Identifying organ donors attended by prehospital healthcare professionals - A scoping review.

INTRODUCTION: Organ donation is a life-saving intervention that provides hope for patients with end-stage organ failure, improving their longevity and quality of life. However, the demand for organs far exceeds the supply, leading to a significant disparity between patients on transplant waiting lists and the availability of suitable organs. To address this issue, innovative strategies, such as uncontrolled donation after circulatory death (uDCD) programs, have been proposed to expand the donor pool to the prehospital setting. AIM: This study aimed to systematically map the literature and comprehensively evaluate the involvement of prehospital healthcare professionals in identifying potential organ donors, as well as the barriers and systems impacting this process. METHODS: A scoping literature review was conducted guided by the PRISMA Extension for Scoping Reviews. Four electronic databases and grey literature were searched for articles examining the participation of prehospital healthcare professionals in the organ or tissue donation process. Relevant data were extracted, organised into narrative and tabular formats, and presented. RESULTS: A total of 33 articles were included for analysis, predominantly focusing on uDCD programs. The review identified a limited evidence-base regarding the role of prehospital healthcare professionals in organ donation. Four common themes emerged: discrepancies in criteria, decision-making processes, bridging strategies, and ethical considerations. CONCLUSION: This scoping literature review highlights the significant role of prehospital healthcare professionals in identifying and recruiting organ donors from non-traditional settings. Established uDCD systems show promise in alleviating the burden on transplant waitlists. However, there is a lack of consensus on enrolment criteria, transportation, and ethical considerations for uDCD. Further research is needed to address these gaps, establish evidence-based guidelines, and ensure the efficient and ethical utilisation of potential organ donors from unconventional settings.

Prevalence of work-related musculoskeletal disorders and associated factors affecting emergency medical services professionals in Jordan: a cross-sectional study.

OBJECTIVES: Emergency medical services (EMSs) personnel are at high risk for developing work-related musculoskeletal disorders (WMSDs). However, no studies have yet investigated the prevalence and effect of these disorders on the Jordanian EMS personnel. Therefore, this study aimed to determine the prevalence of WMSDs among Jordanian EMS personnel and its associated factors. DESIGN: This study used a cross-sectional design. Participants were asked to complete a self-administrated and validated questionnaire to measure the WMSDs, including a demographic survey and the Nordic Musculoskeletal Questionnaire. Descriptive and multivariable regression analyses were used. SETTING: The Jordanian Civil Defence stations in the main cities of Jordan. PARTICIPANTS: The sample consisted of 435 EMS workers which were obtained across the country of Jordan. A total of 79.0% of the participants were male, with a mean age of 27.9 (±4.3 SD) years. RESULTS: The pain in the lower back (308, 70.8%) and neck (252, 57.9%) were the most reported in the last 12 months. Furthermore, about half of the participants reported having pain in their upper back (234, 53.8%), knee (227, 52.2%) and shoulder (226, 52.0%) pain in the last 12 months. Overall, WMSDs in at least one body part were significantly associated with age, experience, being a male, increased body mass index and lower educational level. CONCLUSIONS: There is a high prevalence of musculoskeletal complaints among EMS personnel. Multiple variables may be incorporated into a national prevention campaign and professional development programme to educate EMS personnel on avoiding WMSDs.

Temporal trends in the incidence and outcomes of shock-refractory ventricular fibrillation out-of-hospital cardiac arrest.

Aim: We aimed to describe trends in the incidence and outcomes of refractory ventricular fibrillation (RVF) compared to non-refractory ventricular fibrillation (non-RVF) in out-of-hospital cardiac arrest (OHCA). Methods: Between 2010 and 2019, we included all OHCA cases involving adults ≥ 16 years old with an initial shockable rhythm and who received an attempted resuscitation by Emergency Medical Services (EMS) or a bystander shock prior to EMS arrival in Victoria, Australia. Trends in incidence and survival outcomes over the study period were examined. Adjusted logistic regression analyses were conducted to examine factors associated with RVF, as well as the association of RVF on survival to hospital discharge. RVF refers to patients receiving three or more consecutive shocks without a return of spontaneous circulation (ROSC). Results: Of the 57,749 OHCA attended by EMS, 7,267 met the inclusion criteria. Of these, 4,168 (57.4%) were non-RVF and 3,099 (42.6%) were RVF. The incidence of RVF decreased significantly from 7.7 per 100,000 population in 2010 to 5.6 per 100,000 population in 2019 (p-trend = 0.01). Survival to hospital discharge increased significantly for both the RVF and non-RVF groups (26% vs 41% in 2010 to 31% vs 53% in 2019, p-trend = 0.004 for RVF; and p-trend = 0.01 for non-RVF). Compared to non-RVF, RVF was associated with reduced odds of survival to hospital discharge (Odds Ratio = 0.503 [95% confidence interval 0.448 - 0.565]). Factors associated with a lower likelihood of RVF and improved survival to hospital discharge included being witnessed to arrest by EMS, receiving bystander defibrillation and bystander cardiopulmonary resuscitation (CPR). Conclusion: The incidence of RVF is declining, and survival rates are improving. Early treatment of VF patients with bystander CPR and defibrillation is likely to reduce RVF incidence.

The role of organizational culture and communication skills in predicting the quality of nursing care.

AIMS: This study aims to identify the level of nursing care quality and examine its predictors considering nurses' demographic data, organizational culture, and communication skills. BACKGROUND: Quality of care is a determinant of the sustainability of any healthcare organization. Therefore, it is imperative to understand how factors may contribute to the quality of nursing care. Limited research is available on the interaction between the concepts of quality of nursing care, communication skills, and organizational culture. METHODS: A cross-sectional multi-site correlational design was used in this study. A convenience sample of 200 nurses from four Jordanian hospitals was recruited. Data was collected using self-reported questionnaires. Descriptive statistics, Pearson correlations, and multiple regression were performed to achieve the study's aims. RESULTS: The majority of the nurses in this study were females with bachelor's degrees. Age ranged between 22 and 53 years whereas experience ranged from 1 to 30 years. Communication skills significantly predicted the quality of nursing care; however, organizational culture was not a significant predictor of the quality of nursing care. Nevertheless, Pearson r correlation results revealed a significant correlation between organizational culture and communication skills (r = 0.57, p < 0.05). CONCLUSION: Nurses and organizational managers can increase the level of quality of nursing care by investing in programs that target improving nurses' communication skills. Providing a good environment in the hospital can increase communication skills between staff members, ultimately increasing the quality of nursing care. Further studies are recommended to elaborate and further uncover concerns related to the current research.

Validation and cross-cultural adaptation of the six-dimension scale of nursing performance- arabic version.

BACKGROUND: Nursing performance is a key indicator of patients' care quality and safety. Most healthcare research tools are available in the English language; however, nurses around the world can employ these tools if rigorously adapted and cross-culturally validated. AIMS AND OBJECTIVES: This study aims to provide a cross-cultural adaptation and validation of the six-dimension scale of nursing performance to be used among Arabic-speaking nurses. DESIGN: The study employed a descriptive, correlational design with a cross-sectional approach. METHODS: A five-step cross-cultural adaptation process was adopted. The scale was administered to 216 Jordanian nurses between January 2022 to April 2022. SPSS and AMOS were used for descriptive and correlation analyses and testing the six-dimension model through structural equation modeling (SEM). RESULTS: The current study produced a valid, reliable, culturally adapted Arabic language version of the six-dimension scale of nursing performance. The internal consistency of the tool was supported by a Cronbach Alpha's value of 0.99. The model's goodness of fit indices were: CFI = 0.96, RMSEA = 0.048, and CMIN/df = 1.49. The exploratory factor analysis (EFA) of the scale identified three factors with eigenvalues greater than 1.00., explaining 75.22% of the variance. A subsequent EFA, specifying six factors, yielded 79.79% explained variance. All item factor loadings exceeded 0.30, confirming the scale's robust factor structure. CONCLUSIONS: This study proved that following a robust cross-cultural adaptation process results in a reliable and valid measure of nursing performance to be used among Arabic-speaking nurses. The study supports the dimensionality of nursing performance as evidenced by the SEM results. Therefore, the findings have the potential to considerably enhance studying nursing performance in healthcare fields in Arabic-speaking nurses. RELEVANCE TO CLINICAL PRACTICE: The validation and cross-cultural adaptation of the Arabic version of the Six-Dimension Scale of Nursing Performance have direct implications for improving the quality of nursing services, enhancing patient safety, promoting cultural competence, and supporting the professional growth of Arabic-speaking nurses.

