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Objectives: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome., Study Design: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified., Results: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes., Conclusions: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The glycolysis process of flexible polyurethane foams containing styrene-acrylonitrile and calcium carbonate as fillers was explored in detail. The use of DABCO as a catalyst allowed us to reduce the catalyst concentration and the polyurethane-to-glycol mass ratio to 0.1% and 1:1, respectively. The glycolysis process allowed us to obtain a high-purity polyol (99%), which can totally replace raw polyols in the synthesis of new flexible polyurethane foams, maintaining the standard mechanical properties of the original one and modifying the ratio of isocyanates employed to correct the closed cell structure caused by the impurities present in the recovered polyol. This isocyanate mixture was also optimized, resulting in a ratio of 30 and 70% of the isocyanates TDI80 and TDI65, respectively. Additionally, the fillers incorporated in the glycolyzed foams were recovered. Both recovered fillers, styrene-acrylonitrile and calcium carbonate, were fully characterized, showing a quality very similar to that of commercial compounds. Finally, the replacement of commercial fillers by the recovered ones in the synthesis of new polyurethane foams was studied, demonstrating the feasibility of using them in the synthesis of new foams without significantly altering their properties.

Mutations in DNA damage response (DDR) factors are associated with human infertility, which affects up to 15% of the population. The DDR is required during germ cell development and meiosis. One pathway implicated in human fertility is DNA translesion synthesis (TLS), which allows replication impediments to be bypassed. We find that TLS is essential for pre-meiotic germ cell development in the embryo. Loss of the central TLS component, REV1, significantly inhibits the induction of human PGC-like cells (hPGCLCs). This is recapitulated in mice, where deficiencies in TLS initiation (Rev1 -/- or Pcna K164R/K164R ) or extension (Rev7  -/- ) result in a > 150-fold reduction in the number of primordial germ cells (PGCs) and complete sterility. In contrast, the absence of TLS does not impact the growth, function, or homeostasis of somatic tissues. Surprisingly, we find a complete failure in both activation of the germ cell transcriptional program and in DNA demethylation, a critical step in germline epigenetic reprogramming. Our findings show that for normal fertility, DNA repair is required not only for meiotic recombination but for progression through the earliest stages of germ cell development in mammals., (© 2024. The Author(s).)

Background: Augmented renal clearance (ARC) holds a risk of subtherapeutic drug concentrations. Knowledge of patient-, disease-, and therapy-related factors associated with ARC would allow predicting which patients would benefit from intensified dosing regimens. This study aimed to identify ARC predictors and to describe ARC time-course in critically ill children, using iohexol plasma clearance (CL iohexol ) to measure glomerular filtration rate (GFR)., Methods: This is a retrospective analysis of data from the "IOHEXOL" study which validated GFR estimating formulas (eGFR) against CL iohexol . Critically ill children with normal serum creatinine were included, and CL iohexol was performed as soon as possible after pediatric intensive care unit (PICU) admission (CL iohexol1 ) and repeated (CL iohexol2 ) after 48-72 h whenever possible. ARC was defined as CL iohexol exceeding normal GFR for age plus two standard deviations., Results: Eighty-five patients were included; 57% were postoperative patients. Median CL iohexol1 was 122 mL/min/1.73 m 2 (IQR 75-152). Forty patients (47%) expressed ARC on CL iohexol1 . Major surgery other than cardiac surgery and eGFR were found as independent predictors of ARC. An eGFR cut-off value of 99 mL/min/1.73 m 2 and 140 mL/min/1.73 m 2 was suggested to identify ARC in children under and above 2 years, respectively. ARC showed a tendency to persist on CL iohexol2 ., Conclusions: Our findings raise PICU clinician awareness about increased risk for ARC after major surgery and in patients with eGFR above age-specific thresholds. This knowledge enables identification of patients with an ARC risk profile who would potentially benefit from a dose increase at initiation of treatment to avoid underexposure., Trial Registration: ClinicalTrials.gov NCT05179564, registered retrospectively on January 5, 2022., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: The minimal clinically important difference (MCID) is a valuable tool for patient-based outcome analysis, for which limited data is available in the literature, especially after arthroscopic rotator cuff repair (ARCR). Although several studies have reported MCID after ARCR, few have studied the impact of various clinical factors such as Diabetes, pseudoparalysis, type of cuff repair, and retear over MCID. This study attempts to determine the MCID in shoulder functional scores after ARCR and the impact of various factors on MCID., Methods: 144 patients undergoing ARCR were prospectively evaluated at six and 12 months by ASES and UCLA scores. MCID for American Shoulder and Elbow Surgeons (ASES) and the University of California and Los Angeles (UCLA) scores were calculated using an anchor-based and distribution-based approach. MCID was also calculated for diabetic and non-diabetic patients, smokers vs. non-smokers, presence or absence of pseudoparalysis, type of cuff repair (single row vs. suture bridge), and presence of retears. Uni- and multivariate analysis was performed to identify factors affecting the MCID of both scores., Results: Mean MCID for ASES score was 13.3 and 16.6 using an anchor-based and distribution-based approach, respectively. For the UCLA score, the mean MCID was 10.0 and 12.6 by anchor-based and 12.6 by distribution-based approach, respectively. Patients with higher pre-operative ASES scores demonstrated lower MCID values. No significant difference was observed in MCID scores of diabetic vs. non-diabetic patients, smoker vs. non-smoker, patients with or without pseudoparalysis, and type of cuff repair. The age, gender, and presence of retear did not affect MCID values., Conclusion: This study establishes the MCID values of ASES and UCLA scores for rotator cuff repair by anchor and distribution methods. No patient or surgical factors appear to affect the MCID except pre-operative ASES scores., Study Design: Prospective cohort, Level II., (© 2024. The Author(s).)

Purpose: The shift from adjuvant to neoadjuvant treatment in colon cancer demands the radiological selection of patients for systemic therapy. The aim of this study was to evaluate the accuracy of the CT-based TNM stage and high-risk features, including extramural venous invasion (EMVI) and tumour deposits, in the identification of patients with histopathological advanced disease, currently considered for neoadjuvant treatment (T3-4 disease)., Methods: All consecutive patients surgically treated for non-metastatic colon cancer between January 2018 and January 2020 in a referral centre for colorectal cancer were identified retrospectively. All tumours were staged on CT according to the TNM classification system. Additionally, the presence of EMVI and tumour deposits on CT was evaluated. The histopathological TNM classification was used as reference standard., Results: A total of 176 patients were included. Histopathological T3-4 colon cancer was present in 85.0% of the patients with CT-detected T3-4 disease. Histopathological T3-4 colon cancer was present in 96.4% of the patients with CT-detected T3-4 colon cancer in the presence of both CT-detected EMVI and CT-detected tumour deposits. Histopathological T0-2 colon cancer was present in 50.8% of the patients with CT-detected T0-2 disease, and in 32.4% of the patients without CT-detected EMVI and tumour deposits., Conclusion: The diagnostic accuracy of CT-based staging was comparable with previous studies. The presence of high-risk features on CT increased the probability of histopathological T3-4 colon cancer. However, a substantial part of the patients without CT-detected EMVI and tumour deposits was diagnosed with histopathological T3-4 disease. Hence, more accurate selection criteria are required to correctly identify patients with locally advanced disease., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Prospective audit with feedback during infectious diseases ward rounds (IDWR) is a common antimicrobial stewardship (AMS) practice on the Paediatric Intensive Care Unit (PICU). These interdisciplinary meetings rely on the quality of handover, with high risk of omission of information. We developed an electronic platform integrating infection-related patient data (COSARAPed). In the mixed PICU of a Belgian tertiary hospital we conducted an observational prospective cohort study comparing patient handovers during IDWRs using the COSARAPed-platform to those with access only to conventional resources. The quality of handover was investigated directly by assessment if the narrative was in accordance with Situation-Background-Assessment-Recommendation principles and if adequate demonstration of diagnostic information occurred, and also indirectly by registration if this was only achieved after intervention by the non-presenting AMS team members. We also recorded all AMS-recommendations. During a 6-month study period, 24 IDWRs and 82 patient presentations were assessed. We could only find a statistically significant advantage in favor of COSARAPed by indirect evaluation. We registered 92 AMS-recommendations, mainly resulting in reduced antibiotic pressure. We concluded that the IDWR is an appropriate platform for AMS on the PICU and that the utilisation of COSARAPed may enhance the quality of patient handover., (© 2024. The Author(s).)

