Ruby Tsang

BACKGROUND The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) is one of Europe’s oldest sentinel systems, working with the UK Health Security Agency (UKHSA) and its predecessor bodies for 55 years. Its surveillance report now runs twice weekly, supplemented by online observatories. In addition to conducting sentinel surveillance from a nationally representative group of practices, the RSC is now also providing data for syndromic surveillance. OBJECTIVE Describe the cohort profile at the start of the 2021-2022 surveillance season and changes to our surveillance practice. METHODS The RSC’s pseudonymised primary care data, linked to hospital and other data, are held in the Oxford-RCGP Clinical Informatics Digital Hub (ORCHID), a trusted research environment (TRE). We describe the RSC’s cohort profile as of September 2021, divided into a primary care sentinel cohort (PCSC) - collecting virological and serological specimens - and a larger grou...

Late-life depression is one of the most common psychiatric disorders in older adults with a prevalence of 2–10 % in people aged 65 and above. Depression in old age has been associated with functional impairment and many adverse health effects. While there are overlapping symptoms and outcomes of depression throughout the life span, there is evidence for distinct medical, clinical, cognitive, neuroimaging, neuropathological, inflammatory and genetic features for geriatric depression in comparison with depression in young age (see Naismith et al. 2012). Older people with major depression have an increased risk of developing dementia, in particular Alzheimer’s disease and vascular dementia. There is strong evidence for cardiovascular risk factors being an underlying link between depression and dementia. A recent systematic review and meta-analysis showed that late-life depression is associated with a significant risk of all-cause dementia, Alzheimer’s disease and vascular dementia. However, the risk to develop vascular dementia was significantly higher than for Alzheimer’s disease (Diniz et al. 2013). Studies suggest that recurrent depression with an onset in midlife may reflect a long-term process of cerebrovascular changes that may be aetiologically related to the development of vascular dementia (Barnes et al. 2012).

The aim of this document is to provide guidance for DBMAS clinicians in their role of assisting residential aged care facility staff, community care staff and family members caring for persons living with dementia, who present with behaviours and psychological symptoms associated with dementia (BPSD). A comprehensive evidence and practice-based overview of BPSD management principles is provided with practical strategies and interventions for assisting care staff and care partners to manage behaviours in dementia. The empirical evidence contained in this Guide to Good Practice, in combination with clinical expertise may assist in achieving improved outcomes for those with dementia.

Background Caring for a person with dementia has profound physical, psychological, social and financial impacts on the carer, while morbidity in carers has detrimental effects on outcomes in people with dementia. A 10-day hospital-based residential carer training program (BMJ 299(6712):1375–1379, 1989) delayed residential care placement, delayed mortality, reduced carer’s psychological morbidity and lowered care costs. This study aims to evaluate the effects of a similar program adapted for use with residential respite. Methods/Design This is a single-arm longitudinal study conducted at a residential aged care facility involving 100 people with dementia and their primary carers. In a 7-day residential program, carers will attend intensive training sessions while the people with dementia are engaged in daily activities. Data will be collected at the start of the residential program (baseline), at 6 months (post 1) and at 12 months (post 2) after completion of the program. The primary...

IntroductionThe novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK.Methods and analysisWe will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case–control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-mode...

Introduction In July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. Aim Using a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection. Methods Individuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination. Results Overall VE was 74% (95% CI: 69–79), 76% (95% CI: 71–80), 63% (95% CI: 48–75) and 63% (95% CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥ 75 years, respectively. VE among those aged 30–59 years was 78% (95% CI: 75–81), 66% (95% CI: 58–73), 91% (95% CI: 87–94) and 52% (95% CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52–77), 65% (95% CI: 48–76) and 83% (95% CI: 64–92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirn...

BACKGROUND The Data and Connectivity COVID-19 Vaccines Pharmacovigilance (DaC-VaP) UK-wide collaboration was created to monitor vaccine uptake and effectiveness and provide pharmacovigilance using routine clinical and administrative data. To monitor these, pooled analyses may be needed. However, variation in terminologies present a barrier as, England uses the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), while the rest of the UK uses the Readv2 terminology in primary care. The availability of data sources is not uniform across the UK. OBJECTIVE To use the concept mappings in the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to identify common concepts recorded and to report these in a repeated cross-sectional study. We plan to do this for vaccine coverage and two adverse events of interest (AEIs), cerebral venous sinus thrombosis (CVST) and anaphylaxis. We identified concept mappings to SNOMED CT, Readv2, the World Health Organisation...

BackgroundPeople with multiple health conditions are more likely to have poorer health outcomes and greater care and service needs; a reliable measure of multimorbidity would inform management strategies and resource allocation. This study aims to develop and validate a modified version of the Cambridge Multimorbidity Score in an extended age range, using clinical terms which are routinely used in electronic health records across the world (SNOMED CT).Methods and FindingsWe curated new variables describing 37 health conditions and modelled the associations between these and 1-year mortality risk using the Cox proportional hazard model in a development dataset (n=300,000). We then developed two simplified models – a 20-condition model as per the original Cambridge Multimorbidity Score, and a variable reduction model using backward elimination with Akaike information criterion as the stopping criterion. The results were compared and validated for 1-year mortality in a synchronous vali...

COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness among individuals with clinical conditions that place them at increased risk of severe disease are limited. We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 among individuals in clinical risk groups using cohort and test-negative case control designs. There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group; after a second dose, effectiveness was moderate (Pfizer: 59.6%, 95%CI 18.0-80.1%; AstraZeneca 60.0%, 95%CI -63.6-90.2%). In most clinical risk groups, immune response to primary vaccination was maintained and high levels of vaccine effectiveness were seen. Reduced antibody response and vaccine effectiveness were seen after 1 dose of vaccine among a broad immunosuppressed group, and second dose vaccine effectiveness was moderate. These findings support maximising coverage in immunosuppressed individuals and the policy of prioritisation of this group for third doses.

While population estimates suggest high vaccine effectiveness against SARS-CoV-2 infection, the protection for health care workers, who are at higher risk of SARS-CoV-2 exposure, is less understood. We conducted a national cohort study of health care workers in Wales (UK) from 7 December 2020 to 30 September 2021. We examined uptake of any COVID-19 vaccine, and the effectiveness of BNT162b2 mRNA (Pfizer-BioNTech) against polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection. We used linked and routinely collected national-scale data within the SAIL Databank. Data were available on 82,959 health care workers in Wales, with exposure extending to 26 weeks after second doses. Overall vaccine uptake was high (90%), with most health care workers receiving theBNT162b2 vaccine (79%). Vaccine uptake differed by age, staff role, socioeconomic status; those aged 50-59 and 60+ years old were 1.6 times more likely to get vaccinated than those aged 16-29. Medical and dental staff, and Allied Health Practitioners were 1.5 and 1.1 times more likely to get vaccinated, compared to nursing and midwifery staff. The effectiveness of the BNT162b2 vaccine was found to be strong and consistent across the characteristics considered; 52% three to six weeks after first dose, 86% from two weeks after second dose, though this declined to 53% from 22 weeks after the second dose. With some variation in rate of uptake, those who were vaccinated had a reduced risk of PCR-confirmed SARS-CoV-2 infection, compared to those unvaccinated. Second dose has provided stronger protection for longer than first dose but our study is consistent with waning from seven weeks onwards.

At the end of 2020, many countries commenced a vaccination programme against SARS-CoV-2. Public health authorities aim to prevent and interrupt outbreaks of infectious disease in social care settings. We aimed to investigate the association between the introduction of the vaccination programme and the frequency and duration of COVID-19 outbreaks in Northern Ireland (NI). We undertook an ecological study using routinely available national data. We used Poisson regression to measure the relationship between the number of RT-PCR confirmed COVID-19 outbreaks in care homes, and as a measure of community COVID-19 prevalence, the Office for National Statistics COVID-19 Infection Survey estimated the number of people testing positive for COVID-19 in NI. We estimated the change in this relationship and estimated the expected number of care home outbreaks in the absence of the vaccination programme. A Cox proportional hazards model estimated the hazard ratio of a confirmed COVID-19 care home outbreak closure. Care home outbreaks reduced by two-thirds compared to expected following the introduction of the vaccination programme, from a projected 1625 COVID-19 outbreaks (95% prediction interval 1553-1694) between 7 December 2020 and 28 October 2021 to an observed 501. We estimated an adjusted hazard ratio of 2.53 of the outbreak closure assuming a 21-day lag for immunity. These findings describe the association of the vaccination with a reduction in outbreak frequency and duration across NI care homes. This indicates probable reduced harm and disruption from COVID-19 in social care settings following vaccination. Future research using individual level data from care home residents will be needed to investigate the effectiveness of the vaccines and the duration of their effects.

IntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. We measured COVID-19 vaccine effectiveness (VE) against symptomatic infection, using a multicentre test-negative study at primary care/community level in Europe.MethodsPatients presenting with COVID-19/ARI symptoms at primary care/community level in 10 countries were tested for SARS-CoV-2. We measured complete primary course overall VE among those aged 30–44, 45–59, 60–74 and ≥75 years, and among those 30–59 and ≥60 years by vaccine brand and by time since vaccination.ResultsOverall VE was 74% (95%CI: 69–79), 76% (95%CI: 71–80), 63% (95%CI: 48–75), 63% (95%CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥75 years, respectively. VE among those aged 30–59 years was 78% (95%CI: 75–81), 66% (95%CI: 58–73), 91% (95%CI: 87–94) and 52% (95%CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among those aged ≥60 years was 67% (95%CI: 52–77), 65% (95%CI: 48–76)...

BACKGROUND Vaccination is the most effective form of prevention of seasonal influenza; the UK has a national influenza vaccination programme to cover targeted population groups. Influenza vaccines are known to be associated with some common minor adverse events of interest (AEIs), but it is not known if the adjuvanted trivalent influenza vaccine (aTIV), first offered in the 2018/19 season) would be associated with more AEIs than other types of vaccines. OBJECTIVE We aim to compare the incidence of AEIs associated with different types of seasonal influenza vaccines offered in the 2018/19 season. METHODS We carried out a retrospective cohort study using computerised medical record data from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network database. We extracted data on vaccine exposure and consultations for European Medicines Agency (EMA)-specified AEIs for the 2018/19 influenza season. We used a self-controlled case series desi...

BackgroundIndividuals with depression are often found to perform worse on cognitive tests and to have an increased risk of dementia. The causes and the direction of these associations are however not well understood. We looked at two specific hypotheses, the aetiological risk factor hypothesis and the reverse causality hypothesis.MethodWe analysed observational data from two cohorts, English Longitudinal Study of Ageing (ELSA) and Health and Retirement Study (HRS), using cross-lagged panel models with unit fixed effects. Each model was run once with depression and repeated with cognition as the dependent variable and the other variable as the main explanatory variable. All models were estimated separately for contemporaneous effects and lagged effects up to 8 years in the past. We contrasted the results with models making the random effects assumption.ResultsEvidence from the fixed effects models is mixed. We find no evidence for the reverse causality hypothesis in ELSA and HRS. Whi...

Children may have a foundational role in efforts to raise community awareness about dementia. There is some qualitative work with children with a relative with dementia, but little work into the insights of children as general citizens without affected family. One issue is an absence of measurement tools; thus the study aimed to design and pilot a psychometrically sound self-report measure of dementia attitudes for children. Using a multi-staged scale development process, stakeholder and expert input informed a 52-item Kids Insight into Dementia Survey (KIDS). After a pretest of KIDS with 21 Australian schoolchildren aged 10-12 years, exploratory factor analysis and reliability and validity testing were run on a revised KIDS with data from 203 similar-aged schoolchildren. The KIDS was reduced from 52 to 14 items, and a three-factor solution identified: 'Personhood,' 'Stigma,' and 'Dementia Understanding.' A strong positive correlation with an adult measure of...

We measured COVID-19 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection at primary care/outpatient level among adults ≥ 65 years old using a multicentre test-negative design in eight European countries. We included 592 SARS-CoV-2 cases and 4,372 test-negative controls in the main analysis. The VE was 62% (95% CI: 45–74) for one dose only and 89% (95% CI: 79–94) for complete vaccination. COVID-19 vaccines provide good protection against COVID-19 presentation at primary care/outpatient level, particularly among fully vaccinated individuals.

