Treatment-related mortality among children with cancer in Denmark during 2001-2021.

BACKGROUND: Survival of children with cancer has markedly improved over recent decades, largely due to intensified treatment regimes. The intensive treatment may, however, result in fatal complications. In this retrospective cohort study, we assessed temporal variation in the incidence of treatment-related death and associated risk factors among children diagnosed with cancer in Denmark during 2001-2021. METHOD: Among all children diagnosed with first incident cancer before age 15 years recorded in the Danish Childhood Cancer Register (n = 3,255), we estimated cumulative incidence of treatment-related death (death in the absence of progressive cancer) within 5 years from diagnosis using Aalen-Johansen estimators and assessed associated risk factors using Cox regression. RESULTS: Among all 3,255 children with cancer, 93 (20% of all 459 deaths) died from treatment. Of these treatment-related deaths, 39 (42%) occurred within 3 months of diagnosis. The 5-year cumulative incidences of treatment-related death were 3.3% during 2001-2010 and 2.5% during 2011-2021 (p = 0.20). During 2011-2021, treatment-related deaths accounted for more than half of all deaths among children with haematological cancers. Risk factors varied according to cancer group and included female sex, age below 1 year at diagnosis, disease relapse, stem cell transplantation, central nervous system involvement, and metastasis at diagnosis. INTERPRETATION: Despite increasing treatment intensities, the incidence of treatment-related death has remained stable during the past 20 years in Denmark. Still, clinical attention is warranted to prevent treatment-related deaths, particularly among children with haematological cancers. Patient characteristics associated with increased treatment-related death risk support patient-specific treatment approaches to avoid these fatalities.

The association between sleep duration and detailed measures of obesity: A cross sectional analysis in the ADDITION-PRO study.

Background: Sleep duration is associated with BMI and waist circumference. However, less is known about whether sleep duration affects different measurements of obesity differently. Objective: To investigate the association between sleep duration and different measures of obesity. Methods: In this cross-sectional analysis 1309, Danish, older adults (55% men) completed at least 3 days of wearing a combined accelerometer and heart rate-monitor for assessing sleep duration (hours/night) within self-reported usual bedtime. Participants underwent anthropometry and ultrasonography to assess BMI, waist circumference, visceral fat, subcutaneous fat, and fat percentage. Linear regression analyses examined the associations between sleep duration and obesity-related outcomes. Results: Sleep duration was inversely associated with all obesity-related outcomes, except visceral-/subcutaneous-fat-ratio. After multivariate adjustment the magnitude of associations became stronger and statistically significant for all outcomes except visceral-/subcutaneous-fat-ratio, and subcutaneous fat in women. The associations with BMI and waist circumference demonstrated the strongest associations, when comparing standardized regression coefficients. Conclusions: Shorter sleep duration were associated with higher obesity across all outcomes except visceral-/subcutaneous-fat-ratio. No specifically salient associations with local or central obesity were observed. Results suggest that poor sleep duration and obesity correlate, however, further research is needed to conclude on beneficial effects of sleep duration regarding health and weight loss.

Automated optimisation of solubility and conformational stability of antibodies and proteins.

Biologics, such as antibodies and enzymes, are crucial in research, biotechnology, diagnostics, and therapeutics. Often, biologics with suitable functionality are discovered, but their development is impeded by developability issues. Stability and solubility are key biophysical traits underpinning developability potential, as they determine aggregation, correlate with production yield and poly-specificity, and are essential to access parenteral and oral delivery. While advances for the optimisation of individual traits have been made, the co-optimization of multiple traits remains highly problematic and time-consuming, as mutations that improve one property often negatively impact others. In this work, we introduce a fully automated computational strategy for the simultaneous optimisation of conformational stability and solubility, which we experimentally validate on six antibodies, including two approved therapeutics. Our results on 42 designs demonstrate that the computational procedure is highly effective at improving developability potential, while not affecting antigen-binding. We make the method available as a webserver at www-cohsoftware.ch.cam.ac.uk.

Veterans Affairs Health Care Provider Perceptions of Virtual Reality: Brief Exploratory Survey.

