The Bronchopulmonary Dysplasia score: A predictive model for bronchopulmonary dysplasia or death in high-risk preterm infants.

AIM: Progressive respiratory deterioration in infants at high risk of bronchopulmonary dysplasia (BPD) is associated with patent ductus arteriosus (PDA) exposure. This study aimed to design an early predictive model for BPD or death in preterm infants using early echocardiographic markers and clinical data. METHODS: Infants born with gestational age (GA) ≤ 29 weeks and/or birth weight (BW) < 1500 g at Cork University Maternity Hospital, Ireland were retrospectively evaluated. Those with echocardiography performed between 36 h and 7 days of life were eligible for inclusion. Exclusion criteria were pulmonary hypertension and major congenital anomalies. The primary outcome was a composite of BPD and death before discharge. RESULTS: The study included 99 infants. A predictive model for the primary outcome was developed, which included three variables (BW, Respiratory Severity Score and flow pattern across the PDA), and yielding an area under the curve of 0.98 (95% CI 0.96-1.00, p < 0.001). Higher scores were predictive of the primary outcome. A cut-off of -1.0 had positive and negative predictive values of 89% and 98%, and sensitivity and specificity of 98% and 88%, respectively. CONCLUSION: Our prediction model is an accessible bedside tool that predicts BPD or death in premature infants.

Expiry dates in surgical equipment: What are the options?

INTRODUCTION: Hospitals and the healthcare system contribute significantly to global warming, due to the energy use, water use and waste produce going directly to landfill. The operating theatre environment contributes to 70% of all hospital waste, and a proportion of this is due to unused surgical supplies, such as those stocked but never used as they go past their use-by date. AIM: To evaluate how use-by dates are identified and assigned to surgical equipment, and if there are opportunities to re-use, or re-sterilise this equipment in order to reduce waste from the operating theatre environment. RESULTS: Use-by dates are assigned to ensure sterility and longevity of the device, and are assigned based on risk analysis, retrospective and prospective assessment. Incineration is the mainstay of disposal of unused medical devices, but there are alternative options such as re-processing in specific circumstances. CONCLUSION: A large volume of hospital waste is due to operating theatres, and there is movement towards developing more sustainable methods of dealing with expired surgical equipment. This is however in the early stages, with further research required to confirm if these methods will be safe for patients, and beneficial to the environment.

Type I interferon regulation by USP18 is a key vulnerability in cancer.

Precise regulation of Type I interferon signaling is crucial for combating infection and cancer while avoiding autoimmunity. Type I interferon signaling is negatively regulated by USP18. USP18 cleaves ISG15, an interferon-induced ubiquitin-like modification, via its canonical catalytic function, and inhibits Type I interferon receptor activity through its scaffold role. USP18 loss-of-function dramatically impacts immune regulation, pathogen susceptibility, and tumor growth. However, prior studies have reached conflicting conclusions regarding the relative importance of catalytic versus scaffold function. Here, we develop biochemical and cellular methods to systematically define the physiological role of USP18. By comparing a patient-derived mutation impairing scaffold function (I60N) to a mutation disrupting catalytic activity (C64S), we demonstrate that scaffold function is critical for cancer cell vulnerability to Type I interferon. Surprisingly, we discovered that human USP18 exhibits minimal catalytic activity, in stark contrast to mouse USP18. These findings resolve human USP18's mechanism-of-action and enable USP18-targeted therapeutics.

Examining the transition from print to electronic journals through the lens of sustainability.

This paper presents a comparative analysis of the sustainability aspects between print and electronic journals. A narrative synthesis is presented under the three key areas of environmental impact, social impact, and impact on research practices. Over the past decades, the gradual transition from print to electronic media has facilitated greater global access to academic research, reshaped research methodologies through innovative tools and systems, and arguably, reduced the ecological footprint of academia.

Impact of cord clamping on haemodynamic transition in term newborn infants.