Examining distress among Saudi paramedics in responding to traumatic events: A mixed-methods study.

INTRODUCTION: Paramedics are critical in providing timely medical care to injured patients and responding to trauma events. However, they are often exposed to traumatic events such as death, serious injuries, and violence, which can increase their risk of developing mental health disorders. The nature of their work, including uncontrolled environments and frequent exposure to trauma, as well as the severity of the patient's conditions, all contribute to this risk. This study aims to investigate the distress experienced by Saudi paramedics in response to traumatic events. METHODS: An explanatory sequential mixed-methods approach was used to explore the experiences of distress among a sample of paramedics following traumatic events. RESULTS: The study found that the participants ranked assaults and road traffic collisions as the most concerning traumatic events. Qualitative analysis of the data revealed several themes related to the participants' experiences, including emotional well-being, violence, road traffic collisions, death, personal limitations, culture, coping strategies, and professional support. CONCLUSIONS: The study highlights the high levels of distress experienced by paramedics in response to road traffic collisions, with intrusion and avoidance symptoms being the most commonly reported.

Tripogon loliiformis tolerates rapid desiccation after metabolic and transcriptional priming during initial drying.

Crop plants and undomesticated resilient species employ different strategies to regulate their energy resources and growth. Most crop species are sensitive to stress and prioritise rapid growth to maximise yield or biomass production. In contrast, resilient plants grow slowly, are small, and allocate their resources for survival in challenging environments. One small group of plants, termed resurrection plants, survive desiccation of their vegetative tissue and regain full metabolic activity upon watering. However, the precise molecular mechanisms underlying this extreme tolerance remain unknown. In this study, we employed a transcriptomics and metabolomics approach, to investigate the mechanisms of desiccation tolerance in Tripogon loliiformis, a modified desiccation-tolerant plant, that survives gradual but not rapid drying. We show that T. loliiformis can survive rapid desiccation if it is gradually dried to 60% relative water content (RWC). Furthermore, the gene expression data showed that T. loliiformis is genetically predisposed for desiccation in the hydrated state, as evidenced by the accumulation of MYB, NAC, bZIP, WRKY transcription factors along with the phytohormones, abscisic acid, salicylic acid, amino acids (e.g., proline) and TCA cycle sugars during initial drying. Through network analysis of co-expressed genes, we observed differential responses to desiccation between T. loliiformis shoots and roots. Dehydrating shoots displayed global transcriptional changes across broad functional categories, although no enrichment was observed during drying. In contrast, dehydrating roots showed distinct network changes with the most significant differences occurring at 40% RWC. The cumulative effects of the early stress responses may indicate the minimum requirements of desiccation tolerance and enable T. loliiformis to survive rapid drying. These findings potentially hold promise for identifying biotechnological solutions aimed at developing drought-tolerant crops without growth and yield penalties.

The cytoprotective co-chaperone, AtBAG4, supports increased nodulation and seed protein content in chickpea without yield penalty.

