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"Aldridge, Robert W"
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Spike-antibody waning after second dose of BNT162b2 or ChAdOx1
by
Fong, Wing Lam Erica
,
Aldridge, Robert W
,
Navaratnam, Annalan M D
in
Adults
,
Aged
,
Antibodies
2021
To identify early indications of waning antibody levels to the spike protein (S-antibody) after complete two-dose vaccination, we did a cross-sectional analysis of fully vaccinated adults (aged ≥18 years) who submitted capillary blood samples for Virus Watch, a longitudinal community cohort study in England and Wales.4 The study received ethical approval from the Hampstead NHS Health Research Authority Ethics Committee (20/HRA/2320). Sera were tested using Elecsys Anti-SARS-CoV-2 S and N electro-chemiluminescent immunoassays (Roche Diagnostics, Basel, Switzerland); the S assay targets total antibodies to the S1 subunit of the spike protein (range 0·4–25 000 units per mL [U/mL]), whereas the N assay targets total antibodies to the full-length nucleocapsid protein, which we took as a proxy for previous SARS-CoV-2 infection (specificity 99·8% [99·3–100]).5 Serological results were linked with demographic and clinical information collected at enrolment and with weekly self-reported vaccination status. 605 adults submitted a valid sample on June 14–15, 2021. In the context of recent advice in support of booster vaccinations from the UK's Joint Committee on Vaccination and Immunisation,13 and given the potentially rapid S-antibody decline suggested by these data, heterologous regimens, which preliminary data suggest elicit stronger antibody and T-cell responses,14,15 might provide more durable immunity and greater protection against emerging variants.
Journal Article
Global patterns of mortality in international migrants: a systematic review and meta-analysis
by
Aldridge, Robert W
,
Abubakar, Ibrahim
,
Barr, Anna Louise
in
Birth
,
Cause of Death
,
Clinical microbiology
2018
258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants.
In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608.
Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15·2 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0·70 [95% CI 0·65–0·76]; I2=99·8%). All-cause SMR was lower in both male migrants (0·72 [0·63–0·81]; I2=99·8%) and female migrants (0·75 [0·67–0·84]; I2=99·8%) compared with the general population. A mortality advantage was evident for refugees (SMR 0·50 [0·46–0·54]; I2=89·8%), but not for asylum seekers (1·05 [0·89–1·24]; I2=54·4%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population.
Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries.
Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants.
Journal Article
The UCL–Lancet Commission on Migration and Health: the health of a world on the move
by
Abubakar, Ibrahim
,
Aldridge, Robert W
,
Barreto, Mauricio L
in
Accountability
,
Bronchitis
,
Civil society
2018
With one billion people on the move or having moved in 2018, migration is a global reality, which has also become a political lightning rod. Although estimates indicate that the majority of global migration occurs within low-income and middle-income countries (LMICs), the most prominent dialogue focuses almost exclusively on migration from LMICs to high-income countries (HICs). Nowadays, populist discourse demonises the very same individuals who uphold economies, bolster social services, and contribute to health services in both origin and destination locations. Those in positions of political and economic power continue to restrict or publicly condemn migration to promote their own interests. Meanwhile nationalist movements assert so-called cultural sovereignty by delineating an us versus them rhetoric, creating a moral emergency. In response to these issues, the UCL-Lancet Commission on Migration and Health was convened to articulate evidence-based approaches to inform public discourse and policy. The Commission undertook analyses and consulted widely, with diverse international evidence and expertise spanning sociology, politics, public health science, law, humanitarianism, and anthropology. The result of this work is a report that aims to be a call to action for civil society, health leaders, academics, and policy makers to maximise the benefits and reduce the costs of migration on health locally and globally. The outputs of our work relate to five overarching goals that we thread throughout the report. First, we provide the latest evidence on migration and health outcomes. This evidence challenges common myths and highlights the diversity, dynamics, and benefits of modern migration and how it relates to population and individual health. Migrants generally contribute more to the wealth of host societies than they cost. Our Article shows that international migrants in HICs have, on average, lower mortality than the host country population. However, increased morbidity was found for some conditions and among certain subgroups of migrants, (eg, increased rates of mental illness in victims of trafficking and people fleeing conflict) and in populations left behind in the location of origin. Currently, in 2018, the full range of migrants’ health needs are difficult to assess because of poor quality data. We know very little, for example, about the health of undocumented migrants, people with disabilities, or lesbian, gay, bisexual, transsexual, or intersex (LGBTI) individuals who migrate or who are unable to move. Second, we examine multisector determinants of health and consider the implication of the current sector-siloed approaches. The health of people who migrate depends greatly