Qualitative Description of Exercise Perceptions and Experiences Among People With Human Immunodeficiency Virus in the High-Intensity Exercise to Attenuate Limitations and Train Habits Study.

BACKGROUND: The benefits of physical activity (PA), specifically exercise, among older adults in general are well known. Yet globally, there is concern regarding limited engagement in PA, increased obesity, and frailty among older people with human immunodeficiency virus related to low levels of PA. METHODS: We conducted in-depth interviews among 30 older, sedentary people with human immunodeficiency virus participating in the ongoing High-Intensity Exercise to Attenuate Limitations and Train Habits (HEALTH study, NCT04550676) between February 2021 and August 2022. A semistructured interview guide, informed by two minds theory, which frames behavior change as an intention-behavior gap between 2 neurocognitive systems, was used to elicit data from participants. Interviews explored general exercise perceptions, self-efficacy for exercise, mobile health intervention tailoring, outcome expectations, and PA goals. Thirty interviews from 33 participants were recorded and transcribed verbatim, and deductive and inductive thematic analysis were used using Dedoose. RESULTS: Physical activity was defined as maintaining daily living activities and addressing health goals. Previous experiences with PA varied among participants and were influenced by chronic illnesses, including human immunodeficiency virus; motivation; work commitments; interest; and social support. Reported barriers to PA included antiretroviral adverse effects, comorbidities, aging, and the COVID-19 pandemic. Changes in health status, body changes, and relationships were identified as benefits of PA. Conversations with healthcare providers supporting exercise goals were perceived to be important but rarely received by the participants. CONCLUSION: Understanding how older people with human immunodeficiency virus perceive PA is crucial to developing tailored strategies and structuring service delivery within the healthcare setting to promote a physically active life.

Safety of teropavimab and zinlirvimab with lenacapavir once every 6 months for HIV treatment: a phase 1b, randomised, proof-of-concept study.

BACKGROUND: Long-acting treatment for HIV has potential to improve adherence, provide durable viral suppression, and have long-term individual and public health benefits. We evaluated treatment with two antibodies that broadly and potently neutralise HIV (broadly neutralising antibodies; bNAbs), combined with lenacapavir, a long-acting capsid inhibitor, as a long-acting regimen. METHODS: This ongoing, randomised, blind, phase 1b proof-of-concept study conducted at 11 HIV treatment centres in the USA included adults with a plasma HIV-1 RNA concentration below 50 copies per mL who had at least 18 months on oral antiretroviral therapy (ART), CD4 counts of at least 500 cells per µL, and protocol-defined susceptibility to bNAbs teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS). Participants stopped oral ART and were randomly assigned (1:1) to one dose of 927 mg subcutaneous lenacapavir plus an oral loading dose, 30 mg/kg intravenous teropavimab, and 10 mg/kg or 30 mg/kg intravenous zinlirvimab on day 1. Investigational site personnel and participants were masked to treatment assignment throughout the randomised period. The primary endpoint was incidence of serious adverse events until week 26 in all randomly assigned participants who received one dose or more of any study drug. This study is registered with ClinicalTrials.gov, NCT04811040. FINDINGS: Between June 29 and Dec 8, 2021, 21 participants were randomly assigned, ten in each group received the complete study regimen and one withdrew before completing the regimen on day 1. 18 (86%) of 21 participants were male; participants ranged in age from 25 years to 61 years and had a median CD4 cell count of 909 (IQR 687-1270) cells per µL at study entry. No serious adverse events occurred. Two grade 3 adverse events occurred (lenacapavir injection-site erythaema and injection-site cellulitis), which had both resolved. The most common adverse events were symptoms of injection-site reactions, reported in 17 (85%) of 20 participants who received subcutaneous lenacapavir; 12 (60%) of 20 were grade 1. One (10%; 95% CI 0-45) participant had viral rebound (confirmed HIV-1 RNA concentration of ≥50 copies per mL) in the zinlirvimab 10 mg/kg group, which was resuppressed on ART, and one participant in the zinlirvimab 30 mg/kg group withdrew at week 12 with HIV RNA <50 copies per mL. INTERPRETATION: Lenacapavir with teropavimab and zinlirvimab 10 mg/kg or 30 mg/kg was generally well tolerated with no serious adverse events. HIV-1 suppression for at least 26 weeks is feasible with this regimen at either zinlirvimab dose in selected people with HIV-1. FUNDING: Gilead Sciences.