BACKGROUND: Virtual reality (VR), a simulated experience that can be similar to or completely different from the real world, has become increasingly useful within the psychiatric and medical fields. This VR technology has been applied in medical school trainings, exposure therapy for individuals with posttraumatic stress disorder (PTSD), and reminiscence therapy associated with mood disorders for older adults. Perceptions of VR through the lens of the health care provider require further exploration. VR has grown in popularity; however, this modality continues to be underused in most Veterans Affairs (VA) hospitals. OBJECTIVE: A web-based survey was used to explore health care provider perceptions of immersive VR availability and use for older adults and identify potential barriers for immersive VR use in older adults with cognitive impairment. METHODS: An 8-item web-based survey was developed to obtain health care provider feedback. This survey was disseminated throughout a single Veterans Integrated Services Network (VISN). The VR survey was developed via the Survey Monkey platform and distributed through the secure VA email network. Providers were asked to voluntarily participate in the brief, anonymous survey and offer their perceptions of immersive VR use within their patient population. Survey data were reviewed and interpreted using descriptive statistics. RESULTS: A total of 49 respondents completed the survey over a 15-day period. Of them, 36 respondents (73%) had heard of a VR device, though the majority (n=44, 90%) had never used or prescribed a VR device. Respondents identified several potential barriers to immersive VR use in older adults with cognitive impairment (eg, hearing difficulties, perceptions of technology, cognitive concerns, access to resources, and visual impairment). Despite the barriers identified, providers (n=48, 98%) still reported that they would feel comfortable prescribing immersive VR as an intervention for their patient population. CONCLUSIONS: Survey findings revealed that health care providers within this VISN for VAs have heard of VR, although they may not have actively engaged in its use. Most of the providers reported that they would prescribe the use of an immersive VR intervention for their older adult patients. This key point highlights the desire to implement VR strategies for patient use by their providers. If underlying barriers can be addressed and relatively resolved, this technological intervention has the potential to create substantial breakthroughs in clinical care.

Defeated No More: Meaning-Making After Military Sexual Trauma.

INTRODUCTION: Military sexual trauma (MST) has been a concern within our U.S. military for many years. Many interventions have been found to benefit this population, although meaning-based interventions are still lacking in this area. The purpose of this phenomenological study is to understand the meaning-making process and themes that arise for female military veterans as they narrate their experience(s) of MST. MATERIALS AND METHODS: The qualitative study consisted of six female participants, from different areas across the nation, who all reported experiencing MST during their time in service. Their experiences of MST included both sexual harassment and sexual assault. Participants completed a semi-structured interview that was analyzed using an axial coding method to discover the major themes of each participant's interview. The participants discussed the positive and negative aspects of their journey following their MST experience(s). This study's procedures were approved by Adler University's Institutional Review Board. RESULTS: Many found the interview to be a healing experience on their path of post-traumatic growth (PTG). There were eight major themes that arose from the data analysis under the three main domains of (1) creating a work or doing a deed, (2) experiencing something or encountering someone in a way to produce PTG, and (3) altering one's attitude toward unavoidable suffering. The eight themes were as follows: advocacy, adaptive coping, sense of family unit, psychological clarity, meaningful mantra, survivor mentality code, view of self in the world, and resiliency. CONCLUSIONS: All participants endorsed engagement in some type of activity that fell into one of the three major domains identified above. This finding helped highlight the PTG that participants were able to experience through their meaning-making journey. There were several recommendations and study implications that were derived from this research study. With the themes introduced from this study, future treatment planning for individual survivors of MST can be better informed by the utilization of meaning-making techniques. Family and group meaning-based interventions would also be an area of continued exploration for this population. Future implications for practice are also included within this article. Significant limitations of the study include amount of participants, lack of diversity in sample population, qualitative study results, and lack of a more-personal interviewing process.

Bridging the Gap between Clinical Practice Guidelines and Archetype-Based Electronic Health Records: A Novel Model Proposal.

UNLABELLED: The lack of a unique, standardized format for representing data and knowledge is one of the existing difficulties to integrating decision support into Electronic Health Records (EHRs). OBJECTIVE: Propose an archetype-based model to allow the integration of Clinical Practice Guidelines (CPG) and EHRs; design and implement this proposed model. RESULTS: A generic model was designed for the integration of CPG into EHRs, and an archetype-based EHR for Chronic Kidney Disease Prevention based on rules from CPGs, was made as a proof of concept of this novel integration.