OBJECTIVE: To assess the haemodynamic consequences of cord clamping (CC) in healthy term infants. DESIGN: Cohort study. SETTING: Tertiary maternity hospital. PATIENTS: 46 full-term vigorous infants born by caesarean section. INTERVENTIONS: Echocardiography was performed before CC, immediately after CC and at 5 min after birth. MAIN OUTCOME MEASURES: Pulsed wave Doppler-derived cardiac output and the pulmonary artery acceleration time indexed to the right ventricle ejection time were obtained. As markers of loading fluctuations, the myocardial performance indexes and the velocities of the tricuspid and mitral valve annuli were determined with tissue Doppler imaging. Heart rate was derived from Doppler imaging throughout the assessments. RESULTS: Left ventricular output increased throughout the first minutes after birth (mean (SD) 222.4 (32.5) mL/kg/min before CC vs 239.7 (33.6) mL/kg/min at 5 min, p=0.01), while right ventricular output decreased (306.5 (48.2) mL/kg/min before vs 272.8 (55.5) mL/kg/min immediately after CC, p=0.001). The loading conditions of both ventricles were transiently impaired by CC, recovering at 5 min. Heart rate progressively decreased after birth, following a linear trend temporarily increased by CC. The variation in left ventricular output across the CC was directly correlated to the fluctuation of left ventricular preload over the same period (p=0.03). CONCLUSIONS: This study illustrates the cardiovascular consequences of CC in term vigorous infants and offers insight into the haemodynamic transition from fetal to neonatal circulation in spontaneously breathing newborns. Strategies that aim to enhance left ventricular preload before CC may prevent complications of perinatal cardiovascular imbalance.

The correlation between altmetric score and traditional measures of article impact for studies published within the Surgeon Journal.

Alternative metrics, or altmetrics, have emerged as a promising tool for measuring the social impact of research, which is increasingly important in today's digital and social media-driven world. Altmetric Attention Score (AAS) is a weighted count of all the online attention garnered by a study, and it is currently unclear whether a relationship with traditional bibliometrics exists. The purpose of this article was to retrospectively review articles published in the Surgeon Journal from 2003 to 2020 to compare AAS with bibliometric parameters using an Independent t-test and Pearson's correlation analysis. There were statistically significant weakly positive relationships between AAS and sample size, number of reads, and number of citations. There was no statistically significant relationship between AAS and number of authors, H-index, or level of evidence. This study highlights the potential value of altmetrics by measuring the social impact of research as altmetrics can provide valuable information not captured by traditional metrics. It is currently unclear what the optimal balance of social and academic impact is in evaluating research impact and how altmetrics can be integrated into existing research frameworks.

The past, present and future of anticholinergic drugs.

In current medical practice, it is difficult to find any reports claiming that drugs that are primarily anticholinergic or those that have significant anticholinergic effects have any therapeutic benefits. These drugs fell into disrepute within the mental health field from the mid-1960s onwards, and their supposed problems extended to elsewhere in medicine after that. There is considerable evidence that this disrepute stemmed more from marketing copy rather than from hard clinical trial data. Many apparent reviews appear to repeat prior claims rather than present substantial or new evidence. This article offers a perspective rather than a systematic review as there is little evidence other than claims to review. The aim is to challenge the conventional narrative that anticholinergic effects are uniquely hazardous by pointing to the uncertain basis for claims about the harms of anticholinergic drugs, antimuscarinic drugs in particular, ending with pointers to recent research that, if realized, might underpin important possible future benefits.

Longitudinal observational study protocol - Preterm Infants: Microbiome Establishment, Neuro-CrossTalk and Origins (PIMENTO).

INTRODUCTION: Very preterm infants are at risk of abnormal microbiome colonisation in the first weeks to months of life. Several important associated factors have been identified including gestational age, mode of delivery, antibiotic exposure and feeding. Preterm infants are at risk of a number of pathologies for which the microbiome may play a central role, including necrotising enterocolitis and sepsis. The objective of this study is to determine detailed microbiome changes that occur around implementation of different management practices including empiric antibiotic use, advancement of feeds and administration of probiotics during admission to the neonatal intensive care unit. METHODS AND ANALYSIS: A single-site, longitudinal observational study of infants born less than 32 weeks gestation, including collection of maternal samples around delivery and breastmilk and infant samples from admission through discharge from the neonatal unit. ETHICS AND DISSEMINATION: The protocol was approved by the Clinical Research Ethics Committee of the Cork Teaching Hospitals.The findings from this study will be disseminated in peer-reviewed journals, during scientific conferences, and directly to the study participants. Sequencing data will be deposited in public databases. TRIAL REGISTRATION NUMBER: NCT05803577.

Neonatal outcomes following introduction of routine probiotic supplementation to very preterm infants.

