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Exploring NICU nurses' views of a novel genetic point‐of‐care test identifying neonates at risk of antibiotic‐induced ototoxicity: A qualitative study

Abstract

Aim

To explore the views of neonatal intensive care nursing staff on the deliverability of a novel genetic point-of-care test detecting a genetic variant associated with antibiotic-induced ototoxicity.

Design

An interpretive, descriptive, qualitative interview study.

Methods

Data were collected using semi-structured interviews undertaken between January and November 2020. Participants were neonatal intensive care nursing staff taking part in the Pharmacogenetics to Avoid Loss of Hearing trial.

Results

Thematic analysis resulted in four themes: perceived clinical utility; the golden hour; point-of-care device; training and support. Recommendations were made to streamline the protocol and ongoing training and support were considered key to incorporating the test into routine care.

Conclusion

Exploring the views of nurses involved in the delivery of the point-of-care test was essential in its implementation. By the study endpoint, all participants could see the value of routine clinical introduction of the point-of care test.

Implications for the Profession and/or Patient Care

Nurses are in a key position to support the delivery of point-of-care genetic testing into mainstream settings. This study has implications for the successful integration of other genetic point-of-care tests in acute healthcare settings.

Impact

The study will help to tailor the training and support required for routine deployment of the genetic point-of-care test. The study has relevance for nurses involved in the development and delivery of genetic point-of-care tests in other acute hospital settings.

Reporting Method

This qualitative study adheres to the Standards for Reporting Qualitative Research EQUATOR guidelines and utilizes COREQ and SRQR checklists.

Patient or Public Contribution

All staff working on the participating neonatal intensive care units were trained to use the genetic point-of-care test. All inpatients on the participating units were eligible to have testing via the point-of-care test. The Pharmacogenetics to Avoid Loss of Hearing Patient and Public Involvement and Engagement group provided valuable feedback.

Trial and Protocol Registration

Registered within the University of Manchester. Ethics approval reference numbers: IRAS: 253102 REC reference: 19/NW/0400. Also registered with the ISRCTN ref: ISRCTN13704894.

Introduction of a Registered Undergraduate Student of Nursing workforce: A qualitative study of student and registered nurses

Abstract

Aim

To explore the benefits and challenges of a recently introduced Registered Undergraduate Student of Nursing workforce from the perspective of Nurses and Registered Undergraduate Students of Nursing, in a major metropolitan hospital in Australia in 2020.

Design

A qualitative descriptive study was undertaken using individual interviews and focus groups.

Methods

Purposively selected employed Registered Undergraduate Students of Nursing and nurses who worked with them were interviewed, using a semi-structured format. Recordings were transcribed and coded using NVivo software. Reflexive thematic analysis using an inductive approach was undertaken.

Results

Four major themes were revealed: (i) Navigating the programme, (ii) Belonging and integration; (iii) Patient care; and (iv) Continuing Development. Initial challenges were common, often related to clarifying the scope of practice for the new role. Ongoing issues were associated with gaps in understanding the role and lack of integration into the team. Mostly, nurses and Registered Undergraduate Students of Nursing built positive, professional relationships. Nurses valued the Registered Undergraduate Student of Nursing knowledge and skill level, reporting improved workload and work experiences when the Registered Undergraduate Student of Nursing was on shift. Nurses believed that the Registered Undergraduate Students of Nursing enhanced patient care. Registered Undergraduate Students of Nursing described positive, therapeutic relationships with patients. Registered Undergraduate Student of Nursing employment provided opportunities for new learning, leading to increased efficiency and confidence on clinical placement.

Conclusions

This employment model benefited the Registered Undergraduate Students of Nursing and nurses who worked with them. In the absence of adequate training and support, challenges remained unresolved and negatively impacted the experience for nurses. In addition to university-level education and clinical placement, the employment model can create a third space for student learning via on-the-job training. The study supports the ongoing employment of student nurses through the Registered Undergraduate Student of Nursing model.

Implications for the Profession and/or Patient Care

Impact

This study contributes to the very small body of literature investigating Registered Undergraduate Student of Nursing workforces in Australian hospitals. It is the first to explore the experiences of both nurses and students working together in a major metropolitan setting and also the first in the context of the COVID-19 pandemic. This study reflected a mostly positive experience for Registered Undergraduate Student of Nursing and the nurses who worked with them and highlighted the importance of adequate oversight and support in the implementation and maintenance of a Registered Undergraduate Student of Nursing workforce. Employed Registered Undergraduate Students of Nursing reported improved confidence, skills, and felt like they started clinical placement at an advantage, ready to step up and learn the Registered Nurse scope of practice. In addition to university-level education and clinical placement, this employment model creates a third space for learning via on-the-job training.

