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AIMS: To explore levers and barriers to providing culturally responsive care for general practice nurses (GPNs) using normalization process theory. DESIGN: A self-administered online cross-sectional survey. METHODS: A participatory co-designed adapted version of the normalization of complex interventions measure (NoMAD) validated tool was distributed to a convenience sample of GPNs between December 2022 and February 2023. The sample comprised of GPNs working in general practice services in Ireland (n = 122). Data were analysed using descriptive and analytical statistics (Pearson correlations) and principles of content analysis. This study was conducted and reported in line with the Consensus-Based Checklist for Reporting of Survey Studies (CROSS). RESULTS: GPNs in this study indicated their familiarity with, acknowledged the importance of and were committed to, providing culturally responsive care. However, implementing culturally responsive care in daily practice was problematic due to insufficient education and training, scarcity of resources and supports and a lack of organizational leadership. Subsequently, GPNs experience difficulties adapting everyday practices to respond appropriately to the care needs of culturally and linguistically diverse (CaLD) patients. CONCLUSION: This analysis highlights the necessity of exploring the intricacies of factors that influence capabilities and capacity for providing culturally responsive care. Despite demonstrating awareness of the importance of providing nursing care that responds to the needs of CaLD patients, GPNs do not have full confidence or capacity to integrate culturally responsive care into their daily work practices. IMPACT: Using normalization process theory, this study elucidates for the first time how GPNs in Ireland make sense of, legitimize, enact and sustain culturally responsive care as a routine way of working. It illuminates the multitude of micro-level (individual), meso-level (organizational) and macro-level (structural) factors that require attention for normalizing culturally responsive care in general practice services. PATIENT OR PUBLIC CONTRIBUTION: The study question was identified in a participatory research prioritization for Irish research about migrant health that involved migrants in the process.
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BACKGROUND: Pneumococcal carriage in children has been extensively studied, but carriage in healthy adults and its relationship to invasive pneumococcal disease (IPD) is less understood. METHODS: Nasal wash samples from adults without close contact with young children (Liverpool, UK), 2011-2019, were cultured, and culture-negative samples tested by PCR. Pneumococcal carriage in adults 18-44 years was compared with carriage among PCV-vaccinated children 13-48 months (nasopharyngeal swabs, Thames Valley, UK) and IPD data for England for the same ages for 2014-2019. Age-group specific serotype invasiveness was calculated and used with national IPD data to estimate carriage serotype distributions for adults aged 65+ years. RESULTS: In total 98 isolates (97 carriers) were identified from 1,631 adults aged 18+ years (age and sex standardized carriage prevalence 6.4%), with only three identified solely by PCR. Despite different carriage and IPD serotype distributions between adults and children, serotype invasiveness was highly correlated (R=0.9). Serotypes 3, 37 and 8 represented a higher proportion of adult carriage than expected from direct low-level transmission from children to adults. The predicted carriage serotype distributions for 65+ years aligned more closely with the carriage serotype distribution for young adults than young children. CONCLUSIONS: The nasal wash technique is highly sensitive; additional benefit of PCR is limited. Comparison of carriage serotype distributions suggests some serotypes may be circulating preferentially within these specific young adults. Our data suggest that for some serotypes carried by adults 65+ years, other adults may be an important reservoir for transmission. Age groups such as older children should also be considered.