In space, cells sustain strong modifications of their mechanical environment. Mechanosensitive molecules at the cell membrane regulate mechanotransduction pathways that induce adaptive responses through the regulation of gene expression, post-translational modifications, protein interactions or intracellular trafficking, among others. In the current study, human osteoblastic cells were cultured on the ISS in microgravity and at 1 g in a centrifuge, as onboard controls. RNAseq analyses showed that microgravity inhibits cell proliferation and DNA repair, stimulates inflammatory pathways and induces ferroptosis and senescence, two pathways related to ageing. Morphological hallmarks of senescence, such as reduced nuclear size and changes in chromatin architecture, proliferation marker distribution, tubulin acetylation and lysosomal transport were identified by immunofluorescence microscopy, reinforcing the hypothesis of induction of cell senescence in microgravity during space flight. These processes could be attributed, at least in part, to the regulation of YAP1 and its downstream effectors NUPR1 and CKAP2L., (© 2023. The Author(s).)

Introduction: Interprofessional collaboration among healthcare professionals is fostered through interprofessional education (IPE). Work-based IPE has demonstrated effectiveness within interprofessional training wards. We developed the Interprofessional Training Ward in Pediatrics (IPAPED) and employ a combination of established assessment tools and a newly created IPAPED questionnaire, directed at to assess both students' learning experiences and program structure. This paper presents the development and analysis of the psychometric properties of the IPAPED questionnaire., Methods: Nursing trainees and medical students participated in IPAPED. The IPAPED questionnaire was developed to complement established instruments, based on IPE frameworks. Interprofessional collaboration and communication were represented in subscales in part 1 of the questionnaire. Part 2 focused on the IPAPED program itself. Statistical analyses included calculation of internal consistency for part 1 and exploratory factor analyses for part 2., Results: All IPAPED participants between November 2017 and November 2022 completed the questionnaire ( n  = 105). 94 of 105 questionnaires were analyzed. Internal consistency for part 1 was low (Cronbach's α <0.58). Exploratory factor analyses revealed three distinct factors: teaching and learning material, interprofessional learning facilitation and professional guidance by nurses on the ward., Discussion: Our results illustrate the challenge of performing high quality, theory based evaluation in a work-based setting. However, exploratory factor analyses highlighted the opportunity of focusing on both learning facilitators and staff on the wards to ensure a maximum learning output for participants. Developing program-specific questionnaires to gain insight into local structures has the potential to improve work-based IPE formats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Straub, Bode, Willems, Farin-Glattacker and Friedrich.)

Background: Microaggressions are pervasive problems in the workplace; the general practice setting is no exception., Objective: This article examines what microaggressions are and outlines the key roles of protagonist, target, bystander and ally. It explores the effects of microaggressions on target persons (how microaggressions can affect their physical or mental health), and the implications microaggressions might also have for patient safety and broader workforce security., Discussion: The article concludes by considering professional development strategies that can be adopted, including how to move from a position of bystander to ally.

Introduction: Bone loss is present in all revision total knee arthroplasties. Metaphyseal cones allow surgeons to negotiate loss of femoral and tibial bone stock while obtaining stable bony fixation. This study examines the mid-term functional and radiographic outcomes in patients undergoing revision total knee arthroplasty (rTKA) utilizing a novel metaphyseal cone system., Methods: This multicenter retrospective study examined all patients who received a porous, titanium tibial or femoral cone at four academic urban tertiary care institutions and presented for a minimum two-year follow-up. Patient demographics, indications for revision surgery, knee range-of-motion (ROM), re-revision rates, radiographic measurements, bone defect per AORI classification, and implant osseointegration were evaluated according to the Knee Society total knee arthroplasty (TKA) radiographic evaluation system., Results: One-hundred and four patients received 128 cone implants (84 tibial, 44 femoral cones; 24 patients with simultaneous ipsilateral tibial and femoral cones; 104 rTKA) with mean follow-up of 32.75 ± 6.54 months. The pre-operative main revision indications were aseptic loosening 36 (34.61 %), periprosthetic infection (PJI) 23 (22.11 %) and instability 18 (17.3 %). Thirteen rTKA underwent re-revision surgery: 3 for acute PJI, 4 for chronic PJI, 5 for instability, and 1 for mechanical failure of a hinged system. At most recent radiographic follow-up available, all unrevised cones had evidence of osteointegration and no visible implant migration.All-cause re-operation free survivorship was 87.5 % (91/104), and all-cause cone implant survivorship was 96.09 % (123/128 cones) at 2-year follow-up., Conclusion: This study demonstrates excellent mid-term outcomes of a novel porous, titanium metaphyseal cone in patients with large bone defects undergoing complex revision TKA., Level of Evidence: IV, case series., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ran Schwarzkopf, MD, MSc reports financial support was provided by 10.13039/100009026Smith and Nephew Inc. Ran Schwarzkopf reports a relationship with American Association of Hip and Knee Surgeons that includes: board membership. Jose A. Rodriguez reports a relationship with American Association of Hip and Knee Surgeons that includes: board membership. Ran Schwarzkopf reports a relationship with American Academy of Orthopaedic Surgeons that includes: board membership. Jose A. Rodriguez reports a relationship with American Academy of Orthopaedic Surgeons that includes: board membership. Jose A. Rodriguez reports a relationship with Eastern Orthopaedic Association that includes: board membership. Ran Schwarzkopf reports a relationship with Smith and Nephew Inc that includes: consulting or advisory. Jose A. Rodriguez reports a relationship with Smith and Nephew Inc that includes: consulting or advisory. Jose A. Rodriguez reports a relationship with ConforMIS Inc that includes: consulting or advisory. Jose A. Rodriguez reports a relationship with DePuy Orthopaedics Inc that includes: consulting or advisory. Jose A. Rodriguez reports a relationship with Medacta USA INC that includes: consulting or advisory. Jose A. Rodriguez reports a relationship with Exactech Inc that includes: consulting or advisory. William B. Lutes reports a relationship with Smith and Nephew Inc that includes: consulting or advisory. William B. Lutes reports a relationship with Orthoalign that includes: consulting or advisory. Ran Schwarzkopf reports a relationship with Intelijoint that includes: equity or stocks. Ran Schwarzkopf reports a relationship with Gauss Surgical that includes: equity or stocks. Gijs van Hellemondt reports a relationship with Zimmer Biomet Holdings Inc that includes: consulting or advisory. Gijs van Hellemondt reports a relationship with Smith and Nephew Inc that includes: consulting or advisory., (© 2023 Delhi Orthopedic Association. All rights reserved.)

