2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial.

BACKGROUND: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. METHODS: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. FINDINGS: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI -1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. INTERPRETATION: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. FUNDING: The Netherlands Organization for Health Research and Development.

A Randomized Embedded Multifactorial Adaptive Platform for Extra Corporeal Membrane Oxygenation (REMAP ECMO) - Design and Rationale of the Left Ventricular Unloading trial domain.

BACKGROUND: The use of Extracorporeal Membrane Oxygenation (ECMO) remains associated with high rates of complications, weaning failure and mortality which can be partly explained by a knowledge gap on how to properly manage patients on ECMO support. To address relevant patient management issues, we designed a "Randomized Embedded Multifactorial Adaptive Platform (REMAP)" in the setting of ECMO (REMAP ECMO) and a first embedded randomized controlled trial (RCT) investigating the effects of routine early left ventricular (LV) unloading through intra-aortic balloon pumping (IABP). METHODS: REMAP ECMO describes a registry-based platform allowing for the embedding of multiple response adaptive RCTs (trial domains) which can perpetually address the effect of relevant patient management issues on ECMO weaning success. A first trial domain studies the effects of LV unloading by means of an IABP as an adjunct to veno-arterial (V-A) ECMO versus V-A ECMO alone on ECMO weaning success at 30 days in adult cardiogenic shock patients admitted to the Intensive Care Unit (ICU). The primary outcome of this trial is "successful weaning from ECMO" being defined as a composite of survival without the need for mechanical circulatory support, heart transplantation, or left ventricular assist device (LVAD) at 30 days after initiation of ECMO. Secondary outcomes include the need for interventional escalation of LV unloading strategy, mechanistic endpoints, survival characteristics until one year after ECMO initiation, and quality of life. Trial data will be analysed using a Bayesian statistical framework. The adaptive design allows for a high degree of flexibility, such as response adaptive randomization and early stopping of the trial for efficacy or futility. The REMAP ECMO LV unloading study is approved by the Medical Ethical Committee of the Erasmus Medical Center and is publicly registered. CONCLUSION: This REMAP ECMO trial platform enables the efficient roll-out of multiple RCTs on relevant patient management issues. A first embedded trial domain will compare routine LV unloading by means of an IABP as an adjunct to V-A ECMO versus V-A ECMO alone. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05913622.

Predicting haemoglobin deferral using machine learning models: Can we use the same prediction model across countries?

BACKGROUND AND OBJECTIVES: Personalized donation strategies based on haemoglobin (Hb) prediction models may reduce Hb deferrals and hence costs of donation, meanwhile improving commitment of donors. We previously found that prediction models perform better in validation data with a high Hb deferral rate. We therefore investigate how Hb deferral prediction models perform when exchanged with other blood establishments. MATERIALS AND METHODS: Donation data from the past 5 years from random samples of 10,000 donors from Australia, Belgium, Finland, the Netherlands and South Africa were used to fit random forest models for Hb deferral prediction. Trained models were exchanged between blood establishments. Model performance was evaluated using the area under the precision-recall curve (AUPR). Variable importance was assessed using SHapley Additive exPlanations (SHAP) values. RESULTS: Across the validation datasets and exchanged models, the AUPR ranged from 0.05 to 0.43. Exchanged models performed similarly within validation datasets, irrespective of the origin of the training data. Apart from subtle differences, the importance of most predictor variables was similar in all trained models. CONCLUSION: Our results suggest that Hb deferral prediction models trained in different blood establishments perform similarly within different validation datasets, regardless of the deferral rate of their training data. Models learn similar associations in different blood establishments.

Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial.