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BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period. PATIENTS AND METHODS: The multicenter, open-label, single-arm, phase II FIGHT-202 study enrolled patients ≥18 years old with previously treated advanced/metastatic CCA with FGFR2 fusions or rearrangements (cohort A), other FGF/FGFR alterations (cohort B), or no FGF/FGFR alterations (cohort C). Patients received once-daily oral pemigatinib 13.5 mg in 21-day cycles (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) in cohort A assessed as per RECIST v1.1 by an independent review committee; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: FIGHT-202 enrolled 147 patients (cohort A, 108; cohort B, 20; cohort C, 17; unconfirmed FGF/FGFR alterations, 2). By final analysis, 145 (98.6%) had discontinued treatment due to progressive disease (71.4%), withdrawal by patient (8.2%), or adverse events (AEs; 6.8%). Median follow-up was 45.4 months. The ORR in cohort A was 37.0% (95% confidence interval 27.9% to 46.9%); complete and partial responses were observed in 3 and 37 patients, respectively. Median DOR was 9.1 (6.0-14.5) months; median PFS and OS were 7.0 (6.1-10.5) months and 17.5 (14.4-22.9) months, respectively. The most common treatment-emergent AEs (TEAEs) were hyperphosphatemia (58.5%), alopecia (49.7%), and diarrhea (47.6%). Overall, 15 (10.2%) patients experienced TEAEs leading to pemigatinib discontinuation; intestinal obstruction and acute kidney injury (n = 2 each) occurred most frequently. CONCLUSIONS: Pemigatinib demonstrated durable response and prolonged OS with manageable AEs in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in the extended follow-up period of FIGHT-202.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Pirimidinas , Humanos , Colangiocarcinoma/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Neoplasias dos Ductos Biliares/tratamento farmacológico , Pirimidinas/uso terapêutico , Pirimidinas/farmacologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Idoso de 80 Anos ou mais , Morfolinas , PirróisAssuntos
Diretivas Antecipadas , Neoplasias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
The increasing gap between clinical demand for tissue or organ transplants and the availability of donated tissue highlights the emerging opportunities for lab-grown or synthetically engineered tissue. While the field of tissue engineering has existed for nearly half a century, its clinical translation remains unrealised, in part, due to a limited ability to engineer sufficient vascular supply into fabricated tissue, which is necessary to enable nutrient and waste exchange, prevent cellular necrosis, and support tissue proliferation. Techniques to develop anatomically relevant, functional vascular networks in vitro have made significant progress in the last decade, however, the challenge now remains as to how best incorporate these throughout dense parenchymal tissue-like structures to address diffusion-limited development and allow for the fabrication of large-scale vascularised tissue. This review explores advances made in the laboratory engineering of vasculature structures and summarises recent attempts to integrate vascular networks together with sophisticated in vitro avascular tissue and organ-like structures. STATEMENT OF SIGNIFICANCE: The ability to grow full scale, functional tissue and organs in vitro is primarily limited by an inability to adequately diffuse oxygen and nutrients throughout developing cellularised structures, which generally results from the absence of perfusable vessel networks. Techniques to engineering both perfusable vascular networks and avascular miniaturised organ-like structures have recently increased in complexity, sophistication, and physiological relevance. However, integrating these two essential elements into a single functioning vascularised tissue structure represents a significant spatial and temporal engineering challenge which is yet to be surmounted. Here, we explore a range of vessel morphogenic phenomena essential for tissue-vascular co-development, as well as evaluate a range of recent noteworthy approaches for generating vascularised tissue products in vitro.
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Engenharia Tecidual , Alicerces Teciduais , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Neovascularização Fisiológica/fisiologiaRESUMO
OBJECTIVES: Since Russia's full-scale invasion of Ukraine on 24 February 2022, millions of people have fled the country. Most people have gone to the neighbouring countries of Poland, Slovakia, Hungary, Romania, and Moldova. This vulnerable population has significant healthcare needs. Among the most challenging to address will be chronic non-communicable diseases (NCDs), including mental disorders, as these require long-term, continuous care and access to medicines. Host country health systems are faced with the challenge of ensuring accessible and affordable care for NCDs and mental disorders to this population. Our objectives were to review host country health system experiences and identify priorities for research to inform sustainable health system responses to the health care needs of refugees from Ukraine. STUDY DESIGN: In-person conference workshop. METHODS: A workshop on this subject was held in November 2022 at the European Public Health Conference in Berlin. RESULTS: The workshop included participants from academia and non-governmental organisations, health practitioners, and World Health Organisation regional and country offices. This short communication reports the main conclusions from the workshop. CONCLUSION: Addressing the challenges and research priorities identified will require international solidarity and co-operation.
