Integration of nurse-led virtual reviews with growth hormone device-linked patient adherence information: a mixed methods feasibility study.

Introduction: Easypod-connect™ for childhood growth disorders is a unique connected system that enables transmission of injection adherence information for recombinant human growth hormone (r-hGH). Although this system has the potential to facilitate greater adherence, observational studies have shown declining adherence over prolonged periods when used without additional support. Supplemental nurse practitioner support has been envisaged but not investigated; in this study, we have undertaken feasibility analysis of nurse-led virtual reviews (NVR) in combination with easypod-connect™ in a single centre using quantitative and qualitative analyses. Aims: We aimed to test feasibility by assessing compliance with NVR, height standard deviation score (SDS) gain, adherence improvement and patient opinions. Methods: Patients using easypod™ r-hGH were recruited prospectively to a 12-month study with two telephone NVR appointments in addition to standard of care in-person hospital outpatient visits. A subset was recruited for a semi-structured interview for qualitative thematic analysis. Results: Forty-three patients of median (range) age 10.7 (6.7, 15.2) were recruited for a period of 1.1 (0.7, 1.8) years. Thirty-three (76.7%) patients were fully compliant with NVR integration with easypod-connect™, establishing feasibility. Median (inter-quartile range, IQR) height SDS improved from -1.85 (-2.44, -1.37) to -1.48 (-2.14, -1.07) (p<0.001) while adherence remained similar in the majority from study start [96.5 (88.8, 100.0)] to end [99.0 (94.0, 100.0)]. Qualitative analysis identified themes supporting patient benefit: practicalities of appointments, perceived purpose and significance of virtual reviews, and the importance of optimising growth. Four patients complained of injection pain, of whom two switched to an alternative r-hGH device. Conclusion: Our study has demonstrated the feasibility of nurse-led virtual review integration with easypod-connect™ in a mixed methods study, laying the foundation for research in larger groups over longer periods. Nurse practitioner supported application of easypod-connect™ offers the potential for improved growth outcomes in all r-hGH devices providing adherence information.

Corrigendum: What young people think about music, rhythm and trauma: An action research study.

[This corrects the article DOI: 10.3389/fpsyg.2022.905418.].

What Young People Think About Music, Rhythm and Trauma: An Action Research Study.

A number of popular theories about trauma have suggested rhythm has potential as a mechanism for regulating arousal levels. However, there is very little literature examining this proposal from the perspective of the young people who might benefit. This action research project addresses this gap by collaborating with four groups of children in the out-of-home-care system to discover what they wanted from music therapists who brought a strong focus on rhythm-based activities. The four music therapy groups took place over a 12 month period and each cycle of action and reflection led to adjustments in what activities were offered, as well as exploring different levels of structure and ways of building relationships in the groups. The initial group incorporated a strong emphasis on highly structured rhythm-based activities, but young people found the format difficult to engage with. The second cycle included more opportunities for creativity and self-direction within semi-structured activities which children reported enjoying, but too much freedom also became overwhelming at times. The two groups in the third cycle seemed to balance structure and responsiveness successfully but were also influenced by the introduction of individual sessions prior to group commencement, which was designed to contribute to safety and trust building. Final reflections on the role of rhythm in supporting young people who have had adverse experiences were centred around the ideas of co-regulation. This was qualitatively different to our expectations that practicing rhythm-based activities would lead to an expanded window of tolerance that resulted in less time being spent in either hypo-arousal or hyper-arousal. Instead of entraining to an external rhythm, young people felt safe when their rhythms were matched, even if they were irregular, out of time and unpredictable. The small moments of co-regulation resulted in pleasure, comfort, satisfaction and peace and these moments were highly valued by the young people, who described just wanting to be relaxed and happy. Although not as rhythm-specific as the literature might suggest, music making with trusted adults helped the young people in this study feel more content.

Going within, between and beyond: An exploration of regular Ashtanga Yoga practitioners' conceptualizations of five dimensions of wellbeing.