BACKGROUND: To determine whether intermittent intravenous (IV) paracetamol as primary analgesic would significantly reduce morphine consumption in children aged 0-3 years after cardiac surgery with cardiopulmonary bypass. METHODS: Multi-center, randomized, double-blinded, controlled trial in four level-3 Pediatric Intensive Care Units (PICU) in the Netherlands and Belgium. Inclusion period; March 2016-July 2020. Children aged 0-3 years, undergoing cardiac surgery with cardiopulmonary bypass were eligible. Patients were randomized to continuous morphine or intermittent IV paracetamol as primary analgesic after a loading dose of 100 mcg/kg morphine was administered at the end of surgery. Rescue morphine was given if numeric rating scale (NRS) pain scores exceeded predetermined cutoff values. Primary outcome was median weight-adjusted cumulative morphine dose in mcg/kg in the first 48 h postoperative. For the comparison of the primary outcome between groups, the nonparametric Van Elteren test with stratification by center was used. For comparison of the proportion of patients with one or more NRS pain scores of 4 and higher between the two groups, a non-inferiority analysis was performed using a non-inferiority margin of 20%. RESULTS: In total, 828 were screened and finally 208 patients were included; parents of 315 patients did not give consent and 305 were excluded for various reasons. Fourteen of the enrolled 208 children were withdrawn from the study before start of study medication leaving 194 patients for final analysis. One hundred and two patients received intermittent IV paracetamol, 106 received continuous morphine. The median weight-adjusted cumulative morphine consumption in the first 48 h postoperative in the IV paracetamol group was 5 times lower (79%) than that in the morphine group (median, 145.0 (IQR, 115.0-432.5) mcg/kg vs 692.6 (IQR, 532.7-856.1) mcg/kg; P < 0.001). The rescue morphine consumption was similar between the groups (p = 0.38). Non-inferiority of IV paracetamol administration in terms of NRS pain scores was proven; difference in proportion - 3.1% (95% CI - 16.6-10.3%). CONCLUSIONS: In children aged 0-3 years undergoing cardiac surgery, use of intermittent IV paracetamol reduces the median weight-adjusted cumulative morphine consumption in the first 48 h after surgery by 79% with equal pain relief showing equipoise for IV paracetamol as primary analgesic. Trial Registration Clinicaltrials.gov, Identifier: NCT05853263; EudraCT Number: 2015-001835-20.

Minimally invasive surgical approach in children treated for oesophageal atresia is associated with attention problems at school age: a prospective cohort study.

The long-term neurodevelopment of children born with oesophageal atresia (OA) is unclear. Therefore, we assessed the neurocognitive domains and their predictors. Patients born with OA between February 2006 and December 2014, who were routinely seen at eight years as part of a structured prospective longitudinal follow-up program, were included. Main outcome measures were need for school support, performance in various neurocognitive domains and potential predictors of neurocognitive problems. We analysed data of 65 children with a mean (SD) age of 8.1 (0.2) years, of whom 89% with OA type C. Thirty-five (54%) surgical corrections were minimally invasive; the median (interquartile range) duration of exposure to anaesthetics in the first 24 months was 398 (296 - 710) minutes. Forty-four (68%) attended regular education without extra support and intelligence was within normal range (99-108). More than 50% had z-scores ≤ -2 on one or more neurocognitive domains, of which attention was the most frequently affected domain. The speed on the sustained attention task was significantly below normal (z-score -1.48 (2.12), p < .001), as was fluctuation of sustained attention (z-score -3.19 (3.80), p < .001). The minimally invasive approach and a lower socio-economic status (both p = 0.006) proved significant predictors for sustained attention problems in multivariable analyses.  Conclusion: Children who undergo minimally invasive surgery for OA correction are at risk for sustained attention problems at school age. Future studies unravelling the effects of perioperative events on neurodevelopment should lead to optimal surgical, anaesthesiological, and intensive care management in the neonatal period. What is Known: • School-aged children born with oesophageal atresia have normal intelligence but problems with sustained attention at eight years. What is New: • Oesophageal atresia patients, who undergo minimally invasive surgery or who have a background of lower socioeconomic status are at serious risk for sustained attention problems at school age. • Moreover, those who have been intubated for a longer period are at risk for stronger fluctuations in sustained attention.

Mobility level and factors affecting mobility status in hospitalized patients admitted in single-occupancy patient rooms.

BACKGROUND: Although stimulating patients' mobility is considered a component of fundamental nursing care, approximately 35% of hospitalized patients experience functional decline during or after hospital admission. The aim of this study is to assess mobility level and to identify factors affecting mobility status in hospitalized patients admitted in single-occupancy patient rooms (SPRs) on general wards. METHODS: Mobility level was quantified with the Johns Hopkins Highest Level of Mobility Scale (JH-HLM) and EQ-5D-3L. GENEActiv accelerometer data over 24 h were collected in a subset of patients. Data were analyzed using generalized ordinal logistic regression analysis. The STROBE reporting checklist was applied. RESULTS: Wearing pajamas during daytime, having pain, admission in an isolation room, and wearing three or more medical equipment were negatively associated with mobilization level. More than half of patients (58.9%) who were able to mobilize according to the EQ-5D-3L did not achieve the highest possible level of mobility according to the JH-HLM. The subset of patients that wore an accelerometer spent most of the day in sedentary behavior (median 88.1%, IQR 85.9-93.6). The median total daily step count was 1326 (range 22-5362). CONCLUSION: We found that the majority of participating hospitalized patients staying in single-occupancy patient rooms were able to mobilize. It appeared, however, that most of the patients who are physically capable of walking, do not reach the highest possible level of mobility according to the JH-HLM scale. Nurses should take their responsibility to ensure that patients achieve the highest possible level of mobility.

Predicting Lymph Node Metastases in Patients with Biopsy-Proven Ductal Carcinoma In Situ of the Breast: Development and Validation of the DCIS-met Model.

PURPOSE: In patients with a biopsy-proven ductal carcinoma in situ (DCIS), axillary staging is frequently performed, but in hindsight often turns out to be superfluous. The aim of this observational study was to develop a prediction model for risk of lymph node metastasis in patients with a biopsy-proven DCIS. METHODS: Data were received from the Dutch Pathology Databank and the Netherlands Cancer Registry. The population-based cohort consisted of all biopsy-proven DCIS patients diagnosed in the Netherlands in 2011 and 2012. The prediction model was evaluated with the area under the curve (AUC) of the receiver operating characteristic, and a calibration plot and a decision curve analysis and was validated in a Dutch cohort of patients diagnosed in the period 2016-2019. RESULTS: Of 2892 biopsy-proven DCIS patients, 127 had metastasis (4.4%). Risk factors were younger age (OR = 0.97, 95% CI 0.95-0.99), DCIS not detected by screening (OR = 1.55, 95% CI 1.01-2.38), suspected invasive component at biopsy (OR = 1.86, 95% CI 1.01-3.41), palpable tumour (OR = 2.06, 95% CI 1.34-3.18), BI-RADS score 5 (OR = 2.41, 95% CI 1.53-3.78), intermediate-grade DCIS (OR = 3.01, 95% CI 1.27-7.15) and high-grade DCIS (OR = 3.20, 95% CI 1.36-7.54). For 24% (n = 708) of the patients, the predicted risk of lymph node metastasis was above 5%. Based on the decision curve analysis, the model had a net benefit for a predicted risk below 25%. The AUC was 0.745. Of the 2269 patients in the validation cohort, 53 (2.2%) had metastasis and the AUC was 0.741. CONCLUSIONS: This DCIS-met model can support clinical decisions on axillary staging in patients with biopsy-proven DCIS.

Validation and Clinical Utility of a Prediction Model for the Risk of Upstaging to Invasive Breast Cancer After a Biopsy Diagnosis Ductal Carcinoma In Situ.

BACKGROUND: This study aimed to validate the DCIS-upstage model, a previously developed model to predict the risk of upstaging to invasive breast cancer in patients with biopsy-proven ductal carcinoma in situ (DCIS) in a more recent cohort and to assess the model's clinical utility. METHODS: The model was validated in a registry cohort (n = 2269) and in an institution cohort (n = 302). A calibration plot was made, followed by a decision curve analysis (DCA). The model's area under the curve (AUC) was compared with the AUC of another published model and with the AUCs of new models using the risk factors of the DCIS-upstage model and additional risk factors. RESULTS: The DCIS-upstage model had an AUC of 0.67 at development; in the validation, the AUC was 0.65 in the registry cohort and 0.73 in the institution cohort. The DCA showed that the model has clinical utility. The other published model had an AUC of 0.66 in the institution cohort. Adding risk factors to the DCIS-upstage model slightly increased the AUC. CONCLUSIONS: The DCIS-upstage prediction model is valid in other cohorts. The model has clinical utility and may be used to select patients with biopsy-proven DCIS for sentinel lymph node biopsy.

An international comparison of haemoglobin deferral prediction models for blood banking.

BACKGROUND AND OBJECTIVES: Blood banks use a haemoglobin (Hb) threshold before blood donation to minimize donors' risk of anaemia. Hb prediction models may guide decisions on which donors to invite, and should ideally also be generally applicable, thus in different countries and settings. In this paper, we compare the outcome of various prediction models in different settings and highlight differences and similarities. MATERIALS AND METHODS: Donation data of repeat donors from the past 5 years of Australia, Belgium, Finland, the Netherlands and South Africa were used to fit five identical prediction models: logistic regression, random forest, support vector machine, linear mixed model and dynamic linear mixed model. Only donors with five or more donation attempts were included to ensure having informative data from all donors. Analyses were performed for men and women separately and outcomes compared. RESULTS: Within countries and overall, different models perform similarly well. However, there are substantial differences in model performance between countries, and there is a positive association between the deferral rate in a country and the ability to predict donor deferral. Nonetheless, the importance of predictor variables across countries is similar and is highest for the previous Hb level. CONCLUSION: The limited impact of model architecture and country indicates that all models show similar relationships between the predictor variables and donor deferral. Donor deferral is found to be better predictable in countries with high deferral rates. Therefore, such countries may benefit more from deferral prediction models than those with low deferral rates.