Introduction: Supporting care receivers in Activities of Daily Living (ADL), irrespective of diagnosis, setting, or cultural background, lies at the heart of fundamental nursing care. The pursuit of quality ADL care becomes increasingly challenging with the changing complexity of care needs. ADL care delivery is often undervalued and is considered a low-status task despite its crucial importance to care receivers. This study aims to synthesize challenges in ADL care irrespective of the care setting., Methods: In the mixed qualitative methods study, we used expert panel consultations, world café sessions, and a rapid literature review. For data analysis, we simultaneously analyzed the three data sets using inductive and deductive inquiry., Results: We identified four challenges and their corresponding subthemes. They are (1) Undervalued common-sense work versus complex, high-skilled care provision; (2) Limitations in professional reflective clinical decision-making; (3) Missed opportunities for shared ADL decisions; and (4) Meeting ADL care needs in a high-throughput system., Conclusion: These challenges reveal the complexity of ADL care and how its paradoxical narrative relates to the conditions in which nursing professionals struggle to create opportunities, for reflective clinical reasoning and shared ADL decisions, by facing organizational and environmental barriers., Clinical Relevance: This study is relevant to nursing professionals, care organizations, policymakers, and researchers aiming to improve ADL care and provide insights into challenges in ADL care. This study forms the starting point for a changing narrative on ADL nursing care and subsequent quality improvements in the form of, for example, guidelines for nursing professionals., (© 2023 The Authors. Journal of Nursing Scholarship published by Wiley Periodicals LLC on behalf of Sigma Theta Tau International.)

Background: The COVID-19 pandemic disrupted face-to-face delivery of general practitioner supervisor training in an unprecedented way. Simultaneously, the need for continuing professional development (CPD) amplified. The rapid pivot to virtual and blended learning solutions required great organisational agility, and a toolbox of solutions., Objective: Against the backdrop of the COVID-19 restrictions on face-to-face learning, this article shares the strategies employed to achieve the pivot to virtual CPD., Discussion: There was much trial and error, as well as successes and learning opportunities, as training organisations grappled with how to deliver virtual CPD during lockdowns.

Background: Identifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these phenotypes to specific patient populations is unclear. Given that paediatric cancer patients with sepsis have different host response and pathogen profiles and higher mortality rates when compared to non-cancer patients, we determined whether unique, reproducible, and clinically-relevant sepsis phenotypes exist in this specific patient population., Methods: We studied patients with underlying malignancies admitted with sepsis to one of 25 paediatric intensive care units (PICUs) participating in two large, multi-centre, observational cohorts from the European SCOTER study (n = 383 patients; study period between January 1, 2018 and January 1, 2020) and the U.S. Novel Data-Driven Sepsis Phenotypes in Children study (n = 1898 patients; study period between January 1, 2012 and January 1, 2018). We independently used latent class analysis (LCA) in both cohorts to identify phenotypes using demographic, clinical, and laboratory data from the first 24 h of PICU admission. We then tested the association of the phenotypes with clinical outcomes in both cohorts., Findings: LCA identified two distinct phenotypes that were comparable across both cohorts. Phenotype 1 was characterised by lower serum bicarbonate and albumin, markedly increased lactate and hepatic, renal, and coagulation abnormalities when compared to phenotype 2. Patients with phenotype 1 had a higher 90-day mortality (European cohort 29.2% versus 13.4%, U.S. cohort 27.3% versus 11.4%, p < 0.001) and received more vasopressor and renal replacement therapy than patients with phenotype 2. After adjusting for severity of organ dysfunction, haematological cancer, prior stem cell transplantation and age, phenotype 1 was associated with an adjusted OR of death at 90-day of 1.9 (1.04-3.34) in the European cohort and 1.6 (1.2-2.2) in the U.S. cohort., Interpretation: We identified two clinically-relevant sepsis phenotypes in paediatric cancer patients that are reproducible across two international, multicentre cohorts with prognostic implications. These results may guide further research regarding therapeutic approaches for these specific phenotypes., Funding: Part of this study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development., Competing Interests: LDJB is supported by the Amsterdam UMC fellowship, Health Holland, ZonMW, Innovative Medicine Initiative, and by the Dutch Lung Foundation (Longfonds) through the Dirkje Postma Award and personal fees from Scailyte, Sobi NL, Impentri, Novartis, AstraZeneca and CLS Behring, outside the submitted work. AM received personal fees from Dräger, outside the submitted work. CMR reports a research grant from the Indiana University Pediatric Critical Care, outside the submitted work. TDB reports funding from U.S. AHRQ (R18 HS029298), outside the submitted work. EVSF repots funding from US NIH, outside the submitted work. SLW reports grants from the US NIH/NICHD (R01HD102396 and R01HD105939) and NIH/National Institute of General Medical Sciences (R21GM146159), and royalties from Up To Date, outside the submitted work. LNS reports grants from the US NIH (R01HD105939 and R21GM146159), and personal fees from Celldom, Saccharo, Allyx, outside the submitted work., (© 2023 The Authors.)

Aims: To gain insights into the barriers towards the prevention and/or reduction of involuntary treatment in long-term geriatric care., Design: Mixed methods., Background: Measures to which a person resists and/or does not provide consent for are defined as involuntary treatment. The use of involuntary treatment violates the autonomy of (older) persons and causes more harm than benefit. Moreover, it contradicts the values of person-centred care. Nevertheless, its use among people living with dementia (PLWD) is still common practice., Methods: We conducted a cross-sectional, mixed methods study, including an online survey for professional caregivers and a semistructured focus group interview with professional caregivers., Results: A total of 218 participants completed the questionnaire. The percentage of participants who perceived barriers in one of the 22 survey items ranged from 15% to 42%. Lack of time, the experienced need to use involuntary treatment, uncertainty about responsibilities of stakeholders and a lack of knowledge on methods to prevent and/or reduce the use of involuntary treatment were most seen as barriers. Nursing staff perceived a lack of time hindering them in the prevention or reduction of involuntary treatment more often than other professional caregivers. Working in home care and having no former experience with involuntary treatment usage increased perceived barriers. Participants of the focus group interview confirmed these findings and added that professional caregivers in general lack awareness on the concept of involuntary treatment., Conclusions: One out of four professional caregivers experiences barriers hindering prevention and/or reduction of involuntary treatment. More research is needed to gain a better understanding of how professional caregivers can be supported to remove barriers and, consequently, prevent and/or reduce the use of involuntary treatment., Relevance to Clinical Practice: Professional caregivers experience many barriers towards the prevention and reduction of involuntary treatment. Future initiatives should aim to remove the perceived barriers., (© 2023 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Introduction: Spinal muscular atrophy (SMA) is a rare neuromuscular disease requiring various clinical specialists and therapists to provide care. Due to the disease's dynamic nature and the long distances between specialized centers and local providers, integrating care between disciplines can be challenging. Care that is inadequately integrated can compromise the quality of care and become a burden for patients and families. This trial aimed to improve the care of patients through a case management (CM) intervention., Methods: We conducted an exploratory, controlled, two-arm trial with pre-, post-, and follow-up measures (process and outcome evaluation). Proof of efficacy based on statistical significance was not our primary study objective since we were investigating a rare disease. Primary outcomes were caregivers' HRQoL and caregiver-rated quality of care integration. Our secondary outcome was the children's HRQoL., Results: Questionnaires and semi-structured interviews yielded heterogeneous results depending on caregivers' level of experience and desire (or possibility) to delegate care tasks., Discussion: Despite differing perceptions, all participants supported the establishment of a care coordination model. We recommend CM immediately after diagnosis to provide the greatest benefit to families. We hope that our trial will support the further development of CM interventions that can be customized for specific diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Willems, Pechmann, Wider, Ambs, Meyer, Cascante, Sproß, Mund, Farin-Glattacker and Langer.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Purpose: Trachoma is an eye disease caused by the bacterium Chlamydia trachomatis (Ct). It can lead to permanent vision loss. Since 2007, Burundi has included trachoma elimination as part of its fight against neglected tropical diseases and blindness. This study presents the results of trachoma baseline, impact and surveillance surveys conducted in Burundi between 2018 and 2021., Methods: Areas were grouped into evaluation units (EU) with resident populations of between 100,000 and 250,000 people. Baseline surveys were conducted in 15 EUs, impact surveys in 2 EUs and surveillance surveys in 5 EUs; in each survey, 23 clusters of about 30 households were included. Consenting residents of those households were screened for clinical signs of trachoma. Access to water, sanitation and hygiene (WASH) was recorded., Results: A total of 63,800 individuals were examined. The prevalence of TF in 1-9-year-olds was above the elimination threshold of 5% in a single EU at baseline, but fell below the threshold in subsequent impact and surveillance surveys. The prevalence of TT was below the 0.2% elimination threshold in ≥15-year-olds in all EUs surveyed. A high proportion (83%) of households had access to safe drinking water, while only a minority (~8%) had access to improved latrines., Conclusion: Burundi has demonstrated the prevalence levels necessary for trachoma elimination status. With continued effort and the maintenance of existing management plans, trachoma elimination in Burundi is within reach.

Background: Children with medical complexity (CMC) require long-term care accompanied by different health- and social care professionals. Depending on the severity of the chronic condition, caregivers spend a lot of time coordinating appointments, communicating between providers, clarifying social legal issues, and more. Effective care coordination is seen as key to addressing the fragmented care that CMC and their families often face. Spinal muscular atrophy (SMA) is a rare genetic, neuromuscular disease which care involves drug therapy and supportive treatment. We examined the care coordination experiences through a qualitative interview analysis of n = 21 interviews with caregivers of children with SMA I or SMA II., Results: The code system consists of 7 codes and 12 sub-codes. "Disease and coordination management of the caregivers" describes the management of coordination-related illness demands. "General conditions of care" include enduring organizational aspects of the care network. "Expertise and skills" refers to both parent and professional expertise. "Coordination structure" describes the assessment of existing coordination mechanisms as well as the need for new ones. "Information exchange" defines the information exchange between professionals and parents as well as the exchange of parents among themselves and the perceived exchange between professionals. "Role distribution in care coordination" summarizes parents' "distribution" of coordinative roles among care network actors (including their own). "Quality of relationship" describes the perceived quality of the relationship between professionals and family., Conclusion: Care coordination is influenced peripherally (e.g., by general conditions of care) and directly (e.g., by coordination mechanisms, interaction in the care network). Access to care coordination appears to be dependent on family circumstances, geographic location, and institutional affiliation. Previous coordination mechanisms were often unstructured and informal. Care coordination is frequently in the hands of caregivers mainly as the care network's interface. Coordination is necessary and must be addressed on an individual basis of existing resources and family barriers. Existing coordination mechanisms in the context of other chronic conditions could also work for SMA. Regular assessments, centralized shared care pathways, and staff training and empowerment of families for self-management should be central components of all coordination models., Trial Registration: German Clinical Trials Register (DRKS): DRKS00018778; Trial registration date 05. December 2019-Retrospectively registered; https://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00018778 ., (© 2023. The Author(s).)

Objectives: Complex challenges such as political instability, climate change and population displacement are increasing threats to national disease control, elimination and eradication programmes. The objective of this study was to determine the burden and risk of conflict-related and climate-related internal displacements and the need for strategies for countries endemic with neglected tropical diseases (NTDs)., Design, Setting and Outcome Measures: A cross-sectional ecological study was conducted including countries that are endemic with at least one of five NTDs requiring preventive chemotherapy in the African region. For each country, the number of NTDs, population size and the number and rate per 100 000 of conflict-related and natural disaster-related internal displacements reported in 2021 were classified into high and low categories and used in unison to stratify and map the burden and risk., Results: This analysis identified 45 NTD-endemic countries; 8 countries were co-endemic with 4 or 5 diseases and had populations classified as 'high' totalling >619 million people. We found 32 endemic countries had data on internal displacements related to conflict and disasters (n=16), disasters only (n=15) or conflict only (n=1). Six countries had both high conflict-related and disaster-related internal displacement numbers totalling >10.8 million people, and five countries had combined high conflict-related and disaster-related internal displacement rates, ranging from 770.8 to 7088.1 per 100 000 population. Weather-related hazards were the main cause of natural disaster-related displacements, predominately floods., Conclusions: This paper presents a risk stratified approach to better understand the potential impact of these complex intersecting challenges. We advocate for a 'call to action' to encourage national and international stakeholders to further develop, implement and evaluate strategies to better assess NTD endemicity, and deliver interventions, in areas at risk of, or experiencing, conflict and climate disasters, in order to help meet the national targets., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Natural hazards are increasing because of climate change, and they disproportionately affect vulnerable populations. Prior reviews of the mental health consequences of natural hazard events have not focused on the particular experiences of vulnerable groups. Based on the expected increase in fires and droughts in the coming years, the aim of this systematic review is to synthesize the global evidence about the mental health of vulnerable populations after experiencing natural hazards. We searched databases such as Ovid MEDLINE, EMBASE, CINAHL and Ovid PsycInfo using a systematic strategy, which yielded 3,401 publications. We identified 18 eligible studies conducted in five different countries with 15,959 participants. The most common vulnerabilities were living in a rural area, occupying a low socioeconomic position, being a member of an ethnic minority and having a medical condition. Common experiences reported by vulnerable individuals affected by drought included worry, hopelessness, isolation and suicidal thoughts and behaviors. Those affected by fire reported experiencing posttraumatic stress disorder (PTSD) and anger. These mental health problems exacerbated existing health and socioeconomic challenges. The evidence base about mental health in vulnerable communities affected by natural hazards can be improved by including standardized measures and comparison groups, examining the role of intersectional vulnerabilities, and disaggregating data routinely to allow for analyses of the particular experiences of vulnerable communities. Such efforts will help ensure that programs are informed by an understanding of the unique needs of these communities., Competing Interests: The authors declare none., (© The Author(s) 2023.)

Background: Integrated care models aim to strengthen the collaboration between healthcare sectors to ensure a higher quality of care for children with chronic conditions. Assessing pediatric healthcare integration through families' experiences, therefore, is essential. Our study aimed to psychometrically test the PICS-D, the first German-language integrated care questionnaire, which is based on the Pediatric Integrated Care Survey (PICS) developed in the USA., Methods: We examined construct validity using exploratory and confirmatory factor analyses (structural validity). Cronbach's α and McDonald's ω t coefficients explored reliability. Cognitive interviews assessed wording comprehension and item appropriateness., Results: PICS-D was completed by 204 caregivers of children with chronic conditions (women = 84%; mean age = 41.4 years). Factor analyses identified 3 factors: "Team quality & communication", "Family impact", and "Access to care". The 3-factorial structure showed a satisfying fit to confirmatory classical-test-theory-based models. Due to the insufficient reliability of the third factor, we recommend using only factors 1 and 2 for scoring the PICS-D., Conclusion: The PICS-D is a 13-item questionnaire to assess family-reported experiences in pediatric care integration, which has good psychometric properties. It may be useful in guiding quality improvement efforts or measuring the impact of a care plan or care model. Trial registration : German Clinical Trials Register (DRKS): DRKS00018778; Trial registration date 05. December 2019-Retrospectively registered; https://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00018778., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Willems, Bablok, Sehlbrede, Farin-Glattacker and Langer.)

Objectives: Congenital tracheomalacia can be the cause of respiratory failure in young children. Although the indication for surgical treatment has already been discussed vigorously, no clear guidelines about the modality are available., Methods: Through a sternotomy approach, a combination of posterior pexy and anterior tracheopexy using a tailored ringed polytetrafluoroethylene prosthesis is performed. Patient demographic characteristics, as well as operative details and postoperative outcomes, are included in the analysis., Results: Between 2018 and 2022, 9 children underwent the operation under review. All patients showed severe clinical symptoms of tracheomalacia, which was confirmed on bronchoscopy. The median age was 9 months. There was no operative mortality. Eight patients could be weaned from the ventilator. One patient died because of interstitial lung disease with bronchomalacia and concomitant severe cardiac disease. The longest follow-up now is 4 years, and shows overall excellent clinical results, without any reintervention., Conclusions: Surgical treatment of tracheomalacia through a combination of posterior and anterior pexy is feasible, with acceptable short- and midterm results., (© 2022 The Author(s).)

