The lived experience of adults and parents: Transitioning from paediatric to adult health care with oesophageal atresia and tracheo-oesophageal fistula.

AIM AND OBJECTIVE: To explore the experience of healthcare transition from paediatric to adult health care for adults born with oesophageal atresia and tracheo-oesophageal fistula (OA/TOF) and parents. BACKGROUND: OA/TOF is a rare and chronic health condition that can require lifelong medical follow-up and management. There is evidence to suggest that transitioning from paediatric to adult health care can be problematic for people with rare and chronic conditions, including OA/TOF. The previous literature suggests that the experience of transitioning with a rare condition is more complex than transitioning with a common chronic condition. DESIGN: The current study was a qualitative, cross-sectional, survey-based study. METHODS: Data were collected through an online survey. Parents of children born with OA/TOF (n = 23) and adults born with OA/TOF (n = 16) were recruited through a UK-based OA/TOF patient charity. Data from six open-ended questions were analysed using a hybrid approach combining elements of inductive and deductive thematic analyses. Throughout the research process, the SRQR were followed. RESULTS: Five themes were constructed during the analysis, reflecting the experience of parents and adults transitioning from paediatric to adult health care: thrown into the unknown; a cultural shift; stepping back and stepping up; 'no transition as such'; and living with uncertainty. CONCLUSIONS: The findings suggested that a formalised, managed healthcare transition is not commonly experienced by people born with OA/TOF and parents. RELEVANCE TO CLINICAL PRACTICE: We recommend a formalised healthcare transition process in OA/TOF, including preparation for transition and having a named key worker to manage the multidisciplinary transition process. The results also highlighted the need for adults born with OA/TOF to have access to a specialist health service with knowledge and understanding of issues related to OA/TOF.

Parental Experiences of Adolescent Cancer-Related Pain: A Qualitative Study.

OBJECTIVE: Despite advancing medical treatments, pain remains a significant outcome of adolescent cancer, as both a problematic and distressing symptom. With adolescents spending substantial periods of time at home during cancer treatment, parents perceive themselves as central to the experience and management of adolescents' pain. The present study aimed to explore parental experiences of adolescent cancer-related pain during, and recently after, completing cancer treatment. METHODS: We interviewed 21 parents of adolescents (aged 12-18 years) with cancer, recruited through a hospital in South West England. Interviews were analyzed using reflexive inductive thematic analysis. RESULTS: Two themes were generated. The first theme, "Parental perceptions of being at the heart of pain management," focused on the role of parents in adolescents' pain journeys, and the vast knowledge they gained. The second, "Adapting and readjusting expectations," captured parents' journeys in learning to adjust their lives according to adolescents' pain and difficulties they faced throughout this process. CONCLUSIONS: Findings highlighted parents' crucial role throughout adolescents' pain experiences; learning how to manage adolescents' pain, and supporting them with the detrimental impact on their lives. The findings emphasize the importance of a multidisciplinary approach to supporting families to manage pain. They also indicate a need for targeted research studies investigating parental experiences of adolescent cancer-related pain. This will help professionals understand how best to support parents and adolescents throughout the cancer journey and ultimately improve the physical and psychological outcomes of young people in the longer term.

Staphylopine, pseudopaline, and yersinopine dehydrogenases: A structural and kinetic analysis of a new functional class of opine dehydrogenase.

Opine dehydrogenases (ODHs) from the bacterial pathogens Staphylococcus aureus, Pseudomonas aeruginosa, and Yersinia pestis perform the final enzymatic step in the biosynthesis of a new class of opine metallophores, which includes staphylopine, pseudopaline, and yersinopine, respectively. Growing evidence indicates an important role for this pathway in metal acquisition and virulence, including in lung and burn-wound infections (P. aeruginosa) and in blood and heart infections (S. aureus). Here, we present kinetic and structural characterizations of these three opine dehydrogenases. A steady-state kinetic analysis revealed that the three enzymes differ in α-keto acid and NAD(P)H substrate specificity and nicotianamine-like substrate stereoselectivity. The structural basis for these differences was determined from five ODH X-ray crystal structures, ranging in resolution from 1.9 to 2.5 Å, with or without NADP+ bound. Variation in hydrogen bonding with NADPH suggested an explanation for the differential recognition of this substrate by these three enzymes. Our analysis further revealed candidate residues in the active sites required for binding of the α-keto acid and nicotianamine-like substrates and for catalysis. This work reports the first structural kinetic analyses of enzymes involved in opine metallophore biosynthesis in three important bacterial pathogens of humans.

Intrathecal application of the nimodipine slow-release microparticle system eg-1962 for prevention of delayed cerebral ischemia and improvement of outcome after aneurysmal subarachnoid hemorrhage.