on structural and political factors that determine the impetus for migration, the conditions of their journey, and their destination. Discrimination, gender inequalities, and exclusion from health and social services repeatedly emerge as negative health influences for migrants that require cross-sector responses. Third, we critically review key challenges to healthy migration. Population mobility provides economic, social, and cultural dividends for those who migrate and their host communities. Furthermore, the right to the highest attainable standard of health, regardless of location or migration status, is enshrined in numerous human rights instruments. However, national sovereignty concerns overshadow these benefits and legal norms. Attention to migration focuses largely on security concerns. When there is conjoining of the words health and migration, it is either focused on small subsets of society and policy, or negatively construed. International agreements, such as the UN Global Compact for Migration and the UN Global Compact on Refugees, represent an opportunity to ensure that international solidarity, unity of intent, and our shared humanity triumphs over nationalist and exclusionary policies, leading to concrete actions to protect the health of migrants. Fourth, we examine equity in access to health and health services and offer evidence-based solutions to improve the health of migrants. Migrants should be explicitly included in universal health coverage commitments. Ultimately, the cost of failing to be health-inclusive could be more expensive to national economies, health security, and global health than the modest investments required. Finally, we look ahead to outline how our evidence can contribute to synergistic and equitable health, social, and economic policies, and feasible strategies to inform and inspire action by migrants, policy makers, and civil society. We conclude that migration should be treated as a central feature of 21st century health and development. Commitments to the health of migrating populations should be considered across all Sustainable Development Goals (SDGs) and in the implementation of the Global Compact for Migration and Global Compact on Refugees. This Commission offers recommendations that view population mobility as an asset to global health by showing the meaning and reality of good health for all. We present four key messages that provide a focus for future action.
Journal Article
Changes in health in the countries of the UK and 150 English Local Authority areas 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
2018
Previous studies have reported national and regional Global Burden of Disease (GBD) estimates for the UK. Because of substantial variation in health within the UK, action to improve it requires comparable estimates of disease burden and risks at country and local levels. The slowdown in the rate of improvement in life expectancy requires further investigation. We use GBD 2016 data on mortality, causes of death, and disability to analyse the burden of disease in the countries of the UK and within local authorities in England by deprivation quintile.
We extracted data from the GBD 2016 to estimate years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and attributable risks from 1990 to 2016 for England, Scotland, Wales, Northern Ireland, the UK, and 150 English Upper-Tier Local Authorities. We estimated the burden of disease by cause of death, condition, year, and sex. We analysed the association between burden of disease and socioeconomic deprivation using the Index of Multiple Deprivation. We present results for all 264 GBD causes of death combined and the leading 20 specific causes, and all 84 GBD risks or risk clusters combined and 17 specific risks or risk clusters.
The leading causes of age-adjusted YLLs in all UK countries in 2016 were ischaemic heart disease, lung cancers, cerebrovascular disease, and chronic obstructive pulmonary disease. Age-standardised rates of YLLs for all causes varied by two times between local areas in England according to levels of socioeconomic deprivation (from 14 274 per 100 000 population [95% uncertainty interval 12 791–15 875] in Blackpool to 6888 [6145–7739] in Wokingham). Some Upper-Tier Local Authorities, particularly those in London, did better than expected for their level of deprivation. Allowing for differences in age structure, more deprived Upper-Tier Local Authorities had higher attributable YLLs for most major risk factors in the GBD. The population attributable fractions for all-cause YLLs for individual major risk factors varied across Upper-Tier Local Authorities. Life expectancy and YLLs have improved more slowly since 2010 in all UK countries compared with 1990–2010. In nine of 150 Upper-Tier Local Authorities, YLLs increased after 2010. For attributable YLLs, the rate of improvement slowed most substantially for cardiovascular disease and breast, colorectal, and lung cancers, and showed little change for Alzheimer's disease and other dementias. Morbidity makes an increasing contribution to overall burden in the UK compared with mortality. The age-standardised UK DALY rate for low back and neck pain (1795 [1258–2356]) was higher than for ischaemic heart disease (1200 [1155–1246]) or lung cancer (660 [642–679]). The leading causes of ill health (measured through YLDs) in the UK in 2016 were low back and neck pain, skin and subcutaneous diseases, migraine, depressive disorders, and sense organ disease. Age-standardised YLD rates varied much less than equivalent YLL rates across the UK, which reflects the relative scarcity of local data on causes of ill health.
