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INTRODUCTION: Micro- and macrovascular complications are common among persons with type 2 diabetes. Recently there has been growing interest to investigate the potential of circulating small non-coding RNAs (sncRNAs) as contributors to the development of diabetic complications. In this study we investigate to what extent circulating sncRNAs levels associate with prevalent diabetic kidney disease (DKD) in persons with type 2 diabetes. METHODS: Plasma sncRNAs levels were determined using small RNA-seq, allowing detection of miRNAs, snoRNAs, piRNAs, tRNA fragments, and various other sncRNA classes. We tested for differentially expressed sncRNAs in persons with type 2 diabetes, with DKD (n = 69) or without DKD (n = 405). In secondary analyses, we also tested the association with eGFR, albuminuria (UACR), and the plasma proteome. RESULTS: In total seven sncRNAs were negatively associated with prevalent DKD (all PFDR ≤ 0.05). Including one microRNA (miR-143-5p), five snoRNAs (U8, SNORD118, SNORD24, SNORD107, SNORD87) and a piRNA (piR-019825 | DQ597218). Proteomic analyses showed that the seven sncRNAs, and especially the piRNA piR-019825, were associated with plasma levels of 24 proteins of which several have known associations with kidney function including TNF sR-I (TNFRFS1A), DAN (NBL1) and cystatin C (CST3). CONCLUSION: We have identified novel small non-coding RNAs, primarily from classes other than microRNAs, that are associated with diabetic kidney disease. Our results show that the involvement of small non-coding RNAs in DKD goes beyond the already known microRNAs and also involves other classes of sncRNA, in particular snoRNAs and the piRNA piR-019825, that have never been studied before in relation to kidney function.
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As neonatal mortality rates have decreased in esophageal atresia (EA), there is a growing focus on quality of life (QoL) in these children. No study from Africa has reported on this topic. This pilot study aimed to describe disease-specific QoL in EA children and its applicability as part of long-term follow-up in an academic facility in South Africa. Disease-specific QoL in children born with EA was assessed utilizing the EA-QoL questionnaire for children aged 2-17 years during a patient-encounter. The parent-report for children aged 2-7 years compromised 17 items categorized into three domains: eating, physical health and treatment, and social isolation/stress. The 24-item EA-QL questionnaire for children aged 8-18 (child- and parent-report) explored four domains: eating, body perception, social relationships, and health and well-being. A total of 13 questionnaires for children aged 2-7 years were completed by five parents. A negative perceived impact on their child's eating was reported by 46-92% of parents, and less impact in the other two domains. A total of 27 questionnaires were completed by eight children aged 8-17 years and 10 parents. Similar percentages children and parents reported a negative impact in the eating, social relationships, and body perception domains. More than half reported a negative impact on the child's health and well-being. This study supports the concept that assessment of disease-specific QoL should play a vital role in the comprehensive follow-up approach for children born with EA. We identified that parents of younger children were more likely to report eating disorders, whereas parents of older children were more likely to report health difficulties with different perceptions when it came to the child's scar.
