Estimating quality-adjusted life expectancy (QALE) for local authorities in Great Britain and its association with indicators of the inclusive economy: a cross-sectional study.

OBJECTIVES: Quantifying area-level inequalities in population health can help to inform policy responses. We describe an approach for estimating quality-adjusted life expectancy (QALE), a comprehensive health expectancy measure, for local authorities (LAs) in Great Britain (GB). To identify potential factors accounting for LA-level QALE inequalities, we examined the association between inclusive economy indicators and QALE. SETTING: 361/363 LAs in GB (lower tier/district level) within the period 2018-2020. DATA AND METHODS: We estimated life tables for LAs using official statistics and utility scores from an area-level linkage of the Understanding Society survey. Using the Sullivan method, we estimated QALE at birth in years with corresponding 80% CIs. To examine the association between inclusive economy indicators and QALE, we used an open access data set operationalising the inclusive economy, created by the System Science in Public Health and Health Economics Research consortium. RESULTS: Population-weighted QALE estimates across LAs in GB were lowest in Scotland (females/males: 65.1 years/64.9 years) and Wales (65.0 years/65.2 years), while they were highest in England (67.5 years/67.6 years). The range across LAs for females was from 56.3 years (80% CI 45.6 to 67.1) in Mansfield to 77.7 years (80% CI 65.11 to 90.2) in Runnymede. QALE for males ranged from 57.5 years (80% CI 40.2 to 74.7) in Merthyr Tydfil to 77.2 years (80% CI 65.4 to 89.1) in Runnymede. Indicators of the inclusive economy accounted for more than half of the variation in QALE at the LA level (adjusted R2 females/males: 50%/57%). Although more inclusivity was generally associated with higher levels of QALE at the LA level, this association was not consistent across all 13 inclusive economy indicators. CONCLUSIONS: QALE can be estimated for LAs in GB, enabling further research into area-level health inequalities. The associations we identified between inclusive economy indicators and QALE highlight potential policy priorities for improving population health and reducing health inequalities.

Heterologous prime-boost with mRNA-1273 stimulates persistent neutralising antibodies in BBIBP-CorV-vaccinated individuals.

BBIBP-CorV inactivated vaccine is one of the most prevalent vaccines globally, but immune responses are far less studied than novel COVID-19 vaccine platforms. Longitudinal studies on BBIBP-CorV with homologous and heterologous booster doses are limited. This study follows a subset of participants from a national study comparing the immunogenicity of COVID-19 vaccines and levels of SARS-CoV-2 neutralising antibody (NAb). Homologous and heterologous booster dose significantly increased NAb levels in BBIBP-CorV-vaccinated individuals. Similar NAb levels were observed 1 month following BNT162b2 or mRNA-1273 booster. Interestingly, NAb persisted following mRNA-1273 booster (n = 95), but waned significantly at 6 and 9 months following BNT162b2 booster (n = 50; P > 0.001). The persistence of NAb was also observed following breakthrough infection. This study provides evidence that not all mRNA vaccines are equal in the longer term and should provide valuable information for policy makers planning booster programmes for BBIBP-CorV vaccinated populations.

Immunogenicity of COVID-19 vaccines and levels of SARS-CoV-2 neutralising antibody in the Bruneian population: Protocol for a national longitudinal study.

INTRODUCTION: Neutralising antibodies (NAbs) have been shown to be correlative of immune protection against SARS-CoV-2. We report the protocol for a national longitudinal study to assess and compare the level of NAbs generated in response to COVID-19 vaccines in Brunei Darussalam in adults 2-6 weeks post primary series (BBIBP-CorV, AZD1222, or mRNA-1273 vaccines) and their subsequent follow-up after administration of a third (booster-1) dose (BBIBP-CorV, mRNA-1273, or BNT162b2). METHODS AND ANALYSIS: Participant data will be extracted and processed from the national electronic health record system (Bru-HIMS) and the national mobile health application (BruHealth) into a research data platform. Eligible adults who have received their primary or booster vaccine will be invited using a stratified random sampling strategy based on age, gender and vaccine type (baseline target population, n=3000; 2-6 weeks post last dose). Blood serum will be isolated, and NAb levels assessed using the cPass surrogate virus neutralisation test. Baseline participants will then be screened for eligibility for subsequent longitudinal analysis. Those who have received a third dose will be followed up at 1, 3, 6, 9 and up to 12 months. NAb levels will be evaluated across the participant population according to vaccine platform/booster type, time since the last dose and correlated with demographic data. The study period is from December 2021 to January 2023 and aims to evaluate how NAb levels wane following a third vaccine dose across different vaccine platforms and determine the impact and rate of breakthrough infections. ETHICS AND DISSEMINATION: This study has been approved by the Medical and Ethical Research Committee of Ministry of Health, Brunei Darussalam. Individual NAb test results will be shared with each participant by text message. The findings from this study will help policy-makers in Brunei develop future vaccination strategies and establish regulations across multiple agencies.