These estimates at local, regional, and national level will allow policy makers to match resources and priorities to levels of burden and risk factors. Improvement in YLLs and life expectancy slowed notably after 2010, particularly in cardiovascular disease and cancer, and targeted actions are needed if the rate of improvement is to recover. A targeted policy response is also required to address the increasing proportion of burden due to morbidity, such as musculoskeletal problems and depression. Improving the quality and completeness of available data on these causes is an essential component of this response.
Bill & Melinda Gates Foundation and Public Health England.
Journal Article
Black, Asian and Minority Ethnic groups in England are at increased risk of death from COVID-19: indirect standardisation of NHS mortality data
by
Aldridge, Robert W.
,
Lewer, Dan
,
Mathur, Rohini
in
Age groups
,
Censuses
,
Confidence intervals
2020
Background : International and UK data suggest that Black, Asian and Minority Ethnic (BAME) groups are at increased risk of infection and death from COVID-19. We aimed to explore the risk of death in minority ethnic groups in England using data reported by NHS England. Methods : We used NHS data on patients with a positive COVID-19 test who died in hospitals in England published on 28th April, with deaths by ethnicity available from 1st March 2020 up to 5pm on 21 April 2020. We undertook indirect standardisation of these data (using the whole population of England as the reference) to produce ethnic specific standardised mortality ratios (SMRs) adjusted for age and geographical region. Results : The largest total number of deaths in minority ethnic groups were Indian (492 deaths) and Black Caribbean (460 deaths) groups. Adjusting for region we found a lower risk of death for White Irish (SMR 0.52; 95%CIs 0.45-0.60) and White British ethnic groups (0.88; 95%CIs 0.86-0.0.89), but increased risk of death for Black African (3.24; 95%CIs 2.90-3.62), Black Caribbean (2.21; 95%CIs 2.02-2.41), Pakistani (3.29; 95%CIs 2.96-3.64), Bangladeshi (2.41; 95%CIs 1.98-2.91) and Indian (1.70; 95%CIs 1.56-1.85) minority ethnic groups. Conclusion: Our analysis adds to the evidence that BAME people are at increased risk of death from COVID-19 even after adjusting for geographical region, but was limited by the lack of data on deaths outside of NHS settings and ethnicity denominator data being based on the 2011 census. Despite these limitations, we believe there is an urgent need to take action to reduce the risk of death for BAME groups and better understand why some ethnic groups experience greater risk. Actions that are likely to reduce these inequities include ensuring adequate income protection, reducing occupational risks, reducing barriers in accessing healthcare and providing culturally and linguistically appropriate public health communications.
Journal Article
SARS-CoV-2 antibodies and breakthrough infections in the Virus Watch cohort
2022
A range of studies globally demonstrate that the effectiveness of SARS-CoV-2 vaccines wane over time, but the total effect of anti-S antibody levels on risk of SARS-CoV-2 infection and whether this varies by vaccine type is not well understood. Here we show that anti-S levels peak three to four weeks following the second dose of vaccine and the geometric mean of the samples is nine fold higher for BNT162b2 than ChAdOx1. Increasing anti-S levels are associated with a reduced risk of SARS-CoV-2 infection (Hazard Ratio 0.85; 95%CIs: 0.79-0.92). We do not find evidence that this antibody relationship with risk of infection varies by second dose vaccine type (BNT162b2 vs. ChAdOx1). In keeping with our anti-S antibody data, we find that people vaccinated with ChAdOx1 had 1.64 times the odds (95% confidence interval 1.45-1.85) of a breakthrough infection compared to BNT162b2. We anticipate our findings to be useful in the estimation of the protective effect of anti-S levels on risk of infection due to Delta. Our findings provide evidence about the relationship between antibody levels and protection for different vaccines and will support decisions on optimising the timing of booster vaccinations and identifying individuals who should be prioritised for booster vaccination, including those who are older, clinically extremely vulnerable, or received ChAdOx1 as their primary course. Our finding that risk of infection by anti-S level does not interact with vaccine type, but that individuals vaccinated with ChAdOx1 were at higher risk of infection, provides additional support for the use of using anti-S levels for estimating vaccine efficacy.
Here the authors provide data from a sub-cohort of the Virus Watch study (19,556 adults) who completed at-home capillary blood sampling on a monthly basis and describe an association between anti-spike antibody levels and risk of SARS-CoV-2 infection.
Journal Article
Tuberculosis in migrants moving from high-incidence to low-incidence countries: a population-based cohort study of 519 955 migrants screened before entry to England, Wales, and Northern Ireland
by
Aldridge, Robert W
,
Abubakar, Ibrahim
,
White, Peter J
in
Cohort Studies
,
Disease control
,
England - epidemiology
2016
Tuberculosis elimination in countries with a low incidence of the disease necessitates multiple interventions, including innovations in migrant screening. We examined a cohort of migrants screened for tuberculosis before entry to England, Wales, and Northern Ireland and tracked the development of disease in this group after arrival.
As part of a pilot pre-entry screening programme for tuberculosis in 15 countries with a high incidence of the disease, the International Organization for Migration screened all applicants for UK visas aged 11 years or older who intended to stay for more than 6 months. Applicants underwent a chest radiograph, and any with results suggestive of tuberculosis underwent sputum testing and culture testing (when available). We tracked the development of tuberculosis in those who tested negative for the disease and subsequently migrated to England, Wales, and Northern Ireland with the Enhanced Tuberculosis Surveillance system. Primary outcomes were cases of all forms of tuberculosis (including clinically diagnosed cases), and bacteriologically confirmed pulmonary tuberculosis.
Our study cohort was 519 955 migrants who were screened for tuberculosis before entry to the UK between Jan 1, 2006, and Dec 31, 2012. Cases notified on the Enhanced Tuberculosis Surveillance system between Jan 1, 2006, and Dec 31, 2013, were included. 1873 incident cases of all forms of tuberculosis were identified, and, on the basis of data for England, Wales, and Northern Ireland, the estimated incidence of all forms of tuberculosis in migrants screened before entry was 147 per 100 000 person-years (95% CI 140–154). The estimated incidence of bacteriologically confirmed pulmonary tuberculosis in migrants screened before entry was 49 per 100 000 person-years (95% CI 45–53). Migrants whose chest radiographs were compatible with active tuberculosis but with negative pre-entry microbiological results were at increased risk of tuberculosis compared with those with no radiographic abnormalities (incidence rate ratio 3·2, 95% CI 2·8–3·7; p<0·0001). Incidence of tuberculosis after migration increased significantly with increasing WHO-estimated prevalence of tuberculosis in migrants' countries of origin. 35 of 318 983 pre-entry screened migrants included in a secondary analysis with typing data were assumed index cases. Estimates of the rate of assumed reactivation tuberculosis ranged from 46 (95% CI 42–52) to 91 (82–102) per 100 000 population.
Migrants from countries with a high incidence of tuberculosis screened before being granted entry to low-incidence countries pose a negligible risk of onward transmission but are at increased risk of tuberculosis, which could potentially be prevented through identification and treatment of latent infection in close collaboration with a pre-entry screening programme.
Wellcome Trust, UK National Institute for Health Research, UK Medical Research Council, Public Health England, and Department of Health Policy Research Programme.
Journal Article
Spike-antibody responses to COVID-19 vaccination by demographic and clinical factors in a prospective community cohort study
by
Fong, Wing Lam Erica
,
Braithwaite, Isobel
,
Aldridge, Robert W.
in
49/1
,
49/47
,
631/250/2152/2153/1291
2022
Vaccination constitutes the best long-term solution against Coronavirus Disease-2019; however, vaccine-derived immunity may not protect all groups equally, and the durability of protective antibodies may be short. We evaluate Spike-antibody responses following BNT162b2 or ChAdOx1-S vaccination amongst SARS-CoV2-naive adults across England and Wales enrolled in a prospective cohort study (Virus Watch). Here we show BNT162b2 recipients achieved higher peak antibody levels after two doses; however, both groups experience substantial antibody waning over time. In 8356 individuals submitting a sample ≥28 days after Dose 2, we observe significantly reduced Spike-antibody levels following two doses amongst individuals reporting conditions and therapies that cause immunosuppression. After adjusting for these, several common chronic conditions also appear to attenuate the antibody response. These findings suggest the need to continue prioritising vulnerable groups, who have been vaccinated earliest and have the most attenuated antibody responses, for future boosters.
