Lower respiratory tract infections in children with congenital lung abnormalities.

OBJECTIVE: We aimed to determine if the incidence of lower respiratory tract infections (LRTI) among children with asymptomatic, observationally managed congenital lung abnormalities (CLA) differed from that of symptomatic patients who underwent surgery. Second, we sought to compare the pre- and post-resection incidence of LRTI in patients who underwent surgery. METHODS: This retrospective cohort study included patients born between 1999 and 2021 with CLA confirmed by CT scan who were enrolled in a prospective longitudinal follow-up program. The LRTI incidence rates at 1, 2, 5, 8, and 12 years were compared between surgically and observationally managed patients using incidence rate ratios (IRR). Differences in pre- and post-resection LRTI incidence rates among patients who underwent CLA-related surgery were assessed through IRR. RESULTS: Among 217 included patients, 81 (37%) had undergone surgery and 136 (63%) had been observationally managed. The LRTI incidence rates did not significantly differ at any follow-up moment between the surgical and observational groups. Among the children who underwent CLA-related surgery, the pre-resection LRTI incidence rates were significantly higher than the post-resection LRTI incidence rates (IRR of 3.57, 95% confidence interval: [2.00; 6.33], p < .001). CONCLUSION: We could not demonstrate differences in LRTI incidence throughout childhood between patients with surgically and observationally managed CLA. We recommend discussing cases of LRTI in patients with CLA in a multidisciplinary setting, using additional diagnostics such as chest X-ray to screen for CLA involvement, enabling a well-considered decision on surgical resection of the lesion.

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.

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.

Bayesian interim analysis for prospective randomized studies: reanalysis of the acute myeloid leukemia HOVON 132 clinical trial.

Randomized controlled trials (RCTs) are the gold standard to establish the benefit-risk ratio of novel drugs. However, the evaluation of mature results often takes many years. We hypothesized that the addition of Bayesian inference methods at interim analysis time points might accelerate and enforce the knowledge that such trials may generate. In order to test that hypothesis, we retrospectively applied a Bayesian approach to the HOVON 132 trial, in which 800 newly diagnosed AML patients aged 18 to 65 years were randomly assigned to a "7 + 3" induction with or without lenalidomide. Five years after the first patient was recruited, the trial was negative for its primary endpoint with no difference in event-free survival (EFS) between experimental and control groups (hazard ratio [HR] 0.99, p = 0.96) in the final conventional analysis. We retrospectively simulated interim analyses after the inclusion of 150, 300, 450, and 600 patients using a Bayesian methodology to detect early lack of efficacy signals. The HR for EFS comparing the lenalidomide arm with the control treatment arm was 1.21 (95% CI 0.81-1.69), 1.05 (95% CI 0.86-1.30), 1.00 (95% CI 0.84-1.19), and 1.02 (95% CI 0.87-1.19) at interim analysis 1, 2, 3 and 4, respectively. Complete remission rates were lower in the lenalidomide arm, and early deaths more frequent. A Bayesian approach identified that the probability of a clinically relevant benefit for EFS (HR < 0.76, as assumed in the statistical analysis plan) was very low at the first interim analysis (1.2%, 0.6%, 0.4%, and 0.1%, respectively). Similar observations were made for low probabilities of any benefit regarding CR. Therefore, Bayesian analysis significantly adds to conventional methods applied for interim analysis and may thereby accelerate the performance and completion of phase III trials.

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.

Pain during the first year after scoliosis surgery in adolescents, an exploratory, prospective cohort study.

Objective: Approximately 50% of adolescents who have undergone scoliosis surgery still experience severe pain one year postoperatively. We explored the postoperative pain trajectory and the potential value of preoperative Thermal Quantitative Sensory Testing (T-QST) as predictor of chronic postsurgical pain after scoliosis surgery. Design: Single-center prospective cohort study in adolescents undergoing scoliosis surgery. Outcomes: Prevalence of chronic postsurgical pain (CPSP) one year after scoliosis surgery and postsurgical pain course during this year. The need for rescue medication and the relationship between pre-operative T-QST, acute pain and CPSP. Results: Thirty-nine patients (mean age 13.9 years; SD 1.9 years) completed the study. One year postoperatively, ten patients (26%) self-reported pain [numeric rating scale (NRS) score ≥ 4]) when moving and two (5%) when in rest. Four of these patients (10.3%) experienced neuropathic pain. The pre-operative cold pain threshold was lower (p = 0.002) in patients with CPSP at 12 months. Preoperative cold and heat pain thresholds were correlated with the number of moderate or severe pain reports (NRS ≥ 4) in the first week postoperatively (r -.426; p = 0.009 and r.392; p = 0.016, respectively). Conclusions: One year after scoliosis surgery, a significant part of patients (26%) still reported pain, some with neuropathic characteristics. Better diagnosis and treatment is needed; our study suggests that T-QST could be further explored to better understand and treat children with this negative outcome.