Background: Intensified treatment protocols have improved survival of pediatric oncology patients. However, these treatment protocols are associated with increased treatment-related morbidity requiring admission to pediatric intensive care unit (PICU). We aimed to describe the organizational characteristics and processes of care for this patient group across PICUs in Europe., Methods: A web-based survey was sent to PICU directors or representative physicians between February and June 2021., Results: Responses were obtained from 77 PICUs of 12 European countries. Organizational characteristics were similar across the different countries of Europe. The median number of PICU beds was 12 (IQR 8-16). The majority of the PICUs was staffed by pediatric intensivists and had a 24/7 intensivist coverage. Most PICUs had a nurse-to-patient ratio of 1:1 or 1:2. The median numbers of yearly planned and unplanned PICU admissions of pediatric cancer patients were 20 (IQR 10-45) and 10 (IQR 10-30, respectively. Oncology specific practices within PICU were less common in participating centres. This included implementation of oncology protocols in PICU (30%), daily rounds of PICU physicians on the wards (13%), joint mortality and morbidity meetings or complex patients' discussions (30% and 40%, respectively) and participation of parents during clinical rounds (40%)., Conclusion: Our survey provides an overview on the delivery of critical care for oncology patients in PICU across European countries. Multidisciplinary care for these vulnerable and challenging patients remains complex and challenging. Future studies need to determine the effects of differences in PICU organization and processes of care on patients' outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Nielsen, Agbeko, Bate, Jordan, Dohna-Schwake, Potratz, Moscatelli, Bottari, Pappachan, Witt, Crazzolara, Amigoni, Mizia-Malarz, Sánchez Martín, Willems, van den Heuvel-Eibrink, Schlapbach and Wösten-van Asperen.)

Background: The presence of mesorectal fascia (MRF) invasion, grade 4 extramural venous invasion (EMVI), tumour deposits (TD) or extensive or bilateral extramesorectal (lateral) lymph nodes (LLN) on MRI has been suggested to identify patients with indisputable, extensive locally advanced rectal cancer (LARC), at high risk of treatment failure. The aim of this study is to evaluate whether or not intensified chemotherapy prior to neoadjuvant chemoradiotherapy improves the complete response (CR) rate in these patients., Methods: This multicentre, single-arm, open-label, phase II trial will include 128 patients with non-metastatic high-risk LARC (hr-LARC), fit for triplet chemotherapy. To ensure a study population with indisputable, unfavourable prognostic characteristics, hr-LARC is defined as LARC with on baseline MRI at least one of the following characteristics; MRF invasion, EMVI grade 4, enlarged bilateral or extensive LLN at high risk of an incomplete resection, or TD. Exclusion criteria are the presence of a homozygous DPD deficiency, distant metastases, any chemotherapy within the past 6 months, previous radiotherapy within the pelvic area precluding standard chemoradiotherapy, and any contraindication for the planned treatment. All patients will be planned for six two-weekly cycles of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) prior to chemoradiotherapy (25 × 2 Gy or 28 × 1.8 Gy with concomitant capecitabine). A resection will be performed following radiological confirmation of resectable disease after the completion of chemoradiotherapy. A watch and wait strategy is allowed in case of a clinical complete response. The primary endpoint is the CR rate, described as a pathological CR or a sustained clinical CR one year after chemoradiotherapy. The main secondary objectives are long-term oncological outcomes, radiological and pathological response, the number of resections with clear margins, treatment-related toxicity, perioperative complications, health-related costs, and quality of life., Discussion: This trial protocol describes the MEND-IT study. The MEND-IT study aims to evaluate the CR rate after intensified chemotherapy prior to concomitant chemoradiotherapy in a homogeneous group of patients with locally advanced rectal cancer and indisputably unfavourable characteristics, defined as hr-LARC, in order to improve their prognosis., Trial Registration: Clinicaltrials.gov: NCT04838496 , registered on 02-04-2021 Netherlands Trial Register: NL9790., Protocol Version: Version 3 dd 11-4-2022., (© 2022. The Author(s).)

Background and Objectives: There is growing evidence regarding the effectiveness of registrar training through video cameras, which has relevance for quality supervision during times of crises such as the global COVID-19 pandemic., Method: Interviews were conducted in 2012 with supervisors, registrars and patients evaluating video camera use for tele-supervision across six rural sites in Gippsland, Australia. Thematic analysis was employed in 2013 - and re-examined in 2021 in light of the global COVID-19 pandemic - to explore user experience with video technology., Results: Participants identified advantages of video supervision addressing distance and temporal issues, also emphasising quality supervision and education. Challenges included patient confidentiality, internet stability and loss of serendipitous 'corridor conversations'., Discussion: Remote supervision is no longer simply an issue for rural and remote training. During crises such as a global pandemic, tele-supervision becomes the purview of all. There are distinct merits and limitations in adopting video technology, warranting consideration of individual training contexts. These findings can help inform remote supervision via video in varied milieu.

CRISPR/Cas9-mediated knock-in methods enable the labeling of individual endogenous proteins to faithfully determine their spatiotemporal distribution in cells. However, reliable multiplexing of knock-in events in neurons remains challenging because of cross talk between editing events. To overcome this, we developed conditional activation of knock-in expression (CAKE), allowing efficient, flexible, and accurate multiplex genome editing in rat neurons. To diminish cross talk, CAKE is based on sequential, recombinase-driven guide RNA (gRNA) expression to control the timing of genomic integration of each donor sequence. We show that CAKE is broadly applicable to co-label various endogenous proteins, including cytoskeletal proteins, synaptic scaffolds, ion channels and neurotransmitter receptor subunits. To take full advantage of CAKE, we resolved the nanoscale co-distribution of endogenous synaptic proteins using super-resolution microscopy, demonstrating that their co-organization depends on synapse size. Finally, we introduced inducible dimerization modules, providing acute control over synaptic receptor dynamics in living neurons. These experiments highlight the potential of CAKE to reveal new biological insight. Altogether, CAKE is a versatile method for multiplex protein labeling that enables the detection, localization, and manipulation of endogenous proteins in neurons. Significance Statement Accurate localization and manipulation of endogenous proteins is essential to unravel neuronal function. While labeling of individual proteins is achievable with existing gene editing techniques, methods to label multiple proteins in neurons are limiting. We introduce a new CRISPR/Cas9 strategy, CAKE, achieving faithful duplex protein labeling using sequential editing of genes. We use CAKE to visualize the co-localization of essential neuronal proteins, including cytoskeleton components, ion channels and synaptic scaffolds. Using super-resolution microscopy, we demonstrate that the co-organization of synaptic scaffolds and neurotransmitter receptors scales with synapse size. Finally, we acutely modulate the dynamics of synaptic receptors using labeling with inducible dimerization domains. Thus, CAKE mediates accurate duplex endogenous protein labeling and manipulation to address biological questions in neurons., Competing Interests: The authors declare no competing financial interests., (Copyright © 2022 Droogers et al.)

