Traumatic events and their relative PTSD burden in Northern Ireland: a consideration of the impact of the ‘Troubles’

Purpose

Over a 30-year period in its recent history, daily life in Northern Ireland (NI) was characterised by civil violence, colloquially termed as the ‘Troubles’. The current report examines exposure to 29 traumatic event types and the associated conditional prevalence of post-traumatic stress disorder (PTSD) among the Northern Ireland population, with a focus on the impact of traumatic events that were characteristic of the NI ‘Troubles’.

Method

Results presented are based on analysis of data from the Northern Ireland Study of Health and Stress (NISHS). The NISHS is a representative epidemiological study of mental health among the NI adult population (N = 4,340) and part of the World Mental Health Survey Initiative.

Results

Perpetration of violence, physical assault by a spouse or partner and private events were the event types associated with the highest conditional prevalence of PTSD. Despite this elevated risk, collectively these events accounted for just 16.8 % of the overall public burden of PTSD, given their low prevalence among the general population. Events that were characteristic of civil conflict, including unexpected death of a loved one, witnessing death or a dead body or someone seriously injured and being mugged or threatened with a weapon accounted for the highest proportion of the overall public health burden of PTSD (18.6, 9.4 and 7.8 %, respectively). These findings are a feature of the higher prevalence of these events among the general population coupled with their moderate to above average risk of PTSD.

Conclusions

Despite the formal end to conflict in NI in 1999, a substantial proportion of the adult population continue to suffer the adverse mental health effects of chronic trauma exposure. Given rates of recovery of PTSD in the absence of evidence-based treatments, it is likely that the legacy of mental ill health associated with conflict, if not adequately addressed, will endure for many years.     

A detailed evaluation of the current renal response criteria in AL amyloidosis: is it time for a revision?

Organ response correlates with overall survival in patients with immunoglobulin light chain amyloidosis and is the goal of treatment. This study evaluates the current renal response criteria and their ability to predict overall survival. Patients with immunoglobulin light chain amyloidosis who underwent autologous stem cell transplantation between 1995 and 2010 were recruited. Eligibility criteria included >1 g/dL of proteinuria, dialysis independence at baseline and within the first year of autologous stem cell transplantation, and a minimum follow-up of 1 year. Responses were assessed by the best values after autologous stem cell transplantation. The difference between involved and uninvolved serum free light chain levels was used to determine hematologic response. Increases in serum creatinine were calculated from the highest creatinine after autologous stem cell transplantation. Inclusion and exclusion criteria were met by 141 patients. These patients had a median follow-up of 52 months. Superior overall survival was observed in patients with a >75% reduction in proteinuria and those who had a >95% reduction had additional benefits. The overall survival of patients with >50% to ≤75% proteinuria was similar to that of patients with ≤50% reduction. A rise in serum creatinine >25% was not associated with a poorer outcome in patients with a >75% reduction in proteinuria. Deeper hematologic responses were associated with higher rates of proteinuria reduction. These results suggest that further evaluation of the current renal response criteria is needed. In particular, discrimination of the renal response into complete and partial categories and modification of the serum creatinine requirement seem justified.     

SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

Background

Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood.

Objectives

COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination.

Methods

Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs.

Results

A total of 5.6% (n?=?320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n?=?168) compared with 100% of healthy controls (n?=?205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p?=?0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p?=?0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine.

Conclusion

SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

     

Isomer-dependent metabolic effects of conjugated linoleic acid: insights from molecular markers sterol regulatory element-binding protein-1c and LXRalpha

Conjugated linoleic acid (CLA) is a heterogeneous group of positional and geometric isomers of linoleic acid. This study demonstrates the divergent effects of the cis-9 trans-11 (c9,t11-CLA) and trans-10 cis-12 (t10,c12-CLA) isomers of CLA on lipid metabolism and nutrient regulation of gene expression in ob/ob mice. The c9, t11-CLA diet decreased serum triacylglycerol (P = 0.01) and nonesterified fatty acid (NEFA) (P = 0.05) concentrations, and this was associated with reduced hepatic sterol regulatory element-binding protein-1c (SREBP-1c; P = 0.0045) mRNA expression, coupled with reduced levels of both the membrane-bound precursor and the nuclear forms of the SREBP-1 protein. C9,t11-CLA significantly reduced hepatic LXRalpha (P = 0.019) mRNA expression, a novel regulator of SREBP-1c. In contrast, c9,t11-CLA increased adipose tissue SREBP-1c mRNA expression (P = 0.0162) proportionally to the degree of reduction of tumor necrosis factor alpha (TNF-alpha) mRNA (P = 0.012). Recombinant TNF-alpha almost completely abolished adipose tissue SREBP-1c mRNA expression in vivo. The t10,c12-CLA diet promoted insulin resistance and increased serum glucose (P = 0.025) and insulin (P = 0.01) concentrations. T10, c12-CLA induced profound weight loss (P = 0.0001) and increased brown and white adipose tissue UCP-2 (P = 0.001) and skeletal muscle UCP-3 (P = 0.008) mRNA expression. This study highlights the contrasting molecular and metabolic effect of two isomers of the same fatty acids. The ameliorative effect of c9,t11-CLA on lipid metabolism may be ascribed to reduced synthesis and cleavage of hepatic SREBP-1, which in turn may be regulated by hepatic LXRalpha expression.     

Sample size considerations for studies of intervention efficacy in the occupational setting

OBJECTIVE: Due to a shared environment and similarities among workers within a worksite, the strongest analytical design to evaluate the efficacy of an intervention to reduce occupational health or safety hazards is to randomly assign worksites, not workers, to the intervention and comparison conditions. Statistical methods are well described for estimating the sample size when the unit of assignment is a group but these methods have not been applied in the evaluation of occupational health and safety interventions. We review and apply the statistical methods for group-randomized trials in planning a study to evaluate the effectiveness of technical/behavioral interventions to reduce wood dust levels among small woodworking businesses. METHODS: We conducted a pilot study in five small woodworking businesses to estimate variance components between and within worksites and between and within workers. In each worksite, 8 h time-weighted dust concentrations were obtained for each production employee on between two and five occasions. With these data, we estimated the parameters necessary to calculate the percent change in dust concentrations that we could detect (alpha = 0.05, power = 80%) for a range of worksites per condition, workers per worksite and repeat measurements per worker. RESULTS: The mean wood dust concentration across woodworking businesses was 4.53 mg/m3. The measure of similarity among workers within a woodworking business was large (intraclass correlation = 0.5086). Repeated measurements within a worker were weakly correlated (r = 0.1927) while repeated measurements within a worksite were strongly correlated (r = 0.8925). The dominant factor in the sample size calculation was the number of worksites per condition, with the number of workers per worksite playing a lesser role. We also observed that increasing the number of repeat measurements per person had little benefit given the low within-worker correlation in our data. We found that 30 worksites per condition and 10 workers per worksite would give us 80% power to detect a reduction of approximately 30% in wood dust levels (alpha = 0.05). CONCLUSIONS: Our results demonstrate the application of the group-randomized trials methodology to evaluate interventions to reduce occupational hazards. The methodology is widely applicable and not limited to the context of wood dust reduction.