Telehealth Walking Self-Management for Individuals With Amputation: A Qualitative Study of Therapist Perspectives on Adoption.

OBJECTIVE: The aim of this study was to understand therapist-identified factors influencing clinical adoption of a telehealth walking self-management intervention for individuals with lower limb amputation. METHODS: Semi-structured focus groups were completed with actively practicing physical and occupational therapists treating populations that are medically complex. A qualitative explorative design was employed with conventional content analysis and iterative independent parallel coding using 2 analysts. Themes and subthemes were generated with a consensus building process identifying patterns and collapsing codes to represent participant perspectives. RESULTS: Thematic saturation was met after 5 focus groups (24 therapists). Therapists were on average 34 years old and predominantly female (n = 19; 79%) physical therapists (n = 17; 71%). Three primary facilitator and barrier themes were identified for intervention adoption: system, therapist, and person. System considerations included telehealth support and interprofessional care coordination. Therapist facilitators included self-management programming that overlapped with standard of care and personalization methods. However, limited behavioral theory training was a therapist level barrier. Finally, person factors such as patient activation could influence both positively and negatively. Person facilitators included social support and barriers included the complex health condition. CONCLUSION: System, therapist, and person facilitators and barriers must be considered to maximize the adoption of similar telehealth walking self-management interventions and prior to larger scale implementation of the current intervention for individuals with lower limb amputation. IMPACT: A telehealth walking self-management intervention has potential impact for individuals with lower limb amputation and must be considered in terms of optimizing system, therapist, and person level facilitators and barriers to implementation.

Walking Exercise Sustainability Through Telehealth for Veterans With Lower-Limb Amputation: A Study Protocol.

OBJECTIVE: This randomized controlled superiority trial will determine if an 18-month telehealth walking exercise self-management program produces clinically meaningful changes in walking exercise sustainability compared to attention-control education for veterans living with lower-limb amputation. METHODS: Seventy-eight participants with lower-limb amputation (traumatic or nontraumatic) aged 50 to 89 years will be enrolled. Two groups will complete 6 one-on-one intervention sessions, and 6 group sessions over an 18-month intervention period. The experimental arm will receive a self-management program focusing on increasing walking exercise and the control group will receive attention-control education specific to healthy aging. Daily walking step count (primary outcome) will be continuously monitored using an accelerometer over the 18-month study period. Secondary outcomes are designed to assess potential translation of the walking exercise intervention into conventional amputation care across the Veteran Affairs Amputation System of Care. These secondary outcomes include measures of intervention reach, efficacy, likelihood of clinical adoption, potential for clinical implementation, and ability of participants to maintain long-term exercise behavior. IMPACT: The unique rehabilitation paradigm used in this study addresses the problem of chronic sedentary lifestyles following lower-limb amputation through a telehealth home-based walking exercise self-management model. The approach includes 18 months of exercise support from clinicians and peers. Trial results will provide rehabilitation knowledge necessary for implementing clinical translation of self-management interventions to sustain walking exercise for veterans living with lower-limb amputation, resulting in a healthier lifestyle.

Student-Led Stress Reduction Support Groups: A Qualitative Program Evaluation.