Objectives: In critically ill children, severely altered pharmacokinetics may result in subtherapeutic β-lactam antibiotic concentrations when standard pediatric dosing regimens are applied. However, it remains unclear how to recognize patients most at risk for suboptimal exposure and their outcome. This study aimed to: 1) describe target attainment for β-lactam antibiotics in critically ill children, 2) identify risk factors for suboptimal exposure, and 3) study the association between target nonattainment and clinical outcome., Design: Post hoc analysis of the "Antibiotic Dosing in Pediatric Intensive Care" study (NCT02456974, 2012-2019). Steady-state trough plasma concentrations were classified as therapeutic if greater than or equal to the minimum inhibitory concentration of the (suspected) pathogen. Factors associated with subtherapeutic concentrations and clinical outcome were identified by logistic regression analysis., Setting: The pediatric and cardiac surgery ICU of a Belgian tertiary-care hospital., Patients: One hundred fifty-seven patients (aged 1 mo to 15 yr) treated intravenously with amoxicillin-clavulanic acid, piperacillin-tazobactam, or meropenem., Interventions: None., Measurements and Main Results: Three hundred eighty-two trough concentrations were obtained from 157 patients (median age, 1.25 yr; interquartile range, 0.4-4.2 yr). Subtherapeutic concentrations were measured in 39 of 60 (65%), 43 of 48 (90%), and 35 of 49 (71%) of patients treated with amoxicillin-clavulanic acid, piperacillin-tazobactam, and meropenem, respectively. Estimates of glomerular filtration rate (eGFR; 54% increase in odds for each sd increase in value, 95% CI, 0.287-0.736; p = 0.001) and the absence of vasopressor treatment (2.8-fold greater odds, 95% CI, 1.079-7.253; p = 0.034) were independently associated with target nonattainment. We failed to identify an association between antibiotic concentrations and clinical failure., Conclusions: Subtherapeutic β-lactam concentrations are common in critically ill children and correlate with renal function. eGFR equations may be helpful in identifying patients who may require higher dosing. Future studies should focus on the impact of subtherapeutic concentrations on clinical outcome., Competing Interests: Dr. Van Der Heggen received funding from Clinical Research Fund Ghent University Hospital, Belgium. Dr. De Cock received funding from a Clinical Research fund. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

General practice (GP) supervisors - the key resource for training the future GP workforce - are often described as 'occupying a role' or enacting a series of roles. However, as much of the discourse uses a lay understanding of role, or merely hints at theory, a significant body of theoretical literature is underutilised. We reasoned that a more rigorous application of role theory might provide a conceptually clearer account of the GP-supervisor's job. To this end, we describe the use of organisational role theory and job analysis to identify and define the roles of the Australian GP-supervisor. Our search of the academic literature identified 64 role titles, which we condensed to an initial iteration of core roles, using inclusion and exclusion criteria. We analysed GP training organisations' documents to map embedded supervisory tasks against our list of roles to verify their presence, review our role titles and definitions, and look for additional roles that we may have missed. We used subject matter experts iteratively, to authenticate a final list of ten roles and their accompanying definitions, which can be used to support Australian GP-supervisors to perform effectively. We encourage those who support GP-supervisors in other countries and those who educate other health professionals in primary care settings to review the roles to judge whether they are transferable to their contexts.

Background: Medicine is a science; conducting a consultation is an art form. Honing this art enhances patients' satisfaction and good medical outcomes and can also improve general practitioners' satisfaction in their role. A good consultation needs to be effective and efficient. Effectiveness occurs when the patient is heard, understood and acknowledged, and when the doctor is empathic, credible and delivers information and recommendations easily understood by the patient. Efficiency occurs when the consultation is time efficient and flows smoothly., Objective: The aim of this article is to propose an adaptable, patient-centred consultation framework that is well suited to the modern context and practical for teaching to registrars and supervised doctors., Discussion: The model for consultation presented articulates a structure of 10 components. The model can be the basis for teaching registrars and supervised doctors how to better structure their consultations. Later, it can be the basis for analysis and critique of reviewed consultations. While the model was developed for the face-to-face context, this article also includes recommendations for how the framework may be adopted for telehealth consultations.

Background and Objectives: In workplace-based training and assessment of registrars and supervised doctors, the influence of contextual factors such as consultation room layout, including placement of chairs, may be overlooked. The aim was to identify the room's seating arrangements in consultation observation between the assessor, the assessed and the patient., Method: Qualitative research was undertaken to explore the perceptions of consultation observation as a tool in workplace-based training and assessment through semi‑structured one-on-one interviews. Thematic analysis was employed to analyse the data; secondary data analysis highlighted the use of metaphors to describe seating arrangements., Results: Chair placement tended to be discussed by participants in terms of triangles - equilateral, isosceles and scalene. Other metaphors included curved lines, compasses or clock faces. Notions of agency in seating positions and constraints by room layout were also identified., Discussion: There is a tension between the physical layout and structure of the consultation room, seating preferences of the observer and the agency of registrar as the observed.

Background: Molecular detection of SARS-CoV-2 in respiratory samples is the gold standard for COVID-19 diagnosis but it has a long turnaround time and struggles to detect low viral loads. Serology could help to diagnose suspected cases which lack molecular confirmation. Two case reports are presented as illustration., Objectives: The aim of this study was to evaluate the performance of several commercial assays for COVID-19 serology. We illustrated the added value of COVID-19 serology testing in suspect COVID-19 cases with negative molecular test., Study Design: Twenty-three sera from 7 patients with a confirmed molecular diagnosis of SARS-CoV-2 were tested using 14 commercial assays. Additionally, 10 pre-pandemic sera and 9 potentially cross-reactive sera were selected. We calculated sensitivity and specificity. Furthermore, we discuss the diagnostic relevance of COVID-19 serology in a retrospective cohort of 145 COVID-19 cases in which repetitive molecular and serological SARS-CoV-2 tests were applied., Results: The interpretation of the pooled sensitivity of IgM/A and IgG resulted in the highest values (range 14-71% on day 2-7; 88-94% on day 8-18). Overall, the specificity of the assays was high (range 79-100%). Among 145 retrospective cases, 3 cases (2%) remained negative after sequential molecular testing but positive on final SARS-CoV-2 serology., Conclusion: Sensitivity of COVID-19 serological diagnosis was variable but consistently increased at >7 days after symptom onset. Specificity was high. Our data suggest that serology can complement molecular testing for diagnosis of COVID-19, especially for patients presenting the 2 nd week after symptom onset or later.

Visualizing the subcellular distribution of proteins and determining whether specific proteins co-localize is one of the main strategies in determining the organization and potential interactions of protein complexes in biological samples. The development of super-resolution microscopy techniques such as single-molecule localization microscopy (SMLM) has tremendously increased the ability to resolve protein distribution at nanometer resolution. As super-resolution imaging techniques are becoming instrumental in revealing novel biological insights, new quantitative approaches that exploit the unique nature of SMLM datasets are required. Here, we present a new, local density-based algorithm to quantify co-localization in dual-color SMLM datasets. We show that this method is broadly applicable and only requires molecular coordinates and their localization precision as inputs. Using simulated point patterns, we show that this method robustly measures the co-localization in dual-color SMLM datasets, independent of localization density, but with high sensitivity towards local enrichments. We further validated our method using SMLM imaging of the microtubule network in epithelial cells and used it to study the spatial association between proteins at neuronal synapses. Together, we present a simple and easy-to-use, but powerful method to analyze the spatial association of molecules in dual-color SMLM datasets., (© 2022. The Author(s).)

In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis., Competing Interests: Disclosures: No disclosures were reported., (© 2021 Hoste et al.)

