Somatic symptoms, pain, catastrophizing and the association with disability among children with heritable connective tissue disorders.

The aim of the present study was to investigate the nature and prevalence of nonspecific somatic symptoms, pain and catastrophizing in children with Heritable Connective Tissue Disorders (HCTD), and to determine their association with disability. This observational, multicenter study included 127 children, aged 4-18 years, with Marfan syndrome (MFS) (59%), Loeys-Dietz syndrome (LDS) (8%), Ehlers-Danlos syndromes (EDS) (12%) and hypermobile Ehlers-Danlos syndrome (hEDS) (23%). The assessments included the Children's Somatization Inventory or parent proxy (CSI, PCSI), pain visual-analogue scale (VAS), SUPERKIDZ body diagram, Pain Catastrophizing Scale Child or parent proxy (PCS-C, PCS-P) and Childhood Health Assessment Questionnaire (CHAQ-30). Data from children aged ≥8 years were compared to normative data. In children ≥ 8 years (n = 90), pain was present in 59%, with a median of 4 (IQR = 3-9) pain areas. Compared to normative data, the HCTD group reported significantly higher on the CSI (p ≤ 0.001, d = 0.85), VAS pain intensity (p ≤ 0.001, d = 1.22) and CHAQ-30 (p ≤ 0.001, d = 1.16) and lower on the PCS-C (p = 0.017, d = -0.82) and PCS-P (p ≤ 0.001, d = -0.49). The intensity of nonspecific somatic symptoms and pain explained 45% of the variance in disability (r2 = 0.45 F(2,48) = 19.70, p ≤ 0.001). In children ≤ 7 years (n = 37), pain was present in 35% with a median of 5(IQR = 1-13) pain areas. The mean(SD) VAS scores for pain intensity was 1.5(2.9). Functional disability was moderately correlated to the number of pain areas (r = 0.56, p ≤ 0.001), intensity of nonspecific somatic symptoms (r = 0.63, p ≤ 0.001) and pain (r = 0.83, p ≤ 0.001). In conclusion, this study supports the need for comprehensive assessment of nonspecific somatic symptoms, pain, and disability in children with HCTD to allow tailored treatment.

Parental experiences and coping strategies when caring for a child receiving paediatric palliative care: a qualitative study.

Parenting and providing extensive care to a child with a life-limiting or life-threatening disease while being aware of the future loss of the child are among the most stressful parental experiences. Due to technical and medical improvements, children are living longer and are increasingly cared for at home. To align healthcare professionals' support with the needs of parents, a clear understanding of prominent experiences and main coping strategies of parents caring for a child in need of palliative care is needed. An interpretative qualitative study using thematic analysis was performed. Single or repeated interviews were undertaken with 42 parents of 24 children with malignant or non-malignant diseases receiving palliative care. Prominent reported parental experiences were daily anxiety of child loss, confrontation with loss and related grief, ambiguity towards uncertainty, preservation of a meaningful relationship with their child, tension regarding end-of-life decisions and engagement with professionals. Four closely related coping strategies were identified: suppressing emotions by keeping the loss of their child at bay, seeking support, taking control to arrange optimal childcare and adapting to and accepting the ongoing change(s).Conclusion: Parents need healthcare professionals who understand and carefully handle their worries, losses, parent-child relationship and coping strategies. What is Known: • In paediatric palliative care, parents have a daunting task in fulfilling all caregiving tasks while striving for control of their child's symptoms, a life worth living and a family balance. What is New: • Prominent experiences were: continuous management of anxiety of child loss, feelings of uncertainty, tension with end-of-life decision making and engagement with professionals. Parents experienced unique significance to their child, reinforcing a meaningful parent-child relationship. • Relevant coping strategies were: suppressing emotions, seeking support, taking control to arrange optimal care and adapting to the ongoing changes. • To provide tailored support, professionals need to understand parents' perceptions, relationship with their child and coping strategies.