Real-world challenges in the diagnosis of primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Despite the 2017 revisions to the McDonald criteria, diagnosing primary progressive multiple sclerosis (PPMS) remains challenging. To improve clinical practice, the aim was to identify frequent diagnostic challenges in a real-world setting and associate these with the performance of the 2010 and 2017 PPMS diagnostic McDonald criteria. METHODS: Clinical, radiological and laboratory characteristics at the time of diagnosis were retrospectively recorded from designated PPMS patient files. Possible complicating factors were recorded such as confounding comorbidity, signs indicative of alternative diagnoses, possible earlier relapses and/or incomplete diagnostic work-up (no cerebrospinal fluid examination and/or magnetic resonance imaging brain and spinal cord). The percentages of patients fulfilling the 2010 and 2017 McDonald criteria were calculated after censoring patients with these complicating factors. RESULTS: A total of 322 designated PPMS patients were included. Of all participants, it was found that n = 28/322 had confounding comorbidity and/or signs indicative of alternative diagnoses, n = 103/294 had possible initial relapsing and/or uncertainly progressive phenotypes and n = 73/191 received an incomplete diagnostic work-up. When applying the 2010 and 2017 diagnostic PPMS McDonald criteria on n = 118 cases with a full diagnostic work-up and a primary progressive disease course without a better alternative explanation, these were met by 104/118 (88.1%) and 98/118 remaining patients (83.1%), respectively (p = 0.15). CONCLUSION: Accurate interpretation of the initial clinical course, consideration of alternative diagnoses and a full diagnostic work-up are the cornerstones of a PPMS diagnosis. When these conditions are met, the 2010 and 2017 McDonald criteria for PPMS perform similarly, emphasizing the importance of their appropriate application in clinical practice.

Reference values of diaphragmatic dimensions in healthy children aged 0-8 years.

Diaphragmatic thickness (Tdi) and diaphragm thickening fraction (dTF) are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children are scarce. We determined reference values of Tdi and dTF using ultrasound in healthy children aged 0-8 years old and assessed their reproducibility. In a prospective, observational cohort, Tdi and dTF were measured on ultrasound images across four age groups comprising at least 30 children per group: group 1 (0-6 months), group 2 (7 months-1 year), group 3 (2-4 years) and group 4 (5-8 years). Ultrasound images of 137 healthy children were included. Mean Tdi at inspiration was 2.07 (SD 0.40), 2.09 (SD 0.40), 1.69 (SD 0.30) and 1.72 (SD 0.30) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at expiration was 1.64 (SD 0.30), 1.67 (SD 0.30), 1.38 (SD 0.20) and 1.42 (SD 0.20) mm for groups 1, 2, 3 and 4, respectively. Mean Tdi at inspiration and mean Tdi at expiration for groups 1 and 2 were significantly greater than those for groups 3 and 4 (both p < 0.001). Mean dTF was 25.4% (SD 10.4), 25.2% (SD 8.3), 22.8% (SD 10.9) and 21.3% (SD 7.1) for group 1, 2, 3 and 4, respectively. The intraclass correlation coefficients (ICC) representing the level of inter-rater reliability between two examiners performing the ultrasounds was 0.996 (95% CI 0.982-0.999). ICC of the inter-rater reliability between the raters in 11 paired assessments was 0.989 (95% CI 0.973-0.995).   Conclusion: Ultrasound measurements of Tdi and dTF were highly reproducible in healthy children aged 0-8 years.    Trial registration: ClinicalTrials.gov identifier (NCT number): NCT04589910. What is Known: • Diaphragmatic thickness and diaphragm thickening fraction are widely used parameters in ultrasound studies of the diaphragm in mechanically ventilated children, but normal values for healthy children to compare these with are scarce. What is New: • We determined normal values of diaphragmatic thickness and diaphragm thickening fraction using ultrasound in 137 healthy children aged 0-8 years old. The diaphragmatic thickness of infants up to 1 year old was significantly greater than that of children from 2 to 8 years old. Diaphragmatic thickness decreased with an increase in body surface area. These normal values in healthy children can be used to assess changes in respiratory muscle thickness in mechanically ventilated children.