The effective reduction of delayed cerebral ischemia (DCI), a main contributor for poor outcome following aneurysmal subarachnoid hemorrhage (SAH), remains challenging. Previous clinical trials on systemic pharmaceutical treatment of SAH mostly failed to improve outcome, probably because of insensitive pharmaceutical targets and outcome measures, small sample size, insufficient subarachnoid drug concentrations and also detrimental, systemic effects of the experimental treatment per se. Interestingly, in studies that are more recent, intrathecal administration of nicardipine pellets following surgical aneurysm repair was suggested to have a beneficial effect on DCI and neurological outcome. However, this positive effect remained restricted to patients who were treated surgically for a ruptured aneurysm. Because of the favorable results of the preclinical data on DCI and neurological outcome in the absence of neurotoxicity or systemic side effects, we are initiating clinical trials. The PROMISE (Prolonged Release nimOdipine MIcro particles after Subarachnoid hemorrhage) trial is designed as an unblinded, nonrandomized, single-center, single-dose, dose-escalation safety and tolerability phase 1 study in patients surgically treated for aSAH and will investigate the effect of intracisternal EG-1962 administration. The NEWTON (Nimodipine microparticles to Enhance recovery While reducing TOxicity after subarachNoid hemorrhage) trial is a phase 1/2a multicenter, controlled, randomized, open-label, dose-escalation, safety, tolerability, and pharmacokinetic study comparing EG-1962 and nimodipine in patients with aneurysmal SAH.

Illness Perceptions, Fear of Cancer Recurrence, and Mental Health in Teenage and Young Adult Cancer Survivors.

Background: The Common-Sense Model of illness self-regulation underpins illness-specific cognitions (including both illness perceptions and a fear of cancer recurrence; FCR). There is evidence in adults of associations between FCR, illness perceptions, and mental health in adult cancer survivors. However, there is limited empirical research examining these constructs within the developmentally distinct population of adolescent and young adult (AYA) survivors of cancer. The current study aimed to bridge that gap to inform potentially modifiable treatment targets in this population. Method: A cross-sectional, correlational design was used to examine the associations between illness perceptions, FCR, and mental health. A web-based survey was completed by a convenience sample of AYA survivors. Regression and mediation analyses were performed. Results: Overall, more negative illness perceptions were associated with more severe FCR and greater depressive and anxiety symptomatology. Higher FCR was predictive of worse overall mental health. More negative overall illness perceptions predicted the relationship between FCR-depression, mediating 24.1% of the variance. Contrastingly, overall illness perceptions did not predict or mediate the relationship between FCR-anxiety. However, the specific illness perceptions regarding timeline, personal control, and emotional representation, were predictive of the FCR-anxiety relationship. Discussion: Illness perceptions and FCR were predictive of mental health outcomes. Identifying and therapeutically targeting negative illness perceptions in those young adults who have survived adolescent cancer could therefore be a means of reducing anxiety and depressive symptomatology. Limitations and future directions are discussed.

Illness perceptions in adolescents with chronic fatigue syndrome and other physical health conditions: Application of the common sense model.

BACKGROUND: The common sense model (CSM) proposes that illness perceptions guide coping and illness management, which subsequently affects outcomes. Chronic fatigue syndrome (CFS) is associated with severe functional impairment. CFS is distinct from other physical health conditions in that individuals can experience high levels of uncertainty, stigma and disbelief from others. This study aimed to compare illness perceptions in adolescents with CFS with other physical health conditions, using a cross-sectional, between-groups design. METHODS: Adolescents (aged 11-18) with CFS (n = 49), type 1 diabetes (n = 52) and juvenile idiopathic arthritis (n = 42) were recruited through National Health Service (NHS) clinics and online, and completed a series of questionnaires. RESULTS: Adolescents with CFS differed on the perceived consequences, timeline, personal control, treatment control, identity and understanding dimensions of illness perceptions. Except for identity, these dimensions were predicted by health condition even when accounting for age, gender, fatigue, physical functioning, anxiety and depression. CONCLUSIONS: Results offer preliminary evidence for the applicability of the CSM in adolescents, with implications for supporting adolescents with physical health conditions. Results suggest that psychological interventions targeting perceived control, understanding and identity may have particular utility for adolescents with CFS.

Efficacy of platelet-rich plasma on wound healing in rabbits.

BACKGROUND: The purpose of this study was to evaluate if the healing of full-thickness skin wounds was accelerated by platelet-rich plasma (PRP). METHODS: Four 2.5 x 2.5-cm full-thickness skin wounds were created on the backs of 15 New Zealand white rabbits. One wound on each animal received 0.3, 0.6, or 0.9 ml PRP, and the fourth wound served as a control. Seven and eight animals were sacrificed after 1 or 2 weeks, respectively, to determine histomorphometrically the epithelialization rate, contraction rate, healing rate, tissue fill, and volume fractions of fibroblasts, neutrophils, macrophages, and blood vessels. RESULTS: Only the 0.6- and 0.9-ml groups had significantly lower contraction rates than the controls after 2 weeks (P <0.05). Although no statistically significant differences were found in other parameters between the PRP-treated wounds and the controls, the PRP treatment led to increases in average epithelialization rates and volume fraction of blood vessels at both time periods. The PRP also seemed to have the most positive effect on healing rate, tissue fill, and volume fraction of fibroblasts during week 1 compared to week 2. CONCLUSIONS: The PRP treatment enhanced healing in full-thickness wounds by reducing the contraction rate with a trend toward acceleration of the epithelial migration and the angiogenic response. Further studies with larger sample sizes should be conducted to improve statistical sensitivity. Longer time intervals and modifications of PRP volume should also be explored to evaluate the long-term efficacy of PRP on wound healing.

