Pre-registration nursing students' perceptions of a district nursing career: a qualitative descriptive study.

District nursing vacancies are recognised as high in comparison to many other nursing specialities. The role is often considered as an option for nurses after a period of registration as a nurse, which may be informed by multiple factors. The objectives of the study were to explore barriers to district nurse employment from the perspective of undergraduate nurses. A descriptive qualitative design was employed using focus groups as the method of data collection in accordance with study approval reference no: 21/NAH/006, 30/03/23. Participants were recruited from the current undergraduate nursing programme (n=60). Thematic analysis was chosen as a flexible method of qualitative data analysis. The study produced themes relating to role ambiguity, personal preferences, educational opportunities and recruitment and employer engagement. The experiences provided an insight into the barriers to recruitment of student nurses into district nursing on qualification. Increased engagement from community nurse providers is required to inform the role and incentivise entering this career option. Educational strategies that support community career pathways are required to ensure a balanced view of nursing roles among undergraduates.

Long-term safety and tolerability of ambrisentan treatment for pediatric patients with pulmonary arterial hypertension: An open-label extension study.

This open-label, extension study assessed long-term safety, tolerability, and efficacy of ambrisentan in a pediatric population (age 8- < 18 years) with pulmonary arterial hypertension (PAH). Following completion of a 6-month, randomized study, participants entered the long-term extension at individualized ambrisentan dosages (2.5/5/7.5 or 10 mg/day). Safety assessments included adverse events (AEs), AEs of special interest, and serious AEs (SAEs); efficacy outcomes included 6-min walking distance (6MWD) and World Health Organization functional class (WHO FC). Thirty-eight of 41 (93%) randomized study participants entered the extension; 21 (55%) completed (reaching age 18 years). Most participants received concomitant phosphodiesterase-5 inhibitors (n = 25/38, 66%). Median ambrisentan exposure was 3.5 years. Most participants experienced ≥ 1 AE (n = 34/38, 89%), and 21 (55%) experienced SAEs, most commonly worsening PAH (n = 3/38, 8%), acute cardiac failure, pneumonia, or anemia (n = 2/38; 5% each); none considered ambrisentan-related. Seven participants (18%) died, with recorded reasons (MedDRA preferred term): cardiac failure (n = 2), PAH (n = 2), COVID-19 (n = 1), acute right ventricular failure (n = 1), and failure to thrive (n = 1); median time to death: 5.2 years. Anemia and hepatotoxicity AEs were generally mild to moderate and did not require ambrisentan dose adjustment. Assessed at study end in 29 participants (76%), mean 6MWD improved by 17% (standard deviation: 34.3%), and all (29/29, 100%) had improved or unchanged WHO FC.    Conclusion: Long-term weight-based ambrisentan dosing, alone or combined with other PAH therapies in children with PAH aged 8- < 18 years, exhibited tolerability and clinical improvements consistent with prior randomized study results.    Trial registration: NCT01342952, April 27, 2011. What is Known: • The endothelin receptor antagonist, ambrisentan, is indicated for treatment of pulmonary arterial hypertension (PAH). Previous studies have shown similar efficacy and tolerability in pediatric patients as in adults. What is New: • This open-label extension study assessed the long-term use of ambrisentan in pediatric patients (8-<18 years) with PAH, most of whom were also receiving recommended background PAH treatment. • Weight-based dosing of ambrisentan, given alone or in combination with other PAH therapies, was well tolerated with clinical improvements consistent with prior randomized study results.

Research in action-developing and evaluating a student research placement experience.

BACKGROUND: Evidence based practice is essential in the provision of high-quality contemporary nursing practice. Yet nursing students often lack an understanding of the research process because applied research experience is rarely facilitated in undergraduate nursing programmes. Students research knowledge is mostly gained via classroom based theoretical teaching; however, it is a challenging subject to teach and is often evaluated poorly by students who find the subject uninteresting and difficult to apply to their clinical practice. AIM: The aim of the study was to explore the experiences of student nurses after undertaking a nurse led primary research study placement. METHODS: The study explores the students' experiences of a research placement using a phenomenological approach with the data collection method of drawings and narration which were then subject to Interpretive Phenomenological Analysis as a data analysis method. SETTINGS: This study was undertaken with 18 nursing students who were enrolled in a United Kingdom university, who had recently participated in a nurse-led research study exploring the use of sensors to detect atrial fibrillation in members of the public in a supermarket. RESULTS: The following themes were developed by the researchers: Practice makes perfect, Enhancing communication, Research attitude, Making a difference, Increased confidence, Enhanced skills, Researcher collaborations, The views of others. CONCLUSIONS: Students valued the research placement; the experience provided insight into the conduct of research in primary health and allowed students to learn about research in an experiential way which proved to be more effective than usual classroom methods. Students' communication skills were enhanced, through interacting with the public in a different way, who were keen to engage with them because of their student status.