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Atresia Esofágica , Calidad de Vida , Humanos , Proyectos Piloto , Niño , Sudáfrica , Atresia Esofágica/psicología , Masculino , Femenino , Preescolar , Estudios de Seguimiento , Adolescente , Encuestas y Cuestionarios , Padres/psicologíaRESUMEN
BACKGROUND: Children with long-gap esophageal atresia (LGEA) risk living with aerodigestive morbidity and mental health difficulties. No previous study has investigated their experiences of schooling, despite the importance of schools in children's development, learning and social relationships. We aimed to describe experiences of schooling in children with LGEA in Sweden in comparison with children with EA who had primary anastomosis. METHOD: Children with LGEA aged 3-17 were recruited nationwide in Sweden. One parent completed a survey on their child's school-based supports (according to definitions from the Swedish National Agency for Education), school absence, school satisfaction, school functioning (PedsQL 4.0), mental health (Strength and Difficulties Questionnaire) and current symptomatology. School data were compared between 26 children with LGEA to that from 95 children with EA who had PA, a hypothesized milder affected group. Mental health level was determined using validated norms; abnormal ≥ 90 percentile. Data were analyzed using descriptives, correlation and Mann-Whitney-U test. Significance level was p < 0.05. RESULTS: Formal school-based support was reported in 17 (65.4%) children with LGEA and concerned support with nutritional intake (60%), education (50%) and medical/special health needs (35%). The prevalence of school-based support was significantly higher compared to children with PA overall (36.8%, p = 0.013) and regarding nutritional intake support (20%, p < 0.001). In children with LGEA, school-based support was related to low birth weight (p = 0.036), young child age (p = 0.014), height ≤ -2SD for age/sex (p = 0.024) and an increased number of aerodigestive symptoms (p < 0.05). All children with LGEA who had abnormal mental health scores had school-based support, except for one child. Nine children with LGEA (36%) had school absence ≥ 1times/month the past year, more frequently because of colds/airway infections (p = 0.045) and GI-specific problems compared to PA (p = 0.003). School functioning scores were not significantly different from children with PA (p = 0.34) but correlated negatively with school-based support (< 0.001) and school absence (p = 0.002). One parent out of 26 reported their child's school satisfaction as "not good". CONCLUSIONS: Children with LGEA commonly receive school-based support, reflecting multifaceted daily needs and disease severity. School absence is frequent and related to poorer school functioning. Future research focusing on academic achievement in children with EA is needed.
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Atresia Esofágica , Niño , Humanos , Atresia Esofágica/cirugía , Atresia Esofágica/psicología , Suecia , Encuestas y Cuestionarios , Anastomosis Quirúrgica , Salud MentalRESUMEN
Developments in medical big data analytics may bring societal benefits but are also challenging privacy and other ethical values. At the same time, an overly restrictive data protection regime can form a serious threat to valuable observational studies. Discussions about whether data privacy or data solidarity should be the foundational value of research policies, have remained unresolved. We add to this debate with an empirically informed ethical analysis. First, experiences with the implementation of the General Data Protection Regulation (GDPR) within a European research consortium demonstrate a gap between the aims of the regulation and its effects in practice. Namely, strictly formalised data protection requirements may cause routinisation among researchers instead of substantive ethical reflection, and may crowd out trust between actors in the health data research ecosystem; while harmonisation across Europe and data sharing between countries is hampered by different interpretations of the law, which partly stem from different views about ethical values. Then, building on these observations, we use theory to argue that the concept of trust provides an escape from the privacy-solidarity debate. Lastly, the paper details three aspects of trust that can help to create a responsible research environment and to mitigate the encountered challenges: trust as multi-agent concept; trust as a rational and democratic value; and trust as method for priority setting. Mutual cooperation in research-among researchers and with data subjects-is grounded in trust, which should be more explicitly recognised in the governance of health data research.
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Confianza , Humanos , Europa (Continente) , PrivacidadRESUMEN
OBJECTIVES: To extend our investigation of cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients to a follow up of more than 20 years, with a special focus on patients without prevalent CVD. METHODS: The CARRÉ study is an ongoing prospective cohort study on CV endpoints in RA patients. Results were compared to those of a reference cohort (n = 2484) enriched for type 2 diabetes mellitus (DM). Hazard ratios (HR) for RA and DM patients compared to non-RA/-DM controls were calculated with cox proportional hazard models, and adjusted for baseline SCORE1 (estimated 10-year CVD mortality risk based on CV risk factors). RESULTS: 238 RA patients, 117 DM patients and 1282 controls, without prevalent CVD at baseline were included. Analysis of events in these patients shows that after adjustment, no relevant 'RA-specific' risk remains (HR 1.16; 95%CI 0.88 - 1.53), whereas a 'DM-specific' risk is retained (1.73; 1.24 - 2.42). In contrast, adjusted analyses of all cases confirm the presence of an 'RA-specific' risk (1.50; 1.19 - 1.89). CONCLUSIONS: In RA patients without prevalent CVD the increased CVD risk is mainly attributable to increased presence of traditional risk factors. After adjustment for these factors, an increased risk attributable to RA only was thus preferentially seen in the patients with prevalent CVD at baseline. As RA treatment has improved, this data suggests that the 'RA-specific' effect of inflammation is preferentially seen in patients with prevalent CVD. We suggest that with modern (early) treatment of RA, most of the current increased CVD risk is mediated through traditional risk factors.