BACKGROUND: Burnout and attrition in nursing have been accelerated by the coronavirus disease 2019 (COVID-19) pandemic. Nursing students experience greater stress than non-nursing students but often lack adequate institutional support to build resiliency. Support groups are an effective strategy for processing stress that are underused in nursing education. An innovative online stress impact course was developed at a college of nursing to address students' stress during the pandemic. The course culminated in a voluntary virtual support group led by a Psychiatric Mental Health Nurse Practitioner graduate student. The aim of this qualitative program evaluation was to determine how graduate nursing students experienced the stress support group. METHOD: This study used qualitative exploratory analysis of support group reflections from 47 graduate nursing students. RESULTS: Four themes emerged: (1) Making Positive Connections; (2) Leveraging Skills to Manage Stress; (3) Beneficial; and (4) Facing Trauma. CONCLUSION: Graduate student-led support groups are a feasible and effective strategy to mitigate stress and improve nursing student resiliency. [J Nurs Educ. 2023;62(12):711-715.].

MicroRNAs: Small but Key Players in Viral Infections and Immune Responses to Viral Pathogens.

Since the discovery of microRNAs (miRNAs) in C. elegans in 1993, the field of miRNA research has grown steeply. These single-stranded non-coding RNA molecules canonically work at the post-transcriptional phase to regulate protein expression. miRNAs are known to regulate viral infection and the ensuing host immune response. Evolving research suggests miRNAs are assets in the discovery and investigation of therapeutics and diagnostics. In this review, we succinctly summarize the latest findings in (i) mechanisms underpinning miRNA regulation of viral infection, (ii) miRNA regulation of host immune response to viral pathogens, (iii) miRNA-based diagnostics and therapeutics targeting viral pathogens and challenges, and (iv) miRNA patents and the market landscape. Our findings show the differential expression of miRNA may serve as a prognostic biomarker for viral infections in regard to predicting the severity or adverse health effects associated with viral diseases. While there is huge market potential for miRNA technology, the novel approach of using miRNA mimics to enhance antiviral activity or antagonists to inhibit pro-viral miRNAs has been an ongoing research endeavor. Significant hurdles remain in terms of miRNA delivery, stability, efficacy, safety/tolerability, and specificity. Addressing these challenges may pave a path for harnessing the full potential of miRNAs in modern medicine.

Is high sensitivity troponin, taken regardless of a clinical indication, associated with 1 year mortality in critical care patients?

The aim of this study was to assess whether high sensitivity troponin (hs-cTnI) is associated with 1 year mortality in critical care (CC). One year mortality data were obtained from NHS Digital for a consecutive cohort of patients admitted to general CC unit (GCCU) and neuroscience CC unit (NCCU) who had hs-cTnI tests performed throughout their CC admission, regardless of whether the test was clinically indicated. Cox proportional hazards were used to estimate the risk of 1-year mortality. A landmark analysis was undertaken to assess whether any relationship at 1 year was driven by mortality within the first 30 days. A total of 1033 consecutive patients were included. At 1 year 254 (24.6%) patients had died. The admission log(10)hs-cTnI concentration in the entire cohort (HR 1.35 (95% CI 1.05-1.75) p = 0.009 with a bootstrap of 1000 samples) was independently associated with 1 year mortality. On landmark analysis the association with 1 year mortality was driven by 30 day mortality. These results indicate that admission hs-cTnI concentration is independently associated with 1 year mortality in CC and this relationship may be driven by differences in mortality at 30 days.

Routine Urinary Biochemistry Does Not Accurately Predict Stone Type Nor Recurrence in Kidney Stone Formers: A Multicentre, Multimodel, Externally Validated Machine-Learning Study.

Objectives: Urinary biochemistry is used to detect and monitor conditions associated with recurrent kidney stones. There are no predictive machine learning (ML) tools for kidney stone type or recurrence. We therefore aimed to build and validate ML models for these outcomes using age, gender, 24-hour urine biochemistry, and stone composition. Materials and Methods: Data from three cohorts were used, Southampton, United Kingdom (n = 3013), Newcastle, United Kingdom (n = 5984), and Bern, Switzerland (n = 794). Of these 3130 had available 24-hour urine biochemistry measurements (calcium, oxalate, urate [Ur], pH, volume), and 1684 had clinical data on kidney stone recurrence. Predictive ML models were built for stone type (n = 5 models) and recurrence (n = 7 models) using the UK data, and externally validated with the Swiss data. Three sets of models were built using complete cases, multiple imputation, and oversampling techniques. Results: For kidney stone type one model (extreme gradient boosting [XGBoost] built using oversampled data) was able to effectively discriminate between calcium oxalate, calcium phosphate, and Ur on both internal and external validation. For stone recurrence, none of the models were able to discriminate between recurrent and nonrecurrent stone formers. Conclusions: Kidney stone recurrence cannot be accurately predicted using modeling tools built using specific 24-hour urinary biochemistry values alone. A single model was able to differentiate between stone types. Further studies to delineate accurate predictive tools should be undertaken using both known and novel risk factors, including radiomics and genomics.