The Trigger Tool as a Method to Measure Harmful Medication Errors in Children.

OBJECTIVES: The aim of this study was to improve medication safety for children; it is important to quantify the occurrence of preventable medication errors (MEs). A trigger tool may be an effective and time-saving strategy, but its measurement performance is unclear. Therefore, we aimed to estimate the performance of a pediatric medication-focused trigger tool in detecting harmful MEs. METHODS: First, we established a multifaceted method as a reference comparison. Second, we compared the pediatric medication-focused trigger tool with the multifaceted method in a new cohort of patients. All patients admitted in February and March 2013 were screened using the trigger tool and the multifaceted method to obtain full verification. Data collection was performed in separate teams to guarantee blinding of the test results. RESULTS: Review of the clinical records and the voluntary incident reports was most effective in detecting harmful MEs, so this approach was chosen as a reference comparison. In the second part of the study, 369 patients were included. The multifaceted method identified 33 harmful MEs. In contrast, the trigger tool did not identify any harm. When the 2 symptoms pain and nausea/vomiting were added to the trigger tool, 19 harmful MEs were identified. This extended trigger tool resulted in a sensitivity of 21.2 and a positive predictive value of 36.8. CONCLUSIONS: The original pediatric medication-focused trigger tool yielded only false-positive scores and left unsafe situations undiscovered. We conclude that a multifaceted method remains the preferred method to detect harmful MEs. The additional value of the trigger tool stays unclear.

Aspects and Intensity of Pediatric Palliative Case Management Provided by a Hospital-Based Case Management Team: A Comparative Study Between Children With Malignant and Nonmalignant Disease.

OBJECTIVES: Anticipating case management is considered crucial in pediatric palliative care. In 2012, our children's university hospital initiated a specialized pediatric palliative care team (PPCT) to deliver inbound and outbound case management for children with life-shortening disease. The aim of this report is to gain insight in the first 9 months of this PPCT. METHODS: Aspects of care during the first 9 months of the PPCT are presented, and comparison is made between patients with malignant disease (MD) and nonmalignant disease (NMD) in a retrospective study design. Insight in the aspects of care of all patients with a life-shortening disease was retrieved from web-based files and the hour registrations from the PPCT. RESULTS: Forty-three children were supported by the PPCT during the first 9 months: 22 with MD with a median of 50 (1-267) days and 29 minutes (4-615) of case management per patient per day and 21 patients with NMD with a median of 79.5 (5-211) days and 16 minutes of case management per day (6-64). Our data show significantly more interprofessional contacts for patients with MD and more in-hospital contacts for patients with NMD. The median number of admission days per patient was 11 (0-22) for MD (44% for anticancer therapy) and 44 (0-303) for NMD (36% for infectious diseases). SIGNIFICANCE OF RESULTS: This overview of aspects of pediatric palliative case management shows shorter but more intensive case management for MD in comparison with NMD. This insight in palliative case management guides the design of a PPCT.

Parental experiences with a paediatric palliative care team: A qualitative study.

BACKGROUND: Parents of children with a life-limiting disease have to rely on themselves at home while adequate paediatric palliative care is lacking. In several countries, paediatric palliative care teams are introduced to ensure continuity and quality of care and to support the child and the family. Yet, little is known about how parents experience such multidisciplinary teams. AIM: To obtain insight into the support provided by a new paediatric palliative care team from the parents' perspective. DESIGN: An interpretative qualitative interview study using thematic analysis was performed. SETTING/PARTICIPANTS: A total of 47 single or repeated interviews were undertaken with 42 parents of 24 children supported by a multidisciplinary paediatric palliative care team located at a university children's hospital. The children suffered from malignant or non-malignant diseases. RESULTS: In advance, parents had limited expectations of the paediatric palliative care team. Some had difficulty accepting the need for palliative care for their child. Once parents experienced what the team achieved for their child and family, they valued the team's involvement. Valuable elements were as follows: (1) process-related aspects such as continuity, coordination of care, and providing one reliable point of contact; (2) practical support; and (3) the team members' sensitive and reliable attitude. As a point of improvement, parents suggested more concrete clarification upfront of the content of the team's support. CONCLUSION: Parents feel supported by the paediatric palliative care team. The three elements valued by parents probably form the structure that underlies quality of paediatric palliative care. New teams should cover these three valuable elements.