Combined Inhibition of Phosphodiesterase-5 and -9 in Experimental Heart Failure.

BACKGROUND: Intracellular second messenger cyclic guanosine monophosphate (cGMP) mediates bioactivity of the natriuretic peptides and nitric oxide, and is key to circulatory homeostasis and protection against cardiovascular disease. Inhibition of cGMP-degrading phosphodiesterases (PDEs) PDE5 and PDE9 are emerging as pharmacological targets in heart failure (HF). OBJECTIVES: The present study investigated dual enhancement of cGMP in experimental HF by combining inhibition of PDE-5 (P5-I) and PDE-9 (P9-I). METHODS: Eight sheep with pacing-induced HF received on separate days intravenous P5-I (sildenafil), P9-I (PF-04749982), P5-I+P9-I, and vehicle control, in counterbalanced order. RESULTS: Compared with control, separate P5-I and P9-I significantly increased circulating cGMP concentrations in association with reductions in mean arterial pressure (MAP), left atrial pressure (LAP), and pulmonary arterial pressure (PAP), with effects of P5-I on cGMP, MAP, and PAP greater than those of P9-I. Only P5-I decreased pulmonary vascular resistance. Combination P5-I+P9-I further reduced MAP, LAP, and PAP relative to inhibition of either phosphodiesterase alone. P9-I and, especially, P5-I elevated urinary cGMP levels relative to control. However, whereas inhibition of either enzyme increased urine creatinine excretion and clearance, only P9-I induced a significant diuresis and natriuresis. Combined P5-I+P9-I further elevated urine cGMP with concomitant increases in urine volume, sodium and creatinine excretion, and clearance similar to P9-I alone, despite the greater MAP reductions induced by combination treatment. CONCLUSIONS: Combined P5-I+P9-I amalgamated the superior renal effects of P9-I and pulmonary effects of P5-1, while concurrently further reducing cardiac preload and afterload. These findings support combination P5-I+P9-I as a therapeutic strategy in HF.

The approaches and motivations to learning of student nurses: a phenomenological study.

This research study was undertaken to elicit a group of final-year student nurses' perceptions of their motivations and approaches to learning, and the implications of their views. It is important to explore this subject because students' motivations and approaches to learning can potentially impact patient care. This study was part of a larger research project. The sample consisted of 18 final-year student nurses at a large UK university. Students completed semi-structured interviews that used a qualitative constructivist approach to explore their educational experience. Students described what motivated them to learn, and how they approached their learning because of their understanding of which subjects they believed were and were not important. Students felt that clinical skills were the most important subjects, and topics such as health promotion, law and ethics, were less important and therefore they approached these subjects in a superficial way, learning just enough to pass their course. Clinical skills were perceived as more useful because they would be used directly in clinical practice. The findings of this study are significant to inform nurse educators as they plan curricula and provide an insight into what may potentially adversely affect patient care when students become registered nurses.

An overview of menopause, and why this should feature within pre-registration education.

BACKGROUND: Over half the population (51%) of England and Wales is female, most of whom will experience menopause, either as a result of endocrine ageing or medical treatment. AIM: The project aimed to undertake a review of the literature to determine the level of knowledge about menopause that healthcare students are exposed to, and to highlight why it is important for them to have an understanding of this subject both for their own clinical practice and for supporting colleagues in the workplace. METHOD: A literature review was conducted by the project team. FINDINGS: There is a lack of education for healthcare students, who will go on to care for those affected by menopause, and will also work with colleagues experiencing menopause. CONCLUSION: Educational programmes should include menopause as a component, which will allow for a breaking down of barriers on a subject that is still generally considered taboo. RECOMMENDATIONS: A national audit should be conducted on menopause coverage in UK pre-registration nursing. The addition of menopause to the Liverpool John Moores University pre-registration nursing curriculum is also recommended based on agreed competencies.

Comparison of SPEED, S-Trap, and In-Solution-Based Sample Preparation Methods for Mass Spectrometry in Kidney Tissue and Plasma.