Reporting Method

COREQ guidelines were followed in the reporting of this study.

Patient or Public Contribution

No patient or public contribution.

Amantadine and/or transcranial magnetic stimulation for fatigue associated with multiple sclerosis (FETEM): study protocol for a phase 3 randomised, double-blind, cross-over, controlled clinical trial

Por: Matias-Guiu · J. A. · Gonzalez-Rosa · J. · Hernandez · M. A. · Martinez-Gines · M. L. · Portoles · A. · Perez-Macias · N. · Benito-Leon · J. · Padron · I. · Prieto · J. · Matias-Guiu · J.
Introduction

Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations. We aim to investigate the effect of 6 weeks of amantadine and/or TMS in fatigue due to MS.

Methods and analysis

The study is a national, multicentre, phase 3, randomised, double-blind, cross-over, placebo-controlled and sham-controlled clinical trial. Adult patients with relapsing-remitting MS, Expanded Disability Status Scale score of 1.5–4.5 and Fatigue Severity Score>4 are eligible for the trial. Participants will be randomised to one of the sequences of the study. Each sequence consists of four periods of 6 weeks of treatment and three washout periods of 12–18 weeks. All patients will receive all the combinations of therapies. The primary outcome is the Modified Fatigue Impact Scale. The secondary outcomes are the Symbol Digit Modalities Test (cognition), Beck Depression Inventory-II (depressive symptoms) and Short-Survey 12 (quality of life). Safety and cost-effectiveness will also be evaluated. An exploratory substudy including MRI and blood biomarkers will be conducted.

Ethics and dissemination

The study is approved by the Ethics Committee of the Hospital Clinico San Carlos and the Spanish Agency of Medications and Medical Devices. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences.

Trial registration number

EudraCT 2021-004868-95; NCT05809414.

Non-fibril form but not fibril form of human islet amyloid polypeptide 8–20 changes brain functions in mice

by Hinaho Suginoma, Ryuji Owada, Akiko Katano-Toki, Ayaka Mori, Jun Fujioka, Kazuhiro Nakamura

Whether fibril formation increases or decreases cytotoxicity remains unclear. Aggregation of human islet amyloid polypeptide (hIAPP), a pivotal regulator of glucose homeostasis, impairs the function and viability of pancreatic β cells. Evidence suggests that low-order oligomers of hIAPP are more toxic to β cells than fibril. However, it remains unclear whether non-fibril form of hIAPP specifically alters brain functions. This study produced fibril and non-fibril forms from a single hIAPP 8–20 peptide. The non-fibril form-injected mice showed changes in spontaneous motor activities, preference for location in the open field and social behavior. In contrast, the fibril-injected mice showed no changes in these behavioral tests. In line with the behavioral changes, the non-fibril form led to impaired neurite outgrowth of cultured neuron-like cells and the loss of neurons in the mouse hippocampus. These findings suggest that non-fibril form but not fibril form of hIAPP changes brain functions.

Caribbean deepwater snappers: Application of the bomb radiocarbon age estimation validation in understanding aspects of ecology and life history

by Katherine E. Overly, Virginia R. Shervette

Reef fishes have been utilized as food fish throughout the U.S. Caribbean and Gulf of Mexico waters for centuries, with increasing fishing effort in recent decades. As a result, many species have experienced declines in landings, including deepwater snappers such as queen snapper Etelis oculatus and blackfin snapper Lutjanus buccanella. However, little to no peer-reviewed published research exists on basic life history parameters for either species. Confirming the accuracy of an age estimation method for a fish species is essential for ensuring sustainable fisheries management. This is because in the assessment of fisheries species population age-based parameters, including longevity, age at sexual maturity, growth rate, mortality, age-specific reproductive output, and lifetime reproductive output, are important in understanding overall life history strategies of managed stocks. The past stock assessment on U.S. Caribbean queen snapper utilized an estimated longevity of 8 y, derived from length frequencies for fish from St. Lucia. Blackfin snapper has an estimated longevity of 27 y based on a relatively small study from offshore waters of the southeastern U.S. The focus of our investigation was to estimate maximum longevity of two data-poor species in the U.S. Caribbean. The accuracy of ageing methods was tested via bomb radiocarbon age estimation validation and effects of depth on Δ14C in otolith cores and eye lens core values were examined. Results from our work indicate a maximum validated age of 45 y for queen snapper, and 43 y for blackfin snapper. Our findings indicate queen snapper and blackfin snapper are long-lived (> 40 y). The resulting Δ14C comparison between eye lens cores and otolith cores has important implications for the study of age validation, specifically when deepwater species are involved.