Situational Awareness and Proactive Engagement Predict Higher Time in Range in Adolescents and Young Adults Using Hybrid Closed-Loop.

Background: Adolescents and young adults with type 1 diabetes have high HbA1c levels and often struggle with self-management behaviors and attention to diabetes care. Hybrid closed-loop systems (HCL) like the t:slim X2 with Control-IQ technology (Control-IQ) can help improve glycemic control. The purpose of this study is to assess adolescents' situational awareness of their glucose control and engagement with the Control-IQ system to determine significant factors in daily glycemic control. Methods: Adolescents (15-25 years) using Control-IQ participated in a 2-week prospective study, gathering detailed information about Control-IQ system engagements (boluses, alerts, and so on) and asking the participants' age and gender about their awareness of glucose levels 2-3 times/day without checking. Mixed models assessed which behaviors and awareness items correlated with time in range (TIR, 70-180 mg/dl, 3.9-10.0 mmol/L). Results: Eighteen adolescents/young adults (mean age 18 ± 1.86 years and 86% White non-Hispanic) completed the study. Situational awareness of glucose levels did not correlate with time since the last glucose check (p = 0.8). In multivariable modeling, lower TIR was predicted on days when adolescents underestimated their glucose levels (r = -0.22), received more CGM alerts (r = -0.31), and had more pump engagements (r = -0.27). A higher TIR was predicted when adolescents responded to CGM alerts (r = 0.20) and entered carbohydrates into the bolus calculator (r = 0.49). Conclusion: Situational awareness is an independent predictor of TIR and may provide insight into patterns of attention and focus that could positively influence glycemic outcomes in adolescents. Proactive engagements predict better TIR, whereas reactive engagement predicted lower TIR. Future interventions could be designed to train users to develop awareness and expertise in effective diabetes self-management.

Stress Impact and Care for COVID-19: Pilot Education and Support Course Decreases Burnout Among Nursing Students.

BACKGROUND: Nurses and nursing students have been at the forefront of the fight against COVID-19, often working in conditions that produce stress injuries and burnout. Early recognition and mitigation of stress and emotional trauma help prevent burnout. AIMS: To evaluate the effectiveness of an online 8-hour stress awareness course and associated 1-hour support group in reducing stress and burnout among nursing students. METHODS: We conducted a program evaluation for an online stress awareness pilot course offered to nursing students. The course, and associated support groups led by trained psychiatric mental health nurse practitioner students, included a common language for talking about stress, screening tools for recognizing stress injuries, and strategies for improving self-care. Students completed pre- and post-course surveys. Outcome measures included changes on course learning objectives, level of burnout, health-related locus of control, and experiences of stress and coping. RESULTS: Nursing students (n = 360) enrolled in the course, and 224 (62%) completed pre- and post-course surveys. Sixty percent rated the course excellent or very good. Depression Anxiety and Stress Scales and Impact of Event Scale Revised scores were within established normal ranges. There was a significant increase in all nine course learning objectives (p < .001) and decreased signs of stress (p < .001). Students' level of burnout decreased by odds ratio = 0.58 (95% CI: [0.4, 0.9], p < .006). CONCLUSIONS: Nursing leaders can use psychoeducational strategies to mitigate the impact of stress, build confidence, and support nursing students entering the workforce during these unprecedented times.

Association between troponin level and medium-term mortality in 20 000 hospital patients.

