Social, health and economic impact of COVID-19: Healthy Ageing In Scotland (HAGIS) - a protocol for a mixed-methods study.

INTRODUCTION: Public health responses to the COVID-19 pandemic have reaped adverse physical, psychological, social and economic effects, with older adults disproportionally affected. Psychological consequences of the pandemic include fear, worry and anxiety. COVID-19 fear may impact individuals' mitigation behaviours, influencing their willingness to (re)engage in health, social and economic behaviours. This study seeks (1) to develop a robust and evidence-based questionnaire to measure the prevalence of COVID-19 fear among older adults (aged ≥50) in Scotland and (2) to examine the impact of COVID-19 fear on the willingness of older adults to (re)engage across health, social and economic domains as society adjusts to the 'new normal' and inform policy and practice. METHODS AND ANALYSIS: This mixed-method study includes a large-scale multimodal survey, focus groups and interviews with older adults (aged ≥50) living in Scotland, and an email-based 'e-Delphi' consultation with professionals working with older adults. The COVID-19 fear scale was developed and validated using exploratory and confirmatory factor analyses. Survey data will be analysed using descriptive and inferential statistics. Thematic analysis will be used to analyse qualitative data. Survey and qualitative findings will be triangulated and used as the starting point for an 'e-Delphi' consensus consultation with expert stakeholders. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of Stirling for multimodal survey development, fieldwork methodology and data management. Anonymised survey data will be deposited with the UK Data Service, with a link provided via the Gateway to Global Ageing. Qualitative data will be deposited with the University of Stirling online digital repository-DataSTORRE. A dedicated work package will oversee dissemination via a coproduced project website, conference presentations, rapid reports and national and international peer-reviewed journal articles. There is planned engagement with Scottish and UK policy makers to contribute to the UK government's COVID-19 recovery strategy.

Psychological correlates of free colorectal cancer screening uptake in a Scottish sample: a cross-sectional observational study.

OBJECTIVES: Colorectal cancer (CRC) screening uptake in Scotland is 56%. This study examined whether psychological factors were associated with CRC screening uptake. DESIGN: Cross-sectional observational study. SETTING: This study used data from the Healthy AGeing In Scotland (HAGIS) pilot study, a study designed to be representative of Scottish adults aged 50 years and older. PARTICIPANTS: 908 (505 female) Scottish adults aged 50-80 years (mean age=65.85, SD=8.23), who took part in the HAGIS study (2016-2017). PRIMARY AND SECONDARY OUTCOME MEASURES: Self-reported participation in CRC screening was the outcome measure. Logistic regression was used to test whether scores on measures of health literacy, cognitive ability, risk aversion, time preference (eg, present oriented or future oriented) and personality were associated with CRC screening when these psychological factors were entered individually and simultaneously in the same model. RESULTS: Controlling for age, age-squared, sex, living arrangement, and sex*living arrangement, a one-point increase in risk aversion (OR=0.66, 95% CI 0.51 to 0.85) and present orientation (OR=0.86, 95% CI 0.80 to 0.94) was associated with reduced odds of screening. Higher scores on health literacy (OR per one-point increase=1.20, 95% CI 1.09 to 1.31), cognitive ability (OR per SD increase=1.51, 95% CI 1.25 to 1.81) and the intellect personality trait (OR per one-point increase=1.05, 95% CI 1.01 to 1.09) were associated with increased odds of screening. Higher risk aversion was the only psychological variable that was associated with CRC screening participation when all psychological variables were entered in the same model and remained associated with CRC screening when additionally adjusting for deprivation and education. A backward elimination model retained two psychological variables as correlates of CRC screening: risk aversion and cognitive ability. CONCLUSION: Individuals who are more risk averse are less likely to participate in free, home CRC screening.

Using Technology the Right Way to Support Social Connectedness for Older People in the Era of COVID-19.

