been confirmed for SNPs in properdin deficiencies, PAI1 and combination of the -511C/T SNP in interleukin 1beta, and the +2018C/T SNP in interleukin RN. Conflicting results are reported for the effect of the -308G/A promoter polymorphism in tumour necrosis factor (TNF) alpha. These differences may reflect discrepancies in group definitions between studies or the influence of additional SNPs in the TNFalpha promoter, which can form haplotypes representing different cytokine production capacity. For several SNPs, the potential effect on susceptibility, severity, or outcome has not yet been confirmed in an independent study.


Assuntos
Glicoproteínas de Membrana/imunologia , Meningite Meningocócica , Neisseria meningitidis/genética , Receptores de Superfície Celular/imunologia , Criança , Citocinas/genética , Citocinas/fisiologia , Humanos , Meningite Meningocócica/classificação , Meningite Meningocócica/genética , Meningite Meningocócica/fisiopatologia , Polimorfismo Genético , Índice de Gravidade de Doença , Ativador de Plasminogênio Tecidual/fisiologia , Receptor 4 Toll-Like , Receptores Toll-Like
15.
Intensive Care Med ; 28(11): 1606-12, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12415448

RESUMO

OBJECTIVE: To assess the prognostic value of procalcitonin levels during the clinical course of meningococcal disease in children. DESIGN: A retrospective, descriptive study. SETTING: University paediatric intensive care unit. PATIENTS: Nine patients with meningococcal sepsis and 55 patients with meningococcal septic shock were included in the study, giving a total of 64. MEASUREMENTS AND RESULTS: Procalcitonin (PCT), C-reactive protein (CRP), cytokines (IL-6, IL-8 and TNF-alpha), plasminogen activator inhibitor-1 (PAI-1) and several routine laboratory parameters were determined and expressed as medians (ranges). PCT levels on hospitalisation were elevated in all children as compared to normal values. Median PCT levels on admission were significantly higher in children with septic shock than in children with sepsis (270 ng/ml (5.7-672.3) versus 64.4 (20.6-283.7); p<0.01). When the patients were categorised to severity using the Pediatric Risk of Mortality (PRISM) score (group 1: <15 points, group 2: 16-30, group 3: >30), the PCT levels were significantly different in the three groups. All markers, with the exception of PCT (p=0.056), were significantly different between survivors and non-survivors. When the duration of petechiae was taken into account, the difference in PCT levels became significant (p=0.04). CONCLUSIONS: Procalcitonin levels on admission are related to severity. In the case of a short disease history (duration of petechiae), PCT levels are also related to mortality. Although PCT levels are elevated in all patients, the levels per se do not allow a prediction about survival versus non-survival, this is in contrast to other markers and scores (PRISM).


Assuntos
Calcitonina/sangue , Infecções Meningocócicas/sangue , Precursores de Proteínas/sangue , Choque Séptico/sangue , Adolescente , Área Sob a Curva , Proteína C-Reativa/análise , Peptídeo Relacionado com Gene de Calcitonina , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Humanos , Lactente , Masculino , Infecções Meningocócicas/mortalidade , Inibidor 1 de Ativador de Plasminogênio/sangue , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Choque Séptico/microbiologia , Choque Séptico/mortalidade , Estatísticas não Paramétricas
16.
J Clin Endocrinol Metab ; 87(7): 3118-24, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12107211

RESUMO

Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs), IGFBP-3 protease, glucose, insulin, and cytokines in 27 children with severe septic shock due to meningococcal sepsis during the first 3 d after admission. The median age was 22 months (range, 4-185 months). Eight patients died. Nonsurvivors had extremely high GH levels that were significant different compared with mean GH levels in survivors during a 6-h GH profile (131 vs. 7 mU/liter; P < 0.01). Significant differences were found between nonsurvivors and survivors for the levels of total IGF-I (2.6 vs. 5.6 nmol/liter), free IGF-I (0.003 vs. 0.012 nmol/liter), IGFBP-1 (44.3 vs. 8.9 nmol/liter), IGFBP-3 protease activity (61 vs. 32%), IL-6 (1200 vs. 50 ng/ml), and TNFalpha (34 vs. 5.3 pg/ml; P < 0.01). The pediatric risk of mortality score correlated significantly with levels of IGFBP-1, IGFBP-3 protease activity, IL-6, and TNFalpha (r = +0.45 to +0.69) and with levels of total IGF-I and free IGF-I (r = -0.44 and -0.55, respectively). Follow-up after 48 h in survivors showed an increased number of GH peaks, increased free IGF-I and IGFBP-3 levels, and lower IGFBP-1 levels compared with admission values. GH levels and IGFBP-1 levels were extremely elevated in nonsurvivors, whereas total and free IGF-I levels were markedly decreased and were accompanied by high levels of the cytokines IL-6 and TNFalpha. These values were different from those for the survivors. Based on these findings and literature data a hypothetical model was constructed summarizing our current knowledge and understanding of the various mechanisms.