INTRODUCTION: Cardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and the significance of this is uncertain. The aim of this study was to assess the relationship between medium-term mortality and cTn concentration in a large consecutive hospital population, regardless of whether there was a clinical indication for performing the test. METHOD: This prospective observational study included 20 000 consecutive in-hospital and outpatient patients who had a blood test for any reason at a large teaching hospital, and in whom a hs-cTnI assay was measured, regardless of the original clinical indication. Mortality was obtained via NHS Digital. RESULTS: A total of 20 000 patients were included in the analysis and 18 282 of these (91.4%) did not have a clinical indication for cardiac troponin I (cTnI) testing. Overall, 2825 (14.1%) patients died at a median of 809 days. The mortality was significantly higher if the cTnI concentration was above the ULN (45.3% vs 12.3% p<0.001 log rank). Multivariable Cox analysis demonstrated that the log10 cTnI concentration was independently associated with mortality (HR 1.76 (95% CI 1.65 to 1.88)). Landmark analysis, excluding deaths within 30 days, showed the relationship between cTnI concentration and mortality persisted. CONCLUSION: In a large, unselected hospital population, in 91.4% of whom there was no clinical indication for testing, cTnI concentration was independently associated with medium-term cardiovascular and non-cardiovascular mortality in the statistical model tested.

Outcomes of Paediatric Cystine Stone Management: Results of a Systematic Review.

PURPOSE OF REVIEW: We wanted to analyse the outcomes of surgical (SWL, URS, PCNL) and medical management of cystine stones in the paediatric population in terms of stone-free status and complication rates, based on all the available literature evidence. RECENT FINDINGS: A systematic review of literature was performed for all studies with paediatric cystine stone management. Twelve studies met the eligibility criteria, of which 4 analysed outcomes of SWL, 2 of URS and 3 of PCNL and 3 focused on the effect of either alkalising agents (potassium citrate, citric acid) or cysteine-binding thiol (CBT) agents (tiopronin, penicillamine). The reported SFR in studies ranged from 50 to 83%, 59 to 100% and 63 to 80.6%, with a complication rate of 2.8-51%, 14-27% and 12.9-15.4% with SWL, URS and PCNL, respectively. Paediatric cystine stones treatment should aim at complete stone clearance, preservation of renal function and prevention of further recurrences. SWL achieves inferior results in case of cystine stones. URS and PCNL are safe and effective procedures in the paediatric population, with a low rate of major complications. Adherence to medical prevention therapies may prolong recurrence-free periods.

Wilson's disease: best practice.

Wilson's disease is an autosomal recessive disorder arising from pathogenic variants in the Atp7b gene on chromosome 13. The defective translated ATPase copper (Cu) transport protein produced leads to Cu accumulation, initially affecting the liver but eventually affecting other cells. It is just over 20 years since the last Best Practice on this topic in this journal. This review is an update on this, covering new disease biomarkers, pathogenesis, assumptions around clinical features and developments in therapy.

Impact of Food Insecurity and Undernutrition on Frailty and Physical Functioning in Aging People With HIV in the United States.

ABSTRACT: We conducted an observational cross-sectional study to explore whether food insecurity or undernutrition was associated with frailty or low physical functioning in aging persons with HIV (PWH). Forty-eight PWH aged 50 years and older were enrolled. Independent samples t -tests and chi-square tests were used to examine the relationship of food insecurity or undernutrition to frailty or physical function. Participants were 58.6 (±6.3) years old, 83% male, 77% White, 21% Hispanic. In total, 44% experienced food insecurity and 71% experienced undernutrition, whereas 23% were frail and 69% were prefrail. Food insecurity was associated with impaired total short physical performance battery score ( p = .02), impaired balance ( p = .02), slower chair rise time ( p = .03), and weight loss within 12 months ( p = .05). Undernutrition was related to female gender ( p = .01), worse frailty ( p = .04), and weaker grip strength ( p = .03). In this sample of undernourished and frail PWH, strong relationships between undernutrition and frailty were observed.

Patient and Provider Perceptions of COVID-19-Driven Telehealth Use From Nurse-Led Care Models in Rural, Frontier, and Urban Colorado Communities.

