Adverse Events in Pediatric Critical Care Nonsurvivors With a Low Predicted Mortality Risk: A Multicenter Case Control Study.

OBJECTIVES: Some patients with a low predicted mortality risk in the PICU die. The contribution of adverse events to mortality in this group is unknown. The aim of this study was to estimate the occurrence of adverse events in low-risk nonsurvivors (LN), compared with low-risk survivors (LS) and high-risk PICU survivors and nonsurvivors, and the contribution of adverse events to mortality. DESIGN: Case control study. Admissions were selected from the national Dutch PICU registry, containing 53,789 PICU admissions between 2006 and 2017, in seven PICUs. PICU admissions were stratified into four groups, based on mortality risk (low/high) and outcome (death/survival). Random samples were selected from the four groups. Cases were "LN." Control groups were as follows: "LS," "high-risk nonsurvivors" (HN), and "high-risk survivors" (HS). Adverse events were identified using the validated trigger tool method. SETTING: Patient chart review study. PATIENTS: Children admitted to the PICU with either a low predicted mortality risk (< 1%) or high predicted mortality risk (≥ 30%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 419 patients were included (102 LN, 107 LS, 104 HN, and 106 HS). LN had more complex chronic conditions (93.1%) than LS (72.9%; p < 0.01), HN (49.0%; p < 0.001), and HS (48.1%; p < 0.001). The occurrence of adverse events in LN (76.5%) was higher than in LS (13.1%) and HN (47.1%) ( p < 0.001). The most frequent adverse events in LN were hospital-acquired infections and drug/fluid-related adverse events. LN suffered from more severe adverse events compared with LS and HS ( p < 0.001). In 30.4% of LN, an adverse event contributed to death. In 8.8%, this adverse event was considered preventable. CONCLUSIONS: Significant and preventable adverse events were found in low-risk PICU nonsurvivors. 76.5% of LN had one or more adverse events. In 30.4% of LN, an adverse event contributed to mortality.

Patient-reported outcomes in autosomal inherited bleeding disorders: A systematic literature review.

AIM: Currently, it is unknown which patient-reported outcomes are important for patients with autosomal inherited bleeding disorders. Therefore, the purpose of this study is to systematically review the available literature assessing patient-reported outcomes and their measurement methods in autosomal inherited bleeding disorders. METHODS: The Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trails and Google Scholar databases were searched from inception until 14 August 2020. Studies on patient-reported outcomes in patients with von Willebrand disease, inherited platelet function disorders and coagulation factor deficiencies were included. RESULTS: Twenty-one articles met the inclusion criteria. Three studies were assessed as having poor quality, and therefore a high risk of bias. Nineteen studies had fair quality rating. Different measurements methods were used, ranging from predefined to self-developed questionnaires. The majority of included studies focused on von Willebrand disease. Patients with von Willebrand disease reported lower health-related quality of life compared to the general population. Overall, this trend was especially visible in the following domains: vitality, physical and social functioning and pain. Women with inherited bleeding disorders scored lower on health-related quality of life compared to men, especially women with heavy menstrual bleeding. Patients with joint bleeds or heavy menstrual bleeding reported an increased level of pain. CONCLUSION: Patients with autosomal inherited bleeding disorders report lower health related quality of life, especially those with joint bleeds or heavy menstrual bleeding. Numerous measurement methods are used in patients with autosomal inherited bleeding disorders, highlighting the need for studies using established, standardized measurement methods.

Patient-Reported Outcome and Experience Measures in Perinatal Care to Guide Clinical Practice: Prospective Observational Study.