Drought and extreme temperatures significantly limit chickpea productivity worldwide. The regulation of plant programmed cell death pathways is emerging as a key component of plant stress responses to maintain homeostasis at the cellular-level and a potential target for crop improvement against environmental stresses. Arabidopsis thaliana Bcl-2 associated athanogene 4 (AtBAG4) is a cytoprotective co-chaperone that is linked to plant responses to environmental stress. Here, we investigate whether exogenous expression of AtBAG4 impacts nodulation and nitrogen fixation. Transgenic chickpea lines expressing AtBAG4 are more drought tolerant and produce higher yields under drought stress. Furthermore, AtBAG4 expression supports higher nodulation, photosynthetic levels, nitrogen fixation and seed nitrogen content under well-watered conditions when the plants were inoculated with Mesorhizobium ciceri. Together, our findings illustrate the potential use of cytoprotective chaperones to improve crop performance at least in the greenhouse in future uncertain climates with little to no risk to yield under well-watered and water-deficient conditions.

The Perceptions and Expectations of the Clinical Learning Environment in Saudi Arabia: a Multidisciplinary Study.

Background: The clinical learning environment is a fundamental component of healthcare education. In this setting, students can develop the skills and knowledge necessary to become competent and efficient healthcare practitioners. Due to the importance of clinically based education, it is crucial to have a valid and reliable tool to enable its evaluation. Objective: The aim of this study was to use the Clinical Learning Environment Inventory (CLEI) to examine the perceptions of Saudi undergraduate healthcare students regarding their actual and preferred clinical learning environment and explore the differences between the two viewpoints. Methods: A cross-sectional survey design was utilised with a cohort of Saudi undergraduate healthcare students. Data regarding perceptions of the 'actual' and 'preferred' clinical learning environments were gathered with the Clinical Learning Environment Inventory tool. Results: A total of 194 students participated and nine healthcare disciplines were represented. The highest mean score for both 'actual' and 'preferred' clinical learning environment was for the subscale Task Orientation. Significant differences between 'actual' and 'preferred' environments were demonstrated for Innovation and Individualization, with both subscales scoring higher for the 'preferred' environment. All five subscales-Individualization, Innovation, Involvement, Personalization, and Task Orientation-appear to be important aspects contributing to student satisfaction with their clinical learning environment. Conclusion: Saudi healthcare students demonstrate a preference for a clinical learning environment with the utilization of new and interesting experiences, as well as recognition and accommodation of student individuality. Additionally, student satisfaction appears to be multifactorial in origin. Therefore, there may be many avenues available to enhance the clinical experiences of healthcare students, which is vitally important for the optimization of clinical learning opportunities.

Sleep and mental health in recruit paramedics: a 6-month longitudinal study.

STUDY OBJECTIVES: To explore potential relationships and longitudinal changes in sleep and mental health in recruit paramedics over the first 6 months of work, and whether sleep disturbances pre-emergency work predict future mental health outcomes. METHODS: Participants (N = 101, 52% female, Mage = 26 years) completed questionnaires prior to (baseline), and after 6 months of emergency work to assess for symptoms of insomnia, obstructive sleep apnea, post-traumatic stress disorder (PTSD), depression, anxiety, and trauma exposure. At each timepoint, participants also completed a sleep diary and wore an actigraph for 14 days to assess sleep patterns. Correlations between baseline sleep and mental health were conducted and changes in these variables across timepoints were examined using linear mixed models. Hierarchical regressions assessed whether sleep at baseline predicted mental health at follow-up. RESULTS: Insomnia and depression symptoms, and total sleep time increased while sleep onset latency decreased across the first 6 months of emergency work. Participants experienced an average of 1 potentially traumatic event during the 6-month period. Baseline insomnia predicted increased depression symptoms at the 6-month follow-up, while baseline wake after sleep onset predicted follow-up PTSD symptoms. CONCLUSION: Results highlight an increase in insomnia and depression across the initial months of emergency work, while sleep disturbances before emergency work were identified as potential risk factors for the development of depression and PTSD among paramedics in their early career. Screening and early interventions targeting poor sleep at the beginning of emergency employment may assist in reducing the risk of future mental health outcomes in this high-risk occupation.

Exploring the behaviors and social preferences of a large, multigenerational herd of zoo-housed southern white rhinoceros (Ceratotherium simum simum).

The zoo-housed southern white rhinoceros (SWR) population is of special concern due to their lack of consistent breeding success. An enhanced understanding of SWR social preferences could better inform management planning by promoting natural social relationships, which can positively affect their well-being. The large, multigeneration herd housed at the North Carolina Zoo provides an ideal opportunity to examine rhino sociality across different ages, kin types, and social groupings. Eight female rhinos' social and nonsocial behaviors were recorded from November 2020 through June 2021 across 242 h. Activity budget analyses revealed strong seasonal and temporal variations in grazing and resting behaviors, with no stereotypic behaviors recorded. Bond strength calculations suggested that each female maintained strong social bonds with one to two partners. Beyond mother-nursing calf bonds, we found that the strongest social ties were maintained between calf-less adults and subadults in these dyads. Considering these findings, we recommend that management plans attempt to house immature females with calf-less adult females, as they may be necessary to the social landscape of immature females and, ultimately, improve their welfare.

CONFERD-HP: recommendations for reporting COmpeteNcy FramEwoRk Development in health professions.

BACKGROUND: Competency frameworks outline the perceived knowledge, skills, attitudes, and other attributes required for professional practice. These frameworks have gained in popularity, in part for their ability to inform health professions education, assessment, professional mobility, and other activities. Previous research has highlighted inadequate reporting related to their development which may then jeopardize their defensibility and utility. METHODS: This study aimed to develop a set of minimum reporting criteria for developers and authors of competency frameworks in an effort to improve transparency, clarity, interpretability and appraisal of the developmental process, and its outputs. Following guidance from the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network, an expert panel was assembled, and a knowledge synthesis, a Delphi study, and workshops were conducted using individuals with experience developing competency frameworks, to identify and achieve consensus on the essential items for a competency framework development reporting guideline. RESULTS: An initial checklist was developed by the 35-member expert panel and the research team. Following the steps listed above, a final reporting guideline including 20 essential items across five sections (title and abstract; framework development; development process; testing; and funding/conflicts of interest) was developed. CONCLUSION: The COmpeteNcy FramEwoRk Development in Health Professions (CONFERD-HP) reporting guideline permits a greater understanding of relevant terminology, core concepts, and key items to report for competency framework development in the health professions.

Mental health risk factors for shift work disorder in paramedics: A longitudinal study.

OBJECTIVES: Depression and anxiety are prominent in paramedics, as is the prevalence of shift work disorder (SWD), a circadian sleep condition comorbid with mental health disorders. However, the role of mental health risk factors for SWD is largely unknown. This study investigated whether mental health levels in recruit paramedics before shift work predicted greater risk of SWD at 6-months into their career and explored whether shift and sleep factors mediated this relationship. DESIGN: A longitudinal study. SETTING: Victoria, Australia. PARTICIPANTS: Recruit paramedics were assessed at baseline (n = 101; ie, pre-shift work) and after 6-months (n = 93) of shift and emergency work. MEASUREMENTS: At both time points, participants completed self-reported measures of depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder Questionnaire-7), and SWD (SWD-Screening Questionnaire). Participants also filled a sleep and work diary for 14-days at each timepoint. RESULTS: After 6-months of emergency work 21.5% of paramedics had a high SWD risk. Logistic regression models showed baseline depression predicted 1.24-times greater odds for SWD at 6-months. Through Lavaan path analysis we found shift and sleep variables did not mediate the relationship between baseline mental health and SWD risk. Baseline depression was associated with increased sleepiness levels following paramedics' major sleep periods at 6-months. Pre-existing depression levels also predicted greater perceived nightshift workload. CONCLUSIONS: Our results highlight depression symptoms before emergency work are a risk factor for SWD within 6-months of work. Depression represents a modifiable risk factor amenable to early interventions to reduce paramedics' risk of SWD.