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Artritis Reumatoide , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Estudios de Cohortes , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Estudios de Seguimiento , Estudios Prospectivos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiología , Factores de Riesgo , IncidenciaRESUMEN
BACKGROUND: Cardiovascular risk factors and lifestyle factors are associated with an increased risk of cognitive decline and dementia in observational studies, and have been targeted by multidomain interventions. OBJECTIVES: We pooled individual participant data from two multi-domain intervention trials on cognitive function and symptoms of depression to increase power and facilitate subgroup analyses. DESIGN: Pooled analysis of individual participant data. SETTING: Prevention of Dementia by Intensive Vascular Care trial (preDIVA) and Multidomain Alzheimer Preventive Trial (MAPT). PARTICIPANTS: Community-dwelling individuals, free from dementia at baseline. INTERVENTION: Multidomain interventions focused on cardiovascular and lifestyle related risk factors. MEASUREMENTS: Data on cognitive functioning, depressive symptoms and apathy were collected at baseline, 2 years and 3-4 years of follow-up as available per study. We analyzed crude scores with linear mixed models for overall cognitive function (Mini Mental State Examination [MMSE]), and symptoms of depression and apathy (15-item Geriatric Depression Scale). Prespecified subgroup analyses were performed for sex, educational level, baseline MMSE <26, history of hypertension, and history of stroke, myocardial infarction and/or diabetes mellitus. RESULTS: We included 4162 individuals (median age 74 years, IQR 72, 76) with a median follow-up duration of 3.7 years (IQR 3.0 to 4.1 years). No differences between intervention and control groups were observed on change in cognitive functioning scores and symptoms of depression and apathy scores in the pooled study population. The MMSE declined less in the intervention groups in those with MMSE <26 at baseline (N=250; MD: 0.84; 95%CI: 0.15 to 1.54; p<0.001). CONCLUSIONS: We found no conclusive evidence that multidomain interventions reduce the risk of global cognitive decline, symptoms of depression or apathy in a mixed older population. Our results suggest that these interventions may be more effective in those with lower baseline cognitive functioning. Extended follow-up for dementia occurrence is important to inform on the potential long-term effects of multidomain interventions.
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Enfermedad de Alzheimer , Apatía , Anciano , Cognición , Depresión/epidemiología , Depresión/prevención & control , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: Out-of-hospital cardiac arrest (OHCA) occurrence has been shown to exhibit a circadian rhythm, following the circadian rhythm of acute myocardial infarction (AMI) occurrence. Diabetes mellitus (DM) is associated with changes in circadian rhythm. We aimed to compare the temporal variation of OHCA occurrence over the day and week between OHCA patients with DM and those without. METHODS: In two population-based OHCA registries (Amsterdam Resuscitation Studies [ARREST] 2010-2016, n = 4163, and Danish Cardiac Arrest Registry [DANCAR], 2010-2014, n = 12,734), adults (≥18y) with presumed cardiac cause of OHCA and available medical history were included. Single and double cosinor analysis was performed to model circadian variation of OHCA occurrence. Stratified analysis of circadian variation was performed in patients with AMI as immediate cause of OHCA. RESULTS: DM patients (22.8% in ARREST, 24.2% in DANCAR) were older and more frequently had cardiovascular risk factors or previous cardiovascular disease. Both cohorts showed 24 h-rhythmicity, with significant amplitudes in single and double cosinor functions (P-range < 0.001). In both registries, a morning peak (10:00-11:00) and an evening peak (20:00-21:00) was observed in both DM and non-DM patients. No septadian variation was observed in either DM or non-DM patients (P-range 0.13-84). CONCLUSIONS: In these two population-based OHCA registries, we observed a similar circadian rhythm of OHCA occurrence in DM and non-DM patients.
