Young Hip: an exploration into young patients' (aged ≤ 50 years) expectations following primary total hip arthroplasty : a qualitative study.

AIMS: Total hip arthroplasties (THAs) are common operations performed in orthopaedics. Though initially developed to address hip conditions in older patients, demand in younger patients is increasing. Research in older populations informs current practice, and it is unclear if outcome priorities are the same in younger patients. The study's aim was to explore the expectations and priorities of younger patients' (aged < 50 years) undergoing THA. METHODS: Using interpretive phenomenological analysis (IPA) methodology, ten patients were recruited from one UK hospital. Semistructured interviews occurred at three timepoints (pre-surgery, six weeks, and six months post-surgery). This study has been reported using the COnsolidated criteria for REporting Qualitative research (COREQ). RESULTS: Six themes were identified: 'I'm just constantly in pain', 'Giving up hope', 'Living a process that does not reflect me', 'This is not who I'm meant to be', 'My family didn't sign up for this', and 'I can't do anything'. Some themes were independent of patient age, such as pain, and experiences of healthcare. However, other findings may be more imperative to the younger patient than the older patient. CONCLUSION: The Young Hip study highlighted aspects currently overlooked in younger THA patients. Participants were aware that they were not the accepted patient profile for THA, and expressed having to fight to be heard. Function was considered in terms of responsibilities and roles in society, rather than traditional clinical perceptions of mobility. The findings demonstrated that current care pathways are not fully addressing the needs of younger THA patients. Further development of a personalized THA pathway, allowing for more focus on person-centred care, could address issues raised by this study, more effectively supporting younger patients

Young Hip: an exploration into young patients’ (aged < 50 years) expectations following primary total hip arthroplasty

AimsTotal hip arthroplasties (THAs) are common operations performed in orthopaedics. Though initially developed to address hip conditions in older patients, demand in younger patients is increasing. Research in older populations informs current practice, and it is unclear if outcome priorities are the same in younger patients. The study’s aim was to explore the expectations and priorities of younger patients’ (aged < 50 years) undergoing THA.MethodsUsing interpretive phenomenological analysis (IPA) methodology, ten patients were recruited from one UK hospital. Semistructured interviews occurred at three timepoints (pre-surgery, six weeks, and six months post-surgery). This study has been reported using the COnsolidated criteria for REporting Qualitative research (COREQ).ResultsSix themes were identified: ‘I’m just constantly in pain’, ‘Giving up hope’, ‘Living a process that does not reflect me’, ‘This is not who I’m meant to be’, ‘My family didn’t sign up for this’, and ‘I can’t do anything’. Some themes were independent of patient age, such as pain, and experiences of healthcare. However, other findings may be more imperative to the younger patient than the older patient.ConclusionThe Young Hip study highlighted aspects currently overlooked in younger THA patients. Participants were aware that they were not the accepted patient profile for THA, and expressed having to fight to be heard. Function was considered in terms of responsibilities and roles in society, rather than traditional clinical perceptions of mobility. The findings demonstrated that current care pathways are not fully addressing the needs of younger THA patients. Further development of a personalized THA pathway, allowing for more focus on person-centred care, could address issues raised by this study, more effectively supporting younger patients

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Genetic mechanisms of critical illness in Covid-19.

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

An exploration into young patients’ (<50 years) expectations following primary total hip arthroplasty; An Interpretative Phenomenological Analysis study.

Title: YOUNG HIP: An exploration into young patients’ (<50 years) expectations following primary total hip arthroplasty: An Interpretative Phenomenological Analysis study. Introduction. Total hip replacements (THR) are common operations performed in orthopaedics. Though initially developed to address hip conditions in older patients, demand in younger patients is increasing. Research in older populations informs current practice and it is unclear if outcome priorities important to older patients are similar in younger patients, or if younger THR patients consider other outcomes more important. Patient-reported outcome measures (PROMs), routinely used in clinical practice, aim to evaluate the success of interventions from the patient’s perspective. However, these standard questionnaires may not account for differences in priorities across various demographic groups. Aims Young Hip’s primary aim was to explore younger patients’ (<50 years) expectations and priorities when undergoing primary elective THR. Methods Four studies were undertaken: a systematic literature review (study 1), a Public and Patient Involvement (PPI) study (study 2), a bibliographic review (study 3), and a qualitative study (study 4). Study 1 highlighted the current absence of qualitative research on THR patients, the aim of study 2 was to reveal themes from the patient perspective not currently addressed by existing healthcare pathways, and study 3 underlined the minimal use of qualitative methodologies in research published in orthopaedic journals. These studies underscored the necessity and rationale for further exploration into the priorities of younger THR patients through qualitative enquiry. Therefore, study 4 utilised Interpretative Phenomenological Analysis (IPA) to examine the experiences of ten patients from a UK hospital. Semi- structured interviews were conducted at three timepoints: pre-surgery, six-weeks post- surgery, and six-months post-surgery. Data was analysed individually before cross-case analysis explored the similarities and differences between participants. Additionally, participants completed validated PROMs questionnaires at each timepoint, these results were compared with the qualitative data to assess whether PROMs accurately reflected the participants’ experiences and concerns. Findings These findings suggest that younger patients face distinct psychological and social challenges that are often overlooked in standard care pathways

Addressing the cross-country PhD dissertations in the nursing domain::a scoping review

Introduction: Doctoral research in nursing plays a key role in advancing the profession and tackling complex healthcare challenges. It fosters evidence-based practice, drives innovation and cultivates highly skilled nurse researchers, academics, and practitioners. It expands knowledge, informs policy and improves patient outcomes. Nonetheless, there is limited evidence on current trends in nursing PhD theses across Europe.Aims: This scoping review aims to map the landscape of PhD theses in the nursing domain.Methods: This study followed PRISMA for Scoping Reviews and included PhD theses in nursing published between 2020 and 2023 in eight European countries. Seven databases were explored for published studies and local repositories for grey literature. A descriptive analysis was conducted to outline the key characteristics of the thesis, while data extracted from the results were examined using content analysis.Findings: This review included 431 theses, most of which were quantitative designs focused on patient populations and healthcare professionals. Key topics included nursing clinical care, quality of care, quality of life, home care, perinatal care, and working environment. Significant advancements in healthcare delivery, patient care, and nursing education were presented, including innovations in digital tools, holistic and patient-centered care, and professional development. However, a lack of research on mental health and marginalised populations was highlighted. Conclusion: This review emphasises the diverse focus of nursing doctoral research across Europe, addressing significant healthcare and nursing issues. However, gaps indicate the need for broader and more inclusive research to improve healthcare equity and inform future nursing practices and policies.<br/