Background: The use of extracorporeal membrane oxygenation (ECMO) in pediatric patients with underlying malignancies remains controversial. However, in an era in which the survival rates for children with malignancies have increased significantly and several recent reports have demonstrated effective ECMO use in children with cancer, we aimed to estimate the outcome and complications of ECMO treatment in these children., Methods: We searched MEDLINE, Embase and CINAHL databases for studies on the use ECMO in pediatric patients with an underlying malignancy from inception to September 2020. This review was conducted in adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Study eligibility was independently assessed by two authors and disagreements resolved by a third author. Included studies were evaluated for quality using the Newcastle-Ottawa Scale (NOS). Random effects meta-analyses (DerSimonian and Laird) were performed. The primary outcomes were mortality during ECMO or hospital mortality., Results: Thirteen retrospective, observational cohort studies were included, most of moderate quality (625 patients). The commonest indication for ECMO was severe respiratory failure (92%). Pooled mortality during ECMO was 55% (95% confidence interval [CI], 47-63%) and pooled hospital mortality was 60% (95% CI 54-67%). Although heterogeneity among the included studies was low, confidence intervals were large. In addition, the majority of the data were derived from registries with overlapping patients which were excluded for the meta-analyses to prevent resampling of the same participants across the included studies. Finally, there was a lack of consistent complications reporting among the studies., Conclusion: Significantly higher mortalities than in general PICU patients was reported with the use of ECMO in children with malignancies. Although these results need to be interpreted with caution due to the lack of granular data, they suggest that ECMO appears to represents a viable rescue option for selected patients with underlying malignancies. There is an urgent need for additional data to define patients for whom ECMO may provide benefit or harm., (© 2022. The Author(s).)

Over the past years several forms of superresolution fluorescence microscopy have been developed that offer the possibility to study cellular structures and protein distribution at a resolution well below the diffraction limit of conventional fluorescence microscopy (<200 nm). A particularly powerful superresolution technique is single-molecule localization microscopy (SMLM). SMLM enables the quantitative investigation of subcellular protein distribution at a spatial resolution up to tenfold higher than conventional imaging, even in live cells. Not surprisingly, SMLM has therefore been used in many applications in biology, including neuroscience. This chapter provides a step-by-step SMLM protocol to visualize the nanoscale organization of endogenous proteins in dissociated neurons but can be extended to image other adherent cultured cells. We outline a number of methods to visualize endogenous proteins in neurons for live-cell and fixed application, including immunolabeling, the use of intrabodies for live-cell SMLM, and endogenous tagging using CRISPR/Cas9., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics., Methods: All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was performed based on the aforementioned characteristics., Results: Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013)., Conclusion: Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prognostically poor characteristics., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by degeneration of the anterior horn cells in the spinal cord, resulting in muscle atrophy, and proximal muscle weakness. SMA presents with a wide range of symptoms requiring multiple clinical specialists and therapists. Integrating care between disciplines can be challenging due to the dynamic course of the disease, and great distances between specialist centers and local providers. Insufficient care integration can lead to suboptimal quality of care and more difficulties for patients and families. This study aims to improve care integration through a Case Management intervention, and taking a mixed-methods approach, to evaluate its impact. Methods: An exploratory, controlled, two-armed study with baseline, post- and follow-up measurement and process evaluation is conducted to evaluate our intervention compared to usual care. Through a multi-perspective state analysis, we investigate the experiences of caregivers and healthcare providers concerning the actual healthcare quality of patients with SMA I and II. Semi-structured interviews and care diaries are used. We apply that data to conceive a tailored Case Management intervention supplemented by a digital platform. The intervention's effect is examined in comparison to a control group taking a mixed-methods approach. As primary endpoints, we investigate the caregivers' health-related quality of life and the quality of care integration. Secondary endpoints are the use of healthcare services (patients and caregivers) and costs. We assess the process quality from the perspectives of caregivers and healthcare providers through semi-structured interviews. Discussion: This is an exploratory, controlled study to assess the impact of a tailored Case Management intervention to improve the care of patients with SMA I and II. After the evaluation, results on feasibility, expected effect sizes, and process quality will be available. On this basis, future randomized controlled trials can be planned. If demonstrated beneficial, the experience gained within this study may also be valuable for care strategies in other regions and other (non-pediatric) patient groups with rare diseases and/or chronic, complex conditions. Clinical Trial registration: https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00018778, identifier: DRKS00018778., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Willems, Farin-Glattacker and Langer.)

Background: High re-tear rates after repairing large-sized posterosuperior rotator cuff tears remain a significant concern which may affect the clinical outcome. The most optimal type of repair (single versus double-row suture bridge) suited for large size tear remains debatable., Methods: In a retrospective cohort study with a minimum of five years follow up, the structural and functional outcome of 103 patients with large size cuff tear repaired with single row (SR) or double row suture bridge (DRSB) were evaluated. The structural outcome was assessed with ultrasonography whereas functional outcome was evaluated with Constant Murley (CM) and American shoulder elbow score (ASES)., Results: There were 55 patients in the SR group and 48 patients in the DRSB group with a mean follow-up of 74.2 months (range, 60-96 months). While comparing the structural integrity in two groups, we found significantly lower re-tear rates in the DRSB group as compared to the SR group (10.4% vs. 32.7%; P=0.006 ). Also, there were more focal defects in the SR group (25.4%) than the DRSB group (8.3%). Overall, there was no significant difference in CM and ASES scores when the SR group was compared to DRSB. However, subgroup analysis between those with intact and retorn tendon revealed significant difference ( P=0.0001 ) in the clinical scores., Conclusion: At a minimum of five years follow-up, the DRSB repair of large posterosuperior cuff tear resulted in superior structural healing over SR repair. Nevertheless, overall there was no significant functional difference between both the techniques. However, the functional outcome of the healed tendon subgroup was superior to retear tendon subgroup.

Background: Writing and digital storage have largely replaced organic memory for encoding and retrieval of information in the modern era, with a corresponding decrease in emphasis on memorization in Western education. In health professional training, however, there remains a large corpus of information for which memorization is the most efficient means of ensuring: A) that the trainee has the required information readily available; and B) that a foundation of knowledge is laid, upon which the medical trainee builds multiple, complex layers of detailed information during advanced training. The carefully staged progression in early- to late- years' medical training from broad concepts (e.g. gross anatomy and pharmacology) to in-depth, specialised disciplinary knowledge (e.g. surgical interventions and follow-on care post-operatively) has clear parallels to the progression of training and knowledge exposure that Australian Aboriginal youths undergo in their progression from childhood to adulthood to Tribal Elders., Methods: As part of the Rural Health curriculum and the undergraduate Nutrition and Dietetics program in the Monash University Faculty of Medicine, Nursing, and Health Sciences, we tested Australian Aboriginal techniques of memorization for acquisition and recall of novel word lists by first-year medical students (N = 76). We also examined undergraduate student evaluations (N = 49) of the use of the Australian Aboriginal memory technique for classroom study of foundational biomedical knowledge (the tricarboxylic acid cycle) using qualitative and quantitative analytic methods drawing from Bloom's taxonomy for orders of thinking and learning. Acquisition and recall of word lists were assessed without memory training, or after training in either the memory palace technique or the Australian Aboriginal narrative technique., Results: Both types of memory training improved the number of correctly recalled items and reduced the frequency of specific error types relative to untrained performance. The Australian Aboriginal method resulted in approximately a 3-fold greater probability of improvement to accurate recall of the entire word list (odds ratio = 2.82; 95% c.i. = 1.15-6.90), vs. the memory palace technique (odds ratio = 2.03; 95% c.i. = 0.81-5.06) or no training (odds ratio = 1.5; 95% c.i. = 0.54-4.59) among students who did not correctly recall all list items at baseline. Student responses to learning the Australian Aboriginal memory technique in the context of biomedical science education were overwhelmingly favourable, and students found both the training and the technique enjoyable, interesting, and more useful than rote memorization. Our data indicate that this method has genuine utility and efficacy for study of biomedical sciences and in the foundation years of medical training., Competing Interests: The authors have declared that no competing interests exist.