BACKGROUND: The International Consortium for Health Outcomes Measurement has published a set of patient-centered outcome measures for pregnancy and childbirth (PCB set), including patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). To establish value-based pregnancy and childbirth care, the PCB set was implemented in the Netherlands, using the outcomes on the patient level for shared decision-making and on an aggregated level for quality improvement. OBJECTIVE: This study aims to report first outcomes, experiences, and practice insights of implementing the PCB set in clinical practice. METHODS: In total, 7 obstetric care networks across the Netherlands, each consisting of 1 or 2 hospitals and multiple community midwifery practices (ranging in number from 2 to 18), implemented the PROM and PREM domains of the PCB set as part of clinical routine. This observational study included all women participating in the clinical project. PROMs and PREMs were assessed with questionnaires at 5 time points: 2 during pregnancy and 3 post partum. Clinical threshold values (alerts) supported care professionals interpreting the answers, indicating possibly alarming outcomes per domain. Data collection took place from February 2020 to September 2021. Data analysis included missing (pattern) analysis, sum scores, alert rates, and sensitivity analysis. RESULTS: In total, 1923 questionnaires were collected across the 5 time points: 816 (42.43%) at T1 (first trimester), 793 (41.23%) at T2 (early third trimester), 125 (6.5%) at T3 (maternity week), 170 (8.84%) at T4 (6 weeks post partum), and 19 (1%) at T5 (6 months post partum). Of these, 84% (1615/1923) were filled out completely. Missing items per domain ranged from 0% to 13%, with the highest missing rates for depression, pain with intercourse, and experience with pain relief at birth. No notable missing patterns were found. For the PROM domains, relatively high alert rates were found both in pregnancy and post partum for incontinence (469/1798, 26.08%), pain with intercourse (229/1005, 22.79%), breastfeeding self-efficacy (175/765, 22.88%), and mother-child bonding (122/288, 42.36%). Regarding the PREM domains, the highest alert rates were found for birth experience (37/170, 21.76%), shared decision-making (101/982, 10.29%), and discussing pain relief ante partum (310/793, 39.09%). Some domains showed very little clinical variation; for example, role of the mother and satisfaction with care. CONCLUSIONS: The PCB set is a useful tool to assess patient-reported outcomes and experiences that need to be addressed over the whole course of pregnancy and childbirth. Our results provide opportunities to improve and personalize perinatal care. Furthermore, we could propose several recommendations regarding methods and timeline of measurements based on our findings. This study supports the implementation of the PCB set in clinical practice, thereby advancing the transformation toward patient-centered, value-based health care for pregnancy and childbirth.

Improving access to healthcare for paediatric sickle cell disease patients: a qualitative study on healthcare professionals' views.

BACKGROUND: In well-resourced countries, comprehensive care programs have increased life expectancy of patients with sickle cell disease, with almost all infants surviving into adulthood. However, families affected by sickle cell disease are more likely to be economically disenfranchised because of their racial or ethnic minority status. As every individual child has the right to the highest attainable standard of health under the United Nations Convention on the Rights of the Child, it is essential to identify both barriers and facilitators with regard to the delivery of adequate healthcare. Optimal healthcare accessibility will improve healthcare outcomes for children with sickle cell disease and their families. Healthcare professionals in the field of sickle cell care have first-hand experience of the barriers that patients encounter when it comes to effective care. We therefore hypothesised that these medical professionals have a clear picture of what is necessary to overcome these barriers and which facilitators will be most feasible. Therefore, this study aims to map best practises and lessons learnt in order to attain more optimal healthcare accessibility for paediatric patients with sickle cell disease and their families. METHODS: Healthcare professionals working with young patients with sickle cell disease were recruited for semi-structured interviews. An interview guide was used to ensure the four healthcare accessibility dimensions were covered. The interviews were transcribed and coded. Based on field notes, initial codes were generated, to collate data (both barriers and solutions) to main themes (such as "transportation", or "telecommunication"). Through ongoing thematic analysis, definitive themes were formulated and best practices were reported as recommendations. Quotations were selected to highlight or illustrate the themes and link the reported results to the empirical data. RESULTS: In 2019, 22 healthcare professionals from five different university hospitals in the Netherlands were interviewed. Participants included (paediatric) haematologists, nurses and allied health professionals. Six themes emerged, all associated with best practices on topics related to the improvement of healthcare accessibility for children with sickle cell disease and their families. Firstly, the full reimbursement of invisible costs made by caregivers. Secondly, clustering of healthcare appointments on the same day to help patients seeing all required specialists without having to visit the hospital frequently. Thirdly, organisation of care according to shared care principles to deliver specialised services as close as possible to the patient's home without compromising quality. Fourthly, optimising verbal and written communication methods with special consideration for families with language barriers, low literacy skills, or both. Fifthly, improving the use of eHealth services tailored to users' health literacy skills, including accessible mobile telephone contact between healthcare professionals and caregivers of children with sickle cell disease. Finally, increasing knowledge and interest in sickle cell disease among key stakeholders and the public to ensure that preventive and acute healthcare measures are understood and safeguarded in all settings. CONCLUSION: This qualitative study describes the views of healthcare professionals on overcoming barriers of healthcare accessibility that arise from the intersecting vulnerabilities faced by patients with sickle cell disease and their families. The recommendations gathered in this report provide high-income countries with a practical resource to meet their obligations towards individual children under the United Nations Convention on the Rights of the Child.