Mass spectrometry is a powerful technique for investigating renal pathologies and identifying biomarkers, and efficient protein extraction from kidney tissue is essential for bottom-up proteomic analyses. Detergent-based strategies aid cell lysis and protein solubilization but are poorly compatible with downstream protein digestion and liquid chromatography-coupled mass spectrometry, requiring additional purification and buffer-exchange steps. This study compares two well-established detergent-based methods for protein extraction (in-solution sodium deoxycholate (SDC); suspension trapping (S-Trap)) with the recently developed sample preparation by easy extraction and digestion (SPEED) method, which uses strong acid for denaturation. We compared the quantitative performance of each method using label-free mass spectrometry in both sheep kidney cortical tissue and plasma. In kidney tissue, SPEED quantified the most unique proteins (SPEED 1250; S-Trap 1202; SDC 1197). In plasma, S-Trap produced the most unique protein quantifications (S-Trap 150; SDC 148; SPEED 137). Protein quantifications were reproducible across biological replicates in both tissue (R2 = 0.85-0.90) and plasma (SPEED R2 = 0.84; SDC R2 = 0.76, S-Trap R2 = 0.65). Our data suggest SPEED as the optimal method for proteomic preparation in kidney tissue and S-Trap or SPEED as the optimal method for plasma, depending on whether a higher number of protein quantifications or greater reproducibility is desired.

Cholesterol synthesis enzyme SC4MOL is fine-tuned by sterols and targeted for degradation by the E3 ligase MARCHF6.

Cholesterol biosynthesis is a highly regulated pathway, with over 20 enzymes controlled at the transcriptional and posttranslational levels. While some enzymes remain stable, increased sterol levels can trigger degradation of several synthesis enzymes via the ubiquitin-proteasome system. Of note, we previously identified four cholesterol synthesis enzymes as substrates for one E3 ubiquitin ligase, membrane-associated RING-CH-type finger 6 (MARCHF6). Whether MARCHF6 targets the cholesterol synthesis pathway at other points is unknown. In addition, the posttranslational regulation of many cholesterol synthesis enzymes, including the C4-demethylation complex (sterol-C4-methyl oxidase-like, SC4MOL; NAD(P)-dependent steroid dehydrogenase-like, NSDHL; hydroxysteroid 17-beta dehydrogenase, HSD17B7), is largely uncharacterized. Using cultured mammalian cell lines (human-derived and Chinese hamster ovary cells), we show SC4MOL, the first acting enzyme of C4-demethylation, is a MARCHF6 substrate and is rapidly turned over and sensitive to sterols. Sterol depletion stabilizes SC4MOL protein levels, while sterol excess downregulates both transcript and protein levels. Furthermore, we found SC4MOL depletion by siRNA results in a significant decrease in total cell cholesterol. Thus, our work indicates SC4MOL is the most regulated enzyme in the C4-demethylation complex. Our results further implicate MARCHF6 as a crucial posttranslational regulator of cholesterol synthesis, with this E3 ubiquitin ligase controlling levels of at least five enzymes of the pathway.

Augmentation of Natriuretic Peptide Bioactivity via Combined Inhibition of Neprilysin and Phosphodiesterase-9 in Heart Failure.

BACKGROUND: The natriuretic peptides (NPs) are potent natriuretic/diuretic and vasodilatory factors, and augmentation of their levels or signaling via inhibition of the enzymes neprilysin (NEP) and phosphodiesterase 9 (PDE9), respectively, has beneficial actions in heart failure (HF). OBJECTIVES: The authors investigated dual enhancement of NP bioactivity by combining PDE9 inhibition and NEP inhibition in HF using an ovine model. METHODS: Eight sheep with pacing-induced HF received on 4 separate days intravenous PDE9 inhibition (PF-04749982), NEP inhibition (SCH-32615), PDE9 inhibition + NEP inhibition (PI+NI), and vehicle control treatment. RESULTS: Compared with the control treatment, NEP inhibition significantly increased plasma NP concentrations with a corresponding rise in second messenger cyclic guanosine monophosphate (cGMP), whereas PDE9 inhibition increased circulating cGMP with a negligible effect on NP levels. Combined PI+NI elevated plasma NPs to an extent comparable to that seen with NEP inhibition alone but further increased cGMP, resulting in a rise in the cGMP-to-NP ratio. All active treatments reduced mean arterial pressure, left atrial pressure, pulmonary arterial pressure, and peripheral resistance, with combined PI+NI further reducing mean arterial pressure and left atrial pressure relative to either inhibitor separately. Active treatments increased urine volume and sodium, potassium and creatinine excretion, and creatinine clearance, in association with rises in urine cGMP levels. PI+NI induced a significantly greater natriuresis and increase in urinary cGMP relative to either inhibitor singly. CONCLUSIONS: The present study demonstrates for the first time that combined PI+NI has additional beneficial hemodynamic and renal effects when compared with either PDE9 inhibition or NEP inhibition alone. The superior efficacy of this 2-pronged augmentation of NP bioactivity supports PI+NI as a potential therapeutic strategy for HF.