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.

Reasons Patients With Primary Progressive Multiple Sclerosis Contact Their Specialist Nurses.

BACKGROUND: Questions asked by patients with primary progressive multiple sclerosis (PPMS) during patient-initiated MS nurse consultations may contain salient information that can help health care providers understand their needs, which, in turn, can help tailor counseling and treatment. METHODS: Records of all patients with PPMS visiting the MS center of a large teaching hospital in the Netherlands between January 2007 and January 2021 were studied retrospectively. Number and type (scheduled or patient initiated) of MS nurse consultations, reasons for consultations (in prespecified categories), and frequency of subsequent referrals were registered. Association between factors (living with partner, Expanded Disability Status Scale score, comorbidities, age, sex) and number of patient-initiated consultations was studied using negative binomial regression analysis. RESULTS: In total, 98 patients with PPMS were included, with 720 MS nurse consultations during follow-up (median duration, 8.1 years), of which 274 (38%) were patient initiated. Patients had a broad spectrum of reasons to contact MS nurses. The most common categories were treatment (36%) and micturition and defecation (31%). Patients living without a partner (incidence rate ratio, 2.340; 95% CI, 1.057-5.178) and male patients (incidence rate ratio, 1.890; 95% CI, 0.925-3.861) consulted MS nurses more frequently. The MS nurses made 146 referrals (20% of all contacts); 59 were after patient-initiated consultation (22%). The most frequent referrals were to neurologists, urologists, and rehabilitation specialists. CONCLUSIONS: Multiple sclerosis nurses have a pivotal role in PPMS care, especially for patients living without a partner and male patients. Recurring questions about (new) treatment options illustrate the pressing need for highly effective treatment. Micturition and defecation problems are also a considerable concern and warrant close monitoring.

Disease activity in primary progressive multiple sclerosis: a systematic review and meta-analysis.

Background: Disease activity in multiple sclerosis (MS) is defined as presence of relapses, gadolinium enhancing lesions and/or new or enlarging lesions on MRI. It is associated with efficacy of immunomodulating therapies (IMTs) in primary progressive MS (PPMS). However, a thorough review on disease activity in PPMS is lacking. In relapsing remitting MS, the prevalence of activity decreases in more contemporary cohorts. For PPMS, this is unknown. Aim: To review disease activity in PPMS cohorts and identify its predictors. Methods: A systematic search in EMBASE, MEDLINE, Web of science Core Collection, COCHRANE CENTRAL register of trials, and GOOGLE SCHOLAR was performed. Keywords included PPMS, inflammation, and synonyms. We included original studies with predefined available data, extracted cohort characteristics and disease activity outcomes and performed meta-regression analyses. Results: We included 34 articles describing 7,109 people with PPMS (pwPPMS). The weighted estimated proportion of pwPPMS with overall disease activity was 26.8% (95% CI 20.6-34.0%). A lower age at inclusion predicted higher disease activity (OR 0.91, p = 0.031). Radiological activity (31.9%) was more frequent than relapses (9.2%), and was predicted by longer follow-up duration (OR 1.27, p = 0.033). Year of publication was not correlated with disease activity. Conclusion: Inflammatory disease activity is common in PPMS and has remained stable over the last decades. Age and follow-up duration predict disease activity, advocating prolonged monitoring of young pwPPMS to evaluate potential IMT benefits.

Twelve-year outcomes of watchful waiting versus surgery of mildly symptomatic or asymptomatic inguinal hernia in men aged 50 years and older: a randomised controlled trial.