Aims and tasks in parental caregiving for children receiving palliative care at home: a qualitative study.

In paediatric palliative care (PPC), parents are confronted with increasing caregiving demands. More children are cared for at home, and the need for PPC of children is lengthened due to technical and medical improvements. Therefore, a clear understanding of the content of parental caregiving in PPC becomes increasingly important. The objective is to gain insight into parental caregiving based on the lived experience of parents with a child with a life-limiting disease. An interpretative qualitative study using thematic analysis was performed. Single or repeated interviews were undertaken with 42 parents of 24 children with a malignant or non-malignant disease, receiving PPC. Based on their ambition to be a 'good parent', parents caring for a child with a life-limiting disease strived for three aims: controlled symptoms and controlled disease, a life worth living for their ill child and family balance. These aims resulted in four tasks that parents performed: providing basic and complex care, organising good quality care and treatment, making sound decisions while managing risks and organising a good family life. CONCLUSION: Parents need early explanation from professionals about balancing between their aims and the related tasks to get a grip on their situation and to prevent becoming overburdened. What is Known: • In paediatric palliative care, parents are confronted with increasing caregiving demands. • Parenting is often approached from the perspective of stress. What is New: • Parents strive for three aims: controlled symptoms and controlled disease, a life worth living for their child and family balance. • Parents perform four tasks: providing basic and complex care, organising good quality care, making decisions while managing risks and organising a good family life. • Professionals need insight into the parents' aims and tasks from the parental perspective to strengthen parents' resilience.

A prospective study on the characteristics and subjects of pediatric palliative care case management provided by a hospital based palliative care team.

BACKGROUND: Case management is a subject of interest within pediatric palliative care. Detailed descriptions of the content of this type of case management are lacking. We aim to describe the contents of care provided, utilization of different disciplines, and times of usage of a pediatric palliative care case management program compared for patients with malignant disease (MD) and non-malignant disease (NMD). METHODS: A three-month prospective study, with questionnaires filled in by members of a pediatric palliative care team (PPCT) for each contact with parents. RESULTS: Four hundred fifty-five contacts took place with parents of 70 patients (27MD, 43NMD). Sixty-two percent of all contacts were with the specialized nurse. The child life specialists, psychologist and social worker were also regularly consulted, the chaplain was not consulted. Ninety-five percent of all contacts took place between 8 am and 6 pm during weekdays, a limited number between 6 pm and 9 pm. Twenty-five percent of all contacts were proactively initiated by the PPCT, 25 % were initiated by parents. In these care characteristics, no differences were seen for MD and NMD patients. Psychosocial topics were addressed most frequently. MD patients consulted the PPCT more often about school and NMD patients about socio-economic issues. CONCLUSIONS: All different disciplines of the PPCT were regularly consulted, except for the chaplain. With an easy accessible team with a highly pro-active approach, availability from 8 am to 9 pm seems sufficient to accommodate patient's and parent's needs. More anticipation seems required for socio-economic topics. This insight in pediatric palliative case management can provide guidance in the development of a new PPCT.

Preventable errors with nonopioid analgesics and antiemetic drugs may increase burden in surgical pediatric patients.