The purpose of this study was to characterize the patient and provider engagement in the sudden telehealth implementation that occurred with the onset of the COVID-19 pandemic. Patients and providers from 3 nurse-led models of care (federally qualified health centers, nurse midwifery practices, and the Nurse-Family partnership program) in Colorado were surveyed. Data from the Patient Attitude toward Telehealth survey and Provider Perceptions about Telehealth were collected. Patient respondents (n = 308) who resided primarily in rural or frontier communities were female, white, and Hispanic. Patients in urban areas used telehealth more frequently than in rural or frontier areas (P < .001). Rural/Frontier patients had significantly lower attitude scores than urban patients across each of 5 domains assessed. Telehealth modality differed across location (P < .023), with video calls, used more frequently by urban providers, and phone calls used by rural/frontier providers. Our data highlight differences in telehealth access and attitudes across rurality. These findings may contribute to future policy while addressing barriers to telehealth access and delivery.

Erratum: Erratum.

[This corrects the article DOI: 10.1177/11795484221119316.].

Cellular miR-6741-5p as a Prognostic Biomarker Predicting Length of Hospital Stay among COVID-19 Patients.

Wide variability exists with host response to SARS-CoV-2 infection among individuals. Circulatory micro RNAs (miRNAs) are being recognized as promising biomarkers for complex traits, including viral pathogenesis. We hypothesized that circulatory miRNAs at 48 h post hospitalization may predict the length of stay (LOS) and prognosis of COVID-19 patients. Plasma miRNA levels were compared between three groups: (i) healthy volunteers (C); (ii) COVID-19 patients treated with remdesivir (an antiviral) plus dexamethasone (a glucocorticoid) (with or without baricitinib, a Janus kinase inhibitor) on the day of hospitalization (I); and COVID-19 patients at 48 h post treatment (T). Results showed that circulatory miR-6741-5p expression levels were significantly different between groups C and I (p < 0.0000001); I and T (p < 0.0000001); and C and T (p = 0.001). Our ANOVA model estimated that all patients with less than 12.42 Log2 CPM had a short LOS, or a good prognosis, whereas all patients with over 12.42 Log2 CPM had a long LOS, or a poor prognosis. In sum, we show that circulatory miR-6741-5p may serve as a prognostic biomarker effectively predicting mortality risk and LOS of hospitalized COVID-19 patients.

Efficacy and Safety of LY3127804, an Anti-Angiopoietin-2 Antibody, in a Randomized, Double-Blind, Placebo-Controlled Clinical Trial in Patients Hospitalized with Pneumonia and Presumed or Confirmed COVID-19.

BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) are characterized by progressive respiratory failure and the development of acute respiratory distress syndrome (ARDS), with high mortality rates for patients requiring mechanical ventilation. Levels of the vascular growth factor Angiopoietin 2 (Ang2) in plasma have been strongly correlated with increased ARDS risk in patients with pneumonia or sepsis. The intent of this study was to determine whether LY3127804, an anti-Ang2 monoclonal antibody, could reduce the need for mechanical ventilation among patients admitted to the hospital with pneumonia and presumed or confirmed COVID-19. METHODS: Patients admitted to hospital with confirmed pneumonia, presumed or confirmed COVID-19, and infiltrates on chest imaging and/or oxygen saturation of ≤ 95% on room air were stratified by age group (< 65 years and ≥ 65 years), sex, and site and randomly assigned 1:1 within each stratum to receive either LY3127804 (20 mg/kg) or placebo on Day 1 and possibly on Day 15. The primary end point for this study was number of days in which a patient did not require a ventilator over the 28-day study period. RESULTS: Interim analysis assessed study futility after 95 randomized patients had 28-day data available and showed no benefit of LY3127804 in reducing the number of ventilator days over placebo. The study was subsequently terminated. CONCLUSION: LY3127804 treatment did not decrease the need for ventilator usage in patients hospitalized with pneumonia and presumed or confirmed COVID-19. ClinicalTrialsgov identifier: NCT04342897.