Association between hearing loss and deprivation among Welsh adults: a cross-sectional observational study.

OBJECTIVE: To index levels of hearing loss with respect to area-level indices of deprivation in a Welsh population. DESIGN: A cross-sectional observational study of all adults (aged >18) that attended Abertawe Bro Morgannwg University (ABMU) Health Board audiology services between 2016 and 2018. Service access, first hearing aid fitting appointment rates and hearing loss at time of first hearing aid provision were used to index population hearing loss versus area-level indices of deprivation based on patient postcode. SETTING: Primary and secondary care. PARTICIPANTS: 59 493 patient entries met the inclusion criteria. Patient entries were grouped by age (18-30, 31-40, 41-50, 51-60, 61-70, 71-80, >80 years) and deprivation decile. RESULTS: The interaction between age group and deprivation decile predicted access rate to ABMU audiology services (b=-0.24, t(6858) = -2.86, p<0.01) with audiology services accessed more frequently by the most deprived versus the least deprived decile in every age group (p<0.05), except the >80 years. First hearing aid fitting rates were highest among the most deprived in the four youngest age groups (p<0.05). Severity of hearing loss at the time of first hearing aid fitting was worse among the most deprived in the five oldest age groups (p<0.01). CONCLUSIONS: Hearing health inequalities are prevalent among adults accessing ABMU audiology services. Our findings suggest that deprivation increases the likelihood of developing hearing loss, brings earlier onset of hearing loss and is linked to delays in getting help for hearing problems. However, it is not possible to know the true scale of these disparities without knowing the hearing health of the Welsh adult population including those who do not seek help for hearing problems.

Whole blood cytokine release assays reveal disparity between capillary blood sampling methods.

INTRODUCTION: The use of whole blood in rapid cytokine release assays (CRAs) is becoming an established technique for screening immune responses following natural infection or vaccination, especially in the context of the SARS-CoV-2 pandemic. Establishing an accurate capillary blood sampling method to replace the need for venipuncture could make CRAs more accessible. In this study, capillary blood was collected via two different methods alongside traditional venipuncture to investigate whether the method of blood draw affects cytokine quantification when performing CRAs. METHODS: Adults previously vaccinated with SARS-CoV-2 vaccines donated three blood samples: one by venipuncture, one by finger prick, and one by a microneedle device. Whole blood was aliquoted and incubated overnight with SARS-CoV-2 peptides or left unstimulated. Cytokine release in plasma was measured by multiplex array. RESULTS: In unstimulated samples, little to no cytokines were detected in blood collected via venipuncture or by microneedle devices. Conversely, capillary blood collected by finger prick showed detectable levels of all cytokines analysed, with significantly inflated levels of TNFα, IL-10 (p < 0.0001), IL-2, GM-CSF, and IL-13 (p < 0.01), and 53% of these samples were also positive for IFN-γ. Following peptide stimulation, 25% of samples collected via finger prick showed dysregulated production of IFN-γ, TNFα, IL-2, and IL-10, with lower cytokine production than unstimulated controls. Contrastingly, this was seen in just 4% of venous blood samples and in none of the microneedle samples. CONCLUSIONS: Capillary blood draw via a microneedle device results in highly comparable immune responses to those seen via venipuncture at baseline and following peptide stimulation, suggesting this is a viable method for rapid whole blood CRAs. Conversely, differential cytokine production is observed following capillary blood draw via finger prick.

Differential cellular and humoral immune responses in immunocompromised individuals following multiple SARS-CoV-2 vaccinations.

Introduction: The heterogeneity of the immunocompromised population means some individuals may exhibit variable, weak or reduced vaccine-induced immune responses, leaving them poorly protected from COVID-19 disease despite receiving multiple SARS-CoV-2 vaccinations. There is conflicting data on the immunogenicity elicited by multiple vaccinations in immunocompromised groups. The aim of this study was to measure both humoral and cellular vaccine-induced immunity in several immunocompromised cohorts and to compare them to immunocompetent controls. Methods: Cytokine release in peptide-stimulated whole blood, and neutralising antibody and baseline SARS-CoV-2 spike-specific IgG levels in plasma were measured in rheumatology patients (n=29), renal transplant recipients (n=46), people living with HIV (PLWH) (n=27) and immunocompetent participants (n=64) post third or fourth vaccination from just one blood sample. Cytokines were measured by ELISA and multiplex array. Neutralising antibody levels in plasma were determined by a 50% neutralising antibody titre assay and SARS-CoV-2 spike specific IgG levels were quantified by ELISA. Results: In infection negative donors, IFN-γ, IL-2 and neutralising antibody levels were significantly reduced in rheumatology patients (p=0.0014, p=0.0415, p=0.0319, respectively) and renal transplant recipients (p<0.0001, p=0.0005, p<0.0001, respectively) compared to immunocompetent controls, with IgG antibody responses similarly affected. Conversely, cellular and humoral immune responses were not impaired in PLWH, or between individuals from all groups with previous SARS-CoV-2 infections. Discussion: These results suggest that specific subgroups within immunocompromised cohorts could benefit from distinct, personalised immunisation or treatment strategies. Identification of vaccine non-responders could be critical to protect those most at risk.

Longitudinal T Cell Responses against Ancestral, Delta, and Omicron SARS-CoV-2 Variants Determined by Rapid Cytokine Release Assay in Whole Blood.

T cell immunity to natural SARS-CoV-2 infection may be more robust and longer lived than Ab responses. Accurate assessment of T cell responses is critical for understanding the magnitude and longevity of immunity across patient cohorts, and against emerging variants. By establishing a simple, accurate, and rapid whole blood test, natural and vaccine-induced SARS-CoV-2 immunity was determined. Cytokine release in whole blood stimulated with peptides specific for SARS-CoV-2 was measured in donors with previous PCR-confirmed infection, suspected infection, or with no exposure history (n = 128), as well as in donors before and after vaccination (n = 32). Longitudinal assessment of T cell responses following initial vaccination and booster vaccination was also conducted (n = 50 and n = 62, respectively). Cytokines were measured by ELISA and multiplex array. IL-2 and IFN-γ were highly elevated in PCR-confirmed donors compared with history-negative controls, with median levels ∼33-fold and ∼48-fold higher, respectively. Receiver operating curves showed IL-2 as the superior biomarker (area under the curve = 0.9950). Following vaccination, all donors demonstrated a positive IL-2 response. Median IL-2 levels increased ∼32-fold from prevaccination to postvaccination in uninfected individuals. Longitudinal assessment revealed that T cell responses were stable up to 6 mo postvaccination. No significant differences in cytokine production were observed between stimulations with Wuhan, Delta, or Omicron peptides. This rapid, whole blood-based test can be used to make comparable longitudinal assessments of vaccine-induced T cell immunity across multiple cohorts and against variants of concern, thus aiding decisions on public health policies.

Finite element analysis of the middle ear transfer functions and related pathologies.

With developments in software and micro-measurement technology, a three-dimensional middle ear finite element (FE) model can now be more easily constructed to study sound transfer function. Many FE models of the middle ear have been constructed to date, and each has its own particular advantages and disadvantages. In this article, we review the latest developments and technologies in the field of the FE models of the middle ear, and the use of FE in the study of middle ear pathology. Proposals are made for future developments in the field of finite element analysis of middle ear transfer function.