The ‘vicious cycle’ of personalised asthma action plan implementation in primary care: a qualitative study of patients and health professionals’ views

Background: Personal asthma action plans (PAAPs) have been guideline recommended for years, but consistentlyunder-issued by health professionals and under-utilised by patients. Previous studies have investigated sub-optimalPAAP implementation but more insight is needed into barriers to their use from the perspective of professionals,patients and primary care teams.Methods: A maximum variation sample of professional and patient participants were recruited from five demographicallydiverse general practices and another group of primary care professionals in one Scottish region. Interviews were digitallyrecorded and data thematically analysed using NVivo.Results: Twenty-nine semi-structured interviews were conducted (11 adults with asthma, seven general practitioners, tenpractice nurses, one hospital respiratory nurse). Three over-arching themes emerged: 1) patients generally do not valuePAAPs, 2) professionals do not fully value PAAPs and, 3) multiple barriers reduce the value of PAAPs in primary care. Sixpatients had a PAAP but these were outdated, not reflecting their needs and not used. Patients reported not wanting orneeding PAAPs, yet identified circumstances when these could be useful. Fifteen professionals had selectively issuedPAAPs with eight having reviewed one. Many professionals did not value PAAPs as they did not see patients using theseand lacked awareness of times when patients could have benefited from one. Multi-level compounding barriers emerged.Individual barriers included poor patient awareness and professionals not reinforcing PAAP use. Organisational barriersincluded professionals having difficulty accessing PAAP templates and fragmented processes including patients not beingasked to bring PAAPs to their asthma appointments.Conclusions: Primary care PAAP implementation is in a vicious cycle. Professionals infrequently review/update PAAPswith patients; patients with out-dated PAAPs do not value or use these; professionals observing patients’ lack of interestin PAAPs do not discuss these. Patients observing this do not refer to their plans and perceive them to be of little valuein asthma self-management. Twenty-five years after PAAPs were first recommended, primary care practices are still notready to support their implementation. Breaking this vicious cycle to create a healthcare context more conducive to PAAPimplementation requires a whole systems approach with multi-faceted interventions addressing patient, professional andorganisational barriers

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

An assessment of lead R&D nursing roles in acute trusts and an evaluation of their status within the NHS research agenda

For over a decade, the need to develop a robust evidence base for nursing, midwifery and health visiting through research has been part of the UK government's R&D strategy. Progress has been slow and little is known about the organisational reality of the most recent strategies. This study aimed to investigate the nature of posts with named responsibilities to lead and develop nursing and midwifery research activity, based in acute NHS hospital trusts. Data were obtained through telephone interviews with directors of nursing services, and a postal survey of relevant staff. Fifty two people responsible for nursing and midwifery R&D were invited to complete the questionnaire, of whom 34 responded. The majority of trusts were able to name an individual responsible for leading nursing R&D, although the remit of the role varied considerably. The effectiveness of implementing any national research strategy is likely to be constrained by the lack of consistency regarding nursing research roles, a factor that may also be implicated in the lack of progress in securing a meaningful contribution to NHS research from nursing R&D

Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients.

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

Histone H3.3 beyond cancer : Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Germ line mutations in H3F3A and H3F3B cause a previously unidentified neurodevelopmental syndrome. Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferatio