Cost-Effectiveness of Introducing Nuvaxovid to COVID-19 Vaccination in the United Kingdom: A Dynamic Transmission Model

Background/Objectives: Vaccination against SARS-CoV-2 remains a key measure to control COVID-19. Nuvaxovid, a recombinant Matrix-M–adjuvanted protein-based vaccine, showed similar efficacy to mRNA vaccines in clinical trials and real-world studies, with lower rates of reactogenicity. Methods: To support decision making on UK vaccine selection, a population-based compartmental dynamic transmission model with a cost-utility component was developed to evaluate the cost-effectiveness of Nuvaxovid compared with mRNA vaccines from a UK National Health Service perspective. The model was calibrated to official epidemiology statistics for mortality, incidence, and hospitalisation. Scenario and sensitivity analyses were conducted. Results: In the probabilistic base case, a Nuvaxovid-only strategy provided total incremental cost savings of GBP 1,338,323 and 1558 additional quality-adjusted life years (QALYs) compared with an mRNA-only vaccination strategy. Cost savings were driven by reduced cold chain-related operational costs and vaccine wastage, while QALY gains were driven by potential differences in vaccine tolerability. Probabilistic sensitivity analysis indicated an approximately 70% probability of cost-effectiveness with Nuvaxovid-only versus mRNA-only vaccination across most cost-effectiveness thresholds (up to GBP 300,000/QALY gained). Conclusions: Nuvaxovid remained dominant over mRNA vaccines in scenario analyses assessing vaccine efficacy waning, Nuvaxovid market shares, and the vaccinated population

Gait Rehabilitation for Early rheumatoid Arthritis Trial (GREAT): lessons learnt from a mixed-methods feasibility study and internal pilot trial

Background: People with rheumatoid arthritis experience foot and lower limb pain due to active synovitis, resulting in impaired lower limb function. Earlier intervention may help with prevention of functional decline. The aims of this research were to develop and evaluate a new gait rehabilitation intervention for people with early rheumatoid arthritis, evaluate its feasibility, and to test whether or not gait rehabilitation plus usual care is more clinically and cost-effective than usual care alone. Design and methods: We undertook a single-arm, repeated measures, pre- and post-intervention, mixed methods feasibility study with embedded qualitative components. We planned to undertake a pragmatic, two-arm, multi-centre, superiority randomised controlled trial, with health economic evaluation, process evaluation, and internal pilot. Setting and participants: Participants with early rheumatoid arthritis (<2 years post-diagnosis) were identified from early arthritis and rheumatology outpatient clinics and referred for intervention in either podiatry or physiotherapy clinics. Intervention(s): Participants were randomised to a gait rehabilitation programme (GREAT Strides) involving a 6-task gait circuit. Sessions were underpinned by motivational interviewing to facilitate behaviour change, supported by trained physiotherapists or podiatrists for a minimum of two sessions. Both groups received their normal usual care from the rheumatology multidisciplinary team. Main outcome measures: Outcome measures for the feasibility study were intervention acceptability, adherence using the Exercise Adherence Rating Scale (EARS) and fidelity using the Motivational Interviewing Treatment Integrity Scale (MITI). The main outcome measure for the internal pilot/RCT was the Foot Function Index disability subscale. Outcomes were measured at baseline, 3-months, 6-months and 12-months. Other outcomes: intervention acceptability questionnaire (IAQ), EARS, exercise treatment beliefs via the Theory of Planned Behaviour Questionnaire, intervention fidelity (MITI), health-related quality of life (EQ5D-5L). Results: Thirty-five participants were recruited for feasibility and 23 (65.7%) completed 12-week follow-up. Intervention acceptability was excellent; 21/23 were confident that it could help and would recommend it; 22/23 indicated it made sense to them. Adherence was good, with a median [IQR] EARS score of 17/24 [12.5–22.5]. Twelve participants’ and 9 therapists’ interviews confirmed intervention acceptability, identified perceptions of benefit, but highlighted some barriers to completion. MITI scores demonstrated good fidelity. The trial did not progress from internal pilot to full main trial as a result of low recruitment and high attrition, after fifty-three participants were recruited from nine sites over 12-months. Process evaluation confirmed good intervention acceptability and adherence, and fair fidelity. Evaluation of clinical and cost-effectiveness was not possible. Limitations: Significant delays were experienced with the impact of COVID-19, regulatory approvals, contracts, and site readiness, resulting in few sites opening in time and low recruitment capacity. Foot and/or ankle pain prevalence was lower than anticipated, resulting in a low potential participant pool and a low conversion rate from screening to enrolment. Conclusions: The GREAT Strides intervention was acceptable to people with early RA and intervention clinicians, safe, with good levels of adherence by participants, and fair intervention fidelity. The RCT stopped early following failure to meet recruitment targets. GREAT Strides is a promising intervention that could be adapted for future evaluations. A definitive trial of the GREAT Strides gait rehabilitation intervention still needs to be done. Study registration: ISRCTN (International Standard Randomised Controlled Trial Number) registry as ISRCTN14277030. Funding details: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (15/165/04)

Effect of ethnicity and other sociodemographic factors on attendance at ophthalmology appointments following referral from a Diabetic Eye Screening Programme: a retrospective cohort study.

BACKGROUND/AIMS: To examine the association between sociodemographic characteristics and attendance at Hospital Eye Service (HES) referrals from the Diabetic Eye Screening Programme (DESP), in a large, ethnically diverse urban population. METHODS: Retrospective cohort study (4 January 2016-12 August 2019) of people with diabetic retinopathy (DR) referred from an English DESP to a tertiary referral eye hospital. We conducted a multivariable logistic regression with attendance as the primary outcome, controlling for age, sex, ethnicity, Index of Multiple Deprivation, best eye visual acuity and baseline DR grade. RESULTS: Of 7793 people referred (mean age 64 years, 62.6% male, 13.9% white, 12.5% black, 25.3% South Asian, 6.5% any other Asian background, 19.3% no recorded ethnicity and 20.9% of 'Other' ethnic origin), 69% attended. Compared with white individuals, people of black ethnic origin were similarly likely to attend. South Asians and those of other Asian backgrounds were more likely, and people with 'Other' or missing ethnicity were less likely to attend. Those with higher levels of deprivation, younger (aged 18-45 years) and older (76-90 years) age groups and worse visual acuity were less likely to attend, whereas people identified as having proliferative DR in both eyes were more likely to attend. CONCLUSION: Sociodemographic patterns in attendance after referral from the DESP to the HES exist, and these do not appear to explain ethnic differences in more severe sight-threatening DR, suggesting other explanations. More work is needed to understand and reduce inequalities in HES attendance

Pitfalls and practical suggestions for using local field potential recordings in DBS clinical practice and research.

&#xD;Local field potential (LFP) recordings using chronically implanted sensing-enabled stimulators are a powerful tool for indexing symptom presence and severity in neurological and neuropsychiatric disorders, and for enhancing our neurophysiological understanding of brain processes. LFPs have gained interest as input signals for closed-loop deep brain stimulation (DBS) and can be used to inform DBS parameter selection. LFP recordings using chronically implanted sensing-enabled stimulators have various implementational challenges.&#xD;Approach: Here we describe our collective experience using BrainSense (Medtronic®) for clinical and research work. We aim to provide insightful tips and practical advice to empower readers with the knowledge needed to navigate the intricacies of the device and make the most out of its features.&#xD;Main results:&#xD;The central issues that apply to several BrainSense features encompass restricted compatibility of stimulation configuration with sensing, differences in electrophysiological signal properties between 'stimulation OFF' and 'stimulation ON at 0.0 mA', and challenges associated with the internal clock of the neurostimulator. In addition, since recordings are obtained from bipolar and not monopolar channels, spatial certainty regarding the distribution of LFPs around the DBS electrode is limited. Several options exist to synchronize LFP time series with external data streams, but standardization and generalization are lacking. The use of at-home chronic LFP recording is limited by a low temporal and spectral resolution. Regarding at-home LFP snapshots, LFP time series are not stored, parts of the power spectrum are censored when stimulating at high or low frequencies, and the stimulation amplitude is not readily available.&#xD;Significance: We discussed practical applications, implementation, system limitations, and pitfalls with the aim that sensing can be better applied for clinical practice and research.&#xD

Antibiotic Use in Pediatric Care in Ghana: A Call to Action for Stewardship in This Population