Hope and sadness: Balancing emotions in tobacco control mass media campaigns aimed at smokers.

ISSUE ADDRESSED: Australia has smoking prevalence of less than 15% among adults, but there are concerns that the rates of decline have stabilised. Sustained mass media campaigns are central to decreasing prevalence, and the emotions evoked by campaigns contribute to their impact. This study investigates the association between potential exposure to campaigns that evoke different emotions on quitting salience (thinking about quitting), quitting intentions and quitting attempts. METHODS: Data on quitting outcomes were obtained from weekly cross-sectional telephone surveys with adult smokers and recent quitters between 2013 and 2018. Campaign activity data were collated, and population-level potential campaign exposure was measured by time and dose. RESULTS: Using multivariate analyses, a positive association between potential exposure to 'hope' campaigns and thinking about quitting and intending to quit was noted, but no association was seen with quit attempts. Potential exposure to 'sadness' evoking campaigns was positively associated with quitting salience and negatively associated with quit attempts, whereas those potentially exposed to campaigns evoking multiple negative emotions (fear, guilt and sadness) were approximately 30% more likely to make a quit attempt. CONCLUSIONS: This study suggests a relationship between the emotional content of campaigns, quitting behaviours. Campaign planners should consider campaigns that evoke negative emotions for population-wide efforts to bring about quitting activity alongside hopeful campaigns that promote quitting salience and quitting intentions. The emotional content of campaigns provides an additional consideration for campaigns targeting smokers and influencing quitting activity. SO WHAT?: This study demonstrates the importance of balancing the emotional content of campaigns to ensure that campaign advertising is given the greatest chance to achieve its objectives. Utilising campaigns that evoke negative emotions appear to be needed to encourage quitting attempts but maintaining hopeful campaigns to promote thinking about quitting and intending to quit is also an important component of the mix of tobacco control campaigns.

The Role of the Rhomboid Superfamily in ER Protein Quality Control: From Mechanisms and Functions to Diseases.

The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells and is a major site for protein folding, modification, and lipid synthesis. Perturbations within the ER, such as protein misfolding and high demand for protein folding, lead to dysregulation of the ER protein quality control network and ER stress. Recently, the rhomboid superfamily has emerged as a critical player in ER protein quality control because it has diverse cellular functions, including ER-associated degradation (ERAD), endosome Golgi-associated degradation (EGAD), and ER preemptive quality control (ERpQC). This breadth of function both illustrates the importance of the rhomboid superfamily in health and diseases and emphasizes the necessity of understanding their mechanisms of action. Because dysregulation of rhomboid proteins has been implicated in various diseases, such as neurological disorders and cancers, they represent promising potential therapeutic drug targets. This review provides a comprehensive account of the various roles of rhomboid proteins in the context of ER protein quality control and discusses their significance in health and disease.

A phenomenological insight into what final year undergraduate student nurses perceive is the role of the Registered Nurse and who they learn this from.

Background: This paper considers the perceptions of 18 final year student nurses around their perception of the role of the nurse. Methods: A qualitative phenomenological research study was undertaken, with final year student nurses as the data source, undertaking semi-structured interviews from a United Kingdom Higher Education Institution. Data analysis was undertaken by using interpretative phenomenological analysis. Results: Findings indicate that student nurses had little insight as to the role of the nurse when commencing the programme. Being on the programme has led them to understand there are many aspects of a nurse's role including, surprisingly for them, much responsibility. It was also found that a lot of the learning that takes place comes from working with healthcare assistants, and due to this, the student nurses perceive that the role of the modern nurse is task orientated and there is little holistic care. Conclusions: The future practice of this group of registrants may be affected depending on how they move forward with their role, alongside the holistic role of the nurse being detracted from. While phenomenology does not account for generalisations but does seek to illuminate this phenomenon; however if this view were to be shared globally, then the caring aspect of nursing may well be in danger of being lost. If this assumption of the role of the nurse is shared globally, then there are inevitably implications for the nursing profession, and more importantly patient care may be affected.

Learning beyond a single field of nursing through a virtual case-based approach to pre-registration nurse education.