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Refugiados , Humanos , Atenção à Saúde , Polônia , Hungria , RomêniaRESUMO
BACKGROUND: Morse taper junction tribocorrosion is recognized as an important failure mode in total hip arthroplasty. Although taper junctions are used in almost all shoulder arthroplasty systems currently available in the United States, with large variation in design, limited literature has described comparable analyses of taper damage in these implants. In this study, taper junction damage in retrieved reverse total shoulder arthroplasty (RTSA) implants was assessed and analyzed. METHODS: Fifty-seven retrieved RTSAs with paired baseplate and glenosphere components with Morse taper junctions were identified via database query; 19 of these also included paired humeral stems and trays or spacers with taper junctions. Components were graded for standard damage modes and for fretting and corrosion with a modified Goldberg-Cusick classification system. Medical records and preoperative radiographs were reviewed. Comparative analyses were performed assessing the impact of various implant, radiographic, and patient factors on taper damage. RESULTS: Standard damage modes were commonly found at the evaluated trunnion junctions, with scratching and edge deformation damage on 76% and 46% of all components, respectively. Fretting and corrosion damage was also common, observed on 86% and 72% of baseplates, respectively, and 23% and 40% of glenospheres, respectively. Baseplates showed greater moderate to severe (grade ≥ 3) fretting (43%) and corrosion (27%) damage than matched glenospheres (fretting, 9%; corrosion, 13%). Humeral stems showed moderate to severe fretting and corrosion on 28% and 30% of implants, respectively; matched humeral trays or spacers showed both less fretting (14%) and less corrosion (17%). On subgroup analysis, large-tapered implants had significantly lower summed fretting and corrosion grades than small-tapered implants (P < .001 for both) on glenospheres; paired baseplate corrosion grades were also significantly lower (P = .031) on large-tapered implants. Factorial analysis showed that bolt reinforcement of the taper junction was also associated with less fretting and corrosion damage on both baseplates and glenospheres. Summed fretting and corrosion grades on glenospheres with trunnions (male) were significantly greater than on glenospheres with bores (female) (P < .001 for both). CONCLUSIONS: Damage to the taper junction is commonly found in retrieved RTSAs and can occur after only months of being implanted. In this study, tribocorrosion predominantly occurred on the taper surface of the baseplate (vs. glenosphere) and on the humeral stem (vs. tray or spacer), which may relate to the flexural rigidity difference between the titanium and cobalt-chrome components. Bolt reinforcement and the use of large-diameter trunnions led to less tribocorrosion of the taper junction. The findings of this study provide evidence for the improved design of RTSA prostheses to decrease tribocorrosion.
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Artroplastia de Quadril , Artroplastia do Ombro , Prótese de Quadril , Masculino , Feminino , Humanos , Falha de Prótese , Desenho de Prótese , Artroplastia de Quadril/efeitos adversos , CorrosãoRESUMO
Egg laying in pulmonate snails is a well-orchestrated process that involves a period of reduced locomotion, followed by substrate cleaning with rhythmic rasping of the surface to make tiny grooves, into which eggs are deposited. Although the neurohormonal control of initiating egg laying has been well established, the signals that modulate the buccal central pattern generator to substrate cleaning during egg laying are not known. Neuropeptides of the invertebrate gonadotropin-releasing hormone/corazonin family (invGnRH/CRZ) have been shown to be involved in reproduction and allied behaviors in many vertebrates and invertebrates. Here, we show that the buccal motor pattern underlying substrate cleaning during egg laying is altered by a vertebrate GnRH agonist. Signals from the intestinal nerve innervating reproductive structures, previously shown to be both necessary and sufficient for egg-laying behaviors, are blocked by a vertebrate GnRH antagonist. Further, the vertebrate GnRH-triggered response elicits rhythmic, phase 2 and non-phase 2 activity in the buccal motor pattern, with a shutdown of phase 3, indicative of repetitive rasping without accompanied swallowing behavior. Using immunohistochemistry, intracellular electrophysiology and extracellular nerve stimulation, we show that a member of the invGnRH/CRZ family of neuropeptides could be the signal that contextually switches the multifunctional buccal CPG to a biphasic rasping rhythm that underlies substrate cleaning behavior during egg laying in the pulmonate snail Planorbella (Helisoma) trivolvis.
