Catharine R Gale’s research while affiliated with University of Southampton and other places

Background: While systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS) is untested. Accordingly, we quantified the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with subsequent ALS occurrence. Methods: We used data from UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centers between 2006 and 2010. Venous blood was collected at baseline in the full cohort and assayed for CRP, and repeat measurement was made 3-7 years later in a representative subgroup (N=14,514) enabling correction for regression dilution. ALS was ascertained via national hospitalization and mortality registries until 2021. We computed multivariable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles. Results: In an analytical sample of 400,884 initially ALS-free individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalizations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviors, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalizations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend ≤0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalizations (1.37; 1.05, 1.76) ascribed to ALS. Conclusions: Higher levels of CRP, a blood-based biomarker widely captured in clinical practice, is associated with moderately increased future risk of amyotrophic lateral sclerosis.

Importance: While systemic inflammation has been implicated in the aetiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS) is untested. Objective: To quantify the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with ALS occurrence. Design, Setting, Participants: UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centres between 2006 and 2010. Exposure: Venous blood was collected at baseline in the full cohort and assayed for CRP. Repeat measurement was made 3-7 years later in a representative subgroup (N=14,514) enabling correction for regression dilution. Main Outcome(s) and Measure(s): ALS as ascertained via national hospitalisation and mortality registries. We computed multi-variable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles. Results: In an analytical sample of 400,884 individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalisations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviours, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalisations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend≤0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalisations (1.37; 1.05, 1.76) ascribed to ALS. Conclusions and Relevance: Higher levels of CRP, a blood-based biomarker widely captured in clinical practice, were associated with a higher subsequent risk of ALS.

Aim In the absence of effective treatments for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder with high case fatality, there is a clear need to identify its primary risk factors. Methods UK Biobank is a prospective cohort study in which baseline data were captured between 2006 and 2010 in 502,649 participants aged 37 to 73 years. Follow-up for ALS hospitalisations and death was made via national registries. Results Eleven years of event surveillance gave rise to 301 hospitalisations and 279 deaths due to ALS. After adjustment for selected confounding factors, being older (hazard ratio per 10 year increase; 95% confidence interval: 1.92; 1.58, 2.33) and male (1.37; 1.00, 1.87) were associated with elevated rates of hospitalisation for ALS. Similar effects were apparent when death ascribed to the disorder was the outcome of interest. Of the remaining 23 social, biological, and behavioural risk indices, however, there was only a suggestion that taller people experienced an increased risk of hospitalisation (per SD increase: 1.31; 1.09, 1.59). Conclusion In the present, large-scale study, other than well known associations, we did not find convincing evidence of links with ALS for other risk indices.

Ethnic inequalities in coronavirus disease 2019 (COVID-19) hospitalizations and mortality have been widely reported but there is scant understanding of how they are embodied. The UK Biobank prospective cohort study comprises around half a million people who were aged 40-69 years at study induction between 2006 and 2010 when information on ethnic background and potential explanatory factors was captured. Study members were prospectively linked to a national mortality registry. In an analytical sample of 448,664 individuals (248,820 women), 705 deaths were ascribed to COVID-19 between 5th March, 2020 and 24th January, 2021. In age- and sex-adjusted analyses, relative to White participants, Black study members experienced around five times the risk of COVID-19 mortality (odds ratio; 95% confidence interval: 4.81; 3.28, 7.05), while there was a doubling in the South Asian group (2.05; 1.30, 3.25). Controlling for baseline comorbidities, social factors (including socioeconomic circumstances), and lifestyle indices attenuated this risk differential by 34% in Black study members (2.84; 1.91, 4.23) and 37% in South Asian individuals (1.57; 0.97, 2.55). The residual risk of COVID-19 deaths in ethnic minority groups may be ascribed to a range of unmeasured characteristics and requires further exploration.

Background As a neurodegenerative disorder with high case-fatality, there is a need to identify primary, modifiable risk factors for amyotrophic lateral sclerosis (ALS). Their detection has, however, proved elusive and this may be ascribed to the scarcity of well-characterised, sufficiently-powered cohort studies necessary to explore the aetiology of this rare condition. Methods UK Biobank is an on-going, closed, prospective cohort study in which 502,524 participants (273,420 women) have been linked to national hospital and mortality registries. Baseline data collection took place between 2006 and 2010 when a range of psychosocial, physiological, and demographic data were captured. Results Approximately 11 years of event surveillance gave rise to 301 hospitalisations and 279 deaths ascribed to ALS. After left censoring to account for reverse causality and adjustment for confounding factors, being older (hazard ratio per 10 year increase; 95% confidence interval: 1.92; 1.58, 2.33) and male (1.37; 1.00, 1.87) were associated with elevated rates of hospitalisation for ALS. Similar effects were apparent when death due to the disorder was the outcome of interest. Of the remaining 23 potential risk indices, however, there was only a suggestion that taller people experienced an increased risk of hospitalisation (per SD increase: 1.31; 1.09, 1.59). Conclusions In the present study, a comprehensive array of potential risk indices were essentially unrelated to later ALS.