Vaccination can provide reliable and long-lasting protection against COVID-19, however the immune response to vaccination can vary between individuals and can decline over time, leading to differences in protective effects. Here the authors assess the immune response to COVID-19 vaccination across a large cohort of previously uninfected adults and demonstrate lower post-vaccination antibody levels amongst those with immune-suppressing conditions and medications, as well as those with several other more common chronic conditions.
Journal Article
Accuracy of Probabilistic Linkage Using the Enhanced Matching System for Public Health and Epidemiological Studies
by
Aldridge, Robert W.
,
Abubakar, Ibrahim
,
Hayward, Andrew C.
in
Accuracy
,
Analysis
,
Antibiotics
2015
The Enhanced Matching System (EMS) is a probabilistic record linkage program developed by the tuberculosis section at Public Health England to match data for individuals across two datasets. This paper outlines how EMS works and investigates its accuracy for linkage across public health datasets.
EMS is a configurable Microsoft SQL Server database program. To examine the accuracy of EMS, two public health databases were matched using National Health Service (NHS) numbers as a gold standard unique identifier. Probabilistic linkage was then performed on the same two datasets without inclusion of NHS number. Sensitivity analyses were carried out to examine the effect of varying matching process parameters.
Exact matching using NHS number between two datasets (containing 5931 and 1759 records) identified 1071 matched pairs. EMS probabilistic linkage identified 1068 record pairs. The sensitivity of probabilistic linkage was calculated as 99.5% (95%CI: 98.9, 99.8), specificity 100.0% (95%CI: 99.9, 100.0), positive predictive value 99.8% (95%CI: 99.3, 100.0), and negative predictive value 99.9% (95%CI: 99.8, 100.0). Probabilistic matching was most accurate when including address variables and using the automatically generated threshold for determining links with manual review.
With the establishment of national electronic datasets across health and social care, EMS enables previously unanswerable research questions to be tackled with confidence in the accuracy of the linkage process. In scenarios where a small sample is being matched into a very large database (such as national records of hospital attendance) then, compared to results presented in this analysis, the positive predictive value or sensitivity may drop according to the prevalence of matches between databases. Despite this possible limitation, probabilistic linkage has great potential to be used where exact matching using a common identifier is not possible, including in low-income settings, and for vulnerable groups such as homeless populations, where the absence of unique identifiers and lower data quality has historically hindered the ability to identify individuals across datasets.
Journal Article
Anti-nucleocapsid and anti-spike antibody trajectories in people with post-covid condition versus acute-only infections: a nested longitudinal case-control study within the Virus Watch prospective cohort
by
Fong, Wing Lam Erica
,
Abubakar, Ibrahim
,
Aldridge, Robert W.
in
631/250/2152/2153/1291
,
631/326/596/4130
,
692/308/174
2025
People with Post-Covid Condition (PCC) may demonstrate aberrant immune responses post-infection; however, serological follow-up studies are limited. We aim to compare SARS-CoV-2 serological responses to infection and vaccination in people who develop PCC versus those with an acute infection only. Participants (
n
= 2010) are a sub-cohort of the Virus Watch community cohort in England who provided monthly finger-prick serological samples. We compare the likelihood of post-infection seroconversion using logistic mixed models and the trajectories of anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies using linear mixed models. Participants who developed PCC (
n
= 394) have 1.8x the odds of post-infection seroconversion for anti-N antibodies compared to those with an acute infection only (
n
= 1616) (odds ratio= 1.81 (95% confidence interval (CI) 1.16-2.90); however, these results are moderated by vaccination status and variant – with differences observed in pre-Omicron, unvaccinated participants. Anti-N levels, however, were elevated within 200 days post-infection in people with PCC compared to those without, after accounting for variant and vaccination status. Vaccination response (anti-S) pre- or post-infection did not systematically differ between groups. People with PCC demonstrate persistently higher anti-N antibody levels following primary infection compared to those with an acute infection only. These findings extend emerging evidence around infection-related immune activation and PCC.
In a sample of UK adults with mild-moderate infections, the authors find that anti-SARS-CoV-2 antibody responses to infection—but not vaccination—are persistently higher in people with Post-Covid Condition compared to people with an acute infection only.
Journal Article