INTRODUCTION: Many hospitalized patients are affected by medication errors (MEs) that may cause discomfort, harm, and even death. Especially, children are considered to be at high risk of experiencing harm due to MEs. More insight into the prevalence, type, and severity of harm caused by MEs could help reduce the frequency of these harmful events. The primary objectives of our study were to establish the prevalence of different types of MEs and the severity of harm caused by MEs in hospitalized children from birth to 18 years of age. In addition, we investigated correlations between harmful MEs and characteristics of the collected data from 426 hospitalized children admitted, and the medication process. METHODS: In this cross-sectional study, we identified MEs by reviewing clinical records, making direct observations, monitoring pharmacy logs, and reviewing voluntary incident reports. Subsequently, the MEs were classified according to type of error, medication group and stage of the medication process. Pediatricians rated the severity of the observed harm. RESULTS: We collected data from 426 hospitalized children admitted during August to October 2011. A total of 322 MEs were identified, of which 39 caused patient harm. Harmful events were mainly because of wrong time (41%). Pediatricians rated the observed harm as minor in 77% of the incidents and significant in 23%. None of the harmful MEs resulted in permanent harm or was considered life-threatening or fatal. Patients admitted for a surgical procedure were at higher risk for a harmful event compared with patients admitted for nonsurgical reasons (adjusted odds ratio 2.79, 95% confidence interval; 1.35-5.80). Nonopioid analgesics and antiemetic drugs accounted for 67% of the harmful MEs. Harmful MEs occurred most frequently during medication prescription (28%) and administration (62%). CONCLUSION: Surgical pediatric patients seem to be at high risk for harmful MEs. Although the harm was considered minor in most cases, it still caused discomfort for the patients, and the high prevalence is a source of concern. Interventions to prevent the MEs should focus on the prescription and administration of nonopioid analgesics and antiemetic drugs.

High-alert medications for pediatric patients: an international modified Delphi study.

BACKGROUND: The available knowledge about high-alert medications for children is limited. Because children are particularly vulnerable to medication errors, a list of high-alert medication specifically for children would help to develop effective strategies to prevent patient harm. Therefore, we conducted an international modified Delphi study and validated the results with reports on medication incidents in children based on national data. OBJECTIVE: The objective of this study was to generate an internationally accepted list of high-alert medications for a pediatric inpatient population from birth to 18-years old. RESULTS: The rating panel consisted of 34 experts from 13 countries. In total, 14 medications and 4 medication classes were included with the predefined level of consensus of 75%. The high-alert medications were: amiodarone, digoxin, dopamine, epinephrine, fentanyl, gentamycin, heparine, insulin, morphine, norepinephrine, phenytoin, potassium, propofol and tacrolimus. The high-alert medication classes included in the final list were: chemotherapeutic drugs, immunosuppressive medications, lipid/total parenteral nutrition and opioids. CONCLUSION: An international group of experts defined 14 medications and 4 medication classes as high-alert for children. This list might be helpful as a starting point for individual hospitals to develop their own high-alert list tailored to their unique situation.

What brings children home? A prognostic study to predict length of hospitalisation.

UNLABELLED: Adequate discharge planning could improve patient health and reduce readmissions. Increased accessibility and adequate use of hospital capacity are asking for an adequate discharge planning by means of efficient prediction of length of stay (LOS). Predictive factors of LOS for paediatric patients are lacking in the current available evidence. We aimed to identify these predictive factors in order to predict an optimal LOS. We conducted a prognostic study of all patients admitted to five different paediatric wards of Emma Children's Hospital, a tertiary university hospital in the Netherlands. We investigated possible predictive factors based on the literature and an expert panel categorised in patient characteristics and medical and non-medical factors. This preliminary list was scored for all patients at the moment of discharge. All significant or relevant factors were used in a linear regression model to predict the LOS. We included 142 patients and explored the relationship between 28 variables, reflecting a mix of patient characteristics, medical and non-medical factors and LOS. In a univariable analysis, 17 variables were significantly related with LOS. Multivariable analysis found seven independent variables: sex, age category, specialism, risk of malnutrition, complications, home care and the involvement of other disciplines. These seven variables explained 48 % of the LOS (R(2) of 0.476). CONCLUSION: Predictors of LOS consist patient characteristics, medical factors as well as non-medical factors (i.e. the need for home care and other disciplines). The latter factors can be influenced by changes in hospital policies.