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INTRODUCTION: In cardiac arrest, ventricular fibrillation (VF) waveform characteristics such as amplitude spectrum area (AMSA) are studied to identify an underlying myocardial infarction (MI). Observational studies report lower AMSA-values in patients with than without underlying MI. Moreover, experimental studies with 12-lead ECG-recordings show lowest VF-characteristics when the MI-localisation matches the ECG-recording direction. However, out-of-hospital cardiac arrest (OHCA)-studies with defibrillator-derived VF-recordings are lacking. METHODS: Multi-centre (Amsterdam/Nijmegen, the Netherlands) cohort-study on the association between AMSA, ST-elevation MI (STEMI) and its localisation. AMSA was calculated from defibrillator pad-ECG recordings (proxy for lead II, inferior vantage point); STEMI-localisation was determined using ECG/angiography/autopsy findings. RESULTS: We studied AMSA-values in 754 OHCA-patients. There were statistically significant differences between no STEMI, anterior STEMI and inferior STEMI (Nijmegen: no STEMI 13.0mVHz [7.9-18.6], anterior STEMI 7.5mVHz [5.6-13.8], inferior STEMI 7.5mVHz [5.4-11.8], p = 0.006. Amsterdam: 11.7mVHz [5.0-21.9], 9.6mVHz [4.6-17.2], and 6.9mVHz [3.2-16.0], respectively, p = 0.001). Univariate analyses showed significantly lower AMSA-values in inferior STEMI vs. no STEMI; there was no significant difference between anterior and no STEMI. After correction for confounders, adjusted absolute AMSA-values were numerically lowest for inferior STEMI in both cohorts, and the relative differences in AMSA between inferior and no STEMI was 1.4-1.7 times larger than between anterior and no STEMI. CONCLUSION: This multi-centre VF-waveform OHCA-study showed significantly lower AMSA in case of underlying STEMI, with a more pronounced difference for inferior than for anterior STEMI. Confirmative studies on the impact of STEMI-localisation on the VF-waveform are warranted, and might contribute to earlier diagnosis of STEMI during VF.
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Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Infarto del Miocardio con Elevación del ST , Cardioversión Eléctrica , Electrocardiografía , Humanos , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/diagnóstico , Fibrilación VentricularRESUMEN
The increased use of the automated external defibrillator (AED) contributes to the rising survival rate after sudden cardiac arrest in the Netherlands. When used, the AED records the unconscious person's medical data (heart rhythm and information about cardiopulmonary resuscitation), which may be important for further diagnosis and treatment. In practice, ethical and legal questions arise about what can and should be done with these 'AED data'. In this article, the authors advocate the development of national guidelines on the handling of AED data. These guidelines should serve two purposes: (1) to safeguard that data are handled carefully in accordance with data protection principles and the rules of medical confidentiality; and (2) to ensure nationwide availability of data for care of patients who survive resuscitation, as well as for quality monitoring of this care and for related scientific research. Given the medical ethical duties of beneficence and fairness, existing (sometimes lifesaving) information about AED use ought to be made available to clinicians and researchers on a structural basis. Creating a national AED data infrastructure, however, requires overcoming practical and organisational barriers. In addition, further legal study is warranted.