A value-based healthcare approach: Health-related quality of life and psychosocial functioning in women with Turner syndrome.

OBJECTIVE: As part of the value-based healthcare programme in our hospital, a set of patient-reported outcome measures was developed together with patients and implemented in the dedicated Turner Syndrome (TS) outpatient clinic. This study aims to investigate different aspects of health-related quality of life (HR-QoL) and psychosocial functioning in women with TS in order to establish new possible targets for therapy. DESIGN/PARTICIPANTS: A comprehensive set of questionnaires (EQ-5D, PSS-10, CIS-20, Ferti-QoL, FSFI) was developed and used to capture different aspects of HR-QoL and psychosocial functioning in a large cohort of adult women with Turner syndrome. All consecutive women, ≥18 years, who visited the outpatient clinic of our tertiary centre were eligible for inclusion. RESULTS: Of the eligible 201 women who were invited to participate, 177 women (age 34 ± 12 years, mean ± SD) completed at least one of the validated questionnaires (88%). Women with TS reported a lower health-related quality of life (EQ-5D: 0.857 vs 0.892, P = .003), perceived more stress (PSS-10:14.7 vs 13.3; P = .012) and experienced increased fatigue (CIS-20: P < .001) compared to the general Dutch population. A relationship between noncardiac comorbidities (eg diabetes, orthopaedic complaints) and HR-QoL was found (R = .508). CONCLUSIONS: We showed that TS women suffer from impaired HR-QoL, more perceived stress and increased fatigue compared to healthy controls. A relationship between noncardiac comorbidities and HR-QoL was found. Especially perceived stress and increased fatigue can be considered targets for improvement of HR-QoL in TS women.

Patient-Reported Morbidity Instruments: A Systematic Review.

OBJECTIVES: Although comorbidities play an essential role in risk adjustment and outcomes measurement, there is little consensus regarding the best source of this data. The aim of this study was to identify general patient-reported morbidity instruments and their measurement properties. METHODS: A systematic review was conducted using multiple electronic databases (Embase, Medline, Cochrane Central, and Web of Science) from inception to March 2018. Articles focusing primarily on the development or subsequent validation of a patient-reported morbidity instrument were included. After including relevant articles, the measurement properties of each morbidity instrument were extracted by 2 investigators for narrative synthesis. RESULTS: A total of 1005 articles were screened, of which 34 eligible articles were ultimately included. The most widely assessed instruments were the Self-Reported Charlson Comorbidity Index (n = 7), the Self-Administered Comorbidity Questionnaire (n = 3), and the Disease Burden Morbidity Assessment (n = 3). The most commonly included conditions were diabetes, hypertension, and myocardial infarction. Studies demonstrated substantial variability in item-level reliability versus the gold standard medical record review (κ range 0.66-0.86), meaning that the accuracy of the self-reported comorbidity data is dependent on the selected morbidity. CONCLUSIONS: The Self-Reported Charlson Comorbidity Index and the Self-Administered Comorbidity Questionnaire were the most frequently cited instruments. Significant variability was observed in reliability per comorbid condition of patient-reported morbidity questionnaires. Further research is needed to determine whether patient-reported morbidity data should be used to bolster medical records data or serve as a stand-alone entity when risk adjusting observational outcomes data.

Cost of health care for paediatric patients with sickle cell disease: An analysis of resource use and costs in a European country.

BACKGROUND: While multiple studies have examined the cost of health care for one aspect of sickle cell disease care, few have focussed on the overall cost of comprehensive care for sickle cell disease. METHODS: We conducted a retrospective cohort study of children with sickle cell disease treated in a comprehensive care centre from 1 January 2015 to 31 December 2016. Health care utilisation of included patients was based upon data from two main sources. The clinical practice guideline was used to determine the expected resource use of routine comprehensive care (planned elective care), and the financial claims database was used to estimate real-world resource use associated with acute and inpatient care (additional care). RESULTS: A total of 125 children with sickle cell disease were analysed. Expenditures for these patients averaged €5049 [standard deviation (SD) €1634] per child per year. Total yearly costs per patient varied considerably, ranging from €669 to €84 010, and less than 15% of patients were responsible for 50% of the health care costs. The majority (37%) of costs was associated with inpatient hospital care, which increased by age group, 27% with diagnostics, 19% with treatment, 11% with outpatients' visits and 6% with emergency care. CONCLUSION: We have described real-world resource use and expenditures for children with sickle cell disease in a European comprehensive care centre. It seems that costs of a comprehensive approach with effective management in the outpatient setting is favourable when compared to episodic health care.