Late-life depression (LLD) is thought to be multifactorial in etiology, with a significant genetic component. While a number of candidate gene studies have been carried out, results remain inconclusive. We undertook a systematic review of all genetic association studies of depression or depressive symptoms in late life published before February 2016, and performed meta-analyses on polymorphisms investigated in three or more independent studies. A total of 46 candidate gene studies examining 56 polymorphisms in 23 genes as well as a genome-wide association study (GWAS) were included. Meta-analyses were conducted for four polymorphisms using random effects models, of which three (APOE, BDNF, SLC6A4) were associated with LLD. These genes are implicated in hippocampal plasticity and stress reactivity, suggesting that dysregulation of these pathways may contribute to LLD. Despite using a large sample, the only GWAS published to date identified only one genome-wide significant locus in the 5q21 region. In the future, larger genetic studies specifically examining LLD, including non-hypothesis-driven GWAS, are required to further identify genetic determinants of LLD.

Background: Caring for a person with dementia has profound physical, psychological, social and financial impacts
on the carer, while morbidity in carers has detrimental effects on outcomes in people with dementia. A 10-day
hospital-based residential carer training program (BMJ 299(6712):1375–1379, 1989) delayed residential care
placement, delayed mortality, reduced carer’s psychological morbidity and lowered care costs. This study aims to
evaluate the effects of a similar program adapted for use with residential respite.

Methods/Design: This is a single-arm longitudinal study conducted at a residential aged care facility involving 100
people with dementia and their primary carers. In a 7-day residential program, carers will attend intensive training
sessions while the people with dementia are engaged in daily activities. Data will be collected at the start of the
residential program (baseline), at 6 months (post 1) and at 12 months (post 2) after completion of the program. The
primary outcome is carer psychological distress. Secondary outcomes include carer burden, carer quality of life and
time to residential care placement.

Discussion: This study will provide evidence on the effectiveness of the program in reducing carer distress and
burden as well as delaying institutionalisation of the person with dementia, which may have important implications
for policy.

Non-demented community-dwelling older adults aged 70 – 90 years (n  1,037) randomly recruited from the electoral roll
completed neuropsychological and medical assessments over six years. The overall prevalence of mild cognitive impairment
(MCI) at baseline was 36.7%. Risk factors for MCI include APOE ε 4 allele carrier status, high homocysteine, heart disease,
poor odour identifi cation, low visual acuity and low mental activity, but notable age and sex differences were observed.
Neuropsychiatric symptoms were rare; depression was the most common and was associated with cognitive impairment in
at least one domain as well as subsequent dementia 2 years later. Poorer cognitively demanding functional abilities were
associated with cognitive impairment.

Biomarkers for cognitive impairment and decline were identified. Inflammatory markers and plasma apolipoprotein levels
were associated with poorer performance in the attention/processing speed domain. Measures of white matter lesions, white matter integrity, sulcal morphology and tractography were identified as novel biomarkers of early cognitive decline. Stronger deactivation in the posteromedial cortex with increasing memory load on functional MRI predicted future decline.

Compared to previous reports, our prevalence rates of MCI were higher but rates of progression to dementia and
reversion to normal were similar, as were risk factors for progression to dementia.

Background: The use of informant rating scales in older adults at risk of dementia may assist with early detection and intervention strategies. This study aims to evaluate whether informants rate greater cognitive change in patients with mild cognitive impairment (MCI) compared to cognitively intact individuals, and to determine the relationship between informant ratings of cognitive change and neuropsychological performance.Methods: One hundred and nine health-seeking older adults underwent clinical and neuropsychological assessments, and informants completed the Cambridge Behavioral Inventory-Revised (CBI-R). Patients were rated according to MCI criteria, including amnestic and non-amnestic subtypes, or as being cognitively intact. CBI-R ratings were evaluated with respect to MCI diagnosis and neuropsychological performance.Results: Compared to cognitively intact individuals, informants rated patients with MCI as having significantly more change in overall functioning (p < 0.05) as well as in specific domains of memory and orientation (p < 0.01), everyday skills (p < 0.05), and motivation (p < 0.05), even after controlling for depressive symptom severity. In further analyses, the non-amnestic MCI subgroup only had more informant-rated mood changes compared to the amnestic subgroup. In relation to neuropsychological performance, informant ratings were related to poorer visual memory, verbal learning and memory, language, and psychomotor speed, with correlations ranging from –0.19 to –0.43 (p < 0.05).Conclusions: These findings indicate that informants are sensitive to subtle early cognitive change in individuals with MCI, and that their ratings are related to objectively measured neuropsychological performance. Thus, the CBI-R may be valuable in assisting early screening and intervention processes.(Received November 03 2011)(Revised November 22 2011)(Revised December 16 2011)(Accepted December 18 2011)(Online publication February 03 2012)