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INTRODUCTION: Cumulative disease burden may be associated with survival chances after out-of-hospital cardiac arrest (OHCA). The relative contributions of cumulative disease burden on survival rates at the pre-hospital and in-hospital phases of post-resuscitation care are unknown. METHODS: The association between cumulative comorbidity burden as measured by the Charlson Comorbidity Index (CCI) and pre-hospital and in-hospital survival rates was studied using data (2010-2014) from a prospective OHCA registry in the Netherlands. The association between CCI and survival rate (overall survival [OHCA-hospital discharge], pre-hospital survival [OHCA-hospital admission] and in-hospital survival [hospital admission-hospital discharge]) was assessed using logistic regression analyses. The relative contributions of CCI on pre-hospital and in-hospital survival rates were determined using the Nagelkerke test. RESULTS: We included 2510 OHCA patients aged ≥18y. CCI was significantly associated with overall survival rate (OR 0.71; 95%CI 0.61-0.83; Pâ¯<â¯0.01). CCI was not associated with pre-hospital survival rate (OR 0.96; 95%CI 0.76-1.23; Pâ¯=â¯0.92) whereas high CCI was significantly associated with low in-hospital survival rate (OR 0.41; 95%CI 0.27-0.62; Pâ¯=â¯0.01). The relative contributions of CCI on pre-hospital and in-hospital survival were 1.1% and 8.1%, respectively. CONCLUSION: Pre-existing high comorbidity burden plays a modest role in reducing survival rate after OHCA, and only in the in-hospital phase. The present study offers data that may guide clinicians in discussing resuscitation options during advance care planning with patients with high comorbidity burden. This may be helpful in creating a patients' informed choice.
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Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Paro Cardíaco Extrahospitalario , Comorbilidad , Hospitales , Humanos , Países Bajos/epidemiología , Paro Cardíaco Extrahospitalario/epidemiología , Paro Cardíaco Extrahospitalario/terapia , Estudios Prospectivos , Sistema de Registros , Tasa de SupervivenciaRESUMEN
PURPOSE: Bladder-bowel questionnaires are an important tool in diagnosing nonneurogenic bladder-bowel dysfunction in children. We report the validity and reliability of a bladder-bowel questionnaire that has been in clinical use at our institution for decades. MATERIALS AND METHODS: The bladder-bowel questionnaire contains 13 questions, with answers ranging from never (score of 0) to daily (3). The questionnaire was answered by 139 healthy controls and 134 children 3 to 16 years old diagnosed with bladder-bowel dysfunction by a pediatric urologist/urotherapist. A subdiagnosis of overactive bladder or dysfunctional voiding was made in each patient. Bladder-bowel questionnaire scales were developed and evaluated against hypotheses of validity (known groups/convergent/discriminating) and reliability (internal consistency/retest reliability), sensitivity and specificity. Responsiveness was tested in 80 patients who answered the bladder-bowel questionnaire after treatment. RESULTS: A total bladder-bowel dysfunction score scale demonstrated the ability to discriminate between patients with bladder-bowel dysfunction and healthy subjects. It resulted in a ROC curve with AUC of 0.96. The maximized sensitivity was 94% and specificity was 89% for a cutoff score of 7. Two subscales were identified referring to 6 filling phase items and 3 voiding phase items. When tested in patients with overactive bladder and dysfunctional voiding, respectively, multivariable scales performed sufficiently to discriminate between those with and without overactive bladder, and those with and without dysfunctional voiding. All of these scales fulfilled the evaluated requirements for validity and reliability. At 1 year after treatment all scale scores corresponded to patient improvement (p <0.0001), suggesting the bladder-bowel questionnaire can detect clinical change over time. CONCLUSIONS: The bladder-bowel questionnaire is valid and reliable for diagnosing bladder-bowel dysfunction in pediatric patients, and overactive bladder and dysfunctional voiding in those with bladder-bowel dysfunction.