Background: Inguinal hernia belongs to the most common surgical pathology worldwide. Approximately, one third is asymptomatic. The value of watchful waiting (WW) in patients with asymptomatic or mildly symptomatic inguinal hernia has been established in a few randomised controlled trials (RCTs). The aim of this study was to assess long-term outcomes of a RCT comparing WW and elective surgery. Methods: In the original study, men aged ≥50 years with an asymptomatic or mildly symptomatic inguinal hernia were randomly assigned to WW or elective repair. In the present study, the primary outcome was the 12-year crossover rate to surgery, secondary outcomes were time-to-crossover, patient regret, pain, quality of life and incarceration. Dutch Trial Registry: NTR629. Findings: Out of 496 originally analysed patients, 488 (98.4%) were evaluable for chart review (WW: n = 258, surgery: n = 230), and 200 (41.0%) for telephone contact (WW: n = 106, surgery: n = 94) between November 2021 and March 2022 with a median 12 years follow-up (IQR 9-14). After 12 years, the estimated cumulative crossover rate to surgery was 64.2%, which was higher in mildly symptomatic than in asymptomatic patients (71.7% versus 60.4%, HR 1.451, 95% CI: 1.064-1.979). Time-to-crossover was longer in asymptomatic patients (50% after 6.0 years versus 2.0 years, p = 0.019). Patient regret was higher in the WW group (37.7 versus 18.0%, p = 0.002), as well as pain/discomfort (p = 0.031). Quality of life did not differ (p = 0.737). In the WW group, incarceration occurred in 10/255 patients (3.9%). Interpretation: During 12-year follow-up, most WW patients crossed over to surgery, significantly earlier with mildly symptomatic hernia. Considering the relatively low incarceration rate, WW might still be an option in asymptomatic patients with a clear preference and being well-informed about pros and cons. Funding: The initial trial was funded by the Netherlands Organisation for Health Research and Development (ZonMW). This long-term study did not receive funding.

The (cost) effectiveness of a very low-energy diet intervention with the use of eHealth in patients with type 2 diabetes and obesity: study protocol for a randomised controlled non-inferiority trial (E-diet trial).

BACKGROUND: Despite preventive measures, the number of people with type 2 diabetes and obesity is increasing. Obesity increases morbidity and mortality in people with type 2 diabetes, making weight loss a cornerstone of treatment. We previously developed a very low energy diet (VLED) intervention that effectively reduced weight in people with type 2 diabetes in the long term. However, this intervention requires considerable time and manpower, which reduces the number of people who can benefit from it. eHealth offers more efficient solutions but has proven to be less effective than face-to-face interventions. Therefore, we want to investigate whether a blended version of our VLED intervention (in which face-to-face contact is partly replaced by an eHealth (mobile) application (E-VLED)) would be more cost-effective than the current face-to-face intervention. METHODS: We will conduct a randomised, controlled trial with non-inferiority design in patients with type 2 diabetes and obesity (BMI > 30 kg/m2), aged 18-75 years. The control group will receive the usual care VLED intervention, while the intervention group will receive the E-VLED intervention for 1 year, where face-to-face contact will be partly replaced by an eHealth (mobile) application. The main study endpoint is the difference in weight (% change) between the control and intervention group after 1 year, plus the difference between the total costs (euro) of the treatment in the control and intervention groups. The secondary aims are to investigate the effectiveness of the E-VLED diet intervention regarding cardiovascular risk factors, quality of life, patient satisfaction, compliance, and to study whether there is a difference in effectiveness in pre-specified subgroups. General linear models for repeated measurements will be applied for the statistical analysis of the data. DISCUSSION: We hypothesise that the E-VLED intervention will be equally effective compared to the usual care VLED but lower in costs due to less time invested by the dietician. This will enable to help more people with type 2 diabetes and obesity to effectively lose weight and improve their health-related quality of life. TRIAL REGISTRATION: Netherlands Trial Register, NL7832, registered on 26 June 2019.

Cardiopulmonary Morbidity in Adults Born With Congenital Diaphragmatic Hernia.