AIM: To evaluate the combined outcome of death and/or severe grade necrotising enterocolitis (NEC) in very preterm infants admitted to Cork University Maternity Hospital, Ireland, before and after introduction of routine supplementation with Bifidobacterium bifidum and Lactobacillus acidophilus probiotics (Infloran®). METHODS: A retrospective study of infants <32 weeks gestation and < 1500 g surviving beyond 72 h of life was performed. Two 6-year epochs; pre-probiotics (Epoch 1: 2008-2013) and with probiotics (Epoch 2: 2015-2020), were evaluated. The primary outcome was defined as death after 72 h or NEC Bell stage 2a or greater. RESULTS: Seven-hundred-and-forty-four infants were included (Epoch 1: 391, Epoch 2: 353). The primary outcome occurred in 67 infants (Epoch 1: 37, Epoch 2: 30, p = 0.646). After adjustment, the difference was significant (OR [95% CI]: 0.53 [0.29 to 0.97], p = 0.038). Differences between epochs did not depend on gestational age group (<28 weeks; ≥28 weeks). CONCLUSION: There was an associated reduction of the composite outcome of severe grade NEC and/or death, after adjustment for confounding variables, with introduction of routine administration of a B. bifidum and L. acidophilus probiotic at our institution.

Structural insights into selective small molecule activation of PKG1α.

cGMP-dependent protein kinase I-α (PKG1α) is a target for pulmonary arterial hypertension due to its role in the regulation of smooth muscle function. While most work has focused on regulation of cGMP turnover, we recently described several small molecule tool compounds which were capable of activating PKG1α via a cGMP independent pathway. Selected molecules were crystallized in the presence of PKG1α and were found to bind to an allosteric site proximal to the low-affinity nucleotide binding domain. These molecules act to displace the switch helix and cause activation of PKG1α representing a new mechanism for the activation and control of this critical therapeutic path. The described structures are vital to understanding the function and control of this key regulatory pathway.

Evaluation of the Hypotensive Preterm Infant: Evidence-Based Practice at the Bedside?

Choosing the appropriate management approach for the preterm infant with low blood pressure during the transition period generally involved intervening when the blood pressure drifted below a certain threshold. It is now clear that this approach is too simplistic and does not address the underlying physiology. In this chapter, we explore the many monitoring tools available for evaluation of the hypotensive preterm and assess the evidence base supporting or refuting their use. The key challenge relates to incorporating these outputs with the clinical status of the patient and choosing the appropriate management strategy.

Exploring the content of the STAND-VR intervention: A qualitative interview study.

Prolonged sedentary behaviour has been identified as a potential independent contributor to a number of chronic conditions as well as mortality. The integration of digital technology into health behaviour change interventions has been shown to contribute to increases in physical activity levels, reductions in time spent sedentary, reductions in systolic blood pressure and improvements physical functioning. Recent evidence suggests that older adults could be motivated to adopt a technology such as immersive virtual reality (IVR) due to the added agency it can potentially afford them in their lives through physical and social activities offered in IVR. To date, little research has attempted to integrate health behaviour change content into an immersive virtual environment. This study aimed to qualitatively explore older adults' perspectives on the content of a novel intervention, STAND-VR, and how it could be integrated into an immersive virtual environment. This study was reported using the COREQ guidelines. Twelve participants aged between 60 and 91 years took part. Semi-structured interviews were conducted and analysed. Reflexive thematic analysis was the chosen method of analysis. Three themes were developed, "Immersive Virtual Reality: The Cover versus the Contents", "Ironing Out the (Behavioural) Details" and, "When Two Worlds Collide". These themes offer insights into how retired and non-working adults perceived IVR before and after use, how they would like to learn how to use IVR, the content and people they would like to interact with and finally, their beliefs about their sedentary activity and using IVR. These findings will contribute to future work which aims to design IVR experiences that are more accessible to retired and non-working adults, offering greater agency to take part in activities that reduce sedentary behaviour and improve associated health outcomes and, importantly, offer further opportunity to take part in activities they can ascribe greater meaning to.

The coverage of medical injuries in company trial informed consent forms.

Best practice consent forms in company clinical trials detail the financial coverage for medical treatment of injuries. In trials undertaken for licensing purposes these arrangements can raise concerns. We detail three cases in which elements of the consent forms appear misleading and designed to elicit a consent to participation that might not be forthcoming if volunteers for these clinical trials were aware that what is outlined in principle is not likely to happen in practice. Beyond clinical trial participants, these consent forms have wider implications. Medical coverage of injuries sustained in a clinical trial is a nexus where business, scientific and ethical considerations meet. It is not clear that anyone to date has grappled with the issues posed. This paper uses three clinical trials to illustrate the problems to be addressed.

Older Adults' Experiences and Perceptions of Immersive Virtual Reality: Systematic Review and Thematic Synthesis.

BACKGROUND: Immersive virtual reality (IVR) can be defined as a fully computer-generated environment shown on a head-mounted display. Existing research suggests that key features of IVR can assist older adults in their everyday lives, providing opportunities for health promotion and tackling social isolation and loneliness. There has been a surge in qualitative studies exploring older adults' experiences and perceptions of IVR. However, there has been no systematic synthesis of these studies to inform the design of new, more accessible IVR technologies. OBJECTIVE: This study aimed to systematically review and synthesize qualitative studies exploring older adults' experiences and perceptions of IVR. METHODS: A systematic review and thematic synthesis were conducted following the ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) guidelines. In total, 2 reviewers completed title and abstract screening, full-text screening, data extraction, and quality appraisal. Thematic synthesis is derived from the qualitative method, thematic analysis. It involves 3 key steps: initial coding and grouping of these codes, the formation of descriptive themes from these codes, and going beyond these data to form analytical themes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research approach. RESULTS: Overall, 13 studies were included in the final synthesis, including 224 participants across 9 countries and 5 continents. Confidence in the evidence ranged from high to moderate. Three descriptive themes were generated: practical aspects of IVR use, experiencing unique features of IVR, and perceptions of IVR. The findings from the descriptive themes suggested that there are several improvements that need to be made to existing IVR devices to facilitate older adults' use of this technology. However, older adults' responses to IVR were generally positive. Three analytical themes were generated: tolerating the bad to experience the good, buying in to IVR (don't judge a book by its cover), and "it proves to me I can do it." The analytical themes illustrated that older adults were willing to tolerate discomforts that accompany existing IVR technologies to experience features such as immersive social networking. There was a discrepancy between older adults' perceptions of IVR before use-which were generally negative-and after use-which were generally positive-and IVR provided a platform for older adults to access certain activities and environments more easily than in the real world because of limitations caused by aging. CONCLUSIONS: This review offers insights into older adults' experiences and perceptions of IVR and suggests how a few improvements to its existing hardware and software as well as how it is first presented could offer new opportunities for older adults to take part in meaningful activities tailored to their needs and preferences. TRIAL REGISTRATION: PROSPERO CRD42020200774; https://tinyurl.com/8f48w2vt. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1177/16094069211009682.

Key Stakeholders' Experiences and Perceptions of Virtual Reality for Older Adults Living With Dementia: Systematic Review and Thematic Synthesis.

BACKGROUND: Technology is increasingly being used and evolving in the dementia care landscape. One such technology that has gained traction over the last decade is virtual reality (VR). VR is being applied in many areas of dementia care, including cognitive assessment and training, reminiscence therapy, music therapy, and other recreational VR applications. Despite the plethora of applications, they are often not shaped by the experiences and perceptions of older adults living with dementia. Currently, there is no qualitative evidence synthesis (QES) to explore this area. This review aimed to provide qualitative evidence supporting existing systematic reviews in this area. OBJECTIVE: The aim of this QES was to explore key stakeholders' experiences and perceptions of VR for older adults living with dementia. It aimed to explore the barriers and facilitators to VR use and provide recommendations for future design and implementation. METHODS: QES was used, which involved a systematic search of 6 databases to identify studies that qualitatively explored key stakeholders' experiences and perceptions of VR for older adults living with dementia. Thematic synthesis was used to integrate the findings of 14 studies (from 15 reports). The Critical Appraisal Skills Programme tool was used to assess the methodological quality of the included studies. The confidence placed in the review findings was assessed using the GRADE-CERQUAL (Confidence in the Evidence from Reviews of Qualitative research). RESULTS: A total of 15 reports from 14 studies were included in the review, consisting of a range of levels of VR immersion, stages of dementia, and care contexts. Three analytical themes were generated: stepping into virtuality, a virtual world, and returning to reality. The results indicate the importance of sensitively designing and introducing VR to this population, as older adults living with dementia often have no prior experience of using this technology. VR can be a positive experience for older adults living with dementia and can provide meaningful interactions, positive expressions, and long-term impacts on everyday functioning. However, it should be acknowledged that some negative associations must be accounted for before, during, and after use. CONCLUSIONS: This review highlights the positive implications as well as negative associations of VR use. It emphasizes the need for VR design and implementation driven by the needs and views of older adults living with dementia as well as with other key stakeholders. Future research needs to explore the vital role that older adults living with dementia can play in the design process and how they can be empowered to meaningfully design and use this technology.