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Enfermedades Intestinales/diagnóstico , Índice de Severidad de la Enfermedad , Vejiga Urinaria Hiperactiva/diagnóstico , Micción/fisiología , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Defecación/fisiología , Femenino , Voluntarios Sanos , Humanos , Enfermedades Intestinales/fisiopatología , Masculino , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Suecia , Vejiga Urinaria Hiperactiva/fisiopatologíaRESUMEN
With increasing age, associations between traditional risk factors (TRFs) and cardiovascular disease (CVD) shift. It is unknown which mid-life risk factors remain relevant predictors for CVD in older people. We systematically searched PubMed and EMBASE on August 16th 2019 for studies assessing predictive ability of >1 of fourteen TRFs for fatal and non-fatal CVD, in the general population aged 60+. We included 12 studies, comprising 11 unique cohorts. TRF were evaluated in 2 to 11 cohorts, and retained in 0-70% of the cohorts: age (70%), diabetes (64%), male sex (57%), systolic blood pressure (SBP) (50%), smoking (36%), high-density lipoprotein cholesterol (HDL) (33%), left ventricular hypertrophy (LVH) (33%), total cholesterol (22%), diastolic blood pressure (20%), antihypertensive medication use (AHM) (20%), body mass index (BMI) (0%), hypertension (0%), low-density lipoprotein cholesterol (0%). In studies with low to moderate risk of bias, systolic blood pressure (SBP) (80%), smoking (80%) and HDL cholesterol (60%) were more often retained. Model performance was moderate with C-statistics ranging from 0.61 to 0.77. Compared to middle-aged adults, in people aged 60+ different risk factors predict CVD and current prediction models perform only moderate at best. According to most studies, age, sex and diabetes seem valuable predictors of CVD in old-age. SBP, HDL cholesterol and smoking may also have predictive value. Other blood pressure and cholesterol related variables, BMI, and LVH seem of very limited or no additional value. Without competing risk analysis, predictors are overestimated.
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Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Factores de Edad , Anciano , Índice de Masa Corporal , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Humanos , Hipertensión , Persona de Mediana Edad , Países BajosRESUMEN
PURPOSE: VACTERL association is a rare and complex condition of congenital malformations, often requiring repeated surgery and entailing various physical sequelae. Due to scarcity of knowledge, the study aim was to investigate self-reported health-related quality of life (HRQoL), anxiety, depression and self-concept in children and adolescents with VACTERL association and self-reported anxiety and depression in their parents. METHODS: Patients aged 8-17 years with VACTERL association and their parents were recruited from three of four Swedish paediatric surgical centres during 2015-2019. The well-established validated questionnaires DISABKIDS, Beck Youth Inventories, Beck Anxiety Inventory and Beck Depression Inventory were sent to the families. Data were analysed using descriptives, t tests and multivariable analysis. Results were compared with norm groups and reference samples. RESULTS: The questionnaires were returned by 40 patients, 38 mothers and 33 fathers. The mean HRQoL was M = 80.4, comparable to children with asthma (M = 80.2) and diabetes (M = 79.5). Self-reported psychological well-being was comparable to the norm group of Swedish school children, and was significantly higher than a clinical sample. Factors negatively influencing children's HRQoL and psychological well-being were identified. The parents' self-reports of anxiety and depression were comparable to non-clinical samples. CONCLUSIONS: Although children and adolescents with VACTERL association reported similar HRQoL to those of European children with chronic conditions, their psychological well-being was comparable to Swedish school children in general. Nevertheless, some individuals among both children and parents were in need of extra support. This attained knowledge is valuable when counselling parents regarding the prognosis for children with VACTERL association.