Paramedic use and understanding of their professional code of conduct.

BACKGROUND: Paramedicine is a newly regulated profession in Australia and with the introduction of regulation in 2018 for this profession came increased responsibilities - including the introduction of a professional code of conduct. Several countries now have regulation of paramedicine and associated professional codes to guide ethical and professional behaviour. Despite this, there has been no published research into paramedic understanding and use of their professional codes. OBJECTIVES: To explore Australian paramedics' use and understanding of their professional code of conduct. Research design: This study used a qualitative descriptive design, underpinned by hermeneutic theory. Reflexive thematic analysis was used to analyse the interview data and identify Australian paramedic perceptions surrounding the use of their code of conduct. RESULTS: 11 Registered Paramedics from several states and territories were interviewed. Participants were invited to interview by advertisement on social media and the Australasian College of Paramedicine Web site. Participants had varied professional backgrounds including clinical work, education providers and policymakers/managers. Four themes were identified as follows: Theme 1 - 'You don't know, what you can't know'; Theme 2 - 'I don't need the code - the code is for others'; Theme 3 - 'It's about time'; Theme 4 - 'Navigating the new profession'. Ethical considerations: Ethics approval was granted by the Monash University Human Research Ethics Committee (MUHREC) Project ID: 28921. All participants provided informed consent. CONCLUSIONS: The results of this study suggest that paramedics' knowledge and use of their code is limited, and participants appeared to mostly rely instead on 'common sense' morals. Participants did appear to want to understand the broad concepts of the code more and have this better integrated into the profession. The code was also interpreted as important to the paramedic profession and its new professional status, helping to legitimise it as a health profession in Australia.

A novel study of situational awareness among out-of-hospital providers during an online clinical simulation.

BACKGROUND: Out-of-hospital providers must be situationally aware in order to maintain safety for themselves, their patients, the public, and their crew. They must be able to recognize situations, interpret them, and predict how those situations may unfold in the future. METHOD: A mixed-methods explanatory sequential design where out-of-hospital providers in Oklahoma, USA, participated in an 18-minute online simulation and then had their situational awareness (SA) measured. Upon completion, participants provided feedback during scheduled interviews. RESULTS: A total of 156 out-of-hospital providers participated. Participants were not situationally aware. While not statistically significant, those with higher education had higher SA scores. Participants perceived that the simulation processes were beneficial to their ongoing care in the field, and were satisfied with the online simulation environment. CONCLUSIONS: Out-of-hospital providers are not situationally aware during an online clinical simulation. While they are focused intently on the surroundings of the scene, they do not put that same focus on the patient. With the appropriate technology and setup, the use of the Situational Awareness Global Assessment Technique (SAGAT) during online simulation is feasible and could enhance clinical performance. Further studies are needed to determine if overall education or years of clinical experience play a role in out-of-hospital SA.

A PSYCHOMETRIC APPRAISAL OF THE MOTIVATED STRATEGIES FOR LEARNING QUESTIONNAIRE IN FINAL YEAR UNDERGRADUATE NURSING STUDENTS.

Background: The purpose of this study was to evaluate the psychometric properties of the Motivated Strategies for Learning Questionnaire (MSLQ) in undergraduate nursing students. Method: An exploratory factor analysis was conducted to assess the reliability and construct validity of the MSLQ, using principal axis factoring (PAF) and varimax rotation on the 81-items. Results: 300 Students completed the MSLQ. The MSLQ with 81-items produced an 8-factor solution, eigenvalues greater than 1.0, with only three of the original MSLQ factors retained. Cronbach alpha ranged from .69 to .89; parallel analysis results ranged from 2.22 to 1.80 across the factors. Conclusion: The difference in the empiric fit between the data and the theoretical model suggests the need for instrument revisions, at least for this learner population.

The development of community paramedicine; a restricted review.