A mixed methods PAR study investigating social capital as a resource for Black and other racially minoritised communities in the UK: A study protocol

by Georgina Gnan, Zara Asif, Sanchika Campbell, Jacqui Dyer, Anna Ehsan, Katrin Hoffmann, Hanna Kienzler, Shabbir Mellick, Nathaniel Martin, Cheryl Osei, Abreen Rebello, Imade Remouche, Rebecca Rhead, Denise Richards, Ibrahim Sabra, Sara Sabra, Pippa Sterk, Charlotte Woodhead, Stephani Hatch

Understanding how different Black and other racially minoritised communities thrive is an emerging priority area in mental health promotion. Literature demonstrates health benefits of social capital (social resources embedded within social networks). However, its effects are not always positive, particularly for certain subpopulations who are already disadvantaged.The CONtributions of social NEtworks to Community Thriving (CONNECT) study will use Participatory Action Research (PAR) to investigate social capital as a resource that benefits (or hinders) racially minoritised communities and their mental health. The CONNECT study was designed within a partnership with community organisations and responds to local policy in two South-East London Boroughs, thereby providing potential channels for the action component of PAR. Taking an anti-racism lens, we acknowledge the underpinning role of racism in creating health inequities. We apply an intersectional framework to be considerate of overlapping forms of oppression such as age, gender, socioeconomic status, and sexual orientation as an essential part of developing effective strategies to tackle health inequities. Key components of this mixed methods PAR study include (1) involving racialised minority community members as peer researchers in the team (2) collecting and analysing primary qualitative data via interviews, photovoice, and community mapping workshops, (3) developing relevant research questions guided by peer researchers and collaborating organisations and analysing secondary quantitative data accordingly, (4) integrating qualitative and quantitative phases, and (5) working closely with community and policy partners to act on our findings and use our research for social change.The PAR approach will allow us to engage community (voluntary sector and government) and academic partners in decision making and help address imbalances in power and resource allocation. Knowledge generated through this collaborative approach will contribute to existing community initiatives, policies, and council strategies. This will ensure the views and experiences of racially minoritised communities drive the changes we are collaboratively committed to achieving.

Predicting child development and school readiness, at age 5, for Aboriginal and non-Aboriginal children in Australia’s Northern Territory

by Abel Fekadu Dadi, Vincent He, Georgina Nutton, Jiunn-Yih Su, Steven Guthridge

Background

Positive early development is critical in shaping children’s lifelong health and wellbeing. Identifying children at risk of poor development is important in targeting early interventions to children and families most in need of support. We aimed to develop a predictive model that could inform early support for vulnerable children.

Methods

We analysed linked administrative records for a birth cohort of 2,380 Northern Territory children (including 1,222 Aboriginal children) who were in their first year of school in 2015 and had a completed record from the Australian Early Development Census (AEDC). The AEDC measures early child development (school readiness) across five domains of development. We fitted prediction models, for AEDC weighted summary scores, using a Partial Least Square Structural Equation Model (PLS-SEM) considering four groups of factors–pre-pregnancy, pregnancy, known at birth, and child-related factors. We first assessed the models’ internal validity and then the out-of-sample predictive power (external validity) using the PLSpredict procedure.

Result

We identified separate predictive models, with a good fit, for Aboriginal and non-Aboriginal children. For Aboriginal children, a significant pre-pregnancy predictor of better outcomes was higher socioeconomic status (direct, β = 0.22 and indirect, β = 0.16). Pregnancy factors (gestational diabetes and maternal smoking (indirect, β = -0.09) and child-related factors (English as a second language and not attending preschool (direct, β = -0.28) predicted poorer outcomes. Further, pregnancy and child-related factors partially mediated the effects of pre-pregnancy factors; and child-related factors fully mediated the effects of pregnancy factors on AEDC weighted scores. For non-Aboriginal children, pre-pregnancy factors (increasing maternal age, socioeconomic status, parity, and occupation of the primary carer) directly predicted better outcomes (β = 0.29). A technical observation was that variance in AEDC weighted scores was not equally captured across all five AEDC domains; for Aboriginal children results were based on only three domains (emotional maturity; social competence, and language and cognitive skills (school-based)) and for non-Aboriginal children, on a single domain (language and cognitive skills (school-based)).

Conclusion

The models give insight into the interplay of multiple factors at different stages of a child’s development and inform service and policy responses. Recruiting children and their families for early support programs should consider both the direct effects of the predictors and their interactions. The content and application of the AEDC measurement need to be strengthened to ensure all domains of a child’s development are captured equally.

A novel, multidomain, primary care nurse-led and mHealth-assisted intervention for dementia risk reduction in middle-aged adults (HAPPI MIND): study protocol for a cluster randomised controlled trial

Por: Cross · A. J. · Geethadevi · G. M. · Magin · P. · Baker · A. L. · Bonevski · B. · Godbee · K. · Ward · S. A. · Mahal · A. · Versace · V. · Bell · J. S. · Mc Namara · K. · O'Reilly · S. L. · Thomas · D. · Manias · E. · Anstey · K. J. · Varnfield · M. · Jayasena · R. · Elliott · R. A. · Lee
Introduction

Middle-aged multidomain risk reduction interventions targeting modifiable risk factors for dementia may delay or prevent a third of dementia cases in later life. We describe the protocol of a cluster randomised controlled trial (cRCT), HAPPI MIND (Holistic Approach in Primary care for PreventIng Memory Impairment aNd Dementia). HAPPI MIND will evaluate the efficacy of a multidomain, nurse-led, mHealth supported intervention for assessing dementia risk and reducing associated risk factors in middle-aged adults in the Australian primary care setting.

Methods and analysis

General practice clinics (n≥26) across Victoria and New South Wales, Australia, will be recruited and randomised. Practice nurses will be trained to implement the HAPPI MIND intervention or a brief intervention. Patients of participating practices aged 45–65 years with ≥2 potential dementia risk factors will be identified and recruited (approximately 15 patients/clinic). Brief intervention participants receive a personalised report outlining their risk factors for dementia based on Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI) scores, education booklet and referral to their general practitioner as appropriate. HAPPI MIND participants receive the brief intervention as well as six individualised dementia risk reduction sessions with a nurse trained in motivational interviewing and principles of behaviour change, a personalised risk reduction action plan and access to the purpose-built HAPPI MIND smartphone app for risk factor self-management. Follow-up data collection will occur at 12, 24 and 36 months. Primary outcome is ANU-ADRI score change at 12 months from baseline. Secondary outcomes include change in cognition, quality of life and individual risk factors of dementia.

Ethics and dissemination

Project approved by Monash University Human Research Ethics Committee (ID: 28273). Results will be disseminated in peer-reviewed journals and at healthcare conferences. If effective in reducing dementia risk, the HAPPI MIND intervention could be integrated into primary care, scaled up nationally and sustained over time.

Trial registration number

ACTRN12621001168842.

Using spatial video geonarratives to improve nursing care for people who use drugs and experience homelessness: A methodology for nurses

Abstract

Background

People who are insecurely housed and use drugs are disproportionately affected by drug poisonings. Nurses are uniquely positioned to utilize harm reduction strategies to address the needs of the whole person. Needle debris encompasses drug paraphernalia discarded in public spaces. Studying needle debris provides a strategic opportunity to identify where drugs are being used and target public health strategies accordingly.

Aim

Our aim in this article is to illustrate how spatial video geonarratives (SVG) combined GPS technology interviews, and videos of locations with needle debris, can elicit valuable data for nursing research.

Methods

Using SVG required knowledge of how to collect data wearing cameras and practice sessions were necessary. A Miufly camera worn at waist height on a belt provided the stability to walk while interviewing stakeholders. We wore the cameras and conducted go-along interviews with outreach workers, while filming the built environment. Upon completion of data collection, both the interview and GPS information were analysed using Wordmapper software.

Conclusions

This methodology resulted in data presented uniquely in both a visual map and narrative. These data were richer than if a single modality had been used. These data highlighted specific contextual factors that were related to the location of needle debris, which created opportunities for nursing interventions to support people experiencing vulnerability.

Understanding and addressing changing administrative workload in primary care in Canada: protocol for a mixed-method study

Por: Lavergne · M. R. · Moravac · C. · Bergin · F. · Buote · R. · Easley · J. · Grudniewicz · A. · Hedden · L. · Leslie · M. · McKay · M. · Marshall · E. G. · Martin-Misener · R. · Mooney · M. · Palmer · E. · Tracey · J.
Introduction

Many Canadians struggle to access the primary care they need while at the same time primary care providers report record levels of stress and overwork. There is an urgent need to understand factors contributing to the gap between a growing per-capita supply of primary care providers and declines in the availability of primary care services. The assumption of responsibility by primary care teams for services previously delivered on an in-patient basis, along with a rise in administrative responsibilities may be factors influencing reduced access to care.

Methods and analysis

In this mixed-methods study, our first objective is to determine how the volume of services requiring primary care coordination has changed over time in the Canadian provinces of Nova Scotia and New Brunswick. We will collect quantitative administrative data to investigate how services have shifted in ways that may impact administrative workload in primary care. Our second objective is to use qualitative interviews with family physicians, nurse practitioners and administrative team members providing primary care to understand how administrative workload has changed over time. We will then identify priority issues and practical response strategies using two deliberative dialogue events convened with primary care providers, clinical and system leaders, and policy-makers.

We will analyse changes in service use data between 2001/2002 and 2021/2022 using annual total counts, rates per capita, rates per primary care provider and per primary care service. We will conduct reflexive thematic analysis to develop themes and to compare and contrast participant responses reflecting differences across disciplines, payment and practice models, and practice settings. Areas of concern and potential solutions raised during interviews will inform deliberative dialogue events.

Ethics and dissemination

We received research ethics approval from Nova Scotia Health (#1028815). Knowledge translation will occur through dialogue events, academic papers and presentations at national and international conferences.

Post-stress changes in the gut microbiome composition in rats with different levels of nervous system excitability

by Alla Shevchenko, Irina Shalaginova, Dmitriy Katserov, Ludmila Matskova, Natalia Shiryaeva, Natalia Dyuzhikova

The gut-brain axis is a critical communication system influencing the interactions between the gastrointestinal tract (GI) and the central nervous system (CNS). The gut microbiota plays a significant role in this axis, affecting the development and function of the nervous system. Stress-induced psychopathologies, such as depression and anxiety, have been linked to the gut microbiota, but underlying mechanisms and genetic susceptibility remain unclear. In this study, we examined stress-induced changes in the gut microbiome composition in two rat strains with different levels of nervous system excitability: high threshold (HT strain) and low threshold (LT strain). Rats were exposed to long-term emotional and painful stress using the Hecht protocol, and fecal samples were collected at multiple time points before and after stress exposure. Using 16S rRNA amplicon sequencing, we assessed the qualitative and quantitative changes in the gut microbiota. Our results revealed distinct microbial diversity between the two rat strains, with the HT strain displaying higher diversity compared to the LT strain. Notably, under prolonged stress, the HT strain showed an increase in relative abundance of microorganisms from the genera Faecalibacterium and Prevotella in fecal samples. Additionally, both strains exhibited a decrease in Lactobacillus abundance following stress exposure. Our findings provide valuable insights into the impact of hereditary nervous system excitability on the gut microbiome composition under stress conditions. Understanding the gut-brain interactions in response to stress may open new avenues for comprehending stress-related psychopathologies and developing potential therapeutic interventions targeted at the gut microbiota. However, further research is needed to elucidate the exact mechanisms underlying these changes and their implications for stress-induced disorders. Overall, this study contributes to the growing body of knowledge on the gut-brain axis and its significance in stress-related neurobiology.

Prospective incidence epidemiology study protocol: conducting active surveillance to assess the burden of Lyme disease (BOLD) in primary care practices in endemic areas of six European countries

Por: Begier · E. · Pilz · A. · Loew-Baselli · A. · Harper · L. R. · Stark · J. H. · Bowdery · M. · Halsby · K. · Dzingina · M. · Bezay · N. · Allen · K. E. · Parslow · B. · Gessner · B. D.
Introduction

Lyme disease (LD) is the most frequent tick-borne disease in the moderate climates of Europe. This study will inform the phase III efficacy study for Pfizer and Valneva’s investigational Lyme disease vaccine, VLA15. VLA15 phase III will be conducted in the USA and Europe due to the vaccine’s serotype coverage and public health burden of LD. In Europe, the existence and location of sites that have access to populations with high LD annual incidence is uncertain. This active, prospective surveillance study assesses annual LD incidence at general practice (GP)/primary care sites, allowing for phase III site vetting and better characterisation of LD burden in selected regions for study size calculations.

Methods and analysis

This burden of Lyme disease (BOLD) study will assess LD incidence overall and by site at 15 GP/primary care practices in endemic areas of 6 European countries from Spring 2021 to December 2022 and will be summarised with counts (n), percentages (%) and associated 95% CIs. Suspected LD cases identified from site’s practice panels are documented on screening logs, where clinical LD manifestations, diagnoses and standard of care diagnostic results are recorded. In the initial 12-month enrolment phase, suspected LD cases are offered enrolment. Participants undergo interview and clinical assessments to establish medical history, final clinical diagnosis, clinical manifestations and quality of life impact. Study-specific procedures include LD serology, skin punch biopsies and Lyme manifestation photographs. For every enrolled participant diagnosed with LD, 6–10 age-matched controls are randomly selected and offered enrolment for an embedded LD risk factor analysis. Persistent symptoms or post-treatment LD will be assessed at follow-up visits up to 2 years after initial diagnosis, while patients remain symptomatic.

Ethics and dissemination

This study has been approved by all sites’ local ethics committees. The results will be presented at conferences and published in peer-reviewed journals.

Reframing care while enduring the traumatic nature of witnessing disrupted family‐patient‐nurses' relationships during COVID‐19

Abstract

Aim

To describe the lived experiences of nurses caring for patients and families in the context of COVID-19 in Brazil and United States.

Design

A phenomenological philosophical approach following the van Manen analysis method.

Methods

Participants were recruited in Brazil and the United States, including nurses working in health care settings caring for COVID-19 patients. Recruitment used purposive and snowball sampling. Participants completed a demographic survey and semi-structured interviews that were audio-recorded and transcribed for analysis. A cross-cultural examination occurred among researchers from each country.

Results

The result was described (n = 35) by the themes, representing the essences of each lifeworld (relationship, time, space and body). The nurses' lived experience was one of reframing care while enduring repeated trauma of witnessing disrupted patient-family-nurse relationships. Themes were as follows: (a) Living a silent and lonely experience; (b) Providing connectedness for disrupted patient and family relationships; (c) Feeling the burden of the demands; (d) Being a helping connector; (e) Reshaping spaces amidst evolving interventions and policies; (f) Creating safe spaces, surrounded by turmoil, threat, and distress within an unsafe environment; (g) Reorganizing care and reframing time; (h) Reconciling losses, regrets, victories and lessons.

Conclusion

The nurses' lived experience of caring for patients and families during the COVID-19 pandemic prompted the need to respond to repeated traumas and distress posed by interrupted patient-family and nurse-own family relationships, vulnerable bodies, threatened space and dynamic and volatile time.

Impact

Cultural nuances were discovered depending on the practice setting, political discourse and the autonomy of the nurse. Innovative models of care that create structures and processes to support nurses in caring for patients in threatening environments and the commitment to connecting family members have potential to contribute to the ongoing health of the nursing profession.

Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis

by Tasnim F. Imran, Ali A. Khan, Phinnara Has, Alexis Jacobson, Stephanie Bogin, Mahnoor Khalid, Asim Khan, Samuel Kim, Sebhat Erqou, Gaurav Choudhary, Karen Aspry, Wen-Chih Wu

Background

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.

Objective

The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.

Methods

Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.

Results

In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12–52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p Conclusion

PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.

Post‐operative nursing activities to prevent wound complications in patients undergoing colorectal surgeries: A scoping review

Abstract

Aims

To identify postoperative interventions and quality improvement initiatives used to prevent wound complications in patients undergoing colorectal surgeries, the types of activities nurses undertake in these interventions/initiatives and how these activities align with nurses' scope of practice.

Design

A scoping review.

Data Sources

Three health databases were searched, and backward and forward citation searching occurred in April 2022. Research and quality improvement initiatives included focussed on adult patients undergoing colorectal surgery, from 2010 onwards. Data were extracted about study characteristics, nursing activities and outcomes. The ‘Dimensions of the scope of nursing practice’ framework was used to classify nursing activities and then the Patterns, Advances, Gaps, Evidence for practice and Research recommendations framework was used to synthesise the review findings.

Results

Thirty-seven studies were included. These studies often reported negative wound pressure therapy and surgical site infection bundle interventions/initiatives. Nurses' scope of practice was most frequently ‘Technical procedure and delegated medical care’ meaning nurses frequently acted under doctors' orders, with the most common delegated activity being dressing removal.

Conclusion

The full extent of possible interventions nurses could undertake independently in the postoperative period requires further exploration to improve wound outcomes and capitalise on nurses' professional role.