The association of ethnicity with electronically measured adherence to inhaled corticosteroids in children.

PURPOSE: To investigate the association of ethnicity with objectively, electronically measured adherence to inhaled corticosteroids (ICS) in a multicultural population of children with asthma in the city of Amsterdam. METHODS: The study was designed as a prospective, observational multicenter study in which adherence to ICS and potential risk factors for adherence to ICS were measured in a cohort of Moroccan and native Dutch children with asthma. Electronic adherence measurements were performed for 3 months per patient using a Real Time Medication Monitoring (RTMM) system. Ethnicity and other potential risk factors, such as socio-economic status, asthma control and parental medication beliefs, were extracted from medical records or parent interviews. The association between adherence and ethnicity was analysed using multivariate linear regression analysis. RESULTS: A total of 90 children (aged 1-11 years) were included in the study and data of 87 children were used for analysis. Average adherence to ICS was 49.3 %. Native Dutch children showed higher adherence to ICS than Moroccan children (55.9 vs. 42.5 %, respectively; p = 0.044, univariate analysis). After correction for confounders (>3 annual visits to the paediatric outpatient clinic, regular use of a spacer during inhalation), the final regression model showed that ethnicity was independently associated with adherence (p = 0.028). CONCLUSIONS: In our Western European population of inner city children with asthma, poor adherence to ICS was a serious problem, and even somewhat more so in ethnic minorities. Paediatricians involved in asthma treatment should be aware of these cultural differences in medication-taking behaviour, but further studies are needed to elucidate the causal mechanism.

Ethnic diversity outpatient clinic in paediatrics.

BACKGROUND: The health status of chronic sick ethnic minority children in the Netherlands is unequal compared with indigenous Dutch children. In order to optimize the health care for these children a specific patient-oriented clinic in ethnic-cultural diversity: the Mosaic Outpatient Clinic (MOC) was integrated in the general Paediatric Outpatient Departments (POPD) of three hospitals in Amsterdam. METHODS: Feasibility of the MOC, factors influencing the health care process and encountered bottlenecks in health care were studied in ethnic minority children with asthma, diabetes type 1 or metabolic disease originating from Morocco, Turkey and Surinam. Feasibility was determined by the number of patients attended, support from the paediatric medical staff and willingness of the patients to participate. Influences on the health care process comprised parents' level of knowledge of disease, sense of disease severity, level of effort, linguistic skills, health literacy, adherence to treatment and encountered bottlenecks in the health care process. Moreover, the number of admissions and visits to the POPD in the years before, during and after the MOC were analysed. RESULTS: In 2006 a total of 189 ethnic minority children were seen. Integration of the MOC within the general POPD of the hospital is feasible. The ability of the parents to speak and understand Dutch was found to be 58%, functional health literacy was 88%; sufficient knowledge of disease and sense of disease severity were 59% and 67%, respectively. The main bottlenecks in the healthcare process: poor knowledge of disease, limited sense of disease severity and low health literacy in the parents proved to be the best predictors for decreased adherence. After attending the MOC there was a decrease in the number of admissions and visits to the POPD for asthma while the number of visits increased in patients with diabetes and the amount of no-shows decreased in patients with a metabolic disease. CONCLUSION: Integration of a MOC in the general POPD is feasible and appreciated by the parents, provides more insight in the problems ethnic minority children and their parents face and shows promising directions for optimizing adherence in these children.

Growth of analytical thinking skills over time as measured with the MATCH test.