Assuntos
Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Infecções Meningocócicas/complicações , Choque Séptico/sangue , Choque Séptico/microbiologia , Adolescente , Glicemia/análise , Criança , Pré-Escolar , Endopeptidases/sangue , Feminino , Hormônio do Crescimento Humano/metabolismo , Humanos , Lactente , Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Interleucina-6/metabolismo , Masculino , Choque Séptico/mortalidade , Fator de Necrose Tumoral alfa/metabolismo
18.
Pediatr Crit Care Med ; 2(3): 284-5, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12813247
19.
Methods Mol Med ; 67: 513-27, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-21337164

RESUMO

Disseminated intravascular coagulation (DIC) is a complex acquired, coagulopathy resulting from excessive thrombin formation. Abnormal tissue factor (TF) expression is a major mechanism initiating DIC in many disorders, including obstetric complications, sepsis, cancer, and trauma. Numerous laboratory tests are available to monitor DIC, but most patients can be adequately managed using only routine hemostasis screening tests, and assays for fibrinogen and D-dimers. Treatment of DIC should focus on reversing the underlying disorder that initiated the coagulopathy. Novel treatments are being investigated for the treatment of DIC; many of these experimental modalities target the excessive TF activity that characterizes DIC.

20.
J Clin Endocrinol Metab ; 85(10): 3746-53, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11061534

RESUMO

To get insight in the endocrine and metabolic responses in children with meningococcal sepsis 26 children were studied the first 48 h after admission. On admission there was a significant difference in cortisol/ACTH levels between nonsurvivors (n = 8) and survivors (n = 18). Nonsurvivors showed an inadequate cortisol stress response in combination to very high ACTH levels, whereas survivors showed a normal stress response with significantly higher cortisol levels (0.62 vs. 0.89 micromol/L) in combination with moderately increased ACTH levels (1234 vs. 231 ng/L). Furthermore, there was a significant difference between nonsurvivors and survivors regarding pediatric risk of mortality score (31 vs. 17), TSH (0.97 vs. 0.29 mE/L), T3 (0.53 vs. 0.38 nmol/L), reverse T3 (rT3) (0.75 vs. 1.44 nmol/L), C-reactive protein (34 vs. 78 mg/L), nonesterified fatty acids (0.32 vs. 0.95 mmol/L), and lactate (7.3 vs. 3.2 mmol/L). In those who survived, the most important changes within 48 h were seen in a normalization of cortisol and ACTH levels, but without a circadian rhythm; a decrease of rT3 and an increase in the T3/rT3 ratio; and a decrease in the levels of the nonesterified free fatty acids and an unaltered high urinary nitrogen excretion. At this moment, it is yet unknown whether the hormonal abnormalities are determining factors in the outcome of acute meningococcal sepsis or merely represent secondary effects. Understanding the metabolic and endocrine alterations is required to design possible therapeutic approaches. The striking difference between nonsurvivors and survivors calls for reconsideration of corticosteroid treatment in children with meningococcal sepsis.


Assuntos
Glândulas Endócrinas/fisiopatologia , Infecções Meningocócicas/metabolismo , Infecções Meningocócicas/fisiopatologia , Adolescente , Hormônio Adrenocorticotrópico/sangue , Glicemia/metabolismo , Criança , Pré-Escolar , Ingestão de Energia , Humanos , Hidrocortisona/sangue , Lactente , Insulina/sangue , Nitrogênio/urina , Sepse/metabolismo , Sepse/fisiopatologia , Sobreviventes , Hormônios Tireóideos/sangue , Fatores de Tempo
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