The restrictions imposed in response to the COVID-19 pandemic pose significant risks to the human rights of older people from limitations in how people are able to engage with their social lives and from increased risk of discrimination linked to conceptualization of COVID-19 as a disease of the old. Further, COVID-19 increases risks of social isolation through public health and societal responses such as lockdowns. These responses have resulted in significant shifts in how citizens and service providers think about technology as a tool to allow people to stay socially connected. However, there are risks to the rights of older people inherent in the use of technology related to their ability to access technology and ageist assumptions that may limit engagement. The 'Technology and Social Connectedness' project was a pre-pandemic mixed-methods study involving evidence review, secondary analyses, and qualitative methods. Cross-dataset analyses led to evidence-based guidance to inform a rights-based approach to using technology. This paper provides analysis from the project that foregrounds a rights-based approach demonstrating how we developed the guidance within this framework and, contextualized within the pandemic response in Scotland, how that guidance can help others to protect and uphold the human rights of older people.

CovidLife: a resource to understand mental health, well-being and behaviour during the COVID-19 pandemic in the UK.

CovidLife is a longitudinal observational study designed to investigate the impact of the COVID-19 pandemic on mental health, well-being and behaviour in adults living in the UK. In total, 18,518 participants (mean age = 56.43, SD = 14.35) completed the first CovidLife questionnaire (CovidLife1) between April and June 2020. To date, participants have completed two follow-up assessments. CovidLife2 took place between July and August 2020 (n = 11,319), and CovidLife3 took place in February 2021 (n = 10,386). A range of social and psychological measures were administered at each wave including assessments of anxiety, depression, well-being, loneliness and isolation. Information on sociodemographic, health, and economic circumstances was also collected. Questions also assessed information on COVID-19 infections and symptoms, compliance to COVID-19 restrictions, and opinions on the UK and Scottish Governments' handling of the pandemic. CovidLife includes a subsample of 4,847 participants from the Generation Scotland cohort (N~24,000, collected 2006-2011); a well-characterised cohort of families in Scotland with pre-pandemic data on mental health, physical health, lifestyle, and socioeconomic factors, along with biochemical and genomic data derived from biological samples. These participants also consented to their study data being linked to Scottish health records. CovidLife and Generation Scotland data can be accessed and used by external researchers following approval from the Generation Scotland Access Committee. CovidLife can be used to investigate mental health, well-being and behaviour during COVID-19; how these vary according to sociodemographic, health and economic circumstances; and how these change over time. The Generation Scotland subsample with pre-pandemic data and linkage to health records can be used to investigate the predictors of health and well-being during COVID-19 and the future health consequences of the COVID-19 pandemic.

Conducting clinical trials in sub-Saharan Africa: challenges and lessons learned from the Malawi Cryptosporidium study.

BACKGROUND: An effective drug to treat cryptosporidial diarrhea in HIV-infected individuals is a global health priority. Promising drugs need to be evaluated in endemic areas which may be challenged by both lack of resources and experience to conduct International Committee of Harmonisation-Good Clinical Practice (ICH-GCP)-compliant clinical trials. METHODS: We present the challenges and lessons learned in implementing a phase 2A, randomized, double-blind, placebo-controlled trial of clofazimine, in treatment of cryptosporidiosis among HIV-infected adults at a single site in Malawi. RESULTS: Primary challenges are grouped under study initiation, study population, study implementation, and cultural issues. The lessons learned primarily deal with regulatory system and operational barriers, and recommendations can be applied to other human experimental trials in low- and middle-income countries, specifically in sub-Saharan Africa. CONCLUSION: This study demonstrated that initiating and implementing human experimental trials in sub-Saharan Africa can be challenging. However, solutions exist and successful execution requires careful planning, ongoing evaluation, responsiveness to new developments, and oversight of all trial operations.

Antibiotic Prescribing for Acute Respiratory Tract Infections 12 Months After Communication and CRP Training: A Randomized Trial.