Yoga is an embodied practice underpinned by philosophical elements, seeking to evolve different dimensions of human existence for optimal functioning in relation to oneself, others and beyond. This mixed-methods research focused on 137 regular Ashtanga Yoga practitioners (AYPs) by investigating their conceptualizations of five dimensions of wellbeing (i.e., physical, emotional, psychological, social, spiritual). Conceptualizations were analysed through word count analysis and Reflexive Thematic Analysis separately for each dimension, yielding four themes in each case, which partly aligned with existing wellbeing and yoga models, and partly extended on the existing literature. Further higher level analysis identified shared meanings across these five dimensions, expressed in themes grouped within five topics (i.e., freedom from and managing suffering, a positive and integrated sense of self, a sense of equanimity and steadiness, the self in relation to others and the world, meta-awareness). Furthermore, it also portrayed each dimension as multileveled, represented in three levels of human functioning. The foundational level encompassed the absence and managing suffering, representing functioning in coping and recovery mode. The optimal functioning level included a positive and integrated sense of self, a sense of equanimity and steadiness, and the self in relation to others and the world, representing functioning in personal development and growth mode. The contemplative and transcendental level involved meta-awareness in every dimension of wellbeing, representing functioning in transpersonal mode. As a result, we propose a preliminary model informed both by this empirical work and previous theories. While the continuousness of themes across dimensions reinforces the importance of embodiment and transcendence in wellbeing frameworks, the notion of the self as a multi-level system could be further explored in relation to knowing about and cultivating wellbeing.

Acute Illness and Death in Children With Adrenal Insufficiency.

Background: Adrenal Insufficiency (AI) can lead to life-threatening Adrenal Crisis (AC) and Adrenal Death (AD). Parents are trained to prevent, recognise and react to AC but there is little available information on what parents are actually doing at home to manage symptomatic AI. Methods: Three approaches were taken: (A) A retrospective analysis of patient characteristics in children and young people with AD over a 13-year period, (B) An interview-aided questionnaire to assess the circumstances around AC in children currently in our adrenal clinic, and (C) a separate study of parent perceptions of the administration of parenteral hydrocortisone. Results: Thirteen patients died (median age 10 years) over a thirteen-year period resulting in an estimated incidence of one AD per 300 patient years. Those with unspecified adrenal insufficiency were overrepresented (P = 0.004). Of the 127 patients contacted, thirty-eight (30%) were identified with hospital attendance with AC. Responses from twenty patients (median age 7.5 years) with AC reported nausea/vomiting (75%) and drowsiness (70%) as common symptoms preceding AC. All patients received an increase in oral hydrocortisone prior to admission but only two received intramuscular hydrocortisone. Questionnaires revealed that 79% of parents reported confidence in the administration of intramuscular hydrocortisone and only 20% identified a missed opportunity for injection. Conclusions: In children experiencing AC, parents followed 'sick day' guidance for oral hydrocortisone, but rarely administered intramuscular hydrocortisone. This finding is discrepant from the 79% of parents who reported confidence in this task. Local training programmes for management of AC are comprehensive, but insufficient to prevent the most serious crises. New strategies to encourage use of parenteral hydrocortisone need to be devised.

Longitudinal Auxological recovery in a cohort of children with Hyperinsulinaemic Hypoglycaemia.

BACKGROUND: Hypoglycaemia due to hyperinsulinism (HI) is the commonest cause of severe, recurrent hypoglycaemia in childhood. Cohort outcomes of HI remain to be described and whilst previous follow up studies have focused on neurodevelopmental outcomes, there is no information available on feeding and auxology. AIM: We aimed to describe HI outcomes for auxology, medications, feeding and neurodevelopmental in a cohort up to age 5 years. METHOD: We reviewed medical records for all patients with confirmed HI over a three-year period in a single centre to derive a longitudinal dataset. RESULTS: Seventy patients were recruited to the study. Mean weight at birth was - 1.0 standard deviation scores (SDS) for age and sex, while mean height at 3 months was - 1.5 SDS. Both weight and height trended to the population median over the follow up period. Feeding difficulties were noted in 17% of patients at 3 months and this reduced to 3% by 5 years. At age 5 years, 11 patients (15%) had neurodevelopmental delay and of these only one was severe. Resolution of disease was predicted by lower maximum early diazoxide dose (p = 0.007) and being born SGA (p = 0.009). CONCLUSION: In a three-year cohort of HI patients followed up for 5 years, in spite of feeding difficulties and carbohydrate loading in early life, auxology parameters are normal in follow up. A lower than expected rate of neurodevelopmental delay could be attributed to prompt early treatment.

Music, Rhythm and Trauma: A Critical Interpretive Synthesis of Research Literature.

Recent theorizing about the connection between the brain and trauma (Perry, 2009; Porges, 2011; van der Kolk, 2015) has led to a burgeoning of interest in the provision of music-based programs with people who have had adverse experiences. Although there has been critique of the lack of scientific basis of these theories and their implications for practice (McLean, 2016), they remain popular with practitioners who are keen to introduce innovative and potentially beneficial approaches to the people with whom they work. Music therapists have a long tradition of working with traumatized clients, however, the brain-based rationales did not seem congruent with the less predictable and more idiosyncratic benefits reported, which seem to occur through more psychodynamic mechanisms of action. In order to unravel what seemed to be a body of literature plagued by the conflation of theories, we undertook a critical interpretive synthesis of literature in the past 10 years to cross-examine the ways that music and trauma have been connected. To do this we extracted data from 36 identified articles to distinguish what music methods were used, what claims were made about benefits, what theoretical justifications were provided and how much research basis there was for the claims being made. Having systematically disentangled the various dimensions, we then constructed a spectrum of approaches that offers a logical categorization of four different ways of using music with people who have had adverse life experiences. These included using music for stabilizing, entrainment, expressive and performative purposes. Specific music-based methods were proposed for those associated with brain-based rationales, and more responsive, multi-method approaches were congruent with recovery and social change models. Future research would benefit from a more clearly articulated connection between theoretical rationale, music-based methods, benefits and research approaches. The resultant spectrum may provide useful guidance for both practice and research design.

A new cistron in the murine hepatitis virus replicase gene.

We report an RNA-negative, temperature-sensitive (ts) mutant of Murine hepatitis virus, Bristol ts31 (MHV-Brts31), that defines a new complementation group within the MHV replicase gene locus. MHV-Brts31 has near-normal levels of RNA synthesis at the permissive temperature of 33 degrees C but is unable to synthesize viral RNA when the infection is initiated and maintained at the nonpermissive temperature of 39.5 degrees C. Sequence analysis of MHV-Brts31 RNA indicated that a single G-to-A transition at codon 1307 in open reading frame 1a, which results in a replacement of methionine-475 with isoleucine in nonstructural protein 3 (nsp3), was responsible for the ts phenotype. This conclusion was confirmed using a vaccinia virus-based reverse genetics system to produce a recombinant virus, Bristol tsc31 (MHV-Brtsc31), which has the same RNA-negative ts phenotype and complementation profile as those of MHV-Brts31. The analysis of protein synthesis in virus-infected cells showed that, at the nonpermissive temperature, MHV-Brtsc31 was not able to proteolytically process either p150, the precursor polypeptide of the replicase nonstructural proteins nsp4 to nsp10, or the replicase polyprotein pp1ab to produce nsp12. The processing of replicase polyprotein pp1a in the region of nsp1 to nsp3 was not affected. Transmission electron microscopy showed that, compared to revertant virus, the number of double-membrane vesicles in MHV-Brts31-infected cells is reduced at the nonpermissive temperature. These results identify a new cistron in the MHV replicase gene locus and show that nsp3 has an essential role in the assembly of a functional MHV replication-transcription complex.

Organ-specific attenuation of murine hepatitis virus strain A59 by replacement of catalytic residues in the putative viral cyclic phosphodiesterase ns2.

The Murine hepatitis virus (MHV) strain A59 ns2 protein is a 30-kDa nonstructural protein that is expressed from a subgenomic mRNA in the cytoplasm of virus-infected cells. Its homologs are also encoded in other closely related group 2a coronaviruses and more distantly related toroviruses. Together, these proteins comprise a subset of a large superfamily of 2H phosphoesterase proteins that are distinguished by a pair of conserved His-x-Thr/Ser motifs encompassing catalytically important residues. We have used a vaccinia virus-based reverse genetic system to produce recombinant viruses encoding ns2 proteins with single-amino-acid substitutions in, or adjacent to, these conserved motifs, namely, inf-ns2 H46A, inf-ns2 S48A, inf-ns2-S120A, and inf-ns2-H126R. All of the mutant viruses replicate in mouse 17 clone 1 fibroblast cells and mouse embryonic cells to the same extent as the parental wild-type recombinant virus, inf-MHV-A59. However, compared to inf-MHV-A59, the inf-ns2 H46A and inf-ns2-H126R mutants are highly attenuated for replication in mouse liver following intrahepatic inoculation. Interestingly, none of the mutant viruses were attenuated for replication in mouse brain following intracranial inoculation. These results show that the ns2 protein of MHV-A59 has an important role in virus pathogenicity and that a substitution of the histidine residues of the MHV-A59 ns2 His-x-Thr/Ser motifs is critical for virus virulence in the liver but not in the brain. This novel phenotype suggests a strategy to investigate the function of the MHV-A59 ns2 protein involving the search for organ-specific proteins or RNAs that react differentially to wild-type and mutant ns2 proteins.

Universal access: but when? Treating the right patient at the right time: access to cardiac rehabilitation.

The Canadian Cardiovascular Society formed an Access to Care Working Group ('Working Group') in the spring of 2004. The mandate of the group was to use the best science and information to establish reasonable triage categories and safe wait times for access to common cardiovascular services and procedures. The present commentary presents the rationale for benchmarks for cardiac rehabilitation (CR) services. The Working Group's search for evidence included: a full literature review of the efficacy of CR, and the factors affecting access and referral to CR; a review of existing guidelines for access to CR; and a national survey of 14 CR programs across Canada undertaken in May 2005 to solicit information on referral to, and wait times for, CR. The Working Group also reviewed the results of The Ontario Cardiac Rehabilitation Pilot Project (2002) undertaken by the Cardiac Care Network of Ontario, which reported the average and median wait times for CR. Some international agencies have formulated their own guidelines relating to the optimal wait time for the onset of CR. However, due to the limited amount of supporting literature, these guidelines have generally been formed as consensus statements. The Canadian national survey showed that few programs had guidelines for individual programs. The Cardiac Care Network of Ontario pilot project reported that the average and median times from a cardiac event to the intake into CR were 99 and 70 days, respectively. The national survey of sampled CR programs also revealed quite remarkable differences across programs in terms of the length of time between first contact to first attendance and to commencement of exercise. Programs that required a stress test before program initiation had the longest wait for exercise initiation. Some patients need to be seen within a very short time frame to prevent a marked deterioration in their medical or psychological state. In some cases, early intervention and advocacy may reduce the risk of loss of employment. Or, there may be profound disturbances in the patient's family as a result of the cardiac event. For other patient groups, preferable wait times vary from one to 30 days, and acceptable wait times vary from seven to 60 days. All cardiovascular disease patients require core aspects of CR services. Patients who would derive benefit from formal CR programs should be provided the opportunity, given the proven efficacy and cost effectiveness of CR.

Functional and genetic analysis of coronavirus replicase-transcriptase proteins.

The coronavirus replicase-transcriptase complex is an assembly of viral and cellular proteins that mediate the synthesis of genome and subgenome-sized mRNAs in the virus-infected cell. Here, we report a genetic and functional analysis of 19 temperature-sensitive (ts) mutants of Murine hepatitis virus MHV-A59 that are unable to synthesize viral RNA when the infection is initiated and maintained at the non-permissive temperature. Both classical and biochemical complementation analysis leads us to predict that the majority of MHV-A59 ORF1a replicase gene products (non-structural proteins nsp1-nsp11) form a single complementation group (cistron1) while the replicase gene products encoded in ORF1b (non-structural proteins nsp12-nsp16) are able to function in trans and comprise at least three, and possibly five, further complementation groups (cistrons II-VI). Also, we have identified mutations in the non-structural proteins nsp 4, nsp5, nsp10, nsp12, nsp14, and nsp16 that are responsible for the ts phenotype of eight MHV-A59 mutants, which allows us to conclude that these proteins are essential for the assembly of a functional replicase-transcriptase complex. Finally, our analysis of viral RNA synthesis in ts mutant virus-infected cells allows us to discriminate three phenotypes with regard to the inability of specific mutants to synthesize viral RNA at the non-permissive temperature. Mutant LA ts6 appeared to be defective in continuing negative-strand synthesis, mutant Alb ts16 appeared to form negative strands but these were not utilized for positive-strand RNA synthesis, and mutant Alb ts22 was defective in the elongation of both positive- and negative-strand RNA. On the basis of these results, we propose a model that describes a pathway for viral RNA synthesis in MHV-A59-infected cells. Further biochemical analysis of these mutants should allow us to identify intermediates in this pathway and elucidate the precise function(s) of the viral replicase proteins involved.