Impact Statement

Nurses' role in preventing postoperative wound complications is unclear, which may inhibit their ability to influence postoperative outcomes. In the postoperative period, nurses undertake technical activities, under doctors' orders to prevent wound infections. For practice, nurses need to upkeep and audit their technical skills. New avenues for researchers include exploration of independent activities for postoperative nurses and the outcomes of these activities.

Implications for the Profession and/or Patient Care

There may be opportunities to broaden nurses' scope of practice to act more autonomously to prevent wound complication.

Reporting Method

Scoping Reviews (PRISMA-ScR) checklist.

Patient or Public Contribution

A health consumer interpreted the data and prepared the manuscript.

Two distinct mechanisms lead to either oocyte or spermatocyte decrease in <i>C</i>. <i>elegans</i> after whole developmental exposure to γ-rays

by Elizabeth Dufourcq Sekatcheff, Christian Godon, Aymeric Bailly, Loïc Quevarec, Virginie Camilleri, Simon Galas, Sandrine Frelon

Wildlife is subject to various sources of pollution, including ionizing radiation. Adverse effects can impact the survival, growth, or reproduction of organisms, later affecting population dynamics. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint. Understanding the underlying molecular pathways inducing this reproduction decrease can help to comprehend species-specific differences in radiosensitivity. From our previous studies, we found that decrease in reproduction is life stage dependent in the roundworm Caenorhabditis elegans, possibly resulting from an accumulation of damages during germ cell development and gamete differentiation. To go further, we used the same experimental design to assess more precisely the molecular determinants of reproductive toxicity, primarily decreases in gamete number. As before, worms were chronically exposed to 50 mGy·h−1 external gamma ionizing radiation throughout different developmental periods (namely embryogenesis, gametogenesis, and full development). To enable cross species extrapolation, conserved molecular pathways across invertebrates and vertebrates were analysed: apoptosis and MAP kinase Ras/ERK (MPK-1), both involved in reproduction and stress responses. Our results showed that these pathways are life-stage dependent, resulting from an accumulation of damages upon chronic exposure to IR throughout the life development. The Ras/ERK pathway was activated in our conditions in the pachytene region of the gonad where it regulates cell fate including apoptosis, but not in the ovulation zone, where it controls oocyte maturation and ovulation. Additionally, assessment of germ cell proliferation via Ras/ERK pathway showed no effect. Finally, a functional analysis of apoptosis revealed that while the decrease of the ovulation rate is caused by DNA-damaged induced apoptosis, this process does not occur in spermatocytes. Thus, sperm decrease seems to be mediated via another mechanism, probably a decrease in germ cell proliferation speed that needs further investigation to better characterize sex-specific responses to IR exposure. These results are of main importance to describe radio-induced reprotoxic effects and contribute as weight of evidence for the AOP #396 “Deposition of ionizing energy leads to population decline via impaired meiosis”.

Two mouse models of Alzheimer’s disease accumulate amyloid at different rates and have distinct Aβ oligomer profiles unaltered by ablation of cellular prion protein

by Silvia A. Purro, Michael Farmer, Elizabeth Noble, Claire J. Sarell, Megan Powell, Daniel Yip, Lauren Giggins, Leila Zakka, David X. Thomas, Mark Farrow, Andrew J. Nicoll, Dominic Walsh, John Collinge

Oligomers formed from monomers of the amyloid β-protein (Aβ) are thought to be central to the pathogenesis of Alzheimer’s disease (AD). Unsurprisingly for a complex disease, current mouse models of AD fail to fully mimic the clinical disease in humans. Moreover, results obtained in a given mouse model are not always reproduced in a different model. Cellular prion protein (PrPC) is now an established receptor for Aβ oligomers. However, studies of the Aβ-PrPC interaction in different mouse models have yielded contradictory results. Here we performed a longitudinal study assessing a range of biochemical and histological features in the commonly used J20 and APP-PS1 mouse models. Our analysis demonstrated that PrPC ablation had no effect on amyloid accumulation or oligomer production. However, we found that APP-PS1 mice had higher levels of oligomers, that these could bind to recombinant PrPC, and were recognised by the OC antibody which distinguishes parallel, in register fibrils. On the other hand, J20 mice had a lower level of Aβ oligomers, which did not interact with PrPC when tested in vitro and were OC-negative. These results suggest the two mouse models produce diverse Aβ assemblies that could interact with different targets, highlighting the necessity to characterise the conformation of the Aβ oligomers concomitantly with the toxic cascade elicited by them. Our results provide an explanation for the apparent contradictory results found in APP-PS1 mice and the J20 mouse line in regards to Aβ toxicity mediated by PrPC.

Decision‐making experiences related to mastectomy: A descriptive qualitative study

Abstract

Aim

To obtain an in-depth understanding of women's decision-making experiences related to mastectomy.

Design

A descriptive qualitative interview study.

Methods

Individual semi-structured interviews were conducted face-to-face with 27 Chinese women with breast cancer who underwent mastectomy at two tertiary hospitals in mainland China between September 2020 and December 2021 after obtaining the appropriate ethical approvals. Interviews were conducted in Mandarin. Data were analysed using inductive content analysis.

Results

Mean age of participants was 48 years (range 31–70). Most participants had low education, low monthly family income, had a partner and health insurance, had been diagnosed with early breast cancer, and had not undergone reconstructive surgery. Six categories related to decision-making experiences emerged: (1) Emotions affecting decision-making, (2) Information seeking for decision-making, (3) Beliefs about mastectomy and the breast, (4) Participation in decision-making, (5) People who influence decision-making, and (6) Post-decision reflection. Participants did not mention the role of nurses in their decision-making process for mastectomy.

Conclusions

This study adds valuable insights into the limited evidence on women's experience with decision-making about mastectomy from a Chinese perspective, which is important given the continuing high prevalence of mastectomy in many regions. Future studies from other countries and ethnic groups are recommended to gain diverse knowledge.

Impact

The findings of this study are useful for nurses and other healthcare professionals in the multidisciplinary team to better support women with breast cancer in their decision-making process regarding mastectomy. The findings could inform future interventions to support treatment decision-making and may be relevant to women living in similar socio-medical contexts to those in mainland China.

Reporting Method

The study was reported following the Standards for Reporting Qualitative Research checklist.

Patient or Public Contribution

No patient or public contribution.

Clinical deterioration as a nurse sensitive indicator in the out‐of‐hospital context: A scoping review

Abstract

Aims

To explore and summarise the literature on the concept of ‘clinical deterioration’ as a nurse-sensitive indicator of quality of care in the out-of-hospital context.

Design

The scoping review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review and the JBI best practice guidelines for scoping reviews.

Methods

Studies focusing on clinical deterioration, errors of omission, nurse sensitive indicators and the quality of nursing and midwifery care for all categories of registered, enrolled, or licensed practice nurses and midwives in the out-of-hospital context were included regardless of methodology. Text and opinion papers were also considered. Study protocols were excluded.

Data Sources

Data bases were searched from inception to June 2022 and included CINAHL, PsychINFO, MEDLINE, The Allied and Complementary Medicine Database, EmCare, Maternity and Infant Care Database, Australian Indigenous HealthInfoNet, Informit Health and Society Database, JSTOR, Nursing and Allied Health Database, RURAL, Cochrane Library and Joanna Briggs Institute.

Results

Thirty-four studies were included. Workloads, education and training opportunities, access to technology, home visits, clinical assessments and use of screening tools or guidelines impacted the ability to recognise, relay information and respond to clinical deterioration in the out-of-hospital setting.

Conclusions

Little is known about the work of nurses or midwives in out-of-hospital settings and their recognition, reaction to and relay of information about patient deterioration. The complex and subtle nature of non-acute deterioration creates challenges in defining and subsequently evaluating the role and impact of nurses in these settings.

Implications for the profession and/or patient care

Further research is needed to clarify outcome measures and nurse contribution to the care of the deteriorating patient in the out-of-hospital setting to reduce the rate of avoidable hospitalisation and articulate the contribution of nurses and midwives to patient care.

Impact

What Problem Did the Study Address?

Factors that impact a nurse's ability to recognise, relay information and respond to clinical deterioration in the out-of-hospital setting are not examined to date.

What Were the Main Findings?

A range of factors were identified that impacted a nurse's ability to recognise, relay information and respond to clinical deterioration in the out-of-hospital setting including workloads, education and training opportunities, access to technology, home visits, clinical assessments, use of screening tools or guidelines, and avoidable hospitalisation.

Where and on whom will the research have an impact?

Nurses and nursing management will benefit from understanding the factors that act as barriers and facilitators for effective recognition of, and responding to, a deteriorating patient in the out-of-hospital setting. This in turn will impact patient survival and satisfaction.

Reporting Method

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines guided this review. The PRISMA-Scr Checklist (Tricco et al., 2018) is included as (supplementary file 1).Data sharing is not applicable to this article as no new data were created or analysed in this study.”

No Patient or Public Contribution

Not required as the Scoping Review used publicly available information.

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