Community paramedic roles are expanding internationally, and no review of the literature could be found to guide services in the formation of community paramedicine programmes. For this reason, the aim of this restricted review was to explore and better understand the successes and learnings of community paramedic programmes across five domains being; education requirements, models of delivery, clinical governance and supervision, scope of roles and outcomes. This restricted review was conducted by searching four databases (CENTRAL, ERIC, EMBASE, MEDLINE and Google Scholar) as well as grey literature search from 2001 until 28/12/2021. After screening, 98 articles were included in the narrative synthesis. Most studies were from the USA (n = 37), followed by Canada (n = 29). Most studies reported on outcomes of community paramedicine programmes (n = 50), followed by models of delivery (n = 28). The findings of this review demonstrate a lack of research and understanding in the areas of education and scope of the role for community paramedics. The findings highlight a need to develop common approaches to education and scope of role while maintaining flexibility in addressing community needs. There was an observable lack of standardisation in the implementation of governance and supervision models, which may prevent community paramedicine from realising its full potential. The outcome measures reported show that there is evidence to support the implementation of community paramedicine into healthcare system design. Community paramedicine programmes result in a net reduction in acute healthcare utilisation, appear to be economically viable and result in positive patient outcomes with high patient satisfaction with care. There is a developing pool of evidence to many aspects of community paramedicine programmes. However, at this time, gaps in the literature prevent a definitive recommendation on the impact of community paramedicine programmes on healthcare system functionality.

Discovery of BLU-945, a Reversible, Potent, and Wild-Type-Sparing Next-Generation EGFR Mutant Inhibitor for Treatment-Resistant Non-Small-Cell Lung Cancer.

While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have changed the treatment landscape for EGFR mutant (L858R and ex19del)-driven non-small-cell lung cancer (NSCLC), most patients will eventually develop resistance to TKIs. In the case of first- and second-generation TKIs, up to 60% of patients will develop an EGFR T790M mutation, while third-generation irreversible TKIs, like osimertinib, lead to C797S as the primary on-target resistance mutation. The development of reversible inhibitors of these resistance mutants is often hampered by poor selectivity against wild-type EGFR, resulting in potentially dose-limiting toxicities and a sub-optimal profile for use in combinations. BLU-945 (compound 30) is a potent, reversible, wild-type-sparing inhibitor of EGFR+/T790M and EGFR+/T790M/C797S resistance mutants that maintains activity against the sensitizing mutations, especially L858R. Pre-clinical efficacy and safety studies supported progression of BLU-945 into clinical studies, and it is currently in phase 1/2 clinical trials for treatment-resistant EGFR-driven NSCLC.

Saudi female paramedics' perceptions of challenges in the workplace: A qualitative study.

BACKGROUND: It is immensely important that Saudi women become involved in the field of paramedicine in larger numbers; however, anecdotally they continue to experience significant challenges that limit their opportunities for recruitment and deployment in the field. This study set out to explore working female paramedics' perceptions of challenges in their workplace in the Kingdom of Saudi Arabia (KSA). METHODS: This study utilised a descriptive qualitative approach. Fifteen Saudi female paramedics were recruited to attend one of four focus groups in Riyadh, Saudi Arabia. Data were assessed using thematic analysis. RESULTS: Three themes emerged from the focus groups that described the perceptions of Saudi female paramedics: personal factors, social factors and employment-related factors. They faced several challenges that could affect their family responsibilities, workplace duties and capacity to work in the field of paramedicine. Saudi society also challenged female paramedics, as the culture and traditions of the KSA limited their participation in the paramedicine workforce. Furthermore, they reported experiencing many employment issues related to recruitment to pre-hospital settings, resulting from organisational policies and procedures. CONCLUSION: This study investigated the perceptions held by a cohort of female Saudi paramedics of the personal and professional challenges they faced in the workplace in the KSA. The study findings and their implications for female paramedics suggest further research is required to understand the unique challenges they face and to develop various strategies to manage them.

Persisting uropathogenic Escherichia coli lineages show signatures of niche-specific within-host adaptation mediated by mobile genetic elements.

Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution.