COVID-19 related mortality and hospital admissions in the VIVALDI study cohort: October 2020-March 2023

Background: Long-term care facilities (LTCFs) were heavily affected by COVID-19 early in the pandemic, but the impact of the virus has reduced over time with vaccination campaigns and build-up of immunity from prior infection. // Objectives: To evaluate the mortality and hospital admissions associated with SARS-CoV-2 in LTCFs in England over the course of the VIVALDI study, from October 2020 to March 2023. // Methods: We included residents aged ≥65 years of participating LTCFs who had available follow-up time within the analysis period. We calculated incidence rates (IR) of COVID-19 linked mortality and hospital admissions per calendar quarter, along with infection fatality ratios (IFR, within 28d) and infection hospitalisation ratios (IHR, within 14d) following positive SARS-CoV-2 test. // Results: A total of 26286 residents were included, with at least one positive test for SARS-CoV-2 in 8513 (32.4%). The IR of COVID-19 related mortality peaked in the first quarter (Q1) 2021 at 0.47 per 1000 person-days (1kpd) (around a third of all deaths), in comparison to 0.10 per 1kpd for Q1 2023 which had a similar IR of SARS-CoV-2 infections. There was a fall in observed IFR for SARS-CoV-2 infections from 24.9% to 6.7% between these periods, with a fall in IHR from 12.1% to 8.8%. The population had high overall IRs for mortality for each quarter evaluated, corresponding to annual mortality probability of 28.8-41.3%. // Conclusions: Standardised real-time monitoring of hospitalisation and mortality following infection in LTCFs could inform policy on the need for non-pharmaceutical interventions to prevent transmission

Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of long-term care facilities in the VIVALDI study

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused severe disease in unvaccinated long-term care facility (LTCF) residents. Initial booster vaccination following primary vaccination is known to provide strong short-term protection, but data are limited on duration of protection and the protective effect of further booster vaccinations. OBJECTIVE: To evaluate the effectiveness of third, fourth and fifth dose booster vaccination against SARS-CoV-2 related mortality amongst older residents of LTCFs. DESIGN: Prospective cohort study. SETTING: LTCFs for older people in England participating in the VIVALDI study. METHODS: Residents aged >65 years at participating LTCFs were eligible for inclusion if they had at least one polymerase chain reaction or lateral flow device result within the analysis period 1 January 2022 to 31 December 2022. We excluded individuals who had not received at least two vaccine doses before the analysis period. Cox regression was used to estimate relative hazards of SARS-CoV-2 related mortality following 1-3 booster vaccinations compared with primary vaccination, stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF size (total beds). RESULTS: A total of 13,407 residents were included. Our results indicate that third, fourth and fifth dose booster vaccination provide additional short-term protection against SARS-CoV-2 related mortality relative to primary vaccination, with consistent stabilisation beyond 112 days to 45-75% reduction in risk relative to primary vaccination. CONCLUSIONS: Successive booster vaccination doses provide additional short-term protection against SARS-CoV-2 related mortality amongst older LTCF residents. However, we did not find evidence of a longer-term reduction in risk beyond that provided by initial booster vaccination

Fractional Brownian motion and multivariate-t models for longitudinal biomedical data, with application to CD4 counts in HIV-positive patients.

Longitudinal data are widely analysed using linear mixed models, with 'random slopes' models particularly common. However, when modelling, for example, longitudinal pre-treatment CD4 cell counts in HIV-positive patients, the incorporation of non-stationary stochastic processes such as Brownian motion has been shown to lead to a more biologically plausible model and a substantial improvement in model fit. In this article, we propose two further extensions. Firstly, we propose the addition of a fractional Brownian motion component, and secondly, we generalise the model to follow a multivariate-t distribution. These extensions are biologically plausible, and each demonstrated substantially improved fit on application to example data from the Concerted Action on SeroConversion to AIDS and Death in Europe study. We also propose novel procedures for residual diagnostic plots that allow such models to be assessed. Cohorts of patients were simulated from the previously reported and newly developed models in order to evaluate differences in predictions made for the timing of treatment initiation under different clinical management strategies. A further simulation study was performed to demonstrate the substantial biases in parameter estimates of the mean slope of CD4 decline with time that can occur when random slopes models are applied in the presence of censoring because of treatment initiation, with the degree of bias found to depend strongly on the treatment initiation rule applied. Our findings indicate that researchers should consider more complex and flexible models for the analysis of longitudinal biomarker data, particularly when there are substantial missing data, and that the parameter estimates from random slopes models must be interpreted with caution

Economic evaluation of a conditional cash transfer to retain women in the continuum of care during pregnancy, birth and the postnatal period in Kenya

There is limited evidence on the cost and cost-effectiveness of cash transfer programmes to improve maternal and child health in Kenya and other sub-Saharan African countries. This article presents the economic evaluation results of the Afya trial, assessing the costs, cost-effectiveness and equity impact of a demand-side financing intervention that promotes utilisation of maternal health services in rural Kenya. The cost of implementing the Afya intervention was estimated from a provider perspective. Cost data were collected prospectively from all implementing and non-implementing partners, and from health service providers. Cost-efficiency was analysed using cost-transfer ratios and cost per mother enrolled into the intervention. Cost-effectiveness was assessed as cost per additional eligible antenatal care visit as a result of the intervention, when compared with standard care. The equity impact of the intervention was also assessed using a multidimensional poverty index (MPI). Programme cost per mother enrolled was International (INT)$313 of which INT$ 92 consisted of direct transfer payments, suggesting a cost transfer ratio of 2.4. Direct healthcare utilisation costs reflected a small proportion of total provider costs, amounting to INT$21,756. The total provider cost of the Afya intervention was INT$808,942. The provider cost per additional eligible ANC visit was INT$1,035. This is substantially higher than estimated annual health expenditure per capita at the county level of$INT61. MPI estimates suggest around 27.4% of participant households were multidimensionally poor. MPI quintiles did not significantly modify the intervention effect, suggesting the impact of the intervention did not differ by socioeconomic status. Based on the available evidence, it is not possible to conclude whether the Afya intervention was cost-effective. A simple comparison with current health expenditure in Siaya county suggests that the intervention as implemented is likely to be unaffordable. Consideration needs to be given to strengthening the supply-side of the cash transfer intervention before replication or uptake at scale

Clinical effectiveness of SARS-CoV-2 booster vaccine against Omicron infection in residents and staff of Long-Term Care Facilities: a prospective cohort study (VIVALDI)

Background: Successive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused severe disease in long-term care facility (LTCF) residents. Primary vaccination provides strong short-term protection, but data are limited on duration of protection following booster vaccines, particularly against the Omicron variant. We investigated the effectiveness of booster vaccination against infections, hospitalizations, and deaths among LTCF residents and staff in England. Methods: We included residents and staff of LTCFs within the VIVALDI study (ISRCTN 14447421) who underwent routine, asymptomatic testing (December 12, 2021–March 31, 2022). Cox regression was used to estimate relative hazards of SARS-CoV-2 infection, and associated hospitalization and death at 0–13, 14–48, 49–83, 84–111, 112–139, and 140+ days after dose 3 of SARS-CoV-2 vaccination compared with 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex, LTCF capacity, and local SARS-CoV-2 incidence. Results: A total of 14 175 residents and 19 793 staff were included. In residents without prior SARS-CoV-2 infection, infection risk was reduced 0–111 days after the first booster, but no protection was apparent after 112 days. Additional protection following booster vaccination waned but was still present at 140+ days for COVID-associated hospitalization (adjusted hazard ratio [aHR], 0.20; 95% CI, 0.06–0.63) and death (aHR, 0.50; 95% CI, 0.20–1.27). Most residents (64.4%) had received primary course vaccine of AstraZeneca, but this did not impact pre- or postbooster risk. Staff showed a similar pattern of waning booster effectiveness against infection, with few hospitalizations and no deaths. Conclusions: Our findings suggest that booster vaccination provided sustained protection against severe outcomes following infection with the Omicron variant, but no protection against infection from 4 months onwards. Ongoing surveillance for SARS-CoV-2 in LTCFs is crucial

The Edinburgh claudication questionnaire has poor diagnostic accuracy in people with intermittent claudication

Background The screening and diagnosis of intermittent claudication is a challenging process and often relies on the expertise of specialist vascular clinicians. We sought to investigate the diagnostic performance of the Edinburgh Claudication Questionnaire (ECQ) as a screening tool for referrals of suspected intermittent claudication from primary to secondary care. Method Prospectively, 100 referrals from primary care with a stated diagnosis or query regarding intermittent claudication were recruited. All participants who completed the ECQ, underwent an anklebrachial pressure index (ABPI) assessment and treadmill exercise testing. Outcomes of the ECQ were compared to clinical diagnoses of intermittent claudication. Results The ECQ had a sensitivity of 46.8% (95% CI: 27–65%), specificity of 63.2% (95% CI: 43–82%) and accuracy of 53.0% (95% CI: 43–63%). The diagnostic performance was not changed by combining the ECQ with a positive ABPI or post-exercise ABPI outcome for PAD. Conclusion The ECQ had a poor diagnostic performance in this cohort. Considering the results found here and in other recent studies, the utility of the ECQ as a screening tool and epidemiological survey tool must be questioned. Novel, low-resource diagnostic tools are needed in this population

Protocol for the COG-UK hospital-onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in UK NHS hospitals

OBJECTIVES: Nosocomial transmission of SARS-CoV-2 has been a significant cause of mortality in National Health Service (NHS) hospitals during the COVID-19 pandemic. The COG-UK Consortium Hospital-Onset COVID-19 Infections (COG-UK HOCI) study aims to evaluate whether the use of rapid whole-genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, can inform infection prevention and control (IPC) practice within NHS hospital settings. DESIGN: Multicentre, prospective, interventional, superiority study. SETTING: 14 participating NHS hospitals over winter–spring 2020/2021 in the UK. PARTICIPANTS: Eligible patients must be admitted to hospital with first-confirmed SARS-CoV-2 PCR-positive test result >48 hour from time of admission, where COVID-19 diagnosis not suspected on admission. The projected sample size is 2380 patients. INTERVENTION: The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab processing) and within 5–10 days in a second phase (mimicking central lab), comparing the viral genome from an eligible study participant with others within and outside the hospital site. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes are incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. Health economic analysis will be conducted to determine cost benefit of the intervention. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study. TRIAL REGISTRATION NUMBER: ISRCTN50212645. Pre-results stage. This manuscript is based on protocol V.6.0. 2 September 2021

SARS-CoV-2 anti-spike antibody levels following second dose of ChAdOx1 nCov-19 or BNT162b2 in residents of long-term care facilities in England (VIVALDI)

General population studies have shown strong humoral response following SARS-CoV-2 vaccination with subsequent waning of anti-spike antibody levels. Vaccine-induced immune responses are often attenuated in frail and older populations, but published data are scarce. We measured SARS-CoV-2 anti-spike antibody levels in Long-Term Care Facility residents and staff following second vaccination dose with Oxford-AstraZeneca or Pfizer-BioNTech. Vaccination elicited robust antibody responses in older residents, suggesting comparable levels of vaccine-induced immunity to that in the general population. Antibody levels are higher after Pfizer-BioNTech vaccination but fall more rapidly compared to Oxford-AstraZeneca recipients and are enhanced by prior infection in both groups