PURPOSE: C-reactive-protein (CRP) is useful for diagnosis of lower respiratory tract infections (RTIs). A large international trial documented that Internet-based training in CRP point-of-care testing, in enhanced communication skills, or both reduced antibiotic prescribing at 3 months, with risk ratios (RRs) of 0.68, 0.53, 0.38, respectively. We report the longer-term impact in this trial. METHODS: A total of 246 general practices in 6 countries were cluster-randomized to usual care, Internet-based training on CRP point-of-care testing, Internet-based training on enhanced communication skills and interactive booklet, or both interventions combined. The main outcome was antibiotic prescribing for RTIs after 12 months. RESULTS: Of 228 practices providing 3-month data, 74% provided 12-month data, with no demonstrable attrition bias. Between 3 months and 12 months, prescribing for RTIs decreased with usual care (from 58% to 51%), but increased with CRP training (from 35% to 43%) and with both interventions combined (from 32% to 45%); at 12 months, the adjusted RRs compared with usual care were 0.75 (95% CI, 0.51-1.00) and 0.70 (95% CI, 0.49-0.93), respectively. Between 3 months and 12 months, the reduction in prescribing with communication training was maintained (41% and 40%, with an RR at 12 months of 0.70 [95% CI, 0.49-0.94]). Although materials were provided for free, clinicians seldom used booklets and rarely used CRP point-of-care testing. Communication training, but not CRP training, remained efficacious for reducing prescribing for lower RTIs (RR = 0.7195% CI, 0.45-0.99, and RR = 0.76; 95% CI, 0.47-1.06, respectively), whereas both remained efficacious for reducing prescribing for upper RTIs (RR = 0.60; 95% CI, 0.37-0.94, and RR = 0.58; 95% CI, 0.36-0.92, respectively). CONCLUSIONS: Internet-based training in enhanced communication skills remains effective in the longer term for reducing antibiotic prescribing. The early improvement seen with CRP training wanes, and this training becomes ineffective for lower RTIs, the only current indication for using CRP testing.

Pilot study protocol to inform a future longitudinal study of ageing using linked administrative data: Healthy AGeing in Scotland (HAGIS).

INTRODUCTION: Population ageing is a welcome testament to improvements in the social, economic and health circumstances over the life course. However, these successes necessitate that we understand more about the pathways of ageing to plan and cost our health and social care services, to support our ageing population to live healthier for longer and to make adequate provisions for retirement. Longitudinal studies of ageing facilitate such understanding in many countries around the world. Scotland presently does not have a longitudinal study of ageing, despite dramatic increases to its ageing population and its poor health record. Healthy AGeing in Scotland (HAGIS) constitutes the launch of Scotland's first comprehensive longitudinal study of ageing. METHODS: A sample of 1000 people aged 50+ years will be invited to take part in a household social survey. The innovative sampling procedure used administrative data to identify eligible households. Anonymised survey responses will be linked to administrative data. ETHICS AND DISSEMINATION: Ethics approval was obtained from the host institution for the study design and from the Public Benefits and Privacy Panel for administrative data linkage. Anonymised survey data will be deposited with the UK Data Service. A subset of survey data, harmonised with other global ageing studies, will be available via the Gateway to Global Aging platform. These data will enable powerful cross-country comparisons across the social, economic and health domains that will be relevant for national and international research.Research publications from the HAGIS team will be disseminated through journal articles and national and international conferences. The findings will support current and future research and policy debate on ageing populations.

Socioeconomic inequalities in breast and cervical screening coverage in England: are we closing the gap?

OBJECTIVE: Health policy in the UK is committed to tackling inequalities in cancer screening participation. We examined whether socioeconomic inequalities in breast and cervical cancer screening participation in England have reduced over five years. METHODS: Cross-sectional analyses compared cervical and breast screening coverage between 2007/8 and 2012/13 in Primary Care Trusts (PCTs) in England in relation to area-level income deprivation. RESULTS: At the start and the end of this five year period, there were socioeconomic inequalities in screening coverage for breast and cervical screening. Inequalities were highest for breast screening. Over time, the coverage gap between the highest and lowest quintiles of income deprivation significantly reduced for breast screening (from 12.3 to 8.3 percentage points), but not for cervical screening (5.3 to 4.9 percentage points). CONCLUSIONS: Efforts to reduce screening inequalities appear to have resulted in a significant improvement in equitable delivery of breast screening, although not of cervical screening. More work is needed to understand the differences, and see whether broader lessons can be learned from the reduction of inequalities in breast screening participation.

Variation in cervical and breast cancer screening coverage in England: a cross-sectional analysis to characterise districts with atypical behaviour.

OBJECTIVES: Reducing cancer screening inequalities in England is a major focus of the 2011 Department of Health cancer outcome strategy. Screening coverage requires regular monitoring in order to implement targeted interventions where coverage is low. This study aimed to characterise districts with atypical coverage levels for cervical or breast screening. DESIGN: Observational study of district-level coverage in the English Cervical and Breast screening programmes in 2012. SETTING: England, UK. PARTICIPANTS: All English women invited to participate in the cervical (age group 25-49 and 50-64) and breast (age group 50-64) screening programmes. OUTCOMES: Risk adjustment models for coverage were developed based on district-level characteristics. Funnel plots of adjusted coverage were constructed, and atypical districts examined by correlation analysis. RESULTS: Variability in coverage was primarily explained by population factors, whereas general practice characteristics had little independent effect. Deprivation and ethnicity other than white, Asian, black or mixed were independently associated with poorer coverage in both screening programmes, with ethnicity having the strongest effect; by comparison, the influence of Asian, black or mixed ethnic minority was limited. Deprivation, ethnicity and urbanisation largely accounted for the lower cervical screening coverage in London. However, for breast screening, being located in London remained a strong negative predictor. A subset of districts was identified as having atypical coverage across programmes. Correlates of deprivation in districts with relatively low adjusted coverage were substantially different from overall correlates of deprivation. DISCUSSION: These results inform the continuing drive to reduce avoidable cancer deaths in England, and encourage implementation of targeted interventions in communities residing in districts identified as having atypically low coverage. Sequential implementation to monitor the impact of local interventions would help accrue evidence on 'what works'.

Promoting early presentation of breast cancer: a preliminary evaluation of a written intervention.

OBJECTIVES: Older women are more likely to delay presentation with breast cancer, which contributes to poorer survival. We evaluated a written intervention that was designed to provide women with the knowledge, motivation, confidence and skills to present promptly with breast cancer symptoms. METHODS: We assessed acceptability and understanding of the intervention by interviewing 43 women. We used their responses to refine the intervention. We tested the effect of the intervention on breast cancer awareness, confidence and intentions to check breasts and perceived barriers to help-seeking using a self-report questionnaire administered to 61 women prior to and one month after receiving the intervention. Quantitative data were analysed using the McNemar test. RESULTS: Women were not made anxious by the intervention and understood its messages. At one month, a greater proportion of women knew that breast cancer risk increases with age, identified ≥5 non-lump symptoms and reported breast checking at least monthly in comparison to before the intervention was implemented. DISCUSSION: The intervention does not induce anxiety, is understandable, and appears to increase breast cancer awareness. The results provide justification for a more rigorous trial to test efficacy.

Evaluation of a web-based intervention to reduce antibiotic prescribing for LRTI in six European countries: quantitative process analysis of the GRACE/INTRO randomised controlled trial.

BACKGROUND: To reduce the spread of antibiotic resistance, there is a pressing need for worldwide implementation of effective interventions to promote more prudent prescribing of antibiotics for acute LRTI. This study is a process analysis of the GRACE/INTRO trial of a multifactorial intervention that reduced antibiotic prescribing for acute LRTI in six European countries. The aim was to understand how the interventions were implemented and to examine effects of the interventions on general practitioners' (GPs') and patients' attitudes. METHODS: GPs were cluster randomised to one of three intervention groups or a control group. The intervention groups received web-based training in either use of the C-reactive protein (CRP) test, communication skills and use of a patient booklet, or training in both. GP attitudes were measured before and after the intervention using constructs from the Theory of Planned Behaviour and a Website Satisfaction Questionnaire. Effects of the interventions on patients were assessed by a post-intervention questionnaire assessing patient enablement, satisfaction with the consultation, and beliefs about the risks and need for antibiotics. RESULTS: GPs in all countries and intervention groups had very positive perceptions of the intervention and the web-based training, and felt that taking part had helped them to reduce prescribing. All GPs perceived reducing prescribing as more important and less risky following the intervention, and GPs in the communication groups reported increased confidence to reduce prescribing. Patients in the communication groups who received the booklet reported the highest levels of enablement and satisfaction and had greater awareness that antibiotics could be unnecessary and harmful. CONCLUSIONS: Our findings suggest that the interventions should be broadly acceptable to both GPs and patients, as well as feasible to roll out more widely across Europe. There are also some indications that they could help to engender changes in GP and patient attitudes that will be helpful in the longer-term, such as increased awareness of the potential disadvantages of antibiotics and increased confidence to manage LRTI without them. Given the positive effects of the booklet on patient beliefs and attitudes, it seems logical to extend the use of the patient booklet to all patients.