Neuropsychological outcome in survivors of congenital diaphragmatic hernia at 5 years of age, what does it tell?

Previous studies have frequently reported neurocognitive deficits in children born with congenital diaphragmatic hernia (CDH) at school age, which may contribute to academic difficulties. Yet, age at onset of these deficits is currently unknown. We evaluated neurocognitive skills with possible determinants in preschool children born with CDH. Eligible 5-year-old children born with CDH (2010-2015) who participated in our prospective structural follow-up program were included. We used the WPPSI-III to assess intelligence, subtests of the Kaufman-ABC for memory, and NEPSY-II to assess inhibition and attention. We included 63 children. Their test scores generally were within or significantly above normal range: total IQ = 103.4 (15.7) (p = 0.13); Verbal memory = 10.2 (2.8) (p = 0.61); Visuospatial memory = 11.4 (2.6) (p < 0.01); Inhibition = 10.5 (2.2), (p = 0.10). In univariable analyses, length of ICU-stay was negatively associated with IQ, and maximum vasoactive inotropic score and open repair were negatively associated with inhibition skills. In multivariable regression analysis, the latter association remained (B = 5.52, p = 0.04 (CI 0.32-10.72)).   Conclusions: In these tested 5-year-old children born with CDH, neuropsychological outcome was normal on average. While problems in 8-year-olds are common, we did not detect onset of these problems at age 5. Yet, we cannot rule out that this cohort had a relatively mild level of disease severity; therefore, conclusions should be interpreted with caution. However, given the growing-into-deficit hypothesis, meaning that deviant brain development in early life is revealed once higher cognitive brain functions are demanded, follow-up should be conducted up to school age, and preferably beyond. What is Known: • Children born with CDH are at risk for academic difficulties at school age. • Whether these difficulties can be detected already before school age is unknown. What is New: • At age 5 years, intelligence, inhibition, attention, and memory skills were all within normal range, or even above, in children with CDH. This is supportive of the growing-into-deficit hypothesis in this patient population. • Those who underwent open surgical correction had poorer inhibition skills than those who were corrected with minimal access surgery.

Higher mean cerebral oxygen saturation shortly after extracorporeal cardiopulmonary resuscitation in patients who regain consciousness.

INTRODUCTION: In cardiac arrest, cerebral ischemia and reperfusion injury mainly determine the neurological outcome. The aim of this study was to investigate the relation between the course of cerebral oxygenation and regain of consciousness in patients treated with extracorporeal cardiopulmonary resuscitation (ECPR). We hypothesized that rapid cerebral oxygenation increase causes unfavorable outcomes. METHODS: This prospective observational study was conducted in three European hospitals. We included adult ECPR patients between October 2018 and March 2020, in whom cerebral regional oxygen saturation (rSO2 ) measurements were started minutes before ECPR initiation until 3 h after. The primary outcome was regain of consciousness, defined as following commands, analyzed using binary logistic regression. RESULTS: The sample consisted of 26 ECPR patients (23% women, Agemean 46 years). We found no significant differences in rSO2 values at baseline (49.1% versus 49.3% for regain versus no regain of consciousness). Mean cerebral rSO2 values in the first 30 min after ECPR initiation were higher in patients who regained consciousness (38%) than in patients who did not regain consciousness (62%, odds ratio 1.23, 95% confidence interval 1.01-1.50). CONCLUSION: Higher mean cerebral rSO2 values in the first 30 min after initiation of ECPR were found in patients who regained consciousness.

Development and validation of a condition-specific quality of life instrument for adults with esophageal atresia: the SQEA questionnaire.