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Geradores de Padrão Central , Neuropeptídeos , Animais , Caramujos/fisiologia , Neuropeptídeos/fisiologia , Hormônio Liberador de Gonadotropina , Oviposição/fisiologiaRESUMO
Plastic deformation of samples compressed to Mbar pressures at high strain rates at the National Ignition Facility (NIF) forms the basis of ongoing material strength experiments in conditions relevant to meteor impacts, geophysics, armor development, and inertial confinement fusion. Hard x-ray radiography is the primary means of measuring the evolution of these samples, typically employing a slit-collimated high-Z microdot driven by the NIF laser to generate >40 keV x rays [E. Gumbrell et al., Rev. Sci. Instrum. 89, 10G118 (2018) and C. M. Huntington et al., Rev. Sci. Instrum. 89, 10G121 (2018)]. Alternatively, a dysprosium "micro-flag" target driven by the Advanced Radiographic Capability laser (â¼2 kJ, 10 ps) can deliver significantly higher spatiotemporal resolution [M. P. Hill et al., Rev. Sci. Instrum. 92, 033535 (2021)], especially in high-opacity samples. Initial experiments revealed problematic brightness and spectral gradients from this source, but by radiographing a set of diamond-turned, 105 µm-thick Pb test objects and supported by simulations using the 3D Monte Carlo code GEANT4, these geometry-dependent gradients across the field of view are quantified and mitigation strategies are assessed. In addition to significantly enhancing the modulation transfer function compared to the existing system, image stacking from multiple layers of image plate is shown to almost double the signal to noise ratio that will reduce uncertainties in future dynamic strength experiments.
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INTRODUCTION AND AIMS: Objective structured clinical examinations (OSCEs) play a pivotal role in medical education assessment. The Advanced Clinical Skills (ACS) OSCE examines clinical skills in psychiatry, general practice, obstetrics and gynaecology and paediatrics. This study examined if the 2020 ACS OSCE for fourth year medical students attending the National University of Ireland, Galway, was associated with any significant result differences compared to the equivalent 2019 OSCE. Additionally, we assessed students' satisfaction and explored any organisational difficulties in conducting a face-to-face OSCE during the COVID-19 pandemic. MATERIALS AND METHODS: This study compared anonymised data between the 2019 and 2020 ACS OSCEs and analysed anonymised student feedback pertaining to the modified 2020 OSCE. RESULTS: The mean total ACS OSCE result achieved in 2020 was statistically higher compared to the 2019 OSCE [62.95% (SD = 6.21) v. 59.35% (SD = 5.54), t = 6.092, p < 0.01], with higher marks noted in psychiatry (p = 0.001), paediatrics (p = 0.001) and general practice (p < 0.001) with more students attaining honours grades (χ2 = 27.257, df = 3, p < 0.001). No difference in failure rates were found. Students reported feeling safe performing the 2020 OSCE (89.2%), but some expressed face-mask wearing impeded their communication skills (47.8%). CONCLUSION: This study demonstrates that conducting a face-to-face OSCE during the pandemic is feasible and associated with positive student feedback. Exam validity has been demonstrated as there was no difference in the overall pass rate.