Better safe than sorry? Frequent attendance in a hospital emergency department: an exploratory study.

INTRODUCTION: Pain accounts for the majority of attendances to the Emergency Department (ED), with insufficient alleviation of symptoms resulting in repeated attendance. People who frequently attend the ED are typically considered to be psychologically and socially vulnerable in addition to experiencing health difficulties. This service development study was commissioned to identify the defining characteristics and unmet needs of frequent attenders (FAs) in a UK acute district general hospital ED, with a view to developing strategies to meet the needs of this group. METHODS: A mixed-methods multi-pronged exploratory approach was used, involving staff interviews, focus groups, business data and case note analysis. RESULTS: Findings reflect an absence of a coherent approach to meeting the needs of FAs in the ED, especially those experiencing pain. FAs to this ED tend to be vulnerable, complex and report significant worry and anxiety. Elevated anxiety on the part of the patient may be contributing to a 'better safe than sorry' culture within the ED and is reported to bear some influence on the clinical decision-making process. DISCUSSION: It is recommended that a systemic approach is taken to improve the quality and accessibility of individualised care plans, provision of patient education, psychological care and implementation of policies and procedures. Change on an organisational level is likely to improve working culture, staff satisfaction and staff relationships with this vulnerable group of patients. A structured care pathway and supportive changes are likely to lead to economic benefits. Further research should build on findings to implement and test the efficacy of these interventions.

A Site-Specific, Sustained-Release Drug Delivery System for Aneurysmal Subarachnoid Hemorrhage.

Nimodipine is the only drug approved for use by the Food and Drug Administration for improving outcome after aneurysmal subarachnoid hemorrhage (SAH). It has less than optimal efficacy, causes dose-limiting hypotension in a substantial proportion of patients, and is administered enterally 6 times daily. We describe development of site-specific, sustained-release nimodipine microparticles that can be delivered once directly into the subarachnoid space or cerebral ventricles for potential improvement in outcome of patients with aneurysmal SAH. Eight injectable microparticle formulations of nimodipine in poly(DL-lactide-co-glycolide) (PLGA) polymers of varying composition were tested in vitro, and 1 was advanced into preclinical studies and clinical application. Intracisternal or intraventricular injection of nimodipine-PLGA microparticles in rats and beagles demonstrated dose-dependent, sustained concentrations of nimodipine in plasma and cerebrospinal fluid for up to 29 days with minimal toxicity in the brain or systemic tissues at doses <2 mg in rats and 51 mg in beagles, which would be equivalent of up to 612-1200 mg in humans, based on scaling relative to cerebrospinal fluid volumes. Efficacy was tested in the double-hemorrhage dog model of SAH. Nimodipine-PLGA microparticles significantly attenuated angiographic vasospasm. This therapeutic approach shows promise for improving outcome after SAH and may have broader applicability for similar diseases that are confined to body cavities or spaces, are self-limited, and lack effective treatments.

A comparison of midline and tracheal gene regulation during Drosophila development.

Within the Drosophila embryo, two related bHLH-PAS proteins, Single-minded and Trachealess, control development of the central nervous system midline and the trachea, respectively. These two proteins are bHLH-PAS transcription factors and independently form heterodimers with another bHLH-PAS protein, Tango. During early embryogenesis, expression of Single-minded is restricted to the midline and Trachealess to the trachea and salivary glands, whereas Tango is ubiquitously expressed. Both Single-minded/Tango and Trachealess/Tango heterodimers bind to the same DNA sequence, called the CNS midline element (CME) within cis-regulatory sequences of downstream target genes. While Single-minded/Tango and Trachealess/Tango activate some of the same genes in their respective tissues during embryogenesis, they also activate a number of different genes restricted to only certain tissues. The goal of this research is to understand how these two related heterodimers bind different enhancers to activate different genes, thereby regulating the development of functionally diverse tissues. Existing data indicates that Single-minded and Trachealess may bind to different co-factors restricted to various tissues, causing them to interact with the CME only within certain sequence contexts. This would lead to the activation of different target genes in different cell types. To understand how the context surrounding the CME is recognized by different bHLH-PAS heterodimers and their co-factors, we identified and analyzed novel enhancers that drive midline and/or tracheal expression and compared them to previously characterized enhancers. In addition, we tested expression of synthetic reporter genes containing the CME flanked by different sequences. Taken together, these experiments identify elements overrepresented within midline and tracheal enhancers and suggest that sequences immediately surrounding a CME help dictate whether a gene is expressed in the midline or trachea.