The importance of multidisciplinary long-term follow-up for adults born with esophageal atresia (EA) is increasingly recognized. Hence, a valid, condition-specific instrument to measure health-related quality of life (HRQoL) becomes imperative. This study aimed to develop and validate such an instrument for adults with EA. The Specific Quality of life in Esophageal atresia Adults (SQEA) questionnaire was developed through focus group-based item generation, pilot testing, item reduction and a multicenter, nationwide field test to evaluate the feasibility, reliability (internal and retest) and validity (structural, construct, criterion and convergent), in compliance with the consensus-based standards for the selection of health measurement instruments guidelines. After pilot testing (n = 42), items were reduced from 144 to 36 questions. After field testing (n = 447), three items were discarded based on item-response theory results. The final SQEA questionnaire (33 items) forms a unidimensional scale generating an unweighted total score. Feasibility, internal reliability (Cronbach's alpha 0.94) and test-retest agreement (intra-class coefficient 0.92) were good. Construct validity was discriminative for esophageal replacement (P < 0.001), dysphagia (P < 0.001) and airway obstruction (P = 0.029). Criterion validity showed a good correlation with dysphagia (area under the receiver operating characteristic 0.736). SQEA scores correlated well with other validated disease-specific HRQoL scales such as the GIQLI and SGRQ, but poorly with the more generic RAND-36. Overall, this first condition-specific instrument for EA adults showed satisfactory feasibility, reliability and validity. Additionally, it shows discriminative ability to detect disease burden. Therefore, the SQEA questionnaire is both a valid instrument to assess the HRQoL in EA adults and an interesting signaling tool, enabling clinicians to recognize more severely affected patients.

Prevalence and determinants of medication administration errors in clinical wards: A two-centre prospective observational study.

AIMS AND OBJECTIVES: To identify the prevalence and determinants of medication administration errors (MAEs). BACKGROUND: Insight into determinants of MAEs is necessary to identify interventions to prevent MAEs. DESIGN: A prospective observational study in two Dutch hospitals, a university and teaching hospital. METHODS: Data were collected by observation. The primary outcome was the proportion of administrations with one or more MAEs. Secondary outcomes were the type, severity and determinants of MAEs. Multivariable mixed-effects logistic regression analyses were used for determinant analysis. Reporting adheres to the STROBE guideline. RESULTS: MAEs occurred in 352 of 2576 medication administrations (13.7%). Of all MAEs (n = 380), the most prevalent types were omission (n = 87) and wrong medication handling (n = 75). Forty-five MAEs (11.8%) were potentially harmful. The pharmaceutical forms oral liquid (odds ratio [OR] 3.22, 95% confidence interval [CI] 1.43-7.25), infusion (OR 1.73, CI 1.02-2.94), injection (OR 3.52, CI 2.00-6.21), ointment (OR 10.78, CI 2.10-55.26), suppository/enema (OR 6.39, CI 1.13-36.03) and miscellaneous (OR 6.17, CI 1.90-20.04) were more prone to MAEs compared to oral solid. MAEs were more likely to occur when medication was administered between 10 a.m.-2 p.m. (OR 1.91, CI 1.06-3.46) and 6 p.m.-7 a.m. (OR 1.88, CI 1.00-3.52) compared to 7 a.m.-10 a.m. and when administered by staff with higher professional education compared to staff with secondary vocational education (OR 1.68, CI 1.03-2.74). MAEs were less likely to occur in the teaching hospital (OR 0.17, CI 0.08-0.33). Day of the week, patient-to-nurse ratio, interruptions and other nurse characteristics (degree, experience, employment type) were not associated with MAEs. CONCLUSIONS: This study identified a high MAE prevalence. Identified determinants suggest that focusing interventions on complex pharmaceutical forms and error-prone administration times may contribute to MAE reduction. RELEVANCE TO CLINICAL PRACTICE: The findings of this study can be used to develop targeted interventions to improve patient safety.

Quality improvement intervention to stimulate early mobilisation of critically ill children.

BACKGROUND: Immobility during hospital stay is associated with muscle weakness, delirium, and delayed neurocognitive recovery. Early mobilisation of critically ill adults improves their physical functioning and shortens the duration of mechanical ventilation. However, comparable research in children is lacking. AIMS: To determine the effects of the implementation of an early mobilisation (EM) program on mobility activities for critically ill children and to explore barriers and facilitators and clinical outcomes before and after implementation. STUDY DESIGN: A prospective single-centre before-and-after study. This study was conducted in a PICU of a large tertiary hospital. Children aged from 3 months to 18 years, with an expected stay of ≥3 days were eligible to participate. In the "before" phase, participants received usual care; in the "after" phase we implemented a multicomponent, multidisciplinary EM protocol. The primary outcome was a change in the process outcome "mobilisation activities". Secondary outcomes were PICU staff opinions on mobilisation (survey), safety, process measures, involvement of parents and physical therapist, and clinical outcomes (sedative use and prevalence of delirium). RESULTS: A total of 113 children were included; 55 before and 58 after, with a median age of 31 months (IQR: 10-103) and 35 months (IQR: 7-152), respectively. The number of mobilisation activities (per patient per day) had significantly increased from 5 (IQR: 2-7) to 6 (IQR: 4-8) (U = 272185.0; p < .001). PT consultations for mobilisation had significantly increased from 23.6% (13/55) to 46.5% (27/58) (X2  = 6.48; p = .011). In both phases, no mobilisation-related adverse events were documented. The survey showed that PICU staff found EM of critically ill children useful and feasible. In the after phase, PICU staff rated the perceived benefit of the support of the physical therapist during mobilisation activities significantly higher than in the before phase (X2  = 34.80; p < .001). CONCLUSIONS: Implementation of a structured EM program for critically ill children is feasible and safe. RELEVANCE TO CLINICAL PRACTICE: It is suggested to start the implementation of a structed EM program with the idendentification of local barriers and facilitators by an interdisciplinary PICU team. Further, an increased presence of physiotherapists on the PICU would improve mobilisation levels, and facilitate mobilisation in critically ill children. Also, they can support and advice PICU nurses and parents in mobilising children.

Implementation of a nursing oral health care protocol in a university teaching hospital: A cluster-randomized stepped-wedge design.

INTRODUCTION: Providing oral care is an essential part of basic nursing care but receives little priority in daily practice, with a risk of adverse events. Also, nurses report many barriers to adequate provision of oral care, such as time restraints, insufficient materials, fear of causing pain, lack of knowledge and a negative attitude towards providing oral care. METHODS: We performed a cluster-randomized, stepped-wedge study to explore the effect of the the implementation of a new nursing evidence-based oral care protocol on nurses' knowledge, attitude and protocol adherence. The study population included both nursing students, graduated nurses and patients in selected wards. The implementation strategy included oral and written information, instruction videos and reminders. Nurses' knowledge and attitude towards oral care were assessed at baseline and after the implementation of the protocol with a validated 47-item questionnaire with a score range of 0-100. Secondarily, nurses' protocol adherence to teeth brushing, measured in Activities of Daily Living (ADL) dependent patients, was evaluated. The Standards for Reporting Implementation Studies (StaRI) Statement was used. RESULTS: At baseline, the questionnaire was completed by 226 nurses; after implementation by 283. Knowledge had significantly improved from 68.8 to 72.3. Nurses' attitude improved not significantly. Protocol adherence was assessed in 73 ADL-dependent patients at baseline, in 51 after implementation. Adherence to teeth brushing significantly decreased in patients with permanent teeth. Also, adherence to both teeth brushing and usage of soap decreased in patients with (partial) dentures. CONCLUSION: Nurses' knowledge and attitude of oral care increased somewhat after the implementation of a new nursing evidence-based protocol. After implementation, there was an unexplained decreased adherence to oral care in ADL-dependent patients.

Association Between Geriatric Assessment and Post-Chemotherapy Functional Status in Older Patients with Cancer.

BACKGROUND: Maintaining functional status is among the most important patient-centered outcomes for older adults with cancer. This study investigated the association between comprehensive geriatric assessment (CGA) and progressive disease or decline of IADL-independence 1 year after chemotherapy, overall survival (OS), and premature termination of chemotherapy. CGA-based functional status and quality of life (QOL) 1 year after chemotherapy are also described. METHODS: This prospective cohort study involved patients aged ≥65 years treated with chemotherapy for any cancer type. CGA and the G8-screening tool were performed before and after the completion of chemotherapy. Analyses were adjusted for tumor type and treatment intent: (a) indolent hematological malignancies, (b) aggressive hematological malignancies, c) solid malignancies treated with curative intent, and (d) solid malignancies treated with palliative intent. RESULTS: All 291 included patients lived in The Netherlands; 193 (67.4%) lived fully independent prior to chemotherapy. The median age was 72 years; 164 (56.4%) were male. IADL independence, CGA-based functional status, and QOL were maintained in half of the patients 1 year after chemotherapy. An abnormal G8-score before chemotherapy was a higher risk for progressive disease or a decline of IADL-independence (OR 3.60, 95% CI, 1.98-6.54, P < .0001), prematurely terminated chemotherapy (OR 2.12, 95% CI, 1.24-3.65, P = .006), and shorter median OS (HR 1.71, 95% CI, 1.16-2.52, P = .007). The impact of an abnormal G8-score differed across tumor type (oncological or hematological) and treatment indication (adjuvant or palliative). CONCLUSION: An abnormal G8 score before chemotherapy is associated with progressive disease and functional decline after chemotherapy and shorter median OS, especially in patients with solid malignancies.