Machine learning with PROs in breast cancer surgery; caution: Collecting PROs at baseline is crucial.

As high breast cancer survival rates are achieved nowadays, irrespective of type of surgery performed, prediction of long-term physical, sexual, and psychosocial outcomes is very important in treatment decision-making. Patient-reported outcomes (PROs) can help facilitate this shared decision-making. Given the significance of more personalized medicine and the growing trend on the application of machine learning techniques, we are striving to develop an algorithm using machine learning techniques to predict PROs in breast cancer patients treated with breast surgery. This short communication describes the bottlenecks in our attempt to predict PROs.

Target attainment of cefotaxime in critically ill children with meningococcal septic shock as a model for cefotaxime dosing in severe pediatric sepsis.

Reduced target attainment of ß-lactam antibiotics is reported in critically ill patients. However, as target attainment of cefotaxime in severely ill pediatric sepsis patients may differ from adults due to age-related variation in pharmacokinetics, we aimed to assess target attainment of cefotaxime in this pilot study using meningococcal septic shock patients as a model for severe sepsis. Secondary analysis of prospectively collected data from a randomized controlled trial. Children with meningococcal septic shock (1 month to 18 years) included in this study received cefotaxime 100-150 mg/kg/day as antibiotic treatment. Left-over plasma samples were analyzed using LC-MS/MS to determine cefotaxime concentrations. MIC values from EUCAST were used to determine target attainment of cefotaxime for Neisseria meningitidis (0.125 mg/l), but also for Streptococcus pneumoniae (0.5 mg/l), Enterobacteriaceae (1 mg/l), and Staphylococcus aureus (4 mg/l). Target attainment was adequate when all samples exceeded MIC or fourfold MIC values. One thirty-six plasma samples of 37 severe septic shock patients were analyzed for cefotaxime concentrations. Median age was 2 years with a median PRISM-score of 24 and mortality of 24.8%. The median unbound cefotaxime concentration was 4.8 mg/l (range 0-48.7). Target attainment ranged from 94.6% for the MIC of N. meningitidis to 16.2% for fourfold the MIC S. aureus. Creatinine levels were significantly correlated with cefotaxime levels. Target attainment of cefotaxime with current dosing guidelines seems to be adequate for N. meningitidis but seems to fail for more frequently encountered pathogens in severely ill children.

Implementing Patient-Reported Outcome Measures in Clinical Breast Cancer Care: A Systematic Review.

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly being used to improve care delivery and are becoming part of routine clinical practice. OBJECTIVE: This systematic review aims to give an overview of PROM administration methods and their facilitators and barriers in breast cancer clinical practice. METHODS: A systematic literature search was conducted in Embase, MEDLINE, PsycINFO, Cochrane Central, CINAHL, and Web of Science for potentially relevant articles from study inception to November 2017. Reference lists of screened reviews were also checked. After inclusion of relevant articles, data were extracted and appraised by 2 investigators. RESULTS: A total of 2311 articles were screened, of which 34 eligible articles were ultimately included. Method and frequency of PROM collection varied between studies. The majority of studies described a promising effect of PROM collection on patients (adherence, symptom distress, quality of life, acceptability, and satisfaction), providers (willingness to comply, clinical decision making, symptom management), and care process or system outcomes (referrals, patient-provider communication, hospital visits). A limited number of facilitators and barriers were identified, primarily of a technical and behavioral nature. CONCLUSION: Although interpreting the impact of PROM collection in breast cancer care is challenging owing to considerations of synergistic (multicomponent) interventions and generalizability issues, this review found that systematic PROM collection has a promising impact on patients, providers, and care processes/ systems. Further standardization and reporting on method and frequency of PROM collection might help increase the effectiveness of PROM interventions and is warranted to enhance their overall impact.

Value-based healthcare in ischemic stroke care: case-mix adjustment models for clinical and patient-reported outcomes.

BACKGROUND: Patient-Reported Outcome Measures (PROMs) have been proposed for benchmarking health care quality across hospitals, which requires extensive case-mix adjustment. The current study's aim was to develop and compare case-mix models for mortality, a functional outcome, and a patient-reported outcome measure (PROM) in ischemic stroke care. METHODS: Data from ischemic stroke patients, admitted to four stroke centers in the Netherlands between 2014 and 2016 with available outcome information (N = 1022), was analyzed. Case-mix adjustment models were developed for mortality, modified Rankin Scale (mRS) scores and EQ-5D index scores with respectively binary logistic, proportional odds and linear regression models with stepwise backward selection. Predictive ability of these models was determined with R-squared (R2) and area-under-the-receiver-operating-characteristic-curve (AUC) statistics. RESULTS: Age, NIHSS score on admission, and heart failure were the only common predictors across all three case-mix adjustment models. Specific predictors for the EQ-5D index score were sex (ß = 0.041), socio-economic status (ß = - 0.019) and nationality (ß = - 0.074). R2-values for the regression models for mortality (5 predictors), mRS score (9 predictors) and EQ-5D utility score (12 predictors), were respectively R2 = 0.44, R2 = 0.42 and R2 = 0.37. CONCLUSIONS: The set of case-mix adjustment variables for the EQ-5D at three months differed considerably from the set for clinical outcomes in stroke care. The case-mix adjustment variables that were specific to this PROM were sex, socio-economic status and nationality. These variables should be considered in future attempts to risk-adjust for PROMs during benchmarking of hospitals.

Retrospective cohort study on factors associated with mortality in high-risk pediatric critical care patients in the Netherlands.

BACKGROUND: High-risk patients in the pediatric intensive care unit (PICU) contribute substantially to PICU-mortality. Complex chronic conditions (CCCs) are associated with death. However, it is unknown whether CCCs also increase mortality in the high-risk PICU-patient. The objective of this study is to determine if CCCs or other factors are associated with mortality in this group. METHODS: Retrospective cohort study from a national PICU-database (2006-2012, n = 30,778). High-risk PICU-patients, defined as patients < 18 years with a predicted mortality risk > 30% according to either the recalibrated Pediatric Risk of Mortality-II (PRISM) or the Paediatric Index of Mortality 2 (PIM2), were included. Patients with a cardiac arrest before PICU-admission were excluded. RESULTS: In total, 492 high-risk PICU patients with mean predicted risk of 24.8% (SD 22.8%) according to recalibrated PIM2 and 40.0% (SD 23.8%) according to recalibrated PRISM were included of which 39.6% died. No association was found between CCCs and non-survival (odds ratio 0.99; 95% CI 0.62-1.59). Higher Glasgow coma scale at PICU admission was associated with lower mortality (odds ratio 0.91; 95% CI 0.87-0.96). CONCLUSIONS: Complex chronic conditions are not associated with mortality in high-risk PICU patients.

Mortality and morbidity in community-acquired sepsis in European pediatric intensive care units: a prospective cohort study from the European Childhood Life-threatening Infectious Disease Study (EUCLIDS).

BACKGROUND: Sepsis is one of the main reasons for non-elective admission to pediatric intensive care units (PICUs), but little is known about determinants influencing outcome. We characterized children admitted with community-acquired sepsis to European PICUs and studied risk factors for mortality and disability. METHODS: Data were collected within the collaborative Seventh Framework Programme (FP7)-funded EUCLIDS study, which is a prospective multicenter cohort study aiming to evaluate genetic determinants of susceptibility and/or severity in sepsis. This report includes 795 children admitted with community-acquired sepsis to 52 PICUs from seven European countries between July 2012 and January 2016. The primary outcome measure was in-hospital death. Secondary outcome measures were PICU-free days censured at day 28, hospital length of stay, and disability. Independent predictors were identified by multivariate regression analysis. RESULTS: Patients most commonly presented clinically with sepsis without a source (n = 278, 35%), meningitis/encephalitis (n = 182, 23%), or pneumonia (n = 149, 19%). Of 428 (54%) patients with confirmed bacterial infection, Neisseria meningitidis (n = 131, 31%) and Streptococcus pneumoniae (n = 78, 18%) were the main pathogens. Mortality was 6% (51/795), increasing to 10% in the presence of septic shock (45/466). Of the survivors, 31% were discharged with disability, including 24% of previously healthy children who survived with disability. Mortality and disability were independently associated with S. pneumoniae infections (mortality OR 4.1, 95% CI 1.1-16.0, P = 0.04; disability OR 5.4, 95% CI 1.8-15.8, P < 0.01) and illness severity as measured by Pediatric Index of Mortality (PIM2) score (mortality OR 2.8, 95% CI 1.3-6.1, P < 0.01; disability OR 3.4, 95% CI 1.8-6.4, P < 0.001). CONCLUSIONS: Despite widespread immunization campaigns, invasive bacterial disease remains responsible for substantial morbidity and mortality in critically ill children in high-income countries. Almost one third of sepsis survivors admitted to the PICU were discharged with some disability. More research is required to delineate the long-term outcome of pediatric sepsis and to identify interventional targets. Our findings emphasize the importance of improved early sepsis-recognition programs to address the high burden of disease.

The occurrence of adverse events in low-risk non-survivors in pediatric intensive care patients: an exploratory study.

We studied the occurrence of adverse events (AEs) in low-risk non-survivors (LNs), compared to low-risk survivors (LSs), high-risk non-survivors (HNs), and high-risk survivors (HSs) in two pediatric intensive care units (PICUs). The study was performed as a retrospective patient record review study, using a PICU-trigger tool. A random sample of 48 PICU patients (0-18 years) was chosen, stratified into four subgroups of 12 patients: LNs, LSs, HNs, and HSs. Primary outcome was the occurrence of AEs. The severity, preventability, and nature of the indentified AEs were determined. In total, 45 AEs were found in 20 patients. The occurrence of AEs in the LN group was significantly higher compared to that in the LS group and HN group (AE occurrence: LN 10/12 patients, LS 1/12 patients; HN 2/12 patients; HS 7/12 patients; LN-LS difference, p < 0.001; LN-HN difference, p < 0.01). The AE rate in the LN group was significantly higher compared to that in the LS and HN groups (median [IQR]: LN 0.12 [0.07-0.29], LS 0 [0-0], HN 0 [0-0], and HS 0.03 [0.0-0.17] AE/PICU day; LN-LS difference, p < 0.001; LN-HN difference, p < 0.01). The distribution of the AEs among the four groups was as follows: 25 AEs (LN), 2 AEs (LS), 8 AEs (HN), and 10 AEs (HS). Fifteen of forty-five AEs were preventable. In 2/12 LN patients, death occurred after a preventable AE. CONCLUSION: The occurrence of AEs in LNs was higher compared to that in LSs and HNs. Some AEs were severe and preventable and contributed to mortality. What is Known: • 59-76% of all PICU patients encounter at least one adverse event during their PICU stay. • It is unknown if adverse events play a role in death of low-risk PICU patients. What is New: • In low-risk PICU non-survivors, occurrence of adverse events is higher compared to low-risk PICU survivors and to high-risk PICU non-survivors. • Severe and preventable adverse events occur in low-risk PICU non-survivors, some contributing to mortality.

Neutrophil Extracellular Traps in Children With Meningococcal Sepsis.

OBJECTIVES: Children with meningococcal sepsis are highly at risk for fulminant disease, multiple organ failure, and death. Recently, neutrophil extracellular traps levels have been indicated as a marker for severity in different kinds of sepsis. Our aim was to study the role of neutrophil extracellular traposis in meninogococcal sepsis in children. DESIGN: We measured myeloperoxidase-DNA, a marker for neutrophil extracellular traps, in serum of meningococcal sepsis patients upon admission to PICU, at 24 hours, and at 1 month and studied the association with clinical outcome. Subsequently, we tested whether Neisseria meningitidis, isolated from children with meningococcal sepsis, were able to induce neutrophil extracellular traposis, using confocal microscopy live imaging. SETTING: We used enzyme-linked immunosorbent assays to measure myeloperoxidase-DNA in patient serum. We also included inflammatory markers that were previously measured in this group. PATIENTS: We included exclusively children with meningococcal sepsis. INTERVENTIONS: From each patient, serum was collected for analysis. MEASUREMENTS AND MAIN RESULTS: Myeloperoxidase-DNA levels at admission (n = 35; median, 0.21 AU/mL; interquartile range, 0.12-0.27) and at 24 hours (n = 39; median, 0.14 AU/mL; interquartile range, 0.09-0.25) were significantly higher than the myeloperoxidase-DNA levels after 1 month (controls: n = 36; median, 0.07 AU/mL; interquartile range, 0.05-0.09; p < 0.001). We did not observe a correlation between myeloperoxidase-DNA levels and mortality, cell-free DNA, or other inflammatory markers. In addition, N. meningitidis are fast and strong inducers of neutrophil extracellular traposis. CONCLUSIONS: Children admitted to PICU for meningococcal sepsis have higher neutrophil extracellular traps levels at admission and after 24 hours than controls. Neutrophil extracellular traps levels were not associated with outcome, cell-free DNA, or other inflammatory markers. These neutrophil extracellular traps may be induced by N. meningitidis, since these are strong neutrophil extracellular traposis inducers.

Gene Variations in the Protein C and Fibrinolytic Pathway: Relevance for Severity and Outcome in Pediatric Sepsis.

The host response to infection involves complex interplays between inflammation, coagulation, and fibrinolysis. Deregulation of hemostasis and fibrinolysis are major causes of critical illness and important determinants of outcome in severe sepsis. The hemostatic responses to infection vary widely between individuals, and are in part explained by polymorphisms in genes responsible for the protein C and fibrinolytic pathway. This review gives an overview of genetic polymorphisms in the protein C and fibrinolytic pathway associated with susceptibility and severity of pediatric sepsis. In addition, genetic polymorphisms associated with adult sepsis and other pediatric thromboembolic disorders are discussed, as these polymorphisms might be candidates for future molecular genetic research in pediatric sepsis.

Factors Associated With Mortality in Low-Risk Pediatric Critical Care Patients in The Netherlands.

OBJECTIVE: To determine differences between survivors and nonsurvivors and factors associated with mortality in pediatric intensive care patients with low risk of mortality. DESIGN: Retrospective cohort study. SETTING: Patients were selected from a national database including all admissions to the PICUs in The Netherlands between 2006 and 2012. PATIENTS: Patients less than 18 years old admitted to the PICU with a predicted mortality risk lower than 1% according to either the recalibrated Pediatric Risk of Mortality or the Pediatric Index of Mortality 2 were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 16,874 low-risk admissions were included of which 86 patients (0.5%) died. Nonsurvivors had more unplanned admissions (74.4% vs 38.5%; p < 0.001), had more complex chronic conditions (76.7% vs 58.8%; p = 0.001), were more often mechanically ventilated (88.1% vs 34.9%; p < 0.001), and had a longer length of stay (median, 11 [interquartile range, 5-32] d vs median, 3 [interquartile range, 2-5] d; p < 0.001) when compared with survivors. Factors significantly associated with mortality were complex chronic conditions (odds ratio, 3.29; 95% CI, 1.97-5.50), unplanned admissions (odds ratio, 5.78; 95% CI, 3.40-9.81), and admissions in spring/summer (odds ratio, 1.67; 95% CI, 1.08-2.58). CONCLUSIONS: Nonsurvivors in the PICU with a low predicted mortality risk have recognizable risk factors including complex chronic condition and unplanned admissions.

Determinants of a successful problem list to support the implementation of the problem-oriented medical record according to recent literature.

BACKGROUND: A problem-oriented approach is one of the possibilities to organize a medical record. The problem-oriented medical record (POMR) - a structured organization of patient information per presented medical problem- was introduced at the end of the sixties by Dr. Lawrence Weed to aid dealing with the multiplicity of patient problems. The problem list as a precondition is the centerpiece of the problem-oriented medical record (POMR) also called problem-oriented record (POR). Prior to the digital era, paper records presented a flat list of medical problems to the healthcare professional without the features that are possible with current technology. In modern EHRs a POMR based on a structured problem list can be used for clinical decision support, registries, order management, population health, and potentially other innovative functionality in the future, thereby providing a new incentive to the implementation and use of the POMR. METHODS: On both 12 May 2014 and 1 June 2015 a systematic literature search was conducted. From the retrieved articles statements regarding the POMR and related to successful or non-successful implementation, were categorized. Generic determinants were extracted from these statements. RESULTS: In this research 38 articles were included. The literature analysis led to 12 generic determinants: clinical practice/reasoning, complete and accurate problem list, data structure/content, efficiency, functionality, interoperability, multi-disciplinary, overview of patient information, quality of care, system support, training of staff, and usability. CONCLUSIONS: Two main subjects can be distinguished in the determinants: the system that the problem list and POMR is integrated in and the organization using that system. The combination of the two requires a sociotechnical approach and both are equally important for successful implementation of a POMR. All the determinants have to be taken into account, but the weight given to each of the determinants depends on the organizationusing the problem list or POMR.

Variation Between Hospitals in Outcomes and Costs of IBD Care: Results From the IBD Value Study.

BACKGROUND: Data on variation in outcomes and costs of the treatment of inflammatory bowel disease (IBD) can be used to identify areas for cost and quality improvement. It can also help healthcare providers learn from each other and strive for equity in care. We aimed to assess the variation in outcomes and costs of IBD care between hospitals. METHODS: We conducted a 12-month cohort study in 8 hospitals in the Netherlands. Patients with IBD who were treated with biologics and new small molecules were included. The percentage of variation in outcomes (following the International Consortium for Health Outcomes Measurement standard set) and costs attributable to the treating hospital were analyzed with intraclass correlation coefficients (ICCs) from case mix-adjusted (generalized) linear mixed models. RESULTS: We included 1010 patients (median age 45 years, 55% female). Clinicians reported high remission rates (83%), while patient-reported rates were lower (40%). During the 12-month follow-up, 5.2% of patients used prednisolone for more than 3 months. Hospital costs (outpatient, inpatient, and medication costs) were substantial (median: €8323 per 6 months), mainly attributed to advanced therapies (€6611). Most of the variation in outcomes and costs among patients could not be attributed to the treating hospitals, with ICCs typically between 0% and 2%. Instead, patient-level characteristics, often with ICCs above 50%, accounted for these variations. CONCLUSIONS: Variation in outcomes and costs cannot be used to differentiate between hospitals for quality of care. Future quality improvement initiatives should look at differences in structure and process measures of care and implement patient-level interventions to improve quality of IBD care. TRIAL REGISTRATION NUMBER: NL8276.

Variation in outcomes and costs cannot be used to differentiate between hospitals for quality of inflammatory bowel disease care. Future quality improvement initiatives should look at differences in structure and process measures and implement patient-level interventions to improve quality of inflammatory bowel disease care.

Decreased expression of serum and microvascular vascular endothelial growth factor receptor-2 in meningococcal sepsis*.

OBJECTIVES: To determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis. DESIGN: Observational study. SETTING: Two tertiary academic children hospital PICUs. PATIENTS: Children with meningococcal sepsis. INTERVENTION: Skin biopsy and blood sample collection. MEASUREMENTS AND MAIN RESULTS: Determination of skin microvessel vascular endothelial growth factor receptor 2 expression in skin biopsies by immunohistochemistry and measurement of serum-soluble vascular endothelial growth factor receptor 2 by enzyme-linked immunosorbent assay. Percentage of vascular endothelial growth factor receptor 2-positive skin microvessels and the staining intensity were significantly lower in children with meningococcal sepsis (n = 10) compared to controls (7.6% ± 8.8% vs 44.6% ± 39.2%; p = 0.009 and 0.7% ± 0.7% vs 1.7% ± 1.1%; p = 0.033, respectively). In addition, circulating serum levels of soluble vascular endothelial growth factor receptor 2 were decreased in sepsis (8,148 ± 1,140 pg/mL vs 13,414 ± 2,692 pg/mL; p < 0.001). Serum-soluble vascular endothelial growth factor receptor 2 levels (n = 28) were inversely correlated with Pediatric Risk of Mortality III score (r = -0.43; p = 0.023) and more decreased in nonsurvivors compared to survivors (5,640 ± 1,940 pg/mL vs 7,378 ± 2,336 pg/mL; p = 0.037). CONCLUSIONS: Microvascular expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels are decreased in children with sepsis. Serum-soluble vascular endothelial growth factor receptor 2 levels are inversely correlated with disease severity indicated by Pediatric Risk of Mortality III score and survival. Decreased vascular endothelial growth factor receptor 2 expression may hinder natural recovery from sepsis-associated microvascular injury and the effectiveness of therapeutic strategies targeting vascular endothelial growth factor-vascular endothelial growth factor receptor 2 signaling in sepsis patients.