Background: As a neurodegenerative disorder with high case-fatality, there is a need to identify primary, modifiable risk factors for amyotrophic lateral sclerosis (ALS). Their detection has, however, proved elusive and this may be ascribed to the scarcity of well-characterised, sufficiently-powered cohort studies necessary to explore the aetiology of this rare condition. Methods: UK Biobank is an on-going, closed, prospective cohort study in which 502,524 participants (273,420 women) have been linked to national hospital and mortality registries. Baseline data collection took place between 2006 and 2010 when a range of psychosocial, physiological, and demographic data were captured. Results: Approximately 11 years of event surveillance gave rise to 301 hospitalisations and 279 deaths ascribed to ALS. After left censoring to account for reverse causality and adjustment for confounding factors, being older (hazard ratio per 10 year increase; 95% confidence interval: 1.92; 1.58, 2.33) and male (1.37; 1.00, 1.87) were associated with elevated rates of hospitalisation for ALS. Similar effects were apparent when death due to the disorder was the outcome of interest. Of the remaining 23 potential risk indices, however, there was only a suggestion that taller people experienced an increased risk of hospitalisation (per SD increase: 1.31; 1.09, 1.59). Conclusions: In the present study, a comprehensive array of potential risk indices were essentially unrelated to later ALS.

Background: The onset of psychological distress most commonly occurs in adolescence and, in keeping with other exposures, is time-varying across the life course. Most studies of its association with mortality risk are, however, conducted in middle- and older-aged populations with a single baseline assessment of this characteristic. This may lead to an underestimation of the magnitude of distress-mortality relationship. Methods: We used data from the 1970 British Cohort Study, a prospective cohort study. Psychological distress and covariates were collected at ages 5, 10, and 26. Vital status was ascertained between ages 26 and 44 years. Results: Eighteen years of mortality surveillance of 5901 individuals (3221 women) gave rise to 74 deaths. After adjustment for a series of confounding factors which included early life socioeconomic status, birth characteristics, and cognition, relative to the unaffected group, distress in childhood only was associated with around a 50% elevation in mortality risk (hazard ratio; 95% confidence interval: 1.45; 0.84, 2.51), while distress in adulthood only was related to a doubling of risk (1.95; 0.90, 4.21). In study members with persistent distress symptoms (childhood and adulthood) there was a tripling of the death rate (3.10; 1.42, 6.74) (p-value for trend across these categories: 0.002). Conclusion: The suggestion of a strong association between life course distress and death warrants replication in a study with a greater number of events.

There is growing evidence of, and biological plausibility for, elevated levels of high-density lipoprotein cholesterol (HDL-C) being related to lower rates of respiratory disease. We tested whether pre-pandemic HDL-C within the normal range is associated with subsequent COVID-19 hospitalisations and death. We analysed data on participants from UK Biobank, a prospective cohort study, baseline data for which were collected between 2006 and 2010. Follow-up for COVID-19 was via hospitalisation records (1845 events in 317,306 individuals) and a national mortality registry (458 deaths in 317,833 individuals). After controlling for a series of confounding factors which included health behaviours, inflammatory markers, and socio-economic status, higher levels of HDL-C were related to a lower risk of later hospitalisation. The effect was linear (p-value for trend 0.001), whereby a 0.2 mmol/L increase in HDL-C was associated with a 7% lower risk (odds ratio; 95% confidence interval: 0.93; 0.90, 0.96). Corresponding relationships for mortality were markedly weaker, such that statistical significance at conventional levels were not apparent for both the linear trend (p-value 0.25) and the odds ratio per 0.2 mmol/L increase (0.98; 0.91, 1.05). While our finding for HDL-C and hospitalisations for COVID-19 raise the possibility that favourable modification of this cholesterol fraction via lifestyle changes or drug intervention may impact upon the risk of the disease, it warrants testing in other studies.

Background Whereas several predictors of COVID-19 vaccine hesitancy have been examined, the role of cognitive function following the widely publicised development of an inoculation is unknown. Accordingly, our objective was to test the association between scores from an array of cognitive function tests and self-reported vaccine hesitancy after the announcement of the successful testing of the Oxford University/AstraZeneca vaccine. Methods We used individual-level data from a pandemic-focused study (COVID Survey), a prospective cohort study nested within United Kingdom Understanding Society (Main Survey). In the week immediately following the announcement of successful testing of the first efficacious inoculation (November/December 2020), data on vaccine intentionality were collected in 11740 individuals (6702 women) aged 16-95. Pre-pandemic scores on general cognitive function, ascertained from a battery of six tests, were captured in 2011/12 wave of the Main Survey. Study members self-reported their intention to take up a vaccination for COVID-19. Results Of the study sample, 17.2% (N=1842) indicated they were hesitant about having the vaccine. After adjustment for age, sex, and ethnicity, study members with a lower baseline cognition score were markedly more likely to be vaccine hesitant (odds ratio per standard deviation lower score in cognition; 95% confidence interval: 1.76; 1.62, 1.90). Adjustment for mental and physical health plus household shielding status had no impact on these results, whereas controlling for educational attainment led to partial attenuation but the probability of hesitancy was still elevated (1.52; 1.37, 1.67). There was a linear association for vaccine hesitancy across the full range of cognition scores (p for trend: p<0.0001). Conclusions Erroneous social media reports might have complicated personal decision-making, leading to people with lower cognitive ability test scores being vaccine-hesitant. With people with lower cognition also experiencing higher rates of COVID-19 in studies conducted prior to vaccine distribution, these new findings are suggestive of a potential additional disease burden.