Ensuring that pre-registration student nurses gain the richness of clinical practice to allow them to feel confident and knowledgeable to care for patients of the 21st century is often a challenge. Clinical practice challenges often mean that students will be strategic learners. This article discusses the development of a virtual case-based learning site to provide a rich experience for students to learn.

Growth factors: avenues for the treatment of myocardial infarction and potential delivery strategies.

Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Despite recent advances in clinical management, reoccurence of heart failure after AMI remains high, in part because of the limited capacity of cardiac tissue to repair after AMI-induced cell death. Growth factor-based therapy has emerged as an alternative AMI treatment strategy. Understanding the underlying mechanisms of growth factor cardioprotective and regenerative actions is important. This review focuses on the function of different growth factors at each stage of the cardiac repair process. Recent evidence for growth factor therapy in preclinical and clinical trials is included. Finally, different delivery strategies are reviewed with a view to providing workable strategies for clinical translation.

Acute myocardial infarction is a serious, life-threatening disease. Current treatments for acute myocardial infarction are unsatisfactory, and new treatments are required. Growth factors are promising treatments for myocardial infarction. It is intriguing to understand how growth factors provide cardioprotective benefits. This article describes the various growth factors used to treat myocardial infarction and how they are delivered to the infarcted heart.

Cancer care clinicians' provision of smoking cessation support: A mixed methods study in New South Wales, Australia.

OBJECTIVES: Given the importance of supporting cancer patients to quit smoking, we sought to ascertain cancer care clinicians' beliefs and practices regarding providing smoking cessation brief interventions. METHODS: We used a cross-sectional sequential explanatory mixed method design, including a survey of multidisciplinary cancer care clinicians and semistructured interviews. RESULTS: One hundred and sixty-five cancer care clinicians completed the survey and 21 participated in interviews. Over half of survey respondents (53%) said they do not regularly undertake smoking cessation brief interventions and 40% rarely or never advise quitting. Nonmetropolitan clinicians were more likely to discuss medication options and refer to the Quitline. Physicians were more likely to do brief interventions with patients and radiation therapists were least likely. Barriers were lack of training and experience, lack of knowledge of the Quitline referral process, lack of role clarity, lack of resources and systems, and perceived psychological ramifications of cancer for patients. CONCLUSION: There is a need to upskill cancer clinicians and improve systems to provide smoking cessation brief interventions as part of routine clinical practice. All cancer care clinicians should complete brief intervention smoking cessation training relevant to the cancer context, including making referrals to Quitline, and be supported by systems to record and follow-up care.

Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: Older patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression. Objective: To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease. Design, Setting, and Participants: Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27, 2020, through March 11, 2021; follow-up data were collected through April 8, 2021. Interventions: Patients were randomized (1:1) to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529). Main Outcomes and Measures: The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation. Results: Enrollment was stopped early for efficacy at the prespecified interim analysis. Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ≥65 years of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, -4.53% [95% CI, -6.70% to -2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, -4.91% [95% CI, -7.50% to -2.32%]; P < .001) and progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, -3.97% [95% CI, -6.11% to -1.82%]; P = .002). Adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%). Conclusions and Relevance: Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown. Trial Registration: ClinicalTrials.gov Identifier: NCT04545060.

Perceptions of transition into clinical placement.

INTRODUCTION: A major transition for medical students is the change from the pre-clinical to clinical years of their curriculum. Interventions to help students manage this transition effectively, such as preparatory skills courses and peer mentoring, are used in many medical schools, yet students remain apprehensive about this period. This study aims to investigate student feelings and perceptions around the transition from the pre-clinical to clinical part of the curriculum to inform interventions for helping them better manage the experience. METHOD: A cross-sectional study of all students starting their first clinical placement was undertaken. Questionnaires were administered online. Ordinal data were collected via Likert-scale responses. Free text responses were analysed using thematic analysis. RESULTS: Likert-scale responses showed that most students (69%) agreed or strongly agreed that they looked forward to the range of wards they would spend time on. Respectively, 41% and 43% of students agreed they would be supported in taking histories or carrying out clinical. The majority of students disagreed (28%) or were not sure (27%) that they would have a clear role on the ward. Free text responses identified that students looked forward to patient contact and new ways of learning but were apprehensive about making mistakes, poor staff attitude, personal wellbeing and a lack of purpose in the clinical environment. CONCLUSIONS: The transition into the clinical phase is complex, and students have a wide variety of concerns beyond skills or knowledge deficits. To address these worries, interventions for both improving psychological wellbeing and academic achievement should be developed.