Sentinel lymph node procedure in patients with recurrent vulvar squamous cell carcinoma: a proposed protocol for a multicentre observational study.

BACKGROUND: Standard groin treatment in recurrent vulvar cancer consists of uni- or bilateral inguinofemoral lymphadenectomy (IFL), whereas in the primary setting women with selected unifocal tumours will undergo a sentinel lymph node (SLN) procedure. The SLN procedure results in fewer short and long-term sequelae compared to IFL, but some concerns must first be considered. Lymph drainage of the vulvar region can be affected by a previous surgery, which might reduce the number of detectable SLN nodes (feasibility) but increase the chance of encountering aberrant lymph drainage patterns such as bilateral SLNs in lateral tumours or SLNs at unexpected locations. Therefore, the SLN procedure potentially carries a higher risk of groin recurrence if a tumour positive node is not retrieved, but may also improve outcomes for women with aberrant drainage patterns. Since the relative benefits and drawbacks of the SLN procedure are still unclear we will investigate the safety of the SLN procedure in women with a first recurrent vulvar cancer. In a simultaneously started registration study we prospectively gather information on women with a first recurrence of vulvar cancer ineligible for the SLN procedure. METHOD: In this prospective multicentre observational study all women with a first recurrence of vulvar cancer will be asked to consent to the collection of information on their diagnostics, treatment and outcome, and to complete quality of life and lymph oedema questionnaires. Women with unifocal tumours smaller than 4 cm and unsuspicious groin nodes will be offered the SLN procedure, with follow-up every 3 months together with imaging at 6 and 12 months when the SLN is tumour negative. The primary outcome is groin recurrence within 2 years of initial surgery. A total of 150 women with negative SLNs will be required to demonstrate safety, a stopping rule will apply and an extensive statistical analysis has been designed. DISCUSSION: Should the SLN procedure prove feasible and safe in recurrent vulvar cancer, it will be available for implementation in clinics worldwide. The inclusion of women ineligible for the SLN procedure in the current prospective study will help to bridge knowledge gaps and define future research questions. TRIAL REGISTRATION: Medical Ethical Committee approval number NL70149.078.19 (trial protocol version 2.0, date March 2nd, 2020). Affiliation: Erasmus Medical Centre. Dutch trial register NL8467 . Date of registration 19.03.2020.

Language lateralization in very preterm children: associating dichotic listening to interhemispheric connectivity and language performance.

BACKGROUND: Language difficulties of very preterm (VPT) children might be related to weaker cerebral hemispheric lateralization of language. Language lateralization refers to the development of an expert region for language processing in the left hemisphere during the first years of life. Children born VPT might not develop such a dominant left hemisphere for language processing. A dichotic listening task may be a functional task to show the dominance of the left hemisphere during language processing. During this task, different acoustic events are simultaneously presented to both ears. Due to crossing fibers in the brain, right ear stimuli are transferred directly to the left hemisphere, and left ear stimuli are transferred first to the right hemisphere and then, through the corpus callosum (CC), to the left hemisphere. Dichotic listening typically shows a right ear advantage, assuming to reflect left hemispherical language dominance. The CC, in particular the splenium, is associated with auditory processing and is considered important for language lateralization. The objective of this work was to explore whether dichotic listening performance in school-aged VPT children are associated with language performance and interhemispheric connectivity. METHODS: This is a cross-sectional study of 58 VPT children and 30 full term controls at age 10 years. Language performance and dichotic digit test (DDT) were assessed. In 44 VPT children, additionally diffusion weighted imaging (DWI) was performed using a 3 T MRI scanner. Fractional anisotropy (FA) and mean diffusivity (MD) values of the splenium of the CC were extracted. RESULTS: Poorer right ear DDT scores were associated with poorer language performance in VPT children only (p = 0.015). Association between right ear DDT scores and MD of the splenium approached the level of significance (p = 0.051). CONCLUSIONS: These results support the hypothesis that poor language performance in VPT children may be a consequence of weaker lateralized language organization, due to a poorly developed splenium of the CC. Dichotic listening may reflect the level of language lateralization in VPT children. IMPACT: Poor language performance in VPT children may be a consequence of weaker lateralized language organization, due to a poorly developed splenium of the CC. Dichotic listening performance may reflect the level of language lateralization in VPT children and right ear scores of a dichotic listening task are associated with both the splenium of the corpus callosum and language performance. If our results could be validated in future research, it suggests that poor CC development may indicate VPT children at risk for long-term language problems.