Effects of internet-based training on antibiotic prescribing rates for acute respiratory-tract infections: a multinational, cluster, randomised, factorial, controlled trial.

BACKGROUND: High-volume prescribing of antibiotics in primary care is a major driver of antibiotic resistance. Education of physicians and patients can lower prescribing levels, but it frequently relies on highly trained staff. We assessed whether internet-based training methods could alter prescribing practices in multiple health-care systems. METHODS: After a baseline audit in October to December, 2010, primary-care practices in six European countries were cluster randomised to usual care, training in the use of a C-reactive protein (CRP) test at point of care, in enhanced communication skills, or in both CRP and enhanced communication. Patients were recruited from February to May, 2011. This trial is registered, number ISRCTN99871214. RESULTS: The baseline audit, done in 259 practices, provided data for 6771 patients with lower-respiratory-tract infections (3742 [55·3%]) and upper-respiratory-tract infections (1416 [20·9%]), of whom 5355 (79·1%) were prescribed antibiotics. After randomisation, 246 practices were included and 4264 patients were recruited. The antibiotic prescribing rate was lower with CRP training than without (33% vs 48%, adjusted risk ratio 0·54, 95% CI 0·42-0·69) and with enhanced-communication training than without (36% vs 45%, 0·69, 0·54-0·87). The combined intervention was associated with the greatest reduction in prescribing rate (CRP risk ratio 0·53, 95% CI 0·36-0·74, p<0·0001; enhanced communication 0·68, 0·50-0·89, p=0·003; combined 0·38, 0·25-0·55, p<0·0001). INTERPRETATION: Internet training achieved important reductions in antibiotic prescribing for respiratory-tract infections across language and cultural boundaries. FUNDING: European Commission Framework Programme 6, National Institute for Health Research, Research Foundation Flanders.

Women's responses to information about overdiagnosis in the UK breast cancer screening programme: a qualitative study.

OBJECTIVES: To explore the influence of overdiagnosis information on women's decisions about mammography. DESIGN: A qualitative focus group study with purposive sampling and thematic analysis, in which overdiagnosis information was presented. SETTING: Community and university settings in London. PARTICIPANTS: 40 women within the breast screening age range (50-71 years) including attenders and non-attenders were recruited using a recruitment agency as well as convenience sampling methods. RESULTS: Women expressed surprise at the possible extent of overdiagnosis and recognised the information as important, although many struggled to interpret the numerical data. Overdiagnosis was viewed as less-personally relevant than the possibility of 'under diagnosis' (false negatives), and often considered to be an issue for follow-up care decisions rather than screening participation. Women also expressed concern that information on overdiagnosis could deter others from attending screening, although they rarely saw it as a deterrent. After discussing overdiagnosis, few women felt that they would make different decisions about breast screening in the future. CONCLUSIONS: Women regard it as important to be informed about overdiagnosis to get a complete picture of the risks and benefits of mammography, but the results of this study indicate that understanding overdiagnosis may not always influence women's attitudes towards participation in breast screening. The results also highlight the challenge of communicating the individual significance of information derived from population-level modelling.

General practitioners' views on the acceptability and applicability of a web-based intervention to reduce antibiotic prescribing for acute cough in multiple European countries: a qualitative study prior to a randomised trial.