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We present the first direct measurement of an astrophysical reaction using a radioactive beam of isomeric nuclei. In particular, we have measured the strength of the key 447-keV resonance in the ^{26m}Al(p,γ)^{27}Si reaction to be 432_{-226}^{+146} meV and find that this resonance dominates the thermally averaged reaction rate for temperatures between 0.3 and 2.5 GK. This work represents a critical development in resolving one of the longest standing issues in nuclear astrophysics research, relating to the measurement of proton capture reactions on excited quantum levels, and offers unique insight into the destruction of isomeric ^{26}Al in astrophysical plasmas.
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Fasciola hepatica is a zoonotic parasite that not only economically burdens the agribusiness sector, but also infects up to 1 million people worldwide, with no commercial vaccine yet available. An ideal vaccine would induce protection in the gut, curtailing the extensive tissue damage associated with parasite's migration from the gut to the bile ducts. The design of such a vaccine requires greater knowledge of gut mucosal responses during the early stage of infection. We examined total mRNA expression of the peyer's patches at 6 and 18 h post F. hepatica infection using RNA sequencing. Differential expression analysis revealed 1341 genes upregulated and 61 genes downregulated at 6 h post infection, while 1562 genes were upregulated and 10 genes downregulated after 18 h. Gene-set enrichment analysis demonstrated that immune specific biological processes were amongst the most downregulated. The Toll-like receptor pathway in particular was significantly affected, the suppression of which is a well-documented immune evasive strategy employed by F. hepatica. In general, the genes identified were associated with suppression of inflammatory responses, helminth induced immune responses and tissue repair/homeostasis. This study provides a rich catalogue of the genes expressed in the early stages of F. hepatica infection, adding to the understanding of early host-parasite interactions and assisting in the design of future studies that look to advance the development of a novel F. hepatica vaccine.
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Fasciola hepatica , Fasciolíase , Doenças dos Roedores , Animais , Fasciola hepatica/genética , Fasciolíase/veterinária , Interações Hospedeiro-Parasita , Camundongos , Nódulos Linfáticos Agregados , RNA-Seq/veterinária , Análise de Sequência de RNA/veterináriaAssuntos
Diabetes Mellitus Tipo 1/complicações , Hipertrigliceridemia/complicações , Pele/patologia , Xantomatose/etiologia , Adolescente , Biópsia , Diabetes Mellitus Tipo 1/diagnóstico , Diagnóstico Diferencial , Humanos , Hipertrigliceridemia/diagnóstico , Masculino , Xantomatose/diagnóstico , Xantomatose/patologiaRESUMO
We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.
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PURPOSE: Oral anti-cancer medication (OAM) has revolutionised oncology care. Due to their potential toxicities and associated safety challenges ongoing assessment and monitoring is essential; currently generally performed in acute care settings. Internationally there exists a transformative vision to shift patient care from acute to primary care. A nurse-led integrated model of care could be developed for OAM patient management in primary care. The aim of this study was to examine international literature regarding current clinical management practices for assessment and monitoring of patients receiving OAM. METHODS: Following PRISMA-ScR guidelines, databases MEDLINE, CINAHL and Web of Science were searched for English studies published between 2010 and 2020 using keywords: assessment, cancer, care, management, oral anticancer medications. Articles were screened and assessed for eligibility. From eligible studies, data were extracted to summarize, collate and make a narrative account of the findings. RESULTS: 2261 papers were reviewed, 14 met inclusion criteria. Three phases of management are reported: 1. Patient treatment plan development; 2. Patient education; 3. Patient monitoring. Within these phases seven specific stages of care were identified broadly representing the patient's journey: (1) treatment decision, (2) prescribing of OAM, (3) OAM dispensing and administration, (4) maximising patient safety (5) ongoing patient assessment (6) patient support (7) communication with other health-care professionals. CONCLUSIONS: Despite a paucity of international literature, a dedicated OAM clinic was endorsed as a means to achieve improved care. Nurses and pharmacists were identified as being of particular importance especially in education and ongoing management of patients receiving OAMs.