Technology-assisted adaptive recruitment strategy for a large nation-wide COVID-19 vaccine immunogenicity study in Brunei.

A national study was conducted in Brunei to assess and compare the immunogenicity of the various brands of COVID-19 vaccines administered to the population as part of the National COVID-19 Vaccination Programme. Most of the population have had received at least 2 doses of BBIBP-CorV, AZD1222 or MRNA-1273 vaccines. Neutralising antibodies against SARS-CoV-2 induced by these vaccines will be analysed to infer population-level immune protection against COVID-19. During the 5-week recruitment period, 24,260 eligible individuals were invited to the study via SMS, out of which 2,712 participants were enrolled into the study. This paper describes the novel adaptive strategy used to recruit the study participants. Digital technology was leveraged to perform targeted online recruitment to circumvent the limitations of traditional recruitment methods. Technology also enabled stratified random selection of these eligible individuals who were stratified based on age, gender and vaccine brand. Data was extracted from the electronic health records, the national mobile health application and a third-party survey platform and integrated into a dedicated research platform called EVYDResearch. The instant availability and access to up-to-date data on EVYDResearch enabled the study team to meet weekly and adopt an adaptive recruitment strategy informed by behavioural science, where interventions could be quickly implemented to improve response rates. Some examples of these include incorporating nudge messaging into SMS invitations, involving the Minister of Health to make press announcements on this study, media coverage, setting up an enquiries hotline and reaching out to foreign language speaking expatriates of a local multinational company to participate in this study. Data integration from various data sources, real time information sharing and a strong teamwork led to good outcomes adaptable to the progress of recruitment, compared to the more time-consuming and static traditional recruitment methods.

Herbal Plants: The Role of AhR in Mediating Immunomodulation.

The prevalence of chronic inflammatory diseases including inflammatory bowel disease (IBD), autoimmunity and cancer have increased in recent years. Herbal-based compounds such as flavonoids have been demonstrated to contribute to the modulation of these diseases although understanding their mechanism of action remains limited. Flavonoids are able to interact with cellular immune components in a distinct way and influence immune responses at a molecular level. In this mini review, we highlight recent progress in our understanding of the modulation of immune responses by the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor whose activity can be regulated by diverse molecules including flavonoids. We focus on the role of AhR in integrating signals from flavonoids to modulate inflammatory responses using in vitro and experimental animal models. We also summarize the limitations of these studies. Medicinal herbs have been widely used to treat inflammatory disorders and may offer a valuable therapeutic strategy to treat aberrant inflammatory responses by modulation of the AhR pathway.

Understanding and responding to COVID-19 in Wales: protocol for a privacy-protecting data platform for enhanced epidemiology and evaluation of interventions.

INTRODUCTION: The emergence of the novel respiratory SARS-CoV-2 and subsequent COVID-19 pandemic have required rapid assimilation of population-level data to understand and control the spread of infection in the general and vulnerable populations. Rapid analyses are needed to inform policy development and target interventions to at-risk groups to prevent serious health outcomes. We aim to provide an accessible research platform to determine demographic, socioeconomic and clinical risk factors for infection, morbidity and mortality of COVID-19, to measure the impact of COVID-19 on healthcare utilisation and long-term health, and to enable the evaluation of natural experiments of policy interventions. METHODS AND ANALYSIS: Two privacy-protecting population-level cohorts have been created and derived from multisourced demographic and healthcare data. The C20 cohort consists of 3.2 million people in Wales on the 1 January 2020 with follow-up until 31 May 2020. The complete cohort dataset will be updated monthly with some individual datasets available daily. The C16 cohort consists of 3 million people in Wales on the 1 January 2016 with follow-up to 31 December 2019. C16 is designed as a counterfactual cohort to provide contextual comparative population data on disease, health service utilisation and mortality. Study outcomes will: (a) characterise the epidemiology of COVID-19, (b) assess socioeconomic and demographic influences on infection and outcomes, (c) measure the impact of COVID-19 on short -term and longer-term population outcomes and (d) undertake studies on the transmission and spatial spread of infection. ETHICS AND DISSEMINATION: The Secure Anonymised Information Linkage-independent Information Governance Review Panel has approved this study. The study findings will be presented to policy groups, public meetings, national and international conferences, and published in peer-reviewed journals.

Counting Coronavirus Disease 2019 (COVID-19) Cases: Case Definitions, Screened Populations and Testing Techniques Matter.

While counting cases of disease appears straightforward, there are issues to consider when enumerating disease counts during an epidemic. For example, for Coronavirus Disease-2019 (COVID-19), how is a case defined? Hubei province in China changed its case definition twice in a fortnight-from laboratory-confirmed cases to clinically-confirmed cases without laboratory tests, and back to laboratory-confirmed cases. This caused confusion in the reported number of cases. If a confirmed case requires laboratory testing, what is the population who are laboratory-tested? Due to limited laboratory testing capacity in the early phase of an emerging epidemic, only "suspected cases" are laboratory-tested in most countries. This will result in underdiagnosis of confirmed cases and also raises the question: how is a "suspect case" defined? With the passage of time and increased capability to perform laboratory tests, more people can be screened and the number of confirmed cases will increase. What are the technical considerations of laboratory testing? This includes specimen collection (variable collection methods), samples collected (upper or lower respiratory tract biospecimens), time of collection in relation to course of disease, different laboratory test methods and kits (not all of which may be standardised or approved by authorities such as the Food and Drug Administration). Are approved laboratory facilities and trained manpower available, and how are test results interpreted and false-negatives excluded? These issues will affect the accuracy of disease counts, which in turn will have implications on how we mount an appropriate response to the outbreak.

Brunei Darussalam: country report on children's environmental health.

This is the country report for Brunei Darussalam pertaining to children's environmental health. It covers the current landscape of environmental risk factors which affect children's health, existing local policies, as well as strategies for moving forward in alignment with the United Nation's Sustainable Development Goals (SDGs).

House dust mite sensitisation and association with atopic dermatitis in Brunei: Allergen sensitization and allergic disease in Brunei.

IgE sensitisation in tropical areas is under-reported. A 2 year retrospective cohort study of allergy data specific to aero and food allergens in Brunei demonstrated that specific IgE levels to house dust mite (Dermatophagoides pteronyssinus, D.farinae, Blomia tropicalis) were highest in this population and correlated with atopic dermatitis (p < 0.001). Shrimp and peanut were the most common food allergens. A dominance of house/storage mite sensitization is seen in Brunei which is consistent with other tropical countries.

Expression of kappa opioid receptors in developing rat brain - Implications for perinatal buprenorphine exposure.

Buprenorphine, a mu opioid receptor partial agonist and kappa opioid receptor (KOR) antagonist, is an emerging therapeutic agent for maternal opioid dependence in pregnancy and neonatal abstinence syndrome. However, the endogenous opioid system plays a critical role in modulating neurodevelopment and perinatal buprenorphine exposure may detrimentally influence this. To identify aspects of neurodevelopment vulnerable to perinatal buprenorphine exposure, we defined KOR protein expression and its cellular associations in normal rat brain from embryonic day 16 to postnatal day 23 with double-labelling immunohistochemistry. KOR was expressed on neural stem and progenitor cells (NSPCs), choroid plexus epithelium, subpopulations of cortical neurones and oligodendrocytes, and NSPCs and subpopulations of neurones in postnatal hippocampus. These distinct patterns of KOR expression suggest several pathways vulnerable to perinatal buprenorphine exposure, including proliferation, neurogenesis and neurotransmission. We thus suggest the cautious use of buprenorphine in both mothers and infants until its impact on neurodevelopment is better defined.

Using social media to support small group learning.

BACKGROUND: Medical curricula are increasingly using small group learning and less didactic lecture-based teaching. This creates new challenges and opportunities in how students are best supported with information technology. We explored how university-supported and external social media could support collaborative small group working on our new undergraduate medical curriculum. METHODS: We made available a curation platform (Scoop.it) and a wiki within our virtual learning environment as part of year 1 Case-Based Learning, and did not discourage the use of other tools such as Facebook. We undertook student surveys to capture perceptions of the tools and information on how they were used, and employed software user metrics to explore the extent to which they were used during the year. RESULTS: Student groups developed a preferred way of working early in the course. Most groups used Facebook to facilitate communication within the group, and to host documents and notes. There were more barriers to using the wiki and curation platform, although some groups did make extensive use of them. Staff engagement was variable, with some tutors reviewing the content posted on the wiki and curation platform in face-to-face sessions, but not outside these times. A small number of staff posted resources and reviewed student posts on the curation platform. CONCLUSIONS: Optimum use of these tools depends on sufficient training of both staff and students, and an opportunity to practice using them, with ongoing support. The platforms can all support collaborative learning, and may help develop digital literacy, critical appraisal skills, and awareness of wider health issues in society.

The Severity of Gliosis in Hippocampal Sclerosis Correlates with Pre-Operative Seizure Burden and Outcome After Temporal Lobectomy.

Astrogliosis and microgliosis in hippocampal sclerosis (HS) are widespread and are postulated to contribute to the pro-excitatory neuropathological environment. This study aimed to establish if seizure burden at the time of surgery or post-surgical outcome were correlated with the extent of gliosis in HS. As a secondary aim, we wanted to determine if the degree of gliosis could be predicted by pre-operative neuroimaging.Children and adults who underwent epilepsy surgery for HS between 2002 and 2011 were recruited (n = 43), and age-matched autopsy controls obtained (n = 15). Temporal lobe specimens were examined by DAB immunohistochemistry for astrocytes (glial fibrillary acidic protein (GFAP)) and microglia (CD68). Cell counting for GFAP and CD68 was performed and quantitative densitometry undertaken for GFAP. Seizure variables and outcome (Engel) were determined through medical record and patient review. Seizure frequency in the 6 months prior to surgery was measured to reflect the acute seizure burden. Duration of seizures, age at onset and age at operation were regarded to reflect chronic seizure burden. Focal, lobar and generalized atrophy on pre-operative MRI were independently correlated with the degree of cortical gliosis in the surgical specimen.In HS, both acute and chronic seizure burden were positively correlated with the degree of gliosis. An increase in reactive astrocyte number in CA3 was the strongest predictor of poor post-operative seizure outcome at 1 and 3 years post-operatively in this cohort. Changes in lower cortical astrocyte and upper cortical microglial number also correlated with post-operative outcome at 1 year. Post-surgical seizure outcome (1, 3 and 5 years) did not otherwise correlate with GFAP immunoreactivity (GFAP-IR) or CD68 immunoreactivity (CD68-IR). Increased microglial activation was detected in patients with pre-operative bilateral convulsive seizures, compared to those without convulsive seizures. Furthermore, focal, lobar and generalized atrophy on pre-operative neuroimaging were independently correlated with the degree of cortical gliosis in the surgical specimen.

Thou shalt not tweet unprofessionally: an appreciative inquiry into the professional use of social media.

BACKGROUND: Social media may blur the line between socialisation and professional use. Traditional views on medical professionalism focus on limiting motives and behaviours to avoid situations that may compromise care. It is not surprising that social media are perceived as a threat to professionalism. OBJECTIVE: To develop evidence for the professional use of social media in medicine. METHODS: A qualitative framework was used based on an appreciative inquiry approach to gather perceptions and experiences of 31 participants at the 2014 Social Media Summit. RESULTS: The main benefits of social media were the widening of networks, access to expertise from peers and other health professionals, the provision of emotional support and the ability to combat feelings of isolation. CONCLUSIONS: Appreciative inquiry is a tool that can develop the positive practices of organisations and individuals. Our results provide evidence for the professional use of social media that may contribute to guidelines to help individuals realise benefits and avoid harms.

Behaviour of transplanted tumours and role of matching in rejection.

BACKGROUND: Tumour transfer/development is one of the more serious risks associated with transplantation. The behaviour of a tumour can be unpredictable in immunosuppressed recipients. We report a highly sensitive method to monitor tumour behaviour in real time in a rodent tumour transplant model. This paper also explores the effect of MHC matching on tumour growth among control and immunosuppressed hosts. METHODS: Luciferase expressing Wistar rat kidney tumour cells were transplanted into either Wistar or Lewis recipients which mimic a well and poorly matched combination to assess the effects of MHC matching on transplanted tumour cells. Experimental groups included controls with no immunosuppression and animals immunosuppressed with cyclosporine. The latter group was further divided into a continuous treatment group which received four weeks of immunosuppression and a treatment withdrawal group where immunosuppression was stopped after two weeks to assess the effects of rejection on tumour growth. RESULTS: All the tumour cells were rejected in the control animals that received no immunosuppression, within 2 weeks among well-matched combination and within one week in the poorly matched combination (p 0.001). The transplanted tumour cells continued to grow in both well-matched and poorly matched groups who were treated with cyclosporine, but growth was significantly faster in the well-matched combination (p 0.033). After treatment withdrawal the tumour cells were rejected in all the animals of the poorly matched group compared to 50% in well matched animals within the four-week study period (p 0.039). CONCLUSION: In the absence of immunosuppression the hosts reject the transplanted tumour cells, and the anti-tumour response is stronger when there is a greater mismatch in MHC with the recipient. In the presence of cyclosporine immunosuppression the tumour continues to grow, however, after withdrawal of the immunosuppression, tumour clearance is quicker in the poorly matched background. This data supports the idea of expansion of the donor pool by using kidneys after ex vivo resection of small renal tumours and that these organs should be transplanted into a less well-matched HLA recipient. We hypothesise that should a tumour recurrence occur a poorly matched recipient could clear the tumour through withdrawal of immunosuppression.

Clinicopathological associations in temporal lobe epilepsy patients utilising the current ILAE focal cortical dysplasia classification.

OBJECTIVES: This study utilised the revised 2011 ILAE classification of focal cortical dysplasia (FCD) (Blümcke et al., 2011) to examine pathology in a cohort of children and adults who underwent temporal lobe epilepsy (TLE) surgery, and to describe the electroclinical and imaging features associated with these pathologies. METHODS: The sample population were children (n=26) and adults (n=47) who underwent TLE surgery between 2002 and 2011 at our institutions. Neuropathology and MRI studies were re-reviewed by experts blinded to the original diagnosis. EEG and clinical data including current seizure outcome were determined by patient file review and/or patient contact. Pre-operative data, post-operative outcome and pathological diagnoses were compared. RESULTS: The commonest pathology in the adult cohort was isolated hippocampal sclerosis (HS) (n=24, 51.1%) and in the paediatric cohort, isolated tumour (n=10, 38.5%). Overall, HS with associated FCD (FCD IIIA) was the third most common pathology (n=12, 16.4%). Temporal grey matter signal changes on MRI were associated with FCD IIIA (p=0.035). FCD IIIA had the poorest post-surgical seizure outcome compared to all other pathologies (p=0.026). A history of bilateral convulsive seizures was more common in adults (n=40, p<0.0005), and was associated with failure to achieve postoperative seizure freedom (p=0.045). Postoperatively, paediatric TLE had higher rates of seizure freedom (p=0.005) and more children had ceased medication (p<0.0005). SIGNIFICANCE: FCD IIIA is a comparatively common pathological subtype in TLE, with a poor post-surgical outcome. Pre-operative recognition of FCD IIIA may be feasible through grey matter signal change on MRI. Paediatric patients had a higher rate of seizure freedom than adults. Pre-operative bilateral convulsive seizures were associated with poor outcome after surgery.

Portal Venous Oxygen Persufflation of the Donation after Cardiac Death pancreas in a rat model is superior to static cold storage and hypothermic machine perfusion.

Success of clinical pancreatic islet transplantation depends on the mass of viable islets transplanted and the proportion of transplanted islets that survive early ischaemia reperfusion injury. Novel pancreas preservation techniques to improve islet preservation and viability can increase the utilization of donation after cardiac death donor pancreases for islet transplantation. Rat pancreases were retrieved after 30 min of warm ischaemia and preserved by static cold storage, hypothermic machine perfusion or retrograde portal venous oxygen persufflation for 6 h. They underwent collagenase digestion and density gradient separation to isolate islets. The yield, viability, morphology were compared. In vitro function of isolated islets was compared using glucose stimulated insulin secretion test. Portal venous oxygen persufflation improved the islet yield, viability and morphology as compared to static cold storage. The percentage of pancreases with good in vitro function (stimulation index > 1.0) was also higher after oxygen persufflation as compared to static cold storage. Retrograde portal venous oxygen persufflation of donation after cardiac death donor rat pancreases has the potential to improve islet yield.