BACKGROUND: Interventions to promote prudent antibiotic prescribing by general practitioners (GPs) have often only been developed for use in one country. We aimed to develop an intervention which would be appropriate to implement in multiple European countries in order to offer greater benefit to practice whilst using fewer resources. The INTRO (INternet TRaining for antibiOtic use) intervention needed to deliver training to GPs in the use of C-Reactive Protein (CRP) near patient tests to help diagnose acute cough and in communication skills to help explain prescribing decisions to patients. We explored GPs' views on the initial version of INTRO to test acceptability and potentially increase applicability for use in multiple countries before the start of a randomised trial. METHOD: 30 GPs from five countries (Belgium, England, the Netherlands, Poland and Spain), were interviewed using a "think aloud" approach. GPs were asked to work through the intervention and discuss their views on the content and format in relation to following the intervention in their own practice. GPs viewed the same intervention but versions were created in five languages. Data were coded using thematic analysis. RESULTS: GPs in all five countries reported the view that the intervention addressed an important topic, was broadly acceptable and feasible to use, and would be a useful tool to help improve clinical practice. However, GPs in the different countries identified aspects of the intervention that did not reflect their national culture or healthcare system. These included perceived differences in communication style used in the consultation, consultation length and the stage of illness at which patient typically presented. CONCLUSION: An online intervention to support evidence-based use of antibiotics is acceptable and feasible to implement amongst GPs in multiple countries. However, tailoring of the intervention to suit national contexts was necessary by adding local information and placing more emphasis on the fact that GPs could select the communication skills they wished to use in practice. Using think aloud methods to complement the development of interventions is a powerful method to identify regional contextual barriers to intervention implementation.

Sequential mutations associated with adaptation of human cytomegalovirus to growth in cell culture.

Mutations that occurred during adaptation of human cytomegalovirus to cell culture were monitored by isolating four strains from clinical samples, passaging them in various cell types and sequencing ten complete virus genomes from the final passages. Mutational dynamics were assessed by targeted sequencing of intermediate passages and the original clinical samples. Gene RL13 and the UL128 locus (UL128L, consisting of genes UL128, UL130 and UL131A) mutated in all strains. Mutations in RL13 occurred in fibroblast, epithelial and endothelial cells, whereas those in UL128L were limited to fibroblasts and detected later than those in RL13. In addition, a region containing genes UL145, UL144, UL142, UL141 and UL140 mutated in three strains. All strains exhibited numerous mutations in other regions of the genome, with a preponderance in parts of the inverted repeats. An investigation was carried out on the kinetic growth yields of viruses derived from selected passages that were predominantly non-mutated in RL13 and UL128L (RL13+UL128L+), or that were largely mutated in RL13 (RL13-UL128L+) or both RL13 and UL128L (RL13-UL128L-). RL13-UL128L- viruses produced greater yields of infectious progeny than RL13-UL128L+ viruses, and RL13-UL128L+ viruses produced greater yields than RL13+UL128L+ viruses. These results suggest strongly that RL13 and UL128L exert at least partially independent suppressive effects on growth in fibroblasts. As all isolates proved genetically unstable in all cell types tested, caution is advised in choosing and monitoring strains for experimental studies of vulnerable functions, particularly those involved in cell tropism, immune evasion or growth temperance.

The products of human cytomegalovirus genes UL23, UL24, UL43 and US22 are tegument components.

We have investigated the human cytomegalovirus (HCMV) US22 gene family members UL23, UL24, UL43 and US22. Specific antibodies were generated to identify pUL23 (33 kDa), pUL24 (40 kDa) and pUL43 (48 kDa), while pUS22 was identified by monoclonal antibody HWLF1. A C-terminally truncated UL43 product (pUL43t; 21 kDa) produced by a deletion mutant was also investigated. The UL24 and UL43 genes were expressed with early-late (gamma1) and true-late (gamma2) kinetics, respectively. Immunoblot and immuno-EM studies demonstrated that pUL23, pUL24, pUL43 and pUS22 were virion tegument components. Immunofluorescence and immuno-EM studies showed that pUL23, pUL24, pUL43 and pUL43t were located in cytoplasmic protein aggregates, manifesting two forms: complex juxtanuclear structures and smaller, membrane-bound aggregates resembling dense bodies. The complex-type aggregate is a putative site of particle maturation. Because pUL43t was present in protein aggregates, but under-represented in virus particles compared to pUL43, it was concluded that N-terminal sequences target pUL43 to protein aggregates and that C-terminal sequences are important for incorporation into particles. Since three other US22 family products (pUL36, pTRS1 and pIRS1) are documented tegument components, at least seven of the twelve US22 family genes encode tegument proteins, suggesting that the products of the remaining five genes might be similarly located. These findings demonstrate a common biological feature among most, if not all, US22 family proteins and implicate the family in events occurring immediately after virus penetration.