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Canal Anal/anomalías , Esófago/anomalías , Cardiopatías Congénitas/psicología , Riñón/anomalías , Deformidades Congénitas de las Extremidades/psicología , Padres/psicología , Calidad de Vida/psicología , Columna Vertebral/anomalías , Tráquea/anomalías , Adolescente , Ansiedad/psicología , Niño , Depresión/psicología , Femenino , Humanos , Masculino , Psicometría/métodos , Autoinforme/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
Ataxia telangiectasia (A-T) is a severe neurodegenerative disorder with variable immunodeficiency. Together with the Dutch A-T community, we investigated the opinion of A-T parents on an early A-T diagnosis in the asymptomatic phase of the disease. During an annual national meeting for A-T patients and families, the topic of an early A-T diagnosis was discussed in relation to the recent introduction of neonatal screening for severe combined immunodeficiency (SCID) in the Netherlands. Based on the discussion, individual arguments were identified and processed into a questionnaire, which was sent out to 64 A-T parents (32 families). Arguments included were insecurity to diagnosis, possible medical advantages, appropriate genetic counseling and family planning, loss of "golden" year(s), and early cancer screening for parents. The response rate was 55% (n = 35 parents). Twenty-six (74%) parents felt that the advantages of an early diagnosis outweighed the disadvantages, five parents thought that the disadvantages would outweigh the advantages (14%), and four parents did not indicate a preference.Conclusion: The majority of parents of a child with A-T would have preferred an early diagnosis during the asymptomatic phase of the disease, because the uncertainty during the diagnostic process had had a major impact on their lives. In addition, the knowledge of being carriers of an ATM gene mutation influenced decisions about family planning. Parents who opposed against an early diagnosis emphasized the joy of having a seemingly healthy child until diagnosis.What is Known:⢠Ataxia telangiectasia (A-T) is a devastating DNA repair disorder with a huge impact on quality of life of patients and their parents.⢠Patients with A-T may incidentally be identified at birth as the consequence of neonatal screening for severe combined immunodeficiency (SCID).What is New:⢠The majority of Dutch parents of A-T patients (74%) would have preferred an early diagnosis of their child in the asymptomatic phase of the disease.⢠Major arguments for an early A-T diagnosis were (1) the experienced insecurity in diagnostic trajectories and its impact on families and (2) the knowledge of being ATM mutation carriers when deciding about family planning. An argument against an early diagnosis is losing the joy of having a seemingly healthy child until diagnosis.
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Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/genética , Diagnóstico Precoz , Asesoramiento Genético , Tamizaje Neonatal/métodos , Encuestas y Cuestionarios , Adulto , Ataxia Telangiectasia/epidemiología , Preescolar , Femenino , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Recién Nacido , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Relaciones Padres-Hijo , Padres/psicología , Medición de RiesgoRESUMEN
Microfluidic systems enable automated and highly parallelized cell culture with low volumes and defined liquid dosing. To achieve this, systems typically integrate all functions into a single, monolithic device as a "one size fits all" solution. However, this approach limits the end users' (re)design flexibility and complicates the addition of new functions to the system. To address this challenge, we propose and demonstrate a modular and standardized plug-and-play fluidic circuit board (FCB) for operating microfluidic building blocks (MFBBs), whereby both the FCB and the MFBBs contain integrated valves. A single FCB can parallelize up to three MFBBs of the same design or operate MFBBs with entirely different architectures. The operation of the MFBBs through the FCB is fully automated and does not incur the cost of an extra external footprint. We use this modular platform to control three microfluidic large-scale integration (mLSI) MFBBs, each of which features 64 microchambers suitable for cell culturing with high spatiotemporal control. We show as a proof of principle that we can culture human umbilical vein endothelial cells (HUVECs) for multiple days in the chambers of this MFBB. Moreover, we also use the same FCB to control an MFBB for liquid dosing with a high dynamic range. Our results demonstrate that MFBBs with different designs can be controlled and combined on a single FCB. Our novel modular approach to operating an automated microfluidic system for parallelized cell culture will enable greater experimental flexibility and facilitate the cooperation of different chips from different labs.