OBJECTIVES: Studies concerning cardiopulmonary outcomes of adults born with congenital diaphragmatic hernia (CDH) are sparse. Moreover, they don't include participants who have been treated with extracorporeal membrane oxygenation (ECMO) during the neonatal period. This study evaluated the cardiopulmonary morbidities in young adults born with CDH. METHODS: We assessed 68 participants between the ages of 18 and 30 years. The assessment included auxology assessment, lung function tests, pulmonary imaging, cardiopulmonary exercise testing, and echocardiography. RESULTS: Lung function parameters in the overall group were significantly worse than normal values. Mean (SD) scores postbronchodilator forced expiratory volume in 1 second were -2.91 (1.38) in the ECMO-treated and -1.20 (1.53) in the non-ECMO-treated participants. Chest computed tomography scans showed mild to moderate abnormal lung structure in all ECMO-treated participants, and to a lesser extent in non-ECMO treated participants. A recurrent diaphragmatic defect was observed in 77% of the ECMO-treated group and in 43% of the non-ECMO-treated group. Except for 2 cases with acute symptoms, no clinical problems were noted in cases of recurrence. Cardiopulmonary exercise testing revealed mean (SD) percentage predicted peak oxygen consumption per kilogram of 73 (14)% and 88 (16)% in ECMO-treated and non-ECMO-treated participants, respectively. The mean (SD) workload was normal in the non-ECMO-treated group (111 [25]% predicted); in the ECMO-treated group, it was 89 (23)%. Cardiac evaluation at rest revealed no signs of pulmonary hypertension. CONCLUSIONS: In young adults who survived treatment of CDH, significant pulmonary morbidity, reduced exercise capacity, and frequent hernia recurrence should be anticipated. Lifelong follow-up care, with the emphasis on prevention of further decline, is to be recommended.

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.

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.

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.

Acquired von Willebrand disease in children undergoing extracorporeal membrane oxygenation: a prospective observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides cardiopulmonary support for children with severe cardiac and/or pulmonary failure. The incidence of bleeding complications during ECMO support is high. Acquired von Willebrand disease (AVWD) might contribute to the development of bleeding complications. OBJECTIVE: To study the incidence and longitudinal profile of AVWD during the first 14 days of ECMO support in children and to investigate the association between AVWD and bleeding complications. METHODS: This prospective observational study included pediatric patients (0-17 years) receiving ECMO. Blood was sampled prior to and after ECMO start, daily and 12 to 24 hours after stopping ECMO. von Willebrand factor (VWF) parameters and multimer patterns were determined. Clinical data were collected for each patient. AVWD was defined as loss of high-molecular weight multimers (ie, decreased compared with baseline) or a VWF:collagen binding/VWF: antigen (Ag) ratio or VWF:activity/VWF:Ag ratio below 0.7. RESULTS: All of 50 (100%) patients developed AVWD during ECMO. The VWF:collagen binding /VWF:Ag ratio, VWF:activity/VWF:Ag ratio, and high-molecular weight multimers decreased during the initial days and recovered to baseline level within 24 hours after stopping ECMO. The incidence and longitudinal profile of AVWD were similar in patients with and without major bleeding complications. CONCLUSION: Children receiving ECMO support commonly develop AVWD. AVWD develops rapidly after ECMO initiation and recovers quickly after ECMO cessation. Importantly, AVWD appears to be independent of major bleeding.

The effect of recorded music on pain endurance (CRESCENDo) - A randomized controlled trial.

INTRODUCTION: Clarifying the effect of music on pain endurance in an experimental design could aid in how music should be applied during both surgical and non-surgical interventions. This study aims to investigate the effect of music on pain endurance and the involvement of the sympathetic adrenomedullary axis (SAM) and the hypothalamic-pituitary-adrenocortical axis (HPA). MATERIALS AND METHODS: In this randomized controlled trial all participants received increasing electric stimuli through their non-dominant index finger. Participants were randomly assigned to the music group (M) receiving a 20-minute music intervention or control group (C) receiving a 20-minute resting period. The primary outcome was pain endurance, defined as amount milliampere tolerated. Secondary outcomes included anxiety level, SAM-axis based on heart rate variability (HRV) and salivary alpha-amylase, and HPA-axis activity based on salivary cortisol. RESULTS: In the intention-to-treat analysis, the effect of music on pain tolerance did not statistically differ between the M and C group. A significant positive effect of music on pain endurance was noted after excluding participants with a high skin impedance (p = 0.013, CI 0.35; 2.85). Increased HRV was observed in the M-group compared to the C-group for SDNN (B/95%CI:13.80/2.22;25.39, p = 0.022), RMSSD (B/95%CI:15.97/1.64;30.31, p = 0.032), VLF (B/95%CI:212.08/60.49;363.67, p = 0.008) and HF (B/95%CI:821.15/150.78;1491.52, p = 0.0190). No statistical significance was observed in other secondary outcomes. CONCLUSIONS: The effect of the music intervention on pain endurance was not statistically significant in the intention-to-treat analysis. The subgroup analyses revealed an increase in pain endurance in the music group after correcting for skin impedance, which could be attributed to increased parasympathetic activation.