CONTEXT: Ber's Comprehensive Integrative Puzzle aims to assess analytical clinical thinking in medical students. We developed a paediatric version, the MATCH test, in which we added two irrelevant options to each question in order to reduce guessing behaviour. We tested its construct validity and studied the development of integrative skills over time. METHODS: We administered a test (MATCH 1) to subjects from two universities, both with a 6-year medical training course. Subjects included 30 students from university 1 who had completed a paediatric clerkship in Year 4, 23 students from university 2 who had completed a paediatric clerkship in Year 5, 13 students from both universities who had completed an advanced paediatric clerkship in Year 6, 28 paediatric residents and 17 paediatricians. We repeated this procedure using a second test with different domains in a new, comparable group of subjects (MATCH 2). RESULTS: Mean MATCH 1 scores for the respective groups were: Year 4 students: 61.2% (standard deviation [SD] 1.3); Year 5 students: 71.3% (SD 1.6); Year 6 students: 76.2% (SD 1.5); paediatric residents: 88.5% (SD 0.7), and paediatricians: 92.2% (SD 1.1) (one-way ANOVA F = 104.00, P < 0.0001). Students of both universities had comparable scores. MATCH 1 and 2 scores were comparable. Cronbach's alpha-values in MATCH 1 and 2 were 0.92 and 0.91, respectively, for all subjects, and 0.82 and 0.87, respectively, for all students. CONCLUSIONS: Analytical clinical thinking develops over time, independently of the factual content of the course. This implies that shortened medical training programmes could produce less skilled graduates.

MOVE: a multi-level ontology-based visualization and exploration framework for genomic networks.

Among the various research areas that comprise bioinformatics, systems biology is gaining increasing attention. An important goal of systems biology is the unraveling of dynamic interactions between components of living cells (e. g., proteins, genes). These interactions exist among others on genomic, transcriptomic, proteomic and metabolomic levels. The levels themselves are heavily interconnected, resulting in complex networks of different interacting biological entities. Currently, various bioinformatics tools exist which are able to perform a particular analysis on a particular type of network. Unfortunately, each tool has its own disadvantages hampering it to be used consistently for different types of networks or analytical methods. This paper describes the conceptual development of an open source extensible software framework that supports visualization and exploration of highly complex genomic networks, like metabolic or gene regulatory networks. The focus is on the conceptual foundations, starting from requirements, a description of the state of the art of network visualization systems, and an analysis of their shortcomings. We describe the implementation of some initial modules of the framework and apply them to a biological test case in bacterial regulation, which shows the relevance and feasibility of the proposed approach.

Tissue distribution and induction of human multidrug resistant protein 3.

The multidrug resistance protein (MRP) family consists of several members and, for some of these transporter proteins, distinct roles in multidrug resistance and normal tissue functions have been well established (MRP1 and MRP2) or are still under investigation (MRP3). MRP3 expression studies in human tissues have been largely restricted to the mRNA level. In this report we extended these studies and further explored MRP3 expression at the protein level. Western blot and immunohistochemistry with two MRP3-specific monoclonal antibodies, M(3)II-9 and M(3)II-21, showed MRP3 protein to be present in adrenal gland, and kidney and in tissues of the intestinal tract: colon, pancreas, gallbladder, and liver. In epithelia, MRP3 was found to be located at the basolateral sides of cell membranes. In normal liver, MRP3 was detected at lower levels than anticipated from the mRNA data and was found present mainly in the bile ducts. In livers from patients with various forms of cholestasis, MRP3 levels were frequently increased in the proliferative cholangiocytes, with sometimes additional staining of the basolateral membranes of the hepatocytes. This was especially evident in patients with type 3 progressive familial intrahepatic cholestasis. The present results support the view that MRP3 plays a role in the cholehepatic and enterohepatic circulation of bile and in protection within the biliary tree and tissues along the bile circulation route against toxic bile constituents. The possible functional roles for MRP3 in the adrenal gland and in the kidney remain as yet unknown. In a panel of 34 tumor samples of various histogenetic origins, distinct amounts of MRP3 were detected in a limited number of cases, including lung, ovarian, and pancreatic cancers. These findings may be of potential clinical relevance when considering the drug treatment regimens for these tumor types.