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This study describes results of a condition-specific approach to the assessment of coping strategies in nutritional intake situations used by children with esophageal atresia. One hundred three families of children 2-17 years old with esophageal atresia participated (94% response rate). Following standardized focus groups with 30 families, nine coping items were developed, reflecting nine different coping strategies in nutritional intake situations. The coping items were pilot tested by 73 new families and evaluated for feasibility, validity, and reliability. The families also completed a validated condition-specific quality-of-life questionnaire for children with esophageal atresia, which included the scale Eating-Quality-of-life. Data were analyzed using descriptives, between-group analysis, and Spearman's rho (P < 0.05). Altogether, the coping items were feasible, valid, and reliable. Items reflecting problem-focused strategies revealed that 89% of 2-17 years old 'recognized their responsibility' and managed nutritional intake problems on their own, 79% 'tried to solve their feeding problems' testing different solutions, 79% took a 'confronting approach' to do what peers did in eating situations, and 54% 'sought other people's support'. Items reflecting emotion-focused strategies showed that 86% of the children 'accepted' their feeding difficulties, 68% 'reappraised feeding difficulties into positive outcomes' such as to eat only when food tasted good. Moreover, 63% of the children 'avoided' nutritional intake situations, 29% 'expressed worry or fear' when faced with these situations, while 25% 'distanced' themselves from eating problems by hiding or throwing away food. The children's use of coping strategies were mostly related to the existence of digestive symptoms (P < 0.05). Positive and negative coping strategies were identified. Of particular note was a correlation cluster of the so-called disengagement strategies 'avoidance', 'expression of emotional concerns' and 'distancing'. These strategies were negatively correlated with Eating-Quality-of-Life. Conversely, taking a 'confronting approach' correlated positively with Eating-Quality-of-life (P < 0.05). Hence, most children with esophageal atresia employ various coping strategies in nutritional intake situations. A good Eating-Quality-of-life may be positively affected by treating digestive morbidity and encouraging children to take an active approach to their eating problems rather than using disengagement coping.
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Adaptación Psicológica , Ingestión de Alimentos/psicología , Atresia Esofágica/psicología , Conducta Alimentaria/psicología , Adolescente , Ansiedad/etiología , Reacción de Prevención , Niño , Preescolar , Emociones , Femenino , Grupos Focales , Humanos , Masculino , Calidad de Vida , Encuestas y CuestionariosRESUMEN
A sputter ion source with a solid graphite target has been used to produce dianions with a focus on carbon cluster dianions, Cn2-, with n = 7-24. Singly and doubly charged anions from the source were accelerated together to kinetic energies of 10 keV per atomic unit of charge and injected into one of the cryogenic (13 K) ion-beam storage rings of the Double ElectroStatic Ion Ring Experiment facility at Stockholm University. Spontaneous decay of internally hot Cn2- dianions injected into the ring yielded Cn- anions with kinetic energies of 20 keV, which were counted with a microchannel plate detector. Mass spectra produced by scanning the magnetic field of a 90° analyzing magnet on the ion injection line reflect the production of internally hot C72- - C242- dianions with lifetimes in the range of tens of microseconds to milliseconds. In spite of the high sensitivity of this method, no conclusive evidence of C62- was found while there was a clear C72- signal with the expected isotopic distribution. This is consistent with earlier experimental studies and with theoretical predictions. An upper limit is deduced for a C62- signal that is two orders-of-magnitude smaller than that for C72-. In addition, CnO2- and CnCu2- dianions were detected.
RESUMEN
Out-of-hospital cardiac arrest (OHCA) is a major health problem that affects approximately four hundred and thousand patients annually in the United States alone. It is a major challenge for the emergency medical system as decreased survival rates are directly proportional to the time delay from collapse to defibrillation. Historically, defibrillation has only been performed by physicians and in-hospital. With the development of automated external defibrillators (AEDs), rapid defibrillation by nonmedical professionals and subsequently by trained or untrained lay bystanders has become possible. Much hope has been put to the concept of Public Access Defibrillation with a massive dissemination of public available AEDs throughout most Western countries. Accordingly, current guidelines recommend that AEDs should be deployed in places with a high likelihood of OHCA. Despite these efforts, AED use is in most settings anecdotal with little effect on overall OHCA survival. The major reasons for low use of public AEDs are that most OHCAs take place outside high incidence sites of cardiac arrest and that most OHCAs take place in residential settings, currently defined as not suitable for Public Access Defibrillation. However, the use of new technology for identification and recruitment of lay bystanders and nearby AEDs to the scene of the cardiac arrest as well as new methods for strategic AED placement redefines and challenges the current concept and definitions of Public Access Defibrillation. Existing evidence of Public Access Defibrillation and knowledge gaps and future directions to improve outcomes for OHCA are discussed. In addition, a new definition of the different levels of Public Access Defibrillation is offered as well as new strategies for increasing AED use in the society.