Background/Objectives: Antibiotic use is common among hospitalized pediatric patients. However, inappropriate use, including excessive use of Watch antibiotics, can contribute to antimicrobial resistance, adverse events, and increased healthcare costs. Consequently, there is a need to continually assess their usage among this vulnerable population. This was the objective behind this study. Methods: The medical records of all pediatric patients (under 12 years) admitted and treated with antibiotics at a Ghanaian Teaching Hospital between January 2022 and March 2022 were extracted from the hospital’s electronic database. The prevalence and appropriateness of antibiotic use were based on antibiotic choices compared with current guidelines. Influencing factors were also assessed. Results: Of the 410 admitted patients, 319 (77.80%) received at least one antibiotic. The majority (68.65%; n = 219/319) were between 0 and 2 years, and males (54.55%; n = 174/319). Ceftriaxone was the most commonly prescribed antibiotic (20.69%; n = 66/319), and most of the systemic antibiotics used belonged to the WHO Access and Watch groups, including a combination of Access and Watch groups (42.90%; n = 136/319). Neonatal sepsis (24.14%; n = 77/319) and pneumonia (14.42%; n = 46/319) were the most common diagnoses treated with antibiotics. Antibiotic appropriateness was 42.32% (n = 135/319). Multivariate analysis revealed ceftriaxone prescriptions (aOR = 0.12; CI = 0.02–0.95; p-value = 0.044) and surgical prophylaxis (aOR = 0.07; CI = 0.01–0.42; p-value = 0.004) were associated with reduced antibiotic appropriateness, while a pneumonia diagnosis appreciably increased this (aOR = 15.38; CI = 3.30–71.62; p-value < 0.001). Conclusions: There was high and suboptimal usage of antibiotics among hospitalized pediatric patients in this leading hospital. Antibiotic appropriateness was influenced by antibiotic type, diagnosis, and surgical prophylaxis. Targeted interventions, including education, are needed to improve antibiotic utilization in this setting in Ghana and, subsequently, in ambulatory care

Sudden cardiac death in patients with kidney failure on renal replacement therapy: An unsolved problem

Sudden cardiac death is an important cause of mortality in patients with kidney failure undergoing renal replacement therapy, either hemodialysis or peritoneal dialysis. The risk factors associated with sudden cardiac death in these patients only partly overlap with those in the general population. Kidney failure per se and hemodialysis therapy expose these patients to an increased risk of sudden cardiac death compared with individuals with preserved renal function. Studies of the implantable cardioverter defibrillator for primary prevention of sudden cardiac death in patients with kidney failure have failed to demonstrate its usefulness. Moreover, the incidence of complications associated with cardiac electronic device implantation in this population is extremely high. This review aims to provide an update on the available studies on the pathophysiology and prevention of sudden cardiac death in patients with kidney failure undergoing dialysis and to propose the adoption of clinical practices to reduce its incidence

Factors Associated With Retinal Vessel Traits in the Canadian Longitudinal Study on Aging

PURPOSE: To determine the factors cross-sectionally and longitudinally associated with retinal vessel diameter, total area, and tortuosity in the Canadian Longitudinal Study on Aging (CLSA). METHODS: Of the 30,097 adults between ages 45 and 85 years old in the CLSA Comprehensive Cohort, 26,076 had at least one retinal image gradable by QUARTZ, a deep-learning algorithm that automatically assessed image quality, distinguished between arterioles and venules, and estimated retinal vessel traits over the entire retina. Questions were asked about demographic, lifestyle, and medical factors. Blood pressure, cholesterol, and C-reactive protein were measured. Participants returned for follow-up 3 years later. Multiple linear regression was used to provide adjusted estimates. RESULTS: Current smoking was strongly associated with wider arteriolar and venular diameters and their widening over 3 years (P < 0.05). Current smoking was also associated with a larger arteriolar and venular area and a 3-year increase in venular area (P < 0.05). Obesity was positively associated with venular diameter, total venular area, 3-year change in total venular area, and venular tortuosity (P < 0.05). Diastolic blood pressure was negatively associated with both arteriolar and venular diameter, area, and tortuosity, both cross-sectionally and longitudinally (P < 0.05). Diabetes was associated with wider arteriolar diameters cross-sectionally, and type 1 diabetes was associated with 3-year widening of arteriolar diameters (P < 0.05). CONCLUSIONS: This work provides comprehensive information on the factors associated with retinal vessel traits and their change. Factors such as smoking, obesity, blood pressure, and diabetes were longitudinally related to retinal vessel traits, which play a role in the development of eye disease

Uptake rates of influenza vaccination in over 65s in Denmark: a comparison between Danish-born and migrant populations, 2015–21

WHO’s Immunization Agenda 2030 has placed renewed focus on life-course vaccination, including among migrants. Despite the availability of a seasonal vaccine, influenza remains a key contributor to winter excess mortality in Northern Europe, yet limited data on influenza vaccination uptake in migrants has been published. We analyzed Danish national registry data to determine influenza vaccine uptake across six flu seasons (2015/16–2020/21) among migrants (asylum-pathway and quota refugees, family reunified migrants) ≥65 years matched 1:6 on age and gender to Danish-born individuals. We used multivariate logistic regression models controlling for migrant status (immigration status, time in Denmark) and other sociodemographic variables (age, gender, nationality, urban/rural residence) to identify factors associated with influenza vaccination uptake. All analyses were done in R v4.2.1. Across all six seasons, overall flu vaccination uptake was 49.3% (Danish-born: 50.9%; migrant cohort: 39.4%). Migrants were less likely [odds ratio (OR): 0.66; 95% confidence interval (CI): 0.64–0.67] to receive an influenza vaccine across all seasons, with this gap widening from 2015/16 (OR: 0.78; 95% CI: 0.74–0.84) to the 2020/21 season (OR: 0.44; 95% CI: 0.42–0.46). Family-reunified migrants were less likely to receive an influenza vaccine across the study period than asylum-pathway and quota refugees and those from the Sub-Saharan Africa region had the lowest uptake in terms of area of origin. This large and unique dataset shows that migrant groups have lower uptake rates for influenza vaccination compared with Danish-born individuals, with the gap widening over time. Going forward, developing tailored interventions, co-developed in collaboration with communities themselves, will be key

Comparative analysis of glucuronoxylomannogalactan (GXMGal) and glucuronoxylomannan (GXM) antibody responses and their associations with cryptococcal disease status in people living with HIV

Background Cryptococcosis remains a major cause of mortality in people with HIV (PWH). While glucuronoxylomannan-binding immunoglobulin G (GXM-IgG) levels have been associated with disease status and survival, the clinical significance of glucuronoxylomannogalactan-binding IgG (GXMGal-IgG) has not been investigated. Methods We analyzed serological data from two previously reported cohorts of PWH: a prospective asymptomatic South African cohort (67 cryptococcal antigen [CrAg]-positive, 130 CrAg-negative), and a Vietnamese case-control cohort (30 with symptomatic cryptococcal meningitis [CM], 30 without), both followed for mortality for six months. Serum/plasma GXMGal-IgG levels were quantified by enzyme-linked immunosorbent assay and compared to previously reported GXM-IgG levels. Logistic regression adjusted for age, sex, and CD4 count examined associations between antibody levels and CrAg positivity or CM status, while Cox proportional hazards models adjusted for CD4 count estimated associations with time to mortality. Results Higher GXMGal-IgG was associated with CrAg positivity (odds ratio [OR], 1.64; 95% CI, 1.14-2.36), not CM status. Among individuals with asymptomatic cryptococcal antigenemia, higher GXMGal-IgG trended toward higher survival (hazards ratio [HR], 0.67; 95% CI, 0.41-1.09), but this was not statistically significant and no significant survival benefit was observed for those with CM. Conclusion GXMGal-IgG was associated with CrAg positivity and showed a modest trend toward survival for individuals with asymptomatic cryptococcal antigenemia but had limited predictive value for CM or mortality. These findings in antigenemia largely parallel previous observations for GXM-IgG, although associations observed were generally weaker. Further studies are needed to clarify the immune response to GXMGal and its potential diagnostic or prognostic significance

WHO defeating meningitis symposium, 3rd international symposium on Streptococcus agalactiae disease (ISSAD) in Rio de Janeiro, Brazil: State-of-the-art overview of S. agalactiae meningitis

A World Health Organization (WHO) Defeating Meningitis Symposium took place as part of the 3rd International Symposium on Streptococcus agalactiae disease (ISSAD) conference which was held in Rio de Janeiro, Brazil, from October 16–18, 2023. The symposium highlighted WHO's Defeating meningitis by 2030 global road map focusing on Group B Streptococcus (GBS) meningitis and provided an overview of the meningitis burden and main challenges faced to tackle the disease across the Americas, Africa, and Asia