[Amniotic fluid analysis as a screening test in term and post-term pregnancy]. / La valutazione del liquido amniotico come test di screening nella gravidanza a termine ed oltre il termine.

BACKGROUND: To verify the hypothesis that isolated oligohydramnios in low-risk term or post-term pregnancy does not increase the risk of trauma to the fetus compared with a control group. METHODS: This prospective study compared a group of patients with low-risk pregnancy and oligohydramnios (AFI = or <50) and a control group which on ultrasonography performed 24 hours before delivery had an AFI volume >50 and = or <250 mm. The evaluation criteria included incidence of induction, modality of delivery and neonatal outcome. Statistical analysis was carried out using Student's "t"-test and the data set of categories was compared using the chi square test. RESULTS: From January 1997 to April 1999, 105 cases of oligohydramnios were compared with a control group (105 patients) matched for maternal age, gestation period and parity. The incidence of induction, fetal distress and variable deceleration was significantly higher in the group with AFI = or <50. The incidence of vacuum extractor, cesarean section, duration of labor and late deceleration did not differ between the two groups. No significant differences in neonatal outcome were found between the two groups. CONCLUSIONS: In patients with oligohydramnios without risk factors, the modality of delivery and neonatal outcome do not differ compared with those with normal amniotic fluid volume.

Osteogenesis coordinated in C3H10T1/2 cells by adipogenesis-dependent BMP-2 expression system.

A novel tissue engineering for bone formation has been proposed, to make osteoblast differentiation balanced by transfecting the mesenchymal stem cells with a gene encoding human bone morphogenetic protein-2 (hBMP-2) under the control of adipocyte specific lipoprotein lipase (LPL) promoter. Due to the promoter specificity, the initiation of BMP transcription is dependent on adipogenesis. For 14-day culture in the presence of ascorbic acid (asc) and beta-glycerophosphate (gly), nontransfected mouse embryonic fibroblast C3H10T1/2 (10T1/2) cells showed extensive accumulation of lipid droplets and adipocyte specific enzyme glycerol-3-phosphate dehydrogenase (G3PDH) mRNA expression, but exhibited neither BMP-2 expression, high alkaline phosphatase (ALP) activity which reflects osteoblast phenotype. On the other hand, transfected 10T1/2 cells showed hBMP-2 expression, high ALP activity and low level of G3PDH. mRNA expression accompanied with minimal lipid droplets. These results indicate that 10T1/2 cells are proved to be differentiated with maintaining coordinated balance of adipogenesis and osteogenesis, when they are transfected by the gene encoding hBMP-2 under the control of LPL promoter.

[Influence of the environment on perineal tears in physiological delivery]. / L'influenza dell'ambiente sulle lesioni perineali nel parto fisiologico.

INTRODUCTION: In the last decades there was a growing interest in new methods of delivery-assistance and in the literature appeared many new studies. This study shows an analysis of all physiological deliveries (581 women) at the Burresi Hospital of Poggibonsi (SI), Italy, in 1993. From 1984, in this hospital an experimental delivery-room (SPN), where new methods of delivery-assistance are tested (151 women in the period of study), has been used in parallel with a conventional delivery-room (SP)(430 women). RESULTS: The most important difference between the two environments is that in SPN the woman is free to choose her positions during all the phases of delivery. We have evaluated the effect of the different environments on the perineal outcome-intact perineum (41% SPN vs 32% SP), first-degree tears (32% SPN vs 21% SP), second-degree tears (23% SPN vs 21% SP) and mediolateral episiotomy (3% SPN vs 26% SP). Age of the woman, weight of the infant and parity appeared to be most important factors for perineal tears. The SPN reduces significantly the number of perineal tears, when allowing for the other factors. CONCLUSION: It was commonly felt that a reduction in the episiotomy-rate increases the number of perineal tears. Our study shows a protective effect for all levels of perineal outcomes associated with the natural delivery-room. However, for primiparous women a higher risk for first-degree tears is documented in the SPN and should be further evaluated. A selection bias cannot be excluded, due to the observational nature of the present investigation.