Background: Complex emergencies resulting from conflict and political instability are a major challenge for national neglected tropical diseases (NTDs) control and elimination programmes, especially in sub-Saharan Africa. Currently, there are no formal guidelines for national programmes to use and plan activities in these humanitarian situations, therefore the aim of this study was to develop a new methodological approach for making decisions about the implementation of safe and effective mapping and mass drug administration (MDA) intervention strategies., Methods: The study focussed on the 47 World Health Organization's African Region (AFR) countries. NTD data were based on five diseases controlled by preventive chemotherapy (PC; i.e. lymphatic filariasis, onchocerciasis, schistosomiasis, soil transmitted helminths, trachoma), obtained from the WHO data portals and The Global Trachoma Atlas for 2018. Data on complex emergencies were obtained from the Armed Conflict Location and Event Data Project for 2018-2019. NTD and conflict data were summarised and mapped. A decision tree was developed using NTD mapping, endemicity, MDA and implementing partners data, together with conflict status information at district level. South Sudan was used as a case study, given its current nexus of high NTD prevalence, incidences of conflict, and the presence of a national NTD programme and supporting partners., Results: For the five NTDs, between 26 and 41 countries required PC, 69.2-212.7 million people were treated with coverage between 54.8-71.4%. In total 15,273 conflict events were reported including high rates of violence against civilians (29.4%), protests (28.8%), and battles (18.1%). The decision tree process included four main steps including i) information gathering ii) determine a disease mapping strategy iii) determine an MDA implementation strategy and iv) create a disease and conflict database. Based on these steps, risk maps were created. The South Sudan case study on onchocerciasis found the majority of the districts requiring mapping or MDA had a conflict event, and required specialised methods adapted to context and risk, with support from implementation partners in selected areas., Conclusions: The paper presents a new methodological approach for implementing safe and effective mapping and intervention strategies in NTD endemic countries with ongoing complex emergencies, which will help to address challenges and make progress toward the NTD Roadmap targets of 2030.

To date, little understanding exists of how first-year students in professionally oriented higher-education (HE) programs (i.e., those that provide vocational education to prepare students for a particular occupation) experience their academic transition process. In the present study, we first argued how the constructs of academic adjustment and academic integration can provide complementary perspectives on the academic transition of first-year students in (professional) HE. Next, we examined what first-year students in professional HE contexts perceive to be the most important experiences associated with their academic transition process in the first semester of their first year of higher education (FYHE). To this end, we adopted the fundamentals of the critical incident technique and asked 104 students in a Flemish (Dutch-speaking part of Belgium) university college (which offers professional HE programs, such as nursing) to complete "reflective logs" with open questions at the start of the second semester of their FYHE, wherein they reflected on three critical academic experiences during their first semester. An inductive, cross-case content analysis of the collected narratives showed that students reported on nine themes of academic experiences, which relate to five adjustment themes (dealing with the organization of the study program, organizing study work, committing to the study, following class and taking notes, and processing learning content outside class) and four integration themes (feeling competent, feeling stressed, feeling prepared, and feeling supported). Further analyses showed that although some of the nine themes of academic experiences appear to be more important at different times in the first semester, they all seem to be meaningful throughout the whole semester., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Willems, Coertjens and Donche.)

Objective: The normal limits of symmetry for the compound muscle action potential of the shin muscles (CMAPshin) have not been determined yet. The goal of this study is to provide extensive data on the limits of symmetry and the reliability of CMAPshin., Methods: The study was conducted in normal healthy males and females. All subjects underwent CMAPshin measurements bilaterally. The median percent differences of right/left amplitude/area, with range of these measurements, were calculated. In addition, the intra- and interobserver reliability was examined in a separate population., Results: The study group consisted of 58 healthy individuals. The median percent right/left difference for amplitude and area were respectively 7.2% (range 0-23.6%) and 5.4% (range 0.7-25.6%). Right/left difference of the amplitude/area of the CMAPshin greater than 24%/26% respectively can be considered as pathological. The Pearson correlation coefficients (r) for the intra-observer reliability amplitude/area are 0.905/0.882 and for the inter-observer reliability are 0.968/0.981., Conclusions: The results confirm symmetry and good intra- and interobserver reliability in CMAPshin measurements., Significance: CMAPshin can be used in practice to estimate axonal loss in case of a foot drop. Data studies examining symmetry of CMAPshin can facilitate in the clinical interpretation of these nerve conduction studies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

Antibiotics are one of the most prescribed drug classes in the pediatric intensive care unit, yet the incidence of inappropriate antibiotic prescribing remains high in critically ill children. Optimizing the use of antibiotics in this population is imperative to guarantee adequate treatment, avoid toxicity and the occurrence of antibiotic resistance, both on a patient level and on a population level. Antibiotic stewardship encompasses all initiatives to promote responsible antibiotic usage and the PICU represents a major target environment for antibiotic stewardship programs. This narrative review provides a summary of the available knowledge on the optimal selection, duration, dosage, and route of administration of antibiotic treatment in critically ill children. Overall, more scientific evidence on how to optimize antibiotic treatment is warranted in this population. We also give our personal expert opinion on research priorities.

Background: Pulmonary artery (PA) dilatation is often seen in pulmonary hypertension (PH) and is considered a long-term consequence of elevated pressure. The PA dilates over time and therefore may reflect disease severity and duration. Survival is related to the stage of the disease at the time of diagnosis and therefore PA diameter might be used to predict prognosis. This study evaluates the outcome of patients with pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) and investigates whether PA diameter at the time of diagnosis is associated with mortality., Methods: Patients visiting an outpatient clinic of a tertiary centre between 2004 and 2018 with a cardiac catheterisation confirmed diagnosis of PAH or CTEPH and a CT scan available for PA diameter measurement were included. PA diameter and established predictors of survival were collected (New York Heart Association (NYHA) class, N‑terminal pro-brain natriuretic peptide (NT-proBNP) level and 6‑min walking distance (6MWD))., Results: In total 217 patients were included (69% female, 71% NYHA class ≥III). During a median follow-up of 50 (22-92) months, 54% of the patients died. Overall survival was 87% at 1 year, 70% at 3 years and 58% at 5 years. The mean PA diameter was 34.2 ± 6.2 mm and was not significantly different among all the diagnosis groups. We found a weak correlation between PA diameter and mean PA pressure ( r = 0.23, p < 0.001). Male sex, higher age, shorter 6MWD and higher NT-proBNP level were independently associated with mortality, but PA diameter was not., Conclusion: The prognosis of PAH and CTEPH is still poor. Known predictors of survival were confirmed, but PA diameter at diagnosis was not associated with survival in PAH or CTEPH patients.

Introduction: Workplace social capital (WSC) has been shown to affect employees' well-being and health, yet it is not clear how public managers can create WSC and which forms of WSC are most important. This study is the first prospective cohort study to examine the relationship between management behaviour, WSC, well-being and sickness absence. It uses a validated and detailed scale on WSC, which can distinguish between bonding, bridging, linking and organisational WSC over time. The study thereby provides rich data giving a much-needed detailed image of how WSC impacts on public employees' well-being and health. Additionally, the study pays special attention to the fact that these relationships can be different for different types of employees and therefore tests a set of relevant employee and context-related variables., Methods and Analysis: Project preparations in terms of agreements and data preparation of existing data started in 2019. This prospective cohort study considers and collects organisational data from 2016 to 2025. Annual employee surveys of more than 8000 employees (in a large Danish municipality) will be combined with register data in all years. This generates a unique cohort of public employees in different professions that are traceable over several years. The annual surveys include information on the management behaviour, WSC and employee outcomes. Fine-grained information on sickness absences will be matched for all employees and years under study. Moreover, confounders and the nested nature of the data will be considered., Ethics and Dissemination: Approval has been obtained from The Regional Committee on Health Research Ethics from Southern Denmark and from the University of Southern Denmark. The results will be presented at conferences and published in international peer-reviewed journals and in a practice-oriented monography targeted at public managers. The result will furthermore be disseminated to the involved employees through seminars and workshops in the participating organisations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)